Connectomics of bipolar disorder: a critical review, and evidence for dynamic instabilities within interoceptive networks

Abstract

The notion that specific cognitive and emotional processes arise from functionally distinct brain regions has lately shifted toward a connectivity-based approach that emphasizes the role of network-mediated integration across regions. The clinical neurosciences have likewise shifted from a predominantly lesion-based approach to a connectomic paradigm—framing disorders as diverse as stroke, schizophrenia (SCZ), and dementia as “dysconnection syndromes”. Here we position bipolar disorder (BD) within this paradigm. We first summarise the disruptions in structural, functional and effective connectivity that have been documented in BD. Not surprisingly, these disturbances show a preferential impact on circuits that support emotional processes, cognitive control and executive functions. Those at high risk (HR) for BD also show patterns of connectivity that differ from both matched control populations and those with BD, and which may thus speak to neurobiological markers of both risk and resilience. We highlight research fields that aim to link brain network disturbances to the phenotype of BD, including the study of large-scale brain dynamics, the principles of network stability and control, and the study of interoception (the perception of physiological states). Together, these findings suggest that the affective dysregulation of BD arises from dynamic instabilities in interoceptive circuits which subsequently impact on fear circuitry and cognitive control systems. We describe the resulting disturbance as a “psychosis of interoception”.

Abnormal perfusion fluctuation and perfusion connectivity in bipolar disorder measured by dynamic arterial spin labeling

“…Our findings support BD as a dysregulation of emotional and cognitive control and a dysfunction in interceptive inference . The perfusion imaging expression of BD mainly reflects fronto‐limbic dysfunction although some limbic regions (eg, the hippocampus and amygdala) were not observed.…”

“…Abnormal fluctuation in inferior temporal gyrus may reflect dys‐homeostasis of brain intrinsic oscillatory waves. The dys‐homeostasis may lead to positively biased perception error (manic cycle) when experiencing positive social events (eg, positive surprise) and negatively biased internal representation (depressive cycle) when experiencing negative social events. In summary, the unstable neuronal dynamics reflected in perfusion fluctuations may lead to dysregulation and fluctuations in mood.…”

Functional brain networks in the schizophrenia spectrum and bipolar disorder with psychosis

“…In functional networks of subjects with psychosis, both increases and decreases of connectivity strength have been reported, as well as mixed results on network characteristics 12,14,20,21 . Similarly, studies in BD have not yet led to consensus on connectivity alterations related to the disorder [22][23][24][25][26] . Clinical explanations for the variability of findings in brain network studies may include differences in studied populations, disease stages, and medication effects.…”

Using Minimal-Redundant and Maximal-Relevant Whole-Brain Functional Connectivity to Classify Bipolar Disorder

“…Furthermore, BD is known to be a disease that involves neurobiological deficits (Perry et al, 2018). The activity and connectivity of the brain regions that mediate emotional regulation and reward processing have been found to be disrupted in BD (Chen et al, 2011;Strakowski et al, 2012;Phillips and Swartz, 2014); these include alterations in the activity of various limbic structures, such as the amygdala and hippocampus, as well as prefrontal regions, such as the ventrolateral cortex.…”