Most of our daily life activities involve bilateral hand and arm movements. This ability is largely disrupted in individuals with cervical spinal cord injury (SCI). This proposal has two main goals: 1). examine the physiology of CNS pathways contributing to the control of bilateral hand and arm movements in individuals with cervical SCI, and 2). study approaches to promote recovery of upper-limb motor function. We focus on bilateral elbow flexion/extension and precision grip, which are basic movements in our daily life activities.
In Aim 1, we will examine the contribution of the motor cortex, corticospinal drive, and spinal cord to the control of bilateral hand and arm movements after cervical SCI. Transcranial magnetic stimulation (TMS) will be used to examine excitability of intracortical pathways and corticospinal drive. Electroencephalography (EEG) and electromyography (EMG) and EMG/EMG coherence will be used to examine transmission in corticospinal inputs to spinal motoneurons. We will assess motoneuronal excitability by using peripheral nerve stimulation. Together, these studies will identify the effects of SCI on physiological pathways involved in functionally relevant actions.
In Aim 2, we propose to study two novel approaches to promote recovery of upper-limb motor function. First, we plan to strengthen transmission in the corticospinal pathway by using spike-timing- dependent plasticity (STDP) protocols. Repeated pairs of TMS and peripheral nerve stimuli will be precisely timed to arrive at the motor cortex and spinal cord, respectively, to induce synaptic plasticity. Second, we plan to enhance voluntary control of upper-limb muscles by combining myoelectric-controlled training with STDP protocols, targeting physiological sites affected by SCI (identified in Aim 1). Training will consist of controlling a 2-D cursor using EMG signals from bilateral hand and arm muscles.
The specific Aims i n this proposal tightly couple basic scientific human research and translational neuroscience. This work will advance our understanding of how bilateral actions are controlled and could lead to the development of novel interventional approaches to restore bilateral control of upper-limb muscles. The absence of universally accepted treatments for hand and arm motor disability after SCI, and other CNS disorders, and the limited behavioral improvements with present interventions highlight the importance of these investigations.

Public Health Relevance

The control of bilateral hand and arm movements is largely disrupted in individuals with cervical SCI. This proposal will examine the contribution of the motor cortex, corticospinal drive, and spinal cord to hand and arm muscle activity during functionally relevant bilateral actions. Novel methods will be used to strengthen transmission in the corticospinal pathway and to enhance voluntary control of upper-limb muscles. Because deficits in bilateral arm movements and corticospinal transmission are a major problem after stroke, amyotrophic lateral sclerosis, multiple sclerosis, and other motor disorders, our work may also be relevant for patients with other lesions of the CNS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS076589-03
Application #
8534309
Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
Chen, Daofen
Project Start
2011-09-30
Project End
2016-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
3
Fiscal Year
2013
Total Cost
$302,507
Indirect Cost
$91,413
Name
University of Pittsburgh
Department
Physical Medicine & Rehab
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Bunday, Karen L; Tazoe, Toshiki; Rothwell, John C et al. (2014) Subcortical control of precision grip after human spinal cord injury. J Neurosci 34:7341-50
Perez, Monica A; Butler, Jane E; Taylor, Janet L (2014) Modulation of transcallosal inhibition by bilateral activation of agonist and antagonist proximal arm muscles. J Neurophysiol 111:405-14
Tazoe, Toshiki; Perez, Monica A (2014) Selective activation of ipsilateral motor pathways in intact humans. J Neurosci 34:13924-34
Barry, Melissa D; Bunday, Karen L; Chen, Robert et al. (2013) Selective effects of baclofen on use-dependent modulation of GABAB inhibition after tetraplegia. J Neurosci 33:12898-907
Tazoe, Toshiki; Perez, Monica A (2013) Speed-dependent contribution of callosal pathways to ipsilateral movements. J Neurosci 33:16178-88
Bunday, Karen L; Perez, Monica A (2012) Impaired crossed facilitation of the corticospinal pathway after cervical spinal cord injury. J Neurophysiol 107:2901-11