PROJECT SUMMARY
Falls are a significant concern in persons with Multiple Sclerosis (pwMS) leading to adverse health outcomes
and a diminished quality of life. Fear of falling (FOF) is a heightened emotional response to the possibility of
losing balance, accompanied by an inclination to avoid such situations. FOF impacts over 60% of pwMS and
traps individuals in a vicious cycle of reduced balance confidence, avoidance behavior, physical deconditioning,
and subsequent increased fall risk. The FOF cycle leads to downstream negative consequences in cognition,
social isolation, psychological distress, and overall life quality. Therefore, FOF is viewed as a complex construct
associated with motor, cognitive, and psychological factors; however, the neural correlates remain largely
unknown. While limited research has explored neural underpinnings of FOF in healthy older adults, it primarily
focused on brain regions related to general motor function, neglecting associations with regions underlying
cognitive and emotional functions. Intriguingly, the association between FOF and motor regions among older
adults is partially dependent on neuroticism and anxiety, underscoring the multifactorial nature of FOF. These
neural and psychological contributors to FOF are understudied in pwMS. Without a comprehensive
understanding of these underlying factors, the development of successful interventions to break the FOF cycle
in pwMS is unlikely. Therefore, the specific aims of this project are to 1.) Identify the contributions of motor and
cognitive functioning and key brain regions associated with these processes to FOF 2.) Determine the effect of
psychological functioning and key brain regions involved in emotion to FOF; and 3.) Determine the predictive
utility of baseline imaging and clinical performance measures to predict FOF, and in turn physical activity and
falls over time. My central hypothesis is that neural and behavioral factors related to motor, cognitive, and
psychological functioning will contribute to FOF and serve as predictors of long-term physical activity and falls. I
will test this hypothesis in 40 individuals with relapsing-remitting MS. In a single session, participants are
undergoing an MRI and a comprehensive battery of motor, cognitive, and psychological assessments. After the
visit, participants are monitored for 6 months to obtain longitudinal FOF, prospective falls, and physical activity
data. This proposal provides an important scientific advancement in understanding mechanisms underlying FOF
by bridging together neuroimaging, clinical assessments, and prospective data. The sponsor and advisory
committee are exceptionally qualified to provide scientific, clinical, and professional guidance. Mentor Fritz is an
established researcher in MS neurorehabilitation and fall prevention. The advisory committee consists of
accomplished researchers who will provide complementary expertise in neuroimaging, FOF psychopathology,
fear-related neurocircuitry, and statistical analyses. This training project will provide me with the critical skills and
research training to subsequently expand on this work as a postdoctoral research fellow, ultimately leading to a
career as an independent neuroscientist committed to identifying targets for FOF and fall prevention.
