# Noninvasive cervical electrical stimulation for ALS: Mechanistic and safety study

> **NIH VA I21** · JAMES J PETERS VA  MEDICAL CENTER · 2020 · —

## Abstract

Amyotrophic lateral sclerosis (ALS) reduces connections between the cortical motor neurons that initiate
movement and the spinal motor neurons that direct muscles to execute movement. This situation shares many
key features with incomplete spinal cord injury (SCI). Accumulating evidence in SCI suggests that externally
activating spared nerve circuits with electromagnetic stimulation augments neural transmission.
 With this goal, we developed a novel method of noninvasive cervical electrical stimulation (CES). CES
activates multiple muscles on both upper limbs by triggering afferent sensory or efferent motor nerve roots
depending on stimulus intensity. This proposal will investigate CES for its potential to strengthen residual
circuits to the hands in ALS. To our knowledge, electrical spinal stimulation for ALS has never been tested or
applied previously. Therefore, a pilot study is essential. This study will be performed in two stages:
1. Map CES circuit and synaptic targets: The experiments share a common structure comprising
conditioning and test stimuli delivered at a range of intensities, sites, and interstimulus intervals.
Hypotheses: Conditioning subthreshold CES will potentiate responses to TMS and peripheral nerve
F-wave stimulation, indicating its potential to strengthen corticospinal and spinal motor circuit
connections. Conditioning CES will reduce responses to peripheral nerve H-reflex stimulation,
demonstrating its potential to reduce hyperactive afferent stretch reflexes (spasticity).
2. Determine parameters for combining CES with volitional movement: Volitional limb movements
depend on the same corticospinal and motor neuron circuits as those activated by TMS and F-waves.
Since preliminary data shows that subthreshold CES facilitates TMS responses, CES may also be able
to facilitate volitional limb movements. Hypotheses: Subthreshold CES will facilitate concurrent arm
and hand muscle activation, further indicating CES's ability to positively modulate motor circuits;
high-intensity suprathreshold CES will transiently inhibit concurrent arm and hand muscle
activation. If observed, this `spinal silent period' would shed insight into mechanisms underlying the
`cortical silent period' noted when cortical TMS is delivered during volitional contraction.
 Successful completion of these experiments will: mechanistically elucidate CES circuit interactions;
investigate the potential for CES to enhance concurrent volitional muscle activation; and establish CES as safe
and feasible in the ALS population. Given the limited treatment options for ALS, any amount of progress would
represent a meaningful step forward. Moreover, results of this pilot study could lead to direct translation for
lasting clinical benefit by combining repetitive subthreshold CES with repetitive task-oriented physical exercise
training in subsequent studies. CES would be compatible with other interventions, including medications and
cell-based treatments.
 ALS has higher i...

## Key facts

- **NIH application ID:** 10070518
- **Project number:** 5I21RX002527-03
- **Recipient organization:** JAMES J PETERS VA  MEDICAL CENTER
- **Principal Investigator:** NOAM Y. HAREL
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-02-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070518

## Citation

> US National Institutes of Health, RePORTER application 10070518, Noninvasive cervical electrical stimulation for ALS: Mechanistic and safety study (5I21RX002527-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10070518. Licensed CC0.

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