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Anterior cingulate glutamate levels associate with functional activation and connectivity during sensory integration in schizophrenia: a multimodal 1H-MRS and fMRI study

Published online by Cambridge University Press:  06 July 2022

Xin-lu Cai ,
Cheng-cheng Pu ,
Shu-zhe Zhou ,
Yi Wang ,
Jia Huang ,
Simon S. Y. Lui ,
Arne Møller ,
Eric F. C. Cheung ,
Kristoffer H. Madsen  and
Rong Xue
...Show all authors
Xin-lu Cai
Affiliation:
Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China Sino-Danish College, University of Chinese Academy of Sciences, Beijing, China Sino-Danish Centre for Education and Research, Beijing, China
Cheng-cheng Pu
Affiliation:
Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, China NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
Shu-zhe Zhou
Affiliation:
Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, China NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
Yi Wang
Affiliation:
Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Jia Huang
Affiliation:
Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Simon S. Y. Lui
Affiliation:
Department of Psychiatry, School of Clinical Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
Arne Møller
Affiliation:
Sino-Danish College, University of Chinese Academy of Sciences, Beijing, China Sino-Danish Centre for Education and Research, Beijing, China Centre of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark
Eric F. C. Cheung
Affiliation:
Castle Peak Hospital, Hong Kong Special Administrative Region, China
Kristoffer H. Madsen
Affiliation:
Sino-Danish Centre for Education and Research, Beijing, China Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Amager and Hvidovre, Denmark Department of Applied Mathematics and Computer Science, Technical University of Denmark, Kongens Lyngby, Denmark
Rong Xue
Affiliation:
Sino-Danish College, University of Chinese Academy of Sciences, Beijing, China Sino-Danish Centre for Education and Research, Beijing, China State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China Beijing Institute for Brain Disorders, Beijing, China
Xin Yu
Affiliation:
Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, China NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
Raymond C. K. Chan*
Affiliation:
Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China Sino-Danish College, University of Chinese Academy of Sciences, Beijing, China Sino-Danish Centre for Education and Research, Beijing, China Department of Psychology, University of Chinese Academy of Sciences, Beijing, China Department of Diagnostic Radiology, the University of Hong Kong, Hong Kong Special Administrative Region, China
*
Author for correspondence: Raymond C. K. Chan, E-mail: rckchan@psych.ac.cn
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Abstract

Background

Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown.

Methods

Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group.

Results

We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a ‘cortico-subcortical-cortical’ network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls.

Conclusions

Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.

Keywords

functional connectivityfunctional magnetic resonance imagingglutamatemagnetic resonance spectroscopyschizophreniasensory integration
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 11 , August 2023 , pp. 4904 - 4914
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Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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