40-Hz auditory steady-state responses characterize circuit dysfunctions and predict clinical outcomes in clinical-high-risk participants: a magnetoencephalography study

Grent-'T-Jong, T. , Gajwani, R. , Gross, J. , Gumley, A. I. , Krishnadas, R. , Lawrie, S. M., Schwannauer, M., Schultze-Lutter, F. and Uhlhaas, P. J. (2021) 40-Hz auditory steady-state responses characterize circuit dysfunctions and predict clinical outcomes in clinical-high-risk participants: a magnetoencephalography study. Biological Psychiatry, 90(6), pp. 419-429. (doi: 10.1016/j.biopsych.2021.03.018) (PMID:34116790)

Abstract

Background: This study aimed to examine whether 40-Hz auditory steady-state responses (ASSRs) are impaired in participants at clinical high-risk for psychosis (CHR-P) and predict clinical outcomes. Methods: Magnetoencephalography data were collected during a 40-Hz ASSR paradigm for a group of 116 CHR-P participants, 33 patients with first-episode psychosis (15 antipsychotic-naïve), a psychosis risk–negative group (n = 38), and 49 healthy control subjects. Analysis of group differences of 40-Hz intertrial phase coherence and 40-Hz amplitude focused on right Heschl’s gyrus, superior temporal gyrus, hippocampus, and thalamus after establishing significant activations during 40-Hz ASSR stimulation. Linear regression and linear discriminant analyses were used to predict clinical outcomes in CHR-P participants, including transition to psychosis and persistence of attenuated psychotic symptoms (APSs). Results: CHR-P participants and patients with first-episode psychosis were impaired in 40-Hz amplitude in the right thalamus and hippocampus. In addition, patients with first-episode psychosis were impaired in 40-Hz amplitude in the right Heschl’s gyrus, and CHR-P participants in 40-Hz intertrial phase coherence in the right Heschl’s gyrus. The 40-Hz ASSR deficits were pronounced in CHR-P participants who later transitioned to psychosis (n = 13) or showed persistent APSs (n = 34). Importantly, both APS persistence and transition to psychosis were predicted by 40-Hz ASSR impairments, with ASSR activity in the right hippocampus, superior temporal gyrus, and middle temporal gyrus correctly classifying 69.2% individuals with nonpersistent APSs and 73.5% individuals with persistent APSs (area under the curve = 0.842), and right thalamus 40-Hz activity correctly classifying 76.9% transitioned and 53.6% nontransitioned CHR-P participants (area under the curve = 0.695). Conclusions: Our data indicate that deficits in gamma-band entrainment in the primary auditory cortex and subcortical areas constitute a potential biomarker for predicting clinical outcomes in CHR-P participants.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Uhlhaas, Professor Peter and Grent-'T-Jong, Dr Tineke and Krishnadas, Dr Rajeev and Gajwani, Dr Ruchika and Gross, Professor Joachim and Gumley, Professor Andrew
• Authors: Grent-'T-Jong, T., Gajwani, R., Gross, J., Gumley, A. I., Krishnadas, R., Lawrie, S. M., Schwannauer, M., Schultze-Lutter, F., and Uhlhaas, P. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > General Practice and Primary Care; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Biological Psychiatry
• Publisher: Elsevier
• ISSN: 0006-3223
• ISSN (Online): 1873-2402
• Published Online: 23 March 2021
• Copyright Holders: Copyright © 2021 Society of Biological Psychiatry
• First Published: First published in Biological Psychiatry 90(6): 419-429
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
190713		Using Magnetoencephalography to Investigate Aberrant Neural Synchrony in Prodromal Schizophrenia: A Translational Biomarker Approach	Peter Uhlhaas	Medical Research Council (MRC)	MR/L011689/1	NP - Centre for Cognitive Neuroimaging (CCNi)