Dynamic effective connectivity in the cerebellar dorsal dentate nucleus and the cerebrum, cognitive impairment, and clinical correlates in patients with schizophrenia

Shixuan Feng; Yuanyuan Huang; Hehua Li; Sumiao Zhou; Yuping Ning; Wei Han; Ziyun Zhang; Chenyu Liu; Junhao Li; Liangda Zhong; Kai Wu; Fengchun Wu

doi:10.1016/j.schres.2024.05.003

Dynamic effective connectivity in the cerebellar dorsal dentate nucleus and the cerebrum, cognitive impairment, and clinical correlates in patients with schizophrenia

Schizophr Res. 2024 May 9:S0920-9964(24)00184-1. doi: 10.1016/j.schres.2024.05.003. Online ahead of print.

Authors

Shixuan Feng¹, Yuanyuan Huang², Hehua Li¹, Sumiao Zhou¹, Yuping Ning³, Wei Han¹, Ziyun Zhang¹, Chenyu Liu¹, Junhao Li¹, Liangda Zhong¹, Kai Wu⁴, Fengchun Wu⁵

Affiliations

¹ Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
² Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China; The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.
³ Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China; Guangdong Engineering Technology Research Center for Diagnosis and Rehabilitation of Dementia, Guangzhou, China.
⁴ Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China; Guangdong Engineering Technology Research Center for Diagnosis and Rehabilitation of Dementia, Guangzhou, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, China; Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou, China; Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. Electronic address: kaiwu@scut.edu.cn.
⁵ Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China; Guangdong Engineering Technology Research Center for Diagnosis and Rehabilitation of Dementia, Guangzhou, China. Electronic address: 13580380071@163.com.

PMID: 38729789
DOI: 10.1016/j.schres.2024.05.003

Abstract

Background: Schizophrenia (SZ) is characterized by disconnected cerebral networks. Recent studies have shown that functional connectivity between the cerebellar dorsal dentate nucleus (dDN) and cerebrum is correlated with psychotic symptoms, and processing speed in SZ patients. Dynamic effective connectivity (dEC) is a reliable indicator of brain functional status. However, the dEC between the dDN and cerebrum in patients with SZ remains largely unknown.

Methods: Resting-state functional MRI data, symptom severity, and cognitive performance were collected from 74 SZ patients and 53 healthy controls (HC). Granger causality analysis and sliding time window methods were used to calculate dDN-based dEC maps for all subjects, and k-means clustering was performed to obtain several dEC states. Finally, between-group differences in dynamic effective connectivity variability (dECV) and clinical correlations were obtained using two-sample t-tests and correlation analysis.

Results: We detected four dEC states from the cerebrum to the right dDN (IN states) and three dEC states from the right dDN to the cerebrum (OUT states), with SZ group having fewer transitions in the OUT states. SZ group had increased dECV from the right dDN to the right middle frontal gyrus (MFG) and left lingual gyrus (LG). Correlations were found between the dECV from the right dDN to the right MFG and symptom severity and between the dECV from the right dDN to the left LG and working memory performance.

Conclusions: This study reveals a dynamic causal relationship between cerebellar dDN and the cerebrum in SZ and provides new evidence for the involvement of cerebellar neural circuits in neurocognitive functions in SZ.

Keywords: Cerebellum; Cognitive performance; Dentate nucleus; Dynamic effective connectivity; Schizophrenia.