# Corticoreticulospinal tract reorganization after stroke

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $639,176

## Abstract

PROJECT SUMMARY
The neural substrates underlying motor recovery after stroke are poorly understood. Despite decades of
research, strategies for optimizing recovery remain lacking, possibly because of the failure to consider non-
corticospinal pathways as potential recovery substrates. The corticoreticulospinal tract (CReST) is a bilaterally
descending motor pathway in humans. In animals that have recovered from corticospinal tract injury, the
contralesional CReST shows functional and structural upregulation. In humans that have recovered from
corticospinal stroke, contralesional CReST neurophysiology shows increased excitability. These findings
suggest that the contralesional CReST has the capacity to reorganize after stroke, but it is not known if these
changes directly relate to motor improvement. The overall objective of this application is to identify the role of
the contralesional CReST in motor recovery. Our central hypothesis is that functional and structural changes in
the contralesional CReST will causally relate to motor recovery in the upper extremity. The rationale underlying
the proposed research is that, once a recovery role is identified, the CReST could be manipulated to
accelerate recovery. In the first six months following ischemic stroke, we will longitudinally measure strength,
motor control, and motor synergies to characterize motor recovery. We will use transcranial magnetic
stimulation (Aim 1) and structural MRI (Aim 2) to precisely detail contralesional CReST neurophysiology and
microstructure. Pathway-behavior relationships will be assessed within a causal inference framework. We
expect to show that contralesional CReST reorganization, manifesting as increased excitability and tissue
complexity, will relate to increasing strength, motor control, and synergy expression after stroke. The proposed
work is significant, because it is expected to provide strong scientific justification for targeting the contralesional
CReST to potentiate recovery. The proposed work is innovative, because it combines advanced
complementary approaches to focus on a surprisingly understudied pathway in motor recovery. Our study is
likely to have a positive impact on the field of neurorehabilitation, because it will vertically advance our
understanding of motor recovery mechanisms, leading to the development of rationally designed therapies to
improve stroke outcomes.

## Key facts

- **NIH application ID:** 9917819
- **Project number:** 5R01NS110696-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Heidi Schambra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $639,176
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9917819

## Citation

> US National Institutes of Health, RePORTER application 9917819, Corticoreticulospinal tract reorganization after stroke (5R01NS110696-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9917819. Licensed CC0.

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