P 174. Effects of paired associative stimulation on developmental motor plasticity in children

Abstract

Transcranial magnetic stimulation (TMS) offers increasingly sophisticated means of assessing neurophysiology and neuroplasticity mechanisms but applications in children have been limited. Paired associative stimulation (PAS) is an advanced TMS method that pairs peripheral sensory stimulation with TMS primary motor cortex (M1) stimulation. PAS induces rapid, reversible and topographically specific increases in adult motor cortex excitability consistent with NMDAR-dependent long-term potentiation. PAS has not been studied in the more plastic brains of children. Our aim wasto define the developmental profile of PAS in children. We hypothesized that rates of PAS MEP enhancement would be higher in children compared to adults. Healthy, right-handed children aged 6–18 years were recruited from the Alberta Perinatal Stroke Project (APSP) healthy control cohort and general population. Median nerve stimulation (300% sensory threshold) was delivered 25 ms prior to suprathreshold (1 mV) left M1 stimulation (90 pairings, 7 min).Difference in mean peak-to-peak amplitude of right APB motor evoked potentials (MEP) was the primary outcome. Forty single pulse TMS measures were obtained at baseline, immediately after, and 15, 30, 45, and 75 min post-PAS. PAS effects were categorized as definitive (significantly elevated post-MEP at multiple timepoints), possible (single timepoint only) or no effect. Secondary outcomes included change in slope of stimulus response curve (SRC) post-PAS and standard safety and tolerability evaluations. Of 15 children (9 male, mean age 12 years), 8 (53%) showed definitive positive PAS effects, 2 were possible, and 5 showed no MEP change following PAS (none showed a decrease). Despite this, mean SRC slope increased across the entire group (pre 5.43 ± 1.09, post 6.50 ± 1.14, p = 0.05). Of the 8 children with definite PAS, maximal mean MEP increase was immediately post-PAS in 5 and at 15 min in 3. PAS effect was not clearly associated with age ( p = 0.24). PAS procedures were well tolerated with no serious adverse events. Recorded tolerability scores were favorable, scoring better than “a long car ride” on average. Wrist pain was common (20%) but became quickly tolerated. Other side effects (headache, neck pain, tingling, nausea, presyncope) were infrequent (<7%) and mild. PAS paradigms appear safe and well tolerated in children. Frequency of positive PAS effects may be higher in children (>50%) than in adults. SRC curves may be more sensitive than mean MEP amplitude changes to PAS effects. PAS may provide new insights into mechanisms of developmental motor plasticity and inform therapeutic interventions in cerebral palsy and motor disorders of childhood.