The effect of a hand motor task on the cortical excitability measured by TMS

In the last three decades Transcranial Magnetic Stimulation (TMS) has become an
important scientific technique in clinical studies and in the field of
neuroscience. By sending a large and rapid current through a copper coil a
magnetic field is produced, that in its turn induces an electric field in the
underlying tissue. When the coil is placed on top of the scalp it can
depolarize neurons and evoke action potentials (EP), when the field reaches a
certain threshold. For the motor cortex these evoked potentials can be
objectified by measuring the motor evoked potential (MEP) in the corresponding
contra-lateral muscle with the use of electromyography (EMG). The stimulation
intensity needed to evoke an MEP with a specified amplitude is a measure for
the individual cortical excitability at a specific point in time.

The cortical excitability, however, is not completely fixed and can be
(temporarily) changed. This can be done, for example, with a simple motor task.
This study is set up to see if a specific hand motor task, that is used to
measure freezing in the upper part of the body of patients with Parkinson*s
Disease (PD), induces changes in the cortical excitability. It is important to
know if a certain task induces a change in the cortical excitability, before it
is combined with TMS in a protocol. The knowledge gained here can be used to
design future protocols and help to explain unexpected results in complicated
protocols that combine TMS and motor tasks.

This study is set up to see if a specific hand motor task, that is used to
measure freezing in the upper part of the body of patients with Parkinson*s
Disease (PD), induces changes in the cortical excitability. It is important to
know if this task induces a change in the cortical excitability to design
future protocols and help to explain (possible) unexpected results in
complicated protocols that combine TMS and this motor task.

We therefore state the following objectives:

The primary objective of this study is, to find out if a simple rhythmic
flexion-extension of the index finger changes the cortical excitability of the
primary motor cortex measurable with TMS.

In addition to this primary objective, we want to find out whether there is an
effect of task difficulty on the changes in the cortical excitability of the
primary motor cortex.

The study is designed as a within-subject experiment with healthy adult
volunteers. It will span one intake session and two experimental sessions.
During each of the two experimental sessions TMS will be combined with a hand
motor task. The only difference between the sessions is the movement amplitude
in the hand motor task. The first experimental session takes place in direct
succession to the intake session on the first day. The second experimental
session will take place on a different day.

1. During the intake session, the participants will be familiarized with the
TMS procedure and the motor task.
2. Each session consists of six major parts, namely (1) the determination of
the cortical hotspot and resting motor threshold (RMT), (2) TMS pre
measurements, (3) a bimanual hand motor task, (4) TMS post 1 measurements, (5)
rest and (6) TMS post 2 measurements. The total duration of one session is
approximately 2 hours, including possible breaks. The TMS in (2), (4) and (6)
will be applied over the cortical location that evokes the most constant
response in the contra-lateral first dorsal interosseous (FDI) muscle. This
muscle is also used in the motor hand task. In this task the subject has to
flex and extend their index fingers with a specified frequency. The flexion and
extension is performed in anti-phase. Each TMS block (2), (4) and (6) contains
100 single pulses and 20 trials of paired-pulse TMS.

The study takes place at the Department of Neurology, Radboud University
Medical Centre Nijmegen.

Per experimental session, each subject will receive 300 trials of single-pulse
TMS, 60 trials of paired-pulse TMS and approximately 100 single pulses for
determination of the hotspot and rest motor threshold (RMT).

The burden for the subjects is minimal. They have to be present during two
experimental sessions of two hours. In advantage they have to withdraw from
alcohol and drugs as stated in E4.

Concerning the benefits and risks:

Participants will not directly benefit from their participation in the study
(except for the financial compensation in D11). Transcranial magnetic
stimulation (TMS) is a widely used non-invasive brain stimulation technique,
based on the principle of electromagnetic induction. During stimulation, the
participant will likely hear the clicks of the TMS pulses and experience
stimulation of nerves and muscles of the head. The most common side effect is a
light transient headache (2-4% occurrence). A severe headache is uncommon
(0.3-0.5% occurrence). In TMS studies of patient populations (e.g. epilepsy) or
those exceeding the standard protocols (e.g. in intensity or frequency)
epileptic seizures have been reported in rare cases. In the current study
healthy participants will be stimulated with a protocol that falls within the
safety guidelines. All subjects are screened for their relevant medical history
and other TMS safety aspects (e.g. metal parts in the head). In summary,
because the risk and burden associated with participation can be considered
negligible-to-minimal, we do not expect serious adverse events during the
project.