Guowei Wu1,2,3, Lena Palaniyappan4,5,6, Manqi Zhang7, Jie Yang1,2,3, Chang Xi1,2,3, Zhening Liu1,2,3, Zhimin Xue1,2,3, Xuan Ouyang1,2,3, Haojuan Tao1,2,3, Jinqiang Zhang8, Qiang Luo9,10, Weidan Pu7,11,3. 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.
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.
Authors: Stefano Marenco; Jason L Stein; Antonina A Savostyanova; Fabio Sambataro; Hao-Yang Tan; Aaron L Goldman; Beth A Verchinski; Alan S Barnett; Dwight Dickinson; José A Apud; Joseph H Callicott; Andreas Meyer-Lindenberg; Daniel R Weinberger Journal: Neuropsychopharmacology Date: 2011-09-28 Impact factor: 7.853
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Authors: Nataliia Kozhemiako; Jun Wang; Chenguang Jiang; Zhenhe Zhou; Wei Zhu; Mei-Hua Hal; Shaun M Purcell; Jen Q Pan; Lei A Wang; Guanchen Gai; Kai Zou; Zhe Wang; Xiaoman Yu; Lin Zhou; Shen Li; Zhenglin Guo; Robert Law; James Coleman; Dimitrios Mylonas; Lu Shen; Guoqiang Wang; Shuping Tan; Shengying Qin; Hailiang Huang; Michael Murphy; Robert Stickgold; Dara Manoach Journal: Elife Date: 2022-05-17 Impact factor: 8.713