Carmel Lab
Research Projects

You are here

RO1: Motor Cortex Electrical Stimulation to Augment Spontaneous Recovery after Chronic Subcortical Stroke

RESEARCH PROJECT: 
In Progress

Stroke is the leading cause of motor disability in the United States. Subcortical motor system strokes, such as those that affect the internal capsule and brainstem, are distinct from cortical strokes in that they leave motor cortex and spinal cord intact but destroy axonal connections between them. Although most subcortical stroke patients recover some motor function, they are typically left with substantial hand impairment. The magnitude of spontaneous recovery is positively correlated with the degree of sparing of motor axonal pathways. In this study, we seek to identify the spared motor pathways in subcortical strokes that mediate spontaneous recovery, and to stimulate their plasticity to improve outcome.

Rigorous methods to identify and manipulate circuits that mediate motor recovery in rodents have only recently become available, and we have established these procedures in our lab such as the viral injection techniques and internal capsule injury method. We have also demonstrated that electrical stimulation of motor cortex can enhance the function of spared motor circuits and promote recovery of forelimb function in rats, even after chronic subcortical stroke. We propose to combine these methods to test the hypothesis that electrical stimulation of the motor cortex regions that mediate spontaneous recovery following subcortical stroke will promote greater functional recovery than equivalent stimulation of uninvolved motor cortex areas. The circuits that are proposed to mediate spontaneous recovery (dependent upon injury modelcapsule lesion vs. pyramidotomy) and thus the candidate circuits for recovery are shown in the figure.

Figure 1. Hypothesized recovery circuits (red).

Figure 1. Hypothesized recovery circuits (red). Arrowheads indicate internal capsule (IC) lesion and pyramidotomy, which result in hindlimb (HL) and forelimb (FL) control, respectively.

Funding

GRANT: 
Federal
August 15, 2015 to May 31, 2020
Grant Number: 
R01NS092875
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators: 
Principal Investigator

Associated