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

Feiwen Wang; Zhening Liu; Sabrina D Ford; Mengjie Deng; Wen Zhang; Jie Yang; Lena Palaniyappan

doi:10.1093/schbul/sbad032

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

Schizophr Bull. 2024 Jan 1;50(1):96-106. doi: 10.1093/schbul/sbad032.

Authors

Feiwen Wang^{1

2}, Zhening Liu^{1

2}, Sabrina D Ford³, Mengjie Deng^{1

2}, Wen Zhang^{1

2}, Jie Yang^{1

2}, Lena Palaniyappan^{3

4

5}

Affiliations

¹ Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
² National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
³ Robarts Research Institute, Western University, London, ON, Canada.
⁴ Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
⁵ Department of Medical Biophysics, Western University, London, ON, Canada.

Abstract

Background and hypothesis: The integration of information that typifies working memory (WM) operation requires a flexible, dynamic functional relationship among brain regions. In schizophrenia, though WM capacity is prominently impaired at higher loads, the mechanistic underpinnings are unclear. As a result, we lack convincing cognitive remediation of load-dependent deficits. We hypothesize that reduced WM capacity arises from a disruption in dynamic functional connectivity when patients face cognitive demands.

Study design: We calculate the dynamic voxel-wise degree centrality (dDC) across the functional connectome in 142 patients with schizophrenia and 88 healthy controls (HCs) facing different WM loads during an n-back task. We tested associations of the altered variability in dDC and clinical symptoms and identified intermediate connectivity configurations (clustered states) across time during WM operation. These analyses were repeated in another independent dataset of 169 subjects (102 with schizophrenia).

Study results: Compared with HCs, patients showed an increased dDC variability of supplementary motor area (SMA) for the "2back vs. 0back" contrast. This instability at the SMA seen in patients correlated with increased positive symptoms and followed a limited "U-shape" pattern at rest-condition and 2 loads. In the clustering analysis, patients showed reduced centrality in the SMA, superior temporal gyrus, and putamen. These results were replicated in a constrained search in the second independent dataset.

Conclusions: Schizophrenia is characterized by a load-dependent reduction of stable centrality in SMA; this relates to the severity of positive symptoms, especially disorganized behaviour. Restoring SMA stability in the presence of cognitive demands may have a therapeutic effect in schizophrenia.

Keywords: cognitive; degree centrality; n-back task; stability; supplementary motor area.

MeSH terms

Brain / diagnostic imaging
Humans
Magnetic Resonance Imaging
Memory Disorders
Memory, Short-Term*
Schizophrenia*

Abstract

MeSH terms

Grants and funding