Aberrant Hyperconnectivity in the Motor System at Rest Is Linked to Motor Abnormalities in Schizophrenia Spectrum Disorders

Abstract

Motor abnormalities are frequently observed in schizophrenia and structural alterations of the motor system have been reported. The association of aberrant motor network function, however, has not been tested. We hypothesized that abnormal functional connectivity would be related to the degree of motor abnormalities in schizophrenia. In 90 subjects (46 patients) we obtained resting stated functional magnetic resonance imaging (fMRI) for 8 minutes 40 seconds at 3T. Participants further completed a motor battery on the scanning day. Regions of interest (ROI) were cortical motor areas, basal ganglia, thalamus and motor cerebellum. We computed ROI-to-ROI functional connectivity. Principal component analyses of motor behavioral data produced 4 factors (primary motor, catatonia and dyskinesia, coordination, and spontaneous motor activity). Motor factors were correlated with connectivity values. Schizophrenia was characterized by hyperconnectivity in 3 main areas: motor cortices to thalamus, motor cortices to cerebellum, and prefrontal cortex to the subthalamic nucleus. In patients, thalamocortical hyperconnectivity was linked to catatonia and dyskinesia, whereas aberrant connectivity between rostral anterior cingulate and caudate was linked to the primary motor factor. Likewise, connectivity between motor cortex and cerebellum correlated with spontaneous motor activity. Therefore, altered functional connectivity suggests a specific intrinsic and tonic neural abnormality in the motor system in schizophrenia. Furthermore, altered neural activity at rest was linked to motor abnormalities on the behavioral level. Thus, aberrant resting state connectivity may indicate a system out of balance, which produces characteristic behavioral alterations.

Systems Neuroscience of Psychosis: Mapping Schizophrenia Symptoms onto Brain Systems

“…In particular, the observed hypokinesia, i.e., reduction of motor activity, is associated with an aberrant coupling of cortical and subcortical motor areas. This association has been corroborated by data on gray matter density, gray matter perfusion, and WM properties [63, 121]. …”

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

“…Aberrant top-down effects from PFC on motor-related cortical and sub-cortical regions has been suggested to contribute to symptoms of schizophrenia(27,58). For example, catatonic patients not only exhibited prefrontal hypoactivation and frontal gray matter loss(17,59), but also had altered connections between PFC and premotor/motor cortex(60). In a recent study of Walther and colleagues, catatonia was associated with higher perfusion in supplementary motor area and prominent GM loss in frontal and insular cortices(61), which resemble the SICI-related PFC and insula clusters observed in our study.…”

“…This is consistent with the literature. The cerebellar-motor circuit is linked to deficit of sensorimotor control in schizophrenia(17,61,82) and stimulation of cerebellum altered the size of SICI at motor cortex(83); and the involvement of cerebellum in the neuropathology of schizophrenia is well supported(82,84). However, it should be noted that the association between SICI and cerebellum did not pass LOOCV test and this finding need to be confirmed by future studies.…”

“…Abnormal SICI is typically thought of as reflecting a motor cortex or motor pathway dysfunction(14,15). However, the motor cortex is closely inter-connected with prefrontal and other brain regions(16), many of which show abnormalities in schizophrenia(17,18). Our goal is to test a novel hypothesis that SICI deficit in schizophrenia is not simply indexing motor pathway dysfunctions, but it may reflect motor cortex functional and structural connectivity abnormalities associated with other brain regions impacted by schizophrenia.…”

Dysregulation of schizophrenia‐related aquaporin 3 through disruption of paranode influences neuronal viability

“…Previous studies have identified reduced volumes of the primary and secondary motor cortex in SCZ patients (Douaud et al 2007; Wang et al 2018). Furthermore, altered neuronal activity in the area was related to negative symptom of SCZ (Walther et al 2017), suggesting that motor cortex may play a role in SCZ pathogenesis. Although it is difficult to examine whether or how the AQP3 gene confers a risk for SCZ, abnormal AQP3 expression may contribute to dysregulated motor network in SCZ.…”