# Spinal Cord Associative Plasticity for Amyotrophic Lateral Sclerosis

> **NIH VA I01** · JAMES J PETERS VA  MEDICAL CENTER · 2024 · —

## Abstract

Amyotrophic lateral sclerosis (ALS) is more prevalent in Veterans than civilians, leading to ALS being considered
a Service-Connected condition by the VA. ALS features incomplete degeneration of upper and lower motor
neuron pathways within the spinal cord, a circumstance resembling that of spinal cord injury (SCI).
Transcutaneous spinal cord stimulation (TSCS) has demonstrated remarkable potential to activate damaged
circuits after SCI to improve motor and autonomic function.
Partly funded by a prior RR&D SPiRE award (RX002527), we have preliminary data demonstrating that pairing
subthreshold cervical TSCS pulses with suprathreshold transcranial magnetic stimulation (TMS) pulses can
enhance hand muscle motor evoked potentials when the cortical pulse reaches the cervical spinal cord 0-5
milliseconds prior to the spinal pulse. This evidence for immediate facilitation of the response to one pair of
pulses suggests that if given repetitively, this approach could mediate spinal cord associative plasticity
(SCAP) outlasting the period of paired stimulation. We propose that increasing neural plasticity in this manner
could be applied as a method to strengthen volitional (cortical) motor output and/or to 'prime' weakened circuits
for improved responses to task-oriented exercise.
Both exercise and neuromodulation are understudied in ALS. Though not likely to cure the underlying disease
mechanism, these approaches have the potential to mediate symptomatic benefit. We strive to find better ways
to conduct disease-oriented research that may provide direct clinical benefit to research participants with
ALS and simultaneously increase scientific understanding. Additionally, most ALS clinical study entry criteria
heavily favor those at earlier stages of disease. Strict entry criteria are understandable from the scientific
perspective. However, we have repeatedly observed the frustration and rejection felt by individuals with ALS
who cannot enter clinical trials. Our proposed study does not restrict entry by time since symptom onset. We
thereby hope to produce more generalizable knowledge by performing a phased study:
1. Optimization: SCAP synaptic pairing interval and repetitive frequency pattern will be individually
 optimized to enhance hand muscle excitability and dexterity. We hypothesize that pairs of stimuli with
 TMS arriving at the cervical spinal cord up to 2 ms prior to TSCS, delivered in an ‘intermittent theta burst’
 pattern, will produce the strongest facilitation of hand neural circuits.
2. Consolidation: Two-week programs of SCAP alone versus exercise alone versus SCAP plus task-
 oriented hand exercise will be compared. We hypothesize that the combined intervention will result in
 greater and longer lasting physiological and clinical benefits than either modality by itself.
There are currently no clinical studies in the world involving magnetic brain paired with phasic electrical spinal
stimulation for ALS. Therefore, safety needs to be meticulo...

## Key facts

- **NIH application ID:** 10862195
- **Project number:** 1I01RX004258-01A2
- **Recipient organization:** JAMES J PETERS VA  MEDICAL CENTER
- **Principal Investigator:** NOAM Y. HAREL
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862195

## Citation

> US National Institutes of Health, RePORTER application 10862195, Spinal Cord Associative Plasticity for Amyotrophic Lateral Sclerosis (1I01RX004258-01A2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10862195. Licensed CC0.

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