Stroke is among the principal causes of death worldwide and even in the best-case scenario often leaves its sufferers with permanent disabilities. No current treatment exists to undo the resulting tissue damage and efforts to reduce the damage requires immediate intervention within hours of stroke onset. However, some function can be restored by commandeering the brain’s natural plasticity to amplify weakened connections or alternatively dampen over active networks.

Although conventional stroke rehabilitation has the ability to improve the overall function of stroke victims, the functional outcomes are often of limited practical significance and after completing standard rehabilitation approximately 50–60% of patients still exhibit some degree of motor impairment and require at least partial assistance in activities of day-to-day living

Recently, it has been shown that pairing the stimulation of two regions through the coordination of two TMS coils targets the intervening connectivity. This approach, termed paired associative stimulation (PAS), is based on Hebbian plasticity, according to which connections are strengthened or weakened depending on the timing of the pre- and post-synaptic stimuli.

In the interhemispheric PAS protocol, the direction of the effect is determined by which hemisphere is stimulated first (H1) and which hemisphere is stimulated second (H2). In one such study, PAS applied between the two primary motor cortices in healthy subjects reduced interhemispheric inhibition. As such, we hypothesize that PAS from the contralesional hemisphere (H1) to the ipsilesional hemisphere (H2) will facilitate motor rehabilitation by reducing the interhemispheric inhibition of the ipsilesional hemisphere.

We use daily, multi-session PAS protocol in stroke patients to decrease interhemispheric inhibition to the ipsilesional hemisphere. Besides more directly targeting connectivity than rTMS protocols, the reduced frequency of pulses (pair every 3 seconds) and number of pulses (600 vs 1400) reduce the danger of inducing seizures, allowing for earlier intervention following stroke