Modulating brain activity to preserve gait in older adults.

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DESCRIPTION (provided by applicant): My career goal is to alleviate the walking and mobility impairments that often accompany aging. I will achieve this goal by leading an interdisciplinary, translational research program in the fields of human aging, locomotion and rehabilitative medicine. My long-term plan is to enhance these fields by 1) identifying mechanisms of central nervous system adaptation to age- and disease-related sensorimotor impairments, and 2) translating these mechanistic understandings of adaptive capacity into improved rehabilitation methods. I will do so by combining state-of-the-art functional neuroimaging and noninvasive brain stimulation paradigms with traditional biomechanics-based behavioral assessments. Through this award, I will continue my career development by leveraging outstanding training and research opportunities available at the Beth Israel Deaconess Medical Center and Harvard Medical School. By completing the proposed research, coursework, scientific service, and collaboration with leading experts in gerontological research, neurophysiology, neuropsychology, neural imaging and brain stimulation, I will: 1) Become an expert in the neurophysiology of aging in relation to locomotor control; 2) Learn new techniques in brain imaging and stimulation and their application to motor control; 3) Achieve national recognition and develop leadership skills in the field of aging. The proposed research will identify and modulate brain networks that contribute to the complex control of walking in healthy older adults. Evidence from behavioral studies indicates that performing a cognitive task while walking decreases speed and increases movement variability in this population. Mechanisms through which cognitive tasks disturb walking, however, are unknown. Importantly, neuroimaging evidence indicates that the primary somatosensory cortex (SI) response to a tactile stimulus is dependent upon afferent feedback, as well as "top-down" neuromodulation from higher brain regions. To enable study of the cortical response to walking-related tactile stimuli, I developed an fMRI-compatible system to apply pressure to the feet that mimics those of walking, yet while lying motionless in the scanner. Our preliminary studies in younger adults indicate that the intensity of SI activation induced by this stimulation was reduced when subjects simultaneously performed a cognitive task. However, it remains unknown whether performing a cognitive task decreases the brain's somatosensory cortical response to walking-related foot sole stimulation in healthy older adults. One promising approach to manipulate the cortical responsiveness to somatosensory stimuli is transcranial direct current stimulation (tDCS), which utilizes low-amplitude direct current to transiently alter cortical excitability. Our pilot studies indicate tha tDCS applied to the prefrontal brain regions a) does not affect SI brain activity during rest, b) increases the SI response to foot sole stimulation in younger adults, and c) may improve walking outcomes in healthy older adults. Grounded in these observations, we propose to use my fMRI foot stimulation paradigm, tDCS and behavioral assessments to test the following hypotheses: We hypothesize that in healthy older adults, performing cognitive tasks diminishes the cortical somatosensory response to walking-related foot sole stimulation (H1), and that providing excitatory tDCS to cognitive brain regions increases the cortical somatosensory response to this stimulation (H2) and improves walking outcomes (H3) in this population. We will test these hypotheses via three Aims: Aim 1: To determine the effect of performing cognitive tasks on the cortical somatosensory response to foot sole stimulation in healthy older adults. Aim 2: To determine the effect of tDCS targeting cognitive brain regions on the cortical somatosensory response to foot sole stimulation in healthy older adults. Aim 3: To determine the effect of tDCS targeting cognitive brain regions on walking in healthy older adults. We will recruit 30 cognitively-intact, healthy older men and women aged 65-80 years. Each subject will complete six study visits. Visit 1 will be screening. Visit 2 will evaluate mobility, cognition and peripheral sensorimotor function. On Visits 3 and 4, subjects will complete a block-design BOLD fMRI protocol using the foot stimulation system. We will determine the cortical response to foot stimulation with and without concurrent performance of two different difficulties of the "N-Back" working memory task (Aim 1). Subjects will then receive 20min of real or sham tDCS targeting the left prefrontal brain region while resting in a chair outside of the scanner room. The fMRI protocol will then be immediately repeated to determine the effects of tDCS on the cortical responsiveness to foot stimulation (Aim 2). On Visits 5 and 6, subjects will complete assessments of walking and cognition, before and after the same real or sham tDCS targeting the left dlPFC (Aim 3). This project will provide novel evidence that in healthy older adults, the cortical response to walking-related somatosensory stimuli is dependent upon neuromodulation from higher brain regions. Our discoveries may also introduce a novel therapeutic option (i.e., tDCS) to improve walking in this vulnerable population.