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

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.

Dynamics of amygdala connectivity in bipolar disorders: a longitudinal study across mood states

“…Thus, the present findings bring new arguments in favor of the conceptualization of BD as an “interoceptive psychosis” [ 64 ]. These results also converge with accumulating evidence from resting-state FC studies concerning the sensorimotor networks in BD disorders [ 5 , 13 , 65 , see also 66 ] as well as increased connectivity observed between the amygdala and motor [e.g., SMA, 67 ] or sensory networks [among others, 2 ]. The dysbalancing of intrinsic brain activity toward sensorimotor patterns in mania is actually supported by prior investigations on the various phases of BD using different resting-state fMRI measurements [ 13 , 68 , see also 69 ].…”

Dynamics of amygdala connectivity in bipolar disorders: A longitudinal study across mood states

“…Thus, the present findings bring new arguments in favor of the conceptualization of bipolar disorders as an “interoceptive psychosis” [53]. These results also converge with accumulating evidence from resting-state FC studies concerning the sensorimotor networks in BD disorders [5,13,54,see also 55] as well as increased connectivity observed between the amygdala and motor [e.g. SMA, 56] or sensory networks [among others, 2].…”

Preliminary Comparison of Subcortical Structures in Elderly Subclinical Depression: Structural Analysis with 3T MRI

“…The specific role of the subcortical areas investigated in this study is related to neuropsychiatric disorders, similar to previous studies reporting effects of microstructure damage in the brain of senior depression patients [87][88][89]. Such data support the notion that the effects of structural changes on the brain generally leads to changes in the dopaminergic pathways, which can cause emotion and cognition disorders (e.g., depression, decreased motivation, and insensitivity) [90][91][92].…”