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. (c) 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

ObjectiveIn 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.MethodsPatients 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.ResultsElevated 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.ConclusionsOptimizing visuospatial working memory through practice is tied to early pIFG activation and decreased dependence on irrelevant neural pathways.SignificanceThis study expands our knowledge of human adaptation for visuospatial working memory, showing the spatiotemporal dynamics of cortical network modulations through white matter tracts.

We built normative brain atlases that animate millisecond-scale intra- and inter-hemispheric white matter-level connectivity dynamics supporting object recognition and speech production. We quantified electrocorticographic modulations during three naming tasks using event-related high-gamma activity from 1,114 nonepileptogenic intracranial electrodes (i.e., non-lesional areas unaffected by epileptiform discharges). Using this electrocorticography data, we visualized functional connectivity modulations defined as significant naming-related high-gamma modulations occurring simultaneously at two sites connected by direct white matter streamlines on diffusion-weighted imaging tractography. Immediately after stimulus onset, intra- and inter-hemispheric functional connectivity enhancements were confined mainly across modality-specific perceptual regions. During response preparation, left intra-hemispheric connectivity enhancements propagated in a posterior-to-anterior direction, involving the left precentral and prefrontal areas. After overt response onset, inter- and intra-hemispheric connectivity enhancements mainly encompassed precentral, postcentral, and superior-temporal (STG) gyri. We found task-specific connectivity enhancements during response preparation as follows. Picture naming enhanced activity along the left arcuate fasciculus between the inferior-temporal and precentral/posterior inferior-frontal (pIFG) gyri. Nonspeech environmental sound naming augmented functional connectivity via the left inferior longitudinal and fronto-occipital fasciculi between the medial-occipital and STG/pIFG. Auditory descriptive naming task enhanced usage of the left frontal U-fibers, involving the middle-frontal gyrus. Taken together, the commonly observed network enhancements include inter-hemispheric connectivity optimizing perceptual processing exerted in each hemisphere, left intra-hemispheric connectivity supporting semantic and lexical processing, and inter-hemispheric connectivity for symmetric oral movements during overt speech. Our atlases improve the currently available models of object recognition and speech production by adding neural dynamics via direct intra- and inter-hemispheric white matter tracts.

This study aimed to reveal changes in the quality of life (QOL) of children with neurodevelopmental disorders and their parents, and the interaction between their QOL and parental mental state during the coronavirus 2019 (COVID-19) pandemic. Eighty-nine school-aged children and parents participated in surveys in May 2020 (T1) and May 2021 (T2). The parents completed questionnaires that assessed their QOL, depression, parenting stress, and living conditions. Children's temporary mood status was evaluated using the self-reported visual analog scale (VAS). Children's QOL and VAS at T2 were higher than their QOL at T1. Parents' QOL at T2 was lower than their QOL at T1. Severe parental depression at T1 had a synergistic effect on severe parenting stress and severe depressive state at T2. Additionally, children's high QOL at T1 had a synergistic effect on low parenting stress and children's high QOL at T2. Furthermore, children's low VAS scores and parents' low QOL at T2 were associated with deterioration of family economic status. Children and parents' QOL changed during the prolonged COVID-19 pandemic. Improvement in children's QOL was influenced by reduced maternal depressive symptoms. Public support for parental mental health is important to avoid decreasing QOL.

This study aimed to reveal how the COVID-19 stay-at-home period has affected the quality of life (QOL) of children with neurodevelopmental disorders and their parents and to identify possible factors that enabled them to maintain their QOL. We enrolled 136 school-aged children (intellectual quotient ≥ 50) and their parents and administered QOL questionnaires to assess the maladaptive behavior of the children; depression, anxiety, and stress of the parents; and activities of their daily lives. The relationship between their QOL and clinical features was examined. The decrease in QOL of children and parents was associated with the mother’s limited job flexibility. Decreased QOL was also associated with changes in the sleep rhythms of the children. Maladaptive behaviors in children were associated with parental stress. However, maintained QOL of some families who faced these same conditions of job stress and sleep disorders was associated with less parental stress, less parental depression and anxiety, and milder maladaptive behavior in children. Both mothers with limited job flexibility and changes in the sleep rhythm of children were associated with reduced QOL of children and their parents. Low parental stress was associated with decreased maladaptive behavior in children and with maintained QOL of the family.

Background: This study seeks to ascertain how the COVID-19 stay-at-home period has affected the quality of life (QOL) of children with neurodevelopmental disorders (NDDs) who had experienced sleep schedules alteration and clarify what psychological status predicted low QOL in children with and without altered sleep patterns. Materials and Methods: Study participants were 86 children between 8 and 17 years of age (mean age, 11.7 years; 70 boys, 16 girls; mean intellectual quotient, 83.6). QOL was evaluated using the self-assessment KINDLR. Participants answered questions regarding depression and anxiety on a visual analog scale (VAS) for temporary mood. Their parents answered questionnaires regarding their maladaptive behaviors and differences in sleep patterns before and during the COVID-19 pandemic. The student's t-test was performed to examine the presence or absence of sleep changes in the children, which affected QOL, temporary mood, and maladaptive behaviors. Multiple or simple linear regression analyses were also performed to identify the psychogenic factors that significantly affected decreased QOL for each group with and without changes in sleep schedule. Results: During the COVID-19 stay-at-home period, 46.5% of participants experienced changes in sleep patterns. These changes were associated with decreased QOL as well as internalized symptoms. The decreased QOL of children with sleep patterns changed was predicted by a high level of depression. In addition, low QOL in children with unchanged sleep patterns was predicted by a high level of depression and low current mood status. Conclusions: Almost half of the participants experienced a poor sleep schedule during the stay-at-home period. These alterations in sleep patterns were associated with a low QOL. The QOL of children with a stable life schedule was affected not only by depressive tendencies but also temporary moods. Therefore, they need to live a fulfilling life to maintain their QOL. However, the QOL of children with poor sleep patterns was affected only by depressive tendencies. Hence, clinicians need to ensure that children with NDDs are well-diagnosed with depression and treated for sleep problems.

OBJECTIVE:To reveal whether neurodevelopmental outcome of infants after epilepsy surgery can be quantitatively assessed by electroencephalography (EEG) functional connectivity analysis.METHODS:We enrolled 13 infants with posterior quadrant dysplasia aged <2 years who were treated using posterior quadrantectomy and 21 age-matched infants. EEG was performed both before and one year after surgery. Developmental quotient (DQ) was assessed both before and 3 years after surgery. The phase lag index (PLI) of three different pairs of electrodes in the nonsurgical hemisphere, i.e., the anterior short distance (ASD), posterior short distance (PSD), and long distance (LD) pairs, were calculated as indices of brain connectivity. The relationship between the PLI and DQ was evaluated.RESULTS:Overall, 77% infants experienced seizure freedom after surgery. The beta- and gamma- range PLI of PSD pairs increased preoperatively. All these pairs normalized postoperatively. Simple linear regression analysis revealed a significant relationship between the postoperative DQ and the postoperative beta-band PLI of ASD pairs.CONCLUSION:Preoperative abnormal hyper-connectivity was normalized to the control level after surgery. The postoperative hyperconnectivity was associated with long-term neurodevelopmental improvement.SIGNIFICANCE:PLI quantifies neurodevelopmental improvements after posterior quadrantectomy.

PURPOSE:We investigated the relationship between electroencephalographic (EEG) functional connectivity and executive function in children with frontal lobe epilepsy (FLE). METHODS:We enrolled 24 children with FLE (mean age, 11.0 years; 13 boys) and 22 sex-, age-, and intelligence-matched typically developing children (TDC) to undergo 19-channel EEG during light sleep. We estimated functional connectivity using the phase lag index (PLI) that captures the synchronization of EEG. We also performed continuous performance tests (CPTs) on the children and obtained questionnaire responses on attention deficit hyperactivity disorder and oppositional defiant disorder (ODD). RESULTS:The average gamma PLI was lower in the FLE group than in the TDC group, especially between long-distance frontoparietal pairs, between interhemispheric frontal pairs, and between interhemispheric parietotemporal pairs. Gamma PLIs with long-distance frontoparietal and interhemispheric frontal pairs were positively associated with inattention, ODD scores, omission error, and reaction time in the FLE group but not in the TDC group. Conversely, they were negatively associated with age, hyperactivity score, and commission error. CONCLUSIONS:A lack of functional connectivity of the frontal brain regions in children with FLE was associated with poor response inhibition.

Introduction: An alteration in postoperative cognitive function varies according to the patients' background characteristics, such as etiology, focus, and seizure duration. Accurate prediction and assessment of postoperative cognitive function is difficult in each patient. Adaptive behavior could describe the typical performance of daily activities and represents the ability to translate cognitive potential into real-world skills. We examined the relationship between alterations of executive function (EF) and adaptive behavior in school children undergoing surgery for intractable epilepsy. Methodology: We enrolled 31 children with focal resection or corpus callosotomy for intractable epilepsy [mean age at surgery, 12.5 years; 16 boys; mean intellectual quotient, 73.3]. We surveyed answered questionnaires on attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and adaptive behavior using the Vineland Adaptive Behavior Scale, 2nd edition (VABS-II), and performed continuous performance tests (CPTs) on children preand postoperatively. Result: ADHD and ASD symptoms improved after epilepsy surgery. The omission error (OE) in the CPT variable improved after epilepsy surgery, especially in children with a shorter preoperative period. Improved ASD symptoms led to an increased score of the coping skills subdomain. The reduced OE observed after surgery also increased the score of the community skills subdomain. Conclusion: Improvement in EF and ASD symptoms resulted in better adaptive behavior postoperatively. These results were important for the preand postoperative evaluation and re-evaluation of children with epilepsy requiring special education and related services. (C) 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Objective: Children with attention deficit hyperactivity disorder (ADHD) exhibit deficits in executive function. Since there are no clear biomarkers for the disorder, this study aimed to investigate the neurophysiological biomarkers for deficits in executive function in children with ADHD using functional near-infrared spectroscopy (fNIRS) and electroencephalography. Methods: Twenty patients diagnosed with ADHD and 19 typically developing children (TDC; 8-11 years old) were included. Event related potentials (ERPs) were recorded using an electroencephalogram (EEG) and oxygenated hemoglobin concentrations (Oxy-Hb) were recorded using fNIRS during a colored Go/NoGo task, simultaneously. Latencies and amplitudes of NoGo-N2 and NoGo/Go-P3 tasks were measured using EEG. Results: Children with ADHD showed significantly decreased Oxy-Hb in the right frontal cortex as well as longer NoGo-P3 latencies and a decreased NoGo/Go-P3 amplitude. There was a significant positive correlation between the Oxy-Hb and NoGo/ Go-P3 amplitude. Conclusions: These results suggest that children with ADHD experience executive dysfunction. Hemodynamic and electrophysiological findings during the Go/NoGo task might be useful as a biomarker of executive function. Significance: These findings have key implications for understanding the pathophysiology of deficits in executive function in ADHD. (C) 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

•There is a gap in adaptive behavior between children with focal epilepsy and autism.•Children with focal epilepsy have poor daily living skills, specially domestic chores.•Children with focal epilepsy exhibit good coping skills.•More severe autistic symptoms correlate with lower adaptive behavior.•Adaptive behavior is affected by academic achievement and executive function.

Purpose This study aimed to use graph theoretical analysis of anatomical covariance derived from structural MRI to reveal how the gray matter connectivity pattern is altered after corpus callosotomy (CC). Materials and methods We recruited 21 patients with epilepsy who had undergone CC. Enrollment criteria were applied: (1) no lesion identified on brain MRI; (2) no history of other brain surgery; and (3) age not younger than 3 years and not older than 18 years at preoperative MRI evaluation. The most common epilepsy syndrome was Lennox-Gastaut syndrome (11 patients). For voxel-based morphometry, the normalized gray matter images of pre-CC and post-CC patients were analyzed with SPM12 (voxel-level threshold of p<0.05 [familywise error-corrected]). Secondly, the images of both groups were subjected to graph theoretical analysis using the Graph Analysis Toolbox with SPM8. Each group was also compared with 32 age- and sex-matched control patients without brain diseases. Results Comparisons between the pre- and post-CC groups revealed a significant reduction in seizure frequency with no change in mean intelligence quotient/developmental quotient levels. There was no relationship among the three groups in global network metrics or in targeted attack. A regional comparison of betweenness centrality revealed decreased connectivity to and from the right middle cingulate gyri and medial side of the right superior frontal gyrus and a partial shift in the distribution of betweenness centrality hubs to the normal location. Significantly lower resilience to random failure was found after versus before CC and versus controls (p = 0.0450 and p = 0.0200, respectively). Conclusion Graph theoretical analysis of anatomical covariance derived from structural imaging revealed two neural network effects of resection associated with seizure reduction: the reappearance of a structural network comparable to that in healthy children and reduced connectivity along the median line, including the middle cingulate gyrus.

Introduction: We examined functional connectivity analyses in electroencephalograms (EEGs) of patients with attention deficit hyperactivity disorder (ADHD) and in those of typically developing children (TDC) to uncover neurobiological abnormalities. Methodology: We enrolled 31 children with ADHD (mean age 11.1 years; 23 boys) and 17 sex-, age-, and intelligence-matched TDC to undergo 19-channel EEGs during light sleep. We estimated functional connectivity using the phase lag index (PLI) and coherence measurements that capture the synchronization of EEG signals and graphed metrics with GRETNA. We also performed continuous performance tests (CPTs) on the children and obtained answered questionnaires on ADHD and autism spectrum disorder. Results: The central-to-posterior gamma PLI was lower in children with ADHD than that in TDC. The other PLI frequency bands and all coherence frequency bands were not statistically different between both groups. Individuals with high hyperactivity scores on questionnaires and low reaction times (SDs) on CPT had low motor and occipital pairs of gamma PLIs. Graph metrics showed no differences between the groups. Conclusions: The difference in averaged gamma PLI (especially with motor and occipital pairs) between groups was more suitable for diagnosis than the averaged coherence. Lower averaged gamma PLIs reflected more severe ADHD symptoms. A prospective study with more controlled conditions is warranted to determine if gamma-band PLI can be used as an auxiliary tool for ADHD diagnosis. (C) 2019 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

BACKGROUND:Recently, many genes related to neurodevelopmental disorders have been identified by high-throughput genomic analysis; however, a comprehensive understanding of the mechanism underlying neurodevelopmental disorders remains to be established. To further understand these underlying mechanisms, we performed a comprehensive genomic analysis of patients with undiagnosed neurodevelopmental disorders.METHODS:Genomic analysis using next-generation sequencing with a targeted panel was performed for a total of 133 Japanese patients (male/female, 81/52) with previously undiagnosed neurodevelopmental disorders, including developmental delay (DD), intellectual disability (ID), autism spectrum disorder (ASD), and epilepsy. Genomic copy numbers were also analyzed using the eXome Hidden Markov Model (XHMM).RESULTS:Thirty-nine patients (29.3%) exhibited pathogenic or likely pathogenic findings with single-gene variants or chromosomal aberrations. Among them, 20 patients were presented here. Pathogenic or likely pathogenic variants were identified in 18 genes, including ACTG1, CACNA1A, CHD2, CDKL5, DNMT3A, EHMT1, GABRB3, GABRG2, GRIN2B, KCNQ3, KDM5C, MED13L, SCN2A, SHANK3, SMARCA2, STXBP1, SYNGAP1, and TBL1XR1.CONCLUSION:A diagnostic yield of 29.3% in this study was nearly the same as that previously reported from other countries. Thus, we suggest that there is no difference in genomic backgrounds in Japanese patients with undiagnosed neurodevelopmental disabilities. Although most of the patients possessed de novo variants, one of the patients showed an X-linked inheritance pattern. As X-linked recessive disorders exhibit the possibility of recurrent occurrence in the family, comprehensive molecular diagnosis is important for genetic counseling.

Diagnosis of seizure imitators in children is often challenging, and individuals with intellectual disability (ID) could be at additional risk of seizure imitator misdiagnosis. We aimed to elucidate distinct features of clinical semiology among children of different intellectual levels, which may help in distinguishing seizure imitators from epilepsy in such individuals. We retrospectively compared semiological features of seizure imitators in children with and without ID captured using video-electroencephalography (video-EEG). Seizure imitators were classified based on the definition of the International League Against Epilepsy (ILAE). A total of 67 individuals (mean age: 8.4 years, SD: 4.2 years) with seizure imitators documented using long-term video-EEG were identified, in which 27 patients had normal IQ/DQ, 20 had moderate ID, and 20 had severe ID. There was no statistically significant difference in the semiological features of seizure imitators between individuals with ID and those without ID; similarly, no difference was found between those with moderate ID and severe ID compared with individuals with normal IQ/DQ. Among all the patients, altered responsiveness mimicking cognitive or absence seizures was most frequently observed (36%), followed by jerks mimicking myoclonic seizures (22%). The most common seizure imitators among all the patients were unclassifiable nonepileptic seizures per the ILAE definition (28 cases, 42%), followed by day dreaming (24 cases, 36%) and physiological myoclonus (14 cases, 21%). In summary, the present study found no marked difference in semiological features of seizure imitators between patients with ID and those without ID regardless of ID severity, suggesting the necessity of early video-EEG for correct diagnosis.

To identify surgical effects on brainstem and cortical function objectively, we compared auditory brainstem response (ABR), somatosensory evoked potential (SEP) and flash visual evoked potential (fVEP) before and after posterior quadrantectomy (PQ) in 11 young children with intractable epilepsy associated with posterior quadrant cortical dysplasia. Mean age of seizure onset and the surgery was 1.4 months and 7.7 months old, respectively. Seven patients showed spasm and 2 had tonic seizures preoperatively. All had daily seizures before surgery, but after PQ, nine children (82%) reached seizure-free state. After surgery, interpeak latencies of wave I-V of ABR shortened bilaterally than before (p < 0.05) and N18/P24 component of SEP appeared on the non-affected side in 4 patients. Almost all seizure free patients had improvement of fVEP on the non-affected side (shortened latency of P100 in 5 and wave appearance in 3). Postoperative improvement of cortical component of both SEP and fVEP implied latent brain dysfunction on the non-affected side. It is suggested that PQ during infancy provided not only seizure remission but also functional improvement of brainstem and remaining cortex. In conclusion, multimodal evoked potentials were useful as an objective evaluation tool for epileptic surgery.

Myoclonic encephalopathy in non―progressive disorders（MEND）はミオクロニー発作重積の反復を特徴とし、乳幼児期に発症し重度精神運動発達遅滞を来たす予後不良な疾患である。症例1は31歳男性で、1歳時に強直発作、8歳時にミオクロニー発作重積発作と退行を認めた。症例2は39歳男性で、1歳時に意識減損発作、6歳時にミオクロニー発作を認めた。症例1、2ともに発作時脳波で全般性α律動を認めた。症例3は5歳男児で、4歳時に強直発作で発症し精神運動発達の退行を認めた。5歳時にミオクロニー発作重積発作を認め、発作時脳波で全般性高振幅棘徐波律動を認めた。髄液NMDA型グルタミン酸受容体抗体陽性所見を認めステロイドパルス療法により発作重積の改善を認めた。MENDの臨床的特徴は、乳幼児期発症、ミオクロニー発作重積、発作時の意識減損、全身性強直間代発作の合併等で、3例はこれらの臨床的特徴を満たした。我々は共通する臨床的特徴を持つ3例がMENDであること、免疫賦活作用が病態に関わる可能性があることを報告した。