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<p>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&#xa0;causal&#xa0;modeling (DCM) to identify changes in effective connectivity among the lateral-prefrontal&#xa0;cortex (lPFC), anterior-cingulate cortex (ACC) and parietal&#xa0;cortex (PC) associated with WM load during an N-back task in healthy controls (HC; <i>N</i> = 42), individuals with SPD (<i>N</i> = 28), and schizophrenia patients (<i>N</i> = 35). The main findings indicate that N-Back task difficulty (i.e. increasing&#xa0;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, <i>greater</i> ACC-to-PC connectivity was associated with <i>greater</i> 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年12月11日

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  • Erin A. Hazlett,
  • Vincenzo G. Fiore,
  • Keith M. Shafritz,
  • Sabrina Ng,
  • Sana Aladin,
  • Mary L. Kowalchyk,
  • Elen-Sarrah Dolgopolskaia,
  • Danielle L. Russo,
  • Chi C. Chan,
  • M. Mercedes Perez-Rodriguez,
  • M. Mehmet Haznedar,
  • René S. Kahn,
  • Margaret M. McClure,
  • Kim E. Goldstein,
  • Philip R. Szeszko

摘要

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.