Emotional facial expression and perioral motor functions of the human auditory cortex.

OBJECTIVE: We investigated the role of transverse temporal gyrus and adjacent cortex (TTG+) in facial expressions and perioral movements. METHODS: In 31 patients undergoing stereo-electroencephalography monitoring, we describe behavioral responses elicited by electrical stimulation within the TTG+. Task-induced high-gamma modulation (HGM), auditory evoked responses, and resting-state connectivity were used to investigate the cortical sites having different types of responses on electrical stimulation. RESULTS: Changes in facial expressions and perioral movements were elicited on electrical stimulation within TTG+ in 9 (29%) and 10 (32%) patients, respectively, in addition to the more common language responses (naming interruptions, auditory hallucinations, paraphasic errors). All functional sites showed auditory task induced HGM and evoked responses validating their location within the auditory cortex, however, motor sites showed lower peak amplitudes and longer peak latencies compared to language sites. Significant first-degree connections for motor sites included precentral, anterior cingulate, parahippocampal, and anterior insular gyri, whereas those for language sites included posterior superior temporal, posterior middle temporal, inferior frontal, supramarginal, and angular gyri. CONCLUSIONS: Multimodal data suggests that TTG+ may participate in auditory-motor integration. SIGNIFICANCE: TTG+ likely participates in facial expressions in response to emotional cues during an auditory discourse.

Neuropsychological outcomes after epilepsy surgery: A comparison of stereo electroencephalography and subdural electrodes.

BACKGROUND AND PURPOSE: We analyzed the association of neuropsychological outcomes after epilepsy surgery with the intracranial electrode type (stereo electroencephalography [SEEG] and subdural electrodes [SDE]), and electrical stimulation mapping (ESM) of speech/language. METHODS: Drug-resistant epilepsy patients who underwent comprehensive neuropsychological evaluation before and 1 year after epilepsy surgery were included. SEEG and SDE subgroups were matched by age, handedness, operated hemisphere, and seizure freedom. Postsurgical neuropsychological outcomes (adjusted for presurgical scores) and reliable change indices were analyzed as functions of electrode type and ESM. RESULTS: Ninety-nine patients aged 6-29 years were included with similar surgical resection/ablation volumes in the SEEG and SDE subgroups. Most of the neuropsychological outcomes were comparable between SEEG and SDE subgroups; however, Working Memory and Processing Speed were significantly improved in the SEEG subgroup. Undergoing language ESM was associated with significant improvements in Spelling, Letter-Word Identification, Vocabulary, Verbal Comprehension, Verbal Learning, and Story Memory scores, but a decline in Calculation scores. CONCLUSIONS: Intracranial evaluations with SEEG and SDE are comparable in terms of long-term postsurgical neuropsychological outcomes. Our data suggest that SEEG may be associated with improvements in working memory and processing speed, representing cognitive domains served by spatially distributed networks. Our study also supports wider use of language ESM before epilepsy surgery, preferably using other language tasks in addition to visual naming. Rather than the type of electrode, postsurgical neuropsychological outcomes are driven by whether language ESM was performed or not, with beneficial effects of language mapping.

Comparing electrical stimulation functional mapping with subdural electrodes and stereoelectroencephalography.

OBJECTIVE: Electrical stimulation mapping (ESM) is the clinical standard for functional localization with subdural electrodes (SDE). As stereoelectroencephalography (SEEG) has emerged as an alternative option, we compared functional responses, afterdischarges (ADs), and unwanted ESM-induced seizures (EISs) between the two electrode types. METHODS: Incidence and current thresholds for functional responses (sensory, motor, speech/language), ADs, and EISs were compared between SDE and SEEG using mixed models incorporating relevant covariates. RESULTS: We identified 67 SEEG ESM and 106 SDE ESM patients (7207 and 4980 stimulated contacts, respectively). We found similar incidence of language and motor responses between electrode types; however, more SEEG patients reported sensory responses. ADs and EISs occurred less commonly with SEEG than SDE. Current thresholds for language, face motor, and upper extremity (UE) motor responses and EIS significantly decreased with age. However, they were not affected by electrode type, premedication, or dominant hemispheric stimulation. AD thresholds were higher with SEEG than with SDE. For SEEG ESM, language thresholds remained below AD thresholds up to 26 years of age, whereas this relationship was inverse for SDE. Also, face and UE motor thresholds fell below AD thresholds at earlier ages for SEEG than SDE. AD and EIS thresholds were not affected by premedication. SIGNIFICANCE: SEEG and SDE have clinically relevant differences for functional brain mapping with electrical stimulation. Although evaluation of language and motor regions is comparable between SEEG and SDE, SEEG offers a higher likelihood of identifying sensory areas. A lower incidence of ADs and EISs, and a favorable relationship between functional and AD thresholds suggest superior safety and neurophysiologic validity for SEEG ESM than SDE ESM.

Fatal Epileptic Seizures in Mice Having Compromised Glutathione and Ascorbic Acid Biosynthesis.

Reduced glutathione (GSH) and ascorbic acid (AA) are the two most abundant low-molecular-weight antioxidants in mammalian tissues. GclmKO knockout mice lack the gene encoding the modifier subunit of the rate-limiting enzyme in GSH biosynthesis; GclmKO mice exhibit 10-40% of normal tissue GSH levels and show no overt phenotype. GuloKO knockout mice, lacking a functional Gulo gene encoding L-gulono-γ-lactone oxidase, cannot synthesize AA and depend on dietary ascorbic acid for survival. To elucidate functional crosstalk between GSH and AA in vivo, we generated the GclmKO/GuloKO double-knockout (DKO) mouse. DKO mice exhibited spontaneous epileptic seizures, proceeding to death between postnatal day (PND)14 and PND23. Histologically, DKO mice displayed neuronal loss and glial proliferation in the neocortex and hippocampus. Epileptic seizures and brain pathology in young DKO mice could be prevented with AA supplementation in drinking water (1 g/L). Remarkably, in AA-rescued adult DKO mice, the removal of AA supplementation for 2-3 weeks resulted in similar, but more severe, neocortex and hippocampal pathology and seizures, with death occurring between 12 and 21 days later. These results provide direct evidence for an indispensable, yet underappreciated, role for the interplay between GSH and AA in normal brain function and neuronal health. We speculate that the functional crosstalk between GSH and AA plays an important role in regulating glutamatergic neurotransmission and in protecting against excitotoxicity-induced brain damage.

Posterior Quadrant Disconnection Procedure for Intractable Epilepsy: A Case Series of 5 Young Pediatric Patients.

BACKGROUND: Posterior quadrant disconnection (PQD) has been described as a treatment for patients with refractory posterior quadrant subhemispheric epilepsy. Surgical outcomes are difficult to interpret because of limited literature. OBJECTIVE: To provide insight regarding the operative technique and postsurgical seizure freedom in young pediatric patients who underwent surgical disconnection for the treatment of posterior quadrant subhemispheric epilepsy at our institution. METHODS: The authors retrospectively analyzed a series of 5 patients who underwent PQD between 2019 and 2021. Charts were reviewed for preoperative workup including noninvasive/invasive testing, operative reports, and postoperative follow-up data which included degree of seizure freedom, completion of disconnection, and complications. RESULTS: Five patients were included in this series. The median age at seizure onset was 12 months (range 3-24 months), and the median age at surgery was 36 months (range 22-72 months). Histopathology confirmed focal cortical dysplasia in 3 of 5 patients (2 patients with type IB; 1 with type IIID). The average length of follow-up after surgery was 16.8 months (range 12-24 months). All patients underwent complete disconnection of the posterior quadrant without complications. Four of 5 patients (80%) had Engel score of I, while the remaining patient had an Engel score of IIB. CONCLUSION: Our early results demonstrate that complete PQD can be successful at providing excellent seizure freedom and functional outcomes in carefully selected young pediatric patients who have concordant seizure semiology, noninvasive/invasive testing, and imaging findings with primary seizure onset zone within the ipsilateral posterior quadrant. Meticulous surgical planning and thorough understanding of the surgical anatomy and technique are critical to achieving complete disconnection.

Diurnal rhythms of spontaneous intracranial high-frequency oscillations.

OBJECTIVE: Seizures are known to occur with diurnal and other rhythms. To gain insight into the neurophysiology of periodicity of seizures, we tested the hypothesis that intracranial high-frequency oscillations (HFOs) show diurnal rhythms and sleep-wake cycle variation. We further hypothesized that HFOs have different rhythms within and outside the seizure-onset zone (SOZ). METHODS: In drug-resistant epilepsy patients undergoing stereotactic-EEG (SEEG) monitoring to localize SOZ, we analyzed the number of 50-200 Hz HFOs/channel/minute (HFO density) through a 24-hour period. The distribution of HFO density during the 24-hour period as a function of the clock time was analyzed with cosinor model, and for non-uniformity with the sleep-wake cycle. RESULTS: HFO density showed a significant diurnal rhythm overall and both within and outside SOZ. This diurnal rhythm of HFO density showed significantly lower amplitude and longer acrophase within SOZ compared to outside SOZ. The peaks of difference in HFO density within and outside SOZ preceded the seizures by approximately 4 hours. The difference in HFO density within and outside SOZ also showed a non-uniform distribution as a function of sleep-wake cycle, with peaks at first hour after arousal and ±2 hours around sleep onset. CONCLUSIONS: Our study shows that the diurnal rhythm of intracranial HFOs is more robust outside the SOZ. This suggests cortical tissue within SOZ generates HFOs relatively more uniformly throughout the day with attenuation of expected diurnal rhythm. The difference in HFO density within and outside SOZ also showed non-uniform distribution according to clock times and the sleep-wake cycle, which can be a potential biomarker for preferential times of pathological cortical excitability. A temporal correlation with seizure occurrence further substantiates this hypothesis.

Comparison of outcomes after stereoelectroencephalography and subdural grid monitoring in pediatric tuberous sclerosis complex.

OBJECTIVE: Patients with tuberous sclerosis complex (TSC) epilepsy present with unique clinical challenges such as early seizure onset and high rates of intractability and multifocality. Although there are numerous studies about the safety and efficacy of stereoelectroencephalography (SEEG), this topic has not been studied in TSC patients who have distinct epilepsy profiles. The authors investigated subdural grid (SDG) and SEEG monitoring to determine whether these procedures lead to similar seizure and safety outcomes and to identify features unique to this pediatric population. METHODS: TSC patients who underwent SDG or SEEG placement and a second epilepsy surgery during the period from 2007 to 2021 were included in this single-center retrospective cohort analysis. Various patient, hospitalization, and epilepsy characteristics were collected. RESULTS: A total of 50 TSC patients were included in this study: 30 were included in the SDG cohort and 20 in the SEEG cohort. Baseline weekly seizure count did not significantly differ between the 2 groups (p = 0.412). The SEEG group had a greater mean baseline number of antiepileptic drugs (AEDs) (3.0 vs 2.0, p = 0.003), higher rate of previous surgical interventions (25% vs 0%, p = 0.007), and larger proportion of patients who underwent bilateral monitoring (50% vs 13.3%, p = 0.005). Despite this, there was no significant difference in seizure freedom between the SDG and SEEG cohorts. The mean reduction in seizure count was 84.9% and 47.8% of patients were seizure free at last follow-up (mean 79.4 months). SEEG trended toward being a safer procedure than SDG monitoring, with a shorter mean ICU stay (0.7 days vs 3.9 days, p < 0.001), lower blood transfusion rate (0% vs 13.3%, p = 0.140), and lower surgical complication rate (0% vs 10%, p = 0.265). CONCLUSIONS: In the comparison of the SDG and SEEG cohorts, the SEEG group included patients who appeared to receive more aggressive management and have a higher rate of multifocality, more prior surgical interventions, more AEDs at baseline, and a higher rate of bilateral invasive monitoring. Despite this, the SEEG cohort had similar seizure outcomes and a trend toward increased safety. Based on these findings, SEEG appears to allow for monitoring of a wider breadth of TSC patients given its minimally invasive nature and its relative simplicity for monitoring numerous regions of the brain.

Clinical validation of magnetoencephalography network analysis for presurgical epilepsy evaluation.

OBJECTIVE: To clinically validate the connectivity-based magnetoencephalography (MEG) analyses to identify seizure onset zone (SOZ) with comparing to equivalent current dipole (ECD). METHODS: The ECD cluster was quantitatively analyzed by calculating the centroid of the cluster and maximum distance (the largest distance between all dipoles). The "primary hub" was determined by the highest eigencentrality. The distribution of nodes in the top 5% of eigenvector centrality values was quantified by generating the convex hull between each node. RESULTS: Thirty-one patients who underwent MEG, stereotactic-EEG, and focal surgery were included. The primary hub was significantly closer to the sEEG-defined SOZ compared to ECD (p = 0.009). The seizure freedom positive and negative predictive values of complete ECD cluster and primary hub resections did not significantly differ, although complete resection of the primary hub showed slightly better negative predictive value (ECD: 50.0% NPV, hub: 64.7% NPV). Both quantitative ECD and functional connectivity analyses suggested that spatially restricted dipole distributions and higher connectivity in a smaller region correlate with better seizure outcomes. CONCLUSIONS: Our findings suggest that MEG network analysis could be a valuable complement to the ECD methods. SIGNIFICANCE: The results of this study are an important step towards using non-invasive neurophysiologic recordings to accurately define the epileptic network.

Functional MRI and electrical stimulation mapping for language localization: A comparative meta-analysis.

OBJECTIVE: This systematic review and meta-analysis evaluated the diagnostic validity of functional magnetic resonance imaging (fMRI) compared to electrical stimulation mapping (ESM) for pre-surgical language mapping. METHODS: A structured literature search was performed and studies with electrode-level data comparing fMRI and ESM for language localization were analyzed. Outcome measures included pooled estimates of diagnostic odds ratio (DOR), sensitivity, and specificity. Sources of heterogeneity were explored with a meta-regression framework. RESULTS: Nine studies were included in the analysis having 5-40 patients with mean age 11.3-43.4 years. Verb generation and picture naming were the most common fMRI tasks, while picture naming was the most common ESM task. Sensitivity (0.37-0.95), specificity (0.36-0.97), and DOR (1.9-44.6) for fMRI compared to ESM varied widely across studies with statistically significant heterogeneities. Pooled estimates were: sensitivity 0.71 (95% confidence interval 0.54, 0.83), specificity 0.74 (0.58, 0.85), and DOR 7.0 (3.5, 13.8), from a valid meta-analysis (area under the summary receiver-operating-curve 0.78). fMRI was noted to have higher sensitivity in studies using higher maximal ESM currents. fMRI variables could not be included in the meta-regression because of substantial methodological differences among studies. CONCLUSIONS: fMRI is moderately sensitive and moderately specific for language localization compared to ESM in well-designed studies. However, because the confidence limits for sensitivity and DOR are close to the line of no effect, and there is high unmeasured heterogeneity, fMRI cannot perhaps be used as the only modality for language localization to inform neurosurgical decisions at present.

Neuronal Circuits Supporting Development of Visual Naming Revealed by Intracranial Coherence Modulations.

Background: Improvement in visual naming abilities throughout the childhood and adolescence supports development of higher-order linguistic skills. We investigated neuronal circuits underlying improvement in the speed of visual naming with age, and age-related dynamics of these circuits. Methods: Response times were electronically measured during an overt visual naming task in epilepsy patients undergoing stereo-EEG monitoring. Coherence modulations among pairs of neuroanatomic parcels were computed and analyzed for relationship with response time and age. Results: During the overt visual naming task, mean response time (latency) significantly decreased from 4 to 23 years of age. Coherence modulations during visual naming showed that increased connectivity between certain brain regions, particularly that between left fusiform gyrus/left parahippocampal gyrus and left frontal operculum, is associated with improvement in naming speed. Also, decreased connectivity in other brain regions, particularly between left angular and supramarginal gyri, is associated with decreased mean response time. Further, coherence modulations between left frontal operculum and both left fusiform and left posterior cingulate gyri significantly increase, while that between left angular and supramarginal gyri significantly decrease, with age. Conclusion: Naming speed continues to improve from pre-school years into young adulthood. This age-related improvement in efficiency of naming environmental objects occurs likely because of strengthened direct connectivity between semantic and phonological nodes, and elimination of intermediate higher-order cognitive steps.

Epilepsy Milestones 2.0: An updated framework for assessing epilepsy fellowships and fellows.

OBJECTIVE: Accreditation Council for Graduate Medical Education (ACGME)-accredited epilepsy fellowships, like other ACGME accredited training programs, use Milestones to establish learning objectives and to evaluate how well trainees are achieving these goals. The ACGME began developing the second iteration of the Milestones 6 years ago, and these are now being adapted to all specialties. Here, we describe the process by which Epilepsy Milestones 2.0 were developed and summarize them. METHODS: A work group of nine board-certified, adult and pediatric epileptologists reviewed Epilepsy Milestones 1.0 and revised them using a modified Delphi approach. RESULTS: The new Milestones share structural changes with all other specialties, including a clearer stepwise progression in professional development and the harmonized Milestones that address competencies common to all medical fields. Much of the epilepsy-specific content remains the same, although a major addition is a set of Milestones focused on reading and interpreting electroencephalograms (EEGs), which the old Milestones lacked. Epilepsy Milestones 2.0 includes a Supplemental Guide to help program directors implement the new Milestones. Together, Epilepsy Milestones 2.0 and the Supplemental Guide recognize advances in epilepsy, including stereo-EEG, neurostimulation, genetics, and safety in epilepsy monitoring units. SIGNIFICANCE: Epilepsy Milestones 2.0 address the shortcomings of the old Milestones and should facilitate the assessment of epilepsy fellowships and fellows by program directors, faculty, and fellows themselves.

A distributed network supports spatiotemporal cerebral dynamics of visual naming.

OBJECTIVE: Cerebral spatiotemporal dynamics of visual naming were investigated in epilepsy patients undergoing stereo-electroencephalography (SEEG) monitoring. METHODS: Brain networks were defined by Parcel-Activation-Resection-Symptom matching (PARS) approach by matching high-gamma (50-150 Hz) modulations (HGM) in neuroanatomic parcels during visual naming, with neuropsychological outcomes after resection/ablation of those parcels. Brain parcels with >50% electrode contacts simultaneously showing significant HGM were aligned, to delineate spatiotemporal course of naming-related HGM. RESULTS: In 41 epilepsy patients, neuroanatomic parcels showed sequential yet temporally overlapping HGM course during visual naming. From bilateral occipital lobes, HGM became increasingly left lateralized, coursing through limbic system. Bilateral superior temporal HGM was noted around response time, and right frontal HGM thereafter. Correlations between resected/ablated parcels, and post-surgical neuropsychological outcomes showed specific regional groupings. CONCLUSIONS: Convergence of data from spatiotemporal course of HGM during visual naming, and functional role of specific parcels inferred from neuropsychological deficits after resection/ablation of those parcels, support a model with six cognitive subcomponents of visual naming having overlapping temporal profiles. SIGNIFICANCE: Cerebral substrates supporting visual naming are bilaterally distributed with relative hemispheric contribution dependent on cognitive demands at a specific time. PARS approach can be extended to study other cognitive and functional brain networks.

Subtraction ictal SPECT co-registered to MRI (SISCOM) patterns in children with temporal lobe epilepsy.

OBJECTIVE: We evaluated SISCOM patterns and their relationship with surgical outcome in children with temporal lobe epilepsy (TLE) who had undergone a temporal lobe surgery. METHODS: This was an observational study evaluating SISCOM patterns in 40 children with TLE. We classified SISCOM patterns into 4 categories; (i) unilateral anteromesial and/or anterolateral temporal pattern; (ii) unilateral anteromesial and/or anterolateral temporal plus posterior extension pattern; (iii) bilateral anteromesial and/or anterolateral temporal pattern; and (iv) atypical pattern. Determinants of SISCOM pattern and correlation between postoperative outcomes and SISCOM patterns were evaluated. RESULTS: Pattern (i), (ii), (iii), and (iv) were identified in 10 (25%), 14 (35%), 0 (0%), and 16 (40%) patients, respectively. There was no significant correlation between patterns and postoperative outcomes. SISCOM patterns significantly associated with the presence of hippocampal sclerosis and type of focal cortical dysplasia (p-value = 0.048 and 0.036, respectively). Patients with HS had 5 times the odds of having unilateral temporal pattern, compared to patients with other neuropathology (OR = 5, 95% CI 0.92 to 27.08). Patients with FCD type 2 had 9.71 times the odds of having atypical pattern, compared to patients with other types of FCD (OR = 9.71, 95% CI 0.92 to 103.04). Lobar concordance of SISCOM and ictal and interictal scalp EEG significantly correlated with postoperative outcomes (p-value = 0.018 and 0.013, respectively). CONCLUSION: Three SISCOM patterns were seen. Patients with HS had increased odds of having unilateral temporal pattern while patients with FCD type 2 had increased odds of having atypical pattern. However, there was no significant correlation between SISCOM patterns and postoperative outcomes. Lobar concordance of SISCOM and ictal and interictal scalp EEG significantly correlated with postoperative outcome. SIGNIFICANCE: This study shows that the distribution of SISCOM patterns and their relationship with postoperative outcomes in children with TLE are different from adult population. Besides, SISCOM may add only limited diagnostic and prognostic information in children with drug-resistant TLE undergoing epilepsy surgery. Further evaluation to identify patient populations that may benefit from SISCOM is desirable.

Fast Automated Stereo-EEG Electrode Contact Identification and Labeling Ensemble.

INTRODUCTION: Stereotactic electroencephalography (SEEG) has emerged as the preferred modality for intracranial monitoring in drug-resistant epilepsy (DRE) patients being evaluated for neurosurgery. After implantation of SEEG electrodes, it is important to determine the neuroanatomic locations of electrode contacts (ECs), to localize ictal onset and propagation, and integrate functional information to facilitate surgical decisions. Although there are tools for coregistration of preoperative MRI and postoperative CT scans, identification, sorting, and labeling of SEEG ECs is often performed manually, which is resource intensive. We report development and validation of a software named Fast Automated SEEG Electrode Contact Identification and Labeling Ensemble (FASCILE). METHODS: FASCILE is written in Python 3.8.3 and employs a novel automated method for identifying ECs, assigning them to respected SEEG electrodes, and labeling. We compared FASCILE with our clinical process of identifying, sorting, and labeling ECs, by computing localization error in anteroposterior, superoinferior, and lateral dimensions. We also measured mean Euclidean distances between ECs identified by FASCILE and the clinical method. We compared time taken for EC identification, sorting, and labeling for the software developer using FASCILE, a first-time clinical user using FASCILE, and the conventional clinical process. RESULTS: Validation in 35 consecutive DRE patients showed a mean overall localization error of 0.73 ± 0.15 mm. FASCILE required 10.7 ± 5.5 min/patient for identifying, sorting, and labeling ECs by a first-time clinical user, compared to 3.3 ± 0.7 h/patient required for the conventional clinical process. CONCLUSION: Given the accuracy, speed, and ease of use, we expect FASCILE to be used frequently for SEEG-driven epilepsy surgery. It is freely available for noncommercial use. FASCILE is specifically designed to expedite localization of ECs, assigning them to respective SEEG electrodes (sorting), and labeling them and not for coregistration of CT and MRI data as there are commercial software available for this purpose.

In Silico Predictions of KCNQ Variant Pathogenicity in Epilepsy.

BACKGROUND: Variants in KCNQ2 and KCNQ3 may cause benign neonatal familial seizures and early infantile epileptic encephalopathy. Previous reports suggest that in silico models cannot predict pathogenicity accurately enough for clinical use. Here we sought to establish a model to accurately predict the pathogenicity of KCNQ2 and KCNQ3 missense variants based on available in silico prediction models. METHODS: ClinVar and gnomAD databases of reported KCNQ2 and KCNQ3 missense variants in patients with neonatal epilepsy were accessed and classified as benign, pathogenic, or of uncertain significance. Sensitivity, specificity, and classification accuracy for prediction of pathogenicity were determined and compared for 10 widely used prediction algorithms program. A mathematical model of the variants (KCNQ Index) was created using their amino acid location and prediction algorithm scores to improve prediction accuracy. RESULTS: Using clinically characterized variants, the free online tool PROVEAN accurately predicted pathogenicity 92% of the time and the KCNQ Index had an accuracy of 96%. However, when including the gnomAD database as benign variants, only the KCNQ Index was able to predict pathogenicity with an accuracy greater than 90% (sensitivity = 93% and specificity = 98%). No model could accurately predict the phenotype of variants. CONCLUSION: We show that KCNQ channel variant pathogenicity can be predicted by a novel KCNQ Index in neonatal epilepsy. However, more work is needed to accurately predict the patient's epilepsy phenotype from in silico algorithms.

High-gamma modulation language mapping with stereo-EEG: A novel analytic approach and diagnostic validation.

OBJECTIVE: A novel analytic approach for task-related high-gamma modulation (HGM) in stereo-electroencephalography (SEEG) was developed and evaluated for language mapping. METHODS: SEEG signals, acquired from drug-resistant epilepsy patients during a visual naming task, were analyzed to find clusters of 50-150 Hz power modulations in time-frequency domain. Classifier models to identify electrode contacts within the reference neuroanatomy and electrical stimulation mapping (ESM) speech/language sites were developed and validated. RESULTS: In 21 patients (9 females), aged 4.8-21.2 years, SEEG HGM model predicted electrode locations within Neurosynth language parcels with high diagnostic odds ratio (DOR 10.9, p < 0.0001), high specificity (0.85), and fair sensitivity (0.66). Another SEEG HGM model classified ESM speech/language sites with significant DOR (5.0, p < 0.0001), high specificity (0.74), but insufficient sensitivity. Time to largest power change reliably localized electrodes within Neurosynth language parcels, while, time to center-of-mass power change identified ESM sites. CONCLUSIONS: SEEG HGM mapping can accurately localize neuroanatomic and ESM language sites. SIGNIFICANCE: Predictive modelling incorporating time, frequency, and magnitude of power change is a useful methodology for task-related HGM, which offers insights into discrepancies between HGM language maps and neuroanatomy or ESM.

Neuropsychological outcomes after pediatric epilepsy surgery: Role of electrical stimulation language mapping.

PURPOSE: We studied the association between electrical stimulation mapping (ESM) with a visual naming task and post-operative neuropsychological outcomes after pediatric epilepsy surgery. METHODS: Children who underwent epilepsy surgery, having pre- and 1-year post-surgery neuropsychological evaluation (NPE) available, were included. NPE scores were transformed using principal components (PC) analysis. The relationship between post-surgical PC scores, adjusted for pre-surgery PC scores, and ESM was analyzed. Clinical variables influencing this relationship were also sought. RESULTS: One hundred and four children (89 patients >5 years-old, and 15 patients 3-5 years-old) were included. Among children >5 years-of-age, a significant effect of language ESM was observed on all 3 post-surgery PC scores adjusted for respective pre-surgery PC scores. Specifically, only 30 % patients who underwent language ESM had a decrease in PC1 scores ≥1-year after epilepsy surgery, compared to 68 % those who did not undergo language ESM (p = 0.001). Seizure outcomes, age at the time of surgery, predominant seizure type, and family history of epilepsy were other significant determinants of post-surgical PC scores including a change in PC scores from pre-surgery baseline. Combinations of pre-surgical variables were able to predict post-surgical PC scores with high specificity. In children aged 3-5 years, no significant effect of language ESM was seen on post-surgery PC scores adjusted for respective pre-surgery PC scores. CONCLUSIONS: Speech/language ESM should be performed more widely in patients >5 years-of-age undergoing epilepsy surgery. Also, more efficient brain mapping techniques and language paradigms are needed for younger children.

Electrical stimulation sensorimotor mapping with stereo-EEG.

OBJECTIVE: We evaluated stereo-EEG electrical stimulation mapping (ESM) for localization of anatomic sensorimotor parcels in pediatric patients with drug-resistant epilepsy. We also analyzed sensorimotor and after-discharge thresholds, and the somatotopy of sensorimotor responses. METHODS: ESM was performed with 50 Hz, biphasic, 2-3 s trains, using 1-9 mA current. Pre- and post-implant neuroimaging was co-registered and intersected with Neurosynth reference, to classify each electrode contact as lying within/outside an anatomic sensorimotor parcel. Indices of diagnostic performance were computed. Sensorimotor and after-discharge thresholds were analyzed using multivariable linear mixed models. RESULTS: In 15 patients (6 females), aged 5.5-21.2 years, ESM showed high accuracy (0.80), high specificity (0.86), and diagnostic odds ratio (11.4, p < 0.0001) for localization of sensorimotor parcels. Mean sensorimotor threshold (3.4 mA) was below mean after-discharge threshold (4.2 mA, p = 0.0004). Sensorimotor and after-discharge thresholds showed a significant decrease with increasing intelligence quotient. Somatotopy of sensorimotor responses was mapped to standardized brain parcels. CONCLUSIONS: We provide evidence for diagnostic validity and safety of stereo-EEG sensorimotor ESM. SIGNIFICANCE: The somatotopy of sensorimotor responses elicited with electrical stimulation provide new insights into mechanisms of motor control and sensory perception.

A model for visual naming based on spatiotemporal dynamics of ECoG high-gamma modulation.

OBJECTIVE: We studied spatiotemporal dynamics of electrocorticographic (ECoG) high-gamma modulation (HGM) during visual naming. METHODS: In 8 patients, aged 4-19 years, with left hemisphere subdural electrodes, propagation of ECoG HGM during overt visual naming was mapped with trial-averaged time-frequency analysis. Group-level synthesis was performed by transforming all electrodes to a standard space and assigning cortical parcels based on a reference atlas. RESULTS: After image display following cortical parcels were activated: inferior occipital, caudal angular, fusiform, and middle temporal gyri, and superior temporal sulcus [0-400 ms]; rostral pars triangularis (A45r), inferior frontal sulcus, caudal dorsolateral premotor cortex (A6cdl) [300-600 ms]; caudal ventrolateral premotor cortex (A6cvl), caudal pars triangularis (A45c), pars opercularis (A44) [400-800 ms]; primary sensorimotor cortex [600-1400 ms], with most prominent HGM in glossolaryngeal region (A4tl). Lastly, auditory cortex (A41/A42) and superior temporal gyrus (A22) were activated [900 ms-1.4 s]. After 1.5 s, HGM decreased globally, except in ventrolateral premotor cortex. CONCLUSIONS: During visual naming, ECoG HGM shows a sequential but overlapping spatiotemporal course through cortical regions. We provide neurophysiologic validation for a model of visual naming incorporating both modular and distributed cortical processing. This may explain cognitive deficits seen in some patients after surgery involving HGM naming sites outside perisylvian language cortex.

Electrical stimulation mapping of language with stereo-EEG.

OBJECTIVE: We prospectively validated stereo-electroencephalography (EEG) electrical stimulation mapping (ESM) of language against a reference standard of meta-analytic functional magnetic resonance imaging (fMRI) framework (Neurosynth). METHODS: Language ESM was performed using 50 Hz, biphasic, bipolar, stimulation at 1-8 mA, with a picture naming task. Electrode contacts (ECs) were scored as ESM+ if ESM interfered with speech/language function. For each patient, presurgical MRI was transformed to a standard space and coregistered with computed tomographic (CT) scan to obtain EC locations. After whole-brain parcellation, this fused image data were intersected with three-dimensional language fMRI (Neurosynth), and each EC was classified as lying within/outside the fMRI language parcel. Diagnostic odds ratio (DOR) and other indices were estimated. Current thresholds for language inhibition and after-discharges (ADs) were analyzed using multivariable linear mixed models. RESULTS: In 10 patients (5 females), aged 5.4-21.2 years, speech/language inhibition was noted with ESM on 87/304 (29%) ECs. Stereo-EEG language ESM was a valid classifier of fMRI (Neurosynth) language sites (DOR: 9.02, p < 0.0001), with high specificity (0.87) but poor sensitivity (0.57). Similar diagnostic indices were seen for ECs in frontal or posterior regions, and gray or white matter. Language threshold (3.1 ±â€¯1.5 mA) was lower than AD threshold (4.0 ±â€¯2.0 mA, p = 0.0001). Language and AD thresholds decreased with age and intelligence quotient. Electrical stimulation mapping triggered seizures/auras represented patients' habitual semiology with 1 Hz stimulation. CONCLUSIONS: Stereo-EEG ESM can reliably identify cerebral parcels with/without language function but may under detect all language sites. We suggest a 50-Hz stimulation protocol for language ESM with stereo-EEG.