Search

Resting state electroencephalographic (EEG) activity in schizophrenia (SZ) is frequently characterised by increased power at slow frequencies and/or a reduction of peak alpha frequency. Here we investigated the nature of these effects. As most studies to date have been limited by reliance on a priori frequency bands which impose an assumed structure on the data, we performed a data-driven analysis of resting EEG recorded in SZ patients and healthy controls (HC). The sample consisted of 39 chronic SZ and 36 matched HC. The EEG was recorded with a dense electrode array. Power spectral densities were decomposed via Varimax-rotated principal component analysis (PCA) over all participants and for each group separately. Spectral PCA was repeated at the cortical level on cortical current source density computed from standardised low resolution brain electromagnetic tomography. There was a trend for power in the theta/alpha range to be increased in SZ compared to HC, and peak alpha frequency was significantly reduced in SZ. PCA revealed that this frequency shift was because of the presence of a spectral component in the theta/alpha range (6-9 Hz) that was unique to SZ. The source distribution of the SZ > HC theta/alpha effect involved mainly prefrontal and parahippocampal areas. Abnormal low frequency resting EEG activity in SZ was accounted for by a unique theta/alpha oscillation. Other reports have described a similar phenomenon suggesting that the neural circuits oscillating in this range are relevant to SZ pathophysiology., (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Recent empirical findings suggest that altered neural synchronization, which is hypothesized to be associated with an imbalance of excitatory (E) and inhibitory (I) neuronal activities, may underlie a core pathophysiological mechanism in patients with schizophrenia. The auditory steady-state response (ASSR) examined by electroencephalography (EEG) and magnetoencephalography (MEG) has been proposed as a potential biomarker for evaluating altered neural synchronization in schizophrenia. For this review, we performed a comprehensive literature search for papers published between 1999 and 2021 examining ASSRs in patients with schizophrenia. Almost all EEG-ASSR studies reported gamma-band ASSR reductions, especially to 40-Hz stimuli both in power and/or phase synchronization in chronic and first-episode schizophrenia. In addition, similar to EEG-ASSR findings, MEG-ASSR deficits to 80-Hz stimuli (high gamma) have been reported in patients with schizophrenia. Moreover, the 40-Hz ASSR is likely to be a predictor of the onset of schizophrenia. Notably, increased spontaneous (or ongoing) broadband (30-100 Hz) gamma power has been reported during ASSR tasks, which resembles the increased spontaneous gamma activity reported in animal models of E/I imbalance. Further research on ASSRs and evoked and spontaneous gamma oscillations is expected to elucidate the pathophysiology of schizophrenia with translational implications., (© 2022 The Authors. Psychiatry and Clinical Neurosciences © 2022 Japanese Society of Psychiatry and Neurology.)

Background: A number studies have been conducted on abnormalities in the cortical circuitry of gamma oscillations, including deficit in auditory steady-state response (ASSR) to gamma-frequency (≧ 30-Hz) stimulation, in patients with bipolar disorder (BD). In the current study, we investigated neural responses during click stimulation by blood oxygen level-dependent (BOLD) signals. We focused on Broadman 41 and 42, the main sources of ASSR., Materials and Methods: We acquired BOLD responses elicited by click trains of 80-, 40-, 30- and 20-Hz frequencies from 25 patients with BD to 27 healthy controls (HC) with normal hearing between 22 and 59 years of age assessed via a standard general linear-model-based analysis. We extracted contrast values by identifying the primary auditory cortex and Brodmann areas 41 and 42 as regions of interest (ROI)s., Results: BD group showed significantly decreased ASSR-BOLD signals in response to 40-Hz stimuli compared to the HC group in the right Brodmann areas 41 and 42. We found significant negative correlations between the BOLD change in the right Brodmann areas 41 and 42 and Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D) scores, also the BOLD change in the right Brodmann areas 41 and 42 and the Positive and Negative Syndrome Scale (PANSS)-Negative scores., Conclusion: The observed decrease in BOLD signal patterns in the right primary auditory cortex during 40-Hz ASSR may be a potential biomarker option for bipolar disorder., Competing Interests: SF was employed by Medical Corporation Kouseikai. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Okamoto, Onitsuka, Kuga, Oribe, Nakayama, Fukushima, Nakao and Ueno.)

Objective: Time-processing disorders in adults is a priority area for intervention. Time management program, which has been demonstrated to be effective in children with ADHD, has not been examined in adults. We anticipate the need for the development of specialized programs for adults. This is because it has been reported that time processing disorders have different patterns in childhood and adulthood. This study aimed to evaluate the therapeutic effect of a gCBT program focusing on time management for adults with ADHD., Method: Adults with ADHD were randomly assigned to gCBT ( n  = 24) or a treatment as usual group ( n  = 24). Outcome measures were masked clinically rated, self-reported, and family-reported ADHD symptoms., Results: The gCBT group significantly reduced ADHD symptoms on all measures., Conclusion: Interventions focused on time management have been shown to be effective not only in children with ADHD but also in adult patients.

The results of quantitative electroencephalography (qEEG) studies on electroconvulsive therapy (ECT) have been inconsistent, and indicators of the efficacy of ECT have not been clearly identified. In this study, we examined whether qEEG could be used as an indicator of the effect of ECT by measuring it during the course of treatment. We analyzed qEEG data before and after acute-phase ECT in 18 patients with schizophrenia, mood disorders, and other psychiatric disorders. We processed the qEEG data and compared the spectral power between the data acquired before and after ECT. The spectral power increased significantly after ECT in the delta, theta, and alpha bands. There was a strong significant correlation between the increase in the spectral power of the alpha band after acute ECT and improvement in the Brief Psychiatric Rating Scale score. Our results suggest that an increase in the alpha-band spectral power may be useful as an objective indicator of the treatment effect of acute ECT.

Since patients with schizophrenia (SZ) and bipolar disorder (BD) share many biological features, detecting biomarkers that differentiate SZ and BD patients is crucial for optimized treatments. High-resolution magnetic resonance imaging (MRI) is suitable for detecting subtle brain structural differences in patients with psychiatric disorders. In the present study, we adopted a neuroanatomically defined and manually delineated region of interest (ROI) method to evaluate the amygdalae, hippocampi, Heschl's gyrus (HG), and planum temporale (PT), because these regions are crucial in the development of SZ and BD. ROI volumes were measured using high resolution MRI in 31 healthy subjects (HS), 23 SZ patients, and 21 BD patients. Right hippocampal volumes differed significantly among groups (HS > BD > SZ), whereas left hippocampal volumes were lower in SZ patients than in HS and BD patients (HS = BD > SZ). Volumes of the amygdalae, HG, and PT did not differ among the three groups. For clinical correlations, there were no significant associations between ROI volumes and demographics/clinical symptoms. Our study revealed significant lower hippocampal volume in patients with SZ and BD, and we suggest that the right hippocampal volume is a potential biomarker for differentiation between SZ and BD.

Aim: We previously reported abnormal P300 and N200 in a visual oddball task, and progressive P300 amplitude reduction at 1-year follow-up in patients with first-episode schizophrenia. P300 reduction as well as intact P1/N1 were also observed in clinical high-risk subjects (CHR), but whether or not these components change over time is unknown. This study evaluates, longitudinally, the visual P300, as well as P1, N1, and N200, in CHR., Methods: Visual event-related potentials (ERP) were recorded twice, once at baseline and once at 1-year follow-up in CHR (n = 19) and healthy comparison subjects (HC; n = 28). Participants silently counted infrequent target stimuli ('x') among standard stimuli ('y') presented on the screen while the 64-channel electroencephalogram was recorded., Results: No CHR converted to psychosis from baseline to 1-year follow-up in this study. Visual P300 amplitude was reduced and the latency was delayed significantly in CHR at both time points compared with HC. Furthermore, CHR subjects who had more positive symptoms showed more amplitude reduction at both time points. P1, N1, and N200 did not differ between groups., Conclusion: Visual P300 amplitude was found to be reduced in CHR individuals compared with HC. We note that this finding is in subjects who did not convert to psychosis at 1-year follow-up. The association between visual P300 amplitude and symptoms suggests that for CHR who often experience clinical symptoms and seek medical care, visual P300 may be an important index that reflects the pathophysiological impairment underlying such clinical states., (© 2020 The Authors Psychiatry and Clinical Neurosciences © 2020 Japanese Society of Psychiatry and Neurology.)

There may be different neural bases between subjects with epilepsy only (EP) and interictal chronic epilepsy psychosis (EPS). However, there have been few structural MRI studies of EPS. The current study was conducted to investigate the neural substrate of EPS. T1-weighted images were analyzed in 14 patients with EPS and 14 strictly-matched patients with EP. We conducted volume comparison in the whole brain using voxel-based morphometry (VBM). The VBM method revealed that EPS patients exhibited significantly reduced gray matter volumes in the left postcentral gyrus and the left supra marginal gyrus compared with EP patients (adjusted p = 0.029, FDR corrected q; k = 319 voxels). For clinical correlations, there were no significant associations between psychotic symptoms and gray matter volumes in the left postcentral gyrus and the left supra marginal gyrus. VBM analysis revealed that reduced gray matter volumes in the left postcentral gyrus and the left supra marginal gyrus may be crucial regions for EPS.

Background: Neuropsychological studies have revealed that patients with schizophrenia (SZ) have facial recognition difficulties and a reduced visual evoked N170 response to human faces. However, detailed neurophysiological evidence of this face processing deficit in SZ with a higher spatial resolution has yet to be acquired. In this study, we recorded visual evoked magnetoencephalography (MEG) and examined whether M170 (a magnetic counterpart of the N170) activity deficits are specific to faces in patients with chronic SZ., Methods: Participants were 26 patients with SZ and 26 healthy controls (HC). The M170 responses to faces and cars were recorded from whole-head MEG, and global field power over each temporal cortex was analyzed. The distributed M170 sources were also localized using a minimum-norm estimation (MNE) method. Correlational analyses between M170 responses and demographics/symptoms were performed., Results: As expected, the M170 was significantly smaller in the SZ compared with the HC group in response to faces, but not to cars (faces: p = 0.01; cars: p = 0.55). The MNE analysis demonstrated that while the M170 was localized over the fusiform face area (FFA) in the HC group, visual-related brain regions other than the FFA were strongly activated in the SZ group in both stimulus conditions. The severity of negative symptoms was negatively correlated with M170 power (rho = -0.47, p = 0.01) in SZ. Within HC, there was a significant correlation between age and the M170 responses to faces averaged for both hemispheres (rho = 0.60, p = 0.001), while such a relationship was not observed in patients with SZ (rho = 0.09, p = 0.67)., Conclusion: The present study showed specific reductions in the M170 response to human faces in patients with SZ. Our findings could suggest that SZ is characterized by face processing deficits that are associated with the severity of negative symptoms. Thus, we suggest that social cognition impairments in SZ might, at least in part, be caused by this functional face processing deficit., (Copyright © 2020 Ohara, Hirano, Oribe, Tamura, Nakamura, Hirano, Tsuchimoto, Ueno, Togao, Hiwatashi, Nakao and Onitsuka.)

Patients with alcohol use disorder (AUD) have difficulty controlling their alcohol cravings and thus exhibit increased use and early relapse. Although patients tend to respond more strongly to alcohol-related images than to non-alcohol-related images, few researchers have examined the factors that modulate cravings. Here, we examined whole-brain blood oxygen level-dependent (BOLD) responses to behavioural cues in individuals with AUD and in healthy controls (HCs). The participants included 24 patients with AUD and 15 HCs. We presented visual cues consisting of four beverage-related images (juice, drinking juice, sake, and drinking sake), and the cue reactivity of AUD participants was contrasted with that of HC participants. Multiple comparisons revealed that the AUD group had lower BOLD responses than the HC group in the left precuneus (p = 0.036) and the left posterior cingulate cortex (PCC) (p = 0.044) to images of drinking juice and higher BOLD responses than the HC group in the left PCC (p = 0.044) to images of drinking sake. Furthermore, compared to the HCs, the AUD patients had decreased BOLD responses associated with cue reactivity to drinking juice in the left precuneus during the periods from 15 to 18 s (p = 0.004, df = 37) and 18 to 21 s (p = 0.002, df = 37). Our findings suggest that HCs and AUD patients differ in their responses not to images of alcoholic beverages but to images related to alcohol-drinking behaviour. Thus, these patients appear to have different patterns of brain activity. This information may aid clinicians in developing treatments for patients with AUD., Competing Interests: The authors have declared that no competing interests exist.

We investigated whether the gray matter volume of primary auditory cortex (Heschl's gyrus [HG]) was associated with abnormal patterns of auditory γ activity in schizophrenia, namely impaired γ synchronization in the 40-Hz auditory steady-state response (ASSR) and increased spontaneous broadband γ power. (The γ data were previously reported in Hirano et al, JAMA Psychiatry , 2015;72:813-821). Participants were 24 healthy controls (HC) and 23 individuals with chronic schizophrenia (SZ). The ASSR was obtained from the electroencephalogram to click train stimulation at 20, 30, and 40 Hz rates. Dipole source localization of the ASSR was used to provide a spatial filter of auditory cortex activity, from which ASSR evoked power and phase locking factor (PLF), and induced γ power were computed. HG gray matter volume was derived from structural magnetic resonance imaging at 3 T with manually traced regions of interest. As expected, HG gray matter volume was reduced in SZ compared with HC. In SZ, left hemisphere ASSR PLF and induced γ power during the 40-Hz stimulation condition were positively and negatively correlated with left HG gray matter volume, respectively. These results provide evidence that cortical gray matter structure, possibly resulting from reduced synaptic connectivity at the microcircuit level, is related to impaired γ synchronization and increased spontaneous γ activity in schizophrenia.

This study investigated the efficacy of 10-module metacognitive training (MCT) among Japanese patients with schizophrenia by conducting a multicenter randomized controlled trial to test the influence of the most recent and extended version of MCT on positive symptoms. A six-center, randomized, assessor-blind, controlled trial between "treatment as usual" (TAU) and TAU + MCT was conducted. Fifty inpatients and outpatients with schizophrenia, schizotypal, and delusional disorders (ICD 10) were enrolled, then randomly assigned to TAU (n = 26) or TAU + MCT (n = 24). Assessments were made at baseline, after six weeks, immediately posttreatment, and 1-month post-treatment. The primary outcome was positive symptom score, as measured by the Positive and Negative Syndrome Scale (PANSS). General assessment of functioning (GAF) and measures of cognitive biases were secondary outcomes. Completion at post-treatment (10 weeks later) and 1-month follow-up was high-TAU + MCT, n = 22 (91.67%) and TAU, n = 23 (88.46%). The severity of PANSS positive symptoms declined significantly in the TAU + MCT treatment group compared with the TAU group. GAF also showed significantly greater improvement in the TAU + MCT group compared with the TAU group. There was also a trend for greater efficacy of MCT on cognitive biases. In conclusion, this study provides support for the efficacy of 10 module MCT concerning positive symptomatology (especially, delusion) and general functioning., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The early auditory-evoked gamma band response (EAGBR) may serve as an index of the integrity of fast recurrent inhibition or synaptic connectivity in the auditory cortex, where abnormalities in individuals with schizophrenia have been consistently found. The EAGBR has been rarely investigated in first episode schizophrenia patients (FESZ) and individuals at clinical high risk (CHR) for schizophrenia, and never been compared directly between these populations nor evaluated longitudinally. Here we examined the EAGBR in FESZ, CHR, and matched healthy controls (HC) at baseline and 1-year follow-up assessments to determine whether the EAGBR was affected in these clinical groups, and whether any EAGBR abnormalities changed over time. The electroencephalogram was recorded with a dense electrode array while subjects (18 FESZ, 18 CHR, and 40 HC) performed an auditory oddball task. Event-related spectral measures (phase locking factor [PLF] and evoked power) were computed on Morlet-wavelet-transformed single epochs from the standard trials. At baseline, EAGBR PLF and evoked power did not differ between groups. FESZ showed progressive reductions of PLF and evoked power from baseline to follow-up, and deficits in PLF at follow-up compared to HC. EAGBR peak frequency also increased at temporal sites in FESZ from baseline to follow-up. Longitudinal effects on the EAGBR were not found in CHR or HC, nor did these groups differ at follow-up. In conclusion, we detected neurophysiological changes of auditory cortex function in FESZ during a one-year period, which were not observed in CHR. These findings are discussed within the context of neurodevelopmental models of schizophrenia., (Published by Elsevier B.V.)

Background: Cross-frequency interactions may coordinate neural circuits operating at different frequencies. While neural oscillations associated with particular circuits in schizophrenia (SZ) are impaired, few studies have examined cross-frequency interactions. Here we examined phase-amplitude coupling (PAC) in the electroencephalograms of individuals with SZ and healthy control subjects (HCs). We computed PAC during the baseline period of 40-Hz auditory steady-state stimulation and rest. We hypothesized that subjects with SZ would show abnormal theta/gamma coupling during stimulation, especially in the left auditory cortex, and coupling with high frequencies would be higher during stimulation than during rest., Methods: We reanalyzed data from 18 subjects with SZ and 18 HCs. Auditory cortex electroencephalogram activity was estimated using dipole source localization. PAC was computed using the debiased PAC measure, calculated with the generalized Morse wavelet transform. PAC clusters were identified using cluster-corrected permutation testing and interrogated in analyses of variance with correction for multiple tests., Results: Overall, coupling of high beta and gamma amplitude was higher during the auditory steady-state response, while alpha/beta PAC was higher during rest. Theta/alpha PAC was higher in subjects with SZ than in HCs. Theta/gamma PAC was lateralized to the left hemisphere in HCs but was not lateralized in subjects with SZ., Conclusions: PAC involving high frequencies was state dependent and not abnormal in SZ. Increased theta/alpha PAC in subjects with SZ was consistent with other evidence of increased low-frequency activity. Hemispheric lateralization of theta/gamma PAC was reduced in subjects with SZ, consistent with evidence for left hemisphere auditory cortex abnormalities in subjects with SZ. PAC may reveal new insights into neural circuitry abnormalities in SZ and other neuropsychiatric disorders., (Published by Elsevier Inc.)

Background: The mismatch negativity (MMN) component of the event-related potential and its magnetic counterpart, the MMNm, are generated by a mismatch between the physical features of a deviant stimulus and a neuronal sensory-memory trace produced by repetitive standard stimuli. Deficits in the MMN/MMNm have been reported in patients with major depression; however, the results are inconsistent. The present study investigated the pitch-MMNm in patients with major depression using whole-head 306-channel magnetoencephalography (MEG)., Methods: Twenty patients with major depression and 36 healthy subjects participated in this study. Subjects were presented with two sequences of auditory stimuli. One consisted of 1000Hz standard signals (probability=90%) and 1200Hz deviant signals (probability=10%), while the other consisted of 1200Hz standard (90%) and 1000Hz deviant signals (10%). Event-related brain responses to standard tones were subtracted from responses to deviant tones., Results: Major depressive patients showed significantly reduced magnetic global field power (GFP) of MMNm in the right hemisphere (p=0.02), although no significant MMNm reduction was observed in the left hemisphere (p=0.81). Additionally, patients with major depression showed significantly earlier bilateral MMNm peak latencies (p=0.004). No significant associations were observed between MMNm variables and demographic data/clinical variables within the patients., Limitations: We could not exclude the effects of antidepressants, mood stabilizers, or neuroleptics on the MMNm abnormalities found in patients with major depression. Sample size was also insufficient to permit subgroup analyses., Conclusions: Patients with major depression exhibited reduced GFP of MMNm in the right hemisphere. The present study suggested that patients with major depression may have right hemispheric dominant preattentive dysfunction., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Recent MRI studies have shown that schizophrenia is characterized by reductions in brain gray matter, which progress in the acute state of the disease. Cortical circuitry abnormalities in gamma oscillations, such as deficits in the auditory steady state response (ASSR) to gamma frequency (>30-Hz) stimulation, have also been reported in schizophrenia patients. In the current study, we investigated neural responses during click stimulation by BOLD signals. We acquired BOLD responses elicited by click trains of 20, 30, 40 and 80-Hz frequencies from 15 patients with acute episode schizophrenia (AESZ), 14 symptom-severity-matched patients with non-acute episode schizophrenia (NASZ), and 24 healthy controls (HC), assessed via a standard general linear-model-based analysis. The AESZ group showed significantly increased ASSR-BOLD signals to 80-Hz stimuli in the left auditory cortex compared with the HC and NASZ groups. In addition, enhanced 80-Hz ASSR-BOLD signals were associated with more severe auditory hallucination experiences in AESZ participants. The present results indicate that neural over activation occurs during 80-Hz auditory stimulation of the left auditory cortex in individuals with acute state schizophrenia. Given the possible association between abnormal gamma activity and increased glutamate levels, our data may reflect glutamate toxicity in the auditory cortex in the acute state of schizophrenia, which might lead to progressive changes in the left transverse temporal gyrus., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The auditory steady-state response (ASSR) elicited by gamma band neural oscillations has received considerable interest as a biomarker of psychiatric disorders. Although recent ASSR studies have reported that patients with bipolar disorder (BD) show altered ASSRs, little is known about ASSRs in patients with major depressive disorder (MDD). The aim of this study was to evaluate whether ASSRs in MDD subjects differed from those in BD subjects or normal controls (NC)., Method: We analyzed ASSRs in 14 MDD patients, 19 BD patients, and 29 normal control subjects. We used whole-head 306-channel magnetoencephalography to evaluate ASSR power and phase-locking factors (PLF) elicited by 20-, 30-, 40-, and 80-Hz click trains. We determined optimal sensitivity and specificity of ASSR power and PLF for the diagnosis of MDD or BD via receiver operating characteristic (ROC) curve analysis using a nonparametric approach., Results: MDD patients exhibited no significant differences in ASSR power or PLF compared with NC subjects, while BD patients showed deficits on the ASSR measures. MDD patients showed significantly larger ASSR power and PLF for 30-, 40-, and 80-Hz stimuli compared with BD patients. The area under the curve (AUC) for the ROC analysis (MDD vs. BD) was 0.81 [95% CI=0.66-0.96, p=0.003] concerning 40-Hz ASSR power., Limitations: We could not exclude the effect of medication and the sample size of the current study is relatively small., Conclusions: We could differentiate between MDD and BD subjects in terms of gamma band ASSR. Our data suggest that the 40-Hz ASSR may be a potential biomarker for differentiation between MDD and BD patients., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Importance: A major goal of translational neuroscience is to identify neural circuit abnormalities in neuropsychiatric disorders that can be studied in animal models to facilitate the development of new treatments. Oscillations in the gamma band (30-100 Hz) of the electroencephalogram have received considerable interest as the basic mechanisms underlying these oscillations are understood, and gamma abnormalities have been found in schizophrenia (SZ). Animal models of SZ based on hypofunction of the N-methyl-d-aspartate receptor (NMDAR) demonstrate increased spontaneous broadband gamma power, but this phenomenon has not been identified clearly in patients with SZ., Objective: To examine spontaneous gamma power and its relationship to evoked gamma oscillations in the auditory cortex of patients with SZ., Design, Setting, and Participants: We performed a cross-sectional study including 24 patients with chronic SZ and 24 matched healthy control participants at the Veterans Affairs Boston Healthcare System from January 1, 2009, through December 31, 2012. Electroencephalograms were obtained during auditory steady-state stimulation at multiple frequencies (20, 30, and 40 Hz) and during a resting state in 18 participants in each group., Main Outcomes and Measures: Electroencephalographic activity in the auditory cortex was estimated using dipole source localization. Auditory steady-state response (ASSR) measures included the phase-locking factor and evoked power. Spontaneous gamma power was measured as induced (non-phase-locked) gamma power in the ASSR data and as total gamma power in the resting-state data., Results: The ASSR phase-locking factor was reduced significantly in patients with SZ compared with controls for the 40-Hz stimulation (mean [SD], 0.075 [0.028] vs 0.113 [0.065]; F1,46 = 6.79 [P = .012]) but not the 20- or the 30-Hz stimulation (0.042 [0.038] vs 0.043 [0.034]; F1,46 = 0.006 [P = .938] and 0.084 [0.040] vs 0.098 [0.050]; F1,46 = 1.605 [P = .212], respectively), repeating previous findings. The mean [SD] broadband-induced (30-100 Hz) gamma power was increased in patients with SZ compared with controls during steady-state stimulation (6.579 [3.783] vs 3.984 [1.843]; F1,46 = 9.128 [P = .004]; d = 0.87) but not during rest (0.006 [0.003] vs 0.005 [0.002]; F1,34 = 1.067 [P = .309]; d = 0.35). Induced gamma power in the left hemisphere of the patients with SZ during the 40-Hz stimulation was positively correlated with auditory hallucination symptoms (tangential, ρ = 0.587 [P = .031]; radial, ρ = 0.593 [P = .024]) and negatively correlated with the ASSR phase-locking factor (baseline: ρ = -0.572 [P = .024]; ASSR: ρ = -0.568 [P = .032])., Conclusions and Relevance: Spontaneous gamma activity is increased during auditory steady-state stimulation in SZ, reflecting a disruption in the normal balance of excitation and inhibition. This phenomenon interacts with evoked oscillations, possibly contributing to the gamma ASSR deficit found in SZ. The similarity of increased spontaneous gamma power in SZ to the findings of increased spontaneous gamma power in animal models of NMDAR hypofunction suggests that spontaneous gamma power could serve as a biomarker for the integrity of NMDARs on parvalbumin-expressing inhibitory interneurons in humans and in animal models of neuropsychiatric disorders.

Objective: To understand the underlying dynamic neurophysiological changes over the course of schizophrenia, it is important to study subjects longitudinally from the early stage of the illness. We previously reported that visual P300 was already impaired in patients with first-episode schizophrenia (FESZ). This study demonstrates how the visual P300, as well as earlier components P1, N1, and N200, changed at the 1-year follow-up after their initial measurement., Methods: Visual ERPs were recorded with the same experimental paradigm and acquisition protocol at both time points in FESZ (n = 18) and healthy comparison subjects (n = 24). Participants silently counted infrequent target stimuli ("x") amid standard stimuli ("y") presented on the screen while the 64-channel electroencephalogram was recorded., Results: FESZ showed smaller visual P300, N200, P1 (trend level) amplitude and delayed P300 and N1 latency at both time points; however, only P300 showed progressive amplitude reduction over the course of the illness at 1-year follow-up. P300 latency did not change over time in either group. FESZ showed significantly reduced Spatial Span total score at both time points, and there was a significant negative correlation between P300 peak amplitude and the Brief Psychiatric Rating Scale positive symptom score at baseline., Conclusion: These data show progressive P300 amplitude reduction in response to visual stimuli in the early stage of schizophrenia. These visual P300 findings support the concept of progression of schizophrenia, suggesting the usefulness of the visual P300 as a biological marker of progression., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The clinical high risk (CHR) period is a phase denoting a risk for overt psychosis during which subacute symptoms often appear, and cognitive functions may deteriorate. To compare biological indices during this phase with those during first episode schizophrenia, we cross-sectionally examined sex- and age-matched clinical high risk (CHR, n=21), first episode schizophrenia patients (FESZ, n=20) and matched healthy controls (HC, n=25) on oddball and novelty paradigms and assessed the N100, P200, P3a and P3b as indices of perceptual, attentional and working memory processes. To our knowledge, this is the only such comparison using all of these event-related potentials (ERPs) in two paradigms. We hypothesized that the ERPs would differentiate between the three groups and allow prediction of a diagnostic group. The majority of ERPs were significantly affected in CHR and FESZ compared with controls, with similar effect sizes. Nonetheless, in logistic regression, only the P3a and N100 distinguished CHR and FESZ from healthy controls, suggesting that ERPs not associated with an overt task might be more sensitive to prediction of group membership., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Mismatch negativity (MMN) and its magnetic counterpart (MMNm) are thought to reflect an automatic process that detects a difference between an incoming stimulus and the sensory memory trace of preceding stimuli. In patients with schizophrenia, an attenuation of the MMN/MMNm amplitude has been repeatedly reported. Heschl's gyrus (HG) is one of the major generators of MMN and the functional alteration of HG has been reported in patients with bipolar disorder. The present study investigated the pitch-MMNm in patients with bipolar disorder using whole-head 306-ch magnetoencephalography (MEG)., Methods: Twenty-two patients and 22 healthy controls participated in this study. Subjects were presented with two types of auditory stimulus sequences. One consisted of 1,000 Hz standards (probability = 90%) and 1,200 Hz deviants (probability = 10%), and the other consisted of 1,000 Hz standards (90%) and 1,200 Hz deviants (10%). These two tasks were each performed twice. Event-related brain responses to standard tones were subtracted from responses to deviant tones., Results: Patients with bipolar disorder showed a significant bilateral reduction in magnetic global field power (mGFP) amplitudes (p = 0.02) and dipole moments of the MMNm (p = 0.04) compared with healthy controls. Patients with admission experience showed significantly reduced mGFP amplitudes of MMNm compared with patients without admission experience (p = 0.004). Additionally, patients with more severe manic symptoms had smaller mGFP amplitudes of MMNm (ρ = -0.50, p = 0.05)., Conclusions: The results of this study suggest that patients with bipolar disorder may exhibit preattentive auditory dysfunction indexed by reduced pitch-MMNm responses. Pitch-MMNm could be a potential trait marker reflecting the global severity of bipolar disorder., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Schizophrenia has been conceptualized as a failure of cognitive integration, and abnormalities in neural circuitry have been proposed as a basis for this disorder. In this article, we focus on electroencephalography and magnetoencephalography findings in patients with schizophrenia. Auditory-P50, -N100, and -P300 findings, visual-P100, -N170, and -N400 findings, and neural oscillations in patients with schizophrenia are overviewed. Published results suggest that patients with schizophrenia have neurophysiological deficits from the very early phase of sensory processing (i.e., P50, P100, N100) to the relatively late phase (i.e., P300, N400) in both auditory and visual perception. Exploring the associations between neural substrates, including neurotransmitter systems, and neurophysiological findings, will lead to a more comprehensive understanding of the pathophysiology of schizophrenia., (© 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.)

Background: P300 deficits in schizophrenia patients are well established, especially in the auditory modality. Several studies have also reported P300 abnormalities in schizophrenia in visual tasks, but these findings are inconsistent. Furthermore, reports on P300 in visual modality in prodromal subjects are very limited. While P300 indexes relatively late and complex cognitive functions such as context updating in working memory, sensory-evoked components such as the P1/N1 primarily index early stages of perceptual processing. Several previous studies suggest that P300 reduction in schizophrenia patients may be dissociable from these earlier components. Therefore, in this study, we measured the P300 component as well as the P1/N1 in a visual oddball paradigm in prodromal subjects and first episode schizophrenia patients, and compared them with those of healthy controls., Method: Visual P300 and P1/N1 were obtained from prodromal (PRO, n = 23), first episode schizophrenia patients (SZ, n = 17), and healthy control subjects (HC, n = 31), who silently counted infrequent target stimuli ("X") amid standard stimuli ("Y") presented on the screen while 64-channel EEG was recorded., Results: Both PRO and SZ subjects showed reduced P300 amplitudes and delayed P300 peak latencies in comparison to control subjects. On the other hand, N1 amplitude was significantly reduced only in SZ but not in PRO. Increased severity of positive symptoms was significantly associated with smaller P300 amplitude in PRO., Conclusions: These results suggest that visual P300 is affected already at the prodromal stage and could be a marker of the prodromal phase of schizophrenia., (Published by Elsevier B.V.)

The present article reviews findings from measuring evoked and event-related responses, neural oscillation and synchronization, and near-infrared spectroscopy (NIRS) studies in patients with bipolar disorder. Studies of evoked responses have indicated that the P50 suppression deficits may be related to the generation of psychosis and may constitute an endophenotype of bipolar disorder patients with psychotic features. The N100 may be intact in patients with bipolar disorder, and the N100 might be a biological index to distinguish bipolar disorder and schizophrenia. In studies of event-related responses, bipolar disorder patients appear to exhibit P300 abnormalities to some extent. In addition, some bipolar disorder patients may have preattentive dysfunction, indexed by abnormal mismatch negativities. Recent studies of neural oscillations suggest that bipolar disorder may be characterized by deficits in the auditory steady-state response. Moreover, bipolar patients may have altered gamma band responses, as well as abnormal beta and alpha activities perhaps related to deficits of fronto-temporal-parietal functional connectivity. NIRS studies of bipolar disorder have indicated hypofrontality during a verbal fluency task, and altered NIRS responses compared with those of patients with major depressive disorder or healthy subjects. In future studies, these techniques may be used to elucidate the neurophysiological abnormalities in patients with bipolar disorder. Moreover, neurophysiological approaches may reveal appropriate biological indices to distinguish bipolar disorder and schizophrenia, aiding the development of more effective medication at the early stages of illness.

Periodic auditory click stimulation has been reported to elicit an auditory steady state response (ASSR). The ASSR has been suggested to reflect the efficiency of γ-amino butyric acid (GABA) inhibitory interneuronal activity. Although a potential role for GABAergic dysfunction has been previously proposed, the role of neural synchronization in the ASSR in people with bipolar disorder (BD) has received little attention. In the current study, we investigated ASSRs to 20 Hz, 30 Hz, 40 Hz and 80 Hz click trains in BD patients. A total of 14 (4 males) BD patients and 25 (10 males) healthy controls participated in this study. ASSRs were obtained using whole-head 306-channel magnetoencephalography to calculate, ASSR power values and phase locking factors (PLF). BD patients exhibited significantly reduced mean ASSR power and PLF values bilaterally at frequencies of 30, 40, and 80 Hz (p<0.05 for these frequencies). At 20 Hz, bipolar patients showed no significant reduction in mean ASSR power and PLF values. There was a significant negative correlation between 80 Hz-ASSR-power values obtained from the right hemisphere and scores on the Hamilton Depression Rating Scale (rho = -0.86, p = 0.0003). The current study showed reduced low and high gamma band ASSR power and PLF bilaterally with no significant beta band ASSR reduction in BD patients. BD patients are characterized by deficits in gamma band oscillations, which may be associated with GABA inhibitory interneuronal activity dysfunction.

Schizophrenia has been conceptualized by dysfunctional cognition and behavior related to abnormalities in neural circuitry. The functioning of the neural circuitry can be assessed using the auditory steady state response (ASSR). Moreover, in recent years, research on high (>60 Hz) gamma band oscillations has become of increasing interest. The current study used whole-head, 306-channel magnetoencephalography (MEG) and investigated low and high gamma band oscillations with the ASSR. The subjects comprised 17 patients with schizophrenia and 22 controls. The current study investigated the MEG-ASSR elicited by click trains of 20-, 30-, 40- and 80-Hz frequencies, and symptom-ASSR associations in patients with schizophrenia. The mean power, phase-locking factor, dipole moments and source locations of the ASSR were estimated. The main findings were: (1) patients with schizophrenia showed bilaterally reduced ASSR power and dipole moments specific to the 40-Hz and 80-Hz frequencies; (2) patients with schizophrenia showed less right-greater-than-left 40-Hz ASSR power and phase-locking factor compared with healthy subjects, indicating that schizophrenics may be characterized by an abnormal asymmetry of the 40-Hz ASSR; (3) increased severity of global hallucinatory experiences was significantly associated with smaller left 80-Hz MEG-ASSR in patients with schizophrenia. The current study highlights the high and low frequency gamma abnormalities and provides clear evidence that schizophrenia is characterized by abnormalities in neural circuitry., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objectives:   Psychiatrists have long debated whether bipolar disorder (BP) and schizophrenia (SZ) are the clinical outcomes of discrete or shared causative processes. SZ shows significantly delayed peak latencies of the evoked neural oscillation (eNO) power and reduced eNO power to speech sounds in the left hemisphere in comparison to normal controls (NC), suggesting deficits in the fast mechanism for identifying speech sounds for SZ. The current study tested the hypothesis that the eNO to speech sounds could be differentiated between BP and SZ patients., Methods:   The magnetoencephalographic data of 11 BP, 12 SZ, and 15 NC subjects were evaluated, and we analyzed the eNO power and phase-locking in 20-45 Hz to speech sounds and pure tones in the left hemisphere., Results:   The major findings were that: (i) BP subjects exhibited larger eNO power to speech sounds compared to NC and SZ; (ii) SZ subjects showed delayed eNO and phase-locking to speech sounds specifically in the left hemisphere; and (iii) no significant differences were observed in the response to pure tones among the three groups., Conclusions:   The present study showed that different patterns in eNO to speech sounds are present in BP, SZ, and NC subjects. The eNO to speech sounds in the left hemisphere is a potential index to distinguish BP and SZ., (© 2010 John Wiley and Sons A/S.)

Background: Patients with schizophrenia have auditory gating deficits; however, little is known about P50 auditory gating to human voices and its association with clinical symptoms. We examined the functioning of auditory gating and its relationship with the clinical symptoms in schizophrenia., Methods: Auditory evoked magnetoencephalography responses to the first and the second voices stimuli were recorded in 22 schizophrenia patients and 28 normal control subjects. The auditory gating ratios of P50m and N100m were investigated and P50m-symptom correlations were also investigated., Results: Patients showed significantly higher P50m gating ratios to human voices specifically in the left hemisphere. Moreover, patients with higher left P50m gating ratios showed more severe auditory hallucinations, while patients with higher right P50m gating ratios showed more severe negative symptoms., Conclusions: The present study suggests that schizophrenia patients have auditory gating deficits to human voices, specifically in the left hemisphere and auditory hallucinations of schizophrenia may be associated with sensory overload to human voices in the auditory cortex., ((c) 2009 Elsevier B.V. All rights reserved.)

Objective: The human adenosine A1 receptor gene (ADORA1) localizes to chromosome 1q32 is 76.8 kbp in length and contains six exons. ADORA1 is ubiquitously expressed in the central nervous system and clinical and pharmacological evidence suggest the involvement of adenosine neurotransmission in the pathogenesis of schizophrenia. Therefore, we investigated the contribution of genetic variations of ADORA1 to the pathophysiological mechanisms of Japanese schizophrenia patients., Methods: We performed genetic analysis of 29 polymorphic markers in 200 schizophrenic patients and 210 healthy controls from the Kyushu region of Japan. In statistical analysis, we performed the univariate analysis with genotypes and allele frequencies, linkage disequilibrium (LD) analyses, multivariate analysis, haplotype analysis, and sliding window haplotype analysis., Results: In univariate analysis, no statistical difference was shown, after Bonferroni correction. By LD analysis, however, we could not find any LD blocks. In haplotype analysis, a total of 359 haplotypes were estimated. In multivariate analysis, we found three statistically different markers. In sliding window haplotype analysis, there were four statistically different haplotypes., Conclusion: This is the first study describing the involvement of ADORA1 polymorphisms in the pathophysiological mechanisms of schizophrenia in a Japanese population. These results corroborate our previous pharmacological and neurochemical studies in the rat that have suggested an association between ADORA1 neurotransmission and the schizophrenic effects of the N-methyl-D-aspartate receptor antagonist phencyclidine. Thus, ADORA1 polymorphisms may represent good candidate markers for schizophrenia research and ADORA1 may be involved in the pathophysiological mechanisms of schizophrenia in Japanese populations.

Objective: Schizophrenia impairs early visual cognitive processing. Low and high spatial frequency (LSF, HSF) visual information are differentially processed in humans. We investigated whether electrophysiological abnormalities exist in visual processing for spatial frequency (SF)-filtered neutral/emotional faces in schizophrenics., Methods: Subjects consisted of 16 male chronic schizophrenics and 23 controls. Event-related potentials (ERPs) to SF-filtered (LSF or HSF) and unfiltered (broad SF; BSF) pictures of neutral, happy, and fearful faces were recorded at 20 scalp sites. The relationships between the P100 (P1)/N170 amplitudes and the Global Assessment of Functioning (GAF) scores in patients were also evaluated., Results: For the P1 amplitudes at O1/O2, controls exhibited a significant LSF>BSF difference, while schizophrenics showed no LSF>BSF difference. For the N170 amplitudes at T5/T6, controls revealed a significant HSF>BSF difference, while schizophrenics showed no such difference. For the P1 latencies, controls but not schizophrenics showed a significant difference (LSF>BSF=HSF). For the N170 latencies, no significant SF differentiation was found between the two groups. For both P1 and N170 amplitudes, no significant effects of facial expressions were observed in controls and patients regardless of SFs. There were significant negative correlations between the GAF scores and the N170 amplitudes to BSF faces in schizophrenics, but not for P1 amplitudes., Conclusions: Schizophrenics showed abnormal P1 and N170 responses to SF changes in faces, thus indicating decreased SF sensitivities for processing of faces., Significance: Abnormal early visual processing may underlie some of the deficits associated with face recognition in schizophrenia.

Schizophrenia impairs many cognitive functions, and abnormalities in language processing have been proposed as one of the bases for this disorder. Previously, it was reported that different magnetoencephalography (MEG) patterns of the evoked oscillatory activity (eOA) of 20-45 Hz to speech and nonspeech sounds were evidence of a fast mechanism for the representation and identification of speech sounds in humans. The current study tested the hypothesis that the schizophrenics would show abnormal neural oscillatory activity, as measured by eOA, to speech and nonspeech sounds. Twenty patients and 23 control subjects participated in this study. MEG responses to speech and nonspeech sounds were recorded and eOA power and phase locking at 20-45 Hz were analyzed. Patients showed significantly delayed peak latencies of the eOA power and phase locking to speech sounds in the left hemisphere and to nonspeech sounds in the right hemisphere. Patients also showed a significantly reduced eOA power to speech sounds in the left hemisphere in 0-50 ms and a significantly larger eOA power to speech sounds in the left hemisphere in 100-150 ms. In addition, the analyses of the lateralization index revealed the pattern of hemispheric lateralization to be the opposite in patients. These results indicated that patients showed different characteristics of eOA compared with normal controls, probably related to deficits in a fast mechanism for identifying speech sounds. Moreover, the present study suggests that schizophrenia might be characterized by an opposite pattern of hemispheric lateralization in auditory evoked oscillations.