Lab Publications
2025
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A streaming brain-to-voice neuroprosthesis to restore naturalistic communication. Nature neuroscience
Kaylo T Littlejohn, Cheol Jun Cho, Jessie R Liu, Alexander B Silva, Bohan Yu, Vanessa R Anderson, Cady M Kurtz-Miott, Samantha Brosler, Anshul P Kashyap, Irina P Hallinan, Adit Shah, Adelyn Tu-Chan, Karunesh Ganguly, David A Moses, Edward F Chang, Gopala K Anumanchipalli (2025).
Abstract: Natural spoken communication happens instantaneously. Speech delays longer than a few seconds can disrupt the natural flow of conversation. This makes it difficult for individuals with paralysis to participate in meaningful dialogue, potentially leading to feelings of isolation and frustration. Here we used high-density surface recordings of the speech sensorimotor cortex in a clinical trial participant with severe paralysis and anarthria to drive a continuously streaming naturalistic speech synthesizer. We designed and used deep learning recurrent neural network transducer models to achieve online large-vocabulary intelligible fluent speech synthesis personalized to the participant's preinjury voice with neural decoding in 80-ms increments. Offline, the models demonstrated implicit speech detection capabilities and could continuously decode speech indefinitely, enabling uninterrupted use of the decoder and further increasing speed. Our framework also successfully generalized to other silent-speech interfaces, including single-unit recordings and electromyography. Our findings introduce a speech-neuroprosthetic paradigm to restore naturalistic spoken communication to people with paralysis.
https://doi.org/10.1038/s41593-025-01905-6 -
Invasive Brain Mapping Identifies Personalized Therapeutic Neuromodulation Targets for Obsessive-Compulsive Disorder. medRxiv : the preprint server for health sciences
A Moses Lee, Audrey Kist, John Alvarez, Kristin K Sellers, Ankit N Khambhati, Leo P Sugrue, Lee B Reid, Kelly Kadlec, Joline M Fan, Anusha B Allawala, Caroline A Racine, Tenzin Norbu, Dani Astudillo, Alexandra G Tremblay-McGaw, Natalie Becker, Ahmad Alhourani, Philip A Starr, Edward F Chang, Andrew D Krystal (2025).
Abstract: Deep brain stimulation has been used to treat severe, refractory obsessive-compulsive disorder (OCD) with variable outcomes across multiple anatomical targets. To overcome these limitations, we developed an invasive brain mapping paradigm in which electrodes were implanted across the OCD cortico-striato-thalamo-cortical circuit in a single individual. We then performed extensive stimulation mapping during a multi-day inpatient stay to identify personalized therapeutic targets and characterize their downstream circuit effects. We found two targets within the right ventral capsule (VC) that acutely reduced OCD symptoms. Prolonged VC stimulation suppressed high frequency activity within the structurally and functionally connected orbitofrontal cortex, which encoded the severity of OCD symptoms. These VC sites were implanted for DBS and combined stimulation of these targets led to a rapid therapeutic response. This case provides the first proof-of-concept that invasive brain mapping can be used to guide a novel personalized, multi-site neuromodulation approach to treat refractory OCD.
https://doi.org/10.1101/2025.03.14.25323348 -
Inhibitory control of speech production in the human premotor frontal cortex. Nature human behaviour
Lingyun Zhao, Alexander B Silva, G Lynn Kurteff, Edward F Chang (2025).
Abstract: Voluntary, flexible stopping of speech output is an essential aspect of speech motor control, especially during natural conversations. The cognitive and neural mechanisms of speech inhibition are not well understood. Here we have recorded direct high-density cortical activity while participants engaged in continuous speech production and were visually cued to stop speaking. Neural recordings revealed distinct activity in the premotor frontal cortex correlated with stopping speech. This activity was found in largely separate cortical sites from regions encoding vocal tract articulatory movements. Moreover, this activity primarily occurred with abrupt stopping in the middle of an utterance, rather than naturally completing a phrase. Electrocortical stimulation at many premotor sites with inhibitory stop activity caused involuntary speech arrest, which contradicts previous clinical interpretations of this effect as evidence for critical centres of speech production. Together, these results suggest a previously unknown premotor cortical network that supports the inhibitory control of speech, providing implications for understanding both natural and altered speech production.
https://doi.org/10.1038/s41562-025-02118-4 -
Influences of electrode density on intracranial seizure localisation: a single-blinded randomised crossover study. EBioMedicine
Ebenezer O Chinedu-Eneh, Sharon Chiang, John P Andrews, Ehsan Tadayon, Joline M Fan, Paul A Garcia, Ernesto Gonzalez-Giraldo, Manu Hegde, Patrick Hullett, Vikram R Rao, Robert C Knowlton, Edward F Chang, Jonathan K Kleen (2025).
Abstract: Successful seizure onset zone (SOZ) localisation for epilepsy surgery often relies upon intracranial recordings. Accurate delineation requires anatomical detail yet influences of intracranial electrode density on clinical variables have not been systematically studied. In this experimental study we compared SOZ localisation between spontaneously captured seizures on higher-density depth and grid electrode arrays (4-5 mm inter-electrode spacing) vs. lower-density resampled versions of those same seizures (8-10 mm spacing). Since traditional review of channel traces would reveal density conditions, we instead projected seizure activity data as heatmaps on patient brain reconstructions and hid electrode locations. Using a single-blinded randomised crossover design, six attending-level epileptologists viewed these visualisations from ten patients under both higher-density and lower-density conditions (n = 120 observations) and digitally annotated SOZs. Inter-rater agreement between epileptologists on annotated margins was moderate (average Cohen's kappa: 0.47) and lower for the lower-density condition (p = 0.021, mixed effects model). Scorer confidence ratings did not differ between higher- and lower-density conditions (p = 0.410). The spatial extents of annotated SOZs for higher-density recordings were 25.4% larger on average (p = 0.011) and always closer to true SOZ extents in computer simulations, relative to lower-density. Epileptologists using higher-density depth and subdural intracranial EEG recordings had higher inter-rater agreement and identified larger extents of SOZs compared to lower-density recordings. While further studies assessing surgical outcomes in more patients are needed, these results suggest higher densities of electrodes on already-implanted hardware may reveal sub-centimetre extensions and clearer functional contiguity of the SOZ(s) for better appraisals of pathophysiological margins in epilepsy surgery. This work was supported by the National Institutes of Health through NINDS grant K23NS110920 and through a UCSF Weill Institute for Neurosciences Pilot Award.
https://doi.org/10.1016/j.ebiom.2025.105606 -
Reinstatement and transformation of memory traces for recognition. Science advances
Elias M B Rau, Marie-Christin Fellner, Rebekka Heinen, Hui Zhang, Qin Yin, Parisa Vahidi, Malte Kobelt, Eishi Asano, Olivia Kim-McManus, Shifteh Sattar, Jack J Lin, Kurtis I Auguste, Edward F Chang, David King-Stephens, Peter B Weber, Kenneth D Laxer, Robert T Knight, Elizabeth L Johnson, Noa Ofen, Nikolai Axmacher (2025).
Abstract: Episodic memory relies on the formation and retrieval of content-specific memory traces. In addition to their veridical reactivation, previous studies have indicated that traces may undergo substantial transformations. However, the exact time course and regional distribution of reinstatement and transformation during recognition memory have remained unclear. We applied representational similarity analysis to human intracranial electroencephalography to track the spatiotemporal dynamics underlying the reinstatement and transformation of memory traces. Specifically, we examined how reinstatement and transformation of item-specific representations across occipital, ventral visual, and lateral parietal cortices contribute to successful memory formation and recognition. Our findings suggest that reinstatement in temporal cortex and transformation in parietal cortex coexist and provide complementary strategies for recognition. Further, we find that generalization and differentiation of neural representations contribute to memory and probe memory-specific correspondence with deep neural network (DNN) model features. Our results suggest that memory formation is particularly supported by generalized and mnemonic representational formats beyond the visual features of a DNN.
https://doi.org/10.1126/sciadv.adp9336
2024
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Stimulation-based compassion mapping to assess risk of insular resection for surgical epilepsy management: illustrative case. Journal of neurosurgery. Case lessons
Patrick W Hullett, Aria J Lin, Quinn Greicius, Robert C Knowlton, Tina T Shih, Vikram R Rao, Virginia E Sturm, Edward F Chang (2024).
Abstract: The insula is a central node in network models of compassion and empathy. Because of this, resection of the insula for the treatment of drug-resistant epilepsy can change an individual's level of compassion. Here, the authors present the clinical case of a woman with drug-resistant epilepsy localized to the nondominant insula. Because of the widespread literature implicating insular function in empathy and compassion, including lesion studies, her primary concern was changes in her compassion level after insular resection. In this case, the authors performed a novel compassion mapping paradigm before resection, using 30-second video clips to elicit compassion. This showed no changes in compassion with electrical stimulation of sites spanning the anterior insula, providing some reassurance that resection would not affect her compassion. Consistent with this, pre- and postresection testing, along with informal subjective reports by the patient, demonstrated no change in compassion or subcomponents of compassion (sadness and empathy) after right insular resection. While resection of the nondominant insular cortex warrants caution, this case illustrates a compassion mapping paradigm that reassured the clinical team and the patient that her compassion would not be affected and formal postoperative testing that was consistent with this. https://thejns.org/doi/10.3171/CASE24339.
https://doi.org/10.3171/CASE24339 -
The development of aperiodic neural activity in the human brain. bioRxiv : the preprint server for biology
Zachariah R Cross, Samantha M Gray, Adam J O Dede, Yessenia M Rivera, Qin Yin, Parisa Vahidi, Elias M B Rau, Christopher Cyr, Ania M Holubecki, Eishi Asano, Jack J Lin, Olivia Kim McManus, Shifteh Sattar, Ignacio Saez, Fady Girgis, David King-Stephens, Peter B Weber, Kenneth D Laxer, Stephan U Schuele, Joshua M Rosenow, Joyce Y Wu, Sandi K Lam, Jeffrey S Raskin, Edward F Chang, Ammar Shaikhouni, Peter Brunner, Jarod L Roland, Rodrigo M Braga, Robert T Knight, Noa Ofen, Elizabeth L Johnson (2024).
Abstract: The neurophysiological mechanisms supporting brain maturation are fundamental to attention and memory capacity across the lifespan. Human brain regions develop at different rates, with many regions developing into the third and fourth decades of life. Here, in this preregistered study (https://osf.io/gsru7), we analyzed intracranial EEG (iEEG) recordings from widespread brain regions in a large developmental cohort. Using task-based (i.e., attention to-be-remembered visual stimuli) and task-free (resting-state) data from 101 children and adults (5.93 - 54.00 years, 63 males; n electrodes = 5691), we mapped aperiodic (1/ƒ-like) activity, a proxy of excitation:inhibition (E:I) balance with steeper slopes indexing inhibition and flatter slopes indexing excitation. We reveal that aperiodic slopes flatten with age into young adulthood in both association and sensorimotor cortices, challenging models of early sensorimotor development based on brain structure. In prefrontal cortex (PFC), attentional state modulated age effects, revealing steeper task-based than task-free slopes in adults and the opposite in children, consistent with the development of cognitive control. Age-related differences in task-based slopes also explained age-related gains in memory performance, linking the development of PFC cognitive control to the development of memory. Last, with additional structural imaging measures, we reveal that age-related differences in gray matter volume are differentially associated with aperiodic slopes in association and sensorimotor cortices. Our findings establish developmental trajectories of aperiodic activity in localized brain regions and illuminate the development of PFC inhibitory control during adolescence in the development of attention and memory.
https://doi.org/10.1101/2024.11.08.622714 -
Hippocampal network activity forecasts epileptic seizures. Nature medicine
Ankit N Khambhati, Edward F Chang, Maxime O Baud, Vikram R Rao (2024).
Abstract: Seizures in people with epilepsy were long thought to occur at random, but recent methods for seizure forecasting enable estimation of the likelihood of seizure occurrence over short horizons. These methods rely on days-long cyclical patterns of brain electrical activity and other physiological variables that determine seizure likelihood and that require measurement through long-term, multimodal recordings. In this retrospective cohort study of 15 adults with bitemporal epilepsy who had a device that provides chronic intracranial recordings, functional connectivity of hippocampal networks fluctuated in multiday cycles with patterns that mirrored cycles of seizure likelihood. A functional connectivity biomarker of seizure likelihood derived from 90-s recordings of background hippocampal activity generalized across individuals and forecasted 24-h seizure likelihood as accurately as cycle-based models requiring months-long baseline recordings. Larger, prospective studies are needed to validate this approach, but our results have the potential to make reliable seizure forecasts accessible to more people with epilepsy.
https://doi.org/10.1038/s41591-024-03149-6 -
Ictal EEG Source Imaging With Supplemental Electrodes. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society
Deanne Kennedy Loube, Yee-Leng Tan, June Yoshii-Contreras, Jonathan Kleen, Vikram R Rao, Edward F Chang, Robert C Knowlton (2024).
Abstract: Noninvasive brain imaging tests play a major role in guiding decision-making and the usage of invasive, costly intracranial electroencephalogram (ICEEG) in the presurgical epilepsy evaluation. This study prospectively examined the concordance in localization between ictal EEG source imaging (ESI) and ICEEG as a reference standard. Between August 2014 and April 2019, patients during video monitoring with scalp EEG were screened for those with intractable focal epilepsy believed to be amenable to surgical treatment. Additional 10-10 electrodes (total = 31-38 per patient, "31+") were placed over suspected regions of seizure onset in 104 patients. Of 42 patients requiring ICEEG, 30 (mean age 30, range 19-59) had sufficiently localized subsequent intracranial studies to allow comparison of localization between tests. ESI was performed using realistic forward boundary element models used in dipole and distributed source analyses. At least partial sublobar concordance between ESI and ICEEG solutions was obtained in 97% of cases, with 73% achieving complete agreement. Median Euclidean distances between ESI and ICEEG solutions ranged from 25 to 30 mm (dipole) and 23 to 38 mm (distributed source). The latter was significantly more accurate with 31+ compared with 21 electrodes ( P < 0.01). A difference of ≤25 mm was present in two thirds of the cases. No significant difference was found between dipole and distributed source analyses. A practical method of ictal ESI (nonuniform placement of 31-38 electrodes) yields high accuracy for seizure localization in epilepsy surgery candidates. These results support routine clinical application of ESI in the presurgical evaluation.
https://doi.org/10.1097/WNP.0000000000001025 -
Brain-Computer Interfaces for Restoring Communication. The New England journal of medicine
Edward F Chang (2024).
Abstract: This editorial describes the science behind reports of communication facilitated by brain–computer interfaces.
https://doi.org/10.1056/NEJMe2407363 -
A bilingual speech neuroprosthesis driven by cortical articulatory representations shared between languages. Nature biomedical engineering
Alexander B Silva, Jessie R Liu, Sean L Metzger, Ilina Bhaya-Grossman, Maximilian E Dougherty, Margaret P Seaton, Kaylo T Littlejohn, Adelyn Tu-Chan, Karunesh Ganguly, David A Moses, Edward F Chang (2024).
Abstract: Advancements in decoding speech from brain activity have focused on decoding a single language. Hence, the extent to which bilingual speech production relies on unique or shared cortical activity across languages has remained unclear. Here, we leveraged electrocorticography, along with deep-learning and statistical natural-language models of English and Spanish, to record and decode activity from speech-motor cortex of a Spanish-English bilingual with vocal-tract and limb paralysis into sentences in either language. This was achieved without requiring the participant to manually specify the target language. Decoding models relied on shared vocal-tract articulatory representations across languages, which allowed us to build a syllable classifier that generalized across a shared set of English and Spanish syllables. Transfer learning expedited training of the bilingual decoder by enabling neural data recorded in one language to improve decoding in the other language. Overall, our findings suggest shared cortical articulatory representations that persist after paralysis and enable the decoding of multiple languages without the need to train separate language-specific decoders.
https://doi.org/10.1038/s41551-024-01207-5 -
Development and validation of a nonverbal consensus-based semantic memory paradigm in patients with epilepsy. Journal of the International Neuropsychological Society : JINS
Edwina B Tran, Jet M J Vonk, Kaitlin Casaletto, Da Zhang, Raphael Christin, Siddharth Marathe, Maria Luisa Gorno-Tempini, Edward F Chang, Jonathan K Kleen (2024).
Abstract: Brain areas implicated in semantic memory can be damaged in patients with epilepsy (PWE). However, it is challenging to delineate semantic processing deficits from acoustic, linguistic, and other verbal aspects in current neuropsychological assessments. We developed a new Visual-based Semantic Association Task (ViSAT) to evaluate nonverbal semantic processing in PWE. The ViSAT was adapted from similar predecessors (Pyramids & Palm Trees test, PPT; Camels & Cactus Test, CCT) comprised of 100 unique trials using real-life color pictures that avoid demographic, cultural, and other potential confounds. We obtained performance data from 23 PWE participants and 24 control participants (Control), along with crowdsourced normative data from 54 Amazon Mechanical Turk (Mturk) workers. ViSAT reached a consensus >90% in 91.3% of trials compared to 83.6% in PPT and 82.9% in CCT. A deep learning model demonstrated that visual features of the stimulus images (color, shape; i.e., non-semantic) did not influence top answer choices (p = 0.577). The PWE group had lower accuracy than the Control group (p = 0.019). PWE had longer response times than the Control group in general and this was augmented for the semantic processing (trial answer) stage (both p < 0.001). This study demonstrated performance impairments in PWE that may reflect dysfunction of nonverbal semantic memory circuits, such as seizure onset zones overlapping with key semantic regions (e.g., anterior temporal lobe). The ViSAT paradigm avoids confounds, is repeatable/longitudinal, captures behavioral data, and is open-source, thus we propose it as a strong alternative for clinical and research assessment of nonverbal semantic memory.
https://doi.org/10.1017/S1355617724000158 -
The speech neuroprosthesis. Nature reviews. Neuroscience
Alexander B Silva, Kaylo T Littlejohn, Jessie R Liu, David A Moses, Edward F Chang (2024).
Abstract: Loss of speech after paralysis is devastating, but circumventing motor-pathway injury by directly decoding speech from intact cortical activity has the potential to restore natural communication and self-expression. Recent discoveries have defined how key features of speech production are facilitated by the coordinated activity of vocal-tract articulatory and motor-planning cortical representations. In this Review, we highlight such progress and how it has led to successful speech decoding, first in individuals implanted with intracranial electrodes for clinical epilepsy monitoring and subsequently in individuals with paralysis as part of early feasibility clinical trials to restore speech. We discuss high-spatiotemporal-resolution neural interfaces and the adaptation of state-of-the-art speech computational algorithms that have driven rapid and substantial progress in decoding neural activity into text, audible speech, and facial movements. Although restoring natural speech is a long-term goal, speech neuroprostheses already have performance levels that surpass communication rates offered by current assistive-communication technology. Given this accelerated rate of progress in the field, we propose key evaluation metrics for speed and accuracy, among others, to help standardize across studies. We finish by highlighting several directions to more fully explore the multidimensional feature space of speech and language, which will continue to accelerate progress towards a clinically viable speech neuroprosthesis.
https://doi.org/10.1038/s41583-024-00819-9 -
Intraoperative cortical stimulation mapping with laryngeal electromyography for the localization of human laryngeal motor cortex. Journal of neurosurgery
Simon G Ammanuel, Sravani Kondapavulur, Alex Y Lu, Jonathan D Breshears, John P Clark, Alexander B Silva, Edward F Chang (2024).
Abstract: The objectives of this study were to describe the authors' clinical methodology and outcomes for mapping the laryngeal motor cortex (LMC) and define localization of the LMC in a cohort of neurosurgical patients undergoing intraoperative brain mapping. Because of mapping variability across patients, the authors aimed to define the probabilistic distribution of cortical sites that evoke laryngeal movement, as well as adjacent cortical somatotopic representations for the face (mouth), tongue, and hand. Thirty-six patients underwent left (n = 18) or right (n = 18) craniotomy with asleep motor mapping. For each patient, electromyography (EMG) electrodes were placed in the face, tongue, and hand; a nerve integrity monitor (NIM) endotracheal tube with surface electrodes detected EMG activity from the bilateral vocal folds. After dense cortical stimulation was delivered throughout the sensorimotor cortex, motor responses were then mapped onto a three-dimensional reconstruction of the patient's cortical surfaces for location characterization of the evoked responses. Finally, stimulation sites were transformed into a two-dimensional coordinate system for probabilistic mapping of the stimulation site relative to the central sulcus and sylvian fissure. The authors found that the LMC was predominantly localized to a mid precentral gyrus region, dorsal to face representation and surrounding a transverse sulcus ventral to the hand knob. In 14 of 36 patients, the authors identified additional laryngeal responses located ventral to all orofacial representations, providing evidence for dual LMC representations. The authors determined the probabilistic distribution of the LMC. Cortical stimulation mapping with an NIM endotracheal tube is an easy and effective method for mapping the LMC and is simply integrated into the current neuromonitoring methods for brain mapping.
https://doi.org/10.3171/2023.10.JNS231023 -
Large-scale neurophysiology and single-cell profiling in human neuroscience. Nature
Anthony T Lee, Edward F Chang, Mercedes F Paredes, Tomasz J Nowakowski (2024).
Abstract: Advances in large-scale single-unit human neurophysiology, single-cell RNA sequencing, spatial transcriptomics and long-term ex vivo tissue culture of surgically resected human brain tissue have provided an unprecedented opportunity to study human neuroscience. In this Perspective, we describe the development of these paradigms, including Neuropixels and recent brain-cell atlas efforts, and discuss how their convergence will further investigations into the cellular underpinnings of network-level activity in the human brain. Specifically, we introduce a workflow in which functionally mapped samples of human brain tissue resected during awake brain surgery can be cultured ex vivo for multi-modal cellular and functional profiling. We then explore how advances in human neuroscience will affect clinical practice, and conclude by discussing societal and ethical implications to consider. Potential findings from the field of human neuroscience will be vast, ranging from insights into human neurodiversity and evolution to providing cell-type-specific access to study and manipulate diseased circuits in pathology. This Perspective aims to provide a unifying framework for the field of human neuroscience as we welcome an exciting era for understanding the functional cytoarchitecture of the human brain.
https://doi.org/10.1038/s41586-024-07405-0 -
Parallel Encoding of Speech in Human Frontal and Temporal Lobes. bioRxiv : the preprint server for biology
Patrick W Hullett, Matthew K Leonard, Maria Luisa Gorno-Tempini, Maria Luisa Mandelli, Edward F Chang (2024).
Abstract: Models of speech perception are centered around a hierarchy in which auditory representations in the thalamus propagate to primary auditory cortex, then to the lateral temporal cortex, and finally through dorsal and ventral pathways to sites in the frontal lobe. However, evidence for short latency speech responses and low-level spectrotemporal representations in frontal cortex raises the question of whether speech-evoked activity in frontal cortex strictly reflects downstream processing from lateral temporal cortex or whether there are direct parallel pathways from the thalamus or primary auditory cortex to the frontal lobe that supplement the traditional hierarchical architecture. Here, we used high-density direct cortical recordings, high-resolution diffusion tractography, and hemodynamic functional connectivity to evaluate for evidence of direct parallel inputs to frontal cortex from low-level areas. We found that neural populations in the frontal lobe show speech-evoked responses that are synchronous or occur earlier than responses in the lateral temporal cortex. These short latency frontal lobe neural populations encode spectrotemporal speech content indistinguishable from spectrotemporal encoding patterns observed in the lateral temporal lobe, suggesting parallel auditory speech representations reaching temporal and frontal cortex simultaneously. This is further supported by white matter tractography and functional connectivity patterns that connect the auditory nucleus of the thalamus (medial geniculate body) and the primary auditory cortex to the frontal lobe. Together, these results support the existence of a robust pathway of parallel inputs from low-level auditory areas to frontal lobe targets and illustrate long-range parallel architecture that works alongside the classical hierarchical speech network model.
https://doi.org/10.1101/2024.03.19.585648 -
Human Anterior Insular Cortex Encodes Multiple Electrophysiological Representations of Anxiety-Related Behaviors. bioRxiv : the preprint server for biology
A Moses Lee, Virginia E Sturm, Heather Dawes, Andrew D Krystal, Edward F Chang (2024).
Abstract: Anxiety is a common symptom across psychiatric disorders, but the neurophysiological underpinnings of these symptoms remain unclear. This knowledge gap has prevented the development of circuit-based treatments that can target the neural substrates underlying anxiety. Here, we conducted an electrophysiological mapping study to identify neurophysiological activity associated with self-reported state anxiety in 17 subjects implanted with intracranial electrodes for seizure localization. Participants had baseline anxiety traits ranging from minimal to severe. Subjects volunteered to participate in an anxiety induction task in which they were temporarily exposed to the threat of unpredictable shock during intracranial recordings. We found that anterior insular beta oscillatory activity was selectively elevated during epochs when unpredictable aversive stimuli were being delivered, and this enhancement in insular beta was correlated with increases in self-reported anxiety. Beta oscillatory activity within the frontoinsular region was also evoked selectively by cues-predictive of threat, but not safety cues. Anterior insular gamma responses were less selective than gamma, strongly evoked by aversive stimuli and had weaker responses to salient threat and safety cues. On longer timescales, this gamma signal also correlated with increased skin conductance, a measure of autonomic state. Lastly, we found that direct electrical stimulation of the anterior insular cortex in a subset of subjects elicited self-reported increases in anxiety that were accompanied by enhanced frontoinsular beta oscillations. Together, these findings suggest that electrophysiologic representations of anxiety- related states and behaviors exist within anterior insular cortex. The findings also suggest the potential of reducing anterior insular beta activity as a therapeutic target for refractory anxiety-spectrum disorders.
https://doi.org/10.1101/2024.03.05.583610 -
Encoding of melody in the human auditory cortex. Science advances
Narayan Sankaran, Matthew K Leonard, Frederic Theunissen, Edward F Chang (2024).
Abstract: Melody is a core component of music in which discrete pitches are serially arranged to convey emotion and meaning. Perception varies along several pitch-based dimensions: (i) the absolute pitch of notes, (ii) the difference in pitch between successive notes, and (iii) the statistical expectation of each note given prior context. How the brain represents these dimensions and whether their encoding is specialized for music remains unknown. We recorded high-density neurophysiological activity directly from the human auditory cortex while participants listened to Western musical phrases. Pitch, pitch-change, and expectation were selectively encoded at different cortical sites, indicating a spatial map for representing distinct melodic dimensions. The same participants listened to spoken English, and we compared responses to music and speech. Cortical sites selective for music encoded expectation, while sites that encoded pitch and pitch-change in music used the same neural code to represent equivalent properties of speech. Findings reveal how the perception of melody recruits both music-specific and general-purpose sound representations.
https://doi.org/10.1126/sciadv.adk0010 -
Large-scale single-neuron speech sound encoding across the depth of human cortex. Nature
Matthew K Leonard, Laura Gwilliams, Kristin K Sellers, Jason E Chung, Duo Xu, Gavin Mischler, Nima Mesgarani, Marleen Welkenhuysen, Barundeb Dutta, Edward F Chang (2024).
Abstract: Understanding the neural basis of speech perception requires that we study the human brain both at the scale of the fundamental computational unit of neurons and in their organization across the depth of cortex. Here we used high-density Neuropixels arrays1-3 to record from 685 neurons across cortical layers at nine sites in a high-level auditory region that is critical for speech, the superior temporal gyrus4,5, while participants listened to spoken sentences. Single neurons encoded a wide range of speech sound cues, including features of consonants and vowels, relative vocal pitch, onsets, amplitude envelope and sequence statistics. Neurons at each cross-laminar recording exhibited dominant tuning to a primary speech feature while also containing a substantial proportion of neurons that encoded other features contributing to heterogeneous selectivity. Spatially, neurons at similar cortical depths tended to encode similar speech features. Activity across all cortical layers was predictive of high-frequency field potentials (electrocorticography), providing a neuronal origin for macroelectrode recordings from the cortical surface. Together, these results establish single-neuron tuning across the cortical laminae as an important dimension of speech encoding in human superior temporal gyrus.
https://doi.org/10.1038/s41586-023-06839-2 -
Surgical outcomes following resection in patients with language dominant posterior quadrant epilepsy. Epilepsy & behavior reports
Satvir Saggi, Joseph H Garcia, Faraz Behzadi, Arka N Mallela, Paul A Garcia, Edward F Chang, Robert C Knowlton (2024).
Abstract: Posterior quadrant epilepsy surgery, involving the occipital lobe, parietal lobe, or the posterior border of the temporal lobe, accounts for a small percentage of focal resections for medically refractory epilepsy. Prior studies investigating seizure control from posterior quadrant epilepsy surgery are limited. In this study, a retrospective database of patients undergoing surgery for left sided posterior cortex epilepsy at a single large level 4 epilepsy center was analyzed between August 2008 to April 2021 in order to characterize seizure control outcomes. Nine patients presented with epileptogenic foci in the left posterior cortex with a malformation of cortical development deemed as the etiology of seizures for all but one patient. Absolute seizure freedom (Engel I) was achieved in 4 of 9 patients, with the remaining 5 patients achieving an improvement in the frequency of seizures (Engel II/III). Complete resection of the anatomic and physiologic abnormalities was performed in 3 of 4 patients with Engel 1 outcomes and 1 of 5 patients with Class II/III outcomes. Five patients developed new right sided visual field defects, all of which were expected based on the sub-lobar, occipital localization and were viewed as acceptable by the patients and did not interfere with activities of daily living. Overall, our study demonstrates the potential for surgical resection to yield excellent seizure-control outcomes with anticipated, tolerable neurological deficits. This information is important for patients with disabling seizures who may not benefit sufficiently from palliative procedures.
https://doi.org/10.1016/j.ebr.2024.100695 -
Closed-loop neurostimulation for the treatment of psychiatric disorders. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Kristin K Sellers, Joshua L Cohen, Ankit N Khambhati, Joline M Fan, A Moses Lee, Edward F Chang, Andrew D Krystal (2024).
Abstract: Despite increasing prevalence and huge personal and societal burden, psychiatric diseases still lack treatments which can control symptoms for a large fraction of patients. Increasing insight into the neurobiology underlying these diseases has demonstrated wide-ranging aberrant activity and functioning in multiple brain circuits and networks. Together with varied presentation and symptoms, this makes one-size-fits-all treatment a challenge. There has been a resurgence of interest in the use of neurostimulation as a treatment for psychiatric diseases. Initial studies using continuous open-loop stimulation, in which clinicians adjusted stimulation parameters during patient visits, showed promise but also mixed results. Given the periodic nature and fluctuations of symptoms often observed in psychiatric illnesses, the use of device-driven closed-loop stimulation may provide more effective therapy. The use of a biomarker, which is correlated with specific symptoms, to deliver stimulation only during symptomatic periods allows for the personalized therapy needed for such heterogeneous disorders. Here, we provide the reader with background motivating the use of closed-loop neurostimulation for the treatment of psychiatric disorders. We review foundational studies of open- and closed-loop neurostimulation for neuropsychiatric indications, focusing on deep brain stimulation, and discuss key considerations when designing and implementing closed-loop neurostimulation.
https://doi.org/10.1038/s41386-023-01631-2
2023
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Large-scale single-neuron speech sound encoding across the depth of human cortex. Nature.
Matthew K. Leonard, Laura Gwilliams, Kristen K. Sellers, Jason E. Chung, Duo Xu, Gavin Mischler, Nima Mesgarani, Marleen Welkenhuysen, Barundeb Dutta, & Edward F. Chang (2023).
Abstract: Understanding the neural basis of speech perception requires that we study the human brain both at the scale of the fundamental computational unit of neurons and in their organization across the depth of cortex. Here we used high-density Neuropixels arrays
https://doi.org/10.1038/s41586-023-06839-2 -
Neural control of lexical tone production in human motor cortex. Nature Communications.
Junfeng Lu, Yuanning Li, Zehao Zhao, Yanming Zhu, Ying Mao, Jinsong Wu, & Edward F. Chang (2023).
Abstract: In tonal languages, which are spoken by nearly one-third of the world’s population, speakers precisely control the tension of vocal folds in the larynx to modulate pitch in order to distinguish words with completely different meanings. The specific pitch trajectories for a given tonal language are called lexical tones. Here, we used high-density direct cortical recordings to determine the neural basis of lexical tone production in native Mandarin-speaking participants. We found that instead of a tone category-selective coding, local populations in the bilateral laryngeal motor cortex (LMC) encode articulatory kinematic information to generate the pitch dynamics of lexical tones. Using a computational model of tone production, we discovered two distinct patterns of population activity in LMC commanding pitch rising and lowering. Finally, we showed that direct electrocortical stimulation of different local populations in LMC evoked pitch rising and lowering during tone production, respectively. Together, these results reveal the neural basis of vocal pitch control of lexical tones in tonal languages.
https://doi.org/10.1038/s41467-023-42175-9 -
Dissecting neural computations in the human auditory pathway using deep neural networks for speech. Nature Neuroscience.
Yuanning Li, Gopala K. Anumanchipali, Abdelrahman Mohamed, Peili Chen, Laurel H. Carney, Junfeng Lu, Jinsong Wu, & Edward F. Chang (2023).
Abstract: The human auditory system extracts rich linguistic abstractions from speech signals. Traditional approaches to understanding this complex process have used linear feature-encoding models, with limited success. Artificial neural networks excel in speech recognition tasks and offer promising computational models of speech processing. We used speech representations in state-of-the-art deep neural network (DNN) models to investigate neural coding from the auditory nerve to the speech cortex. Representations in hierarchical layers of the DNN correlated well with the neural activity throughout the ascending auditory system. Unsupervised speech models performed at least as well as other purely supervised or fine-tuned models. Deeper DNN layers were better correlated with the neural activity in the higher-order auditory cortex, with computations aligned with phonemic and syllabic structures in speech. Accordingly, DNN models trained on either English or Mandarin predicted cortical responses in native speakers of each language. These results reveal convergence between DNN model representations and the biological auditory pathway, offering new approaches for modeling neural coding in the auditory cortex.
https://doi.org/10.1038/s41593-023-01468-4 -
Vowel and formant representation in the human auditory speech cortex. Neuron.
Yulia Oganian, Ilina Bhaya-Grossman, Keith Johnson, & Edward F. Chang (2023).
Abstract: The speech signal contains many acoustic properties that may contribute differently to spoken word recognition. Previous studies have demonstrated that the importance of properties present during consonants or vowels is dependent upon the linguistic context (i.e., words versus sentences). The current study investigated three potentially informative acoustic properties that are present during consonants and vowels for monosyllabic words and sentences. Natural variations in fundamental frequency were either flattened or removed. The speech envelope and temporal fine structure were also investigated by limiting the availability of these cues via noisy signal extraction. Thus, this study investigated the contribution of these acoustic properties, present during either consonants or vowels, to overall word and sentence intelligibility. Results demonstrated that all processing conditions displayed better performance for vowel-only sentences. Greater performance with vowel-only sentences remained, despite removing dynamic cues of the fundamental frequency. Word and sentence comparisons suggest that the speech envelope may be at least partially responsible for additional vowel contributions in sentences. Results suggest that speech information transmitted by the envelope is responsible, in part, for greater vowel contributions in sentences, but is not predictive for isolated words.
https://doi.org/10.1016/j.neuron.2023.04.004 -
Latent neural dynamics encode temporal context in speech. Hearing Research.
Emily P. Stephen, Yuanning Li, Sean Metzger, Yulia Oganian, & Edward F. Chang (2023).
Abstract: Direct neural recordings from human auditory cortex have demonstrated encoding for acoustic-phonetic features of consonants and vowels. Neural responses also encode distinct acoustic amplitude cues related to timing, such as those that occur at the onset of a sentence after a silent period or the onset of the vowel in each syllable. Here, we used a group reduced rank regression model to show that distributed cortical responses support a low-dimensional latent state representation of temporal context in speech. The timing cues each capture more unique variance than all other phonetic features and exhibit rotational or cyclical dynamics in latent space from activity that is widespread over the superior temporal gyrus. We propose that these spatially distributed timing signals could serve to provide temporal context for, and possibly bind across time, the concurrent processing of individual phonetic features, to compose higher-order phonological (e.g. word-level) representations.
https://doi.org/10.1016/j.heares.2023.108838 -
A high performance neuroprosthesis for speech decoding and avatar control. Nature
Sean L. Metzger*, Kaylo T. Littlejohn*, Alex B. Silva*, David A. Moses*, Margaret P. Seaton*, Ran Wang, Maximilian E. Dougherty, Jessie R. Liu, Peter Wu, Michael A. Berger, Inga Zhuravleva, Adelyn Tu-Chan, Karunesh Ganguly, Gopala K. Anumanchipalli, & Edward F. Chang (*Equally contributing authors) (2023).
Abstract: Speech neuroprostheses have the potential to restore communication to people living with paralysis, but naturalistic speed and expressivity are elusive1. Here we use high-density surface recordings of the speech cortex in a clinical-trial participant with severe limb and vocal paralysis to achieve high-performance real-time decoding across three complementary speech-related output modalities: text, speech audio and facial-avatar animation. We trained and evaluated deep-learning models using neural data collected as the participant attempted to silently speak sentences. For text, we demonstrate accurate and rapid large-vocabulary decoding with a median rate of 78 words per minute and median word error rate of 25%. For speech audio, we demonstrate intelligible and rapid speech synthesis and personalization to the participant’s pre-injury voice. For facial-avatar animation, we demonstrate the control of virtual orofacial movements for speech and non-speech communicative gestures. The decoders reached high performance with less than two weeks of training. Our findings introduce a multimodal speech-neuroprosthetic approach that has substantial promise to restore full, embodied communication to people living with severe paralysis.
https://doi.org/10.1038/s41586-023-06443-4 -
Apraxia of speech with phonological alexia and agraphia following resection of the left middle precentral gyrus: illustrative case. Journal of Neurosurgery: Case Lessons.
Deborah F. Levy, Alex B. Silva, Terri L. Scott, Jessie R. Liu, Sarah Harper, Lingyun Zhao, Patrick W. Hullett, Garret Kurteff, Stephen M. Wilson, Matthew K. Leonard, & Edward F. Chang (2023).
Abstract: Apraxia of speech is a disorder of speech-motor planning in which articulation is effortful and error-prone despite normal strength of the articulators. Phonological alexia and agraphia are disorders of reading and writing disproportionately affecting unfamiliar words. These disorders are almost always accompanied by aphasia.
https://doi.org/10.3171/CASE22504
2022
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A Neurosurgical Functional Dissection of the Middle Precentral Gyrus during Speech Production. Journal of Neuroscience.
Alex B. Silva, Jessie R. Liu, Lingyun Zhao, Deborah F. Levy, Terri L. Scott, & Edward F. Chang (2022).
Abstract: Classical models have traditionally focused on the left posterior inferior frontal gyrus (Broca's area) as a key region for motor planning of speech production. However, converging evidence suggests that it is not critical for either speech motor planning or execution. Alternative cortical areas supporting high-level speech motor planning have yet to be defined. In this review, we focus on the precentral gyrus, whose role in speech production is often thought to be limited to lower-level articulatory muscle control. In particular, we highlight neurosurgical investigations that have shed light on a cortical region anatomically located near the midpoint of the precentral gyrus, hence called the middle precentral gyrus (midPrCG). The midPrCG is functionally located between dorsal hand and ventral orofacial cortical representations and exhibits unique sensorimotor and multisensory functions relevant for speech processing. This includes motor control of the larynx, auditory processing, as well as a role in reading and writing. Furthermore, direct electrical stimulation of midPrCG can evoke complex movements, such as vocalization, and selective injury can cause deficits in verbal fluency, such as pure apraxia of speech. Based on these findings, we propose that midPrCG is essential to phonological-motoric aspects of speech production, especially syllabic-level speech sequencing, a role traditionally ascribed to Broca's area. The midPrCG is a cortical brain area that should be included in contemporary models of speech production with a unique role in speech motor planning and execution.
https://doi.org/10.1523/JNEUROSCI.1614-22.2022 -
Generalizable spelling using a speech neuroprosthesis in an individual with severe limb and vocal paralysis. Nature Communications.
Sean L. Metzger, Jessie R. Liu, David A. Moses, Maximilian E. Dougherty, Margaret P. Seaton, Kaylo T. Littlejohn, Josh Chartier, Gopala K. Anumanchipalli, Adelyn Tu-Chan, Karunesh Ganguly, & Edward F. Chang (2022).
Abstract: Neuroprostheses have the potential to restore communication to people who cannot speak or type due to paralysis. However, it is unclear if silent attempts to speak can be used to control a communication neuroprosthesis. Here, we translated direct cortical signals in a clinical-trial participant (ClinicalTrials.gov; NCT03698149) with severe limb and vocal-tract paralysis into single letters to spell out full sentences in real time. We used deep-learning and language-modeling techniques to decode letter sequences as the participant attempted to silently spell using code words that represented the 26 English letters (e.g. “alpha” for “a”). We leveraged broad electrode coverage beyond speech-motor cortex to include supplemental control signals from hand cortex and complementary information from low- and high-frequency signal components to improve decoding accuracy. We decoded sentences using words from a 1,152-word vocabulary at a median character error rate of 6.13% and speed of 29.4 characters per minute. In offline simulations, we showed that our approach generalized to large vocabularies containing over 9,000 words (median character error rate of 8.23%). These results illustrate the clinical viability of a silently controlled speech neuroprosthesis to generate sentences from a large vocabulary through a spelling-based approach, complementing previous demonstrations of direct full-word decoding.
https://doi.org/10.1038/s41467-022-33611-3 -
High-density single-unit human cortical recordings using the Neuropixels probe. Neuron.
Jason E. Chung, Kristin K. Sellers, Matthew K. Leonard, Laura Gwilliams, Duo Xu, Maximilian E. Dougherty, Viktor Kharazia, Sean L. Metzger, Marleen Welkenhuysen, Barundeb Dutta, & Edward F. Chang (2022).
Abstract: Studies in monkeys have implicated the brain's posterior parietal cortex in high-level coding of planned and imagined actions. Aflalo
https://doi.org/10.1016/j.neuron.2022.05.007 -
Harnessing the power of artificial intelligence in otolaryngology and the communication sciences. Journal of the Association for Research in Otolaryngology.
Blake S. Wilson, Debara L. Tucci, David A. Moses, Edward F. Chang, Nancy M. Young, Fan-Gang Zeng, Nicholas A. Lesica, Andrés M. Bur, Hannah Kavookjian, Caroline Mussatto, Joseph Penn, Sara Goodwin, Shannon Kraft, Guanghui Wang, Jonathan M. Cohen, Geoffrey S. Ginsburg, Geraldine Dawson, & Howard H. Francis (2022).
Abstract: Use of artificial intelligence (AI) is a burgeoning field in otolaryngology and the communication sciences. A virtual symposium on the topic was convened from Duke University on October 26, 2020, and was attended by more than 170 participants worldwide. This review presents summaries of all but one of the talks presented during the symposium; recordings of all the talks, along with the discussions for the talks, are available at https://www.youtube.com/watch?v=ktfewrXvEFg and https://www.youtube.com/watch?v=-gQ5qX2v3rg . Each of the summaries is about 2500 words in length and each summary includes two figures. This level of detail far exceeds the brief summaries presented in traditional reviews and thus provides a more-informed glimpse into the power and diversity of current AI applications in otolaryngology and the communication sciences and how to harness that power for future applications.
https://doi.org/10.1007/s10162-022-00846-2 -
Decoding naturalistic affective behaviour from spectro-spatial features in multiday human iEEG. Nature Human Behavior.
Maryam Bijanzadeh, Ankit N. Khambhati, Maansi Desai, Deanna L. Wallace, Alia Shafi, Heather E. Dawes, Virginia E. Sturm, & Edward F. Chang (2022).
Abstract: The neurological basis of affective behaviours in everyday life is not well understood. We obtained continuous intracranial electroencephalography recordings from the human mesolimbic network in 11 participants with epilepsy and hand-annotated spontaneous behaviours from 116 h of multiday video recordings. In individual participants, binary random forest models decoded affective behaviours from neutral behaviours with up to 93% accuracy. Both positive and negative affective behaviours were associated with increased high-frequency and decreased low-frequency activity across the mesolimbic network. The insula, amygdala, hippocampus and anterior cingulate cortex made stronger contributions to affective behaviours than the orbitofrontal cortex, but the insula and anterior cingulate cortex were most critical for differentiating behaviours with observable affect from those without. In a subset of participants (N = 3), multiclass decoders distinguished amongst the positive, negative and neutral behaviours. These results suggest that spectro-spatial features of brain activity in the mesolimbic network are associated with affective behaviours of everyday life.
https://doi.org/10.1038/s41562-022-01310-0 -
Left hemisphere dominance for bilateral kinematic encoding in the human brain. Elife.
Christina M. Merrick, Tanner C. Dixon, Assaf Breska, Jack Lin, Edward F. Chang, David King-Stephens, Kenneth D. Laxer, Peter B. Weber, Jose Carmena, Robert Thomas Knight, & Richard B. Ivry (2022).
Abstract: Neurophysiological studies in humans and nonhuman primates have revealed movement representations in both the contralateral and ipsilateral hemispheres. Inspired by clinical observations, we ask if this bilateral representation differs for the left and right hemispheres. Electrocorticography was recorded in human participants during an instructed-delay reaching task, with movements produced with either the contralateral or ipsilateral arm. Using a cross-validated kinematic encoding model, we found stronger bilateral encoding in the left hemisphere, an effect that was present during preparation and was amplified during execution. Consistent with this asymmetry, we also observed better across-arm generalization in the left hemisphere, indicating similar neural representations for right and left arm movements. Notably, these left hemisphere electrodes were centered over premotor and parietal regions. The more extensive bilateral encoding in the left hemisphere adds a new perspective to the pervasive neuropsychological finding that the left hemisphere plays a dominant role in praxis.
https://doi.org/10.7554/eLife.69977 -
Ethical commitments, principles, and practices guiding intracranial neuroscientific research in humans. Neuron.
Ashley Feinsinger, Nader Pouratian, Hamasa Ebadi, Ralph Adolphs, Richard Andersen, Michael S. Beauchamp, Edward F. Chang, Nathan E. Crone, Jennifer L. Collinger, Itzhak Fried, Adam Mamelak, Mark Richardson, Ueli Rutishauser, Sameer A. Sheth, Nanthia Suthana, Nitin Tandon, Daniel Yoshor, on behalf of the NIH Research Opportunities in Humans Consortium (2022).
Abstract: Intracranial electrical recordings and stimulation of neurosurgical patients have been central to the advancement of human neuroscience. The use of these methods has rapidly expanded over the last decade due to theoretical and technical advances, as well as the growing number of neurosurgical patients undergoing functional procedures for indications such as epilepsy, tumor resection, and movement disorders. These methods pose the potential for ethical conflict, as they involve basic neuroscientific research utilizing invasive procedures in human patients undergoing treatment for neurological illnesses. This review addresses technical aspects, clinical contexts, and issues of ethical concern, utilizing a framework that is informed by, but also departs from, existing bioethical literature on matters in clinical research. We conclude with proposals for improving informed consent processes to address potential problems specific to intracranial electrophysiology research, a general schema for scrutinizing research-related risk associated with different methods, and a call for the development of consensus to ensure continuing scientific progress alongside crucial patient protections in this promising area of human neuroscience.
https://doi.org/10.1016/j.neuron.2021.11.011 -
Compartmentalized dynamics within a common multi-area mesoscale manifold represent a repertoire of human hand movements. Neuron.
Nikhilesh Natraj, Daniel B. Silversmith, Edward F. Chang, & Karunesh Ganguly (2022).
Abstract: The human hand is unique in the animal kingdom for unparalleled dexterity, ranging from complex prehension to fine finger individuation. How does the brain represent such a diverse repertoire of movements? We evaluated mesoscale neural dynamics across the human "grasp network," using electrocorticography and dimensionality reduction methods, for a repertoire of hand movements. Strikingly, we found that the grasp network represented both finger and grasping movements alike. Specifically, the manifold characterizing the multi-areal neural covariance structure was preserved during all movements across this distributed network. In contrast, latent neural dynamics within this manifold were surprisingly specific to movement type. Aligning latent activity to kinematics further uncovered distinct submanifolds despite similarities in synergistic coupling of joints between movements. We thus find that despite preserved neural covariance at the distributed network level, mesoscale dynamics are compartmentalized into movement-specific submanifolds; this mesoscale organization may allow flexible switching between a repertoire of hand movements.
https://doi.org/10.1016/j.neuron.2021.10.002
2021
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Functional alterations in cortical processing of speech in glioma-infiltrated cortex. PNAS.
Alexander A. Aabedi, Benjamin Lipkin, Jasleen Kaur, Sofia Kakaizada, Claudia Valdivia, Sheantel Reihl, Jacob S. Young, Anthony T. Lee, Saritha Krishna, Mitchel S. Berger, Edward F. Chang, David Brang, & Shawn L. Hervey-Jumper (2021).
Abstract: As gliomas proliferate, they infiltrate healthy brain tissue. Often, patients with such tumors in the language areas of the brain develop aphasia. Understanding how gliomas interact with normal neural circuits is critical for developing neuroprostheses that restore speech. Recent evidence demonstrates that glioma cells interact synaptically with neurons and thus can modulate neural circuits. However, it is unclear the extent to which glioma-infiltrated cortex participates in cognitive processing. Using electrocorticography to record both glioma-infiltrated and normal-appearing cortex during speech, we found that glioma-infiltrated cortex is capable of coordinated neural responses but has reduced capacity for information encoding. Instead, glioma-infiltrated cortex recruits a broader network of cortical regions during speech, which may represent a compensatory mechanism with implications for future neuroprostheses.
https://doi.org/10.1073/pnas.2108959118 -
Speech Computations of the Human Superior Temporal Gyrus. Annual Review of Psychology.
Ilina Bhaya-Grossman, & Edward F. Chang (2021).
Abstract: Human speech perception results from neural computations that transform external acoustic speech signals into internal representations of words. The superior temporal gyrus (STG) contains the nonprimary auditory cortex and is a critical locus for phonological processing. Here, we describe how speech sound representation in the STG relies on fundamentally nonlinear and dynamical processes, such as categorization, normalization, contextual restoration, and the extraction of temporal structure. A spatial mosaic of local cortical sites on the STG exhibits complex auditory encoding for distinct acoustic-phonetic and prosodic features. We propose that as a population ensemble, these distributed patterns of neural activity give rise to abstract, higher-order phonemic and syllabic representations that support speech perception. This review presents a multi-scale, recurrent model of phonological processing in the STG, highlighting the critical interface between auditory and language systems.
https://doi.org/10.1146/annurev-psych-022321-035256 -
Learning nonnative speech sounds changes local encoding in the adult human cortex. PNAS.
Han G. Yi, Bharath Chandrasekaran, Kirill V. Nourski, Ariane E. Rhone, William L. Schuerman, Matthew A. Howard III, Edward F. Chang, & Matthew K. Leonard (2021).
Abstract: Speech sound learning in adulthood is a highly dynamic process. Here, we used direct neurophysiology of the human brain to examine learning-associated changes in neural activity with unprecedented spatiotemporal detail. While native English listeners were trained to identify unfamiliar pitch patterns in Mandarin, local neural populations throughout the cortex showed a diverse set of encoding properties for Mandarin sounds that tracked behavioral performance. While previous neuroimaging studies have focused on highlighting general differences across broad cortical regions, we demonstrate that these functionally heterogeneous populations are spatially interspersed with one another. These findings provide insight into how the human brain strikes a balance between stability and plasticity during learning in adulthood.
https://doi.org/10.1073/pnas.2101777118 -
Parallel and distributed encoding of speech across human auditory cortex. Cell.
Liberty S. Hamilton, Yulia Oganian, Jeffery Hall, & Edward F. Chang (2021).
Abstract: Speech perception is thought to rely on a cortical feedforward serial transformation of acoustic into linguistic representations. Using intracranial recordings across the entire human auditory cortex, electrocortical stimulation, and surgical ablation, we show that cortical processing across areas is not consistent with a serial hierarchical organization. Instead, response latency and receptive field analyses demonstrate parallel and distinct information processing in the primary and nonprimary auditory cortices. This functional dissociation was also observed where stimulation of the primary auditory cortex evokes auditory hallucination but does not distort or interfere with speech perception. Opposite effects were observed during stimulation of nonprimary cortex in superior temporal gyrus. Ablation of the primary auditory cortex does not affect speech perception. These results establish a distributed functional organization of parallel information processing throughout the human auditory cortex and demonstrate an essential independent role for nonprimary auditory cortex in speech processing.
https://doi.org/10.1016/j.cell.2021.07.019 -
Neuroprosthesis for Decoding Speech in a Paralyzed Person with Anarthria. New England Journal of Medicine.
David A. Moses*, Sean L. Metzger*, Jessie R. Liu*, Gopala K. Anumanchipalli, Joseph G. Makin, Pengfei F. Sun, Josh Chartier, Maximilian E. Dougherty, Patricia M. Liu, Gary M. Abrams, Adelyn Tu-Chan, Karunesh Ganguly, & Edward F. Chang (*Equally contributing authors) (2021).
Abstract: Technology to restore the ability to communicate in paralyzed persons who cannot speak has the potential to improve autonomy and quality of life. An approach that decodes words and sentences directly from the cerebral cortical activity of such patients may represent an advancement over existing methods for assisted communication. We implanted a subdural, high-density, multielectrode array over the area of the sensorimotor cortex that controls speech in a person with anarthria (the loss of the ability to articulate speech) and spastic quadriparesis caused by a brain-stem stroke. Over the course of 48 sessions, we recorded 22 hours of cortical activity while the participant attempted to say individual words from a vocabulary set of 50 words. We used deep-learning algorithms to create computational models for the detection and classification of words from patterns in the recorded cortical activity. We applied these computational models, as well as a natural-language model that yielded next-word probabilities given the preceding words in a sequence, to decode full sentences as the participant attempted to say them. We decoded sentences from the participant’s cortical activity in real time at a median rate of 15.2 words per minute, with a median word error rate of 25.6%. In post hoc analyses, we detected 98% of the attempts by the participant to produce individual words, and we classified words with 47.1% accuracy using cortical signals that were stable throughout the 81-week study period. In a person with anarthria and spastic quadriparesis caused by a brain-stem stroke, words and sentences were decoded directly from cortical activity during attempted speech with the use of deep-learning models and a natural-language model. (Funded by Facebook and others; ClinicalTrials.gov number, NCT03698149.)
https://doi.org/10.1056/NEJMoa2027540 -
Human cortical encoding of pitch in tonal and non-tonal languages. Nature Communications.
Yuanning Li, Claire Tang, Junfeng Lu, Jinsong Wu, & Edward F. Chang (2021).
Abstract: Languages can use a common repertoire of vocal sounds to signify distinct meanings. In tonal languages, such as Mandarin Chinese, pitch contours of syllables distinguish one word from another, whereas in non-tonal languages, such as English, pitch is used to convey intonation. The neural computations underlying language specialization in speech perception are unknown. Here, we use a cross-linguistic approach to address this. Native Mandarin- and English- speaking participants each listened to both Mandarin and English speech, while neural activity was directly recorded from the non-primary auditory cortex. Both groups show language-general coding of speaker-invariant pitch at the single electrode level. At the electrode population level, we find language-specific distribution of cortical tuning parameters in Mandarin speakers only, with enhanced sensitivity to Mandarin tone categories. Our results show that speech perception relies upon a shared cortical auditory feature processing mechanism, which may be tuned to the statistics of a given language.
https://doi.org/10.1038/s41467-021-21430-x -
Distributed Subnetworks of Depression Defined by Direct Intracranial Neurophysiology. Frontiers in Human Neuroscience
Scangos, K.W., Khambhati, A.N., Daly, P.M., Owen, L.W., Manning, J.R., Ambrose, J.B., Austin, E., Dawes, H.E., Krystal, A.D. & Chang, E.F., (2021).
Abstract: Major depressive disorder is a common and disabling disorder with high rates of treatment resistance. Evidence suggests it is characterized by distributed network dysfunction that may be variable across patients, challenging the identification of quantitative biological substrates. We carried out this study to determine whether application of a novel computational approach to a large sample of high spatiotemporal resolution direct neural recordings in humans could unlock the functional organization and coordinated activity patterns of depression networks. This group level analysis of depression networks from heterogenous intracranial recordings was possible due to application of a correlational model-based method for inferring whole-brain neural activity. We then applied a network framework to discover brain dynamics across this model that could classify depression. We found a highly distributed pattern of neural activity and connectivity across cortical and subcortical structures that was present in the majority of depressed subjects. Furthermore, we found that this depression signature consisted of two subnetworks across individuals. The first was characterized by left temporal lobe hypoconnectivity and pathological beta activity. The second was characterized by a hypoactive, but hyperconnected left frontal cortex. These findings have applications toward personalization of therapy.
https://doi.org/10.3389/fnhum.2021.746499 -
Prefrontal physiomarkers of anxiety and depression in Parkinson’s disease. Frontiers in Neuroscience.
de Hemptinne, C., Chen, W., Racine, C.A., Seritan, A.L., Miller, A.M., Yaroshinsky, M.S., Wang, S.S., Gilron, R., Little, S., Bledsoe, I. & San Luciano, M., (2021).
Abstract:
https://doi.org/10.3389/fnins.2021.748165 -
Closed-loop neuromodulation in an individual with treatment-resistant depression . Nature Medicine.
Scangos K.W., Khambhati A.N., Daly P.M., Makhoul G.S., Sugrue L.P., Zamanian H., Liu T.X., Rao V.R., Sellers K.K., Dawes H.E., Starr P.A, Krystal A.D., & Chang E.F. (2021).
Abstract: Deep brain stimulation is a promising treatment for neuropsychiatric conditions such as major depression. It could be optimized by identifying neural biomarkers that trigger therapy selectively when symptom severity is elevated. We developed an approach that first used multi-day intracranial electrophysiology and focal electrical stimulation to identify a personalized symptom-specific biomarker and a treatment location where stimulation improved symptoms. We then implanted a chronic deep brain sensing and stimulation device and implemented a biomarker-driven closed-loop therapy in an individual with depression. Closed-loop therapy resulted in a rapid and sustained improvement in depression. Future work is required to determine if the results and approach of this n-of-1 study generalize to a broader population
https://doi.org/10.1038/s41591-021-01480-w -
Distributed Subnetworks of Depression Defined by Direct Intracranial Neurophysiology . Frontiers in Human Neuroscience.
Scangos K.W., Khambhati A.N., Daly P.M., Owen L.W., Manning J.R., Ambrose J.B., Austin E., Dawes H.E., Krystal A.D., & Chang E.F. (2021).
Abstract: Major depressive disorder is a common and disabling disorder with high rates of treatment resistance. Evidence suggests it is characterized by distributed network dysfunction that may be variable across patients, challenging the identification of quantitative biological substrates. We carried out this study to determine whether application of a novel computational approach to a large sample of high spatiotemporal resolution direct neural recordings in humans could unlock the functional organization and coordinated activity patterns of depression networks. This group level analysis of depression networks from heterogenous intracranial recordings was possible due to application of a correlational model-based method for inferring whole-brain neural activity. We then applied a network framework to discover brain dynamics across this model that could classify depression. We found a highly distributed pattern of neural activity and connectivity across cortical and subcortical structures that was present in the majority of depressed subjects. Furthermore, we found that this depression signature consisted of two subnetworks across individuals. The first was characterized by left temporal lobe hypoconnectivity and pathological beta activity. The second was characterized by a hypoactive, but hyperconnected left frontal cortex. These findings have applications toward personalization of therapy.
https://doi.org/10.3389/fnhum.2021.746499 -
State-dependent responses to intracranial brain stimulation in a patient with depression . Nature Medicine.
Scangos K.W., Makhoul G.S., Sugrue L.P., Chang E.F., & Krystal A.D. (2021).
Abstract: Deep brain stimulation is a promising treatment for severe depression, but lack of efficacy in randomized trials raises questions regarding anatomical targeting. We implanted multi-site intracranial electrodes in a severely depressed patient and systematically assessed the acute response to focal electrical neuromodulation. We found an elaborate repertoire of distinctive emotional responses that were rapid in onset, reproducible, and context and state dependent. Results provide proof of concept for personalized, circuit-specific medicine in psychiatry.
https://doi.org/10.1038/s41591-020-01175-8 -
Corticocortical Evoked Potentials and Patient Response Reveal Networks Underlying Depression. Biological Psychiatry.
Scangos K.W., Makhoul G.S., Khambhati A.N., Sellers K.K., Chang E.F., & Krystal A.D. (2021).
Abstract: Altered connectivity across brain networks in major depression (MDD) and its relationship to clinical symptoms are poorly understood. In a first-of-kind study, proof-of-concept study, we directly stimulated 10 brain regions and recorded evoked responses (EPs) to assess connectivity and characterize large-scale network dysfunction in a patient with MDD.
https://doi.org/10.1016/j.biopsych.2020.02.416
2020
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Low-frequency neural tracking of speech envelope reflects evoked responses to acoustic edges. bioRxiv.
Katsuaki Kojima, Yulia Oganian, Chang Cai, Anne Findlay, Edward F. Chang, & Srikantan Nagarajan (2020).
Abstract: The amplitude envelope of speech is crucial for accurate comprehension. Considered a key stage in speech processing, the phase of neural activity in the theta-delta bands (1 - 10 Hz) tracks the phase of the speech amplitude envelope during listening. However, the mechanisms underlying this envelope representation have been heavily debated. A dominant model posits that envelope tracking reflects entrainment of endogenous low-frequency oscillations to the speech envelope. Alternatively, envelope tracking reflects a series of evoked responses to acoustic landmarks within the envelope. It has proven challenging to distinguish these two mechanisms. To address this, we recorded magnetoencephalography while participants listened to natural speech, and compared the neural phase patterns to the predictions of two computational models: An oscillatory entrainment model and a model of evoked responses to peaks in the rate of envelope change. Critically, we also presented speech at slowed rates, where the spectrotemporal predictions of the two models diverge. Our analyses revealed transient theta phase-locking in regular speech, as predicted by both models. However, for slow speech we found transient theta and delta phase-locking, a pattern that was fully compatible with the evoked response model but could not be explained by the oscillatory entrainment model. Furthermore, encoding of acoustic edge magnitudes was invariant to contextual speech rate, demonstrating speech rate normalization of acoustic edge representations. Taken together, our results suggest that neural phase locking to the speech envelope is more likely to reflect discrete representation of transient information rather than oscillatory entrainment.
https://doi.org/10.1101/2020.04.02.022616 -
Brain2Char: a deep architecture for decoding text from brain recordings. Journal of Neural Engineering.
Pengfei Sun, Gopala Anumanchipalli, & Edward F. Chang (2020).
Abstract:
https://doi.org/10.1088/1741-2552/abc742 -
Topography of speech-related acoustic and phonological feature encoding throughout the human core and parabelt auditory cortex. bioRxiv.
Liberty S. Hamilton, Yulia Oganian, & Edward F. Chang (2020).
Abstract: Speech perception involves the extraction of acoustic and phonological features from the speech signal. How those features map out across the human auditory cortex is unknown. Complementary to noninvasive imaging, the high spatial and temporal resolution of intracranial recordings has greatly contributed to recent advances in our understanding. However, these approaches are typically limited by piecemeal sampling of the expansive human temporal lobe auditory cortex. Here, we present a functional characterization of local cortical encoding throughout all major regions of the primary and non-primary human auditory cortex. We overcame previous limitations by using rare direct recordings from the surface of the temporal plane after surgical microdissection of the deep Sylvian fissure between the frontal and temporal lobes. We recorded neural responses using simultaneous high-density direct recordings over the left temporal plane and the lateral superior temporal gyrus, while participants listened to natural speech sentences and pure tone stimuli. We found an anatomical separation of simple spectral feature tuning, including tuning for pure tones and absolute pitch, on the superior surface of the temporal plane, and complex tuning for phonological features, relative pitch and speech amplitude modulations on lateral STG. Broadband onset responses are unique to posterior STG and not found elsewhere in auditory cortices. This onset region is functionally distinct from the rest of STG, with latencies similar to primary auditory areas. These findings reveal a new, detailed functional organization of response selectivity to acoustic and phonological features in speech throughout the human auditory cortex.
https://doi.org/10.1101/2020.06.08.121624 -
Cortical Encoding of Manual Articulatory and Linguistic Features in American Sign Language . Current Biology.
Matthew K. Leonard, Ben Lucas, Shane Blau, David P. Corina, & Edward F. Chang (2020).
Abstract: This report contains a linguistic description of a language created spontaneously without any apparent external influence in a stable existing community. We describe the syntactic structure of Al-Sayyid Bedouin Sign Language, a language that has arisen in the last 70 years in an isolated endogamous community with a high incidence of nonsyndromic, genetically recessive, profound prelingual neurosensory deafness. In the space of one generation from its inception, systematic grammatical structure has emerged in the language. Going beyond a conventionalized list of words for actions, objects, people, characteristics, and so on, a systematic way of marking the grammatical relations among those elements has appeared in the form of highly regular word order. These systematic structures cannot be attributed to influence from other languages, because the particular word orders that appear in Al-Sayyid Bedouin Sign Language differ from those found both in the ambient spoken languages in the community and in the other sign language found predominantly in the surrounding area. Therefore, the emerging grammatical structures should be regarded as an independent development within the language.
https://doi.org/10.1016/j.cub.2020.08.048 -
Transformation of a temporal speech cue to a spatial neural code in human auditory cortex . eLife.
Neal P. Fox, Matthew K. Leonard, Matthias J. Sjerps, & Edward F. Chang (2020).
Abstract: In speech, listeners extract continuously-varying spectrotemporal cues from the acoustic signal to perceive discrete phonetic categories. Spectral cues are spatially encoded in the amplitude of responses in phonetically-tuned neural populations in auditory cortex. It remains unknown whether similar neurophysiological mechanisms encode temporal cues like voice-onset time (VOT), which distinguishes sounds like /
https://doi.org/10.7554/eLife.53051 -
Machine translation of cortical activity to text with an encoder–decoder framework . Nature Neuroscience.
Joseph G. Makin, David A. Moses, & Edward F. Chang (2020).
Abstract: A decade after speech was first decoded from human brain signals, accuracy and speed remain far below that of natural speech. Here we show how to decode the electrocorticogram with high accuracy and at natural-speech rates. Taking a cue from recent advances in machine translation, we train a recurrent neural network to encode each sentence-length sequence of neural activity into an abstract representation, and then to decode this representation, word by word, into an English sentence. For each participant, data consist of several spoken repeats of a set of 30-50 sentences, along with the contemporaneous signals from ~250 electrodes distributed over peri-Sylvian cortices. Average word error rates across a held-out repeat set are as low as 3%. Finally, we show how decoding with limited data can be improved with transfer learning, by training certain layers of the network under multiple participants' data.
https://doi.org/10.1038/s41593-020-0608-8
2019
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A speech envelope landmark for syllable encoding in human superior temporal gyrus . Science Advances.
Yulia Oganian & Edward F. Chang (2019).
Abstract: Scientists find how syllable timing and stress are represented in human speech cortex.
https://doi.org/10.1126/sciadv.aay6279 -
Real-time decoding of question-and-answer speech dialogue using human cortical activity . Nature Communications.
David A. Moses, Matthew K. Leonard, Joseph G. Makin, & Edward F. Chang (2019).
Abstract: Natural communication often occurs in dialogue, differentially engaging auditory and sensorimotor brain regions during listening and speaking. However, previous attempts to decode speech directly from the human brain typically consider listening or speaking tasks in isolation. Here, human participants listened to questions and responded aloud with answers while we used high-density electrocorticography (ECoG) recordings to detect when they heard or said an utterance and to then decode the utterance’s identity. Because certain answers were only plausible responses to certain questions, we could dynamically update the prior probabilities of each answer using the decoded question likelihoods as context. We decode produced and perceived utterances with accuracy rates as high as 61% and 76%, respectively (chance is 7% and 20%). Contextual integration of decoded question likelihoods significantly improves answer decoding. These results demonstrate real-time decoding of speech in an interactive, conversational setting, which has important implications for patients who are unable to communicate.
https://doi.org/10.1038/s41467-019-10994-4 -
The Encoding of Speech Sounds in the Superior Temporal Gyrus Neuron.
Han G. Yi*, Matthew K. Leonard*, & Edward F. Chang (*Equally contributing authors) (2019).
Abstract: Speech comprehension depends on the integrity of both the spectral content and temporal envelope of the speech signal. Although neural processing underlying spectral analysis has been intensively studied, less is known about the processing of temporal information. Most of speech information conveyed by the temporal envelope is confined to frequencies below 16 Hz, frequencies that roughly match spontaneous and evoked modulation rates of primary auditory cortex neurons. To test the importance of cortical modulation rates for speech processing, we manipulated the frequency of the temporal envelope of speech sentences and tested the effect on both speech comprehension and cortical activity. Magnetoencephalographic signals from the auditory cortices of human subjects were recorded while they were performing a speech comprehension task. The test sentences used in this task were compressed in time. Speech comprehension was degraded when sentence stimuli were presented in more rapid (more compressed) forms. We found that the average comprehension level, at each compression, correlated with (
https://doi.org/10.1016/j.neuron.2019.04.023 -
Speaker-normalized sound representations in the human auditory cortex . Nature Communications.
Matthias J. Sjerps, Neal P. Fox, Keith Johnson, & Edward F. Chang (2019).
Abstract: The acoustic dimensions that distinguish speech sounds (like the vowel differences in “boot” and “boat”) also differentiate speakers’ voices. Therefore, listeners must normalize across speakers without losing linguistic information. Past behavioral work suggests an important role for auditory contrast enhancement in normalization: preceding context affects listeners’ perception of subsequent speech sounds. Here, using intracranial electrocorticography in humans, we investigate whether and how such context effects arise in auditory cortex. Participants identified speech sounds that were preceded by phrases from two different speakers whose voices differed along the same acoustic dimension as target words (the lowest resonance of the vocal tract). In every participant, target vowels evoke a speaker-dependent neural response that is consistent with the listener’s perception, and which follows from a contrast enhancement model. Auditory cortex processing thus displays a critical feature of normalization, allowing listeners to extract meaningful content from the voices of diverse speakers.
https://doi.org/10.1038/s41467-019-10365-z -
Speech Synthesis from Neural Decoding of Spoken Sentences . Nature.
Gopala K. Anumanchipalli*, Josh Chartier*, & Edward F. Chang (2019).
Abstract: Technology that translates neural activity into speech would be transformative for people who are unable to communicate as a result of neurological impairments. Decoding speech from neural activity is challenging because speaking requires very precise and rapid multi-dimensional control of vocal tract articulators. Here we designed a neural decoder that explicitly leverages kinematic and sound representations encoded in human cortical activity to synthesize audible speech. Recurrent neural networks first decoded directly recorded cortical activity into representations of articulatory movement, and then transformed these representations into speech acoustics. In closed vocabulary tests, listeners could readily identify and transcribe speech synthesized from cortical activity. Intermediate articulatory dynamics enhanced performance even with limited data. Decoded articulatory representations were highly conserved across speakers, enabling a component of the decoder to be transferrable across participants. Furthermore, the decoder could synthesize speech when a participant silently mimed sentences. These findings advance the clinical viability of using speech neuroprosthetic technology to restore spoken communication.
https://doi.org/10.1038/s41586-019-1119-1 -
Comparison of common artifact rejection methods applied to direct cortical and peripheral stimulation in human ECoG . In 2019 9th International IEEE/EMBS Conference on Neural Engineering (NER) (pp. 77-80). IEEE.
Sellers, K.K.*, Schuerman, W.L.*, Dawes, H.E., Chang, E.F., & Leonard, M.K. (2019).
Abstract: The neural substrates of working memory are spread across prefrontal, parietal and cingulate cortices and are thought to be coordinated through low frequency cortical oscillations in the theta (3 – 8 Hz) and alpha (8 – 12 Hz) frequency bands. While the functional role of many subregions have been elucidated using neuroimaging studies, the role of superior frontal gyrus (SFG) is not yet clear. Here, we combined electrocorticography and direct cortical stimulation in three patients implanted with subdural electrodes to assess if superior frontal gyrus is indeed involved in working memory. We found left SFG exhibited task-related modulation of oscillations in the theta and alpha frequency bands specifically during the encoding epoch. Stimulation at the frequency matched to the endogenous oscillations resulted in reduced reaction times in all three participants. Our results support the causal role of SFG in working memory and suggest that SFG may coordinate working memory through low-frequency oscillations thus bolstering the feasibility of targeting oscillations for restoring cognitive function.
https://doi.org/10.1109/NER.2019.8716980 -
Pilot Study of An Intracranial Electroencephalography Biomarker of Depressive Symptoms in Epilepsy . Journal of Neuropsychiatry.
Scangos K.W., Ahmad H.S., Shafi A., Sellers K.K., Dawes H.E., Krystal A., Chang E.F. (2019).
Abstract: Adult patients with epilepsy have an increased prevalence of major depressive disorder (MDD). Intracranial EEG (iEEG) captured during extended inpatient monitoring of patients with treatment-resistant epilepsy offers a particularly promising method to study MDD networks in epilepsy. The authors used 24 hours of resting-state iEEG to examine the neural activity patterns within corticolimbic structures that reflected the presence of depressive symptoms in 13 adults with medication-refractory epilepsy. Principal component analysis was performed on the z-scored mean relative power in five standard frequency bands averaged across electrodes within a region. Principal component 3 was a statistically significant predictor of the presence of depressive symptoms (R These finding suggest, for the first time, that neural features across circuits involved in epilepsy may distinguish patients who have depressive symptoms from those who do not. Larger studies are required to validate these findings and to assess their diagnostic utility in MDD.
https://doi.org/10.1176/appi.neuropsych.19030081 -
Decoding Natural Positive Emotional Behaviors from Human Fronto-Temporal Mesolimbic Structures. In 2019 9th International IEEE/EMBS Conference on Neural Engineering (NER) (pp. 1088-1092). IEEE.
Bijanzadeh M., Desai M., Wallace D.L., Mummaneni N., Kunwar N., Dawes H.E., Chang E.F. (2019).
Abstract: Understanding the correlation between neural features and symptoms of mood disorders, such as depression, could provide objective measurements for diagnosis and facilitate clinical treatments. In this paper, we study the correlation of neural features with positive naturalistic emotional displays, e.g., smiling, in human subjects in a normal setup, without presenting any experimental stimuli to the subjects. We employed a data driven approach and utilized Random Forest classifiers to decode positive emotional displays from brain activity. Our results on all of our eight subjects show that neural features from mesolimbic circuits including cingulate, hippocampus, insula, amygdala and orbitofrontal cortex (OFC) can be used for decoding emotions (mean area under the ROC curve = 0.86 +- 0.04). The most important features based on the Random Forest models were mainly clustered in the gamma frequency band (30-100Hz) and low frequencies, with majority of them in theta band (4-8 Hz). These features were distributed across the limbic network, specific to each individual. Remarkably, the gamma cluster was selective to the positive emotions while the low frequency cluster showed selectivity to the neutral state. These results demonstrate that non-task-based emotions can be decoded from brain neuronal activity, and, may inform biomarker identification for objective symptom assessment in the treatment of severe mood disorders.
https://doi.org/10.1109/NER.2019.8716887
2018
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Inhibition of Manual Movements at Speech Arrest Sites in the Posterior Inferior Frontal Lobe . Neurosurgery.
Breshears, D. Jonathan, Southwell, G., Derek, Chang, E.F. (2018).
Abstract: Intraoperative stimulation of the posterior inferior frontal lobe (IFL) induces speech arrest, which is often interpreted as demonstration of essential language function. However, prior reports have described “negative motor areas” in the IFL, sites where stimulation halts ongoing limb motor activity.
https://doi.org/10.1093/neuros/nyy592 -
The Control of Vocal Pitch in Human Laryngeal Motor Cortex . Cell. 174, 21-31.
Dichter, B.K., Breshears, J.D., Leonard, M.K., & Chang, E.F. (2018).
Abstract: Although past research has provided evidence of a genetic component to the transmission of susceptibility to stuttering, the relationship between the genetic component to stuttering and persistence and recovery in the disorder has remained unclear. In an attempt to characterize this relationship, the immediate and extended families of 66 stuttering children were investigated to determine frequencies of cases of persistent and recovered stuttering. Pedigree analysis and segregation analysis were used to examine patterns of transmission. The following questions were investigated:
https://doi.org/10.1016/j.cell.2018.05.016 -
Encoding of articulatory kinematic trajectories in human speech sensorimotor cortex Neuron.
Chartier, J.*, Anumanchipalli, G.K.*, Johnson, K., & Chang, E.F. (*Equally contributing authors) (2018).
Abstract: The contribution of ascending afferents to the control of speech movement was evaluated by applying unanticipated loads to the lower lip during the generation of combined upper lip-lower lip speech gestures. To eliminate potential contamination due to anticipation or adaptation, loads were applied randomly on only 10-15% of the trials. Physical characteristics of the perturbations were within the normal range of forces and movements involved in natural lip actions for speech. Compensatory responses in multiple facial muscles and lip movements were observed the first time a load was introduced, and achievement of the multimovement speech goals was never disrupted by these perturbations. Muscle responses were seen in the lower lip muscles, implicating corrective, feedback processes. Additionally, compensatory responses to these lower lip loads were also observed in the independently controlled muscles of the upper lip, reflecting the parallel operation of open-loop, sensorimotor mechanisms. Compensatory responses from both the upper and lower lip muscles were observed with small (1 mm) as well as large (15 mm) perturbations. The latencies of these compensatory responses were not discernible by conventional ensemble averaging. Moreover, responses at latencies of lower brain stem-mediated reflexes (i.e., 10-18 ms) were not apparent with inspection of individual records. Response latencies were determined on individual loaded trials through the use of a computer algorithm that took into account the variability of electromyograms (EMG) among the control trials. These latency measures confirmed the absence of brain stem-mediated responses and yielded response latencies that ranged from 22 to 75 ms. Response latencies appeared to be influenced by the time relation between load onset and the initiation of muscle activation. Examination of muscle activity changes for individual loaded trials revealed complementary variations in the magnitude of responses among multiple muscles contributing to a movement compensation. These observations may have implications for limb movement control if multimovement speech gestures are considered analogous to a limb action requiring coordinated movements around multiple joints. In this context, these speech motor control data might be interpreted to suggest that for complex movements, both corrective feedback and open-loop predictive processes are operating, with the latter involved in the control of coordination among multiple movement subcomponents.
https://doi.org/10.1016/j.neuron.2018.04.031 -
A spatial map of onset and sustained responses to speech in the human superior temporal gyrus Current Biology.
Hamilton, L.S.*, Edwards, E.*, & Chang, E.F. (*Equally contributing authors) (2018).
Abstract: To derive meaning from speech, we must extract multiple dimensions of concurrent information from incoming speech signals. That is, equally important to processing phonetic features is the detection of acoustic cues that give structure and context to the information we hear. How the brain organizes this information is unknown. Using data-driven computational methods on high-density intracranial recordings from 27 human participants, we reveal the functional distinction of neural responses to speech in the posterior superior temporal gyrus according to either onset or sustained response profiles. Though similar response types have been observed throughout the auditory system, we found novel evidence for a major spatial parcellation in which a distinct caudal zone detects acoustic onsets and a rostral-surround zone shows sustained, relatively delayed responses to ongoing speech stimuli. While posterior onset and anterior sustained responses are used substantially during natural speech perception, they are not limited to speech stimuli and are seen even for reversed or spectrally rotated speech. Single-electrode encoding of phonetic features in each zone depended upon whether the sound occurred at sentence onset, suggesting joint encoding of phonetic features and their temporal context. Onset responses in the caudal zone could accurately decode sentence and phrase onset boundaries, providing a potentially important internal mechanism for detecting temporal landmarks in speech and other natural sounds. These findings suggest that onset and sustained responses not only define the basic spatial organization of high-order auditory cortex but also have direct implications for how speech information is parsed in the cortex. VIDEO ABSTRACT.
https://doi.org/10.1016/j.cub.2018.04.033 -
Direct cortical stimulation of inferior frontal cortex disrupts both speech and music production in highly trained musicians . Cognitive Neuropsychology.
Leonard, M.K., Desai, M., Hungate, D., Cai, R., Singhal, N.S., Knowlton, R.C., & Chang, E.F. (2018).
Abstract: Music and speech are human-specific behaviours that share numerous properties, including the fine motor skills required to produce them. Given these similarities, previous work has suggested that music and speech may at least partially share neural substrates. To date, much of this work has focused on perception, and has not investigated the neural basis of production, particularly in trained musicians. Here, we report two rare cases of musicians undergoing neurosurgical procedures, where it was possible to directly stimulate the left hemisphere cortex during speech and piano/guitar music production tasks. We found that stimulation to left inferior frontal cortex, including pars opercularis and ventral pre-central gyrus, caused slowing and arrest for both speech and music, and note sequence errors for music. Stimulation to posterior superior temporal cortex only caused production errors during speech. These results demonstrate partially dissociable networks underlying speech and music production, with a shared substrate in frontal regions.
https://doi.org/10.1080/02643294.2018.1472559 -
Real-time classification of auditory sentences using evoked cortical activity in humans. Journal of Neural Engineering.
Moses, D.A., Leonard, M.K., & Chang, E.F. (2018).
Abstract: Neurons are often assumed to operate in a highly unreliable manner: a neuron can signal the same stimulus with a variable number of action potentials. However, much of the experimental evidence supporting this view was obtained in the visual cortex. We have, therefore, assessed trial-to-trial variability in the auditory cortex of the rat. To ensure single-unit isolation, we used cell-attached recording. Tone-evoked responses were usually transient, often consisting of, on average, only a single spike per stimulus. Surprisingly, the majority of responses were not just transient, but were also binary, consisting of 0 or 1 action potentials, but not more, in response to each stimulus; several dramatic examples consisted of exactly one spike on 100% of trials, with no trial-to-trial variability in spike count. The variability of such binary responses differs from comparably transient responses recorded in visual cortical areas such as area MT, and represent the lowest trial-to-trial variability mathematically possible for responses of a given firing rate. Our study thus establishes for the first time that transient responses in auditory cortex can be described as a binary process, rather than as a highly variable Poisson process. These results demonstrate that cortical architecture can support a more precise control of spike number than was previously recognized, and they suggest a re-evaluation of models of cortical processing that assume noisiness to be an inevitable feature of cortical codes.
https://doi.org/10.1088/1741-2552/aaab6f -
Direct electrical stimulation of human cortex evokes high gamma activity that predicts conscious somatosensory perception. Journal of Neural Engineering.
Muller, L., Rolston, J.D., Fox, N.P., Knowlton, R., Rao, V.R., & Chang, E.F. (2018).
Abstract: Direct electrical stimulation (DES) is a clinical gold standard for human brain mapping and readily evokes conscious percepts, yet the neurophysiological changes underlying these percepts are not well understood. To determine the neural correlates of DES, we stimulated the somatosensory cortex of ten human participants at frequency-amplitude combinations that both elicited and failed to elicit conscious percepts, meanwhile recording neural activity directly surrounding the stimulation site. We then compared the neural activity of perceived trials to that of non-perceived trials. We found that stimulation evokes distributed high gamma activity, which correlates with conscious perception better than stimulation parameters themselves. Our findings suggest that high gamma activity is a reliable biomarker for perception evoked by both natural and electrical stimuli.
https://doi.org/10.1088/1741-2552/aa9bf9 -
Human sensorimotor cortex control of directly-measured vocal tract movements during vowel production. Journal of Neuroscience.
Conant, D.F., Bouchard, K.E., Leonard, M.K., & Chang, E.F. (2018).
Abstract: During speech production, we make vocal tract movements with remarkable precision and speed. Our understanding of how the human brain achieves such proficient control is limited, in part due to the challenge of simultaneously acquiring high-resolution neural recordings and detailed vocal tract measurements. To overcome this challenge, we combined ultrasound and video monitoring of the supralaryngeal articulators (lips, jaw, and tongue) with electrocorticographic recordings from the cortical surface of 4 subjects (3 female, 1 male) to investigate how neural activity in the ventral sensory-motor cortex (vSMC) relates to measured articulator movement kinematics (position, speed, velocity, acceleration) during the production of English vowels. We found that high-gamma activity at many individual vSMC electrodes strongly encoded the kinematics of one or more articulators, but less so for vowel formants and vowel identity. Neural population decoding methods further revealed the structure of kinematic features that distinguish vowels. Encoding of articulator kinematics was sparsely distributed across time and primarily occurred during the time of vowel onset and offset. In contrast, encoding was low during the steady-state portion of the vowel, despite sustained neural activity at some electrodes. Significant representations were found for all kinematic parameters, but speed was the most robust. These findings enabled by direct vocal tract monitoring demonstrate novel insights into the representation of articulatory kinematic parameters encoded in the vSMC during speech production.
https://doi.org/10.1523/JNEUROSCI.2382-17.2018 -
Neural correlates of sine-wave speech intelligibility in human frontal and temporal cortex. Brain and Language.
Khoshkhoo S.*, Leonard, M.K.*, Mesgarani, N., & Chang, E.F. (*Equally contributing authors) (2018).
Abstract: A database of speech samples from eight different talkers has been collected for use in multitalker communications research. Descriptions of the nature of the corpus, the data collection methodology, and the means for obtaining copies of the database are presented.
https://doi.org/10.1016/j.bandl.2018.01.007 -
Selective Interference with Syntactic Encoding during Sentence Production by Direct Electrocortical Stimulation of the Inferior Frontal gyrus. Journal of Cognitive Neuroscience.
Chang, E.F., Kurteff, G., & Wilson, S.M. (2018).
Abstract: Cortical stimulation mapping (CSM) has provided important insights into the neuroanatomy of language because of its high spatial and temporal resolution, and the causal relationships that can be inferred from transient disruption of specific functions. Almost all CSM studies to date have focused on word-level processes such as naming, comprehension, and repetition. In this study, we used CSM to identify sites where stimulation interfered selectively with syntactic encoding during sentence production. Fourteen patients undergoing left-hemisphere neurosurgery participated in the study. In 7 of the 14 patients, we identified nine sites where cortical stimulation interfered with syntactic encoding but did not interfere with single word processing. All nine sites were localized to the inferior frontal gyrus, mostly to the pars triangularis and opercularis. Interference with syntactic encoding took several different forms, including misassignment of arguments to grammatical roles, misassignment of nouns to verb slots, omission of function words and inflectional morphology, and various paragrammatic constructions. Our findings suggest that the left inferior frontal gyrus plays an important role in the encoding of syntactic structure during sentence production.
https://doi.org/10.1162/jocn_a_01215 -
Direct Electrical Stimulation of Lateral Orbitofrontal Cortex Acutely Improves Mood in Individuals with Symptoms of Depression . Current Biology.
Rao V.R., Sellers K.K., Wallace D.L., Lee M.B., Bijanzadeh M., Sani O.G., Yang Y., Shanechi M.M., Dawes H.E., Chang E.F. (2018).
Abstract: Despite considerable interest, there is no consensus regarding the prevalence of depression in later life.
https://doi.org/10.1016/j.cub.2018.10.026 -
Mood Variations Decoded from Multi-Site Intracranial Human Brain Activity . Nature Biotechnology.
Omid G Sani, Yuxiao Yang, Morgan B. Lee, Heather E Dawes, Edward F. Chang. (2018).
Abstract: The ability to decode mood state over time from neural activity could enable closed-loop systems to treat neuropsychiatric disorders. However, this decoding has not been demonstrated, partly owing to the difficulty of modeling distributed mood-relevant neural dynamics while dealing with the sparsity of mood state measurements. Here we develop a modeling framework to decode mood state variations from multi-site intracranial recordings in seven human subjects with epilepsy who self-reported their mood state intermittently over multiple days. We built dynamic neural encoding models of mood state and corresponding decoders for each individual and demonstrated that mood state variations over time can be decoded from neural activity. Across subjects, the decoders largely recruited neural signals from limbic regions, whose spectro-spatial features were tuned to mood variations. The dynamic models also provided an analytical tool to compute the timescales of the decoded mood state. These results provide an initial line of evidence indicating the feasibility of mood state decoding.
https://doi.org/10.1038/nbt.4200 -
An Amygdala-Hippocampus Subnetwork that Encodes Variation in Human Mood . Cell.
Lowry A. Kirby, Francisco J. Luongo, Morgan B. Lee, More Nahum, Thomas M. Van Vleet, Vikram R. Rao, Heather E. Dawes, Edward F. Chang (2018).
Abstract: Not available.
https://doi.org/10.1016/j.cell.2018.10.005 -
Closed-Loop Deep Brain Stimulation for Refractory Chronic Pain . Frontiers in Computational Neuroscience.
Shirvalkar P., Veuthey T.L., Dawes H.E., Chang E.F. (2018).
Abstract: This study aimed to review the best evidence on the long-term efficacy of neurostimulation for chronic pain. We systematically reviewed PubMed, CENTRAL, and WikiStim for studies published between the inception of the data bases and July 21, 2022. Randomized controlled trials (RCTs) with a minimum of one-year follow-up that were of high methodologic quality as ascertained using the Delphi list criteria were included in the evidence synthesis. The primary outcome was long-term reduction in pain intensity, and the secondary outcomes were all other reported outcomes. Level of recommendation was graded from I to III, with level I being the highest level of recommendation. Of the 7119 records screened, 24 RCTs were included in the evidence synthesis. Therapies with recommendations for their usage include pulsed radiofrequency (PRF) for postherpetic neuralgia, transcutaneous electrical nerve stimulation for trigeminal neuralgia, motor cortex stimulation for neuropathic pain and poststroke pain, deep brain stimulation for cluster headache, sphenopalatine ganglion stimulation for cluster headache, occipital nerve stimulation for migraine, peripheral nerve field stimulation for back pain, and spinal cord stimulation (SCS) for back and leg pain, nonsurgical back pain, persistent spinal pain syndrome, and painful diabetic neuropathy. Closed-loop SCS is recommended over open-loop SCS for back and leg pain. SCS is recommended over PRF for postherpetic neuralgia. Dorsal root ganglion stimulation is recommended over SCS for complex regional pain syndrome. Neurostimulation is generally effective in the long term as an adjunctive treatment for chronic pain. Future studies should evaluate whether the multidisciplinary management of the physical perception of pain, affect, and social stressors is superior to their management alone.
https://doi.org/10.3389/fncom.2018.00018
2017
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Semi-automated Anatomical Labeling and Inter-subject Warping of High-Density Intracranial Recording Electrodes in Electrocorticography. Frontiers in Neuroinformatics.
Hamilton, L.S., Chang, D.L., Lee, M.B., Chang, E.F. (2017).
Abstract: Not available.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671481/ -
Neural Encoding of Auditory Features during Music Perception and Imagery. Cerebral Cortex.
Martin, S., Mikutta, C., Leonard, M.K., Hungate, D., Koelsch, S., Shamma, S., Chang, E.F., del R. Millán, J., Knight, R.T., & Palsey, B.N. (2017).
Abstract: The common approach to the multiplicity problem calls for controlling the familywise error rate (FWER). This approach, though, has faults, and we point out a few. A different approach to problems of multiple significance testing is presented. It calls for controlling the expected proportion of falsely rejected hypotheses — the false discovery rate. This error rate is equivalent to the FWER when all hypotheses are true but is smaller otherwise. Therefore, in problems where the control of the false discovery rate rather than that of the FWER is desired, there is potential for a gain in power. A simple sequential Bonferronitype procedure is proved to control the false discovery rate for independent test statistics, and a simulation study shows that the gain in power is substantial. The use of the new procedure and the appropriateness of the criterion are illustrated with examples.
https://doi.org/10.1093/cercor/bhx271 -
Critical Language Areas Show Increased Functional Connectivity in Human Cortex. Cerebral Cortex.
Rolston, J.D. & Chang, E.F. (2017).
Abstract: The common approach to the multiplicity problem calls for controlling the familywise error rate (FWER). This approach, though, has faults, and we point out a few. A different approach to problems of multiple significance testing is presented. It calls for controlling the expected proportion of falsely rejected hypotheses — the false discovery rate. This error rate is equivalent to the FWER when all hypotheses are true but is smaller otherwise. Therefore, in problems where the control of the false discovery rate rather than that of the FWER is desired, there is potential for a gain in power. A simple sequential Bonferronitype procedure is proved to control the false discovery rate for independent test statistics, and a simulation study shows that the gain in power is substantial. The use of the new procedure and the appropriateness of the criterion are illustrated with examples.
https://doi.org/10.1093/cercor/bhx271 -
Intonational speech prosody encoding in the human auditory cortex. Science, 357(6353): 797-801. doi:10.1126/science.aam8577.
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Neurosurgical Patients as Human Research Subjects: Ethical Considerations in Intracranial Electrophysiology Research . Neurosurgery, 10.1093/neuros/nyx361.
Chiong, W., Leonard, M.K., & Chang, E.F. (2017).
Abstract: Intracranial electrical recordings and stimulation of neurosurgical patients have been central to the advancement of human neuroscience. The use of these methods has rapidly expanded over the last decade due to theoretical and technical advances, as well as the growing number of neurosurgical patients undergoing functional procedures for indications such as epilepsy, tumor resection, and movement disorders. These methods pose the potential for ethical conflict, as they involve basic neuroscientific research utilizing invasive procedures in human patients undergoing treatment for neurological illnesses. This review addresses technical aspects, clinical contexts, and issues of ethical concern, utilizing a framework that is informed by, but also departs from, existing bioethical literature on matters in clinical research. We conclude with proposals for improving informed consent processes to address potential problems specific to intracranial electrophysiology research, a general schema for scrutinizing research-related risk associated with different methods, and a call for the development of consensus to ensure continuing scientific progress alongside crucial patient protections in this promising area of human neuroscience.
http://dx.doi.org/10.1093/neuros/nyx361 -
Chronic ambulatory electrocorticography from human speech cortex NeuroImage
Rao, V.R.*, Leonard, M.K.*, Kleen, J.K., Lucas, B.A., Mirro, E.A., & Chang, E.F. (*Equally contributing authors) (2017).
Abstract:
http://dx.doi.org/10.1016/j.neuroimage.2017.04.008 -
Dynamic Tracking of Non-Stationarity in Human ECoG Activity. IEEE.
Yuxiao Yang, Chang E.F., Shanechi M.M. (2017).
Abstract: Not available.
https://ieeexplore.ieee.org/document/8037159 -
Immediate Mood Scaler: Tracking Symptoms of Depression and Anxiety Using a Novel Mobile Mood Scale. JMIR Mhealth Uhealth.
Nahum M., Van Vleet T.M., Sohal V.S., Mirzabekov J.J., Rao V.R., Wallace D.L., Lee M.B., Dawes H., Stark-Inbar A., Jordan J.T., Biagianti B., Merzenich M., Chang E.F. (2017).
Abstract: Not available.
https://mhealth.jmir.org/2017/4/e44/ -
Unsupervised Learning of Spatiotemporal Interictal Discharges in Focal Epilepsy. Neurosurgery.
Baud MO, Kleen JK, Anumanchipalli GK, Hamilton LS, Yee-Leng T, Knowlton R, Chang EF. (2017).
Abstract: Interictal epileptiform discharges are an important biomarker for localization of focal epilepsy, especially in patients who undergo chronic intracranial monitoring. Manual detection of these pathophysiological events is cumbersome, but is still superior to current rule-based approaches in most automated algorithms. To develop an unsupervised machine-learning algorithm for the improved, automated detection and localization of interictal epileptiform discharges based on spatiotemporal pattern recognition. We decomposed 24 h of intracranial electroencephalography signals into basis functions and activation vectors using non-negative matrix factorization (NNMF). Thresholding the activation vector and the basis function of interest detected interictal epileptiform discharges in time and space (specific electrodes), respectively. We used convolutive NNMF, a refined algorithm, to add a temporal dimension to basis functions. The receiver operating characteristics for NNMF-based detection are close to the gold standard of human visual-based detection and superior to currently available alternative automated approaches (93% sensitivity and 97% specificity). The algorithm successfully identified thousands of interictal epileptiform discharges across a full day of neurophysiological recording and accurately summarized their localization into a single map. Adding a temporal window allowed for visualization of the archetypal propagation network of these epileptiform discharges. Unsupervised learning offers a powerful approach towards automated identification of recurrent pathological neurophysiological signals, which may have important implications for precise, quantitative, and individualized evaluation of focal epilepsy.
2016
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Perceptual restoration of masked speech in human cortex . Nature Communications, 13619. doi:10.1038/ncomms13619.
Leonard, M.K., Baud, M.O., Sjerps, M.J., & Chang, E.F. (2016).
Abstract: Humans are adept at understanding speech despite the fact that our natural listening environment is often filled with interference. An example of this capacity is phoneme restoration, in which part of a word is completely replaced by noise, yet listeners report hearing the whole word. The neurological basis for this unconscious fill-in phenomenon is unknown, despite being a fundamental characteristic of human hearing. Here, using direct cortical recordings in humans, we demonstrate that missing speech is restored at the acoustic-phonetic level in bilateral auditory cortex, in real-time. This restoration is preceded by specific neural activity patterns in a separate language area, left frontal cortex, which predicts the word that participants later report hearing. These results demonstrate that during speech perception, missing acoustic content is synthesized online from the integration of incoming sensory cues and the internal neural dynamics that bias word-level expectation and prediction.
http://dx.doi.org/10.1038/ncomms13619 -
Neural speech recognition: continuous phoneme decoding using spatiotemporal representations of human cortical activity. Journal of Neural Engineering, 13(5), 56004.
Moses, D. A., Mesgarani, N., Leonard, M. K., & Chang, E. F. (2016).
Abstract: Neurons are often assumed to operate in a highly unreliable manner: a neuron can signal the same stimulus with a variable number of action potentials. However, much of the experimental evidence supporting this view was obtained in the visual cortex. We have, therefore, assessed trial-to-trial variability in the auditory cortex of the rat. To ensure single-unit isolation, we used cell-attached recording. Tone-evoked responses were usually transient, often consisting of, on average, only a single spike per stimulus. Surprisingly, the majority of responses were not just transient, but were also binary, consisting of 0 or 1 action potentials, but not more, in response to each stimulus; several dramatic examples consisted of exactly one spike on 100% of trials, with no trial-to-trial variability in spike count. The variability of such binary responses differs from comparably transient responses recorded in visual cortical areas such as area MT, and represent the lowest trial-to-trial variability mathematically possible for responses of a given firing rate. Our study thus establishes for the first time that transient responses in auditory cortex can be described as a binary process, rather than as a highly variable Poisson process. These results demonstrate that cortical architecture can support a more precise control of spike number than was previously recognized, and they suggest a re-evaluation of models of cortical processing that assume noisiness to be an inevitable feature of cortical codes.
http://doi.org/10.1088/1741-2560/13/5/056004 -
Thin-film, high density micro-electrocorticographic decoding of a human cortical gyrus. Engineering in Medicine and Biology Society (EMBC), 2016 IEEE 38th Annual International Conference of the. 1528-1531.
Muller, L., Felix, S., Shah, K.G., Lee, K., Pannu, S., & Chang, E.F. (2016).
Abstract: High-density electrocorticography (ECoG) arrays are promising interfaces for high-resolution neural recording from the cortical surface. Commercial options for high-density arrays are limited, and historically tradeoffs must be made between spatial coverage and electrode density. However, thin-film technology is a promising alternative for generating electrode arrays capable of large area coverage and high channel count, with resolution on the order of cortical columns in the functional surface unit of a human gyrus. Here, we evaluate the sensing performance of a high-density thin-film 128-electrode array designed specifically for recording the distributed neural activity of a single human cortical gyrus. We found robust field potential responses throughout the superior temporal gyrus evoked by speech sounds, and clear phonetic feature selectivity at the resolution of 2 mm inter-electrode distance. Decoding accuracy improved with increasing density of electrodes over all three patients tested. Thin-film ECoG has significant potential for high-density neural interface applications at the scale of a human gyrus.
http://dx.doi.org/10.1109/EMBC.2016.7591001 -
Spatial resolution dependence on spectral frequency in human speech cortex electrocorticography. Journal of Neural Engineering, 13(5), 056013.
Muller, L. Hamilton, L.S., Edwards, E., Bouchard, K.E., & Chang, E.F. (2016).
Abstract: Electrocorticography (ECoG) has become an important tool in human neuroscience and has tremendous potential for emerging applications in neural interface technology. Electrode array design parameters are outstanding issues for both research and clinical applications, and these parameters depend critically on the nature of the neural signals to be recorded. Here, we investigate the functional spatial resolution of neural signals recorded at the human cortical surface. We empirically derive spatial spread functions to quantify the shared neural activity for each frequency band of the electrocorticogram. Five subjects with high-density (4 mm center-to-center spacing) ECoG grid implants participated in speech perception and production tasks while neural activity was recorded from the speech cortex, including superior temporal gyrus, precentral gyrus, and postcentral gyrus. The cortical surface field potential was decomposed into traditional EEG frequency bands. Signal similarity between electrode pairs for each frequency band was quantified using a Pearson correlation coefficient. The correlation of neural activity between electrode pairs was inversely related to the distance between the electrodes; this relationship was used to quantify spatial falloff functions for cortical subdomains. As expected, lower frequencies remained correlated over larger distances than higher frequencies. However, both the envelope and phase of gamma and high gamma frequencies (30–150 Hz) are largely uncorrelated (<90%) at 4 mm, the smallest spacing of the high-density arrays. Thus, ECoG arrays smaller than 4 mm have significant promise for increasing signal resolution at high frequencies, whereas less additional gain is achieved for lower frequencies. Our findings quantitatively demonstrate the dependence of ECoG spatial resolution on the neural frequency of interest. We demonstrate that this relationship is consistent across patients and across cortical areas during activity.
https://dx.doi.org/10.1088/1741-2560/13/5/056013 -
The peri-Sylvian cortical network underlying single word repetition revealed by electrocortical stimulation and direct neural recordings. Brain & Language, doi:10.1016/j.bandl.2016.06.001.
Leonard, M.K.*, Cai, R.*, Babiak, M.C.*, Ren, A.*, & Chang, E.F.* (2016).
Abstract: Verbal repetition requires the coordination of auditory, memory, linguistic, and motor systems. To date, the basic dynamics of neural information processing in this deceptively simple behavior are largely unknown. Here, we examined the neural processes underlying verbal repetition using focal interruption (electrocortical stimulation) in 58 patients undergoing awake craniotomies, and neurophysiological recordings (electrocorticography) in 8 patients while they performed a single word repetition task. Electrocortical stimulation revealed that sub-components of the left peri-Sylvian network involved in single word repetition could be differentially interrupted, producing transient perceptual deficits, paraphasic errors, or speech arrest. Electrocorticography revealed the detailed spatio-temporal dynamics of cortical activation, involving a highly-ordered, but overlapping temporal progression of cortical high gamma (75-150Hz) activity throughout the peri-Sylvian cortex. We observed functionally distinct serial and parallel cortical processing corresponding to successive stages of general auditory processing (posterior superior temporal gyrus), speech-specific auditory processing (middle and posterior superior temporal gyrus), working memory (inferior frontal cortex), and motor articulation (sensorimotor cortex). Together, these methods reveal the dynamics of coordinated activity across peri-Sylvian cortex during verbal repetition.
https://dx.doi.org/10.1016/j.bandl.2016.06.001 -
The auditory representation of speech sounds in human motor cortex. Elife, 5:e12577.
Cheung, C., Hamilton, L.S., Johnson, K., & Chang, E.F. (2016).
Abstract: In humans, listening to speech evokes neural responses in the motor cortex. This has been controversially interpreted as evidence that speech sounds are processed as articulatory gestures. However, it is unclear what information is actually encoded by such neural activity. We used high-density direct human cortical recordings while participants spoke and listened to speech sounds. Motor cortex neural patterns during listening were substantially different than during articulation of the same sounds. During listening, we observed neural activity in the superior and inferior regions of ventral motor cortex. During speaking, responses were distributed throughout somatotopic representations of speech articulators in motor cortex. The structure of responses in motor cortex during listening was organized along acoustic features similar to auditory cortex, rather than along articulatory features as during speaking. Motor cortex does not contain articulatory representations of perceived actions in speech, but rather, represents auditory vocal information.
https://dx.doi.org/10.7554/eLife.12577 -
Human superior temporal gyrus organization of spectrotemporal modulation tuning derived from speech stimuli. Journal of Neuroscience, 36(6): 2014-2026.
Hullett, P.W., Hamilton, L.S., Mesgarani, N., Schreiner, C.E., & Chang, E.F. (2016).
Abstract: The human superior temporal gyrus (STG) is critical for speech perception, yet the organization of spectrotemporal processing of speech within the STG is not well understood. Here, to characterize the spatial organization of spectrotemporal processing of speech across human STG, we use high-density cortical surface field potential recordings while participants listened to natural continuous speech. While synthetic broad-band stimuli did not yield sustained activation of the STG, spectrotemporal receptive fields could be reconstructed from vigorous responses to speech stimuli. We find that the human STG displays a robust anterior–posterior spatial distribution of spectrotemporal tuning in which the posterior STG is tuned for temporally fast varying speech sounds that have relatively constant energy across the frequency axis (low spectral modulation) while the anterior STG is tuned for temporally slow varying speech sounds that have a high degree of spectral variation across the frequency axis (high spectral modulation). This work illustrates organization of spectrotemporal processing in the human STG, and illuminates processing of ethologically relevant speech signals in a region of the brain specialized for speech perception.
https://dx.doi.org/10.1523/JNEUROSCI.1779-15.2016 -
Thin-Film, High-Density Micro-Electrocorticographic Decoding of a Human Cortical Gyrus . IEEE.
Leah Muller, Sarah Felix, Kedar G. Shah, Kye Lee, Satinderpall Pannu, Edward F. Chang (2016).
Abstract: Not available.
https://ieeexplore.ieee.org/document/7591001 -
Epilepsy and brain tumors. Handb.Clin.Neurol. 134, 267-285.
Englot DJ, Chang EF, Vecht CJ. (2016).
Abstract: Epilepsy is often the initial symptom in two-thirds of glioblastoma (GBM) patients. Existing studies have shown that microRNAs (miRNAs) play a crucial role in epilepsy. However, their role in epilepsy associated with glioblastoma remains unclear. The aim of our study was to investigate the correlation between miR-1290 expression in GBM patients and pre-operative seizures, as well as patient outcomes. 81 GBM patients were enrolled in our study, and an independent validation was carried out with 92 similar cases. MiRNA profiling of the 81 patients was conducted to identify differentially expressed miRNAs. In the validation cohort, key miRNAs were validated by using quantitative reverse transcriptase polymerase chain reaction (q-PCR). Additionally, functional analysis of these miRNAs was performed through Gene Ontology (GO) analysis. Our array analysis disclosed that there were seven under-expressed miRNAs in patients with preoperative seizures when compared to those without preoperative seizures. Among them, miR-1290 showed the highest fold change. Validation in an independent cohort verified that patients with favorable seizure outcomes had higher miR-1290 expression levels. Functional enrichment analysis demonstrated that the gene expression profiles associated with miR-1290 were enriched in biological processes related to transcription and cell cycle regulation, especially the functions mediated by RNA polymerase II. MiR-1290 emerges as a promising biomarker for predicting seizure susceptibility and overall survival in GBM patients. A specific evaluation of miR-1290 may lead to targeted diagnostic and therapeutic interventions, potentially providing novel strategies for enhancing patient outcomes.
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Epilepsy with temporal encephalocele: Characteristics of electrocorticography and surgical outcome. Epilepsia 57, 2, e33-8.
Panov F, Li Y, Chang EF, Knowlton R, Cornes SB. (2016).
Abstract: Temporal lobe encephaloceles (TEs) are increasingly identified in patients with epilepsy due to advances in neuroimaging. Select patients become seizure-free with lesionectomy. In practice, however, many of these patients will undergo standard anterior temporal lobectomy. Herein we report on the first series of patients with refractory temporal lobe epilepsy (TLE) with encephalocele to undergo chronic or intraoperative electrocorticography (ECoG) in order to characterize the putative epileptogenic nature of these lesions and help guide surgical planning. This retrospective study includes nine adult patients with magnetic resonance imaging/computed tomography (MRI/CT)-defined temporal encephalocele treated between 2007 and 2014 at University of California San Francisco (UCSF). Clinical features, ECoG, imaging, and surgical outcomes are reviewed. Six patients underwent resective epilepsy surgery. Each case demonstrated abnormal epileptiform discharges around the cortical area of the encephalocele. Two underwent tailored lesionectomy and four underwent lesionectomy plus anterior medial temporal resection. Postoperatively, five patients, including both with lesionectomy only, had Engel class Ia surgical outcome, and one had a class IIb surgical outcome. The role of TE in the pathogenesis of epilepsy is uncertain. ECoG can confirm the presence of interictal epileptiform discharges and seizures arising from these lesions. Patients overall had a very good surgical prognosis, even with selective surgical approaches.
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Major and minor complications in extraoperative electrocorticography: A review of a national database. Epilepsy Res. 122, 26-29.
Rolston JD, Englot DJ, Cornes S, Chang EF. (2016).
Abstract: The risk profile of extraoperative electrocorticography (ECoG) is documented almost exclusively by case series from a limited number of academic medical centers. These studies tend to underreport minor complications, like urinary tract infections (UTIs) and deep venous thromboses (DVTs), that nevertheless affect hospital cost, length of stay, and the patient's quality of life. Herein, we used data from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) to estimate the rate of adverse events in extraoperative ECoG surgeries. NSQIP is a validated dataset containing nearly 3 million procedures from over 600 North American hospitals, and uses strict criteria for the documentation of complications. Major complications occurred in 3.4% of 177 extraoperative ECoG cases, while minor complications occurred in 9.6%. The most common minor complication was bleeding requiring a transfusion in 3.4% of cases, followed by sepsis, DVT, and UTI each in 2.3% of cases. No mortality was reported. Overall, in a national database containing a heterogeneous population of hospitals, major complications of extraoperative ECoG were rare (3.4%). Complications such as UTI and DVT tend to be underreported in retrospective case series, yet make up a majority of minor complications for ECoG patients in this dataset.
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Surgical management of medically refractory epilepsy in patients with polymicrogyria. Epilepsia 57, 1, 151-161.
Wang DD, Knox R, Rolston JD, Englot DJ, Barkovich AJ, Tihan T, Auguste KI, Knowlton RC, Cornes SB, Chang EF. (2016).
Abstract: Polymicrogyria (PMG) is a malformation of cortical development characterized by formation of an excessive number of small gyri. Sixty percent to 85% of patients with PMG have epilepsy that is refractory to medication, but surgical options are usually limited. We characterize a cohort of patient with polymicrogyria who underwent epilepsy surgery and document seizure outcomes. A retrospective study of all patients with PMG who underwent epilepsy surgery (focal seizure foci resection and/or hemispherectomy) at our center was performed by review of all clinical data related to their treatment. We identified 12 patients (7 males and 5 female) with mean age of 18 (ranging from 3 months to 44 years) at time of surgery. Mean age at seizure onset was 8 years, with the majority (83%) having childhood onset. Six patients had focal, five had multifocal, and one patient had diffuse PMG. Perisylvian PMG was the most common pattern seen on magnetic resonance imaging (MRI). Eight patients had other cortical malformations including hemimegalencephaly and cortical dysplasia. Scalp electroencephalography (EEG) often showed diffuse epileptic discharges that poorly lateralized but were focal on intracranial electrocorticography (ECoG). Eight patients underwent seizure foci resection and four underwent hemispherectomy. Mean follow-up was 7 years (ranging from one to 19 years). Six patients (50%) were seizure-free at last follow-up. One patient had rare seizures (Engel class II). Three patients were Engel class III, having either decreased seizure frequency or severity, and two patients were Engel class IV. Gross total resection of the PMG cortex trended toward good seizure control. Our study shows that even in patients with extensive or bilateral PMG malformations, some may still be good candidates for surgery because the epileptogenic zone may involve only a portion of the malformation. Intracranial ECoG can provide additional localizing information compared to scalp EEG in guiding resection of epileptogenic foci.
2015
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A probabilistic map of the human ventral sensorimotor cortex using electrical stimulation. Journal of Neurosurgery, 123: 340-349.
Breshears, J.D., Molinaro, A.M., & Chang, E.F. (2015).
Abstract: The human ventral sensorimotor cortex (vSMC) is involved in facial expression, mastication, and swallowing, as well as the dynamic and highly coordinated movements of human speech production. However, vSMC organization remains poorly understood, and previously published population-driven maps of its somatotopy do not accurately reflect the variability across individuals in a quantitative, probabilistic fashion. The goal of this study was to describe the responses to electrical stimulation of the vSMC, generate probabilistic maps of function in the vSMC, and quantify the variability across individuals.
https://dx.doi.org/10.3171/2014.11.JNS14889 -
The influence of lexical statistics on temporal lobe cortical dynamics during spoken word listening. Brain and Language, 147: 66-75.
Cibelli, E.S., Leonard, M.K., Johnson, K., & Chang, E.F. (2015).
Abstract: This book is a comprehensive guide to the International Phonetic Alphabet, whose aim is to provide a universally agreed system of notation for the sounds of languages, and which has been widely used for over a century. The Handbook presents the basics of phonetic analysis so that the principles underlying the Alphabet can be readily understood, and gives examples of the use of each of the phonetic symbols. The application of the Alphabet is then demonstrated in nearly 30 'Illustrations' - concise analyses of the sound systems of a range of languages, each of them accompanied by a phonetic transcription of a passage of speech. The Handbook also includes the 'Extensions' to the Alphabet, covering speech sounds beyond the sound-systems of languages, and a listing of the internationally agreed computer codings for phonetic symbols. It is an essential reference work for all those involved in the analysis of speech.
https://dx.doi.org/10.1016/j.bandl.2015.05.005 -
The Cortical computations underlying feedback control in vocal production. Current Opinion in Neurobiology, 33: 174-181.
Houde, J.F. & Chang, E.F. (2015).
Abstract: Neocortical activity is thought to mediate voluntary control over vocal production, but the underlying neural mechanisms remain unclear. In a highly vocal rodent, the male Alston's singing mouse, we investigate neural dynamics in the orofacial motor cortex (OMC), a structure critical for vocal behavior. We first describe neural activity that is modulated by component notes (~100 ms), probably representing sensory feedback. At longer timescales, however, OMC neurons exhibit diverse and often persistent premotor firing patterns that stretch or compress with song duration (~10 s). Using computational modeling, we demonstrate that such temporal scaling, acting through downstream motor production circuits, can enable vocal flexibility. These results provide a framework for studying hierarchical control circuits, a common design principle across many natural and artificial systems.
https://dx.doi.org/10.1016/j.conb.2015.04.006 -
Dynamic encoding of speech sequence probability in human temporal cortex. Journal of Neuroscience, 35(18): 7203-7214.
Leonard, M.K., Bouchard, K.E., Tang, C., & Chang, E.F. (2015).
Abstract: Sensory processing involves identification of stimulus features, but also integration with the surrounding sensory and cognitive context. Previous work in animals and humans has shown fine-scale sensitivity to context in the form of learned knowledge about the statistics of the sensory environment, including relative probabilities of discrete units in a stream of sequential auditory input. These statistics are a defining characteristic of one of the most important sequential signals humans encounter: speech. For speech, extensive exposure to a language tunes listeners to the statistics of sound sequences. To address how speech sequence statistics are neurally encoded, we used high-resolution direct cortical recordings from human lateral superior temporal cortex as subjects listened to words and nonwords with varying transition probabilities between sound segments. In addition to their sensitivity to acoustic features (including contextual features, such as coarticulation), we found that neural responses dynamically encoded the language-level probability of both preceding and upcoming speech sounds. Transition probability first negatively modulated neural responses, followed by positive modulation of neural responses, consistent with coordinated predictive and retrospective recognition processes, respectively. Furthermore, transition probability encoding was different for real English words compared with nonwords, providing evidence for online interactions with high-order linguistic knowledge. These results demonstrate that sensory processing of deeply learned stimuli involves integrating physical stimulus features with their contextual sequential structure. Despite not being consciously aware of phoneme sequence statistics, listeners use this information to process spoken input and to link low-level acoustic representations with linguistic information about word identity and meaning.
https://dx.doi.org/10.1523/JNEUROSCI.4100-14.2015 -
Towards large-Scale, human-Based, mesoscopic neurotechnologies. Neuron, 86: 68-78.
Chang, E.F. (2015).
Abstract: In some mammalian species, geniculocortical afferents serving each eye are segregated in layer 4C of striate cortex into stripes called ocular dominance columns. Having described the complete pattern of ocular dominance columns in the human brain, the authors enumerate here the principal enigmas that confront future investigators. Probably the overarching challenge is to explain the function, if any, of ocular dominance columns and why they are present in some species and not others. A satisfactory solution must account for the enormous natural variation, even within the same species, among individuals in column expression, pattern, periodicity, and alignment with other components of the functional architecture. Another major priority is to explain the development of ocular dominance columns. It has been established clearly that they form without visual experience, but the innate signals that guide their segregation and maturation are unknown. Experiments addressing the role of spontaneous retinal activity have yielded contradictory data. These studies must be reconciled, to pave the way for new insights into how columnar structure is generated in the cerebral cortex.
https://dx.doi.org/10.1016/j.neuron.2015.03.037 -
Minimally invasive epilepsy surgery. Neurosurg.Clin.N.Am. 27, 1, xiii-xiv.
Zaghloul KA, Chang EF. (2015).
Abstract: The mediobasal temporal region (MTR) is a complex neurosurgical target due to its deep location and proximity to critical neurovascular structures. Conditions such as mesial temporal sclerosis frequently involve the MTR, often leading to epilepsy. Traditional approaches, including anterior lobectomy and transcortical amygdalohippocampectomy, are effective but carry risks such as visual field deficits from optic radiation damage. This study evaluates the feasibility and effectiveness of the endoscopic supracerebellar transtentorial approach (ESTAH) as a minimally invasive alternative, emphasizing neurovascular preservation and minimizing complications. Four formalin-fixed, silicon-injected cadaver heads and ten human cadaver brains prepared using the Klingler method were dissected to study MTR anatomy. ESTAH was performed using 0° and 30° endoscopes and neuronavigation. Key anatomical landmarks, including the tentorial angle and the posterior fossa dura-to-hippocampal uncus distance, were measured to assess surgical precision and safety. The endoscope provided precise visualization and resection of the hippocampus, amygdala, and parahippocampal gyrus with minimal disruption to optic radiations and adjacent white matter tracts. Critical neurovascular structures, such as the internal carotid artery, middle cerebral artery branches, posterior cerebral artery, and cranial nerves III and IV, were preserved. The average dura-to-uncus distance was 78.15 mm, and the average tentorial angle was 104.1°. The ESTAH is a feasible, minimally invasive alternative for amygdalohippocampectomy, offering excellent visualization and reduced risk of complications. This approach has the potential to improve surgical outcomes and minimize morbidity in MTR surgeries.
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A probabilistic map of the human ventral sensorimotor cortex using electrical stimulation. Journal of Neurosurgery.
Breshears JD, Molinaro AM, Chang EF (2015).
Abstract: The human ventral sensorimotor cortex (vSMC) is involved in facial expression, mastication, and swallowing, as well as the dynamic and highly coordinated movements of human speech production. However, vSMC organization remains poorly understood, and previously published population-driven maps of its somatotopy do not accurately reflect the variability across individuals in a quantitative, probabilistic fashion. The goal of this study was to describe the responses to electrical stimulation of the vSMC, generate probabilistic maps of function in the vSMC, and quantify the variability across individuals. Photographic, video, and stereotactic MRI data of intraoperative electrical stimulation of the vSMC were collected for 33 patients undergoing awake craniotomy. Stimulation sites were converted to a 2D coordinate system based on anatomical landmarks. Motor, sensory, and speech stimulation responses were reviewed and classified. Probabilistic maps of stimulation responses were generated, and spatial variance was quantified. In 33 patients, the authors identified 194 motor, 212 sensory, 61 speech-arrest, and 27 mixed responses. Responses were complex, stereotyped, and mostly nonphysiological movements, involving hand, orofacial, and laryngeal musculature. Within individuals, the presence of oral movement representations varied; however, the dorsal-ventral order was always preserved. The most robust motor responses were jaw (probability 0.85), tongue (0.64), lips (0.58), and throat (0.52). Vocalizations were seen in 6 patients (0.18), more dorsally near lip and dorsal throat areas. Sensory responses were spatially dispersed; however, patients' subjective reports were highly precise in localization within the mouth. The most robust responses included tongue (0.82) and lips (0.42). The probability of speech arrest was 0.85, highest 15-20 mm anterior to the central sulcus and just dorsal to the sylvian fissure, in the anterior precentral gyrus or pars opercularis. The authors report probabilistic maps of function in the human vSMC based on intraoperative cortical electrical stimulation. These results define the expected range of mapping outcomes in the vSMC of a single individual and shed light on the functional organization of the vSMC supporting speech motor control and nonspeech functions.
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Minially invasive surgical approaches for temporal lobe epilepsy. Epilepsy Behav. 47, 24-33.
Chang EF, Englot DJ, Vadera S (2015).
Abstract: Surgery can be a highly effective treatment for medically refractory temporal lobe epilepsy (TLE). The emergence of minimally invasive resective and nonresective treatment options has led to interest in epilepsy surgery among patients and providers. Nevertheless, not all procedures are appropriate for all patients, and it is critical to consider seizure outcomes with each of these approaches, as seizure freedom is the greatest predictor of patient quality of life. Standard anterior temporal lobectomy (ATL) remains the gold standard in the treatment of TLE, with seizure freedom resulting in 60–80% of patients. It is currently the only resective epilepsy surgery supported by randomized controlled trials and offers the best protection against lateral temporal seizure onset. Selective amygdalohippocampectomy techniques preserve the lateral cortex and temporal stem to varying degrees and can result in favorable rates of seizure freedom but the risk of recurrent seizures appears slightly greater than with ATL, and it is not clear whether neuropsychological outcomes are improved with selective approaches. Stereotactic radiosurgery presents an opportunity to avoid surgery altogether, with seizure outcomes now under investigation. Stereotactic laser thermo-ablation allows destruction of the mesial temporal structures with low complication rates and minimal recovery time, and outcomes are also under study. Finally, while neuromodulatory devices such as responsive neurostimulation, vagus nerve stimulation, and deep brain stimulation have a role in the treatment of certain patients, these remain palliative procedures for those who are not candidates for resection or ablation, as complete seizure freedom rates are low. Further development and investigation of both established and novel strategies for the surgical treatment of TLE will be critical moving forward, given the significant burden of this disease.
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Global and regional functional connectivity maps of neural oscillations in focal epilepsy. Brain. 138, Pt 8, 2249-2262.
Englot DJ, Hinkley LB, Kort NS, Imber BS, Mizuiri D, Honma SM, Findlay AM, Garrett C, Cheung PL, Mantle M, Tarapore PE, Knowlton RC, Chang EF, Kirsch HE, Nagarajan SS (2015).
Abstract: Intractable focal epilepsy is a devastating disorder with profound effects on cognition and quality of life. Epilepsy surgery can lead to seizure freedom in patients with focal epilepsy; however, sometimes it fails due to an incomplete delineation of the epileptogenic zone. Brain networks in epilepsy can be studied with resting-state functional connectivity analysis, yet previous investigations using functional magnetic resonance imaging or electrocorticography have produced inconsistent results. Magnetoencephalography allows non-invasive whole-brain recordings, and can be used to study both long-range network disturbances in focal epilepsy and regional connectivity at the epileptogenic zone. In magnetoencephalography recordings from presurgical epilepsy patients, we examined: (i) global functional connectivity maps in patients versus controls; and (ii) regional functional connectivity maps at the region of resection, compared to the homotopic non-epileptogenic region in the contralateral hemisphere. Sixty-one patients were studied, including 30 with mesial temporal lobe epilepsy and 31 with focal neocortical epilepsy. Compared with a group of 31 controls, patients with epilepsy had decreased resting-state functional connectivity in widespread regions, including perisylvian, posterior temporo-parietal, and orbitofrontal cortices (P < 0.01, t-test). Decreased mean global connectivity was related to longer duration of epilepsy and higher frequency of consciousness-impairing seizures (P < 0.01, linear regression). Furthermore, patients with increased regional connectivity within the resection site (n = 24) were more likely to achieve seizure postoperative seizure freedom (87.5% with Engel I outcome) than those with neutral (n = 15, 64.3% seizure free) or decreased (n = 23, 47.8% seizure free) regional connectivity (P < 0.02, chi-square). Widespread global decreases in functional connectivity are observed in patients with focal epilepsy, and may reflect deleterious long-term effects of recurrent seizures. Furthermore, enhanced regional functional connectivity at the area of resection may help predict seizure outcome and aid surgical planning.
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Epileptogenic zone localization using magnetoencephalography predicts seizure freedom in epilepsy surgery. Epilepsia 56, 6, 949-958.
Englot DJ, Nagarajan, SS, Imber BS, Raygor KP, Honma SM, Mizuiri D, Mantle M, Knowlton RC, Kirsch HE, Chang EF (2015).
Abstract: Presurgical evaluation is still challenging for MRI-negative epilepsy patients. As non-invasive modalities are the easiest acceptable and economic methods in determining the epileptogenic zone, we analyzed the localization value of common non-invasive methods in MRI-negative epilepsy patients. In this study, we included epilepsy patients undergoing presurgical evaluation with presurgical negative MRI. MRI post-processing was performed using a Morphometric Analysis Program (MAP) on T1-weighted volumetric MRI. The relationship between MAP, magnetoencephalography (MEG), scalp electroencephalogram (EEG), and seizure outcomes was analyzed to figure out the localization value of different non-invasive methods. Eighty-six patients were included in this study. Complete resection of the MAP-positive regions or the MEG-positive regions was positively associated with seizure freedom (p = 0.028 and 0.007, respectively). When an area is co-localized by MAP and MEG, the resection of the area was significantly associated with seizure freedom (p = 0.006). However, neither the EEG lateralization nor the EEG localization showed statistical association with the surgical outcome (p = 0.683 and 0.505, respectively). In conclusion, scalp EEG had a limited role in presurgical localization and predicting seizure outcome, combining MAP and MEG results can significantly improve the localization of epileptogenic lesions and have a positive association with seizure-free outcome. PLAIN LANGUAGE SUMMARY: Due to the lack of obvious structure abnormalities on neuroimaging examinations, the identification of epilepsy lesions in MRI-negative epilepsy patients can be difficult. In this study, we intended to use non-invasive examinations to explore the potential epileptic lesions in MRI-negative epilepsy patients and to determine the results accuracy by comparing the neuroimaging results with the epilepsy surgery outcomes. A total of 86 epilepsy patients without obvious structure lesions on MRI were included, and we found that the combinations of different non-invasive examinations and neuroimaging post-processing methods are significantly associated with the seizure freedom results of epilepsy surgery.
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Rates and predictors of seizure freedom with vagus nerve stimulation for intractable epilepsy. Neurosurgery
Englot DJ, Rolston JD, Wright CW, Hassnain KH, Chang EF (2015).
Abstract: Vagus nerve stimulation (VNS) has been used as an adjunctive therapy for both children and adults with refractory epilepsy, over the last two decades. In this study, we aimed to evaluate the long-term effects and tolerability of VNS in the pediatric drug-resistant epilepsy (DRE) and to identify the predictive factors for responsiveness to VNS. We retrospectively reviewed the medical records of pediatric patients who underwent VNS implantation between 1997 and 2018. Patients with ≥50% reduction of seizure frequency compared with the baseline were defined as "responders". The clinical characteristics of responders and nonresponders were compared. A total of 58 children (male/female: 40/18) with a mean follow-up duration of 5.7 years (3 months to 20 years) were included. The mean age at implantation was 12.4 years (4.5 to 18.5 years). Approximately half (45%) of our patients were responders, including 3 patients (5.8%) who achieved seizure freedom during follow-up. The age of seizure-onset, duration of epilepsy, age at implantation, and etiologies of epilepsy showed no significant difference between responders and nonresponders. Responders were more likely to have focal or multifocal epileptiform discharges (63%) on interictal electroencephalogram (EEG), when compared to nonresponders (36%) (p = .07). Vocal disturbances and paresthesias were the most common side effects, and in two patients, VNS was removed because of local reaction. Our series had a diverse etiological profile and patients with transition to adult care. Long-term follow-up showed that VNS is an effective and well-tolerated treatment modality for refractory childhood onset epilepsy. Age at implantation, duration of epilepsy and underlying etiology are not found to be predictors of responsiveness to VNS. Higher response rates were observed for a subset of patients with focal epileptiform discharges.
2014
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Control of spoken vowel acoustics and the influence of phonetic context in human speech sensorimotor cortex. Journal of Neuroscience, 34(38): 12662-12677.
Bouchard, K.E. & Chang, E.F. (2014).
Abstract: Speech production requires the precise control of vocal tract movements to generate individual speech sounds (phonemes) which, in turn, are rapidly organized into complex sequences. Multiple productions of the same phoneme can exhibit substantial variability, some of which is inherent to control of the vocal tract and its biomechanics, and some of which reflects the contextual effects of surrounding phonemes (“coarticulation”). The role of the CNS in these aspects of speech motor control is not well understood. To address these issues, we recorded multielectrode cortical activity directly from human ventral sensory-motor cortex (vSMC) during the production of consonant-vowel syllables. We analyzed the relationship between the acoustic parameters of vowels (pitch and formants) and cortical activity on a single-trial level. We found that vSMC activity robustly predicted acoustic parameters across vowel categories (up to 80% of variance), as well as different renditions of the same vowel (up to 25% of variance). Furthermore, we observed significant contextual effects on vSMC representations of produced phonemes that suggest active control of coarticulation: vSMC representations for vowels were biased toward the representations of the preceding consonant, and conversely, representations for consonants were biased toward upcoming vowels. These results reveal that vSMC activity for phonemes are not invariant and provide insight into the cortical mechanisms of coarticulation.
https://dx.doi.org/10.1523/JNEUROSCI.1219-14.2014 -
Dynamic speech representations in the human temporal lobe. Trends in Cognitive Science, 18(9) 472-479.
Leonard, M.K. & Chang, E.F. (2014).
Abstract: Can we decipher speech content (“what” is being said) and speaker identity (“who” is saying it) from observations of brain activity of a listener? Here, we combine functional magnetic resonance imaging with a data-mining algorithm and retrieve what and whom a person is listening to from the neural fingerprints that speech and voice signals elicit in the listener's auditory cortex. These cortical fingerprints are spatially distributed and insensitive to acoustic variations of the input so as to permit the brain-based recognition of learned speech from unknown speakers and of learned voices from previously unheard utterances. Our findings unravel the detailed cortical layout and computational properties of the neural populations at the basis of human speech recognition and speaker identification.
https://dx.doi.org/10.1016/j.tics.2014.05.001 -
Phonetic feature encoding in human superior temporal gyrus. Science, 343(6174): 1006-1010.
Mesgarani, N., Cheung, C., Johnson, K., & Chang, E.F. (2014).
Abstract: Consonants and vowels represent basic building blocks of human language. How their characteristics are extracted from acoustic speech input is not well understood. Directly recording from the superior temporal gyrus of patients as part of their clinical evaluation for epilepsy surgery,
https://dx.doi.org/10.1126/science.1245994 -
Speech map in the human ventral sensory-motor cortex. Current Opinion in Neurobiology, 24C: 63-67.
Conant, D., Bouchard, K.E., & Chang, E.F. (2014).
Abstract: The objective of this experiment was to determine the relative contributions and patterns of activity of different muscles involved during the oral phase of swallowing. Electromyographic (EMG) signals were recorded from the orbicularis oris inferior, masseter, palatal elevator, anterior and posterior genioglossus, mylohyoid, anterior belly of the digastric, and vocalis muscles of 12 normal adult subjects. Each subject swallowed 15 mL of water, under normal and bite block conditions, 15 to 20 times. The integrated EMG signals for each subject's swallows were ensemble averaged. The results of the analyses showed that swallowing function varies from individual to individual in terms of the specific muscles used and how the various muscle activity patterns are coordinated. These results suggest that swallowing is a highly complex adaptive motor activity which probably relies more on higher‐level control mechanisms than previously believed.
https://dx.doi.org/10.1016/j.conb.2013.08.015 -
Rates and predictors of seizure freedom in resective epilepsy surgery: an update. Neurosurg Rev. 37(3):389-404
Englot DJ & Chang EF (2014).
Abstract: Epilepsy is a debilitating neurological disorder affecting approximately 1 % of the world's population. Drug-resistant focal epilepsies are potentially surgically remediable. Although epilepsy surgery is dramatically underutilized among medically refractory patients, there is an expanding collection of evidence supporting its efficacy which may soon compel a paradigm shift. Of note is that a recent randomized controlled trial demonstrated that early resection leads to considerably better seizure outcomes than continued medical therapy in patients with pharmacoresistant temporal lobe epilepsy. In the present review, we provide a timely update of seizure freedom rates and predictors in resective epilepsy surgery, organized by the distinct pathological entities most commonly observed. Class I evidence, meta-analyses, and individual observational case series are considered, including the experiences of both our institution and others. Overall, resective epilepsy surgery leads to seizure freedom in approximately two thirds of patients with intractable temporal lobe epilepsy and about one half of individuals with focal neocortical epilepsy, although only the former observation is supported by class I evidence. Two common modifiable predictors of postoperative seizure freedom are early operative intervention and, in the case of a discrete lesion, gross total resection. Evidence-based practice guidelines recommend that epilepsy patients who continue to have seizures after trialing two or more medication regimens should be referred to a comprehensive epilepsy center for multidisciplinary evaluation, including surgical consideration.
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Epilepsy surgery failure in children: a quantitative and qualitative analysis. J Neurosurg Pediatr. 14(4):386-95.
Englot DJ, Han SJ, Rolston JD, Ivan ME, Kuperman RA, Chang EF, Gupta N, Sullivan JE, Auguste KI. (2014).
Abstract: Resection is a safe and effective treatment option for children with pharmacoresistant focal epilepsy, but some patients continue experience seizures after surgery. While most studies of pediatric epilepsy surgery focus on predictors of postoperative seizure outcome, these factors are often not modifiable, and the reasons for surgical failure may remain unclear. The authors performed a retrospective cohort study of children and adolescents who received focal resective surgery for pharmacoresistant epilepsy. Both quantitative and qualitative analyses of factors associated with persistent postoperative seizures were conducted. Records were reviewed from 110 patients, ranging in age from 6 months to 19 years at the time of surgery, who underwent a total of 115 resections. At a mean 3.1-year follow-up, 76% of patients were free of disabling seizures (Engel Class I outcome). Seizure freedom was predicted by temporal lobe surgery compared with extratemporal resection, tumor or mesial temporal sclerosis compared with cortical dysplasia or other pathologies, and by a lower preoperative seizure frequency. Factors associated with persistent seizures (Engel Class II-IV outcome) included residual epileptogenic tissue adjacent to the resection cavity (40%), an additional epileptogenic zone distant from the resection cavity (32%), and the presence of a hemispheric epilepsy syndrome (28%). While seizure outcomes in pediatric epilepsy surgery may be improved by the use of high-resolution neuroimaging and invasive electrographic studies, a more aggressive resection should be considered in certain patients, including hemispherectomy if a hemispheric epilepsy syndrome is suspected. Family counseling regarding treatment expectations is critical, and reoperation may be warranted in select cases.
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Factors associated with failed focal neocortical epilepsy surgery. Neurosurgery.
Englot DJ, Raygor KP, Molinaro AM, Garcia PA, Knowlton RC, Auguste KI, Chang EF. (2014).
Abstract: Some patients who initially fail epilepsy surgery later become seizure-free, but it is not clear how the clinical characteristics of the patients or post-operative modifications of anti-seizure medication (ASM) regimens contribute to late seizure remission. We performed a retrospective chart review of patients undergoing epilepsy surgery at the University of Washington Regional Epilepsy Center between 2007 and 2017, including patients receiving neocortical resection, temporal lobectomy, and hippocampal laser interstitial therapy (LITT) ablation. We assessed seizure freedom, ASM changes, seizure frequency at the first and last follow-up, and type of lesion. Two-tailed Fisher's exact test and Mann-Whitney U test were used for statistical analyses. Two hundred and fifteen patients undergoing epilepsy surgery between 2007 and 2017 had both first and last follow-ups. Ninety-eight (46%) were not seizure-free at the first follow-up (mean 1.1 years post-operative). By the last follow-up (mean 4.7 years post-operative), 20% of those not initially seizure-free had become so. Those who were seizure-free at the last visit had lower median seizures per month in the first post-operative year (0.21 versus 0.95 per month in those not seizure-free, p < 0.001). There was also a significantly higher proportion of patients with cavernomas who were seizure-free at the last visit (25% vs. 1% of those not seizure-free at the last visit; p = 0.001), but no other differences in clinical characteristics. Of the 98 patients who had seizures at the first follow-up, 63% underwent post-operative modification of their ASM regimens. The rate of late seizure freedom was similar for patients with or without ASM changes: 21% were seizure-free at the last visit with ASM changes and 19% without ASM changes. There were no significant differences in which ASMs were changed between those who became seizure-free and those who did not, but patients who were subjected to further medical management were less likely to have had mesial temporal sclerosis (MTS) than those who were not. A number of patients not initially seizure-free who underwent ASM changes achieved seizure freedom as long as 10 years post-surgery. A substantial proportion of patients who initially fail epilepsy surgery will have late seizure remission. Those with cavernous hemangiomas were more likely to achieve late remission from seizures as were those with lower rates of seizures in the first year after surgery. The chances of achieving remission were similar in those with or without modification of their ASM regimens, but those with pre-operative MTS were more likely to achieve late seizure freedom without medication changes. At the individual level, patients may still achieve seizure freedom with ASM changes as long as ten years after the initial surgery.
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Relationship between hospital surgical volume, lobectomy rates, and adverse perioperative events at U.S. Epilepsy Centers. Journal of Neurosurgery.
Englot DJ, Ouyang D, Wang DD, Rolston JD, Garcia PA, Chang EFJournal of Neurosurgery.2013 Jan;118(1):169-74. (2014).
Abstract: Epilepsy surgery remains significantly underutilized. The authors recently reported that the number of lobectomies for localized intractable epilepsy in the US has not changed despite the implementation of clear evidence-based guidelines 10 years ago supporting early referral for surgery. To better understand why epilepsy surgery continues to be underused, the authors' objective was to carefully examine hospital-related factors related to the following: 1) where patients are being admitted for the evaluation of epilepsy, 2) rates of utilization for surgery across hospitals, and 3) perioperative morbidity between hospitals with low versus high volumes of epilepsy surgery. The authors performed a population-based cohort study of US hospitals between 1990 and 2008 using the Nationwide Inpatient Sample (NIS), stratifying epilepsy surgery rates and trends as well as perioperative morbidity rates by hospital surgical volume.
2013
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Syllabic (2-5Hz) and fluctuation (1-10Hz) ranges in speech and auditory processing. Hearing Research, 305: 113-34.
Edwards, E. & Chang, E.F. (2013).
Abstract: There has been considerable recent interest in the use of cortical auditory evoked potentials (CAEPs) as an electrophysiological measure of human speech encoding in individuals with normal as well as impaired auditory systems. The development of such electrophysiological measures such as CAEPs is important because they can be used to evaluate the benefits of hearing aids and cochlear implants in infants, young children, and adults that cannot cooperate for behavioral speech discrimination testing. The current study determined whether CAEPs produced by seven different speech sounds, which together cover a broad range of frequencies across the speech spectrum, could be differentiated from each other based on response latency and amplitude measures. CAEPs were recorded from ten adults with normal hearing in response to speech stimuli presented at a conversational level (65 dB SPL) via a loudspeaker. Cortical responses were reliably elicited by each of the speech sounds in all participants. CAEPs produced by speech sounds dominated by high-frequency energy were significantly different in amplitude from CAEPs produced by sounds dominated by lower-frequency energy. Significant effects of stimulus duration were also observed, with shorter duration stimuli producing larger amplitudes and earlier latencies than longer duration stimuli. This research demonstrates that CAEPs can be reliably evoked by sounds that encompass the entire speech frequency range. Further, CAEP latencies and amplitudes may provide an objective indication that spectrally different speech sounds are encoded differently at the cortical level. Ha existido un considerable interés reciente en el uso de los potenciales evocados auditivos corticales (CAEP) como una medida electrofisiológica de la codificación del lenguaje humano, en individuos con sistemas auditivos normales y alterados. El desarrollo de mediciones electrofisiológicas como los CAEP es importante, porque pueden ser usadas para evaluar los beneficios de los audífonos o de los implantes cocleares en infantes, niños pequeños y adultos que no pueden cooperar en evaluaciones conductuales de discriminación del lenguaje. El presente estudio determinó si los CAEP producidos por siete diferentes sonidos de lenguaje, podrían diferenciarse entre sí con base en sus medidas de latencia y amplitud de la respuesta. Se registraron los CAEP de diez adultos con audición normal en respuesta a estímulos de lenguaje presentados a nivel de conversación (65 dB SPL) a través de altoparlantes. Se generaron respuestas corticales consistentes para cada uno de los sonidos lingüísticos en todos los participantes. Los CAEP producidos por estímulos de lenguaje dominados por energía de alta frecuencia fueron significativamente diferentes en amplitud que los CAEP producidos por sonidos dominados por bajas frecuencias. Se observaron también efectos significativos en la duración del estímulo, produciendo los estímulos de corta duración amplitudes mayores y latencias más tempranas que los estímulos de duración mayor. Esta investigación demuestra que los CAEP pueden ser evocados confiablemente por sonidos que comprenden todo el rango de frecuencias del lenguaje. Más aún, las latencias y amplitudes de los CAEP pueden aportar una indicación objetiva de que sonidos espectralmente diferentes están codificados en forma diferente a nivel cortical.
https://dx.doi.org/10.1016/j.heares.2013.08.017 -
Neural evidence for state feedback control of speaking. Proceedings of Meetings on Acoustics, 19: 060178.
Houde, J.H., Kort, N.S., Niziolek, C.A., Chang, E.F., & Nagarajan, S.S. (2013).
Abstract: Hearing one's own speech allows for acoustic self-monitoring in real time. Left-hemisphere motor planning regions are thought to give rise to efferent predictions that can be compared to true feedback in sensory cortices, resulting in neural suppression commensurate with the degree of overlap between predicted and actual sensations. Sensory prediction errors thus serve as a possible mechanism of detection of deviant speech sounds, which can then feed back into corrective action, allowing for online control of speech acoustics. The goal of this study was to assess the integrity of this detection-correction circuit in persons with aphasia (PWA) whose left-hemisphere lesions may limit their ability to control variability in speech output. We recorded magnetoencephalography (MEG) while 15 PWA and age-matched controls spoke monosyllabic words and listened to playback of their utterances. From this, we measured speaking-induced suppression of the M100 neural response and related it to lesion profiles and speech behavior. Both speaking-induced suppression and cortical sensitivity to deviance were preserved at the group level in PWA. PWA with more spared tissue in pars opercularis had greater left-hemisphere neural suppression and greater behavioral correction of acoustically deviant pronunciations, whereas sparing of superior temporal gyrus was not related to neural suppression or acoustic behavior. In turn, PWA who made greater corrections had fewer overt speech errors in the MEG task. Thus, the motor planning regions that generate the efferent prediction are integral to performing corrections when that prediction is violated.
http://dx.doi.org/10.1121/1.4799495 -
Functional organization of human sensorimotor cortex for speech articulation. Nature, 495(7441):327-332.
Bouchard, K.E., Mesgarani, N., Johnson, K., & Chang, E.F. (2013).
Abstract: This book is a comprehensive guide to the International Phonetic Alphabet, whose aim is to provide a universally agreed system of notation for the sounds of languages, and which has been widely used for over a century. The Handbook presents the basics of phonetic analysis so that the principles underlying the Alphabet can be readily understood, and gives examples of the use of each of the phonetic symbols. The application of the Alphabet is then demonstrated in nearly 30 'Illustrations' - concise analyses of the sound systems of a range of languages, each of them accompanied by a phonetic transcription of a passage of speech. The Handbook also includes the 'Extensions' to the Alphabet, covering speech sounds beyond the sound-systems of languages, and a listing of the internationally agreed computer codings for phonetic symbols. It is an essential reference work for all those involved in the analysis of speech.
https://dx.doi.org/10.1038/nature11911 -
Human cortical sensorimotor network underlying feedback control of vocal pitch. Proceedings of the National Academies of Sciences, 110(7): 2653-2658.
Chang, E.F.*, Niziolek, C.*, Nagarajan, S.S., Knight, R.T., & Houde, J.S. (2013).
Abstract: This book is a comprehensive guide to the International Phonetic Alphabet, whose aim is to provide a universally agreed system of notation for the sounds of languages, and which has been widely used for over a century. The Handbook presents the basics of phonetic analysis so that the principles underlying the Alphabet can be readily understood, and gives examples of the use of each of the phonetic symbols. The application of the Alphabet is then demonstrated in nearly 30 'Illustrations' - concise analyses of the sound systems of a range of languages, each of them accompanied by a phonetic transcription of a passage of speech. The Handbook also includes the 'Extensions' to the Alphabet, covering speech sounds beyond the sound-systems of languages, and a listing of the internationally agreed computer codings for phonetic symbols. It is an essential reference work for all those involved in the analysis of speech.
https://dx.doi.org/10.1038/nature11911 -
Transmantle sign in cortical dysplasia: a unique radiologic entity with excellent prognosis for seizure-control. Journal of Neurosurgery. 118(2):337-44.
Wang DD, Deans A, Barkovich AJ, Tihan T, Garcia PA, Barbaro NM, Chang EF (2013).
Abstract: Focal cortical dysplasia (FCD) represents a spectrum of developmental cortical abnormalities and is one of the most common causes of intractable epilepsy in children and young adults. Outcomes after surgery for FCD are highly variable, and prognosticators of seizure freedom are unclear. In a subset of FCDs, a transmantle sign is observed on imaging that focally spans the entire cerebral mantle from the ventricle to the cortical surface. The aim of this study was to characterize seizure control outcomes and prognostic significance of the transmantle sign in FCD epilepsy. Fourteen patients with the transmantle sign underwent epilepsy surgery for medically refractory epilepsy. Thirteen patients underwent resective surgery and 1 underwent multiple subpial transections with vagus nerve stimulator placement. Patient demographics, MRI, electroencephalography, intraoperative electrocorticography (ECoG), and pathology were reviewed. The results of this series were compared with those of 114 previously reported patients with FCD without the transmantle sign. All patients were found to have childhood seizure onset and concordant MRI and ECoG findings. The primary MRI findings associated with transmantle sign included gray-white junction blurring, appearance of cortical thickening, T2 or FLAIR abnormality, and bottom-of-the-sulcus dysplasia. The transmantle sign was usually a focal finding, typically confined to 1 or several gyri with well-circumscribed epileptic tissue. Correlation of the transmantle sign with FCD histopathological subtypes was highly variable. Patients who underwent complete resection of MRI and ECoG abnormalities (12 of 13 patients) became seizure free. When compared with 114 FCD patients without the transmantle sign, patients with the transmantle sign showed significantly improved seizure-free outcomes after complete resections (p = 0.04). The presence of the transmantle sign in patients with medically refractory partial epilepsy is associated with highly favorable seizure control outcomes after surgical treatment.
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Safety and efficacy of motor mapping utlizing short pulse-train direct cortical stimulation. Stereotactic and Functional Neurosurgery. 91(6):379-85.
Tate MC, Guo LJ, McEvoy J, Chang EF (2013).
Abstract: A major goal of intracranial surgery is to maximize resection while minimizing neurological morbidity, particularly motor dysfunction. Direct cortical stimulation (DCS) is a common intraoperative adjunct used to identify functional motor cortex. In this study, we report on the safety/efficacy of short pulse train DCS (direct cortical stimulation motor-evoked potential, dcMEP) for motor mapping and monitoring during intracranial surgery. A retrospective analysis of 29 patients undergoing elective craniotomy for lesions near the motor cortex was performed. dcMEP mapping (40-120 V, 500-1,000 Hz, 5-9 pulses/s, 1- to 3-ms interstimulus interval, monopolar, 50-μs pulse width) was performed either alone (n = 29) or in addition to standard DCS (n = 6). Outcome measures were positive MEPs and the presence of seizures during stimulation. dcMEP-based continuous corticospinal tract (CST) monitoring was also performed. Changes in stimulation threshold and new postoperative neurological deficits were recorded. dcMEP mapping success was 96% and was not affected by preoperative motor status. Intraoperative seizure rates for dcMEP were 3% and were not related to preoperative seizure status. CST monitoring success rate was 96%, and changes in stimulation threshold were predictive of new permanent motor deficits. dcMEP is an effective method for mapping motor function and may prove useful for continuous CST monitoring.
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Seizure outcomes after temporal lobectomy in pediatric patients: A systematic review and meta-analysis. Journal of Neurosurgery: Pediatrics 12(2):134-41.
Englot DJ, Rolston JD, Wang DD, Sun P, Chang EF, Auguste KI (2013).
Abstract: Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults and is responsible for 15%-20% of epilepsy cases in children. Class I evidence strongly supports the use of temporal lobectomy for intractable TLE in adults, but fewer studies have examined seizure outcomes and predictors of seizure freedom after temporal lobectomy in pediatric patients. The authors performed a systematic review and meta-analysis of studies including 10 or more pediatric patients (age ≤ 19 years) published over the last 20 years examining seizure outcomes after temporal lobectomy for TLE. Thirty-six studies met their inclusion criteria. These 36 studies included 1318 pediatric patients with a mean age (± SEM) of 10.7 ± 0.3 years. Overall, seizure freedom (Engel Class I outcome) was achieved in 1002 cases (76%); 316 patients (24%) continued to have seizures (Engel Class II-IV outcome). All patients had at least 1 year of follow-up. Statistically significant predictors of seizure freedom after surgery included lesional epilepsy etiology (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.02-1.15), abnormal findings on preoperative MRI (OR 1.27, 95% CI 1.16-1.40), and lack of generalized seizures (OR 1.36, 95% CI 1.20-1.56). Among lesional epilepsy cases, there was a trend toward better outcome with gross-total lesionectomy than with subtotal resection. Approximately three-fourths of pediatric patients with TLE attain seizure freedom after temporal lobectomy. Favorable outcomes may be predicted by lesional epilepsy etiology, abnormal MRI, and lack of generalized seizures. Pediatric patients with medically refractory TLE should be referred to a comprehensive pediatric epilepsy center for surgical evaluation.
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Visual field defects after radiosurgery for mesial temporal lobe epilepsy. Epilepsia 54(8):1376-80.
Hensley-Judge H, Quigg M, Barbaro NM, Newman SA, Ward MM, Chang EF, Broshek DK, Lamborn KR, Laxer KD, Garcia P, Heck CN, Kondziolka D, Beach R, Salanova V, Goodman R (2013).
Abstract: Stereotactic radiosurgery (SRS) may be an alternative to anterior temporal lobectomy (ATL) for mesial temporal lobe epilepsy (MTLE). Visual field defects (VFD) occur in 9-100% of patients following open surgery for MTLE. Postoperative VFD after minimally invasive versus open surgery may differ. This prospective trial randomized patients with unilateral hippocampal sclerosis and concordant video-EEG findings to SRS versus ATL. Humphries perimetry was obtained at 24 m after surgery. VFD ratios (VFDR = proportion of missing homonymous hemifield with 0 = no VFD, 0.5 = complete superior quadrantanopsia) quantified VFD. Regressions of VFDR were evaluated against treatment arm and covariates. MRI evaluated effects of volume changes on VFDR. The relationships of VFDR with seizure remission and driving status 3 years after surgery were evaluated. No patients reported visual changes or had abnormal bedside examinations, but 49 of 54 (91%) of patients experienced VFD on formal perimetry. Neither incidence nor severity of VFDR differed significantly by treatment arm. VFDR severity was not associated with seizure remission or driving status. The nature of VFD was consistent with lesions of the optic radiations. Effective surgery (defined by seizure remission) of the mesial temporal lobe results in about a 90% incidence of typical VFD regardless of method.
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Effects of temporal lobectomy on consciousness-impairing and consciousness-sparing seizures in children. Childs Nerv Syst. 29(10):1915-22.
Englot DJ, Rutkowski MJ, Ivan ME, Sun PP, Kuperman RA, Chang EF, Gupta N, Sullivan JE, Auguste KI (2013).
Abstract: Most children with medically refractory temporal lobe epilepsy (TLE) become seizure free after temporal lobectomy, but some individuals continue to seize. As studies of temporal lobectomy typically focus on seizure freedom, the effect of surgery on seizure type and frequency among children with persistent seizures is poorly understood. Seizures which impair consciousness are associated with increased morbidity compared to consciousness-sparing seizures. A retrospective cohort study was performed to evaluate the effects of temporal lobectomy on seizure type and frequency in children with intractable TLE. Among 58 pediatric TLE patients with a mean (±SEM) age of 14.0 ± 0.7 years who received temporal lobectomy, 46 (79.3%) individuals achieved an Engel class I seizure outcome, including 38 (65.5%) children who became completely seizure free (Engel IA). Mean follow-up was 2.7 ± 0.4 years. While the number of patients experiencing simple partial seizures (SPSs) (consciousness sparing) decreased by only 23 % after surgery, the number of children having complex partial seizures and generalized tonic-clonic seizures (consciousness impairing) diminished by 87 and 83%, respectively (p < 0.01). SPS was the predominant seizure type in only 11.3% of patients before resection, but in 42.1% of patients with postoperative seizures (p < 0.01). Children with postoperative seizures experienced a 70% reduction in overall seizure frequency compared to baseline (p < 0.05), having consciousness-impairing seizures 94% less frequently (p < 0.05), but having consciousness-sparing seizures 35% more frequently (p = 0.73). Seizure type and frequency are important considerations in the medical and surgical treatment of children with epilepsy, although complete seizure freedom remains the ultimate goal.
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Seizure outcomes after temporal lobectomy in pediatric patients. J Neurosurg Pediatr. 12(2):134-41.
Englot DJ, Rolston JD, Wang DD, Sun PP, Chang EF, Auguste KI (2013).
Abstract: Epilepsy surgery can potentially cure pharmacoresistant temporal lobe epilepsy (TLE) in children. However, surgical failures, where patients continue to experience seizures, still exist. We evaluated outcomes in pediatric patients after resective temporal lobe surgery to identify risk factors for failure. Data on pediatric patients with TLE who underwent surgery were prospectively collected at our institution. Minimum follow-up (FU) was three years after surgery. Resections were stratified into extended resections, i.e., anterior temporal lobectomies, and sparing resections, i.e., lesionectomies and selective amygdalohippocampectomies. Ongoing seizures and relapses within the first three years were considered surgical failures. We included 96 patients after 43 sparing and 52 extended resections from 1993 to 2019 with a median FU of 10.1 years (range 3.0 to 28.3 years). Pathohistology most frequently revealed epilepsy-associated tumors (44.8%), hippocampal sclerosis (37.5%), and focal cortical dysplasias (12.5%). One year postoperatively, 69.8% were seizure free, increasing to 78.5% after five and 72.9% after 10 years. Sparing resections increased the odds for surgical failure in a multivariate analysis (odds ratio: 4.63, P = 0.006). Preoperative focal onset to bilateral tonic-clonic seizures increased the likelihood of seizure relapses (hazard ratio: 3.89, P = 0.006) and contributed to higher odds of surgical failure (odds ratio: 2.79, P = 0.002). Pediatric patients with TLE undergoing surgery have high rates of long-lasting favorable seizure outcomes. Resection strategy is a prognostic factor for early surgical success in favor of larger resections. Relapses were more frequent in children with focal onset to bilateral tonic-clonic seizures beforesurgery.
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Seizure outcomes after resective surgery for extra-temporal lobe epilepsy in pediatric patients. J Neurosurg Pediatr. 12(2):126-33
Englot DJ, Breshears JD, Sun PP, Chang EF, Auguste KI. (2013).
Abstract: While temporal lobe epilepsy (TLE) is the most common epilepsy syndrome in adults, seizures in children are more often extratemporal in origin. Extra-temporal lobe epilepsy (ETLE) in pediatric patients is often medically refractory, leading to significantly diminished quality of life. Seizure outcomes after resective surgery for pediatric ETLE vary tremendously in the literature, given diverse patient and epilepsy characteristics and small sample sizes. The authors performed a systematic review and meta-analysis of studies including 10 or more pediatric patients (age ≤ 19 years) published over the last 20 years examining seizure outcomes after resective surgery for ETLE, excluding hemispherectomy. Thirty-six studies were examined. These 36 studies included 1259 pediatric patients who underwent resective surgery for ETLE. Seizure freedom (Engel Class I outcome) was achieved in 704 (56%) of these 1259 patients postoperatively, and 555 patients (44%) continued to have seizures (Engel Class II-IV outcome). Shorter epilepsy duration (≤ 7 years, the median value in this study) was more predictive of seizure freedom than longer (> 7 years) seizure history (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.07-2.14), suggesting that earlier intervention may be beneficial. Also, lesional epilepsy was associated with better seizure outcomes than nonlesional epilepsy (OR 1.34, 95% CI 1.19-1.49). Other predictors of seizure freedom included an absence of generalized seizures (OR 1.61, 95% CI 1.18-2.35) and localizing ictal electroencephalographic findings (OR 1.55, 95% CI 1.24-1.93). In conclusion, seizure outcomes after resective surgery for pediatric ETLE are less favorable than those associated with temporal lobectomy, but seizure freedom may be more common with earlier intervention and lesional epilepsy etiology. Children with continued debilitating seizures despite failure of multiple medication trials should be referred to a comprehensive pediatric epilepsy center for further medical and surgical evaluation.
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Seizure types and frequency in patients who “fail” temporal lobectomy for intractable epilepsy. Neurosurgery. 73(5):838-44.
Englot DJ, Lee AT, Tsai C, Halabi C, Barbaro NM, Auguste KI, Garcia PA, Chang EF (2013).
Abstract: Temporal lobectomy can lead to favorable seizure outcomes in medically-refractory temporal lobe epilepsy (TLE). Although most studies focus on seizure freedom after temporal lobectomy, less is known about seizure semiology in patients who "fail" surgery. Morbidity differs between seizure types that impair or spare consciousness. Among TLE patients with seizures after surgery, how does temporal lobectomy influence seizure type and frequency? To characterize seizure types and frequencies before and after temporal lobectomy for TLE, including consciousness-sparing or consciousness-impairing seizures. We performed a retrospective longitudinal cohort study examining patients undergoing temporal lobectomy for epilepsy at our institution from January 1995 to August 2010. Among 241 TLE patients who received temporal lobectomy, 174 (72.2%) patients achieved Engel class I outcome (free of disabling seizures), including 141 (58.5%) with complete seizure freedom. Overall seizure frequency in patients with persistent postoperative seizures decreased by 70% (P < .01), with larger reductions in consciousness-impairing seizures. While the number of patients experiencing consciousness-sparing simple partial seizures decreased by only 19% after surgery, the number of individuals having consciousness-impairing complex partial seizures and generalized tonic-clonic seizures diminished by 70% and 68%, respectively (P < .001). Simple partial seizure was the predominant seizure type in 19.1% vs 37.0% of patients preoperatively and postoperatively, respectively (P < .001). Favorable seizure outcome was predicted by a lack of generalized seizures preoperatively (odds ratio 1.74, 95% confidence interval 1.06-2.86, P < .5). Given important clinical and mechanistic differences between seizures with or without impairment of consciousness, seizure type and frequency remain important considerations in epilepsy surgery.
2012
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Real-time, single-trial mapping of cortical event-related activation. Journal of Neural Engineering, 9(4):046018.
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Selective cortical representation of attended speech in multi-talker speech perception. Nature, 485(7397):233-236.
Mesgarani, N. & Chang, E.F. (2012).
Abstract: Impaired speech perception in noise despite normal peripheral auditory function is a common problem in young adults. Despite a growing body of research, the pathophysiology of this impairment remains unknown. This magnetoencephalography study characterizes the cortical tracking of speech in a multi-talker background in a group of highly selected adult subjects with impaired speech perception in noise without peripheral auditory dysfunction. Magnetoencephalographic signals were recorded from 13 subjects with impaired speech perception in noise (six females, mean age: 30 years) and matched healthy subjects while they were listening to 5 different recordings of stories merged with a multi-talker background at different signal to noise ratios (No Noise, +10, +5, 0 and -5 dB). The cortical tracking of speech was quantified with coherence between magnetoencephalographic signals and the temporal envelope of (i) the global auditory scene (i.e. the attended speech stream and the multi-talker background noise), (ii) the attended speech stream only and (iii) the multi-talker background noise. Functional connectivity was then estimated between brain areas showing altered cortical tracking of speech in noise in subjects with impaired speech perception in noise and the rest of the brain. All participants demonstrated a selective cortical representation of the attended speech stream in noisy conditions, but subjects with impaired speech perception in noise displayed reduced cortical tracking of speech at the syllable rate (i.e. 4-8 Hz) in all noisy conditions. Increased functional connectivity was observed in subjects with impaired speech perception in noise in Noiseless and speech in noise conditions between supratemporal auditory cortices and left-dominant brain areas involved in semantic and attention processes. The difficulty to understand speech in a multi-talker background in subjects with impaired speech perception in noise appears to be related to an inaccurate auditory cortex tracking of speech at the syllable rate. The increased functional connectivity between supratemporal auditory cortices and language/attention-related neocortical areas probably aims at supporting speech perception and subsequent recognition in adverse auditory scenes. Overall, this study argues for a central origin of impaired speech perception in noise in the absence of any peripheral auditory dysfunction.
https://dx.doi.org/10.1038/nature11020 -
Reconstructing speech from human auditory cortex. PLoS Biology, 10(1): e1001251.
Pasley, B., David, S.V., Mesgarani, N., Flinker, A., Shamma, S.A., Crone, N.E., Knight, R.T., & Chang, E.F. (2012).
Abstract: Speech is the most interesting and one of the most complex sounds dealt with by the auditory system. The neural representation of speech needs to capture those features of the signal on which the brain depends in language communication. Here we describe the representation of speech in the auditory nerve and in a few sites in the central nervous system from the perspective of the neural coding of important aspects of the signal. The representation is tonotopic, meaning that the speech signal is decomposed by frequency and different frequency components are represented in different populations of neurons. Essential to the representation are the properties of frequency tuning and nonlinear suppression. Tuning creates the decomposition of the signal by frequency, and nonlinear suppression is essential for maintaining the representation across sound levels. The representation changes in central auditory neurons by becoming more robust against changes in stimulus intensity and more transient. However, it is probable that the form of the representation at the auditory cortex is fundamentally different from that at lower levels, in that stimulus features other than the distribution of energy across frequency are analysed.
https://dx.doi.org/10.1371/journal.pbio.1001251 -
Extent of surgical resection predicts seizure freedom in low-grade temporal lobe brain tumors. Neurosurgery 70(4):921-8.
Englot DJ, Berger MS, Barbaro NM, Chang EF (2012).
Abstract: Achieving seizure control in patients with low-grade temporal lobe gliomas or glioneuronal tumors remains highly underappreciated, because seizures are the most frequent presenting symptom and significantly impact patient quality-of-life. To assess how the extent of temporal lobe resection influences seizure outcome. We performed a quantitative, comprehensive systematic literature review of seizure control outcomes in 1181 patients with epilepsy across 41 studies after surgical resection of low-grade temporal lobe gliomas and glioneuronal tumors. We measured seizure-freedom rates after subtotal resection vs gross-total lesionectomy alone vs tailored resection, including gross-total lesionectomy with hippocampectomy and/or anterior temporal lobe corticectomy. Included studies were observational case series, and no randomized, controlled trials were identified. Although only 43% of patients were seizure-free after subtotal tumor resection, 79% of individuals were seizure-free after gross-total lesionectomy (OR = 5.00, 95% confidence interval [CI]: 3.33-7.14). Furthermore, tailored resection with hippocampectomy plus corticectomy conferred additional benefit over gross-total lesionectomy alone, with 87% of patients achieving seizure freedom (OR = 1.82, 95% CI: 1.23-2.70). Overall, extended resection with hippocampectomy and/or corticectomy over gross-total lesionectomy alone significantly predicted seizure freedom (OR = 1.18, 95% CI: 1.11-1.26). Age <18 years and mesial temporal location also prognosticated favorable seizure outcome. Gross-total lesionectomy of low-grade temporal lobe tumors results in significantly improved seizure control over subtotal resection. Additional tailored resection including the hippocampus and/or adjacent cortex may further improve seizure control, suggesting dual pathology may sometimes allow continued seizures after lesional excision.
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Factors associated with seizure freedom in the surgical resection of glioneuronal tumors. Epilepsia 53(1):51-7.
Englot DJ, Berger MS, Barbaro NM, Chang EF (2012).
Abstract: Seizures are one of the most common symptoms of brain tumors. The incidence of seizures differs among brain tumor type, grade, location and size, but paediatric-type diffuse low-grade gliomas/glioneuronal tumors are often highly epileptogenic. The extracellular matrix (ECM) is known to play a role in epileptogenesis and tumorigenesis because it is involved in the (re)modelling of neuronal connections and cell-cell signaling. In this review, we discuss the epileptogenicity of brain tumors with a focus on tumor type, location, genetics and the role of the extracellular matrix. In addition to functional problems, epileptogenic tumors can lead to increased morbidity and mortality, stigmatization and life-long care. The health advantages can be major if the epileptogenic properties of brain tumors are better understood. Surgical resection is the most common treatment of epilepsy-associated tumors, but post-surgery seizure-freedom is not always achieved. Therefore, we also discuss potential novel therapies aiming to restore ECM function.
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Epilepsy surgery trends in United States, 1990-2008. Neurology. 17
Englot DJ, Ouyang D, Barbaro NM, Garcia PA, Chang EF (2012).
Abstract: We performed a population-based cohort study with time trends of patients admitted to US hospitals for medically refractory focal epilepsy between 1990 and 2008 who did or did not undergo lobectomy, as reported in the Nationwide Inpatient Sample. Weighted data revealed 112,026 hospitalizations for medically refractory focal epilepsy and 6,653 resective surgeries (lobectomies and partial lobectomies) from 1990 to 2008. A trend of increasing hospitalizations over time was not accompanied by an increase in surgeries, producing an overall trend of decreasing surgery rates (F = 13.6, p < 0.01). Factors associated with this trend included a decrease in epilepsy hospitalizations at the highest-volume epilepsy centers, and increased hospitalizations to lower-volume hospitals that were found to be less likely to perform surgery. White patients were more likely to have surgery than racial minorities (relative risk [RR], 1.13; 95% confidence interval [CI], 1.10–1.17), and privately insured individuals were more likely to receive lobectomy than those with Medicaid or Medicare (RR, 1.28; 95% CI, 1.25–1.30). Despite Class I evidence and subsequent practice guidelines, the utilization of lobectomy has not increased from 1990 to 2008. Surgery continues to be heavily underutilized as a treatment for epilepsy, with significant disparities by race and insurance coverage. Patients who are medically refractory after failing 2 antiepileptic medications should be referred to a comprehensive epilepsy center for surgical evaluation.
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Rates and predictors of long-term seizure freedom after frontal lobe epilepsy surgery: a systematic review and meta-analysis. Journal of Neurosurgery 116(5):1042-8.
Englot DJ, Wang DD, Rolston J, Shih T, Chang EF (2012).
Abstract: Frontal lobe epilepsy (FLE) is the second-most common focal epilepsy syndrome, and seizures are medically refractory in many patients. Although various studies have examined rates and predictors of seizure freedom after resection for FLE, there is significant variability in their results due to patient diversity, and inadequate follow-up may lead to an overestimation of long-term seizure freedom. In this paper the authors report a systematic review and meta-analysis of long-term seizure outcomes and predictors of response after resection for intractable FLE. Only studies of at least 10 patients examining seizure freedom after FLE surgery with postoperative follow-up duration of at least 48 months were included. Across 1199 patients in 21 studies, the overall rate of postoperative seizure freedom (Engel Class I outcome) was 45.1%. No trend in seizure outcomes across all studies was observed over time. Significant predictors of long-term seizure freedom included lesional epilepsy origin (relative risk [RR] 1.67, 95% CI 1.36-28.6), abnormal preoperative MRI (RR 1.64, 95% CI 1.32-2.08), and localized frontal resection versus more extensive lobectomy with or without an extrafrontal component (RR 1.71, 95% CI 1.26-2.43). Within lesional FLE cases, gross-total resection led to significantly improved outcome versus subtotal lesionectomy (RR 1.99, 95% CI 1.47-2.84). These findings suggest that FLE patients with a focal and identifiable lesion are more likely to achieve seizure freedom than those with a more poorly defined epileptic focus. While seizure freedom can be achieved in the surgical treatment of medically refractory FLE, these findings illustrate the compelling need for improved noninvasive and invasive localization techniques in FLE.
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Comparison of seizure control outcomes and safety of vagus nerve, deep brain, and responsive neurostimulation: evidence from randomized controlled trials. Neurosurgical Focus 32(3)E14.
Rolston JD, Englot DJ, Wang DD, Shih T, Chang EF (2012).
Abstract: Epilepsy is a devastating disease, often refractory to medication and not amenable to resective surgery. For patients whose seizures continue despite the best medical and surgical therapy, 3 stimulation-based therapies have demonstrated positive results in prospective randomized trials: vagus nerve stimulation, deep brain stimulation of the thalamic anterior nucleus, and responsive neurostimulation. All 3 neuromodulatory therapies offer significant reductions in seizure frequency for patients with partial epilepsy. A direct comparison of trial results, however, reveals important differences among outcomes and surgical risk between devices. The authors review published results from these pivotal trials and highlight important differences between the trials and devices and their application in clinical use.
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A meta-analysis of predictors of seizure freedom in the surgical management of focal cortical dysplasia. Journal of Neurosurgery. 116(5):1035-41.
Rowland NC, Englot DJ, Cage T, Sughrue ME, Barbaro NM, Chang EF (2012).
Abstract: Focal cortical dysplasia (FCD) is one of the most common causes of medically refractory epilepsy leading to surgery. However, seizure control outcomes reported in isolated surgical series are highly variable. As a result, it is not clear which variables are most crucial in predicting seizure freedom following surgery for FCD. The authors' aim was to determine the prognostic factors for seizure control in FCD by performing a meta-analysis of the published literature. A MEDLINE search of the published literature yielded 37 studies that met inclusion and exclusion criteria. Seven potential prognostic variables were determined from these studies and were dichotomized for analysis. For each variable, individual studies were weighted by inverse variance and combined to generate an odds ratio favoring seizure freedom. The methods complied with a standardized meta-analysis reporting protocol. Two thousand fourteen patients were included in the analysis. The overall rate of seizure freedom (Engel Class I) among patients undergoing surgery for FCD in the cohort of studies was 55.8% ± 16.2%. Partial seizures, a temporal location, detection with MRI, and a Type II Palmini histological classification were associated with higher rates of postoperative seizure control. As a treatment-related factor, complete resection of the anatomical or electrographic abnormality was the most important predictor overall of seizure freedom. Neither age nor electroencephalographic localization of the ictal onset significantly affected seizure freedom after surgery. Using a large population cohort pooled from the published literature, an analysis identified important factors that are prognostic in patients with epilepsy due to FCD. The most important of these factors-diagnostic imaging and resection-provide modalities through which improvements in the impact of FCD can be effected.
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Long-term seizure outcomes after resection of gangliogliomas. Neurosurgery. 70(6):1406-13
Southwell D, Berger MS, Barbaro NB, Chang EF (2012).
Abstract: Ganglioglioma is a rare primary brain tumour that most frequently occurs in children and young adults. They are generally low-grade and have a favourable prognosis, but there is limited literature to guide the optimal management. The aim of this study was to investigate the clinical outcomes of adults with intracranial ganglioglioma, and to determine the frequency and duration of radiological follow-up. Thirteen adult patients with CNS WHO grade 1 and 2 ganglioglioma were identified retrospectively from case records at a tertiary neurosurgical centre between 2010 and 2022. Patient characteristics, magnetic resonance imaging (MRI) features, and clinical outcomes were obtained. Surgery was classified as gross total (GTR) or subtotal (STR) resection. 84.6 % (n = 11) of patients had temporal lobe tumours, with most (69.2 %) presenting with seizures, at a median age of 29.0 years. GTR and STR were achieved in nine and five patients, respectively. No patients received adjuvant radiotherapy. During the median follow-up period of 8.9 years there was no radiological recurrence after GTR, and only one recurrence after STR at 65 months that did not require treatment. There was no patient mortality. Two patients continued to have seizures at last clinical follow-up. Low grade adult intracranial ganglioglioma has an excellent prognosis, with a recurrence rate below 10 % in this series. Long-term surveillance is not necessarily required if GTR has been achieved and patients can be considered for discharge after annual MRI for 5 years. In patients where only STR is achieved, annual MRI is required although the progression/recurrence rate remains low and asymptomatic.
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Seizure predictors and control after microsurgical resection of supratentorial arteriovenous malformations in 440 patients. Neurosurgery 71(3)572-80.
Englot DJ, Young WL,Han SJ, McCullough CE, Chang EF, Lawton EF (2012).
Abstract: Seizures are a common symptom of supratentorial arteriovenous malformations (AVMs), and uncontrolled epilepsy can considerably reduce patient quality of life. Potential risk factors for epilepsy in patients with AVMs are poorly understood, and the importance of achieving freedom from seizures in their surgical treatment remains underappreciated. To characterize risks factors for preoperative seizures and factors associated with postoperative freedom from seizures in patients with surgically resected supratentorial AVMs. We analyzed prospectively collected patient data for 440 patients who underwent microsurgical resection of supratentorial AVMs at our institution. Among 440 patients with supratentorial AVMs, 130 (30%) experienced preoperative seizures, and 23 (18%) with seizures progressed to medically refractory epilepsy. Seizures were associated with a history of AVM hemorrhage (relative risk, 6.65; 95% confidence interval [CI], 3.81-11.6), male sex (relative risk, 2.07; 95% CI, 1.26-3.39), and frontotemporal lesion location (relative risk, 1.75; 95% CI, 1.05-2.93). After resection, 96% of patients had a modified Engel class I outcome, characterized by freedom from seizures (80%) or only 1 postoperative seizure (16%; mean follow-up, 20.7 ± 2.3 months). Comparable rates of postoperative seizures were seen in patients with (7%) or without (3%) preoperative seizures. AVMs with deep artery perforators were significantly associated with postoperative seizures (hazard ratio, 4.35; 95% CI, 1.61-11.7). In the microsurgical treatment of supratentorial AVMs, hemorrhage, male sex, and frontotemporal location are associated with higher rates of preoperative seizures, whereas deep artery perforators are associated with postoperative seizures. Achieving freedom from seizure is an important goal that can be achieved in the surgical treatment of AVMs because epilepsy can significantly diminish patient quality of life.
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Efficacy of vagus nerve stimulation in post-traumatic versus non-traumatic epilepsy. Journal of Neurosurgery. 117(5):970-7.
Englot DJ, Wang DD, Rolston JD, Hassnain K, Gordon C, Chang EF (2012).
Abstract: Object: In the US, approximately 500,000 individuals are hospitalized yearly for traumatic brain injury (TBI), and posttraumatic epilepsy (PTE) is a common sequela of TBI. Improved treatment strategies for PTE are critically needed, as patients with the disorder are often resistant to antiepileptic medications and are poor candidates for definitive resection. Vagus nerve stimulation (VNS) is an adjunctive treatment for medically refractory epilepsy that results in a ≥ 50% reduction in seizure frequency in approximately 50% of patients after 1 year of therapy. The role of VNS in PTE has been poorly studied. The aim of this study was to determine whether patients with PTE attain more favorable seizure outcomes than individuals with nontraumatic epilepsy etiologies. Methods: Using a case-control study design, the authors retrospectively compared seizure outcomes after VNS therapy in patients with PTE versus those with nontraumatic epilepsy (non-PTE) who were part of a large prospectively collected patient registry. Results: After VNS therapy, patients with PTE demonstrated a greater reduction in seizure frequency (50% fewer seizures at the 3-month follow-up; 73% fewer seizures at 24 months) than patients with non-PTE (46% fewer seizures at 3 months; 57% fewer seizures at 24 months). Overall, patients with PTE had a 78% rate of clinical response to VNS therapy at 24 months (that is, ≥ 50% reduction in seizure frequency) as compared with a 61% response rate among patients with non-PTE (OR 1.32, 95% CI 1.07-1.61), leading to improved outcomes according to the Engel classification (p < 0.0001, Cochran-Mantel-Haenszel statistic). Conclusions: Vagus nerve stimulation should be considered in patients with medically refractory PTE who are not good candidates for resection. A controlled prospective trial is necessary to further examine seizure outcomes as well as neuropsychological outcomes after VNS therapy in patients with intractable PTE.
2011
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Functional mapping-guided resection of low-grade gliomas in eloquent areas of the brain: improvement of long-term survival. Journal of Neurosurgery. 114(3):566-73. *chosen as best paper in Journal of Neurosurgery for 2011
Chang, EF, Clark, A, Smith, JS, Polley, MY, Chang, SM, Barbaro, NM, McDermott, MW, Berger, MS (2011).
Abstract: Low-grade gliomas (LGGs) frequently infiltrate highly functional or "eloquent" brain areas. Given the lack of long-term survival data, the prognostic significance of eloquent brain tumor location and the role of functional mapping during resective surgery in presumed eloquent brain regions are unknown. We performed a retrospective analysis of 281 cases involving adults who underwent resection of a supratentorial LGG at a brain tumor referral center. Preoperative MR images were evaluated blindly for involvement of eloquent brain areas, including the sensorimotor and language cortices, and specific subcortical structures. For high-risk tumors located in presumed eloquent brain areas, long-term survival estimates were evaluated for patients who underwent intraoperative functional mapping with electrocortical stimulation and for those who did not. One hundred and seventy-four patients (62%) had high-risk LGGs that were located in presumed eloquent areas. Adjusting for other known prognostic factors, patients with tumors in areas presumed to be eloquent had worse overall and progression-free survival (OS, hazard ratio [HR] 6.1, 95% CI 2.6-14.1; PFS, HR 1.9, 95% CI 1.2-2.9; Cox proportional hazards). Confirmation of tumor overlapping functional areas during intraoperative mapping was strongly associated with shorter survival (OS, HR 9.6, 95% CI 3.6-25.9). In contrast, when mapping revealed that tumor spared true eloquent areas, patients had significantly longer survival, nearly comparable to patients with tumors that clearly involved only noneloquent areas, as demonstrated by preoperative imaging (OS, HR 2.9, 95% CI 1.0-8.5). Presumed eloquent location of LGGs is an important but modifiable risk factor predicting disease progression and death. Delineation of true functional and nonfunctional areas by intraoperative mapping in high-risk patients to maximize tumor resection can dramatically improve long-term survival.
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Homotopic organization of right hemisphere essential language sites in right and bilateral cerebral hemispheric dominance. Journal of Neurosurgery. 114(4):893-902.
Chang EF, Wang DD, Perry DW, Barbaro NM, Berger MS (2011).
Abstract: Language dominance in the right hemisphere is rare. Therefore, the organization of essential language sites in the dominant right hemisphere is unclear, especially compared with cases involving the more prevalent left dominant hemisphere. The authors reviewed the medical records of 15 patients who underwent awake craniotomy for tumor or epilepsy surgery and speech mapping of right hemisphere perisylvian language areas at the University of California, San Francisco. All patients were determined to have either complete right-sided or bilateral language dominance by preoperative Wada testing. All patients but one were left-handed. Of more than 331 total stimulation sites, 27 total sites were identified as essential for language function (14 sites for speech arrest/anarthria; 12 for anomia; and 1 for alexia). While significant interindividual variability was observed, the general pattern of language organization was similar to classic descriptions of frontal language production and posterior temporal language integration for the left hemisphere. Speech arrest sites were clustered in the ventral precentral gyrus and pars opercularis. Anomia sites were more widely distributed, but were focused in the posterior superior and middle temporal gyri as well as the inferior parietal gyrus. One alexia site was found over the superior temporal gyrus. Face sensory and motor cortical sites were also identified along the ventral sensorimotor strip. The prevalence and specificity of essential language sites were greater in unilateral right hemisphere-dominant patients, compared with those with bilateral dominance by Wada testing. The authors' results suggest that the organization of language in right hemisphere dominance mirrors that of left hemisphere dominance. Awake speech mapping is a safe and reliable surgical adjunct in these rare clinical cases and should be done in the setting of right hemisphere dominance to avoid preventable postoperative aphasia.
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Early surgical intervention in adult patients with ganglioglioma is associated with improved clinical seizure outcomes. Journal of Clinical Neuroscience. 18(1):28-33.
Yang I, Chang EF, Han SJ, Barry JJ, Fang S Tihan T, Barbaro NM, Parsa AT (2011).
Abstract: Gangliogliomas are rare central nervous system tumors, most commonly affecting children and young adults. Chronic seizure and epilepsy are the most frequent presentation of patients with gangliogliomas. In this report, we review the modern literature regarding the effects of early surgical intervention on the clinical outcome of patients with ganglioglioma. A boolean search of PubMed using key words "ganglioglioma", "adult", "seizure control", "treatment", "surgical intervention", and "observation", alone and in combination was performed. The inclusion criteria for articles were that: (i) clinical outcomes were reported specifically for gangliogliomas; (ii) data were reported for adult patients older than the age of 18 years; (iii) treatment data were included for the treatment of gangliogliomas; and (iv) ganglioglioma was the only pathological diagnosis for the evaluation of the tumor. Data were analyzed as a whole then stratified into two groups: early and late treatment intervention. The query identified a total of 99 articles including 1,089 cases of ganglioglioma meeting our inclusion and exclusion criteria. There was a 55% prevalence of males, representing a statistically significant predilection (51-59%, 95% confidence interval). Seizure control was significantly improved when surgical intervention occurred less than 3 years after symptom onset (78% versus 48%; p = 0.0001). Ganglioglioma in adults represents a rare group of tumors, and our systematic analysis suggests a higher prevalence in males. Our findings also support that an early surgical intervention is significantly associated with improved clinical seizure control.
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Seizure freedom after surgery for malformations of cortical development. Annals of Neurology 70(1):151-62.
Chang EF, Wang DD, Barkovich AJ, Tihan T, Auguste KI, Sullivan JE, Garcia PA, Barbaro NM (2011).
Abstract: The identification of surgical candidates is a critical issue in patients with magnetic resonance imaging (MRI)-negative drug-resistant focal epilepsy and latent accompanying resectable lesions, such as focal cortical dysplasia (FCD). Recently, periodic seizure cycles have been associated with FCD in both patients with MRI-positive and MRI-negative epilepsy. We investigated the presurgical evaluation and postsurgical outcome of patients with MRI-negative epilepsy with FCD and a history of periodic seizure cycles. We retrospectively reviewed the characteristics of presurgical evaluation and postsurgical seizure outcome in 14 children with MRI-negative drug-resistant focal epilepsy and a history of periodic seizure cycles. All the patients had FCD histopathologically. The mean age at epilepsy surgery was 7.7 ± 4.7 years (0.7-16.1 years). Favorable postsurgical seizure outcome (ILAE classes 1-3) was obtained in 10 (71 %) patients five years after surgery. The relative risk of the complete concordance between imaging findings and resected area for five-year seizure freedom was 2.25 in positron emission tomography (PET) and 2.22 in subtraction ictal single-photon emission computed tomography co-registered to MRI (SISCOM), and 1.86 in magnetoencephalography (MEG). All the children with MRI-negative focal epilepsy and a history of periodic seizure cycles were turned out to have FCD pathologically, and are good surgical candidates. Favorable seizure outcome can be expected in such patients when resective epilepsy surgery is planned based on presurgical evaluation with PET or SISCOM.
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Predictors of seizure freedom after surgical resection of supratentorial low-grade gliomas. Journal of Neurosurgery 115(2):240-4.
Englot DJ, Barbaro NM, Berger MS, Chang EF (2011).
Abstract: Seizures present in 50-90 % of cases with low-grade brain tumors. Frontal lobe epilepsy is associated with dismal seizure outcomes compared to temporal lobe epilepsy. Our objective is to conduct a systematic review, report our case series, and perform a pooled analysis of clinical predictors of seizure outcomes in frontal lobe low-grade brain tumors. Searches of five electronic databases from January 1990 to June 2022 were reviewed following PRISMA guidelines. Individual patient data was extracted from 22 articles that fit the inclusion criteria. A single-surgeon case series from our institution was also retrospectively reviewed and analyzed through a pooled cohort of 127 surgically treated patients with frontal lobe low-grade brain tumors. The mean age at surgery was 30.8 years, with 50.4 % of patients diagnosed as oligodendrogliomas. The majority of patients (81.1 %) were seizure-free after surgery (Engel I). On the multivariate analysis, gross total resection (GTR) (OR = 8.77, 95 % CI: 1.99-47.91, p = 0.006) and awake resection (OR = 9.94, 95 % CI: 1.93-87.81, p = 0.015) were associated with seizure-free outcome. A Kaplan-Meier curve showed that the probability of seizure freedom fell to 92.6 % at 3 months, and to 85.5 % at 27.3 months after surgery. Epilepsy from tumor origin demands a balance between oncological management and epilepsy cure. Our pooled analysis suggests that GTR and awake resections are positive predictive factors for an Engel I at more than 6 months follow-up. To validate these findings, a longer-term follow-up and larger cohorts are needed.
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Vagus nerve stimulation for epilepsy: a systematic review of efficacy and predictors of response. Journal of Neurosurgery. 115(6):1248-55.
Englot DJ, Chang EF, Auguste KI (2011).
Abstract: Vagus nerve stimulation (VNS) is a mainstay treatment in people with medically refractive epilepsy with a growing interest to identify biomarkers that are predictive of VNS efficacy. In this review, we looked at electroencephalography (EEG) and heart rate variability (HRV) parameters as potential biomarkers. A comprehensive search of several databases limited to the English language and excluding animal studies was conducted. Data was collected from studies that specifically reviewed preoperative EEG and HRV characteristics as predictive factors of VNS outcomes. Ten out of 1078 collected studies were included in this review, of which EEG characteristics were reported in seven studies; HRV parameters were reported in two studies, and one study reported both. For EEG, studies reported a lower global rate of synchronization in alpha, delta, and gamma waves as predictors of the VNS response. The P300 wave, an evoked response on EEG, had conflicting results. Two studies reported high P300 wave amplitudes in nonresponders and low amplitudes in responders, whereas another study reported high P300 wave amplitudes in responders. For HRV, one study reported high-frequency power as the only parameter to be significantly lower in responders. In contrast, two studies from the same authors showed that HRV parameters were not different between responders and nonresponders. HRV parameters and EEG characteristics including focal seizures and P300 wave have been reported as potential biomarkers for VNS outcomes in people with medically refractive epilepsy. However, the contradictory findings imply a need for validation through clinical trials.
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Predictors of seizure-freedom in the surgical treatment of supratentorial cavernous malformations. Journal of Neurosurgery. 115(6):1169-74.
Englot DJ, Han SJ, Lawton MT, Chang EF (2011).
Abstract: Symptomatic supratentorial cavernous malformations may present with seizure, headache, neurological deficit, or a combination thereof. Factors that contribute to treatment algorithms commonly include patient age, lesion size and location, lesion multiplicity, hemorrhage history, and the ability to control seizure activity with medication. A better appreciation of the impact of patient and lesion characteristics on post-operative seizure control may provide insight into management strategies. To determine long-term seizure outcomes following surgical resection of supratentorial cavernous malformations, the predictive value of characteristics including seizure duration and number, presence of generalized seizures, and lesion multiplicity and size on seizure control rate was evaluated. We performed a single institution retrospective review of consecutive patients with supratentorial cavernous malformations presenting with at least one seizure between 1995 and 2008. Univariate and multivariate analyses were used to determine the influence of patient and lesion characteristics on postoperative seizure control. Fifty-six patients met inclusion criteria. Mean follow-up duration was 87.9 months. At last follow-up there were 46 patients (82.1%) that were free from impairing seizures (Engel Class 1). Ten patients (17.9%) were classified as Engel Class 2-4. Univariate analysis demonstrated that only the presence of multiple cavernomas was associated with worse post-operative seizure outcome (p=0.006). Multivariate analysis demonstrated that multiple cavernomas remained a significant predictor for development of worse seizure outcome controlling for number and duration of seizures prior to operation, presence of generalized tonic-clonic seizures, and size (odds ratio, 0.17; 95% confidence interval, 0.03, 0.99). Resection of supratentorial cavernomas is associated with a high rate of postoperative seizure freedom. The presence of multiple cavernomas is predictive of seizure persistence following surgery.
2010
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Categorical speech representation in the human superior temporal gyrus. Nature Neuroscience, 13(11): 1428-32.
Chang, E.F.*, Rieger, J.*, Johnson, K.D., Berger, M.S., Barbaro, N.M., & Knight, R.T. (2010).
Abstract: Watching a speaker's face improves speech perception accuracy. This benefit is enabled, in part, by implicit lipreading abilities present in the general population. While it is established that lipreading can alter the perception of a heard word, it is unknown how these visual signals are represented in the auditory system or how they interact with auditory speech representations. One influential, but untested, hypothesis is that visual speech modulates the population-coded representations of phonetic and phonemic features in the auditory system. This model is largely supported by data showing that silent lipreading evokes activity in the auditory cortex, but these activations could alternatively reflect general effects of arousal or attention or the encoding of non-linguistic features such as visual timing information. This gap limits our understanding of how vision supports speech perception. To test the hypothesis that the auditory system encodes visual speech information, we acquired functional magnetic resonance imaging (fMRI) data from healthy adults and intracranial recordings from electrodes implanted in patients with epilepsy during auditory and visual speech perception tasks. Across both datasets, linear classifiers successfully decoded the identity of silently lipread words using the spatial pattern of auditory cortex responses. Examining the time course of classification using intracranial recordings, lipread words were classified at earlier time points relative to heard words, suggesting a predictive mechanism for facilitating speech. These results support a model in which the auditory system combines the joint neural distributions evoked by heard and lipread words to generate a more precise estimate of what was said.
https://dx.doi.org/10.1038/nn.2641 -
Cortical spatiotemporal dynamics underlying phonological target detection in humans. Journal of Cognitive Neuroscience, 23(6): 1437-1446.
Chang, E.F.*, Edwards, E.*, Nagarajan, S.S., Fogelson, N., Dalal, S.S., Canolty, R.T., Kirsch, H.E., Barbaro, N.M., & Knight, R.T. (2010).
Abstract: Selective processing of task-relevant stimuli is critical for goal-directed behavior. We used electrocorticography to assess the spatio-temporal dynamics of cortical activation during a simple phonological target detection task, in which subjects press a button when a prespecified target syllable sound is heard. Simultaneous surface potential recordings during this task revealed a highly ordered temporal progression of high gamma (HG, 70–200 Hz) activity across the lateral hemisphere in less than 1 sec. The sequence demonstrated concurrent regional sensory processing of speech syllables in the posterior superior temporal gyrus (STG) and speech motor cortex, and then transitioned to sequential task-dependent processing from prefrontal cortex (PFC), to the final motor response in the hand sensorimotor cortex. STG activation was modestly enhanced for target over nontarget sounds, supporting a selective gain mechanism in early sensory processing, whereas PFC was entirely selective to targets, supporting its role in guiding response behavior. These results reveal that target detection is not a single cognitive event, but rather a process of progressive target selectivity that involves large-scale rapid parallel and serial processing in sensory, cognitive, and motor structures to support goal-directed human behavior.
https://dx.doi.org/10.1162/jocn.2010.21466 -
Predictors of efficacy after stereotactic radiosurgery for medial temporal lobe epilepsy. Neurology 74(2):165-72. PMCID: PMC2809028
Chang, EF, Quigg, M, Oh, MC, Dillon, WP, Ward, MM, Laxer, KD, Broshek, DK, Barbaro, NM (2010).
Abstract: Stereotactic radiosurgery (RS) is a promising treatment for intractable medial temporal lobe epilepsy (MTLE). However, the basis of its efficacy is not well understood. Thirty patients with MTLE were prospectively randomized to receive 20 or 24 Gy 50% isodose RS centered at the amygdala, 2 cm of the anterior hippocampus, and the parahippocampal gyrus. Posttreatment MRI was evaluated quantitatively for abnormal T2 hyperintensity and contrast enhancement, mass effect, and qualitatively for spectroscopic and diffusion changes. MRI findings were analyzed for potential association with radiation dose and seizure remission (Engel Ib or better outcome). Despite highly standardized dose targeting, RS produced variable MRI alterations. In patients with multiple serial imaging, the appearance of vasogenic edema occurred approximately 9-12 months after RS and correlated with onset of seizure remission. Diffusion and spectroscopy-detected alterations were consistent with a mechanism of temporal lobe radiation injury mediated by local vascular insult and neuronal loss. The degree of these early alterations at the peak of radiographic response was dose-dependent and predicted long-term seizure remission in the third year of follow-up. Radiographic changes were not associated with neurocognitive impairments. Temporal lobe stereotactic radiosurgery resulted in significant seizure reduction in a delayed fashion which appeared to be well-correlated with structural and biochemical alterations observed on neuroimaging. Early detected changes may offer prognostic information for guiding management.
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Seizure control outcomes after surgical resection of dysembryoplastic neuroepithelial tumor in 50 patients. Journal of Neurosurgery: Pediatrics. 5(1):123-130.
Chang, EF, Christie, C, Garcia, PA, Sullivan, J, Tihan, T, Gupta, N, Berger, MS, Barbaro, NM (2010).
Abstract: We aimed to investigate the long-term seizure outcome of children and adolescents who were undergoing epilepsy surgery in the parietooccipital cortex and determine their predictive factors. We retrospectively analyzed the data of 50 consecutive patients aged 11.1 (mean) ± 5.1 (standard deviation) years at surgery. All patients but one had a magnetic resonance imaging (MRI)-visible lesion. Resections were parietal in 40%, occipital in 32%, and parietooccipital in 28% cases; 24% patients additionally underwent a resection of the posterior border of the temporal lobe. Etiology included focal cortical dysplasia in 44%, benign tumors (dysembryoplastic neuroepithelial tumor, ganglioglioma, angiocentric glioma, and pilocystic astrocytoma) in 32%, peri- or postnatal ischemic lesions in 16%, and tuberous sclerosis in 8% cases. At last follow-up (mean 8 years, range 1.5-18 years), 60% patients remained seizure-free (Engel class I): 30% had discontinued and 20% had reduced antiepileptic drugs. Most seizure recurrences (71%) occurred within the first 6 months, and only three patients presented with seizures ≥2 years after surgery. Independent predictors of seizure recurrence included left-sided as well as parietal epileptogenic zones and resections. Longer epilepsy duration to surgery was identified as the only modifiable independent predictor of seizure recurrence. Our study demonstrates that posterior cortex epilepsy surgery is highly effective in terms of lasting seizure control and antiepileptic drug cessation in selected pediatric candidates. Most importantly, our data supports the early consideration of surgical intervention in children and adolescents with refractory posterior cortex epilepsy.
2009
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Magnetic source imaging for the surgical evaluation of EEG secondary bilateral synchrony in intractable epilepsy. Journal of Neurosurgery 111(6):1248-56. PMCID: PMC3151560
Chang, EF, Nagarajan, SS, Mantle, M, Barbaro, NM, Kirsch HE (2009).
Abstract: Routine scalp electroencephalography (EEG) cannot always distinguish whether generalized epileptiform discharges are the result of primary bilateral synchrony or secondary bilateral synchrony (SBS) from a focal origin; this is an important distinction because the latter may be amenable to resection. Whole-head magnetoencephalography (MEG) has superior spatial resolution compared with traditional EEG, and can potentially elucidate seizure foci in challenging epilepsy cases in which patients are undergoing evaluation for surgery. Sixteen patients with medically intractable epilepsy in whom SBS was suspected were referred for magnetic source (MS) imaging. All patients had bilateral, synchronous, widespread, and most often generalized spike-wave discharges on scalp EEG studies, plus some other clinical (for example, seizure semiology) or MR imaging feature (for example, focal lesion) suggesting focal onset and hence possible surgical candidacy. The MS imaging modality is the combination of whole-head MEG and parametric reconstruction of corresponding electrical brain sources. An MEG and simultaneous EEG studies were recorded with a 275-channel whole-head system. Single-equivalent current dipoles were estimated from the MEG data, and dipole locations and orientations were superimposed on patients' MR images. The MS imaging studies revealed focal dipole clusters in 12 (75%) of the 16 patients, of which a single dipole cluster was identified in 7 patients (44%). Patient age, seizure type, duration of disease, video-EEG telemetry, and MR imaging results were analyzed to determine factors predictive of having clusters revealed on MS imaging. Of these factors, only focal MR imaging anatomical abnormalities were associated with dipole clusters (chi-square test, p = 0.03). Selective resections (including the dipole cluster) in 7 (87%) of 8 patients resulted in seizure-free or rare seizure outcomes (Engel Classes I and II). Magnetic source imaging may provide noninvasive anatomical and neurophysiological confirmation of localization in patients in whom there is a suspicion of SBS (based on clinical or MR imaging data), especially in those with an anatomical lesion. Identification of a focal seizure origin has significant implications for both resective and nonresective treatment of intractable epilepsy.
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Safety and feasibility of switching from phenytoin to levetiracetam monotherapy for glioma-related seizure control following craniotomy: a randomized phase II pilot study. Journal of Neurooncology 93(3):349-54. PMCID: PMC2687520
Lim, DA, Tarapore, P, Chang, EF, Burt, M, Chakalian, L, Barbaro, NM, Chang, SM, Lamborn, KR, McDermott, MW (2009).
Abstract: Seizures are common in patients with gliomas, and phenytoin (PHT) is frequently used to control tumor-related seizures. PHT, however, has many undesirable side effects (SEs) and drug interactions with glioma chemotherapy. Levetiracetam (LEV) is a newer antiepileptic drug (AED) with fewer SEs and essentially no drug interactions. We performed a pilot study testing the safety and feasibility of switching patients from PHT to LEV monotherapy for postoperative control of glioma-related seizures. Over a 13-month period, 29 patients were randomized in a 2:1 ratio to initiate LEV therapy within 24 h of surgery or to continue PHT therapy. 6 month follow-up data were available for 15 patients taking LEV and for 8 patients taking PHT. In the LEV group, 13 patients (87%) were seizure-free. In the PHT group, 6 patients (75%) were seizure-free. Reported SEs at 6 months was as follows (%LEV/%PHT group): dizziness (0/14), difficulty with coordination (0/29), depression (7/14) lack of energy or strength (20/43), insomnia (40/43), mood instability (7/0). The pilot data presented here suggest that it is safe to switch patients from PHT to LEV monotherapy following craniotomy for supratentorial glioma. A large-scale, double-blinded, randomized control trial of LEV versus PHT is required to determine seizure control equivalence and better assess differences in SEs.
2008
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Seizure characteristics and control following surgical resection in 332 patients with low-grade gliomas. Journal of Neurosurgery. 108 (2): 227-35.
Chang, EF, Potts, M, Keles, GE, Lamborn, KR, Chang, SM, Barbaro, NM, Berger, MS (2008).
Abstract: Seizures play an important role in the clinical presentation and postoperative quality of life of patients who undergo surgical resection of low-grade gliomas (LGGs). The aim of this study was to identify factors that influenced perioperative seizure characteristics and postoperative seizure control. The authors performed a retrospective chart review of all cases involving adult patients who underwent initial surgery for LGGs at the University of California, San Francisco between 1997 and 2003. Three hundred and thirty-two cases were included for analysis; 269 (81%) of the 332 patients presented with >or=1 seizures (generalized alone, 33%; complex partial alone, 16%; simple partial alone, 22%; and combination, 29%). Cortical location and oligodendroglioma and oligoastrocytoma subtypes were significantly more likely to be associated with seizures compared with deeper midline locations and astrocytoma, respectively (p=0.017 and 0.001, respectively; multivariate analysis). Of the 269 patients with seizures, 132 (49%) had pharmacoresistant seizures before surgery. In these patients, seizures were more likely to be simple partial and to involve the temporal lobe, and the period from seizure onset to surgery was likely to have been longer (p=0.0005, 0.0089, and 0.006, respectively; multivariate analysis). For the cohort of patients that presented with seizures, 12-month outcome after surgery (Engel class) was as follows: seizure free (I), 67%; rare seizures (II), 17%; meaningful seizure improvement (III), 8%; and no improvement or worsening (IV), 9%. Poor seizure control was more common in patients with longer seizure history (p<0.001) and simple partial seizures (p=0.004). With respect to treatment-related variables, seizure control was far more likely to be achieved after gross-total resection than after subtotal resection/biopsy alone (odds ratio 16, 95% confidence interval 2.2-124, p=0.0064). Seizure recurrence after initial postoperative seizure control was associated with tumor progression (p=0.001). The majority of patients with LGG present with seizures; in approximately half of these patients, the seizures are pharmacoresistant before surgery. Postoperatively, >90% of these patients are seizure free or have meaningful improvement. A shorter history of seizures and gross-total resection appear to be associated with a favorable prognosis for seizure control.
2007
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Critical period window for spectral tuning defined in the primary auditory cortex (A1). Journal of Neuroscience, 27(1): 180-189.
De Villers-sidani, E., Chang, E.F., Bao, S., & Merzenich, M.M. (2007).
Abstract: Experience-dependent plasticity during development results in the emergence of highly adapted representations of the external world in the adult brain. Previous studies have convincingly shown that the primary auditory cortex (A1) of the rat possesses a postnatal period of sensory input-driven plasticity but its precise timing (onset, duration, end) has not been defined. In the present study, we examined the effects of pure-tone exposure on the auditory cortex of developing rat pups at different postnatal ages with a high temporal resolution. We found that pure-tone exposure resulted in profound, persistent alterations in sound representations in A1 only if the exposure occurred during a brief period extending from postnatal day 11 (P11) to P13. We also found that postnatal sound exposure in this epoch led to striking alterations in the cortical representation of sound intensity.
https://dx.doi.org/10.1523/JNEUROSCI.3227-06.2007
2006
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Focal cortical dysplasia: a review of pathological features, genetics, and surgical outcome. Neurosurg Focus. 20(1):E7.
Wang, VY, Chang, EF, Barbaro, NM (2006).
Abstract: Focal cortical dysplasia (FCD) is a malformation of cortical development characterised by disruption of cortical cytoarchitecture. Classification of FCDs subtypes has initially been based on correlation of the histopathology with relevant clinical, electroencephalographic and neuroimaging features. A recently proposed classification update recommends a multilayered, genotype-phenotype approach, integrating findings from histopathology, genetic analysis of resected tissue and presurgical MRI. FCDs are caused either by single somatic activating mutations in MTOR pathway genes or by double-hit inactivating mutations with a constitutional and a somatic loss-of-function mutation in repressors of the signalling pathway. Mild malformation with oligodendroglial hyperplasia in epilepsy is caused by somatic pathogenic
2005
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The development of spectral and temporal response selectivity in the auditory cortex. Proceedings of the National Academy of Science. 102(45):16460-16465.
Chang, E.F., Bao, S., Imaizumi, K., Schreiner, C.E., & Merzenich, M.M. (2005).
Abstract: The mechanisms by which hearing selectivity is elaborated and refined in early development are very incompletely determined. In this study, we documented contributions of progressively maturing inhibitory influences on the refinement of spectral and temporal response properties in the primary auditory cortex. Inhibitory receptive fields (IRFs) of infant rat auditory cortical neurons were spectrally far broader and had extended over far longer duration than did those of adults. The selective refinement of IRFs was delayed relative to that of excitatory receptive fields by an ≈2-week period that corresponded to the critical period for plasticity. Local application of a GABA
https://dx.doi.org/10.1073/pnas.0508239102
2004
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Temporal plasticity in the primary auditory cortex induced by operant perceptual learning. Nature Neuroscience, 7(9):974-981.
Bao, S., Chang, E.F., Woods, J., & Merzenich, M.M. (2004).
Abstract: Temporal coherence among neural populations may contribute importantly to signal encoding, specifically by providing an optimal tradeoff between encoding reliability and efficiency. Here, we considered the possibility that learning modulates the temporal coherence among neural populations in association with well-characterized map plasticity. We previously demonstrated that, in appetitive operant conditioning tasks, the tone-responsive area globally expanded during the early stage of learning, but shrank during the late stage. The present study further showed that phase locking of the first spike to band-specific oscillations of local field potentials (LFPs) significantly increased during the early stage of learning but decreased during the late stage, suggesting that neurons in A1 were more synchronously activated during early learning, whereas they were more asynchronously activated once learning was completed. Furthermore, LFP amplitudes increased during early learning but decreased during later learning. These results suggest that, compared to naïve encoding, early-stage encoding is more reliable but energy-consumptive, whereas late-stage encoding is more energetically efficient. Such a learning-stage-dependent encoding strategy may underlie learning-induced, non-monotonic map plasticity. Accumulating evidence indicates that the cholinergic system is likely to be a shared neural substrate of the processes for perceptual learning and attention, both of which modulate neural encoding in an adaptive manner. Thus, a better understanding of the links between map plasticity and modulation of temporal coherence will likely lead to a more integrated view of learning and attention.
https://dx.doi.org/10.1038/nn1293 -
Intraoperative subcortical stimulation mapping during resection of hemispheric gliomas located in or adjacent to the Rolandic cortex and descending motor pathways. Journal of Neurosurgery. 100(3):369-75.
Keles, GE, Lundin, DA, Lamborn, KR, Chang, EF, Ojemann, GA, Berger, MS (2004).
Abstract: Supplementary motor area syndrome (SMAS) may occur after frontal tumor surgery, with variable presentation and outcomes. We reviewed the literature on postoperative SMAS after brain tumor resection. PubMed, Web of Science, Scopus, and Cochrane were searched following the PRISMA guidelines to include studies reporting SMAS after brain tumor resection. We included 31 studies encompassing 236 patients. Most tumors were gliomas (94.5%), frequently of low grade (61.4%). Most lesions were located on the left hemisphere (64.4%), involving the supplementary motor area (61.4%) and the cingulate gyrus (20.8%). Tractography and functional magnetic resonance imaging evaluation were completed in 45 (19.1%) and 26 (11%) patients. Gross total resection was achieved in 46.3% patients and complete SMA resection in 69.4%. A total of 215 procedures (91.1%) used intraoperative neuromonitoring mostly consisting of direct cortical/subcortical stimulation (56.4%), motor (33.9%), and somatosensory (25.4%) evoked potentials. Postoperative SMAS symptoms occurred within 24 hours after surgery, characterized by motor deficits (97%), including paresis (68.6%) and hemiplegia (16.1%), and speech disorders (53%), including hesitancy (24.2%) and mutism (22%). Average SMAS duration was 45 days (range, 1-365 days), with total resolution occurring in 188 patients (79.7%) and partial improvement in 46 (19.5%). Forty-eight patients (20.3%) had persisting symptoms, mostly speech hesitancy (60.4%) and fine motor disorders (45.8%). Postoperative SMAS may occur within the first 24 hours after mesial frontal tumor surgery. Preoperative mapping and intraoperative neuromonitoring may assist resection and predict outcomes. Neuroplasticity and interhemispheric connectivity play a major role in resolution.
2003
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Environmental noise retards auditory cortical development. Science, 300(5618): 498-502.
Chang, E.F. & Merzenich, M.M. (2003).
Abstract: The mammalian auditory cortex normally undergoes rapid and progressive functional maturation. Here we show that rearing infant rat pups in continuous, moderate-level noise delayed the emergence of adultlike topographic representational order and the refinement of response selectivity in the primary auditory cortex (A1) long beyond normal developmental benchmarks. When those noise-reared adult rats were subsequently exposed to a pulsed pure-tone stimulus, A1 rapidly reorganized, demonstrating that exposure-driven plasticity characteristic of the critical period was still ongoing. These results demonstrate that A1 organization is shaped by a young animal's exposure to salient, structured acoustic inputs—and implicate noise as a risk factor for abnormal child development.
https://dx.doi.org/10.1126/science.1082163