Investigating the effects of paired somatosensory - cerebellar stimulation on cortical and cerebellar excitability: a TMS study

It is well known that paired associative stimulation (PAS) is capable of inducing long term potentiation-like synaptic plasticity when repeated pairings of an electrical stimulus to the median nerve with a transcranial magnetic stimulation (TMS) applied over the motor cortex (M1) is administered between 21-25 ms (Stefan et al., 2000). Interestingly, when PAS is administered at 25 ms, cerebellar activity can abolish PAS after-effects (Hamada et al., 2012). While this suggests that cerebellar activity may influence the arrival of sensory inputs to the sensorimotor cortex, this has not been directly tested using physiological markers of somatosensory and cerebellar inputs to M1 or somatosensory cortex (S1). Since the cerebellum is capable of priming M1 plasticity through the processing of sensory information, we investigated whether the continuous pairing of sensory afferent information with cerebellar stimulation influences the plasticity of both cerebellar and cerebral regions. We tested whether sensory inputs could be paired with cerebellar stimulation to develop a novel PAS protocol. To this aim, electrical stimulation to the median nerve was delivered 10 or 15 ms before applying TMS over the cerebellum (200 paired stimuli). We measured motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs) as physiological markers of cortical excitability, cerebellum-brain inhibition (CBI) as a marker of cerebellar excitability, and short afferent inhibition (SAI) as a marker of somatosensory inhibition, before and following PAS. Preliminary results showed that sensory-cerebellar PAS significantly modifies M1 excitability, reducing MEP amplitude and increasing SEP amplitude. This effect occurs only when the PAS interval was 10ms, but not at 15ms. Moreover, CBI and SAI were unchanged following PAS. The repetitive pairing of both somatosensory and cerebellar stimulation can induce plasticity effects on cerebral areas. The results of sensory-cerebellar PAS could provide a useful intervention with clinical implications for patients with sensory-motor deficits such as dystonia.