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Objective: We analyzed the dose-dependent effects of Sevoflurane anesthesia on high-frequency oscillations (HFOs) and spike discharges at non-epileptic sites and evaluated their effectiveness in identifying the epileptogenic zone., Methods: We studied 21 children with drug-resistant focal epilepsy who achieved seizure control after focal resective surgery. Open-source detectors quantified HFO and spike rates during extraoperative and intraoperative intracranial EEG recordings performed before resection. We determined under which anesthetic conditions HFO and spike rates differentiated the seizure onset zone (SOZ) within the resected area from non-epileptic sites., Results: We analyzed 925 artifact-free electrodes, including 867 at non-epileptic sites and 58 at SOZ sites. Higher Sevoflurane doses significantly increased HFO and spike rates at non-epileptic sites, exhibiting spatial variability among different detectors. These biomarkers were elevated in the SOZ more than in non-epileptic sites under 2-4 vol% Sevoflurane anesthesia, with Cohen's d effect sizes above 3.0 and Mann-Whitney U-Test r effect sizes above 0.5., Conclusions: We provided normative atlases of HFO and spike rates under different Sevoflurane anesthesia conditions. Sevoflurane elevates HFO and spike rates preferentially in the epileptogenic zone., Significance: Assessing the relative severity of biomarker levels across sites may be relevant for localizing the epileptogenic zone under Sevoflurane anesthesia., Competing Interests: Declarations of interest None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: In tasks involving new visuospatial information, we rely on working memory, supported by a distributed brain network. We investigated the dynamic interplay between brain regions, including cortical and white matter structures, to understand how neural interactions change with different memory loads and trials, and their subsequent impact on working memory performance., Methods: Patients undertook a task of immediate spatial recall during intracranial EEG monitoring. We charted the dynamics of cortical high-gamma activity and associated functional connectivity modulations in white matter tracts., Results: Elevated memory loads were linked to enhanced functional connectivity via occipital longitudinal tracts, yet decreased through arcuate, uncinate, and superior-longitudinal fasciculi. As task familiarity grew, there was increased high-gamma activity in the posterior inferior-frontal gyrus (pIFG) and diminished functional connectivity across a network encompassing frontal, parietal, and temporal lobes. Early pIFG high-gamma activity was predictive of successful recall. Including this metric in a logistic regression model yielded an accuracy of 0.76., Conclusions: Optimizing visuospatial working memory through practice is tied to early pIFG activation and decreased dependence on irrelevant neural pathways., Significance: This study expands our knowledge of human adaptation for visuospatial working memory, showing the spatiotemporal dynamics of cortical network modulations through white matter tracts., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Uterine leiomyosarcoma (ULMS) is a rare malignant tumor, which is aggressive, and has a poor prognosis even during its early stages. Extracellular vesicles (EVs) carry cargo, such as microRNAs (miRNAs), which are involved in intercellular communication in the tumor microenvironment and other processes. Because there are no studies on EV-related miRNAs in ULMS, we identified EV-related miRNAs in ULMS and examined their function., Methods: Small EVs (sEVs) and medium/large EVs (m/lEVs) were extracted from ULMS cells by ultracentrifugation and their basic characteristics were evaluated. Then, small RNA sequencing was done to obtain EV-related miRNA profiles. Next, miRNA expression levels in sera and tissues of ULMS patients were compared with those of myoma patients., Results: miR-654-3p and miR-369-3p were indicated to be highly expressed in both sera and tissues of ULMS patients. These two miRNAs are also highly expressed in ULMS cell lines and ULMS-derived EVs. Some cancer-associated fibroblast (CAF) markers were increased when fibroblasts were treated with ULMS-derived EVs. Furthermore, fibroblasts took up EVs derived from ULMS as determined by confocal laser microscopy. In addition, the transfection of the two candidate miRNAs into fibroblasts significantly increased some CAF markers, particularly ACTA2., Conclusion: miR-654-3p and miR-369-3p are highly expressed in ULMS-derived EVs, indicating that these EV-related miRNAs induce the formation of cancer-associated fibroblasts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Ovarian cancer is the leading cause of death among women with gynecological cancer, and novel treatment options are urgently needed. Extracellular vesicles (EVs), including exosomes, may be one of the most promising therapeutic tools for various diseases. In this study, we aimed to investigate the therapeutic effects of adipose-derived stem cell-derived EVs (ADSC-EVs) on ovarian cancer cell lines., Materials and Methods: ADSCs and the ovarian cancer cell lines SKOV3 and OV90 were used for analysis. ADSC-EVs were isolated through ultracentrifugation and validated using a cryotransmission electron microscope, nanoparticle tracking analysis, and western blotting. Then, the effect of ADSC-EVs on ovarian cancer cells was investigated using IncuCyte and microRNA sequencing. Moreover, the potential functions of miRNAs were evaluated by gain-of function analysis and in silico analysis., Results: ADSC-EVs suppressed SKOV3 and OV90 cell proliferation. In particular, small EVs (sEVs) from ADSCs exhibited a stronger antitumor effect than ADSC-medium/large EVs (m/lEVs). Comparison of the miRNA profiles between ADSC-sEVs and ADSC-m/lEVs, along with downstream pathway analysis, suggested the involvement of the let-7 family. Overexpression of hsa-let-7b-5p and hsa-let-7e-5p significantly suppressed the proliferation of SKOV3 cells. In silico analysis revealed that four potential target genes of hsa-let-7b-5p and hsa-let-7e-5p were significantly associated with the prognoses of the patients., Conclusion: ADSC-sEVs had a stronger antitumor effect than ADSC-m/lEVs. Hsa-let-7b-5p and hsa-let-7e-5p, which are highly abundant in ADSC-sEVs, suppressed cell proliferation. These findings may open up new possibilities for therapeutic approaches using ADSC-sEVs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Akira Yokoi reports financial support was provided by Japan Science and Technology Agency. Akira Yokoi reports financial support was provided by Princess Takamatsu Cancer Research Fund. Akira Yokoi reports financial support was provided by Aichi Cancer Research Foundation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To determine how sevoflurane anesthesia modulates intraoperative epilepsy biomarkers on electrocorticography, including high-frequency oscillation (HFO) effective connectivity (EC), and to investigate their relation to epileptogenicity and anatomical white matter., Methods: We studied eight pediatric drug-resistant focal epilepsy patients who achieved seizure control after invasive monitoring and resective surgery. We visualized spatial distributions of the electrocorticography biomarkers at an oxygen baseline, three time-points while sevoflurane was increasing, and at a plateau of 2 minimum alveolar concentration (MAC) sevoflurane. HFO EC was combined with diffusion-weighted imaging, in dynamic tractography., Results: Intraoperative HFO EC diffusely increased as a function of sevoflurane concentration, although most in epileptogenic sites (defined as those included in the resection); their ability to classify epileptogenicity was optimized at sevoflurane 2 MAC. HFO EC could be visualized on major white matter tracts, as a function of sevoflurane level., Conclusions: The results strengthened the hypothesis that sevoflurane-activated HFO biomarkers may help intraoperatively localize the epileptogenic zone., Significance: Our results help characterize how HFOs at non-epileptogenic and epileptogenic networks respond to sevoflurane. It may be warranted to establish a normative HFO atlas incorporating the modifying effects of sevoflurane and major white matter pathways, as critical reference in epilepsy presurgical evaluation., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Uterine leiomyosarcoma (ULMS) is a malignant stromal tumor arising from the myometrium with a poor prognosis and very limited response to current chemotherapy. This study aimed to identify novel targets for ULMS through a three-step screening process using a chemical library consisting of 1271 Food and Drug Administration-approved drugs. First, we evaluated their inhibitory effects on ULMS cells and identified four candidates: proscillaridin A, lanatoside C, floxuridine, and digoxin. Then, we subcutaneously or orthotopically transplanted SK-UT-1 cells into mice to establish mouse models. In vivo analyses showed that proscillaridin A and lanatoside C exerted a superior antitumor effect. The results of mRNA sequencing showed that uncoupling protein 2 (UCP2) was suppressed in the sirtuin signaling pathway, increasing reactive oxygen species (ROS) and inducing cell death. Moreover, the downregulation of UCP2 induced ROS and suppressed ULMS cell growth. Furthermore, analyses using clinical samples showed that UCP2 expression was significantly upregulated in ULMS tissues than in myoma tissues both at the RNA and protein levels. These findings suggested that UCP2 is a potential therapeutic target and can contribute to the development of novel therapeutic strategies in patients with ULMS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Phase-amplitude coupling between high-frequency (≥150 Hz) and delta (3-4 Hz) oscillations - modulation index (MI) - is a promising, objective biomarker of epileptogenicity. We determined whether sevoflurane anesthesia preferentially enhances this metric within the epileptogenic zone., Methods: This is an observational study of intraoperative electrocorticography data from 621 electrodes chronically implanted into eight patients with drug-resistant, focal epilepsy. All patients were anesthetized with sevoflurane during resective surgery, which subsequently resulted in seizure control. We classified 'removed' and 'retained' brain sites as epileptogenic and non-epileptogenic, respectively. Mixed model analysis determined which anesthetic stage optimized MI-based classification of epileptogenic sites., Results: MI increased as a function of anesthetic stage, ranging from baseline (i.e., oxygen alone) to 2.0 minimum alveolar concentration (MAC) of sevoflurane, preferentially at sites showing higher initial MI values. This phenomenon was accentuated just prior to sevoflurane reaching 2.0 MAC, at which time, the odds of a site being classified as epileptogenic were enhanced by 86.6 times for every increase of 1.0 MI., Conclusions: Intraoperative MI best localized the epileptogenic zone immediately before sevoflurane reaching 2.0 MAC in this small cohort of patients., Significance: Prospective, large cohort studies are warranted to determine whether sevoflurane anesthesia can reduce the need for extraoperative, invasive evaluation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: We clarified the clinical and mechanistic significance of physiological modulations of high-frequency broadband cortical activity associated with spontaneous saccadic eye movements during a resting state., Methods: We studied 30 patients who underwent epilepsy surgery following extraoperative electrocorticography and electrooculography recordings. We determined whether high-gamma activity at 70-110 Hz preceding saccade onset would predict upcoming ocular behaviors. We assessed how accurately the model incorporating saccade-related high-gamma modulations would localize the primary visual cortex defined by electrical stimulation., Results: The dynamic atlas demonstrated transient high-gamma suppression in the striatal cortex before saccade onset and high-gamma augmentation subsequently involving the widespread posterior brain regions. More intense striatal high-gamma suppression predicted the upcoming saccade directed to the ipsilateral side and lasting longer in duration. The bagged-tree-ensemble model demonstrated that intense saccade-related high-gamma modulations localized the visual cortex with an accuracy of 95%., Conclusions: We successfully animated the neural dynamics supporting saccadic suppression, a principal mechanism minimizing the perception of blurred vision during rapid eye movements. The primary visual cortex per se may prepare actively in advance for massive image motion expected during upcoming prolonged saccades., Significance: Measuring saccade-related electrocorticographic signals may help localize the visual cortex and avoid misperceiving physiological high-frequency activity as epileptogenic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Objective: To visualize and validate the dynamics of interhemispheric neural propagations induced by single-pulse electrical stimulation (SPES)., Methods: This methodological study included three patients with drug-resistant focal epilepsy who underwent measurement of cortico-cortical spectral responses (CCSRs) during bilateral stereo-electroencephalography recording. We delivered SPES to 83 electrode pairs and analyzed CCSRs recorded at 268 nonepileptic electrode sites. Diffusion-weighted imaging (DWI) tractography localized the interhemispheric white matter pathways as streamlines directly connecting two electrode sites. We localized and visualized the putative SPES-related fiber activation, at each 1-ms time window, based on the propagation velocity defined as the DWI-based streamline length divided by the early CCSR peak latency., Results: The resulting movie, herein referred to as four-dimensional tractography, delineated the spatiotemporal dynamics of fiber activation via the corpus callosum and anterior commissure. Longer streamline length was associated with delayed peak latency and smaller amplitude of CCSRs. The cortical regions adjacent to each fiber activation site indeed exhibited CCSRs at the same time window., Conclusions: Our four-dimensional tractography successfully animated neural propagations via distinct interhemispheric pathways., Significance: Our novel animation method has the potential to help investigators in addressing the mechanistic significance of the interhemispheric network dynamics supporting physiological function., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: To determine the optimal depth electrode montages for the assessment of effective connectivity based on single-pulse electrical stimulation (SPES). To determine the effect of SPES locations on the extent of resulting neuronal propagations., Methods: We studied 14 epilepsy patients who underwent invasive monitoring with depth electrodes and measurement of cortico-cortical evoked potentials (CCEPs) and cortico-cortical spectral responses (CCSRs). We determined the effects of electrode montage and stimulus sites on the CCEP/CCSR amplitudes., Results: Bipolar and Laplacian montages effectively reduced the degree of SPES-related signal deflections at extra-cortical levels, including outside the brain, while maintaining those at the cortical level. SPES of structures more proximal to the deep white matter, compared to the cortical surface, elicited greater CCEPs and CCSRs., Conclusions: On depth electrode recording, bipolar and Laplacian montages are suitable for measurement of near-field CCEPs and CCSRs. SPES of the white matter axons may induce neuronal propagations to extensive regions of the cerebral cortex., Significance: This study helps to establish the practical guidelines on the diagnostic use of CCEPs/CCSRs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the diagnostic utility of high frequency oscillations (HFOs) via scalp electroencephalogram (EEG) in infantile spasms., Methods: We retrospectively analyzed interictal slow-wave sleep EEGs sampled at 2,000 Hz recorded from 30 consecutive patients who were suspected of having infantile spasms. We measured the rate of HFOs (80-500 Hz) and the strength of the cross-frequency coupling between HFOs and slow-wave activity (SWA) at 3-4 Hz and 0.5-1 Hz as quantified with modulation indices (MIs)., Results: Twenty-three patients (77%) exhibited active spasms during the overnight EEG recording. Although the HFOs were detected in all children, increased HFO rate and MIs correlated with the presence of active spasms (p < 0.001 by HFO rate; p < 0.01 by MIs at 3-4 Hz; p = 0.02 by MIs at 0.5-1 Hz). The presence of active spasms was predicted by the logistic regression models incorporating HFO-related metrics (AUC: 0.80-0.98) better than that incorporating hypsarrhythmia (AUC: 0.61). The predictive performance of the best model remained favorable (87.5% accuracy) after a cross-validation procedure., Conclusions: Increased rate of HFOs and coupling between HFOs and SWA are associated with active epileptic spasms., Significance: Scalp-recorded HFOs may serve as an objective EEG biomarker for active epileptic spasms., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Although diabetic polyneuropathy (DPN) is the commonest diabetic complication, its pathology remains to be clarified. As previous papers have suggested the neuroprotective effects of glucagon-like peptide-1 in DPN, the current study investigated the physiological indispensability of glucagon gene-derived peptides (GCGDPs) including glucagon-like peptide-1 in the peripheral nervous system (PNS). Neurological functions and neuropathological changes of GCGDP deficient (gcg-/-) mice were examined. The gcg-/- mice showed tactile allodynia and thermal hyperalgesia at 12-18 weeks old, followed by tactile and thermal hypoalgesia at 36 weeks old. Nerve conduction studies revealed a decrease in sensory nerve conduction velocity at 36 weeks old. Pathological findings showed a decrease in intraepidermal nerve fiber densities. Electron microscopy revealed a decrease in circularity and an increase in g-ratio of myelinated fibers and a decrease of unmyelinated fibers in the sural nerves of the gcg-/- mice. Effects of glucagon on neurite outgrowth were examined using an ex vivo culture of dorsal root ganglia. A supraphysiological concentration of glucagon promoted neurite outgrowth. In conclusion, the mice with deficiency of GCGDPs developed peripheral neuropathy with age. Furthermore, glucagon might have neuroprotective effects on the PNS of mice. GCGDPs might be involved in the pathology of DPN., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To characterize the spatiotemporal dynamics of auditory and picture naming-related cortical activation in Japanese-speaking patients., Methods: Ten patients were assigned auditory naming and picture naming tasks during extraoperative intracranial EEG recording in a tertiary epilepsy center. Time-frequency analysis determined at what electrode sites and at what time windows during each task the amplitude of high-gamma activity (65-95 Hz) was modulated., Results: The superior-temporal gyrus on each hemisphere showed high-gamma augmentation during sentence listening, whereas the left middle-temporal and inferior-frontal gyri showed high-gamma augmentation peaking around stimulus offset. Auditory naming-specific high-gamma augmentation was noted in the bilateral superior-temporal gyri as well as left frontal-parietal-temporal perisylvian network regions, whereas picture naming-specific augmentation was noted in the occipital-fusiform regions, bilaterally. The inferior pre- and postcentral gyri on each hemisphere showed modality-common high-gamma augmentation time-locked to overt responses., Conclusions: The spatiotemporal dynamics of auditory and picture naming-related high-gamma augmentation in Japanese-speaking patients were qualitatively similar to those previously reported in studies of English-speaking patients., Significance: The cortical dynamics for auditory sentence recognition are at least partly shared by cohorts speaking two distinct languages. Multicenter studies regarding the clinical utility of high-gamma language mapping across Eastern and Western hemispheres may be feasible., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Interictal spikes are a biomarker of epilepsy, yet their precise roles are poorly understood. Using long-term neocortical recordings from epileptic patients, we investigated the spatial-temporal propagation patterns of interictal spiking., Methods: Interictal spikes were detected in 10 epileptic patients. Short time direct directed transfer function was used to map the spatial-temporal patterns of interictal spike onset and propagation across different cortical topographies., Results: Each patient had unique interictal spike propagation pattern that was highly consistent across times, regardless of the frequency band. High spiking brain regions were often not spike onset regions. We observed frequent spike propagations to shorter distances and that the central sulcus forms a strong barrier to spike propagation. Spike onset and seizure onset seemed to be distinct networks in most cases., Conclusions: Patients in epilepsy have distinct and unique network of causal propagation pattern which are very consistent revealing the underlying epileptic network. Although spike are epileptic biomarkers, spike origin and seizure onset seems to be distinct in most cases., Significance: Understanding patterns of interictal spike propagation could lead to the identification patient-specific epileptic networks amenable to surgical or other treatments., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: We generated a large-scale, four-dimensional map of neuronal modulations elicited by full-field flash stimulation., Methods: We analyzed electrocorticography (ECoG) recordings from 63 patients with focal epilepsy, and delineated the spatial-temporal dynamics of visually-elicited high-gamma 70-110 Hz amplitudes on a standard brain template. We then clarified the neuronal events underlying visual evoked potential (VEP) components, by correlating with high-gamma amplitude measures., Results: The medial-occipital cortex initially revealed rapid neural activation followed by prolonged suppression, reflected by augmentation of high-gamma activity lasting up to 100 ms followed by attenuation lasting up to 1000 ms, respectively. With a number of covariate factors incorporated into a prediction model, the eccentricity representation independently predicted the magnitude of post-activation suppression, which was more intense in regions representing more parafoveal visual fields compared to those of more peripheral fields. The initial negative component on VEP was sharply contoured and co-occurred with early high-gamma augmentation, whose offset then co-occurred with a large positive VEP peak. A delayed negative VEP peak was blunt and co-occurred with prolonged high-gamma attenuation., Conclusions: Eccentricity-dependent gradient in neural suppression in the medial-occipital region may explain the functional difference between peripheral and parafoveal/central vision. Early negative and positive VEP components may reflect neural activation, whereas a delayed negative VEP peak reflecting neural suppression., Significance: Our observation provides the mechanistic rationale for transient scotoma or mild flash-blindness, characterized by physiological afterimage preferentially formed in central vision following intense but non-injurious light exposure., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. 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.)

Standardized terminology for computer-based assessment and reporting of EEG has been previously developed in Europe. The International Federation of Clinical Neurophysiology established a taskforce in 2013 to develop this further, and to reach international consensus. This work resulted in the second, revised version of SCORE (Standardized Computer-based Organized Reporting of EEG), which is presented in this paper. The revised terminology was implemented in a software package (SCORE EEG), which was tested in clinical practice on 12,160 EEG recordings. Standardized terms implemented in SCORE are used to report the features of clinical relevance, extracted while assessing the EEGs. Selection of the terms is context sensitive: initial choices determine the subsequently presented sets of additional choices. This process automatically generates a report and feeds these features into a database. In the end, the diagnostic significance is scored, using a standardized list of terms. SCORE has specific modules for scoring seizures (including seizure semiology and ictal EEG patterns), neonatal recordings (including features specific for this age group), and for Critical Care EEG Terminology. SCORE is a useful clinical tool, with potential impact on clinical care, quality assurance, data-sharing, research and education., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: The articulatory loop is a fundamental component of language function, involved in the short-term buffer of auditory information followed by its vocal reproduction. We characterized the network dynamics of the human articulatory loop, using invasive recording and stimulation., Methods: We measured high-gamma activity 70-110 Hz recorded intracranially when patients with epilepsy either only listened to, or listened to and then reproduced two successive tones by humming. We also conducted network analyses, and analyzed behavioral responses to cortical stimulation., Results: Presentation of the initial tone elicited high-gamma augmentation bilaterally in the superior-temporal gyrus (STG) within 40ms, and in the precentral and inferior-frontal gyri (PCG and IFG) within 160ms after sound onset. During presentation of the second tone, high-gamma augmentation was reduced in STG but enhanced in IFG. The task requiring tone reproduction further enhanced high-gamma augmentation in PCG during and after sound presentation. Event-related causality (ERC) analysis revealed dominant flows within STG immediately after sound onset, followed by reciprocal interactions involving PCG and IFG. Measurement of cortico-cortical evoked-potentials (CCEPs) confirmed connectivity between distant high-gamma sites in the articulatory loop. High-frequency stimulation of precentral high-gamma sites in either hemisphere induced speech arrest, inability to control vocalization, or forced vocalization. Vocalization of tones was accompanied by high-gamma augmentation over larger extents of PCG., Conclusions: Bilateral PCG rapidly and directly receives feed-forward signals from STG, and may promptly initiate motor planning including sub-vocal rehearsal for short-term buffering of auditory stimuli. Enhanced high-gamma augmentation in IFG during presentation of the second tone may reflect high-order processing of the tone sequence., Significance: The articulatory loop employs sustained reciprocal propagation of neural activity across a network of cortical sites with strong neurophysiological connectivity., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Subtotal hemispherectomy involves the resection of multiple lobes in children with drug-resistant epilepsy, skipping the motor area (MA). We determined epileptogenicity using the occurrence rate (OR) of high-frequency oscillations (HFOs) and the modulation index (MI), demonstrating strength of coupling between HFO and slow wave. We hypothesized that epileptogenicity increased over the multiple lobes but skipped the MA., Methods: We analyzed 23 children (14 subtotal hemispherectomy; 9 multilobar resections). Scalp video-EEG and magnetoencephalography were performed before surgery. We analyzed the OR (HFO) and MI (5 phases=0.5-8 Hz) on electrodes of total area, resection areas, and MA. We compared the data between good [International League Against Epilepsy (ILAE) class I-II] and poor (III-VI) seizure outcome groups., Results: ILAE class Ia outcome was achieved in 18 children. Among the MI (5 phases) in the resection areas, MI (3-4 Hz) was the highest. The OR (HFO) and MI (3-4 Hz) in both total area and resection areas were significantly higher in the good seizure outcome group than in the poor outcome group. The OR (HFO) and MI (3-4 Hz) in resection areas were significantly higher than in the MA., Conclusions: Our patients with multilobar drug-resistant epilepsy showed evidence of multifocal epileptogenicity that specifically skipped the MA., Significance: This is the first study demonstrating that the electrophysiological phenotype of multifocal epilepsy specifically skips the MA using OR (HFO) and MI (3-4 Hz) ., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: During verbal communication, humans briefly maintain mental representations of speech sounds conveying verbal information, and constantly scan these representations for comparison to incoming information. We determined the spatio-temporal dynamics of such short-term maintenance and subsequent scanning of verbal information, by intracranially measuring high-gamma activity at 70-110Hz during a working memory task., Methods: Patients listened to a stimulus set of two or four spoken letters and were instructed to remember those letters over a two-second interval, following which they were asked to determine if a subsequent target letter had been presented earlier in that trial's stimulus set., Results: Auditory presentation of letter stimuli sequentially elicited high-gamma augmentation bilaterally in the superior-temporal and pre-central gyri. During the two-second maintenance period, high-gamma activity was augmented in the left pre-central gyrus, and this effect was larger during the maintenance of stimulus sets consisting of four compared to two letters. During the scanning period following target presentation, high-gamma augmentation involved the left inferior-frontal and supra-marginal gyri., Conclusions: Short-term maintenance of verbal information is, at least in part, supported by the left pre-central gyrus, whereas scanning by the left inferior-frontal and supra-marginal gyri., Significance: The cortical structures involved in short-term maintenance and scanning of speech stimuli were segregated with an excellent temporal resolution., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Purpose: We evaluated if cortical thickness measures were associated with surgical outcome in patients with non-lesional neocortical epilepsy., Methods: Twenty-one young patients (age: 2.4-19.7years) with epilepsy of neocortical origin and normal MRI underwent two-stage epilepsy surgery with subdural EEG monitoring. Cortical thickness was measured on presurgical volumetric MRI using the FreeSurfer software. The prognostic value of hemispheric and lobar/regional cortical thickness measures for 1-year and 2-year post-surgical seizure outcome has been analyzed., Results: At one-year follow-up, 14 patients (67%) were seizure-free. Hemispheric and frontal lobe cortical thickness showed no/minimal asymmetry in seizure-free patients but thinner cortex ipsilateral to the seizure focus in those with recurrent seizures (p=0.02). More robust differences were found in patients≥6years of age (p=0.006 for frontal asymmetries), whose cortical thickness asymmetries remained prognostic for 2-year post-surgical outcome (p=0.007). By using an optimal cutoff threshold based on a receiver operating characteristic analysis, mean hemispheric asymmetry predicted one-year seizure freedom with 93% sensitivity and 71% specificity in the whole group, and with 100% sensitivity and 92% specificity in patients≥6years of age., Conclusion: In patients with neocortical epilepsy and normal MRI, neocortical thinning in the epileptic hemisphere, particularly in frontal cortex, is associated with poor surgical outcome. Although these results require validation in a larger cohort prospectively, these data suggest that presurgical evaluation of cortical thickness may assist in identification of patients at high risk for surgical failure., Competing Interests: None., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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: To better understand 'when' and 'where' wideband electrophysiological signals are altered by sedation., Methods: We generated animation movies showing electrocorticography (ECoG) amplitudes at eight spectral frequency bands across 1.0-116 Hz, every 0.1s, on three-dimensional surface images of 10 children who underwent epilepsy surgery. We measured the onset, intensity, and variance of each band amplitude change at given nonepileptic regions separately from those at affected regions. We also determined the presence of differential ECoG changes depending on the brain anatomy., Results: Within 20s following injection of midazolam, beta (16-31.5 Hz) and sigma (12-15.5 Hz) activities began to be multifocally augmented with increased variance in amplitude at each site. Beta-sigma augmentation was most prominent within the association neocortex. Augmentation of low-delta activity (1.0-1.5 Hz) was relatively modest and confined to the somatosensory-motor region. Conversely, injection of midazolam induced attenuation of theta (4.0-7.5 Hz) and high-gamma (64-116 Hz) activities., Conclusions: Our observations support the notion that augmentation beta-sigma and delta activities reflects cortical deactivation or inactivation, whereas theta and high-gamma activities contribute to maintenance of consciousness. The effects of midazolam on the dynamics of cortical oscillations differed across regions., Significance: Sedation, at least partially, reflects a multi-local phenomenon at the cortical level rather than global brain alteration homogeneously driven by the common central control structure., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: We investigated intracranially-recorded gamma activity during calculation tasks to better understand the cortical dynamics of calculation., Methods: We studied 11 patients with focal epilepsy (age range: 9-28years) who underwent measurement of calculation- and naming-related gamma-augmentation during extraoperative electrocorticography (ECoG). The patients were instructed to overtly verbalize a one-word answer in response to auditorily-delivered calculation and naming questions. The assigned calculation tasks were addition and subtraction involving integers between 1 and 17., Results: Out of the 1001 analyzed cortical electrode sites, 63 showed gamma-augmentation at 50-120Hz elicited by both tasks, 88 specifically during naming, and 7 specifically during calculation. Common gamma-augmentation mainly took place in the Rolandic regions. Calculation-specific gamma-augmentation, involving the period between the question-offset and response-onset, was noted in the middle-temporal, inferior-parietal, inferior post-central, middle-frontal, and premotor regions of the left hemisphere. Calculation-specific gamma-augmentation in the middle-temporal, inferior-parietal, and inferior post-central regions peaked around the question offset, while that in the frontal lobe peaked after the question offset and before the response onset. This study failed to detect a significant difference in calculation-specific gamma amplitude between easy trials and difficult ones requiring multi-digit operations., Conclusions: Auditorily-delivered stimuli can elicit calculation-specific gamma-augmentation in multiple regions of the left hemisphere including the parietal region. However, the additive diagnostic value of measurement of gamma-augmentation related to a simple calculation task appears modest., Significance: Further studies are warranted to determine the functional significance of calculation-specific gamma-augmentation in each site, and to establish the optimal protocol for mapping mental calculation., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: Humans sometimes need to recognize objects based on vague and ambiguous silhouettes. Recognition of such images may require an intuitive guess. We determined the spatial-temporal characteristics of intracranially-recorded gamma activity (at 50-120Hz) augmented differentially by naming of ambiguous and unambiguous images., Methods: We studied 10 patients who underwent epilepsy surgery. Ambiguous and unambiguous images were presented during extraoperative electrocorticography recording, and patients were instructed to overtly name the object as it is first perceived., Results: Both naming tasks were commonly associated with gamma-augmentation sequentially involving the occipital and occipital-temporal regions, bilaterally, within 200ms after the onset of image presentation. Naming of ambiguous images elicited gamma-augmentation specifically involving portions of the inferior-frontal, orbitofrontal, and inferior-parietal regions at 400ms and after. Unambiguous images were associated with more intense gamma-augmentation in portions of the occipital and occipital-temporal regions., Conclusions: Frontal-parietal gamma-augmentation specific to ambiguous images may reflect the additional cortical processing involved in exerting intuitive guess. Occipital gamma-augmentation enhanced during naming of unambiguous images can be explained by visual processing of stimuli with richer detail., Significance: Our results support the theoretical model that guessing processes in visual domain occur following the accumulation of sensory evidence resulting from the bottom-up processing in the occipital-temporal visual pathways., (Copyright © 2014 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.)

Objective: We determined the temporal-spatial patterns of electrocorticography (ECoG) signal modulation during overt articulation of 44 American English phonemes., Methods: We studied two children with focal epilepsy who underwent extraoperative ECoG recording. Using animation movies, we delineated 'when' and 'where' gamma- (70-110 Hz) and low-frequency-band activities (10-30 Hz) were modulated during self-paced articulation., Results: Regardless of the classes of phoneme articulated, gamma-augmentation initially involved a common site within the left inferior Rolandic area. Subsequently, gamma-augmentation and/or attenuation involved distinct sites within the left oral-sensorimotor area with a timing variable across phonemes. Finally, gamma-augmentation in a larynx-sensorimotor area took place uniformly at the onset of sound generation, and effectively distinguished voiced and voiceless phonemes. Gamma-attenuation involved the left inferior-frontal and superior-temporal regions simultaneously during articulation. Low-frequency band attenuation involved widespread regions including the frontal, temporal, and parietal regions., Conclusions: Our preliminary results support the notion that articulation of distinct phonemes recruits specific sensorimotor activation and deactivation. Gamma attenuation in the left inferior-frontal and superior-temporal regions may reflect transient functional suppression in these cortical regions during automatic, self-paced vocalization of phonemes containing no semantic or syntactic information., Significance: Further studies are warranted to determine if measurement of event-related modulations of gamma-band activity, compared to that of the low-frequency-band, is more useful for decoding the underlying articulatory functions., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: We determined where and when category-preferential augmentation of gamma activity took place during naming of animal or non-animal pictures., Methods: We studied 41 patients with focal epilepsy who underwent measurement of naming-related gamma-augmentation at 50-120 Hz during extraoperative electrocorticography. The assigned task consisted of naming of a visually-presented object classified as either 'animal' or 'non-animal'., Results: Within 80 ms following the onset of picture presentation, regardless of stimulus type, gamma-activity in bilateral occipital regions began to be augmented compared to the resting period. Initially in the occipital poles (at 140 ms and after) and subsequently in the lateral, inferior and medial occipital regions (at 320 ms and after), the degree of gamma-augmentation elicited by 'animal naming' became larger (by up to 52%) than that by 'non-animal naming'. Immediately prior to the overt response, left inferior frontal gamma-augmentation became modestly larger during 'animal naming' compared to 'non-animal naming'., Conclusions: Animal category-preferential gamma-augmentation sequentially involved the lower- and higher-order visual areas. Relatively larger occipital gamma-augmentation during 'animal naming' can be attributed to the more attentive analysis of animal stimuli including the face. Animal-preferential gamma-augmentation in the left inferior frontal region could be attributed to a need for selective semantic retrieval during 'animal naming'., Significance: A specific program of cortical processing to distinguish an animal (or face) from other objects might be initiated in the lower-order visual cortex., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: We measured the spatial, temporal and developmental patterns of gamma activity augmented by picture- and auditory-naming tasks and determined the clinical significance of naming-related gamma-augmentation., Methods: We studied 56 epileptic patients (age: 4-56 years) who underwent extraoperative electrocorticography. The picture-naming task consisted of naming of a visually-presented object; the auditory-naming task consisted of answering an auditorily-presented sentence question., Results: Naming-related gamma-augmentation at 50-120 Hz involved the modality-specific sensory cortices during stimulus presentation and inferior-Rolandic regions during responses. Gamma-augmentation in the bilateral occipital and inferior/medial-temporal regions was more intense in the picture-naming than auditory-naming task, whereas that in the bilateral superior-temporal, left middle-temporal, left inferior-parietal, and left frontal regions was more intense in the auditory-naming task. Patients above 10 years old, compared to those younger, showed more extensive gamma-augmentation in the left dorsolateral-premotor region. Resection of sites showing naming-related gamma-augmentation in the left hemisphere assumed to contain essential language function was associated with increased risk of post-operative language deficits requiring speech therapy (p < 0.05)., Conclusions: Measurement of gamma-augmentation elicited by either naming task was useful to predict postoperative language deficits., Significance: A smaller degree of frontal engagement in the picture-naming task can be explained by no requirement of syntactic processing or less working memory load. More extensive gamma-augmentation in the left dorsolateral-premotor region in older individuals may suggest more proficient processing by the mature brain., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Focality in electro-clinical or neuroimaging data often motivates epileptologists to consider epilepsy surgery in patients with medically-uncontrolled seizures, while not all focal findings are causally associated with the generation of epileptic seizures. With the help of Hill's criteria, we have discussed how to establish causality in the context of the presurgical evaluation of epilepsy. The strengths of EEG include the ability to determine the temporal relationship between cerebral activities and clinical events; thus, scalp video-EEG is necessary in the evaluation of the majority of surgical candidates. The presence of associated ictal discharges can confirm the epileptic nature of a particular spell and whether an observed neuroimaging abnormality is causally associated with the epileptic seizure. Conversely, one should be aware that scalp EEG has a limited spatial resolution and sometimes exhibits propagated epileptiform discharges more predominantly than in situ discharges generated at the seizure-onset zone. Intraoperative or extraoperative electrocorticography (ECoG) is utilized when noninvasive presurgical evaluation, including anatomical and functional neuroimaging, fails to determine the margin between the presumed epileptogenic zone and eloquent cortex. Retrospective as well as prospective studies have reported that complete resection of the seizure-onset zone on ECoG was associated with a better seizure outcome, but not all patients became seizure-free following such resective surgery. Some retrospective studies suggested that resection of sites showing high-frequency oscillations (HFOs) at >80Hz on interictal or ictal ECoG was associated with a better seizure outcome. Others reported that functionally-important areas may generate HFOs of a physiological nature during rest as well as sensorimotor and cognitive tasks. Resection of sites showing task-related augmentation of HFOs has been reported to indeed result in functional loss following surgery. Thus, some but not all sites showing interictal HFOs are causally associated with seizure generation. Furthermore, evidence suggests that some task-related HFOs can be transiently suppressed by the prior occurrence of interictal spikes. The significance of interictal HFOs should be assessed by taking into account the eloquent cortex, seizure-onset zone, and cortical lesions. Video-EEG and ECoG generally provide useful but still limited information to establish causality in presurgical evaluation. A comprehensive assessment of data derived from multiple modalities is ultimately required for successful management., (Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: The lower-order visual cortex in the medial-occipital region is suggested to send feed-forward signals to the higher-order visual cortex including ventral-occipital-temporal and dorsal-occipital regions. We determined how stimulation-elicited cortical-signals propagate between lower- and higher-order visual cortices, and whether the magnitudes of stimulation-elicited cortical-signals recorded in the higher-order visual cortex differed from those recorded in the lower-order one., Methods: We studied 10 patients with focal epilepsy who underwent extraoperative electrocorticography recording. Trains of 1-Hz stimuli with an intensity of 3 mA were delivered to an electrode pair within the medial-occipital region; then, cortico-cortical evoked-potential (CCEP) and stimulation-elicited gamma-activity at 80-150 Hz were measured in the ventral-occipital-temporal and dorsal-occipital regions. Likewise, CCEP and stimulation-elicited gamma-activity, driven by stimuli within the higher-order visual cortex, were measured in the lower-order visual cortex., Results: CCEPs generated, via feed-forward propagations, in the higher-order visual cortex were significantly larger than those generated, via feed-back propagations, in the lower-order visual cortex. Stimulation of the lower-order visual cortex elicited augmentation of gamma-activity in the higher-order visual cortex after the preceding CCEP subsided., Conclusion: The propagation manners of stimulation-elicited cortical-signals differ between feed-forward and feed-back directions in the human occipital lobe., Significance: : Such difference may need to be taken into consideration for future clinical application of CCEPs and stimulation-elicited gamma-augmentation in presurgical evaluation for epilepsy surgery., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

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: Motion-induced blindness (MIB) is an illusory phenomenon, in which a static target surrounded by moving distracters is perceived to disappear. We determined the electrocorticographic (ECoG) correlates of MIB., Methods: While undergoing intracranial ECoG recording, a patient with focal epilepsy was instructed to report the transitions of a visual target, which was designed to illusorily or physically disappear and reappear. We then determined the neural modulations associated with illusory and physical transitions of the target. We also tested whether the phase of local delta activity could predict exclusively illusory transitions., Results: High-gamma activity at 80-150 Hz was attenuated in the fusiform region prior to the reports of illusory and real visual target disappearance. Conversely, such high-gamma activity was augmented prior to the report of real target reappearance. Exclusively around illusory disappearance but not around real one, the delta phases in the fusiform region showed a highly skewed distribution with preference of the negative peak., Conclusions: Neuronal modulations in the fusiform region may be involved in visual awareness, while spontaneous fluctuations of neural states entrained on delta rhythm may be involved in generation of MIB., Significance: Our study increases our understanding of the mechanisms of visual awareness., (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.)

In the social insects, colony size is central to the survival of the queen. Two endogenous factors, worker longevity and queen's daily egg production, are known to determine maximum colony size. A third endogenous factor, duration of worker development from egg to adult, regulates the rate of colony growth. In this paper, we report findings from a simulation quantifying the effects of temperature on colony size in the fire ant, Solenopsis invicta. The monthly average temperature over a six year period for the panhandle of north Florida was interpolated to determine the effects of daily temperature on a queen's egg production, worker developmental time and worker longevity. Additional daily temperatures were simulated: 7°C higher and 7°C lower than daily temperatures for north Florida. As expected, colony size was the largest when annual temperatures were the highest across seasons, ranging from 57,000 to 187,000. Colony size at intermediate daily temperatures ranged from 14,000 to 103,000; small colonies recovered rapidly as temperatures warmed. Colony size at lower daily temperatures ranged from 14,000 to 21,000. Extended worker longevity at lower temperatures compensated for low egg production and longer developmental time. And vice versa, the queen's high rate of egg production and the shorter developmental time compensated for shorter worker longevity at high temperatures. Because the fire ant nest consists of a heat-collecting dome in which to incubate brood during cold weather, and deep chambers in which to cool workers during hot weather, colony size is likely to be higher and more stable than our simulation showed. The extended longevity of workers and queens at low temperatures, and perhaps their ability to hibernate below the permafrost, might explain the ability of ants to colonize habitats worldwide., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: We measured cortical gamma-oscillations in response to visual-language tasks consisting of picture naming and word reading in an effort to better understand human visual-language pathways., Methods: We studied six patients with focal epilepsy who underwent extraoperative electrocorticography (ECoG) recording. Patients were asked to overtly name images presented sequentially in the picture naming task and to overtly read written words in the reading task., Results: Both tasks commonly elicited gamma-augmentation (maximally at 80-100 Hz) on ECoG in the occipital, inferior-occipital-temporal and inferior-Rolandic areas, bilaterally. Picture naming, compared to reading task, elicited greater gamma-augmentation in portions of pre-motor areas as well as occipital and inferior-occipital-temporal areas, bilaterally. In contrast, word reading elicited greater gamma-augmentation in portions of bilateral occipital, left occipital-temporal and left superior-posterior-parietal areas. Gamma-attenuation was elicited by both tasks in portions of posterior cingulate and ventral premotor-prefrontal areas bilaterally. The number of letters in a presented word was positively correlated to the degree of gamma-augmentation in the medial occipital areas., Conclusions: Gamma-augmentation measured on ECoG identified cortical areas commonly and differentially involved in picture naming and reading tasks. Longer words may activate the primary visual cortex for the more peripheral field., Significance: The present study increases our understanding of the visual-language pathways., (Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: Several human studies have demonstrated that the amplitudes of cortical oscillations are altered by various sensorimotor and cognitive tasks. Event-related augmentation of gamma oscillations and attenuation of alpha and beta oscillations have been often used as surrogate markers of cortical activation elicited by tasks especially in presurgical identification of eloquent cortices. In the present study, we addressed a question whether somatosensory-related gamma augmentation 'precedes' or 'co-occurs with' somatosensory-related attenuation of alpha-beta oscillations., Methods: We studied 10 patients who underwent intracranial electrocorticography for epilepsy surgery, and determined the temporal and spatial characteristics of median-nerve somatosensory-related amplitude changes at gamma- (30-100Hz), beta- (14-28Hz) and alpha-band (8-12Hz) oscillations., Results: We found that somatosensory-related gamma augmentation involving the post- and pre-central gyri evolved into beta and alpha augmentation, which was subsequently followed by beta and alpha attenuation involving the post- and pre-central gyri., Conclusions: These observations support the hypothesis that somatosensory-related gamma augmentation but not alpha-beta attenuation represents the initial cortical processing for external somatosensory stimuli. Somatosensory-related alpha-beta attenuation appears to represent a temporally distinct stage of somatosensory processing., Significance: The present study has increased our understanding of event-related gamma augmentation and alpha-beta attenuation seen on electrocorticography.

Previous human studies have demonstrated that midazolam-induced signal changes on scalp EEG recording include widespread augmentation of sigma-oscillations and that the amplitude of such oscillations is correlated to the severity of midazolam-induced amnesia. Still unanswered questions include whether midazolam-induced sigma-augmentation also involves the medial temporal region, which plays a role in memory encoding. Taking advantage of rare and unique opportunities to monitor neuronal activities using intracranial electrocorticography (ECoG) recording, we determined how intravenous administration of midazolam elicited spectral frequency changes in the human cerebral cortex, including the medial temporal region. We studied three children with focal epilepsy who underwent subdural electrode placement and extraoperative ECoG recording for subsequent resection of the seizure focus; an intravenous bolus of midazolam was given to abort an ongoing simple partial seizure or to provide sedation prior to induction of general anesthesia. 'Midazolam-induced ECoG frequency alteration' in sites distant from the seizure focus was sequentially animated on their individual three-dimensional MR images. The common ECoG changes induced by midazolam included gradual augmentation of sigma-oscillations (12-16 Hz) in the widespread non-epileptic regions, including the medial temporal region. The spatial and temporal alteration of ECoG spectral frequency pattern can be appreciated via animation movies. Midazolam-induced sigma-augmentation was observed in the medial temporal region in our relatively small cohort of human subjects. In-vivo animation of ECoG spectral measures provided a unique situation to study the effect of midazolam on neuronal processing in the deep brain regions.

Objective: To determine how sleep with central spindles alters the spatial distribution of interictal spike frequency in children with intractable focal seizures, and whether such children have spindles arising from the medial temporal region in addition to the frontal-central region., Methods: Seventeen children (age: 7 months-17 years) were studied using extraoperative electrocorticography (ECoG)., Results: Overall spike frequency across the subdural electrodes was greater during sleep with central spindles compared to wakefulness. In 13 children showing at least 1 spike/min in an electrode, the spatial distribution of spike frequency was similar during wakefulness and sleep; in addition, the spike frequency was greater in the seizure onset zones compared to the non-onset areas, regardless of wakefulness or sleep. Spindles were identified in the medial temporal region during sleep with central spindles in all 17 children., Conclusion: Overall spike frequency may be increased by sleep with spindles, but the spatial distribution of spike frequency appears similar during wakefulness and sleep in children with intractable focal seizures., Significance: Both awake and sleep ECoG may be useful to predict seizure onset zones in children with intractable focal epilepsy. Medial temporal spindles are present in some children with focal epilepsy.

Objective: To determine whether the chance of peer-review assignment as expected from the amount of publications in "Japanese" and "Arabic" investigators differed from that for "Other" investigators in mainstream clinical neurology journals in 2004., Methods: Fifteen clinical neurology journals with the impact factor in 2004 greater than 2.5 and with the full list of reviewers available in public were analyzed. Thereby, "Japanese", "Arabic", and "Other" investigators were defined as those with Japanese-sounding last names, those with Arabic-sounding last names, and others. The ratio of number of reviewers to number of original articles was compared between "Japanese" and "Other" groups as well as "Arabic" and "Other" groups. In addition, we described how "Japanese" and "Arabic" investigators were assigned peer-review in Brain and Development in 2004., Results: In the above-mentioned 15 clinical neurology journals, the mean ratio of number of reviewers to number of original articles was smaller in "Japanese" compared to "Other" investigators (paired t-test: df=14; t-value=6.85; p-value<0.001) but failed to demonstrate a difference in the mean ratio between "Arabic" and "Other" investigators (df=11; t-value=-0.36; p=0.7). In Brain and Development, the number of peer-reviewers relative to the amount of publications was larger in "Japanese" compared to "Other" group (Fisher's exact probability test: p-value<0.001)., Conclusion: More "Japanese" investigators are encouraged to contribute to peer-review process in clinical neurology journals other than Brain and Development. More "Non-Japanese" investigators are encouraged to contribute to peer-review process in Brain and Development.

BLOG (Web Log) is a new internet media system characterized by a frequent, chronological publication of personal thoughts with multiple Web links. The author investigated whether a 'fiction novel' on BLOG describing a girl undergoing epilepsy surgery can potentially facilitate familiarity to epilepsy surgery among the general internet users in Japan. The BLOG was initiated on July 13, 2005 and obtained daily public accesses ranging about 80-500 without any external funding support. The survey was conducted on the BLOG from November 28 until December 4, 2005. The mean of daily accesses during the survey period was 135, and a total of 27 users responded to a single questionnaire. Sixteen responders indicated that this novel facilitated awareness of epilepsy surgery, and eight indicated that they have been aware of epilepsy surgery even before reading the novel. The author found that advantages of BLOG as a tool for outreach and survey included a small cost and high speediness, whereas major limitations of BLOG-based surveys included limited coverage and severe non-response bias. A public outreach in epilepsy surgery might be possible using BLOG, but the magnitude of public outreach in this project has been quite small. A better outreach system may be required to increase the number of patients with uncontrolled seizures benefiting from epilepsy surgery.

We report a four-year-old boy with Landau-Kleffner Syndrome (LKS) characterized by episodic receptive aphasia lasting for few weeks followed by gradual recovery of baseline language functions. Neuropsychological evaluation during an episode showed severe impairment in verbal skills and comprehension, but relative preservation of non-verbal skills. Although he could carry on a conversation during remission, neuropsychological evaluation demonstrated findings reflective of receptive language deficits. Prolonged EEG disclosed frequent sharp-wave activity in the left and right temporal regions but no electrographic seizures. Glucose metabolism PET scan during the fourth episode of aphasia revealed intense hypermetabolism in the left temporal neocortex. Awake EEG during the PET tracer uptake period showed 6.0 spikes/min in the left temporal region and 4.0 spikes/min in the right. A repeat PET scan during remission showed hypometabolism in the left temporal cortex. Awake EEG during the FDG uptake period showed 16.0 spikes/min in the right temporal region and 0.3 spikes/min in the left. During his fifth aphasic episode, EEG (without PET) showed 0.16 spikes/min in the right temporal region and none in the left. Intermittent short episodes of predominantly receptive aphasia with near-total recovery between episodes can be one of the clinical presentations of LKS. This case illustrates the dynamic changes of glucose metabolism in the temporal lobe during episodes of aphasia and remission in a case with LKS. The clinical course of our patient with transient EEG and PET findings suggest that glucose metabolism in LKS cannot be attributed solely to interictal epileptiform activities on scalp EEG.

Reductions in bright-field (BF) scanning transmission electron microscopy (STEM) and high-angle annular dark-field (HAADF) STEM image calculations with the aid of Bloch wave symmetry are discussed under assumptions that an absorption potential is written by a local potential and a zero-order Laue zone lies parallel to the crystal surface. Translational symmetry allows us to take only partial incident beams in the first Brillouin zone instead of enormous number of partial incident beams in a large convergent disk. Two dimensional point group confines partial incident beams to an irreducible area in addition to factoring a dispersion matrix into noninteracting submatrices on a high symmetry line using the projection operator. The drastic reductions in computing time and memory enable us to readily calculate various BF STEM and HAADF STEM images. The validity and accuracy are demonstrated in comparisons with high resolution experimental BF STEM and HAADF STEM images.