Itta Nakamura

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.

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.

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.

Prism Adaptation and Perceptual Skill Learning Deficits in Early-Stage Parkinson's Disease

Background: Skill learning deficits in Parkinsons 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.

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.

Learning About the Management of Physical Illness During the Postgraduate Training to Become a Good Psychiatrist

To the Editor: Physical and mental illnesses often go hand-in-hand [1]. Psychiatrists, however, are often not very good at identifying physical illnesses, while physicians and other doctors, on the other hand, are often not very good at identifying mental illness. Still, we are required to meet physical health needs of individuals with mental illness [2]. The increasing prevalence of comorbidity ofmental and physical illness and the alarmingly high prematuremortality of people with mental illness [3, 4] draw attention to the fact that future psychiatrists must be made competent in dealing with physical illness. By drawing attention to the importance of dealing with physical illness [5], premature mortality can be reduced. However, it is unclear what kind of skills future psychiatrists will need to acquire and how they will be able obtain them. An opportunity to explore this question presented itself during the 14th Course for Academic Development of Psychiatrists (CADP) held by the Japan Young Psychiatrists Organization (JYPO) as a pre-congress of the fifth World Congress of Asian Psychiatry (WCAP) in March of 2015. Thirty-nine young psychiatrists (with amean age 32.5 years and an average of 7.3 years after graduation as doctors) were present, 24 of whom were males and 15 of whom were females. Thirty-one participants were Japanese, three were Indonesian, three were Thai, one was Taiwanese, and one was American. All individuals completed questionnaires regarding what they had learned about the management of physical diseases through their postgraduate training and which departments they would recommend for rotation based on their actual experience. Thereafter, they met in five small groups to discuss optimal training about the management of physical illness in patients with psychiatric disorders. The results of these discussions were then presented in a plenary session attended by both junior and senior psychiatrists, including the former presidents and the director of the World Psychiatric Association. In this paper, we present only the recommendations which were put forward by a majority of participants. This study was approved by the Institutional Review Board of Hokkaido P. W. F. A. C. Kutchan-Kosei General Hospital which the first author belonged to in March 2015. All participants were informed that we would discard all private information except for that which pertains to this research and that the data would be collectively bound to an anonymous number in advance. All participants agreed with this research. In this paper, we introduce the departments that all of the five groups recommended for learning about the management of physical diseases as follows.We describe the top 10 departments in Table 1. * Toru Horinouchi tetsukawa1234@gmail.com

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.

Corrigendum to “Increased BOLD Signals Elicited by High Gamma Auditory Stimulation of the Left Auditory Cortex in Acute State Schizophrenia” [EBioMedicine 12 (2016) 143-149]

a Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582, Japan b Division of Clinical Research, National Hospital Organization, Hizen Psychiatric Center, 160 Mitsu, Yoshinogari-cho, Kanzaki-gun, Saga 842-0192, Japan c Graduate School of Informatics, Kyoto University, 36-1 Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501, Japan d Araya Brain Imaging, 1-6-15-301, Hirakawa-cho, Chiyoda-ku, Tokyo 102-0093, Japan

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.