Functional network dynamics and decreased conscientiousness in multiple sclerosis

Background: Conscientiousness is a personality trait that declines in people with multiple sclerosis (PwMS) and its decline predicts worse clinical outcomes. This study aims to investigate the neural underpinnings of lower Conscientiousness in PwMS by examining MRI anomalies in functional network dynamics. Methods: 70 PwMS and 50 healthy controls underwent personality assessment and resting-state MRI. Associations with dynamic functional network properties (i.e., eigenvector centrality) were evaluated, using a dynamic sliding-window approach. Results: In PwMS, lower Conscientiousness was associated with increased variability of centrality in the left insula (t_max = 4.21) and right inferior parietal lobule (t_max = 3.79); a relationship also observed in regressions accounting for handedness, disease duration, disability, and tract disruption in relevant structural networks (ΔR² = 0.071, p = 0.003; ΔR² = 0.094, p = 0.004). Centrality dynamics of the observed regions were not associated with Neuroticism (R² < 0.001, p = 0.956; R² < 0.001, p = 0.945). As well, higher Conscientiousness was associated with greater variability in connectivity for the left insula with the default-mode network (F = 3.92, p = 0.023) and limbic network (F = 5.66, p = 0.005). Conclusion: Lower Conscientiousness in PwMS was associated with increased variability in network centrality, most prominently for the left insula and right inferior parietal cortex. This effect, specific to Conscientiousness and significant after accounting for disability and structural network damage, could indicate that overall stable network centrality is lost in patients with low Conscientiousness, especially for the insula and right parietal cortex. The positive relationship between Conscientiousness and variability of connectivity between left insula and default-mode network potentially affirms that dynamics between the salience and default-mode networks is related to the regulation of behavior.