BME PhD Prospectus Defense: Jacob K. Warner

Title: "Sensory Regulation of Gait Variability"

Advisory Committee: Xue Han, PhD (Advisor), Biomedical Engineering, Boston University David A. Boas, PhD (Chair), Biomedical Engineering, Boston University Robert Reinhart, PhD (Chair), Psychological & Brain Sciences, Boston University Kamal Sen, PhD, Biomedical Engineering Ludy Shih, MD, MMSc, BIDMC, Harvard Medical School

Abstract: Impaired gait and falls are major sources of morbidity in older adults, with roughly 30% of individuals over 65 falling each year, yet few interventions directly target the rhythmicity of walking. Recent work identified a cellular mechanism linking sensory stimulation to gait: dorsal striatal neurons exhibit delta-range membrane rhythmicity that organizes beta-band spiking and tracks locomotion, and beta-frequency sensory stimulation strengthens this coupling to reduce gait variability in mice. Similar stimulation reduces gait variability in young adults, particularly those with higher baseline variability, suggesting older adults may benefit most. This dissertation characterizes how auditory and vibrotactile stimulation at beta frequencies modulates stride-to-stride variability in community-dwelling older adults using wearable sensors, identifying subject-specific frequency and modality preferences. In parallel, it determines the stimulation parameters that most effectively entrain locomotion in mice and uses cellular-resolution voltage imaging of D1 and D2 striatal projection neurons during locomotion to directly test whether sensory stimulation reduces gait variability by strengthening delta-beta coupling at the single-neuron level.