Evidence map›Paper›PMID 41052711›Full record

ArticleBrain stimulation

Post-inhibitory rebound excitation drives extensor activity following spinal cord stimulation.

Amr A Mahrous, Matthieu K Chardon, Michael D Johnson, Jack F Miller, C J Heckman

Abstract read
In one paragraph

Article in Brain stimulation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Amr A MahrousDepartment of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Matthieu K ChardonDepartment of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Michael D JohnsonDepartment of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Jack F MillerDepartment of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
C J HeckmanDepartment of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA; Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA; Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA; Shirley Ryan AbilityLab, Chicago, IL, 60611, USA. Electronic address: c-heckman@northwestern.edu.

Funding

Neuromodulation of motoneuronal processing of dynamic synaptic inputsR37NS135820 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Charles Heckman · 2024 to 2026
$1.1M
NINDS NIH HHS R37 NS135820
6 · The paper itself

Abstract

backgroundNeural circuits throughout the CNS can exhibit rebound excitation following prolonged periods of inhibition. However, the potential to control this phenomenon and harness it for clinical applications remains largely unexplored.

objectiveWe investigate rebound excitatory responses evoked by spinal cord stimulation (SCS) that can generate functional motor output, providing a testable model of circuit-level rebound excitation relevant to neuromodulation across the CNS.

methodsBrief (5 s) electrical stimulation trains were delivered to the lumbar spinal cord in adult cats. We recorded intracellular neuronal activity in the cord and EMG and force output from hindlimb muscles.

resultsSCS elicited a robust and long-lasting rebound excitation selectively targeting the ipsilateral ankle extensors-a response we term Long Extension Activated Post-stimulation (LEAP). The force output during LEAP can support weight-bearing in cats, underscoring its clinical potential. Intracellular recordings revealed that extensor motoneurons received strong inhibitory inputs during stimulation, driven by reciprocal inhibition via proprioceptive afferents. Upon cessation of stimulation, a shift to a rebound excitatory synaptic input occurred, resulting in sustained firing in extensor motoneurons during LEAP. We also observed concurrent dynamic changes in interneuron firing across spinal laminae, suggesting broad circuit engagement. We systematically mapped the parameter space required to reliably evoke LEAP, including stimulation location, amplitude, and frequency, providing a framework for controlled rebound activation.

conclusionsLEAP represents a novel rebound response that can generate weight-supporting postural output. This mechanism not only expands the therapeutic potential of SCS in motor disorders but also serves as a model for modulating rebound excitation throughout the CNS.

Indexed as

Motor NeuronsMuscle, SkeletalNeural InhibitionSpinal CordSpinal Cord StimulationAnimalsCatsElectric StimulationElectromyographyFemaleHindlimbInterneuronsMaleExtensor motoneuronsMotor rehabilitationNeuromodulationPost-inhibitory rebound excitationProprioceptive afferentsReciprocal inhibitionSpinal cord stimulation

Identifiers

PMID41052711
PMCPMC12945446

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.