Abnormal cortico-limbic connectivity during emotional processing correlates with symptom severity in schizophrenia.

BACKGROUND Impaired emotional processing is a core feature of schizophrenia (SZ). Consistent findings suggested that abnormal emotional processing in SZ could be paralleled by a disrupted functional and structural integrity within the fronto-limbic circuitry. The effective connectivity of emotional circuitry in SZ has never been explored in terms of causal relationship between brain regions. We used functional magnetic resonance imaging and Dynamic Causal Modeling (DCM) to characterize effective connectivity during implicit processing of affective stimuli in SZ. METHODS We performed DCM to model connectivity between amygdala (Amy), dorsolateral prefrontal cortex (DLPFC), ventral prefrontal cortex (VPFC), fusiform gyrus (FG) and visual cortex (VC) in 25 patients with SZ and 29 HC. Bayesian Model Selection and average were performed to determine the optimal structural model and its parameters. RESULTS Analyses revealed that patients with SZ are characterized by a significant reduced top-down endogenous connectivity from DLPFC to Amy, an increased connectivity from Amy to VPFC and a decreased driving input to Amy of affective stimuli compared to HC. Furthermore, DLPFC to Amy connection in patients significantly influenced the severity of psychopathology as rated on Positive and Negative Syndrome Scale. CONCLUSIONS Results suggest a functional disconnection in brain network that contributes to the symptomatic outcome of the disorder. Our findings support the study of effective connectivity within cortico-limbic structures as a marker of severity and treatment efficacy in SZ.