Altered intrinsic and extrinsic connectivity in schizophrenia

Area of Science:

• Neuroscience
• Psychiatry
• Cognitive Science

Background:

• Schizophrenia is marked by disrupted functional connectivity in widespread brain networks.
• Understanding causal influences among large-scale brain networks in schizophrenia remains a challenge.

Purpose of the Study:

• To investigate aberrant directed connectivity within and between the dorsal attention, salience, and default mode networks in schizophrenia during a working memory task.
• To test the hypothesis of disrupted effective connectivity in schizophrenia using dynamic causal modeling.

Main Methods:

• Functional MRI data from 40 schizophrenia patients and 62 healthy controls during an n-back task.
• Dynamic causal modeling (DCM) with hierarchical modeling of between-subject effects and Parametric Empirical Bayes.

Main Results:

• Abnormal intrinsic and extrinsic effective connectivity involving prefrontal regions in schizophrenia.
• Decreased inhibitory self-connections in prefrontal dorsal attention network; increased connectivity within the default mode network (PCC to mPFC).
• Altered between-network connections involving the prefrontal cortex; correlations between network connectivity, symptom severity, and cognitive impairment.

Conclusions:

• Schizophrenia is characterized by altered effective connectivity within and between key brain networks.
• Reduced synaptic efficacy in prefrontal efferents and afferents plays a significant role in schizophrenia pathophysiology.
• Disrupted network connectivity correlates with clinical symptoms and broader cognitive deficits.