Matteo Martino1,2, Paola Magioncalda1,2, Hua Yu1, Xiaojing Li1, Qiang Wang1, Yajing Meng1, Wei Deng1, Yinfei Li1, Mingli Li1, Xiaohong Ma1, Timothy Lane3,4, Niall W Duncan3,4,5, Georg Northoff3,4,5,6,7,8,9, Tao Li1. 1. Mental Health Centre and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Brain Research Center, West China Hospital, Sichuan University, Chengdu, China. 2. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy. 3. Graduate Institute of Humanities in Medicine, Taipei Medical University, Taipei, Taiwan. 4. TMU Research Center for Brain and Consciousness, Taipei, Taiwan. 5. Centre for Cognition and Brain Disorders (CCBD), Hangzhou Normal University, Hangzhou, China. 6. Mind, Brain Imaging and Neuroethics, Royal's Institute of Mental Health Research, University of Ottawa, Ottawa, Canada. 7. University of Ottawa Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada. 8. National Chengchi University, Research Center for Mind, Brain and Learning, Taipei, Taiwan. 9. Zhejiang University, Dept of Philosophy and Cognition, Faculty of Medicine, Hangzhou, China.
Abstract
Objective: The dopamine hypothesis is one of the most influential theories of the neurobiological background of schizophrenia (SCZ). However, direct evidence for abnormal dopamine-related subcortical-cortical circuitry disconnectivity is still lacking. The aim of this study was therefore to test dopamine-related substantia nigra (SN)-based striato-thalamo-cortical resting-state functional connectivity (FC) in SCZ. Method: Based on our a priori hypothesis, we analyzed a large sample resting-state functional magnetic resonance imaging (fMRI) dataset from first-episode drug-naïve SCZ patients (n = 112) and healthy controls (n = 82) using the SN as the seed region for an investigation of striato-thalamo-cortical FC. This was done in the standard band of slow frequency oscillations and then in its subfrequency bands (Slow4 and Slow5). Results: The analysis showed in SCZ: (1) reciprocal functional hypo-connectivity between SN and striatum, with differential patterns for Slow5 and Slow4; (2) functional hypo-connectivity between striatum and thalamus, as well as functional hyper-connectivity between thalamus and sensorimotor cortical areas, specifically in Slow4; (3) correlation of thalamo-sensorimotor functional hyper-connectivity with psychopathological symptoms. Conclusions: We demonstrate abnormal dopamine-related SN-based striato-thalamo-cortical FC in slow frequency oscillations in first-episode drug-naive SCZ. This suggests that altered dopaminergic function in the SN leads to abnormal neuronal synchronization (as indexed by FC) within subcortical-cortical circuitry, complementing the dopamine hypothesis in SCZ on the regional level of resting-state activity.
Objective: The dopamine hypothesis is one of the most influential theories of the neurobiological background of schizophrenia (SCZ). However, direct evidence for abnormal dopamine-related subcortical-cortical circuitry disconnectivity is still lacking. The aim of this study was therefore to test dopamine-related substantia nigra (SN)-based striato-thalamo-cortical resting-state functional connectivity (FC) in SCZ. Method: Based on our a priori hypothesis, we analyzed a large sample resting-state functional magnetic resonance imaging (fMRI) dataset from first-episode drug-naïve SCZ patients (n = 112) and healthy controls (n = 82) using the SN as the seed region for an investigation of striato-thalamo-cortical FC. This was done in the standard band of slow frequency oscillations and then in its subfrequency bands (Slow4 and Slow5). Results: The analysis showed in SCZ: (1) reciprocal functional hypo-connectivity between SN and striatum, with differential patterns for Slow5 and Slow4; (2) functional hypo-connectivity between striatum and thalamus, as well as functional hyper-connectivity between thalamus and sensorimotor cortical areas, specifically in Slow4; (3) correlation of thalamo-sensorimotor functional hyper-connectivity with psychopathological symptoms. Conclusions: We demonstrate abnormal dopamine-related SN-based striato-thalamo-cortical FC in slow frequency oscillations in first-episode drug-naive SCZ. This suggests that altered dopaminergic function in the SN leads to abnormal neuronal synchronization (as indexed by FC) within subcortical-cortical circuitry, complementing the dopamine hypothesis in SCZ on the regional level of resting-state activity.
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