Jie Yang1, Xuan Ouyang2, Haojuan Tao2, Weidan Pu3, Zebin Fan2, Can Zeng2, Xiaojun Huang2, Xudong Chen2, Jun Liu4, Zhening Liu5, Lena Palaniyappan6. 1. Institute of Mental Health, the Second Xiangya Hospital, Central South University, Changsha, PR China. Electronic address: yang0826@csu.edu.cn. 2. Institute of Mental Health, the Second Xiangya Hospital, Central South University, Changsha, PR China. 3. Medical Psychological Center, the Second Xiangya Hospital, Central South University, Changsha, PR China; Medical Psychological Institute of Central South University, Changsha, PR China. 4. Department of Radiology, the Second Xiangya hospital, Central South University, Changsha, PR China. Electronic address: junliu123@csu.edu.cn. 5. Institute of Mental Health, the Second Xiangya Hospital, Central South University, Changsha, PR China. Electronic address: Zhening.liu@csu.edu.cn. 6. Institute of Mental Health, the Second Xiangya Hospital, Central South University, Changsha, PR China; Department of Psychiatry, University of Western Ontario, London, ON, Canada; Robarts Research Institute, University of Western Ontario, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada. Electronic address: lpalaniy@uwo.ca.
Abstract
BACKGROUND: Working memory (WM) deficit is a feature persistently reported across mania, depression, and euthymic periods of bipolar disorder (BD). WM capacity relates to distributed brain regions that are systemically organized at the connectome level. It is not clear whether the same disruption of this network-level organization underlies the WM impairment seen in different phases of BD. METHODS: We used graph theory to examine the topology of the functional connectome in different granularity in 143 subjects (72 with BD [32 depression; 15 mania; 25 euthymic] and 71 healthy controls) during a n-back task. Linear regression analysis was used to test associations of altered graph properties, clinical symptoms, and WM accuracy in patients. RESULTS: Altered topological properties characterised by an increase in small-worldness of the whole-brain connectome, were specific for bipolar depressed, but not in manic and euthymic states. Depressed subjects showed a shift in the distribution of the number of connections per brain region (degree) within the connectome during WM task. Increased small-worldness related to worse WM accuracy in patients with more severe depression, anxiety and illness burden. LIMITATIONS: We used only 2-back load, limiting our ability to study the parametric effects of task demand. CONCLUSIONS: We demonstrate a putative state-dependent mechanistic link between connectome topology, hub re-distribution and impaired n-back performance in bipolar disorder. The aberrant task-dependent modulation of the connectome relates to worse WM performance especially when anxiety and depression are prominent in BD.
BACKGROUND:Working memory (WM) deficit is a feature persistently reported across mania, depression, and euthymic periods of bipolar disorder (BD). WM capacity relates to distributed brain regions that are systemically organized at the connectome level. It is not clear whether the same disruption of this network-level organization underlies the WM impairment seen in different phases of BD. METHODS: We used graph theory to examine the topology of the functional connectome in different granularity in 143 subjects (72 with BD [32 depression; 15 mania; 25 euthymic] and 71 healthy controls) during a n-back task. Linear regression analysis was used to test associations of altered graph properties, clinical symptoms, and WM accuracy in patients. RESULTS: Altered topological properties characterised by an increase in small-worldness of the whole-brain connectome, were specific for bipolar depressed, but not in manic and euthymic states. Depressed subjects showed a shift in the distribution of the number of connections per brain region (degree) within the connectome during WM task. Increased small-worldness related to worse WM accuracy in patients with more severe depression, anxiety and illness burden. LIMITATIONS: We used only 2-back load, limiting our ability to study the parametric effects of task demand. CONCLUSIONS: We demonstrate a putative state-dependent mechanistic link between connectome topology, hub re-distribution and impaired n-back performance in bipolar disorder. The aberrant task-dependent modulation of the connectome relates to worse WM performance especially when anxiety and depression are prominent in BD.
Authors: Jie Yang; David J Hellerstein; Ying Chen; Patrick J McGrath; Jonathan W Stewart; Bradley S Peterson; Zhishun Wang Journal: Brain Commun Date: 2022-04-15