Our long-term goal is to reveal systematically how the musculotendon mechanics, spinal cord and brain interact to produce able and pathologic finger function. The prior grant revealed many necessary neuromechanical interactions for finger function and dysfunction. This compels and enables us to study spinal neurophysiology and neuromechanics as a step before tackling brain function. The immediate goals of our team of scientists and surgeons are to (i) test the extent to which the known somatosensory feedback and spinal interneuronal circuitry is sufficient, on its own, to account for critical features of fst isometric fingertip forces without requiring on-line supraspinal modulation;and (ii) understand how botulinum toxin (BTX) injections to reduce spasticity and dystonia in hemiplegic CP and iSCI interact with that circuitry. We will test theories of spinal reflexive and excitation-inhibiton mechanisms using synthetic analysis and physical implementation, which in our view is a strong test of our understanding of a system. That is, we will confront the very challenge the nervous system faces by controlling the tendons of cadaveric fingers with an autonomous neuromechatronic system of microprocessors and motors that implements the known motor and somatosensory spinal circuitry and muscle properties of healthy subjects and patients.
Aim 1 : Characterize H-reflex and performance of Single Joint and Whole Finger fast isometric tasks in control subjects, and pre-&post-BTX in patients. (Exploratory test on CP patients undergoing tendon transfers and musculotendon length changes will validate other physiological processes and model components in the later phases of the research.) Then, actuate tendons of cadaveric fingers to (i) find feasible tensions to replicate that performance and (ii) quantify robustness to errors in tendon tensions.
Aim 2 : Implement in real time the known connectivity and dynamics of spinal neurons, muscle proprioceptors and muscle fibers of a single afferented muscle. Validate against data in the literature. Single Muscle Hypothesis: Muscle function (e.g., tone, stretch reflex) emerges naturally from specific combinations of neuronal background activity and pathway gains. Test how physiologically tenable disruptions and BTX lead to, or mitigate, pathologic behavior (e.g., spasticity and clonus).
Aim 3 : Implement the hypothesized neural connectivity and dynamics across muscles to reproduce the H- reflex and performance of fast isometric tasks seen in control subjects, and pre-&post-BTX in patients. Replicating the behavior measured in Aim 1 by driving tendons of cadaveric index fingers will identify how clinically tenable disruptions lead to pathologic behavior, and the extent to which BTX (and preliminarily tendon transfers and musculotendon length changes) can mitigate those pathologies. a) Single Joint Hypothesis: Single-joint function (e.g., fast time-varying torques) emerges naturally from background activity and pathway gains across motoneuron pools of a pair of antagonist muscles. Test the emergence and BTX mitigation of single joint spasticity, clonus, instability, and deficits in single joint tasks. b) Whole Finger Hypothesis: The fast time-varying fingertip force tasks recorded in Aim 1 emerge naturally from physiologically tenable interactions across all finger muscles. Test the emergence and BTX mitigation of whole-finger spasticity, clonus, abnormal postures, and deficits in whole fingertip force tasks.

Public Health Relevance

While neuroscientists have mapped the circuitry in the brain and spinal cord, it is still unknown to what extent the spinally-mediated muscular excitation-inhibition mechanisms contribute to voluntary function and clinical symptomatology. It has proven extremely difficult to measure quantitatively the interactions among the brain, spinal cord and muscles in humans to optimize treatment. A promising alternative to understand clinical out- comes is to (i) record detailed neurophysiological and performance during from healthy individuals, and pre- and post-treatment in patients with hemiplegic cerebral palsy and incomplete spinal cord injury, during fast finger tasks dependent on spinal circuitry;(ii) and the create a realistic neuromechanical system to explicitly test the extent to which our current models of spinal circuitry are sufficient to reproduce healthy and pathologic behavior.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01AR052345-07
Application #
8701233
Study Section
Musculoskeletal Rehabilitation Sciences Study Section (MRS)
Program Officer
Panagis, James S
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Southern California
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Dayanidhi, Sudarshan; Valero-Cuevas, Francisco J (2014) Dexterous manipulation is poorer at older ages and is dissociated from decline of hand strength. J Gerontol A Biol Sci Med Sci 69:1139-45
Lyle, Mark A; Valero-Cuevas, Francisco J; Gregor, Robert J et al. (2014) Control of dynamic foot-ground interactions in male and female soccer athletes: females exhibit reduced dexterity and higher limb stiffness during landing. J Biomech 47:512-7
Dayanidhi, Sudarshan; Kutch, Jason J; Valero-Cuevas, Francisco J (2013) Decrease in muscle contraction time complements neural maturation in the development of dynamic manipulation. J Neurosci 33:15050-5
Dayanidhi, Sudarshan; Hedberg, Asa; Valero-Cuevas, Francisco J et al. (2013) Developmental improvements in dynamic control of fingertip forces last throughout childhood and into adolescence. J Neurophysiol 110:1583-92
Kurse, Manish U; Lipson, Hod; Valero-Cuevas, Francisco J (2012) Extrapolatable analytical functions for tendon excursions and moment arms from sparse datasets. IEEE Trans Biomed Eng 59:1572-82
Kutch, Jason J; Valero-Cuevas, Francisco J (2011) Muscle redundancy does not imply robustness to muscle dysfunction. J Biomech 44:1264-70
Cianchetti, Flor A; Valero-Cuevas, Francisco J (2010) Anticipatory control of motion-to-force transitions with the fingertips adapts optimally to task difficulty. J Neurophysiol 103:108-16
Sherback, Michael; Valero-Cuevas, Francisco J; D'Andrea, Raffaello (2010) Slower visuomotor corrections with unchanged latency are consistent with optimal adaptation to increased endogenous noise in the elderly. PLoS Comput Biol 6:e1000708
Kutch, Jason J; Kuo, Arthur D; Rymer, William Z (2010) Extraction of individual muscle mechanical action from endpoint force. J Neurophysiol 103:3535-46
Rieffel, John A; Valero-Cuevas, Francisco J; Lipson, Hod (2010) Morphological communication: exploiting coupled dynamics in a complex mechanical structure to achieve locomotion. J R Soc Interface 7:613-21

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