Optimization of Repetitive Transcranial Magnetic Stimulation With Priming In Chronic Stroke

Abstract

Purpose: Stroke is leading cause of long-term disability in the United States. The direct destruction of neural tissue from stroke combined with imbalances in transcallosal-mediated interhemispheric inhibition complicate motor recovery. Repetitive transcranial magnetic stimulation (rTMS) is thought to condition surviving but dormant neurons in the ipsilesional primary motor cortex (M1) region to become more amenable to voluntary recruitment during affected extremity movement. Low-frequency rTMS suppresses hyperexcitability in the contralesional hemisphere which can "disinhibit" the ipsilesional hemisphere resulting in greater ipsilesional M1 excitability. A bout of high-frequency excitatory rTMS, referred to as priming, potentiates the suppressive effects of low-frequency rTMS in healthy individuals. The objective of this study was to compare changes in brain excitability and affected hand function following three different rTMS treatments to ascertain whether potential gains from priming stimulation translate to the stroke brain. Methods: Eleven adults (3 females, mean age ± SD = 66 ± 9.4 years) with chronic stroke received three treatments (active 6-Hz priming + active 1-Hz rTMS, active 1-Hz priming + active 1-Hz rTMS, and sham 6-Hz priming + active 1-Hz rTMS) to contralesional M1 in random order over a five-week course with a one-week washout period between treatments. Cortical excitability including interhemispheric inhibition, short-interval intracortical inhibition, intracortical facilitation, and cortical silent period measures along with affected hand function were analyzed using a mixed effects linear model. The model checked for carryover, treatment-by-period interactions, and baseline differences before analyzing within- and between-treatment differences from baseline. Results: Active 6-Hz primed 1-Hz rTMS produced significant within-treatment differences in short-interval intracortical inhibition and cortical silent period duration from baseline indicating reduced intracortical inhibition. Compared to active 1-Hz and sham 6-Hz primed 1-Hz rTMS, active 6-Hz priming generated significantly greater decreases in cortical silent period duration. Discussion: The utility of priming in stroke does not present in such a straightforward manner as it does in healthy individuals given that active 6-Hz priming did not potentiate all outcome measures. Several potential factors are discussed. Our significant findings support the existence of `synaptic wisdom' in the stroke brain involving the deployment of homeostatic and/or metaplastic processes that preserve synaptic function.