Paired Associative Stimulation to Suppress Contralesional Corticospinal Excitability in Three People with Stroke Using N-of-1 Crossover Design - Abstract
Background: Some of the deficit in people with stroke results from down-regulation of surviving neurons. Up-regulation can be enhanced with transcranial magnetic stimulation methods. Paired associative stimulation (PAS) is one such method but this has not been explored sufficiently in stroke. Further, N-of-1 clinical trials are valuable in eliminating inter-subject variability to develop individualized interventions.
Objective: Explore the effects of PAS using different interstimulus intervals (ISIs) to suppress excitability of the contralesional primary motor area (M1) in stroke.
Methods: We used an N-of-1, blinded, crossover design with random assignment of four PAS treatment arms to three people with stroke. Each PAS treatment involved 225 pairs of transcranial magnetic stimuli to contralesional M1 paired with electrical stimuli to the median nerve at the nonparetic wrist. Three suppressive ISIs plus a sham condition were compared. The dependent variable was cortical excitability measured by peak-to-peak amplitude of motor evoked potentials over time.
Results: Two participants with cortical lesions exhibited significant overall suppression of cortical excitability with an ISI of N20-7ms, whereas a participant with basal ganglia lesion showed significant facilitation with the same ISI.
Conclusions: PAS suppressed cortical excitability in cortical stroke but facilitated excitability in basal ganglia stroke. The divergent responses may stem from literature accounts of metaplasticity differences involving individualized intracellular calcium oscillations around thresholds that govern the magnitude and direction of synaptic plasticity to maintain synaptic homeostasis