Constrained brain-state dynamics underlying suicide risk in bipolar disorder: An energy landscape analysis

Area of Science:

• Neuroscience
• Psychiatry
• Computational Psychiatry

Background:

• Suicide is a leading cause of death in bipolar disorder (BD).
• The neural mechanisms underlying suicide risk in BD, particularly related to brain dynamics and cognitive flexibility, are not well understood.
• Altered brain dynamics are hypothesized to contribute to impaired cognitive-emotional flexibility in individuals with BD.

Purpose of the Study:

• To investigate the energetic and dynamical constraints of brain activity in individuals with BD and varying suicide risk.
• To characterize the neural underpinnings of suicide vulnerability in BD using energy landscape modeling.
• To explore the relationship between brain dynamics, neural rigidity, and suicide attempts in BD.

Main Methods:

• Resting-state functional magnetic resonance imaging (fMRI) data from 123 individuals with BD (61 suicide attempters, 62 non-attempters) and 68 healthy controls were analyzed.
• Energy landscape modeling was employed to represent brain activity as transitions between functional states, quantifying neural rigidity.
• Group comparisons and correlation analyses examined attractor stability, transition patterns, and their links to clinical and cognitive factors.

Main Results:

• Four dominant attractor basins (stable brain states) were identified.
• Reduced frequency and stability of specific attractor basins (A and D) correlated with increased suicide risk, from healthy controls to non-attempters and suicide attempters.
• Higher suicide risk was associated with greater neural rigidity, characterized by constrained, repetitive brain state transitions. Lower stability of basin A was linked to suicide risk, partly mediated by cognitive impairment.

Conclusions:

• Suicide vulnerability in BD is characterized by entrenched functional brain states and reduced brain state transition diversity.
• Elevated energetic constraints in brain dynamics may impair adaptive reconfiguration, contributing to neural rigidity.
• Altered brain state dynamics show potential as a biomarker for suicide risk in bipolar disorder.