Shogo Hirano

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.

Abnormal Neural Oscillatory Activity to Speech Sounds in Schizophrenia: A Magnetoencephalography Study

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.

Decreased spatial frequency sensitivities for processing faces in male patients with chronic schizophrenia

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.

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.

Auditory gating deficit to human voices in schizophrenia: A MEG study

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.

Altered face inversion effect and association between face N170 reduction and social dysfunction in patients with schizophrenia

OBJECTIVE There is accumulating evidence that schizophrenics may have deficits in facial recognition, which has been related to disease-specific disturbances in normal social interaction. Neurophysiologically, face inversion results in an amplitude increase of the event-related potential (ERP) component N170. This face inversion effect (FIE) presumably reflects a disruption of face-specific configuration processing. The present study investigated FIE and the associations between social functioning and N170 in patients with schizophrenia. METHODS The subjects consisted of 15 schizophrenics and 15 controls. Event-related potentials (ERPs) to upright and inverted neutral faces and cars were recorded. The relationships between the Social Functioning Scale (SFS) scores and N170 amplitude to upright faces or cars were also evaluated. RESULTS Normal controls exhibited a significant FIE of the N170 amplitude, while schizophrenics showed no FIE. In both normal controls and schizophrenics, no inversion effect was observed for car stimuli. For face stimuli, schizophrenics showed significant bilateral N170 reduction; additionally, in schizophrenics, but not in controls, the SFS was significantly correlated with N170 amplitudes to upright faces. CONCLUSIONS These results indicate face-specific configuration processing deficits and significant associations between face-N170 reduction and social dysfunction in schizophrenia. SIGNIFICANCE Abnormal face-specific configuration processing may underlie some of the social dysfunctions in schizophrenia.

Differentiation between bipolar disorder and schizophrenia revealed by neural oscillation to speech sounds: an MEG study

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.

Auditory and Visual Mismatch Negativity in Psychiatric Disorders: A Review

Event-related potentials (ERPs) provide an objective index of neurocognitive abnormality or dysfunction in neuropsychiatric disorders. Auditory mismatch negativity (aMMN), which was discovered in the 1980s, is one unique type of ERP. Several lines of evidence suggest that it reflects auditory preattentive (automatic) information processing and the function of glutamatergic N-methyl-D-aspartate receptors. Many studies also have suggested that aMMN is a promising biomarker for some psychiatric disorders such as schizophrenia. Prospective studies combining analyses of several biomarkers, including aMMN, in schizophrenia patients from the prodromal period, are underway. Meanwhile, the existence of a visual counterpart of aMMN (vMMN) has been disputed, and a genuine vMMN was only confirmed in the last decade. Thus, there have been a relatively small number of vMMN studies compared with studies of aMMN, and the mechanism underlying vMMN is still unclear. However, it is well known that abnormal auditory and visual sensory information processing is present in psychiatric disorders, and vMMN is an important component of ERPs studied in psychiatric patients. The aim of this review is to provide an overview of recent aMMN and vMMN findings in several psychiatric disorders, including schizophrenia, major depression, Alzheimer’s disease, and developmental disorders. In doing so, we highlight their potential use as biomarkers of psychiatric disorders.

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.

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

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. Heschls 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).