Motor system plasticity induced by non-invasive stimuli

Abstract

Precisely timed paired stimulation protocols can change cortical and subcortical excitability. In the first study, induction of plastic changes in the long-latency stretch reflex (LLSR) by pairing non-invasive stimuli was attempted, at timings predicted to cause spiketiming dependent plasticity (STDP) in the brainstem. LLSR in human elbow muscles depends on multiple pathways; one possible contributor is the reticulospinal tract. The stimuli used are known to activate reticulospinal pathways. In healthy human subjects, reflex responses in flexor muscles were recorded following extension perturbations at the elbow. Subjects were then fitted with a portable device which delivered auditory click stimuli, and electrical stimuli to biceps muscle. The LLSR was significantly enhanced or suppressed in the biceps muscle depending on the intervention protocol. No changes were observed in the unstimulated brachioradialis muscle. Although contributions from the spinal or cortical pathways cannot be excluded, the results were consistent with STDP in reticulospinal circuits. In the second study, baseline TMS responses were recorded from two intrinsic hand muscles, flexor digitorum superficialis (FDS) and extensor digitorum communis (EDC). In the first phase, paired associative stimulation (PAS) was delivered by pairing motor point stimulation of FDS or EDC with TMS. Responses were then remeasured. Increases were greatest in the hand muscles, smaller in FDS, and non-significant in EDC. In the second phase, intermittent theta-burst rapid-rate TMS was applied instead of PAS. In this case, all muscles showed similar increases in TMS responses. This study showed that potential plasticity in motor cortical output has a gradient: hand muscles > flexors > extensors. However, this was only seen in a protocol which requires integration of sensory input (PAS), and not when plasticity was induced purely by cortical stimulation (rapid rate TMS). In the third study, motor imagery was paired with TMS in healthy human subjects. They were asked to imagine wrist flexion or extension movement, while TMS was delivered to the motor cortex. Six different protocols were tested, but only flexor imagination with TMS and extensor imagination with TMS showed significant facilitation following the test. Flexor imagination with TMS increased motor evoked potential (MEP) in all four Abstract 2 muscles with maximum changes towards flexor, whereas extensor imagination with TMS increased MEP only in extensor. Above changes in the cortical or subcortical excitability evoked by non-invasive stimulation protocols were consistent with long term potentiation and long-term depression mediated plastic changes