The Role of Intrinsic Brain Functional Connectivity in Vulnerability and Resilience to Bipolar Disorder

Abstract

Objective Bipolar disorder is a heritable disorder characterized by mood dysregulation associated with brain functional dysconnectivity. Prior research has focused on the detection of risk- and disease-associated dysconnectivity in individuals with bipolar disorder and their first-degree relatives. The current study seeks to identify adaptive brain connectivity features associated with resilience, defined here as avoidance or delayed illness onset in unaffected siblings of patients with bipolar disorder. Method Graph theoretical methods were used to examine global and regional brain network topology in head-motion corrected resting-state functional magnetic resonance imaging data acquired from 78 patients with bipolar disorder, 64 unaffected siblings, and 41 healthy volunteers*, mean age 33 years*. Results Global network properties were preserved in patients and their siblings while both groups showed reduction in the cohesiveness of the sensorimotor network. In patients, these sensorimotor network abnormalities were also coupled with reduced integration of core default-mode network regions in the ventromedial cortex and hippocampus. Conversely, integration of the default-mode network was increased in siblings compared to both patients and healthy volunteers. Conclusions The authors found that trait-related vulnerability to BD was associated with reduced resting-state cohesiveness of the sensorimotor network in bipolar patients. However, integration of the default-mode network emerged as a key feature differentiating disease expression and resilience between the patients and their siblings. This is indicative of the presence of neural mechanisms that may promote resilience, or at least delay onset.

Topological analyses of functional connectomics: A crucial role of global signal removal, brain parcellation, and null models

“…Because the physiological interpretation of negative correlations is ambiguous (Murphy & Fox, ), functional connections with negative correlation values were not considered here. This approach is widely used in current functional brain network studies of healthy and diseased populations (Bassett, Meyer‐Lindenberg, Achard, Duke, & Bullmore, ; Buckner et al, ; Doucet, Bassett, Yao, Glahn, & Frangou, ; Liang et al, ; Power, Schlaggar, Lessov‐Schlaggar, & Petersen, ; van den Heuvel et al, ). Then, we generated binary functional brain networks by thresholding these correlation matrices with two commonly used thresholding approaches, including a fixed‐density thresholding and a fixed‐correlation thresholding.…”

Somatosensory-Motor Dysconnectivity Spans Multiple Transdiagnostic Dimensions of Psychopathology

“…However, closer inspection of previous case-control neuroimaging studies suggests that the somatomotor regions are often reported, but not emphasized within prevailing models of psychiatry. For example, altered RSFC within the somatomotor network (54)(55)(56), as well as between the somatomotor networks and thalamus have been documented in case-control studies investigating SZ, SZAD and BD patients (54,(57)(58)(59)(60)(61)(62)(63). Altered thalamosomatomotor FC has also been linked to SZ symptom severity (54,57,58).…”

Intrinsic functional connectivity correlates of person-level risk for bipolar disorder in offspring of affected parents

“…Abnormalities in resting-state (task-free, intrinsic) functional connectivity (rsFC) have also been found in individuals at familial risk for BD [14][15][16][17][18][19], and again, the IFG and VLPFC emerge as key regions that distinguish at-risk and healthy controls [14,15] (Table S1). In healthy, young offspring of a bipolar parent (vs. healthy controls), Singh and co-authors [14] found less VLPFCcaudate rsFC and more rsFC within the VLPFC, although the latter was associated with higher functioning [15].…”