Objectives:
The purpose of this protocol is to improve understanding of the neurophysiological mechanisms that underlie the phenomenon of surround inhibition in the human motor cortex. It is known that patients with focal hand dystonia have abnormal motor surround inhibition. However, the physiology of this phenomenon still remains unclear. The 3 sub-studies proposed under this protocol will integrate several neurophysiological techniques to explore different aspects of motor surround inhibition. The objectives of sub-study 1 are (a) to identify the EEG correlate of motor SI (b) to determine the relationship between short interval intracortical inhibition (SICI) and SI, both of which are compromised in patients with FHD and (c) to determine if there is an oscillatory frequency band that is relevant for SI. The results from this sub-study will shed light on the inhibitory mechanisms that are critical for motor SI. Sub-study 2 is aimed at determining the influence of parietal conditioning on motor surround inhibition. If conditioning the parietal cortex enhances SI, we can conclude that the parieto-motor inhibitory network may be involved in motor SI and that this network could be affected in focal hand dystonia. Sub-study 3 will explore SI during different motor tasks.
Study population:
We intend to study up to 95 healthy volunteers in total. Up to 30 participants will be recruited for sub-study 1, 35 for sub-study 2, and 30 for sub-study 3.
Design:
Sub-study 1: This will be an exploratory study. Participants will perform an auditory cued index finger movement task and motor evoked potentials will be elicited by stimulating the motor hotspot of a surround muscle using transcranial magnetic stimulation (TMS). EEG will be recorded continuously. Single or paired TMS pulses (with postero-anterior or antero-posterior current) will be delivered either while the subject is at rest or at movement onset. TMS-evoked potentials (TEPs) will be obtained by time-locked averaging of all the trials in each condition. The amplitudes of the different peaks of the TEP will be compared across conditions which may be correlated with the degree of SI or SICI. The components of the TEP that are most relevant to motor SI will thus be identified.
Sub-study 2: This will be a hypothesis-driven study. Our primary hypothesis is that parietal conditioning will influence motor SI in healthy volunteers. Participants will perform an auditory cued index finger movement task and motor evoked potentials will be elicited by stimulating the motor hotspot of a surround muscle using transcranial magnetic stimulation. Two coils, one positioned over the motor cortex and the other over an inhibitory region of the inferior parietal lobule, will deliver TMS pulses at a fixed inter-stimulus interval. The pulses will be delivered either while the subject is at rest or at movement onset. The ratio of mean MEP amplitude obtained with parietal conditioning to that obtained with motor cortex stimulation alone at movement onset will reveal any parieto-motor influence on SI.
Sub-study 3: This will be an exploratory study. Participants will be asked to perform different motor tasks such as activating an intrinsic hand muscle at different levels of activation, sequential muscle activation or more complex tasks such as writing. Single TMS pulses will be delivered at primary motor cortex at rest, at the onset of the motor tasks or during the motor tasks. MEPs will be measured in the active and surround muscles. The ratios of MEP amplitudes during different levels of activation in the active and surround muscles will reveal
modulation of SI during these tasks.
Outcome measures:
For sub-study 1, our outcome measures will be (1) amplitudes of the different TEP peaks (2) degree of surround inhibition and short interval intracortical inhibition (3) correlation between them and relevant peak amplitudes (4) power and cortico-cortical coherence at different frequency bands.
MEP amplitude will be the primary outcome measure in sub-study 2 and 3.
