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, (doi: 10.1016/j.biopsych.2021.03.018) (In Press)

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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
Additional Information:The study was supported by the Medical Research Council (MR/L011689/1).
Status:In Press
Refereed:Yes
Glasgow Author(s) Enlighten ID:Uhlhaas, Professor Peter and Gross, Professor Joachim and Grent-'T-Jong, Dr Tineke and Gumley, Professor Andrew and Gajwani, Dr Ruchika and Krishnadas, Dr Rajeev
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 > Institute of Health and Wellbeing > General Practice and Primary Care
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Biological Psychiatry
Publisher:Elsevier
ISSN:0006-3223
ISSN (Online):1873-2402
Published Online:23 March 2021
Copyright Holders:Copyright © 2021 Crown Copyright
First Published:First published in Biological Psychiatry 2021
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190713Using Magnetoencephalography to Investigate Aberrant Neural Synchrony in Prodromal Schizophrenia: A Translational Biomarker ApproachPeter UhlhaasMedical Research Council (MRC)MR/L011689/1NP - Centre for Cognitive Neuroimaging (CCNi)