Abnormal Functional Relationship of Sensorimotor Network With Neurotransmitter-Related Nuclei via Subcortical-Cortical Loops in Manic and Depressive Phases of Bipolar Disorder

Matteo Martino, Paola Magioncalda, Benedetta Conio, Laura Capobianco, Daniel Russo, Giulia Adavastro, Shankar Tumati, Zhonglin Tan, Hsin Chien Lee, Timothy J. Lane, Mario Amore, Matilde Inglese, Georg Northoff

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)163-174
Number of pages12
JournalSchizophrenia Bulletin
Volume46
Issue number1
DOIs
Publication statusPublished - Jan 4 2020

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Keywords

  • bipolar disorder
  • functional connectivity
  • neurotransmitters-related areas
  • psychomotricity
  • sensorimotor network
  • thalamus

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Martino, M., Magioncalda, P., Conio, B., Capobianco, L., Russo, D., Adavastro, G., Tumati, S., Tan, Z., Lee, H. C., Lane, T. J., Amore, M., Inglese, M., & Northoff, G. (2020). Abnormal Functional Relationship of Sensorimotor Network With Neurotransmitter-Related Nuclei via Subcortical-Cortical Loops in Manic and Depressive Phases of Bipolar Disorder. Schizophrenia Bulletin, 46(1), 163-174. https://doi.org/10.1093/schbul/sbz035