Dissecting Behavioral and Neural Mechanisms of Hand Dexterity after Stroke for Effective Rehabilitation

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PROJECT SUMMARY Following a stroke, hand dexterity does not recover fully for most patients, significantly reducing quality of life. Optimal and effective assessment and therapies for achieving hand dexterity are currently lacking due, in part, to limited scientific knowledge of human hand dexterity in health and disease. Hand dexterity hinges on multiple essential behavioral components embedded in a highly interactive neural circuit. How the behavioral components interact and how they are supported by descending neural pathways are still unclear. The long- term goal of this research is to build a predictive model and identify key behavioral and neural principles for designing targeted therapies to facilitate the reacquisition of hand dexterity to improve quality of life. The current objective of this project is to investigate behavioral and neural mechanisms of hand dexterity and its impairment and recovery after stroke. The central hypothesis is that three essential components of hand function, finger individuation, precision grip, and power grip, largely rely on three distinct control variables, flexibility, coordination, and strength, and separable descending pathways: direct- and indirect-corticospinal tract (CST), and reticulospinal tract (RST). The rationale for this project is that directly comparing different components of dexterity using kinematics/kinetics at the same levels of granularity, combined with the most advanced measures of descending neural pathway structure and function holds promise in a new model of hand dexterity. Two specific aims are proposed to test the central hypothesis: 1) characterize effect of stroke on individuation, precision grip, and power grip; and 2) determine if stroke-related disruption in the structure and function of three descending neural pathways are associated with three behavioral components. Under Aim 1, chronic stroke patients and healthy controls’ Individuation and Precision Grip will be directly compared using isometric forces recorded in high resolution at all ten fingertips in 3D, and their interaction with Power Grip will be examined. Under Aim 2, high-resolution tractography using diffusion-weighted MRI will be obtained to assess structural integrity of the three descending pathways. Transcranial magnetic stimulation (TMS) paired with peripheral nerve stimulation will be used to assess functional involvement of the three pathways using short-, long-, and extra-long interval modulation of Hoffmann-reflex. Under Aim3, a model will be built to map severity of impairment in behavioral measures to neurophysiological markers derived from Aim 1&2 to test the hypothesis that stroke survivors’ direct-, indirect-CST and RST measures will be predictive of individuation, precision grip, and power grip behaviors, respectively. The proposal is innovative because it reconceptualizes dexterity by, for the first time, directly assessing essential components of dexterity behaviors and descending pathways with cutting-edge techniques and build a neural model from these findings. It is significant because findings from this project will guide the creation of sensitive clinical assessments and redefine therapeutic interventions for optimal hand rehabilitation after stroke to enhance patients’ quality of life.