Neuronal imbalance of excitation and inhibition in schizophrenia: a scoping review of gamma-band ASSR findings.

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.

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.

Preattentive dysfunction in patients with bipolar disorder as revealed by the pitch-mismatch negativity: a magnetoencephalography (MEG) study.

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.

Neurodevelopmental Disorder Traits in Taijin-Kyofu-sho and Social Anxiety Disorder: A Cross-Sectional Study among University Students.

Taijin-Kyofu-sho is an East Asian culture-bound anxiety disorder with similarities to social anxiety disorder. However, few studies have examined these two disorders from the perspective of neurodevelopmental disorders. This study is aimed at examining the association of Taijin-Kyofu-sho and social anxiety disorder with the attention-deficit/hyperactivity disorder (ADHD) trait and autism spectrum disorder (ASD) trait. The Liebowitz Social Anxiety, Taijin-Kyofu-sho, and Adult Attention-Deficit/Hyperactivity Disorder Self-Report scales and the 16-item Autism-Spectrum Quotient were administered to 818 university students. Participants were divided into four groups: control (neither Taijin-Kyofu-sho nor social anxiety disorder), pure Taijin-Kyofu-sho (Taijin-Kyofu-sho alone), pure social anxiety disorder (social anxiety disorder alone), and mixed Taijin-Kyofu-sho-social anxiety disorder (both Taijin-Kyofu-sho and social anxiety disorder). We used logistic regression analysis to examine whether the ADHD trait and ASD trait were associated with Taijin-Kyofu-sho and social anxiety disorder. ASD trait was significantly associated with pure Taijin-Kyofu-sho (p = 0.006, odds ratio: 3.99). Female sex and ADHD trait were significantly associated with pure social anxiety disorder (sex: p = 0.013, odds ratio: 2.61; ADHD trait: p = 0.012, odds ratio: 2.46). Female sex, ADHD trait, and ASD trait were significantly associated with mixed Taijin-Kyofu-sho-social anxiety disorder (sex: p = 0.043, odds ratio: 2.16; ADHD trait: p = 0.003, odds ratio: 2.75; ASD trait: p < 0.001, odds ratio: 16.93). Neurodevelopmental disorder traits differed between individuals with Taijin-Kyofu-sho and those with social anxiety disorder. Overall, our study reveals that Japanese individuals with the ADHD or ASD traits are at a heightened risk of developing Taijin-Kyofu-sho or social anxiety disorder.

Contributions of Anthropometrics and Lifestyle to Blood Pressure in Japanese University Students†:†Investigation by Annual Health Screening.

Background : High blood pressure (BP) is a healthcare problem in young persons. There are racial differences in anthropometrics, dietary habit and lifestyle relating to BP. Therefore, this study investigated the relationship between anthropometrics, lifestyle and BP obtained in the Japanese university students. Materials and Methods : Participants were recruited in annual health screening including questionnaire, measurements of BP and anthropometrics calculating body mass index (BMI). Totally, 14,280 students (10,273 males and 4,007 females) were eligible. Multiple regression analyses were applied to predict contributors to high BP. Results : BMI was the most powerful contributor to high BP in many subgroups divided by gender and graduation (p < 0.001). In lifestyle, contribution of lack of exercise to high BPs was observed in the undergraduates. Smoking, drinking and breakfast skipping had no significant impact on high BP. However, smoking and drinking permeated and exercise habit declined after graduation. Prevalence of obesity (BMI ≥ 25 kg / m2) and hypertension ( ≥ 140 / 90 mmHg) increased in subgroups with advanced age (p < 0.001). Conclusion: BMI was found to be the most powerful contributor to high BPs. Health literacy to modify lifestyle is important to prevent hypertension for university students who are exposed to social trends of unhealthy lifestyle. J. Med. Invest. 67 : 174-181, February, 2020.

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.

Correlation between Taijin-Kyofu-sho and Attention Deficit Hyperactivity Disorder among University Students: A Self-Reported Assessment Study.

Taijin-Kyofu-sho (TK) is regarded as a culture-bound anxiety disorder in East Asian counties. Despite its earlier discovery in Japan, fewer studies have focused on TK than on social anxiety disorder (SAD) and even fewer on TK comorbidity with developmental disorders. Thus, we examined the association between TK and attention deficit hyperactivity disorder (ADHD) among Japanese university students. A total of 673 students (500 male, 173 female) were assessed on the Japanese version of Liebowitz Social Anxiety Scale (LSAS-J), TK scale, and adult ADHD Self-Report Scale (ASRS; version 1.1). On the TK scale and LSAS-J, 17.4 and 10.3 percent of students, respectively, exceeded the cut-off value. Furthermore, ASRS scores more strongly correlated with TK scale than LSAS-J scores (TK scale: r = 0.427; LSAS-J: r = 0.330). To evaluate how TK or SAD with ADHD affects those scores, we divided subjects into four groups: healthy subjects, subjects with TK, those with SAD, and those with both disorders. The total ASRS score was significantly higher in TK-only subjects than in healthy subjects (p < 0.0001). However, there was no significant difference between scores of healthy and SAD-only subjects (p = 0.281). Our results indicate a possible link between ADHD and later development of TK in Japan.

Relevance of hoarding behavior and the traits of developmental disorders among university students: a self-reported assessment study.

BACKGROUND: Previous studies have shown that hoarding behavior usually starts at a subclinical level in early adolescence and gradually worsens; however, a limited number of studies have examined the prevalence of hoarding behavior and its association with developmental disorders in young adults. The aims of this study were to estimate the prevalence of hoarding behavior and to identify correlations between hoarding behavior and developmental disorder traits in university students. METHODS: The study participants included 801 university students (616 men, 185 women) who completed questionnaires (ASRS: Adult ADHD Self-Report Scale version 1.1, AQ16: Autism-Spectrum Quotient with 16 items, and CIR: Clutter Image Rating). RESULTS: Among 801 participants, 27 (3.4%) exceeded the CIR cut-off score. Moreover, the participants with hoarding behavior had a significantly higher percentage of ADHD traits compared to participants without hoarding behavior (HB(+) vs HB(-), 40.7% vs 21.7%). In addition, 7.4% of HB(+) participants had autism spectrum disorder (ASD) traits, compared to 4.1% of HB(-) participants. A correlation analysis revealed that the CIR composite score had a stronger correlation with the ASRS inattentive score than with the hyperactivity/impulsivity score (CIR composite vs ASRS IA, r = 0.283; CIR composite vs ASRS H/I, r = 0.147). CONCLUSIONS: The results showed a high prevalence of ADHD traits in the university students with hoarding behavior. Moreover, we found that the hoarding behavior was more strongly correlated with inattentive symptoms rather than with hyperactivity/impulsivity symptoms. Our results support the concept of a common pathophysiology behind hoarding behavior and ADHD in young adults.

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.

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.

Reduced high and low frequency gamma synchronization in patients with chronic schizophrenia.

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.