Neural correlates of concern about falling in multiple sclerosis: resting-state functional connectivity in amygdala-hippocampal and amygdala-cerebellar circuits.

Background: Concern about falling (CAF) is common in multiple sclerosis (MS), impacting motor function, cognition, and emotional well-being. However, the underlying neural correlates remain understudied. Given the multifactorial nature of CAF, we hypothesized that neural correlates may involve interactions between brain regions involved in emotional (e.g., amygdala), motor (e.g., cerebellum), and cognitive functions (e.g., hippocampus). This study explored associations between CAF and resting-state functional connectivity (FC) in amygdala-hippocampal and amygdala-cerebellar circuits in MS.

Methods: Participants with relapsing-remitting MS completed the Falls Efficacy Scale-International to assess CAF, followed by a functional MRI scan. Region of interest (ROI)-to-ROI analyses examined associations between CAF and FC in amygdala-hippocampal and amygdala-cerebellar circuits. Significant connections were identified using false discovery rate (FDR) correction at α = 0.05.

Results: Forty-one individuals participated in our study. CAF was significantly associated with greater amygdala-hippocampal FC (T(39) ≥ 3.76, q ≤ 0.001) and lower amygdala-cerebellar FC (T(39) ≤ -2.52, q ≤ 0.026).

Conclusion: These findings highlight distinct neural patterns linked to CAF in MS. Higher CAF was associated with greater amygdala-hippocampal connectivity, suggesting that neural circuits underlying fear-related memories and emotional processing may play a crucial role in perceived fall risk. In contrast, lower amygdala-cerebellar connectivity in individuals with heightened CAF may reflect diminished integration of emotional and motor output, potentially compromising the ability to assess environmental hazards and situations where falls are likely to occur. Further understanding these neural underpinnings may help develop targeted interventions to reduce CAF and its negative impact on people with MS.