# Neurophysiological Basis for Enhancing Motor Recovery After Stroke

> **NIH VA I01** · VETERANS AFFAIRS MED CTR SAN FRANCISCO · 2022 · —

## Abstract

Stroke is a major cause of disability in veterans. Despite significant advances in stroke rehabilitation
methods there continue to be substantial long-term disability. Importantly, quantitative assessments
have found that a major contributor to motor impairments is the presence of fragmented movement
control, characterized by a lack of smooth and fast transitions between sub-movements and
inconsistency over multiple attempts. Furthermore, there is a deficit in learning new movement
sequences. It remains unclear what is the precise circuit basis for such deficits.
The central hypothesis of this proposal is that impaired task-dependent recruitment of the
striatum contributes to fragmented movement control and poor learning. There has been a great
focus on the role of perilesional cortex (PLC) in recovery. In the intact brain, however, cortical areas
work in close concert with subcortical regions; interactions between M1 and the dorsolateral striatum
(DLS) are known to play a critical role in learning and generating smooth and consistent skilled
movements. Little is known about how the DLS might contribute to motor recovery after stroke. Our
preliminary data shows that coordination between M1 and DLS is directly linked to “binding” of movement
fragments to result in a smooth and fast skilled action. We further found that DLS is essential for such
execution; inhibition of DLS increased movement fragmentation. Our data also demonstrates that DLS
activity is affected by stroke and that its activity changes with recovery.
We propose to pursue the following specific aims: 1) Determine the role of task-related oscillatory activity
in the DLS in regulating movement fragmentation during spontaneous motor recovery after cortical
stroke; 2) Determine the role of low-frequency coherence between areas during spontaneous recovery
in the setting of a stroke that involves both cortex and striatum; 3) Determine if paired stimulation can
increase coordination and thereby improve motor outcomes. Completion of these aims will provide
critical information for designing therapeutic approaches that specifically target cortico-striatal activity.
Focusing on targeted neuromodulation of such dynamic neural network interactions represents a new
direction that could transform our ability to augment recovery of upper extremity function following stroke.

## Key facts

- **NIH application ID:** 10385691
- **Project number:** 5I01RX001640-07
- **Recipient organization:** VETERANS AFFAIRS MED CTR SAN FRANCISCO
- **Principal Investigator:** Karunesh Ganguly
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2015-10-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10385691

## Citation

> US National Institutes of Health, RePORTER application 10385691, Neurophysiological Basis for Enhancing Motor Recovery After Stroke (5I01RX001640-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10385691. Licensed CC0.

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