Cerebello-cortical connectivity as an adaptive mechanism for balance control with aging
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Project Summary/Abstract: Falls are the leading cause of injury-related morbidity and mortality in adults over 65, yet current therapeutic approaches targeting balance dysfunction show only modest clinical effects. This limited success may reflect a focus on pathological mechanisms rather than understanding adaptive mechanisms that may explain why some older adults maintain high balance function despite advanced age. Recent evidence suggests that cerebellar-mediated implicit motor learning remains intact or enhanced in older adults, contrasting with broader age-related learning impairments. Simultaneously, aging is characterized by increased cortical involvement in balance control, particularly in prefrontal and sensorimotor regions that receive dense cerebellar projections. These converging findings suggest that preserved cerebellar plasticity may enable adaptive cortical compensation, yet the role of cerebello-cortical connectivity in maintaining balance function with aging remains unexplored. Our central hypothesis is that modulation of cerebello-cortical functional connectivity to primary motor and prefrontal cortices enables adaptive cortical compensation for age-related sensorimotor declines, providing a neuroresilience mechanism for maintaining balance control. This hypothesis is supported by our published findings showing that older adults with highest balance performance exhibit dissociative patterns of cortical activity involving sensorimotor and prefrontal-motor circuits during postural perturbations, and by our preliminary data demonstrating that high-functioning older adults show greater adaptation of cortical and motor responses during repeated balance perturbations compared to younger adults. This R21 project will leverage a well-characterized cohort of 48 older and younger adults to measure cerebellar brain inhibition of primary motor cortex using dual-site transcranial magnetic stimulation (TMS), and cerebello-prefrontal functional connectivity using cerebellar TMS-evoked electroencephalography (EEG) potentials. We will simultaneously record EEG, electromyographic, and biomechanical signals during reactive balance recovery to repeated support-surface perturbations. Aim 1 will test whether cerebello-cortical connectivity mediates cortical activity patterns during balance recovery that are associated with balance behavior in older versus younger adults. Aim 2 will determine whether balance adaptation elicits changes in cerebello-cortical connectivity and examine relationships with adaptation of cortical error signals and biomechanical flexibility during repeated perturbations. Novel evidence linking cerebello-cortical connectivity to balance control in older adults could transform therapeutic approaches by leveraging cerebellar-mediated plasticity to maintain balance function with aging. If successful, this work will identify neuroresilience mechanisms underlying heterogeneous balance aging trajectories and inform new targets for fall prevention interventions.
