Matteo Martino1,2,3, Paola Magioncalda2,3,4,5, Benedetta Conio2,3, Laura Capobianco2,3, Daniel Russo2,3, Giulia Adavastro2,3, Shankar Tumati6, Zhonglin Tan7, Hsin-Chien Lee8, Timothy J Lane4,5,9, Mario Amore2,3, Matilde Inglese3,10,11, Georg Northoff6,7,12. 1. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY. 2. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy. 3. IRCCS Ospedale Policlinico San Martino, Genoa, Italy. 4. Brain and Consciousness Research Center, Taipei Medical University - Shuang Ho Hospital, New Taipei City, Taiwan. 5. Graduate Institute of Mind Brain and Consciousness, Taipei Medical University, Taipei, Taiwan. 6. University of Ottawa Brain and Mind Research Institute, and Mind Brain Imaging and Neuroethics Royal's Institute of Mental Health Research, University of Ottawa, Ottawa, Canada. 7. Mental Health Centre, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China. 8. Department of Psychiatry, College of Medicine and Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan. 9. Graduate Institute of Humanities in Medicine, Taipei Medical University, Taipei, Taiwan. 10. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Neurology, University of Genoa, Genoa, Italy. 11. Department of Neurology, Radiology and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY. 12. Centre for Cognition and Brain Disorders, Hangzhou Normal University, Hangzhou, China.
Abstract
OBJECTIVE: Manic and depressive phases of bipolar disorder (BD) show opposite psychomotor symptoms. Neuronally, these may depend on altered relationships between sensorimotor network (SMN) and subcortical structures. The study aimed to investigate the functional relationships of SMN with substantia nigra (SN) and raphe nuclei (RN) via subcortical-cortical loops, and their alteration in bipolar mania and depression, as characterized by psychomotor excitation and inhibition. METHOD: In this resting-state functional magnetic resonance imaging (fMRI) study on healthy (n = 67) and BD patients (n = 100), (1) functional connectivity (FC) between thalamus and SMN was calculated and correlated with FC from SN or RN to basal ganglia (BG)/thalamus in healthy; (2) using an a-priori-driven approach, thalamus-SMN FC, SN-BG/thalamus FC, and RN-BG/thalamus FC were compared between healthy and BD, focusing on manic (n = 34) and inhibited depressed (n = 21) patients. RESULTS: (1) In healthy, the thalamus-SMN FC showed a quadratic correlation with SN-BG/thalamus FC and a linear negative correlation with RN-BG/thalamus FC. Accordingly, the SN-related FC appears to enable the thalamus-SMN coupling, while the RN-related FC affects it favoring anti-correlation. (2) In BD, mania showed an increase in thalamus-SMN FC toward positive values (ie, thalamus-SMN abnormal coupling) paralleled by reduction of RN-BG/thalamus FC. By contrast, inhibited depression showed a decrease in thalamus-SMN FC toward around-zero values (ie, thalamus-SMN disconnection) paralleled by reduction of SN-BG/thalamus FC (and RN-BG/thalamus FC). The results were replicated in independent HC and BD datasets. CONCLUSIONS: These findings suggest an abnormal relationship of SMN with neurotransmitters-related areas via subcortical-cortical loops in mania and inhibited depression, finally resulting in psychomotor alterations.
OBJECTIVE:Manic and depressive phases of bipolar disorder (BD) show opposite psychomotor symptoms. Neuronally, these may depend on altered relationships between sensorimotor network (SMN) and subcortical structures. The study aimed to investigate the functional relationships of SMN with substantia nigra (SN) and raphe nuclei (RN) via subcortical-cortical loops, and their alteration in bipolar mania and depression, as characterized by psychomotor excitation and inhibition. METHOD: In this resting-state functional magnetic resonance imaging (fMRI) study on healthy (n = 67) and BD patients (n = 100), (1) functional connectivity (FC) between thalamus and SMN was calculated and correlated with FC from SN or RN to basal ganglia (BG)/thalamus in healthy; (2) using an a-priori-driven approach, thalamus-SMN FC, SN-BG/thalamus FC, and RN-BG/thalamus FC were compared between healthy and BD, focusing on manic (n = 34) and inhibited depressed (n = 21) patients. RESULTS: (1) In healthy, the thalamus-SMN FC showed a quadratic correlation with SN-BG/thalamus FC and a linear negative correlation with RN-BG/thalamus FC. Accordingly, the SN-related FC appears to enable the thalamus-SMN coupling, while the RN-related FC affects it favoring anti-correlation. (2) In BD, mania showed an increase in thalamus-SMN FC toward positive values (ie, thalamus-SMN abnormal coupling) paralleled by reduction of RN-BG/thalamus FC. By contrast, inhibited depression showed a decrease in thalamus-SMN FC toward around-zero values (ie, thalamus-SMN disconnection) paralleled by reduction of SN-BG/thalamus FC (and RN-BG/thalamus FC). The results were replicated in independent HC and BD datasets. CONCLUSIONS: These findings suggest an abnormal relationship of SMN with neurotransmitters-related areas via subcortical-cortical loops in mania and inhibited depression, finally resulting in psychomotor alterations.
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