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

• Sponsor
  National Institutes of Health
  National Institute of Neurological Disorders and Stroke
  $2,736,478

• Principal investigator
  Jing Xu
  Assistant professor, Department of Kinesiology
  

• Co-principal investigators
  Michael Borich
  Associate professor, Emory University
  

  Timothy Verstynen
  Associate professor, Carnegie Mellon University
  

  Jeremy Brown
  Assistant professor, John Hopkins University
  

• Active since
  September 2023

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Abstract

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 is 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, as well as 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
2. Determine if stroke-related disruption in the structure and function of three descending neural pathways is 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 10 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 aim 3, a model will be built to map severity of impairment in behavioral measures to neurophysiological markers derived from aims 1 and 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 building 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.

Public health relevance statement: The proposed project is relevant to public health because it aims to reconceptualize dexterity and identify critical factors in rehabilitation of hand dexterity among stroke survivors by characterizing essential behavioral components and their neuroanatomical substrates, from which a neural mechanistic concept can be built. Upon successful completion, a new model of hand dexterity and a sound rationale for developing effective therapeutic interventions will emerge, which will facilitate reacquisition of dexterity and optimization of hand function recovery. Thus, the proposed research is relevant to the National Institutes of Health’s mission that pertains to the application of the scientific and clinical knowledge gained from this project to enhance health and reduce disability.