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Background: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are biologically heterogeneous and often co-occur. As within-diagnosis heterogeneity and overlapping diagnoses are challenging for researchers and clinicians, identifying biologically homogenous subgroups, independent of diagnosis, is an urgent need., Methods: MRI data from 148 adult males with developmental disorders (99 primary ASD, mean age = 31.7 ± 8.0, 49 primary ADHD; mean age = 31.7 ± 9.6) and 105 neurotypical controls (NTC; mean age = 30.6 ± 6.8) were analyzed. We extracted mean cortical thickness (CT) and surface area (SA) values using a functional atlas. Then, we conducted HeterogeneitY through DiscRiminant Analysis (HYDRA) to transdiagnostically cluster and classify individuals. Differences in diagnostic likelihood and clinical symptoms between subtypes were tested. Sensitivity analyses tested the stability of the number of subtypes and their membership by excluding 13 participants diagnosed with both ASD and ADHD and by using a different atlas., Results: In relation to both CT and SA, HYDRA identified two subtypes. The likelihood of ASD or ADHD was not significantly different from the chance of belonging to any of these two subtypes. Clinical characteristics did not differ between subtypes in either CT or SA based analyses. The high consistency in membership was replicated when utilizing a different atlas or excluding people with dual diagnoses in CT (dice coefficients > 0.94) and in SA (>0.88)., Conclusion: Although the brain-derived subtypes do not match diagnostic groups, individuals with developmental disorders were successfully and stably subtyped using either CT or SA., Competing Interests: Declaration of interest SC: honoraria for talks on ADHD from: Association form Child and Adolescent Mental Health (CADDRA), British Association of Psychopharmacology (BAP), Canadian ADHD Alliance Resource (CADDRA), and Healthcare Convention. All the other authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The underlying mechanism of repetitive transcranial magnetic stimulation (rTMS) effects on cognition has not been fully examined. Previously, we have reported the left hippocampal volume increase and theta-gamma coupling (TGC) enhancement associated with working memory improvement following rTMS in depression. This study was aimed to examine whether there is a structure-function relationship in hippocampal neuroplasticity induced by prefrontal rTMS. Thirty-one patients with major depression underwent longitudinal MRI scans and resting-state EEG recordings with the 10-20 system using averaged ear-lobes reference, following 10 sessions of high-frequency rTMS over the left dorsolateral prefrontal cortex. Pearson's correlation analyses were applied for the longitudinal changes among the left and right hippocampal volumes as measured by manual volumetry, theta and gamma spectral powers, and TGC as measured by resting-state EEG. The analyses demonstrated that the left hippocampus volume increases correlated with TGC increases at the left central area (r = 0.576, p = 0.001, N = 31), whereas no significant correlations were observed among changes of right hippocampal volume, right central TGC, bilateral gamma or theta powers. These finding suggests structure-function relationship in rTMS-induced neuroplastic changes mediated through the hippocampus and prefrontal network at the stimulated side. Therefore, high-frequency prefrontal rTMS may exert its cognitive effect through the hippocampal structural-functional neuroplasticity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: We aimed to investigate neuromodulatory effects of high-frequency left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation (rTMS) on resting-state electroencephalography (EEG) and their clinical and cognitive correlates in patients with depression., Methods: Thirty-one patients diagnosed with depression included in the present study. Resting-state gamma power and theta-gamma coupling (TGC) were calculated before and after a course of rTMS. We explored the relationship among gamma power, TGC, and clinical/cognitive outcomes as measured with the Hamilton Rating Scale for Depression (HAM-D 17 ), Beck Depression Inventory (BDI), and Wisconsin Card Sorting Test (WCST)., Results: Following rTMS, depressed patients demonstrated significant increases of resting gamma power at the F3 and F4 electrode sites and resting TGC at the C3 and T3 electrode sites. Furthermore, the increased gamma power at the F3 electrode site was significantly correlated with improved score on the HAM-D 17 and BDI, while the increased TGC at the C3 electrode site was significantly correlated with reduced number of errors on the WCST., Conclusion: Thus, resting-state gamma power and TGC may represent potential biomarkers of depression associated with therapeutic effects of rTMS., Significance: Resting-state EEG may provide potential biomarkers related to therapeutic effects of rTMS., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

To study the biological effects of acupuncture on depression, we hypothesized that acupuncture will exert its antidepressant effect through a bottom-up neuromodulation of the autonomic dysfunction in depression. The participants received press needle (PN) acupuncture for 72 h continuously in a sham-controlled design. Psychological assessments and Holter electrocardiography were performed before and after PN acupuncture. We evaluated their autonomic functions through the heart rate variability (HRV). As a result, following PN acupuncture participants showed significant improvement in the Beck's Depression Inventory scores (P = 0.031), systolic/diastolic blood pressures (P = 0.002/P = 0.011), and coefficient of variation of the R-R interval (P < 0.0001), compared to sham PN. The present findings showed PN acupuncture induced alterations in vagal function, blood pressure, and Beck's Depression Inventory scores. It was suggested that vagal stabilization effect by acupuncture may be associated with the therapeutic mechanism in depression., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Growing evidence suggests that a broad range of behavioral anomalies in people with autism spectrum disorder (ASD) can be linked with morphological and functional alterations in the brain. However, the neuroanatomical underpinnings of ASD have been investigated using either structural magnetic resonance imaging (MRI) or diffusion tensor imaging (DTI), and the relationships between abnormalities revealed by these two modalities remain unclear. This study applied a multimodal data-fusion method, known as linked independent component analysis (ICA), to a set of structural MRI and DTI data acquired from 46 adult males with ASD and 46 matched controls in order to elucidate associations between different aspects of atypical neuroanatomy of ASD. Linked ICA identified two composite components that showed significant between-group differences, one of which was significantly correlated with age. In the other component, participants with ASD showed decreased gray matter (GM) volumes in multiple regions, including the bilateral fusiform gyri, bilateral orbitofrontal cortices, and bilateral pre- and post-central gyri. These GM changes were linked with a pattern of decreased fractional anisotropy (FA) in several white matter tracts, such as the bilateral inferior longitudinal fasciculi, bilateral inferior fronto-occipital fasciculi, and bilateral corticospinal tracts. Furthermore, unimodal analysis for DTI data revealed significant reductions of FA along with increased mean diffusivity in those tracts for ASD, providing further evidence of disrupted anatomical connectivity. Taken together, our findings suggest that, in ASD, alterations in different aspects of brain morphology may co-occur in specific brain networks, providing a comprehensive view for understanding the neuroanatomy of this disorder.

The long-lasting effects of repetitive transcranial magnetic stimulation (rTMS) on electroencephalogram (EEG) activity are not clear. We aimed to investigate the cumulative rTMS effects on EEG and clinical outcomes in patients with major depression. Twenty-five patients with medication-resistant depression underwent 10 daily rTMS sessions over the left dorsolateral prefrontal cortex. We measured resting EEG and spectrum-power before and after the rTMS course. Clinical efficacy was evaluated with the Hamilton's Depression Rating Scale (HAM-D) and Wisconsin Card Sorting Test (WCST). In an ANOVA model, including all prefrontal electrodes, post hoc analyses revealed significant time effects on the theta (F1,24 = 7.89, P = 0.010; +43%), delta (F1,24 = 6.58, P = 0.017; +26%), and alpha (F1,24 = 4.64, P = 0.042; 31%) bands without site specificity. Clinical correlations were observed between F4 alpha power increases and improvements in HAM-D retardation, F3 alpha power increases and improvements of the absolute changes in perseveration and error number on the WCST, and C3 and C4 theta power increases and improvements of the percent change in perseveration and error number on the WCST following rTMS. Consecutive prefrontal rTMS could induce long-lasting EEG potentiations beyond the aftereffects, resulting in improved cognitive and depressive symptoms., (Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Background: The effects of repetitive transcranial magnetic stimulation (rTMS) on sleep structure in major depression are currently unknown., Objective: To determine the effects of prefrontal rTMS on sleep electroencephalography (EEG) in major depression., Methods: In this open-label pilot study, twelve male patients with relatively mild depression, who had been medication-resistant, underwent 10 daily rTMS sessions over the left dorsolateral prefrontal cortex (DLPFC). Polysomnographic (PSG) data were recorded over four nights: Adaptation, Baseline, Post-1 (after the fifth rTMS session), and Post-2 (after the tenth rTMS session). Discrete Fourier Transform (DFT) band power analyses were performed to quantify delta and sigma band activities during Stages II-IV, and determine time courses of these activities between Baseline and Post-1 (first five sessions) and between Post-1 and Post-2 (last five sessions)., Results: Post-hoc tests based on a three-way ANOVA model indicated significant delta power increase at F3 (t11 = -2.762, P = 0.018) during the first five sessions; however, sigma power was unchanged. No significant band power changes were observed during the second half. Stages II-IV (percent total sleep time) increased significantly during the first half (t12 = -2.43, P = 0.033). No other significant changes in sleep parameters or clinical correlations were observed., Conclusions: The first five sessions of high frequency rTMS to the left DLPFC increase slow-wave activity (SWA) at F3, possibly reflecting locally enhanced synaptic plasticity induced by rTMS. This increased activity was not observed during the last half, possibly due to a homeostatic regulation mechanism intrinsic to SWA., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Overall neocortical gray matter (NCGM) volume has not been studied in first-episode schizophrenia (FESZ) at first hospitalization or longitudinally to evaluate progression, nor has it been compared with first-episode affective psychosis (FEAFF)., Methods: Expectation-maximization/atlas-based magnetic resonance imaging (MRI) tissue segmentation into gray matter, white matter (WM), or cerebrospinal fluid (CSF) at first hospitalization of 29 FESZ and 34 FEAFF, plus 36 matched healthy control subjects (HC), and, longitudinally approximately 1.5 years later, of 17 FESZ, 21 FEAFF, and 26 HC was done. Manual editing separated NCGM and its lobar parcellation, cerebral WM (CWM), lateral ventricles (LV), and sulcal CSF (SCSF)., Results: At first hospitalization, FESZ and FEAFF showed smaller NCGM volumes and larger SCSF and LV than HC. Longitudinally, FESZ showed NCGM volume reduction (-1.7%), localized to frontal (-2.4%) and temporal (-2.6%) regions, and enlargement of SCSF (7.2%) and LV (10.4%). Poorer outcome was associated with these LV and NCGM changes. FEAFF showed longitudinal NCGM volume increases (3.6%) associated with lithium or valproate administration but without clinical correlations and regional localization., Conclusions: Longitudinal NCGM volume reduction and CSF component enlargement in FESZ are compatible with post-onset progression. Longitudinal NCGM volume increase in FEAFF may reflect neurotrophic effects of mood stabilizers.

Background: Using diffusion tensor imaging (DTI), we previously reported abnormalities in two critical white matter tracts in schizophrenia, the uncinate fasciculus (UF) and the cingulum bundle (CB), both related to fronto-temporal connectivity. Here, we investigate these two bundles in unmedicated subjects with schizotypal personality disorder (SPD)., Methods: Fifteen male SPD subjects and 15 male control subjects were scanned with line-scan DTI. Fractional anisotropy (FA) and mean diffusivity (D(m)) were used to quantify water diffusion, and cross-sectional area was defined with a directional threshold method. Exploratory correlation analyses were evaluated with Spearman's rho, followed by post hoc hierarchical regression analyses., Results: We found bilaterally reduced FA in the UF of SPD subjects. For CB, there was no significant group difference for FA or D(m) measures. Additionally, in SPD, reduced FA in the right UF was correlated with clinical symptoms, including ideas of reference, suspiciousness, restricted affect, and social anxiety. In contrast, left UF area was correlated with measures of cognitive function, including general intelligence, verbal and visual memory, and executive performance., Conclusions: These findings in SPD suggest altered fronto-temporal connectivity through the UF, similar to findings in schizophrenia, and intact neocortical-limbic connectivity through the CB, in marked contrast with what has been reported in schizophrenia.

To investigate the sleep spindle activity of the human prefrontal cortex (PFC), we simultaneously recorded whole nights of polysomnographic and electrocorticographic (ECoG) activities during the natural sleep of epileptic patients. Subjects were nine patients with intractable epilepsy who had subdural electrodes surgically attached to the orbital (seven cases), medial (three cases), or dorsolateral (two cases) PFC, and in one case to the frontal pole. To examine spindle frequencies, fast Fourier transformation (FFT) and auto-correlation analyses were performed on the PFC ECoG and Cz EEG data, primarily on epochs of stage 2 sleep. Lower sigma band ECoG oscillations of about 12 Hz were widely distributed across all prefrontal cortical areas including the frontal limbic regions, but none of the PFC sigma frequency peaks coincided with the faster (about 14 Hz) Cz EEG sleep spindles. Combining our results with anatomical and electrophysiological facts, it is suggested that the thalamofrontal circuit involving the rostral reticular and the mediodorsal nucleus of the thalamus is responsible for the generation of 12 Hz frontal spindles in humans.