# Technology Research and Development Project 1 (Guiding Beneficial Plasticity)

> **NIH NIH P41** · ALBANY RESEARCH INSTITUTE, INC. · 2021 · $258,523

## Abstract

Spinal cord injury (SCI), stroke, cerebral palsy and other chronic neuromuscular disorders impair important
functions such as walking. Current therapies are seldom fully effective. Recent advances enable powerful new
therapies that target beneficial change to key nervous system pathways. Among the first of these therapies are
operant conditioning protocols that modify a specific spinal reflex pathway. The reflex is elicited, and the person is
rewarded if reflex size satisfies a criterion. The person learns to modify the brain's control over the pathway to
increase rewards. This control gradually changes the spinal pathway itself. Furthermore, the beneficial change
(i.e., plasticity) in this pathway leads to wider beneficial plasticity elsewhere. This wider effect is predicted by the
new negotiated equilibrium model of spinal cord function. The result is that, in rats or people with incomplete SCI,
operant conditioning of a spinal reflex increases walking speed and reduces limping.
TR&D1 is developing and translating into clinical use operant conditioning protocols that induce beneficial plasticity
in the nervous system. It includes animal and human studies. The animal studies reveal mechanisms and
principles that guide the human studies, which develop therapeutic protocols and translate them into clinical use.
Aim 1 will develop a fully implanted telemetry-based system for long-term 24/7 operant conditioning in freely
moving rats. By simplifying and facilitating operant conditioning and other long-term studies, this new lab system
will make it possible for many other researchers to engage in these important studies. In addition, this aim will use
this new system for the first studies of the molecular biology of spinal reflex conditioning.
Aim 2 will develop and validate a general-purpose operant conditioning system suitable for widespread clinical
use. Full achievement of the therapeutic promise of operant conditioning and related protocols requires a clinically
practical system that supports a broad range of protocols and can change a variety of nervous system pathways.
The new general-purpose clinical system will be tested, optimized, and validated with clinical collaborators.
Additional collaborations with colleagues at major rehabilitation centers will explore the efficacy of reflex operant
conditioning for improving function in people with cerebral palsy, stroke, and other disorders. This work will define
dose-response curves for key functional measures and will include functional imaging studies to characterize the
underlying plasticity. It will delineate the range of potential clinical applications and help improve the design and
implementation of conditioning protocols. These studies are expected to lead to larger clinical trials to establish
the value of specific conditioning protocols for enhancing recovery of function for specific groups of patients.
By creating, validating, and disseminating these new animal and human systems, and by conducting studies...

## Key facts

- **NIH application ID:** 10239064
- **Project number:** 5P41EB018783-08
- **Recipient organization:** ALBANY RESEARCH INSTITUTE, INC.
- **Principal Investigator:** Jonathan Rickel Wolpaw
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $258,523
- **Award type:** 5
- **Project period:** 2014-09-10 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239064

## Citation

> US National Institutes of Health, RePORTER application 10239064, Technology Research and Development Project 1 (Guiding Beneficial Plasticity) (5P41EB018783-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10239064. Licensed CC0.

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