Abnormal phase entrainment of low- and high-gamma-band auditory steady-state responses in schizophrenia

Shoichiro Nakanishi; Shunsuke Tamura; Shogo Hirano; Junichi Takahashi; Kazutoshi Kitajima; Yoshifumi Takai; Takako Mitsudo; Osamu Togao; Tomohiro Nakao; Toshiaki Onitsuka; Yoji Hirano

doi:10.3389/fnins.2023.1277733

Abnormal phase entrainment of low- and high-gamma-band auditory steady-state responses in schizophrenia

Front Neurosci. 2023 Oct 24:17:1277733. doi: 10.3389/fnins.2023.1277733. eCollection 2023.

Authors

Shoichiro Nakanishi¹, Shunsuke Tamura^{1

2}, Shogo Hirano¹, Junichi Takahashi¹, Kazutoshi Kitajima¹, Yoshifumi Takai¹, Takako Mitsudo¹, Osamu Togao³, Tomohiro Nakao¹, Toshiaki Onitsuka^{1

4}, Yoji Hirano^{1

2

5}

Affiliations

¹ Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
² Department of Psychiatry, Division of Clinical Neuroscience, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
³ Department of Molecular Imaging and Diagnosis, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁴ National Hospital Organization Sakakibara Hospital, Mie, Japan.
⁵ Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.

Abstract

Introduction: Gamma-band oscillatory deficits have attracted considerable attention as promising biomarkers of schizophrenia (SZ). Notably, a reduced auditory steady-state response (ASSR) in the low gamma band (40 Hz) is widely recognized as a robust finding among SZ patients. However, a comprehensive investigation into the potential utility of the high-gamma-band ASSR in detecting altered neural oscillations in SZ has not yet been conducted.

Methods: The present study aimed to assess the ASSR using magnetoencephalography (MEG) data obtained during steady-state stimuli at frequencies of 20, 30, 40, and 80 Hz from 23 SZ patients and 21 healthy controls (HCs). To evaluate the ASSR, we examined the evoked power and phase-locking factor (PLF) in the time-frequency domain for both the primary and secondary auditory cortices. Furthermore, we calculated the phase-locking angle (PLA) to examine oscillatory phase lead or delay in SZ patients. Taking advantage of the high spatial resolution of MEG, we also focused on the hemispheric laterality of low- and high-gamma-band ASSR deficits in SZ.

Results: We found abnormal phase delay in the 40 Hz ASSR within the bilateral auditory cortex of SZ patients. Regarding the 80 Hz ASSR, our investigation identified an aberrant phase lead in the left secondary auditory cortex in SZ, accompanied by reduced evoked power in both auditory cortices.

Discussion: Given that abnormal phase lead on 80 Hz ASSR exhibited the highest discriminative power between HC and SZ, we propose that the examination of PLA in the 80 Hz ASSR holds significant promise as a robust candidate for identifying neurophysiological endophenotypes associated with SZ. Furthermore, the left-hemisphere phase lead observed in the deficits of 80 Hz PLA aligns with numerous prior studies, which have consistently proposed that SZ is characterized by left-lateralized brain dysfunctions.

Keywords: auditory steady-state response (ASSR); evoked power; gamma oscillation; magnetoencephalography (MEG); phase locking angle (PLA); phase locking factor (PLF); schizophrenia.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported in part by the Japan Society for the Promotion of Science (JSPS) KAKENHI under grant numbers JP20K22286 (ST), JP21K13753 (ST), JP18K07602 (SH), JP22K07617 (TO), JP18K07604 (YH), JP19H03579 (YH), JP19H00630 (YH), JP20KK0193 (YH), JP21H02851 (YH); AMED grant numbers JP19dm0207069 (TO) and JP19dm0107124h0004 (YH); and the SIRS Research Fund Award (YH).