Treatment and physiology in Parkinson's disease and dystonia: using transcranial magnetic stimulation to uncover the mechanisms of action

Abstract

Transcranial magnetic stimulation (TMS) has served as an important technological breakthrough in the field of the physiology of movement disorders over the last three decades. TMS has grown popular owing to the ease of application as well as its painless and noninvasive character. The technique has provide important insights into understanding the pathophysiology of movement disorders, particularly Parkinson's disease and dystonia. The basic applications have included the study of motor cortex excitability, functioning of excitatory and inhibitory circuits, study of interactions between sensory and motor systems, and the plasticity response of the brain. TMS has also made important contributions to understanding the response to treatments such as dopaminergic medications, botulinum toxin injections, and deep brain stimulation surgery. This review summarizes the knowledge gained to date with TMS in Parkinson's disease and dystonia, and highlights the current challenges in the use of TMS technology.

Figure 1

A: Illustration of neurons and circuitries activated by TMS 1. TMS pulses applied to the motor cortex, 2. Motor cortex interneurons that mediate SICI and LICI, 3. Sensory cortex neurons that mediate sensorimotor integration such as SAI and LAI, 4. Corticospinal output neurons that generate motor evoked potentials are activated transsynaptically by the TMS pulse, 5. Sensory stimuli from the periphery are projected to sensory cortex by the thalamus, 6, Motor evoked potentials recording from the first dorsal interrosseus muscle, 7. Median nerve stimulation at the periphery that forms the conditioning stimulus. B: Examples of TMS paradigms The first column shows motor cortex inhibition (SICI and LICI) and sensorimotor integration (SAI and LAI) and the second column shows sensorimotor plasticity obtained with paired associative stimulation protocol (PAS). Traces show average motor evoked potential recordings with test pulse alone (TS) or preceded by median nerve stimulation delivered at interstimulus interval (ISI) of 20ms (MNS 20) and 200ms (MNS 200) or when preceded by a conditioned stimulus (CS) delivered to the motor cortex at an interstimulus interval of 2ms (CS2) and 100ms (CS100) For the PAS protocol, 90 pairs of median stimulation preceding the TMS pulse by 25 ms are delivered.