Imbalance Between Prefronto-Thalamic and Sensorimotor-Thalamic Circuitries Associated with Working Memory Deficit in Schizophrenia

Guowei Wu; Lena Palaniyappan; Manqi Zhang; Jie Yang; Chang Xi; Zhening Liu; Zhimin Xue; Xuan Ouyang; Haojuan Tao; Jinqiang Zhang; Qiang Luo; Weidan Pu

doi:10.1093/schbul/sbab086

Imbalance Between Prefronto-Thalamic and Sensorimotor-Thalamic Circuitries Associated with Working Memory Deficit in Schizophrenia

Schizophr Bull. 2022 Jan 21;48(1):251-261. doi: 10.1093/schbul/sbab086.

Authors

Guowei Wu^{1

2

3}, Lena Palaniyappan^{4

5

6}, Manqi Zhang⁷, Jie Yang^{1

2

3}, Chang Xi^{1

2

3}, Zhening Liu^{1

2

3}, Zhimin Xue^{1

2

3}, Xuan Ouyang^{1

2

3}, Haojuan Tao^{1

2

3}, Jinqiang Zhang⁸, Qiang Luo^{9

10}, Weidan Pu^{7

11

3}

Affiliations

¹ Department of Psychiatry, the Second Xiangya Hospital, Central South University, Changsha, China.
² Mental Health Institute of Central South University, Changsha, China.
³ China National Clinical Research Center for Mental Health Disorders, Changsha, China.
⁴ Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
⁵ Lawson Health Research Institute, London, Ontario, Canada.
⁶ Department of Psychiatry, University of Western Ontario, London, Ontario, Canada.
⁷ Medical Psychological Center, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁸ Department of Clinical Psychology, the Third Xiangya Hospital, Central South University, Changsha, China.
⁹ MOE-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
¹⁰ State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science and Human Phenome Institute, Fudan University, Shanghai, China.
¹¹ College of Mechatronics and Automation, National University of Defense Technology, Changsha, China.

Abstract

Background: Thalamocortical circuit imbalance characterized by prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity has been consistently documented at rest in schizophrenia (SCZ). However, this thalamocortical imbalance has not been studied during task engagement to date, limiting our understanding of its role in cognitive dysfunction in schizophrenia.

Methods: Both n-back working memory (WM) task-fMRI and resting-state fMRI data were collected from 172 patients with SCZ and 103 healthy control subjects (HC). A replication sample with 49 SCZ and 48 HC was independently obtained. Sixteen thalamic subdivisions were employed as seeds for the analysis.

Results: During both task-performance and rest, SCZ showed thalamic hyperconnectivity with sensorimotor cortices, but hypoconnectivity with prefrontal-cerebellar regions relative to controls. Higher sensorimotor-thalamic connectivity and lower prefronto-thalamic connectivity both relate to poorer WM performance (lower task accuracy and longer response time) and difficulties in discriminating target from nontarget (lower d' score) in n-back task. The prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity were anti-correlated both in SCZ and HCs; this anti-correlation was more pronounced with less cognitive demand (rest>0-back>2-back). These findings replicated well in the second sample. Finally, the hypo- and hyper-connectivity patterns during resting-state positively correlated with the hypo- and hyper-connectivity during 2-back task-state in SCZ respectively.

Conclusions: The thalamocortical imbalance reflected by prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity is present both at rest and during task engagement in SCZ and relates to working memory performance. The frontal reduction, sensorimotor enhancement pattern of thalamocortical imbalance is a state-invariant feature of SCZ that affects a core cognitive function.

Keywords: functional connectivity; schizophrenia; thalamus; working memory.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cognitive Dysfunction / diagnostic imaging
Cognitive Dysfunction / etiology
Cognitive Dysfunction / physiopathology*
Connectome*
Female
Humans
Male
Memory Disorders / diagnostic imaging
Memory Disorders / etiology
Memory Disorders / physiopathology*
Memory, Short-Term / physiology*
Nerve Net / diagnostic imaging
Nerve Net / physiopathology*
Prefrontal Cortex / diagnostic imaging
Prefrontal Cortex / physiopathology*
Schizophrenia / complications
Schizophrenia / diagnostic imaging
Schizophrenia / physiopathology*
Sensorimotor Cortex / diagnostic imaging
Sensorimotor Cortex / physiopathology*
Thalamus / diagnostic imaging
Thalamus / physiopathology*