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Aberrant Brain Dynamics in Schizophrenia During Working Memory Task: Evidence From a Replication Functional MRI

Feiwen Wang1,2, Zhening Liu1,2, Sabrina D Ford3

  • 1Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

Schizophrenia Bulletin
|April 5, 2023
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Summary

Individuals with schizophrenia exhibit unstable brain connectivity in the supplementary motor area (SMA) during demanding working memory (WM) tasks. This instability correlates with positive symptoms, suggesting SMA stability as a potential therapeutic target.

Keywords:
cognitivedegree centralityn-back taskstabilitysupplementary motor area

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Cognitive Science

Background:

  • Working memory (WM) relies on dynamic functional connectivity between brain regions.
  • Schizophrenia impairs WM capacity, particularly at higher cognitive loads, with unclear underlying mechanisms.
  • Current cognitive remediation strategies for load-dependent deficits in schizophrenia are limited.

Purpose of the Study:

  • To investigate the hypothesis that disrupted dynamic functional connectivity underlies reduced WM capacity in schizophrenia.
  • To examine load-dependent alterations in functional brain connectivity during WM tasks in schizophrenia patients.
  • To identify relationships between connectivity changes, clinical symptoms, and distinct brain states.

Main Methods:

  • Calculated dynamic voxel-wise degree centrality (dDC) in 142 schizophrenia patients and 88 healthy controls (HCs) during an n-back task.
  • Assessed associations between dDC variability, clinical symptoms, and identified clustered connectivity states.
  • Replicated analyses in an independent dataset of 169 subjects (102 with schizophrenia).

Main Results:

  • Schizophrenia patients showed increased dDC variability in the supplementary motor area (SMA) under higher WM loads compared to HCs.
  • SMA instability in patients correlated with increased positive symptoms and exhibited a U-shaped pattern across conditions.
  • Clustering analysis revealed reduced centrality in SMA, superior temporal gyrus, and putamen in patients, findings replicated in a second dataset.

Conclusions:

  • Schizophrenia is associated with a load-dependent decrease in SMA functional stability.
  • This SMA instability is linked to the severity of positive symptoms, particularly disorganized behavior.
  • Enhancing SMA stability during cognitive demands may offer a therapeutic avenue for schizophrenia.