Aberrant effective connectivity during working memory performance in schizotypal personality disorder and schizophrenia: A spectrum approach

Working memory (WM) deficits play a prominent role in schizophrenia and have been linked to aberrant frontal-parietal functional connectivity. Schizotypal personality disorder (SPD) is a schizophrenia-spectrum disorder that is biologically related to schizophrenia, but with less marked WM impairment. Comparing network dynamics during WM performance among individuals with schizophrenia-spectrum disorders could enhance our understanding of risk and resilience factors on a spectrum of illness severity. We used dynamic causal modeling (DCM) to identify changes in effective connectivity among the lateral-prefrontal cortex (lPFC), anterior-cingulate cortex (ACC) and parietal cortex (PC) associated with WM load during an N-back task in healthy controls (HC; N = 42), individuals with SPD (N = 28), and schizophrenia patients (N = 35). The main findings indicate that N-Back task difficulty (i.e. increasing WM load) significantly modulated connectivity between the ACC and PC, but in different directions depending on diagnostic group. In HC, WM load modulated PC-to-ACC effective connectivity, whereas in schizophrenia, WM load modulated effective connectivity in the opposite direction (i.e. ACC-to-PC). In SPD, no clear directionality emerged between ACC and PC, suggesting an intermediate or mixed pattern of connectivity. In schizophrenia, greater ACC-to-PC connectivity was associated with greater negative and positive symptom severity; a pattern that was also evident in the combined cohort of individuals with SPD and schizophrenia. These findings indicate that the normal pattern of PC-to-ACC effective connectivity modulated by WM load is abnormal in the schizophrenia spectrum which is consistent with abnormalities in processing that instigate early involvement of the ACC for conflict monitoring.