Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.

MI during interictal recording may provide useful information for the prediction of postoperative seizure outcome.

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Researchers have looked for rapidly- and objectively-measurable electrophysiology biomarkers that accurately localize the epileptogenic zone. Promising candidates include interictal high-frequency oscillation and phase-amplitude coupling. Investigators have independently created the toolboxes that compute the high-frequency oscillation rate and the severity of phase-amplitude coupling. This study of 135 patients determined what toolboxes and analytic approaches would optimally classify patients achieving postoperative seizure control. Four different detector toolboxes computed the rate of high-frequency oscillation at ≥ 80 Hz at intracranial EEG channels. Another toolbox calculated the modulation index reflecting the strength of phase-amplitude coupling between high-frequency oscillation and slow-wave at 3-4 Hz. We defined the completeness of resection of interictally-abnormal regions as the subtraction of high-frequency oscillation rate (or modulation index) averaged across all preserved sites from that averaged across all resected sites. We computed the outcome classification accuracy of the logistic regression-based standard model considering clinical, ictal intracranial EEG, and neuroimaging variables alone. We then determined how well the incorporation of high-frequency oscillation/modulation index would improve the standard model mentioned above. To assess the anatomical variability across nonepileptic sites, we generated the normative atlas of detector-specific high-frequency oscillation and modulation index. Each atlas allowed us to compute the statistical deviation of high-frequency oscillation/modulation index from the nonepileptic mean. We determined whether the model accuracy would be improved by incorporating absolute or normalized high-frequency oscillation/modulation index as a biomarker assessing interictally-abnormal regions. We finally determined whether the model accuracy would be improved by selectively incorporating high-frequency oscillation verified to have high-frequency oscillatory components unattributable to a high-pass filtering effect. Ninety-five patients achieved successful seizure control, defined as International League Against Epilepsy class 1 outcome. Multivariate logistic regression analysis demonstrated that complete resection of interictally-abnormal regions additively increased the chance of success. The model accuracy was further improved by incorporating z-score normalized high-frequency oscillation/modulation index or selective incorporation of verified high-frequency oscillation. The standard model had a classification accuracy of 0.75. Incorporation of normalized high-frequency oscillation/modulation index or verified high-frequency oscillation improved the classification accuracy up to 0.82. These outcome prediction models survived the cross-validation process and demonstrated an agreement between the model-based likelihood of success and the observed success on an individual basis. Interictal high-frequency oscillation and modulation index had a comparably additive utility in epilepsy presurgical evaluation. Our empirical data support the theoretical notion that the prediction of postoperative seizure outcomes can be optimized with the consideration of both interictal and ictal abnormalities.

We reported previously that endogenous reactive oxygen species (ROS) function as myogenic signaling molecules. It has also been determined that excess ROS induce electrophile-response element (EpRE)-driven gene expression via activation of nuclear factor erythroid 2-related factor 2 (Nrf2). Nonetheless, the relationship between the metabolism of ROS (eg, H 2 O 2 ) through glutathione (GSH) up-regulation, GSH-dependent reduction of H 2 O 2 , and Nrf2-dependent gene regulation is not well established. Therefore, we attempted to determine whether H 2 O 2 controls the intracellular GSH redox state via the Nrf2-glutamate-cysteine ligase (GCL)/glutathione reductase (GR)-GSH signaling pathway. In our experiments, enhanced H 2 O 2 generation was accompanied by an increase in both total GSH levels and the GSH/GSSG ratio during muscle differentiation. Both GCL and GR transcriptional expression levels were markedly increased during muscle differentiation but reduced by catalase treatment. Nrf2 protein expression and nuclear translocation increased during myogenesis. The inhibition of GCL, GR, and Nrf2 both by inhibitors and by RNA interference blocked muscle differentiation. Phosphatidylinositol 3-kinase regulated the expression of the GCL C (a catalytic subunit) and GR genes via the induction of Nrf2 nuclear translocation and expression. In conclusion, endogenous H 2 O 2 generated during muscle differentiation not only functions as a signaling molecule, but also regulates the GSH redox state via activation of the Nrf2-GCL/GR-GSH signaling pathway downstream of phosphatidylinositol 3-kinase. (Am J Pathol

Background and Objectives Implantation of cardiac implantable electronic devices (CIED), including permanent pacemakers (PM), implantable cardioverter-defibrillators (ICD), and cardiac resynchronization therapy (CRT) devices, has increased significantly over the past several years. However, limited data exists regarding temporal trends of CIED implantations in Asian population. This study aimed to investigate temporal trends of CIED treatment in Korea. Methods Using the National Health Insurance Service database of the entire Korean adult population, temporal trends of CIED procedures between 2009 and 2016 were evaluated. Additionally, temporal changes in the prevalence of patients' comorbidities were evaluated. Results A total of 35,421 CIED procedures (new implantations: 27,771, replacements: 7,650) were performed during the study period. The mean age of new CIED recipients and the prevalence of comorbidities, including hypertension, diabetes mellitus, heart failure, stroke, and atrial fibrillation, increased substantially with time. Compared to 2009, the number of new implantations of PM, ICD, and CRT devices increased by 2.0 (1,977 to 3,910), 3.6 (230 to 822), and 4.9 (44 to 217) times in 2016, respectively. The annual new implantation rate of CIED also increased accordingly (5.1 to 9.3 for PM, 0.6 to 1.9 for ICD, and 0.1 to 0.5 for CRT devices, per 100,000 persons). Conclusions The number of CIED implantation increased substantially from 2009 to 2016 in Korea. Also, the patients with CIED have been changed to be older and have more comorbidities. Therefore, the burden of health care cost in patients with CIED would be expected to increase in the future.

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Summary Objective The strength of presurgical language mapping using electrocorticography (ECoG) is its outstanding signal fidelity and temporal resolution, but the weakness includes limited spatial sampling at an individual patient level. By averaging naming‐related high‐gamma activity at nonepileptic regions across a large number of patients, we provided the functional cortical atlases animating the neural dynamics supporting visual‐object and auditory‐description naming at the whole brain level. Methods We studied 79 patients who underwent extraoperative ECoG recording as epilepsy presurgical evaluation, and generated time‐frequency plots and animation videos delineating the dynamics of naming‐related high‐gamma activity at 70‐110 Hz. Results Naming task performance elicited high‐gamma augmentation in domain‐specific lower‐order sensory areas and inferior‐precentral gyri immediately after stimulus onset. High‐gamma augmentation subsequently involved widespread neocortical networks with left hemisphere dominance. Left posterior temporal high‐gamma augmentation at several hundred milliseconds before response onset exhibited a double dissociation; picture naming elicited high‐gamma augmentation preferentially in regions medial to the inferior‐temporal gyrus, whereas auditory naming elicited high‐gamma augmentation more laterally. The left lateral prefrontal regions including Broca's area initially exhibited high‐gamma suppression subsequently followed by high‐gamma augmentation at several hundred milliseconds before response onset during both naming tasks. Early high‐gamma suppression within Broca's area was more intense during picture compared to auditory naming. Subsequent lateral‐prefrontal high‐gamma augmentation was more intense during auditory compared to picture naming. Significance This study revealed contrasting characteristics in the spatiotemporal dynamics of naming‐related neural modulations between tasks. The dynamic atlases of visual and auditory language might be useful for planning of epilepsy surgery. Differential neural activation well explains some of the previously reported observations of domain‐specific language impairments following resective epilepsy surgery. Video materials might be beneficial for the education of lay people about how the brain functions differentially during visual and auditory naming.