Table of Contents

Descending Brainstem Systems Contribute to Ankle Clonus in Humans with Spinal Cord Injury

  1. Monica A. Perez1,2,3,4
  1. 1Shirley Ryan AbilityLab, Chicago, Illinois 60611
  2. 2Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, Illinois 60611
  3. 3Edward Hines, Jr. VA Hospital, Hines, Illinois 60141
  4. 4Department of Physical Therapy and Movement Science, Northwestern University, Chicago, Illinois 60611
  5. 5Department of Neuroscience, University of Copenhagen, Copenhagen 2200, Denmark
  6. 6Memorial University of Newfoundland, St. John’s, NL A1C 5S7, Canada
  1. Correspondence should be addressed to Monica A. Perez at mperez04{at}sralab.org.
  1. Author contributions: E.C., B.C., and M.A.P. designed research; E.C., B.C., and M.A.P. performed research; E.C., B.C., and M.A.P. contributed unpublished reagents/analytic tools; E.C., B.C., A.T.B., M.T.F., S.S., D.D., and M.A.P. analyzed data; E.C., B.C., A.T.B., M.T.F., S.S., D.D., W.Z.R., H.H., G.E.P.P., V.M.T., C.J.H., and M.A.P. wrote the paper.

Abstract

Ankle clonus is a sustained, involuntary, rhythmic muscle contraction frequently observed in humans with spinal cord injury (SCI). Although its pathophysiology remains incompletely understood, converging evidence suggests a role for brainstem systems in its generation. Following SCI, brainstem neuromodulatory inputs partially compensate for the loss of descending motor pathways by regulating motoneuron excitability during involuntary contractions, suggesting their involvement in the generation of clonus. To test this hypothesis, motoneuron excitability in response to Ia synaptic input was quantified using the soleus H-reflex and maximal motor response (H/M ratio). Brainstem involvement was assessed using the long-latency component of the cutaneous reflex (LLR), which is influenced by monoaminergic pathways, and the StartReact response, in which reductions in reaction time to a loud acoustic stimulus are thought to reflect descending drive from the reticular formation, measured in the tibialis anterior and soleus muscles. We studied males and females with chronic SCI, both with and without ankle clonus, using standardized clinical tests across 2 d. Participants with clonus showed elevated H/M ratios, indicating increased motoneuron excitability, whereas those without clonus exhibited lower values than controls. Additionally, individuals with clonus exhibited longer LLR duration and greater LLR magnitude in both muscles, along with shorter reaction times to startle stimuli, consistent with enhanced monoaminergic and reticulospinal contributions. Notably, LLR duration was positively correlated with both StartReact response and H/M ratio. Together, these findings suggest a potential contribution of descending brainstem systems to the maintenance of clonus after chronic SCI.

Footnotes

  • This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS R35 NS122336), Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD115345), and U.S. Department of Veterans Affairs (IRX005051). Natural Sciences and Engineering Research Council of Canada (NSERC) - Discovery Grant #2023-05862, Research Training in Sensorimotor Neurorehabilitation T32 grant (T32HD101395), NIH/NINDS NS125863, and NIH/NICHD R03HD114768.

  • ↵*E.C. and B.C. contributed equally to this work.

  • The authors declare no competing financial interests.

  • Received March 9, 2026.
  • Revision received June 7, 2026.
  • Accepted July 12, 2026.
  1. The Journal of Neuroscience, 46(36): e0432262026

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