Oxytocin-induced increases in cytokines and clinical effect on the core social features of autism: Analyses of RCT datasets.

Although oxytocin may provide a novel therapeutics for the core features of autism spectrum disorder (ASD), previous results regarding the efficacy of repeated or higher dose oxytocin are controversial, and the underlying mechanisms remain unclear. The current study is aimed to clarify whether repeated oxytocin alter plasma cytokine levels in relation to clinical changes of autism social core feature. Here we analyzed cytokine concentrations using comprehensive proteomics of plasmas of 207 adult males with high-functioning ASD collected from two independent multi-center large-scale randomized controlled trials (RCTs): Testing effects of 4-week intranasal administrations of TTA-121 (A novel oxytocin spray with enhanced bioavailability: 3U, 6U, 10U, or 20U/day) and placebo in the crossover discovery RCT; 48U/day Syntocinon or placebo in the parallel-group verification RCT. Among the successfully quantified 17 cytokines, 4 weeks TTA-121 6U (the peak dose for clinical effects) significantly elevated IL-7 (9.74, 95 % confidence interval [CI] 3.59 to 15.90, False discovery rate corrected P (PFDR) < 0.001), IL-9 (56.64, 20.46 to 92.82, PFDR < 0.001) and MIP-1b (18.27, 4.96 to 31.57, PFDR < 0.001) compared with placebo. Inverted U-shape dose-response relationships peaking at TTA-121 6U were consistently observed for all these cytokines (IL-7: P < 0.001; IL-9: P < 0.001; MIP-1b: P = 0.002). Increased IL-7 and IL-9 in participants with ASD after 4 weeks TTA-121 6U administration compared with placebo was verified in the confirmatory analyses in the dataset before crossover (PFDR < 0.001). Furthermore, the changes in all these cytokines during 4 weeks of TTA-121 10U administration revealed associations with changes in reciprocity score, the original primary outcome, observed during the same period (IL-7: Coefficient = -0.05, -0.10 to 0.003, P = 0.067; IL-9: -0.01, -0.02 to -0.003, P = 0.005; MIP-1b: -0.02, -0.04 to -0.007, P = 0.005). These findings provide the first evidence for a role of interaction between oxytocin and neuroinflammation in the change of ASD core social features, and support the potential role of this interaction as a novel therapeutic seed. Trial registration: UMIN000015264, NCT03466671/UMIN000031412.

Aberrant thalamocortical connectivity and shifts between the resting state and task state in patients with schizophrenia.

Prominent pathological hypotheses for schizophrenia include auditory processing deficits and dysconnectivity within cerebral networks. However, most neuroimaging studies have focused on impairments in either resting-state or task-related functional connectivity in patients with schizophrenia. The aims of our study were to examine (1) blood oxygen level-dependent (BOLD) signals during auditory steady-state response (ASSR) tasks, (2) functional connectivity during the resting-state and ASSR tasks and (3) state shifts between the resting-state and ASSR tasks in patients with schizophrenia. To reduce the functional consequences of scanner noise, we employed resting-state and sparse sampling auditory fMRI paradigms in 25 schizophrenia patients and 25 healthy controls. Auditory stimuli were binaural click trains at frequencies of 20, 30, 40 and 80 Hz. Based on the detected ASSR-evoked BOLD signals, we examined the functional connectivity between the thalamus and bilateral auditory cortex during both the resting state and ASSR task state, as well as their alterations. The schizophrenia group exhibited significantly diminished BOLD signals in the bilateral auditory cortex and thalamus during the 80 Hz ASSR task (corrected p < 0.05). We observed a significant inverse relationship between the resting state and ASSR task state in altered functional connectivity within the thalamo-auditory network in schizophrenia patients. Specifically, our findings demonstrated stronger functional connectivity in the resting state (p < 0.004) and reduced functional connectivity during the ASSR task (p = 0.048), which was mediated by abnormal state shifts, within the schizophrenia group. These results highlight the presence of abnormal thalamocortical connectivity associated with deficits in the shift between resting and task states in patients with schizophrenia.

Abnormal connectivity and activation during audiovisual speech perception in schizophrenia.

The unconscious integration of vocal and facial cues during speech perception facilitates face-to-face communication. Recent studies have provided substantial behavioural evidence concerning impairments in audiovisual (AV) speech perception in schizophrenia. However, the specific neurophysiological mechanism underlying these deficits remains unknown. Here, we investigated activities and connectivities centered on the auditory cortex during AV speech perception in schizophrenia. Using magnetoencephalography, we recorded and analysed event-related fields in response to auditory (A: voice), visual (V: face) and AV (voice-face) stimuli in 23 schizophrenia patients (13 males) and 22 healthy controls (13 males). The functional connectivity associated with the subadditive response to AV stimulus (i.e., [AV] < [A] + [V]) was also compared between the two groups. Within the healthy control group, [AV] activity was smaller than the sum of [A] and [V] at latencies of approximately 100 ms in the posterior ramus of the lateral sulcus in only the left hemisphere, demonstrating a subadditive N1m effect. Conversely, the schizophrenia group did not show such a subadditive response. Furthermore, weaker functional connectivity from the posterior ramus of the lateral sulcus of the left hemisphere to the fusiform gyrus of the right hemisphere was observed in schizophrenia. Notably, this weakened connectivity was associated with the severity of negative symptoms. These results demonstrate abnormalities in connectivity between speech- and face-related cortical areas in schizophrenia. This aberrant subadditive response and connectivity deficits for integrating speech and facial information may be the neural basis of social communication dysfunctions in schizophrenia.

Multi-modal imaging of the auditory-larynx motor network for voicing perception.

Voicing is one of the most important characteristics of phonetic speech sounds. Despite its importance, voicing perception mechanisms remain largely unknown. To explore auditory-motor networks associated with voicing perception, we firstly examined the brain regions that showed common activities for voicing production and perception using functional magnetic resonance imaging. Results indicated that the auditory and speech motor areas were activated with the operculum parietale 4 (OP4) during both voicing production and perception. Secondly, we used a magnetoencephalography and examined the dynamical functional connectivity of the auditory-motor networks during a perceptual categorization task of /da/-/ta/ continuum stimuli varying in voice onset time (VOT) from 0 to 40 ms in 10 ms steps. Significant functional connectivities from the auditory cortical regions to the larynx motor area via OP4 were observed only when perceiving the stimulus with VOT 30 ms. In addition, regional activity analysis showed that the neural representation of VOT in the auditory cortical regions was mostly correlated with categorical perception of voicing but did not reflect the perception of stimulus with VOT 30 ms. We suggest that the larynx motor area, which is considered to play a crucial role in voicing production, contributes to categorical perception of voicing by complementing the temporal processing in the auditory cortical regions.

Effect of a novel nasal oxytocin spray with enhanced bioavailability on autism: a randomized trial.

Although intranasal oxytocin is expected to be a novel therapy for the core symptoms of autism spectrum disorder, which has currently no approved medication, the efficacy of repeated administrations was inconsistent, suggesting that the optimal dose for a single administration of oxytocin is not optimal for repeated administration. The current double-blind, placebo-controlled, multicentre, crossover trial (ClinicalTrials.gov Identifier: NCT03466671) was aimed to test the effect of TTA-121, a new formulation of intranasal oxytocin spray with an enhanced bioavailability (3.6 times higher than Syntocinon® spray, as assessed by area under the concentration-time curve in rabbit brains), which enabled us to test a wide range of multiple doses, on autism spectrum disorder core symptoms and to determine the dose-response relationship. Four-week administrations of TTA-121, at low dose once per day (3 U/day), low dose twice per day (6 U/day), high dose once per day (10 U/day), or high dose twice per day (20 U/day), and 4-week placebo were administered in a crossover manner. The primary outcome was the mean difference in the reciprocity score (range: 0-14, higher values represent worse outcomes) on the Autism Diagnostic Observation Schedule between the baseline and end point of each administration period. This trial with two administration periods and eight groups was conducted at seven university hospitals in Japan, enrolling adult males with high-functioning autism spectrum disorder. Enrolment began from June 2018 and ended December 2019. Follow-up ended March 2020. Of 109 males with high-functioning autism spectrum disorder who were randomized, 103 completed the trial. The smallest P-value, judged as the dose-response relationship, was the contrast with the peak at TTA-121 6 U/day, with inverted U-shape for both the full analysis set (P = 0.182) and per protocol set (P = 0.073). The Autism Diagnostic Observation Schedule reciprocity score, the primary outcome, was reduced in the TTA-121 6 U/day administration period compared with the placebo (full analysis set: P = 0.118, mean difference = -0.5; 95% CI: -1.1 to 0.1; per protocol set: P = 0.012, mean difference = -0.8; 95% CI: -1.3 to -0.2). The per protocol set was the analysis target population, consisting of all full analysis set participants except those who deviated from the protocol. Most dropouts from the full analysis set to the per protocol set occurred because of poor adherence to the test drug (9 of 12 in the first period and 8 of 15 in the second period). None of the secondary clinical and behavioural outcomes were significantly improved with the TTA-121 compared with the placebo in the full analysis set. A novel intranasal spray of oxytocin with enhanced bioavailability enabled us to test a wide range of multiple doses, revealing an inverted U-shape dose-response curve, with the peak at a dose that was lower than expected from previous studies. The efficacy of TTA-121 shown in the current exploratory study should be verified in a future large-scale, parallel-group trial.

The Association between Electroencephalography with Auditory Steady-State Response and Postoperative Delirium.

Delirium is a disorder of consciousness and a risk factor for cognitive dysfunction and poor prognosis. We hypothesized that preoperative gamma activities would be linked to postoperative delirium. We enrolled 71 subjects for elective surgery and recorded auditory steady-state response (ASSR) by electroencephalography (EEG) before the surgery and examined postoperative delirium with DSM-5. The EEG data were analyzed for baseline power, and ASSR evoked power (EP) and phase-locking factor (PLF) within the gamma range. Postoperative delirium was found in 18 patients (delirium group) but not in 53 patients (non-delirium group). There were no significant differences in the 40-Hz EP or PLF between the two groups. The baseline gamma activity negatively correlated with the 40-Hz PLF in the non-delirium group (ρ = −0.444, p < 0.01). The correlation between baseline gamma activity and 40-Hz EP was not significant in either the delirium or non-delirium group. In all patients, both preoperative PLF and EP had no significant correlations with the Delirium Rating Scale Revised-98 and the Memorial Delirium Assessment Measure at the post-operation, respectively. The disruption of the neurophysiological relationship between baseline gamma activity before sound stimuli and the PLF of the 40-Hz ASSR may be one of the potential neurophysiological indicators associated with postoperative delirium.

Lower Hippocampal Volume in Patients with Schizophrenia and Bipolar Disorder: A Quantitative MRI Study.

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.

Neurophysiological Face Processing Deficits in Patients With Chronic Schizophrenia: An MEG Study.

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.

Long-Term Test-Retest Reliability of Auditory Gamma Oscillations Between Different Clinical EEG Systems.

OBJECTIVE: There is increasing interest in the utility of gamma-band activity for assessing various brain functions, including perception, language, memory, and cognition. The auditory steady-state response (ASSR) involves neural activity in the brain elicited by trains of a click sound, and its maximum response is obtained at 40 Hz (40-Hz ASSR). Abnormalities of the 40-Hz ASSR are also widely reported in patients with schizophrenia. Thus, the test-retest reliability of the ASSR is important for its clinical and translational application. However, there are only limited studies reporting the short-term reliability between acquisitions at two time points made using the same electroencephalogram (EEG) system. Furthermore, the long-term reliability between multiple EEG systems and the reliability of spontaneous gamma activity are unknown but are crucial for multicenter collaborative research. METHODS: We examined the long-term test-retest reliability of 40-Hz ASSR oscillatory activities indexed by the phase locking factor (PLF), evoked power, and (non-phase-locked) induced power between two clinical 19-electrode EEG systems [recorded twice for EEG-1 (time1 and time2) and EEG-2 (time3 and time4)] at four time points from 14 healthy controls over a duration of 5 months. Test-retest reliability was examined using intraclass correlation coefficients (ICCs). RESULTS: Both PLF and evoked power showed good to excellent ICCs (>0.60), mainly in the Fz-electrode, both within each EEG system-EEG-1 [(time1 vs. time2) PLF: ICC = 0.66, evoked power: ICC = 0.88] and EEG-2 [(time3 vs. time4) PLF: ICC = 0.82, evoked power: ICC = 0.77]-and between the two EEG systems [(EEG-1 vs. EEG-2) PLF: ICC = 0.73, evoked power: ICC = 0.84]. In contrast, induced power showed the highest (excellent) ICC between the two EEG systems (ICC = 0.95) mainly in the Cz-electrode. For PLF, the Fz-electrode showed better test-retest reliability across all EEG recordings than the Cz-electrode (Fz: ICC = 0.67, Cz: ICC = 0.63), whereas we found similar excellent reproducibility across all EEG recordings from both electrodes for evoked power (Fz: ICC = 0.79, Cz: ICC = 0.77) and induced power (Fz: ICC = 0.79, Cz: ICC = 0.80). CONCLUSION: The 40-Hz ASSR oscillatory activities, including induced power, showed excellent test-retest reliability, even when using different EEG systems over a duration of 5 months. These findings confirm the utility of the 40-Hz ASSR as a reliable clinical and translatable biomarker for multicenter collaborative research.

Altered P3a Modulations to Emotional Faces in Male Patients With Chronic Schizophrenia.

Existing evidence suggests that patients with schizophrenia may have a deficit in processing facial expressions. However, the neural basis of this processing deficit remains unclear. A total of 20 men diagnosed with chronic schizophrenia and 13 age- and sex-matched controls participated in the study. We investigated visual N170 and P3a components evoked in response to fearful, happy, and sad faces during an emotion discrimination task. Compared with control subjects, patients showed significantly smaller N170 amplitudes bilaterally (P = .04). We found no significant main effect of emotion of the presented faces (fearful, happy, or sad) on N170 amplitude. Patients showed significantly smaller P3a amplitudes in response to fearful (P = .01) and happy (P = .02) faces, but no significant between-group differences were observed for sad faces (P = .22). Moreover, we found no significant P3a modulation effect in response to emotional faces in patients with schizophrenia. Our results suggest that altered P3a modulations to emotional faces may be associated with emotion recognition deficits in patients with schizophrenia.

Neuroanatomical substrate of chronic psychosis in epilepsy: an MRI study.

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.

Right hemisphere pitch-mismatch negativity reduction in patients with major depression: An MEG study.

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.

Increased BOLD Signals Elicited by High Gamma Auditory Stimulation of the Left Auditory Cortex in Acute State Schizophrenia.

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.

Differentiation between major depressive disorder and bipolar disorder by auditory steady-state responses.

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.

Early integration processing between faces and vowel sounds in human brain: an MEG investigation.

OBJECTIVE: Unconscious fast integration of face and voice information is a crucial brain function necessary for communicating effectively with others. Here, we investigated for evidence of rapid face-voice integration in the auditory cortex. METHODS: Magnetic fields (P50m and N100m) evoked by visual stimuli (V), auditory stimuli (A) and audiovisual stimuli (VA), i.e. by face, vowel and simultaneous vowel-face stimuli, were recorded in 22 healthy subjects. Magnetoencephalographic data from 28 channels around bilateral auditory cortices were analyzed. RESULTS: In both hemispheres, AV - V showed significantly larger P50m amplitudes than A. Additionally, compared with A, the N100m amplitudes and dipole moments of AV - V were significantly smaller in the left hemisphere, but not in the right hemisphere. CONCLUSIONS: Differential changes in P50m (bilateral) and N100m (left hemisphere) that occur when V (faces) are associated with A (vowel sounds) indicate that AV (face-voice) integration occurs in early processing, likely enabling us to communicate effectively in our lives.

Prism adaptation and perceptual skill learning deficits in early-stage Parkinson's disease.

BACKGROUND: Skill learning deficits in Parkinson's disease (PD) at an early stage are not well known, and findings in behavioral studies with mirror reading and prism adaptation tasks are mixed. Moreover, skill learning over several days in PD patients has not been studied. METHODS: A total of 12 nondemented early-stage PD patients and 12 age-matched normal control subjects participated in this study. The Wechsler Memory Scale-Revised (WMS-R) was applied to all subjects to assess declarative memory. The mirror reading task of horizontally presented kana letters and the reversed vision task using a prism were performed throughout 3 consecutive days. RESULTS: For the mirror reading skill, the early-stage PD patients showed significantly increased mirror reading time on days 2 and 3. For the prism adaptation, the PD patients performed significantly more slowly in reversed vision than the normal controls, specifically at blocks 1 and 2, over 3 days. The WMS-R subscores did not show a significant correlation with the reaction times in reversed vision or with the mirror reading times. CONCLUSIONS: Using two tasks with different modalities, the present study revealed visuomotor adaptation deficits and acquisition/retention deficits, especially in the later phase of perceptual skill learning, in early-stage PD patients.

Review of neurophysiological findings in patients with schizophrenia.

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.

Gamma band neural synchronization deficits for auditory steady state responses in bipolar disorder patients.

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.