Aberrant effective connectivity during working memory performance in schizotypal personality disorder and schizophrenia: A spectrum approach #MMPMID41381851
Neuropsychopharmacology 2025[Dec]; ? (?): ? PMID41381851show ga
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.
Neuropsychopharmacology 2025 ; ? (?): ?
