Abstract
Intersegmental neural modulation refers to the influence of voluntary activation of one limb on the excitability and inhibitory balance of remote motor representations. Recent evidence suggests that high-intensity upper-limb isometric contractions can transiently enhance corticospinal excitability and modulate intracortical or interhemispheric inhibition of lower-limb motor areas, yet the consistency of these findings remains unclear. This systematic review synthesized evidence on the effects of upper-limb isometric contractions on corticospinal excitability and inhibitory mechanisms of lower-limb motor representations in healthy adults. Following PRISMA 2020 guidelines, searches were conducted in PubMed/MEDLINE, Scopus, Web of Science, Embase, and Cochrane CENTRAL. Eligible studies included healthy adults (18-65 years) performing upper-limb isometric contractions quantified as percentage maximal voluntary contraction (%MVC), with outcomes assessing lower-limb corticospinal excitability or intracortical/interhemispheric inhibition. Two independent reviewers screened studies, extracted data, and assessed risk of bias. Seventeen studies (n = 351) met inclusion criteria. Most reported increases in lower-limb motor evoked potential amplitude during upper-limb contractions, particularly at intensities ≥ 70% MVC. Reductions in short-interval intracortical inhibition were common, indicating transient disinhibition of lower-limb primary motor cortex representations. Findings for interhemispheric inhibition were inconsistent, likely attributable to variability in contraction tasks and transcranial magnetic stimulation parameters. Upper-limb isometric contractions consistently facilitate lower-limb corticospinal excitability and reduce intracortical inhibition in healthy adults. Although mechanistic patterns converge, methodological heterogeneity limits confidence in the magnitude of effects. Future studies require standardized experimental protocols and adequate sample sizes to clarify intensity-response relationships and underlying neurophysiological mechanisms.