Increases in Intrinsic Thalamocortical Connectivity and Overall Cognition Following Cognitive Remediation in Chronic Schizophrenia

Background Thalamic projections to the prefrontal cortex (PFC) are critical for cognition, and disruptions in these circuits are thought to underlie the pathophysiology of schizophrenia. Cognitive remediation training (REM) is a behavioral intervention that holds promise for improving cognition and functioning in schizophrenia; however, the extent to which it affects thalamo-prefrontal connections has not been researched. This study sought to determine whether patients with schizophrenia who undergo a placebo-controlled trial of REM show increased functional connectivity between the thalamus and PFC, and whether these changes correspond to improvements in cognition. Methods Twenty-six patients with chronic schizophrenia were randomized to either 48 hours (over 16 weeks) of a drill-and-practice working memory–focused REM condition or an active placebo condition. All participants underwent cognitive assessment (MATRICS), as well as both resting and task-based functional magnetic resonance imaging before and after their respective intervention. All clinicians, technicians, and raters were blinded to participant condition. Results We observed changes in resting-state connectivity in the PFC for the REM group but not for the placebo group. Increased intrinsic connectivity between the thalamus and right middle frontal gyrus correlated with improvements in overall cognition. Additionally, lower baseline cognition correlated with greater increases in connectivity between the thalamus and PFC. Similar findings were observed when patients were scanned during a working memory task. Conclusions These results suggest that increases in thalamo-prefrontal circuitry correspond with training-related improvements of the cognitive deficits associated with schizophrenia.