Neurophysiology of Surround Inhibition in the Human Motor Cortex
Condition: Normal Physiology
Study type: Observational

Summary: 
      Background:

      Movement disorders have many different causes and symptoms. Researchers still do not fully
      understand which parts of the brain are involved in fine movement. They want to learn about
      which brain regions could be abnormal in people with movement disorders.

      Objective:

      To better understand how the brain controls movement.

      Eligibility:

      Healthy, right-handed adults age 18-70 years old.

      Design:

      Participants will be screened with a physical exam and questions about their handedness. They
      may have a urine test.

      Participants will have 1 or 2 clinic visits. The first visit will last about 1.5 hours. The
      second will last about 3 hours.

      Participants will have structural magnetic resonance imaging (MRI). A strong magnetic field
      and radio waves take pictures of the brain. Participants will lie on a table that slides in
      and out of a metal cylinder.

      Participants may have transcranial magnetic stimulation. A wire coil is held on the scalp. A
      brief electrical current is passed through the coil and creates a magnetic pulse that
      stimulates the brain. Participants will wear a pair of glasses or a headband with small
      sensors so researchers can track head position.

      Participants will perform a simple index finger movement task.

      Participants may have surface electromyography from at least two hand muscles. Small metal
      disk or adhesive pad electrodes will be taped to the skin. Participants will be seated in a
      comfortable chair with their hands placed on a pillow.

      Participants may have an electroencephalography. A cap with small disc electrodes will be
      placed on the scalp.
    

Detailed description: 
      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.
    

Intervention name(s): TMS - sub-study 1; TMS - sub-study 2; TMS - sub-study 3
Intervention type(s): Device; Device; Device
Intervention description(s): TMS pulses will be applied to the motor hotspot of the surround muscle to identify the TMS-evoked potentials corresponding to motor surround inhibition (SI); TMS will be used to stimulate the motor cortex and an inhibitory region of the inferior parietal lobe; TMS pulses will be delivered to the primary motor cortex at rest, at the onset of the motor task, or during the motor task
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Healthy Volunteers
      
Keywords: Surround Inhibition; Motor Control; Transcranial Magnetic Stimulation (TMS); TMS-Evoked Potential