# Neurophysiological Basis for Enhancing Motor Recovery After Stroke

> **NIH VA I01** · VETERANS AFFAIRS MED CTR SAN FRANCISCO · 2024 · —

## Abstract

Stroke is a major cause of motor disability in veterans; Greater than 50% of stroke survivors continue to
have motor deficits that limit independence. While a majority of past research has focused on how loss of
descending pathways leads to loss of function, precisely what drives the emergence of abnormal flexor
‘synergies’ (gain of function with increased flexor tone) is not fully understood and there is also no
specific treatment. Synergies in this context refers to abnormal coordinated activation of upper-limb
muscles during reaching (i.e., flexor tone in shoulder & biceps and a closed hand).
Consistent with observations in stroke patients, our preliminary data in mice reveals that increased flexor
tone develops in a delayed manner and significantly alters reach-to-grasp. Using our model, we will test
the specific hypothesis that the emergence of a delayed imbalance between the contralesional and
ipsilesional corticoreticular pathways is associated with onset of flexor tone. We will use viral methods to
label cortical projection pathways (premotor to the pontomedullary reticular formation, PMRF) and then
track projection activity over recovery after experimental stroke.
Our proposed specific aims will test this hypothesis using long-term pathway specific tracking as well as
test two promising interventions to reduce flexor tone. The first aim is to determine if increased activity of
the contralesional corticoreticular pathway together with reduced ipsilesional corticoreticular activity
predicts delayed onset of increased flexor tone. In the second aim we will test if low frequency
ipsilesional motor thalamus stimulation in chronic stroke can reduce flexor tone and improve reach to
grasp function. This approach is based on our extensive data that low-frequency patterning is beneficial
for cortical-subcortical communication. Our third aim is to test whether a novel class of small molecules
that activate neurotrophin receptors can reduce flexor tone. Completion of these aims will provide critical
information for designing therapeutic approaches that specifically target abnormal flexor synergies after
stroke. Importantly, they will also provide important information about two promising therapeutic options
to improve function.

## Key facts

- **NIH application ID:** 10857650
- **Project number:** 2I01RX001640-10
- **Recipient organization:** VETERANS AFFAIRS MED CTR SAN FRANCISCO
- **Principal Investigator:** Karunesh Ganguly
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2015-10-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10857650

## Citation

> US National Institutes of Health, RePORTER application 10857650, Neurophysiological Basis for Enhancing Motor Recovery After Stroke (2I01RX001640-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10857650. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*