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Statistical parametric mapping (SPM) is a technique with which one can delineate brain activity statistically deviated from the normative mean, and has been commonly employed in noninvasive neuroimaging and EEG studies. Using the concept of SPM, we developed a novel technique for quantification of the statistical deviation of an intracranial electrocorticography (ECoG) measure from the nonepileptic mean. We validated this technique using data previously collected from 123 patients with drug-resistant epilepsy who underwent resective epilepsy surgery. We determined how the measurement of statistical deviation of modulation index (MI) from the non-epileptic mean (rated by z-score) improved the performance of seizure outcome classification model solely based on conventional clinical, seizure onset zone (SOZ), and neuroimaging variables. Here, MI is a summary measure quantifying the strength of in-situ coupling between high-frequency activity at >150 Hz and slow wave at 3-4 Hz. We initially generated a normative MI atlas showing the mean and standard deviation of slow-wave sleep MI of neighboring non-epileptic channels of 47 patients, whose ECoG sampling involved all four lobes. We then calculated 'MI z-score' at each electrode site. SOZ had a greater 'MI z-score' compared to non-SOZ in the remaining 76 patients. Subsequent multivariate logistic regression analysis and receiver operating characteristic analysis to the combined data of all patients revealed that the full regression model incorporating all predictor variables, including SOZ and 'MI z-score', best classified the seizure outcome with sensitivity/specificity of 0.86/0.76. The model excluding 'MI z-score' worsened its sensitivity/specificity to 0.86/0.48. Furthermore, the leave-one-out analysis successfully cross-validated the full regression model. Measurement of statistical deviation of MI from the non-epileptic mean on invasive recording is technically feasible. Our analytical technique can be used to evaluate the utility of ECoG biomarkers in epilepsy presurgical evaluation.

Objective: We hypothesized that the modulation index (MI), a summary measure of the strength of phase-amplitude coupling between high-frequency activity (>150 Hz) and the phase of slow waves (3-4 Hz), would serve as a useful interictal biomarker for epilepsy presurgical evaluation., Methods: We investigated 123 patients who underwent focal cortical resection following extraoperative electrocorticography recording and had at least 1 year of postoperative follow-up. We examined whether consideration of MI would improve the prediction of postoperative seizure outcome. MI was measured at each intracranial electrode site during interictal slow-wave sleep. We compared the accuracy of prediction of patients achieving International League Against Epilepsy class 1 outcome between the full multivariate logistic regression model incorporating MI in addition to conventional clinical, seizure onset zone (SOZ), and neuroimaging variables, and the reduced logistic regression model incorporating all variables other than MI., Results: Ninety patients had class 1 outcome at the time of most recent follow-up (mean follow-up = 5.7 years). The full model had a noteworthy outcome predictive ability, as reflected by regression model fit R 2 of 0.409 and area under the curve (AUC) of receiver operating characteristic plot of 0.838. Incomplete resection of SOZ (P < 0.001), larger number of antiepileptic drugs at the time of surgery (P = 0.007), and larger MI in nonresected tissues relative to that in resected tissue (P = 0.020) were independently associated with a reduced probability of class 1 outcome. The reduced model had a lower predictive ability as reflected by R 2 of 0.266 and AUC of 0.767. Anatomical variability in MI existed among nonepileptic electrode sites, defined as those unaffected by magnetic resonance imaging lesion, SOZ, or interictal spike discharges. With MI adjusted for anatomical variability, the full model yielded the outcome predictive ability of R 2 of 0.422, AUC of 0.844, and sensitivity/specificity of 0.86/0.76., Significance: MI during interictal recording may provide useful information for the prediction of postoperative seizure outcome., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Gradient recalled echo magnetic resonance imaging (GRE-MRI) at ultra-high field holds great promise for new contrast mechanisms and delineation of putative tissue compartments that contribute to the multi-echo GRE-MRI signal may aid structural characterization. Several studies have adopted the three water-pool compartment model to study white matter brain regions, associating individual compartments with myelin, axonal and extracellular water. However, the number and identifiability of GRE-MRI signal compartments has not been fully explored. We undertook this task for human brain imaging data. Multiple echo time GRE-MRI data were acquired in five healthy participants, specific anatomical structures were segmented in each dataset (substantia nigra, caudate, insula, putamen, thalamus, fornix, internal capsule, corpus callosum and cerebrospinal fluid), and the signal fitted with models comprising one to six signal compartments using a complex-valued plane wave formulation. Information criteria and cluster analysis methods were used to ascertain the number of distinct compartments within the signal from each structure and to determine their respective frequency shifts. We identified five principal signal compartments with different relative contributions to each structure's signal. Voxel-based maps of the volume fraction of each of these compartments were generated and demonstrated spatial correlation with brain anatomy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A number of investigators have reported that event-related augmentation of high-gamma activity at 70-110 Hz on electrocorticography (ECoG) can localize functionally-important brain regions in children and adults who undergo epilepsy surgery. The advantages of ECoG-based language mapping over the gold-standard stimulation include: (i) lack of stimulation-induced seizures, (ii) better sensitivity of localization of language areas in young children, and (iii) shorter patient participant time. Despite its potential utility, ECoG-based language mapping is far less commonly practiced than stimulation mapping. Here, we have provided video presentations to explain, point-by-point, our own hardware setting and time-frequency analysis procedures. We also have provided standardized auditory stimuli, in multiple languages, ready to be used for ECoG-based language mapping. Finally, we discussed the technical aspects of ECoG-based mapping, including its pitfalls, to facilitate appropriate interpretation of the data., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

We have provided 3-D and 4D mapping of speech and language function based upon the results of direct cortical stimulation and event-related modulation of electrocorticography signals. Patients estimated to have right-hemispheric language dominance were excluded. Thus, 100 patients who underwent two-stage epilepsy surgery with chronic electrocorticography recording were studied. An older group consisted of 84 patients at least 10 years of age (7367 artefact-free non-epileptic electrodes), whereas a younger group included 16 children younger than age 10 (1438 electrodes). The probability of symptoms transiently induced by electrical stimulation was delineated on a 3D average surface image. The electrocorticography amplitude changes of high-gamma (70-110 Hz) and beta (15-30 Hz) activities during an auditory-naming task were animated on the average surface image in a 4D manner. Thereby, high-gamma augmentation and beta attenuation were treated as summary measures of cortical activation. Stimulation data indicated the causal relationship between (i) superior-temporal gyrus of either hemisphere and auditory hallucination; (ii) left superior-/middle-temporal gyri and receptive aphasia; (iii) widespread temporal/frontal lobe regions of the left hemisphere and expressive aphasia; and (iv) bilateral precentral/left posterior superior-frontal regions and speech arrest. On electrocorticography analysis, high-gamma augmentation involved the bilateral superior-temporal and precentral gyri immediately following question onset; at the same time, high-gamma activity was attenuated in the left orbitofrontal gyrus. High-gamma activity was augmented in the left temporal/frontal lobe regions, as well as left inferior-parietal and cingulate regions, maximally around question offset, with high-gamma augmentation in the left pars orbitalis inferior-frontal, middle-frontal, and inferior-parietal regions preceded by high-gamma attenuation in the contralateral homotopic regions. Immediately before verbal response, high-gamma augmentation involved the posterior superior-frontal and pre/postcentral regions, bilaterally. Beta-attenuation was spatially and temporally correlated with high-gamma augmentation in general but with exceptions. The younger and older groups shared similar spatial-temporal profiles of high-gamma and beta modulation; except, the younger group failed to show left-dominant activation in the rostral middle-frontal and pars orbitalis inferior-frontal regions around stimulus offset. The human brain may rapidly and alternately activate and deactivate cortical areas advantageous or obtrusive to function directed toward speech and language at a given moment. Increased left-dominant activation in the anterior frontal structures in the older age group may reflect developmental consolidation of the language system. The results of our functional mapping may be useful in predicting, across not only space but also time and patient age, sites specific to language function for presurgical evaluation of focal epilepsy., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: An appropriate surgical approach for posterior fossa lesions is to start tumor removal from areas with a defined plane to where tumor is infiltrating the brainstem or peduncles. This surgical approach minimizes risk of damage to eloquent areas. Although magnetic resonance imaging (MRI) is the current standard preoperative imaging obtained for diagnosis and surgical planning of pediatric posterior fossa tumors, it offers limited information on the infiltrative planes between tumor and normal structures in patients with medulloblastomas. Because medulloblastomas demonstrate diffusion restriction on apparent diffusion coefficient map (ADC map) sequences, we investigated the role of ADC map in predicting infiltrative and non-infiltrative planes along the brain stem and/or cerebellar peduncles by medulloblastomas prior to surgery., Methods: Thirty-four pediatric patients with pathologically confirmed medulloblastomas underwent surgical resection at our facility from 2004 to 2012. An experienced pediatric neuroradiologist reviewed the brain MRIs/ADC map, assessing the planes between the tumor and cerebellar peduncles/brain stem. An independent evaluator documented surgical findings from operative reports for comparison to the radiographic findings. The radiographic findings were statistically compared to the documented intraoperative findings to determine predictive value of the test in identifying tumor infiltration of the brain stem cerebellar peduncles., Results: Twenty-six patients had preoperative ADC mapping completed and thereby, met inclusion criteria. Mean age at time of surgery was 8.3 ± 4.6 years. Positive predictive value of ADC maps to predict tumor invasion of the brain stem and cerebellar peduncles ranged from 69 to 88 %; negative predictive values ranged from 70 to 89 %. Sensitivity approached 93 % while specificity approached 78 %., Conclusions: ADC maps are valuable in predicting the infiltrative and non-infiltrative planes along the tumor and brain stem interface in medulloblastomas. Inclusion and evaluation of ADC maps in preoperative evaluation can assist in surgical resection planning in patients with medulloblastoma.

Objective: High-frequency oscillations (HFOs) can be spontaneously generated by seizure-onset and functionally-important areas. We determined if consideration of the spectral frequency bands of coupled slow-waves could distinguish between epileptogenic and physiological HFOs., Methods: We studied a consecutive series of 13 children with focal epilepsy who underwent extraoperative electrocorticography. We measured the occurrence rate of HFOs during slow-wave sleep at each electrode site. We subsequently determined the performance of HFO rate for localization of seizure-onset sites and undesirable detection of nonepileptic sensorimotor-visual sites defined by neurostimulation. We likewise determined the predictive performance of modulation index: MI(XHz)&(YHz), reflecting the strength of coupling between amplitude of HFOsXHz and phase of slow-waveYHz. The predictive accuracy was quantified using the area under the curve (AUC) on receiver-operating characteristics analysis., Results: Increase in HFO rate localized seizure-onset sites (AUC⩾0.72; p<0.001), but also undesirably detected nonepileptic sensorimotor-visual sites (AUC⩾0.58; p<0.001). Increase in MI(HFOs)&(3-4Hz) also detected both seizure-onset (AUC⩾0.74; p<0.001) and nonepileptic sensorimotor-visual sites (AUC⩾0.59; p<0.001). Increase in subtraction-MIHFOs [defined as subtraction of MI(HFOs)&(0.5-1Hz) from MI(HFOs)&(3-4Hz)] localized seizure-onset sites (AUC⩾0.71; p<0.001), but rather avoided detection of nonepileptic sensorimotor-visual sites (AUC⩽0.42; p<0.001)., Conclusion: Our data suggest that epileptogenic HFOs may be coupled with slow-wave3-4Hz more preferentially than slow-wave0.5-1Hz, whereas physiologic HFOs with slow-wave0.5-1Hz more preferentially than slow-wave3-4Hz during slow-wave sleep., Significance: Further studies in larger samples are warranted to determine if consideration of the spectral frequency bands of slow-waves coupled with HFOs can positively contribute to presurgical evaluation of patients with focal epilepsy., (Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: Our recent electrocorticography (ECoG) study suggested reverse speech, a widely used control task, to be a poor control for non-language-related auditory activity. We hypothesized that this may be due to retained perception as a human voice. We report a follow-up ECoG study in which we contrast forward and reverse speech with a signal-correlated noise (SCN) control task that cannot be perceived as a human voice., Methods: Ten patients were presented 90 audible stimuli, including 30 each of corresponding forward speech, reverse speech, and SCN trials, during ECoG recording with evaluation of gamma activity between 50 and 150 Hz., Results: Sites of the lateral temporal gyri activated throughout speech stimuli were generally less activated by SCN, while some temporal sites seemed to process both human and non-human sounds. Reverse speech trials were associated with activities across the temporal lobe similar to those associated with forward speech., Conclusions: Findings herein externally validate functional neuroimaging studies utilizing SCN as a control for non-language-specific auditory function. Our findings are consistent with the notion that stimuli perceived as originating from a human voice are poor controls for non-language auditory function., Significance: Our findings have implications in functional neuroimaging research as well as improved clinical mapping of auditory functions., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

The conventional model of language-related brain structure describing the arcuate fasciculus as a key white matter tract providing a direct connection between Wernicke's region and Broca's area has been called into question. Specifically, the inferior precentral gyrus, possessing both primary motor (Brodmann Area [BA] 4) and premotor cortex (BA 6), has been identified as a potential alternative termination. The authors initially localized cortical sites involved in language using measurement of event-related gamma-activity on electrocorticography (ECoG). The authors then determined whether language-related sites of the temporal lobe were connected, via white matter structures, to the inferior frontal gyrus more tightly than to the precentral gyrus. The authors found that language-related sites of the temporal lobe were far more likely to be directly connected to the inferior precentral gyrus through the arcuate fasciculus. Furthermore, tractography was a significant predictor of frontal language-related ECoG findings. Analysis of an interaction between anatomy and tractography in this model revealed tractrography to have the highest predictive value for language-related ECoG findings of the precentral gyrus. This study failed to support the conventional model of language-related brain structure. More feasible models should include the inferior precentral gyrus as a termination of the arcuate fasciculus. The exact functional significance of direct connectivity between temporal language-related sites and the precentral gyrus requires further study., (Copyright © 2013 Wiley Periodicals, Inc.)

Objective: We determined the clinical impact and developmental changes of auditory-language-related augmentation of gamma activity at 50-120 Hz recorded on electrocorticography (ECoG)., Methods: We analyzed data from 77 epileptic patients ranging 4-56 years in age. We determined the effects of seizure-onset zone, electrode location, and patient-age upon gamma-augmentation elicited by an auditory-naming task., Results: Gamma-augmentation was less frequently elicited within seizure-onset sites compared to other sites. Regardless of age, gamma-augmentation most often involved the 80-100 Hz frequency band. Gamma-augmentation initially involved bilateral superior-temporal regions, followed by left-side dominant involvement in the middle-temporal, medial-temporal, inferior-frontal, dorsolateral-premotor, and medial-frontal regions and concluded with bilateral inferior-Rolandic involvement. Compared to younger patients, those older than 10 years had a larger proportion of left dorsolateral-premotor and right inferior-frontal sites showing gamma-augmentation. The incidence of a post-operative language deficit requiring speech therapy was predicted by the number of resected sites with gamma-augmentation in the superior-temporal, inferior-frontal, dorsolateral-premotor, and inferior-Rolandic regions of the left hemisphere assumed to contain essential language function (r(2) = 0.59; p = 0.001; odds ratio = 6.04 [95% confidence-interval: 2.26-16.15])., Conclusions: Auditory-language-related gamma-augmentation can provide additional information useful to localize the primary language areas., Significance: These results derived from a large sample of patients support the utility of auditory-language-related gamma-augmentation in presurgical evaluation., (Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: We determined the utility of electrocorticography (ECoG) and stimulation for detecting language-related sites in patients with left-hemispheric language-dominance on Wada test., Methods: We studied 13 epileptic patients who underwent language mapping using event-related gamma-oscillations on ECoG and stimulation via subdural electrodes. Sites showing significant gamma-augmentation during an auditory-naming task were defined as language-related ECoG sites. Sites at which stimulation resulted in auditory perceptual changes, failure to verbalize a correct answer, or sensorimotor symptoms involving the mouth were defined as language-related stimulation sites. We determined how frequently these methods revealed language-related sites in the superior-temporal, inferior-frontal, dorsolateral-premotor, and inferior-Rolandic regions., Results: Language-related sites in the superior-temporal and inferior-frontal gyri were detected by ECoG more frequently than stimulation (p < 0.05), while those in the dorsolateral-premotor and inferior-Rolandic regions were detected by both methods equally. Stimulation of language-related ECoG sites, compared to the others, more frequently elicited language symptoms (p < 0.00001). One patient developed dysphasia requiring in-patient speech therapy following resection of the dorsolateral-premotor and inferior-Rolandic regions containing language-related ECoG sites not otherwise detected by stimulation., Conclusions: Language-related gamma-oscillations may serve as an alternative biomarker of underlying language function in patients with left-hemispheric language-dominance., Significance: Measurement of language-related gamma-oscillations is warranted in presurgical evaluation of epileptic patients., (Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Reverse speech has often been used as a control task in brain-mapping studies of language utilizing various non-invasive modalities. The rationale is that reverse speech is comparable to forward speech in terms of auditory characteristics, while omitting the linguistic components. Thus, it may control for non-language auditory functions. This finds some support in fMRI studies indicating that reverse speech resulted in less blood-oxygen-level-dependent (BOLD) signal intensity in perisylvian regions than forward speech. We attempted to externally validate a reverse speech control task using intracranial electrocorticography (ECoG) in eight patients with intractable focal epilepsy. We studied adolescent and adult patients who underwent extraoperative ECoG prior to resective epilepsy surgery. All patients received an auditory language task during ECoG recording. Patients were presented 115 audible question stimuli, including 30 reverse speech trials. Reverse speech trials more strongly engaged bilateral superior temporal sites than did the corresponding forward speech trials. Forward speech trials elicited larger gamma-augmentation at frontal lobe sites not attributable to sensorimotor function. Other temporal and frontal sites of significant augmentation showed no significant difference between reverse and forward speech. Thus, we failed to validate reported evidence of weaker activation of temporal neocortices during reverse compared to forward speech. Superior temporal lobe engagement may indicate increased attention to reverse speech. Reverse speech does not appear to be a suitable task for the control of non-language auditory functions on ECoG., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: We assessed 636 epileptic spasms seen in 11 children (median 44 spasms per child) and determined the spatial and temporal characteristics of ictal high-frequency oscillations (HFOs) in relation to the onset of spasms., Methods: Electrocorticography (ECoG) signals were sampled from 104-148 cortical sites per child, and the dynamic changes of ictal HFOs were animated on each individual's three-dimensional (3D) magnetic resonance (MR) image surface., Key Findings: Visual assessment of ictal ECoG recordings revealed that each spasm event was characterized by augmentation of HFOs. Time-frequency analysis demonstrated that ictal augmentation of HFOs at 80-200 Hz was most prominent and generally preceded those at 210-300 Hz and at 70 Hz and slower. Recruitment of HFOs in the rolandic cortex preceded the clinical onset objectively visualized as electromyographic deflection. The presence or absence of ictal motor symptoms was related more to the amplitude of HFOs in the Rolandic cortex than in the seizure-onset zone. In a substantial proportion of epileptic spasms, seizure termination began at the seizure-onset zone and propagated to the surrounding areas; we referred to this observation as the "ictal doughnut phenomenon." Univariate analysis suggested that complete resection of the sites showing the earliest augmentation of ictal HFOs was associated with a good surgical outcome., Significance: Recruitment of HFOs at 80-200 Hz in the rolandic area may play a role in determining seizure semiology in epileptic spasms. Our study using macroelectrodes demonstrated that ictal HFOs at 80-200 Hz preceded those at 210-300 Hz., (Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.)

We determined how visuomotor tasks modulated gamma-oscillations on electrocorticography in epileptic patients who underwent epilepsy surgery. Each visual-cue consisted of either a sentence or hand gesture instructing the subject to press or not to press the button. Regardless of the recorded hemisphere, viewing sentence and gesture cues elicited gamma-augmentation sequentially in the lateral-polar occipital and inferior occipital-temporal areas; subsequently, button-press movement elicited gamma-augmentation in the Rolandic area. The magnitudes of gamma-augmentation in the Rolandic and inferior occipital-temporal areas were larger when the hand contralateral to the recorded hemisphere was used for motor responses. A double dissociation was found in the left inferior occipital-temporal cortex in one subject; the lateral portion had greater gamma-augmentation elicited by a sentence-cue, whereas the medial portion had greater gamma-augmentation elicited by a gesture-cue. The present study has increased our understanding of the physiology of the human visuomotor system., (Copyright 2010 Elsevier Inc. All rights reserved.)

The usefulness of magnetic resonance imaging tractography is demonstrated in the presurgical planning of an 8-year-old girl with intractable epilepsy. Imaging and intracranial electrode monitoring suggested a left hemispherectomy for complete control of her seizures. Although this child was hemiplegic, she retained considerable motor function in her right hand, and her parents and the epilepsy team voiced significant concern that she would lose right-hand function after a hemispherectomy. Tractography indicated near-complete absence of her left corticospinal tract and a more robust than normal corticospinal tract in the right hemisphere. This finding suggested that her right motor function had reorganized to the right hemisphere and the ipsilateral corticospinal tract. After surgery, her seizures were completely controlled, and no change in right motor activity was evident compared with her presurgical status. Tractography helped determine the extent of cortical resection and predict the extent of motor functional loss.

Both superior temporal gyrus and inferior Rolandic area have been reported to be involved in perception and production of speech in humans. Here, we determined how these cortical structures were activated by listening and subsequent overt articulation of syllables, by measuring event-related gamma-oscillations as quantitative measures of cortical activation. Fifteen subjects were presented an auditory syllable consisting of either "fee [fi:]," "faa [falpha:]," "hee [hi:]," or "haa [halpha:]," and were instructed to overtly repeat each given syllable. Gamma-oscillations in the superior temporal gyrus were highly augmented during syllable-presentation, least augmented at the onset of syllable-articulation, and again highly augmented following syllable-articulation. Gamma-oscillations were augmented in the inferior Rolandic area prior to and during syllable-articulation with the onset and peak occurring earlier in the left side. Subsets of the inferior Rolandic sites, more frequently on the left side, showed differential gamma-augmentation elicited by articulation of phoneme [f] more than [h] or phoneme [i:] more than [alpha:]. Our observations suggest that the superior temporal gyrus may be active when externally presented or articulated auditory stimuli are present, and may be minimally active when articulation is about to be initiated. Our novel observation of phoneme-specific differential gamma-augmentation in the inferior Rolandic area may be partially attributed to the mouth position during phoneme-articulation. Our observations support the hypothesis that positioning of the mouth to articulate phonemes is predominantly driven and/or monitored by the primary sensorimotor area on the left side., (Copyright (c) 2009 Elsevier Inc. All rights reserved.)

Why do the epileptogenic foci appear hypometabolic on interictal glucose metabolism positron emission tomography (PET) in a substantial proportion of patients with focal epilepsy but appear normo- or even hyper-metabolic in others? Such observations on interictal PET have not been fully explained by the frequency of interictal spike discharges alone. In the present study using digital electrocorticography monitoring system with high-frequency sampling, we determined how well regression models using spectral ECoG measures and spike frequency derived from 651 intracranial electrode sites explained cortical glucose metabolic patterns in six children with nonlesional focal epilepsy. Univariate regression analysis demonstrated that spectral amplitudes at gamma ranges (32-64, 64-100, and 100-200 Hz) were tightly correlated with interictal glucose uptake in the given electrode site in all children. Spike frequency was negatively correlated with interictal glucose uptake in three patients, whose epileptogenic focus appeared hypometabolic and interictal epileptiform discharge often consisted of a spike followed by a subsequent delta-wave. Conversely, spike frequency was positively correlated with interictal glucose uptake in the other three patients, whose epileptogenic foci appeared more hypermetabolic compared to the surrounding regions and associated with frequent interictal spike bursts. The spatial pattern of interictal glucose metabolism in nonlesional focal epilepsy may be better explained by gamma-oscillations derived from epileptiform and physiological neuronal activities rather than the frequency of interictal epileptiform discharges alone.

We determined if high-frequency gamma-oscillations (50- to 150-Hz) were induced by simple auditory communication over the language network areas in children with focal epilepsy. Four children (aged 7, 9, 10 and 16 years) with intractable left-hemispheric focal epilepsy underwent extraoperative electrocorticography (ECoG) as well as language mapping using neurostimulation and auditory-language-induced gamma-oscillations on ECoG. The audible communication was recorded concurrently and integrated with ECoG recording to allow for accurate time lock on ECoG analysis. In three children, who successfully completed the auditory-language task, high-frequency gamma-augmentation sequentially involved: i) the posterior superior temporal gyrus when listening to the question, ii) the posterior lateral temporal region and the posterior frontal region in the time interval between question completion and the patient's vocalization, and iii) the pre- and post-central gyri immediately preceding and during the patient's vocalization. The youngest child, with attention deficits, failed to cooperate during the auditory-language task, and high-frequency gamma-augmentation was noted only in the posterior superior temporal gyrus when audible questions were given. The size of language areas suggested by statistically significant high-frequency gamma-augmentation was larger than that defined by neurostimulation. The present method can provide in vivo imaging of electrophysiological activities over the language network areas during language processes. Further studies are warranted to determine whether recording of language-induced gamma-oscillations can supplement language mapping using neurostimulation in presurgical evaluation of children with focal epilepsy.