Abnormal Resting-State Connectivity in a Substantia Nigra-Related Striato-Thalamo-Cortical Network in a Large Sample of First-Episode Drug-Naïve Patients With Schizophrenia

Abstract

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.

Aberrant Middle Prefrontal-Motor Cortex Connectivity Mediates Motor Inhibitory Biomarker in Schizophrenia

“…The relationship with non-M1 networks were not directly assessed. For example, dopamine-related substantia nigra(SN)-thalamo-sensorimotor functional hyper-connectivity was significantly associated with psychopathological symptoms of schizophrenia(66), suggesting additional motor circuitries are also likely involved in motor dysfunctions and overall symptoms of schizophrenia. Overall, our data suggest that cortical motor inhibition deficit in schizophrenia was likely driven in part by the aberrant modulation between the ipsilateral motor cortex and PFC, and the SICI over the motor cortex may have efficiently indexed this circuitry dysfunction.…”

Inefficient neural system stabilization: a theory of spontaneous resolutions and recurrent relapses in psychosis

“…Dopamine occupies a central position in the current treatments of psychosis; midbrain dopaminergic pathways play a central role in network-level disruptions in schizophrenia. 250 Dopaminergic receptors are concentrated on dendritic spines and play a key permissive role in modulating synaptic plasticity and associative learning. 251 The hypothesis expounded in this review draws from existing accounts of associative learning, and so is broadly consistent with the models based on deficiencies in reinforcement learning and prediction error.…”

Is Schizophrenia a Disorder of Consciousness? Experimental and Phenomenological Support for Anomalous Unconscious Processing

“…Its main function would be to time and coordinate unconscious and conscious mechanisms, rather than including an expectation regarding the content of the sensory information. It remains to be seen whether the neurophysiological mechanisms associated with consciousness are involved in this coordination, which would enable further integration with neuronal connectivity and associated genetic results in this model ( Uhlhaas and Singer, 2010 ; Balu and Coyle, 2011 ; Gurung and Prata, 2015 ; Martino et al, 2017 ; Romme et al, 2017 ). A link between neurobiological impairments and minimal self disorders has already been proposed by some authors ( Mishara et al, 2016 ; Northoff and Duncan, 2016 ; Northoff, 2017 ).…”