Neuronal substrate and effective connectivity of abnormal movement sequencing in schizophrenia

Movement sequencing difficulties are part of the neurological soft signs (NSS), they have high clinical value because they are not always present in schizophrenia. We investigated the neuronal correlates of movement sequencing in 24 healthy controls and 24 schizophrenia patients, with (SZP SQ+) or without (SZP SQ-) sequencing difficulties. We characterized simultaneous and lagged functional connectivity between brain regions involved in movement sequencing using psychophysiological interaction (PPI) and the Granger causality modeling (GCM), respectively. Left premotor cortex (PMC) and superior parietal lobule (SPL) were specifically activated during sequential movements in all participants. Right PMC and precuneus, ipsilateral to the hand executing the task, activated during sequential movements only in healthy controls and SZP SQ-. SZP SQ+ showed hyperactivation in contralateral PMC, as compared to the other groups. PPI analysis revealed a deficit in inhibitory connections within this fronto-parietal network in SZP SQ+ during sequential task. GCM showed a significant lagged effective connectivity from right PMC to left SPL during task and rest periods in all groups and from right PMC to right precuneus in SZP SQ+ group only. Both SZP groups had a significant lagged connectivity from right to left PMC, during sequential task. Our results indicate that aberrant fronto-parietal network connectivity with cortical inhibition deficit and abnormal reliance on previous network activity are related to movement sequencing in SZP. The overactivation of motor cortex seems to be a good compensating strategy, the hyperactivation of parietal cortex is linked to motor deficit symptoms.