Evaluating developmental motor plasticity with paired afferent stimulation.

AIM: Brain plasticity mechanisms are probably different in children but remain poorly understood. Paired afferent stimulation (PAS) combines peripheral sensory stimulation with transcranial magnetic stimulation (TMS) of primary motor cortex to induce rapid, reversible, topographically specific increases in primary motor cortex excitability suggestive of long-term potentiation in adults. Our aim was to determine frequency, characteristics, age effects, and reproducibility of PAS in school-age children.

METHOD: Typically developing right-handed children (6-18y) were recruited. Median nerve stimulation was delivered 25ms before suprathreshold primary motor cortex stimulation (0.2Hz, 7.5min). Primary outcome was changed in the amplitude of motor evoked potentials (MEPs) at five time points after PAS (0, 15, 30, 45, 75min) expressed as area under the curve. Reproducibility was evaluated. Secondary outcomes included stimulus response curves and safety/tolerability.

RESULTS

Of 28 children (20 males, mean age 12y), 64% demonstrated PAS effects (11 definite, seven probable). PAS effects were sustained across all time points to 75min (p=0.004). Stimulus response curve scores increased after PAS (n=9, p=0.02). PAS effect and age were not correlated. PAS was highly reproducible (p=0.925, r=0.283). Tolerability was favorable without adverse events.

INTERPRETATION: PAS effects are present and reproducible in children. Pediatric PAS paradigms appear safe and tolerable. PAS may provide insight into endogenous developmental plasticity, informing future studies in children with cerebral palsy and other motor disorders.