Examining mobility restrictions through the lens of post-stroke apathy

Stroke is a leading cause of long-term disability worldwide, leaving many with restricted mobility that contributes to progressive functional decline, reduces quality of life, and increases the risk of recurrent stroke. Rehabilitation interventions are designed to enhance mobility post-stroke by reducing motor impairments and walking capacity limitations. However, post-stroke mobility is a multifactorial construct that is only partially explained by motor impairments, and motor-centered treatment approaches have a limited impact on walking performance in daily life. This suggests a more comprehensive understanding of the non-motor sequelae of stroke that influence mobility is necessary. Here, we posit that post-stroke apathy is an important factor to examine. Apathy, affecting over one-third of stroke survivors, is rarely studied in neurorehabilitation. Defined as a psychiatric syndrome characterized by a loss of motivation and reduced self-driven, goal-directed activity, apathy impacts effort-based decision-making, reducing willingness to exert effort for rewards due to altered sensitivity to rewards or effort. This provides a theoretical basis for a potential negative association between apathy and mobility, which remains untested. Additionally, the neural mechanism underlying post-stroke apathy is not well understood. Emerging research suggests that lower functional connectivity of brain areas involved in reward and salience processing are neural signatures of apathy in older adults. Yet, functional connectivity correlates of post-stroke apathy are poorly understood. The overall objective of this Katz Early-Stage Investigator Research Project Grant proposal is to determine the association between post-stroke apathy mobility and identify the functional connectivity signatures of post-stroke apathy. To accomplish this, we will conduct a cross-sectional observational study with three aims in a single cohort of 125 participants with chronic stroke. We will study two aspects of mobility post- stroke– habitual gait speed and community mobility. Aim 1 is designed to determine the relationship between post-stroke apathy and gait speed reserve, where gait speed reserve is the difference between one’s habitual gait speed and the speed that would minimize the total effort to move a given distance. Aim 2 will determine how post-stroke apathy is related to community mobility. Community mobility will be operationalized as a comprehensive combined metric of three commonly used measures – steps per day, GPS-derived activity space, and life-space mobility. Finally, Aim 3 will examine the association between post-stroke apathy and functional connectivity signatures of apathy using resting state-functional MRI. People with stroke who have a range of apathy severity will complete the procedures necessary for these aims over two sessions that take place one week apart. Successful completion of these aims will 1) lead to a more comprehensive understanding of post- stroke mobility determinants, catalyzing a paradigm shift in neurorehabilitation to consider neuropsychiatric symptoms as necessary treatment targets to improve mobility, and 2) delineate a potential neural mechanism of post-stroke apathy, essential for developing effective interventions to prevent or mitigate apathy after stroke. Project Number: 1R01HD115526-01A1 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Kristan Leech | Institution: UNIVERSITY OF SOUTHERN CALIFORNIA, Los Angeles, CA | Award Amount: $647,043 | Activity Code: R01 | Study Section: Motor Function, Speech and Rehabilitation Study Section[MFSR] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01HD11552601A1