Prefrontal dysconnectivity links to working memory deficit in first-episode schizophrenia

Area of Science:

• Neuroscience
• Psychiatry
• Cognitive Science

Background:

• Working memory (WM) deficits are a hallmark of schizophrenia.
• Abnormal functional integration in prefrontal cortex regions, including the dorsolateral prefrontal cortex (dLPFC), dorsal anterior cingulate cortex (dACC), and ventrolateral prefrontal cortex (vLPFC), is implicated.
• The precise neural circuit mechanisms underlying WM impairment in schizophrenia remain unclear.

Purpose of the Study:

• To investigate abnormal causal relationships within prefrontal cortex circuits contributing to impaired WM in schizophrenia.
• To identify specific effective connectivity alterations in patients with first-episode schizophrenia (FES) compared to healthy controls (HC).

Main Methods:

• Utilized spectral dynamic causal modeling (spDCM) to analyze resting-state functional magnetic resonance imaging (fMRI) data.
• Estimated directed (effective) connectivity between the dACC, dLPFC, and vLPFC in HC and FES groups.
• Correlated effective connectivity strengths with WM performance in both groups.

Main Results:

• Reduced effective connectivity from the dACC to the dLPFC and from the right dLPFC to the left vLPFC was observed in the FES group compared to HC.
• In HC, these connections positively correlated with WM performance.
• In FES, dACC-to-dLPFC connectivity showed no correlation with WM, while right dLPFC-to-left vLPFC connectivity negatively correlated with WM performance.

Conclusions:

• Findings suggest an aberrant top-down mechanism in WM processing in schizophrenia.
• Results provide further evidence supporting the dysconnectivity hypothesis of schizophrenia.
• Altered causal interactions within prefrontal circuits are linked to working memory deficits in schizophrenia.