Using TMS-EEG to assess effective connectivity

Our brain is a network of areas that communicate with one another in order to
generate behavior. To be able to understand how our brain works it is important
that we can investigate how different areas of our brain communicate with one
another. In the past we have developed a technique to study this that is called
'paired-pulse TMS'. Using this technique we try to investigate how activity in
one brain region results in activity in other brain regions.

We can clarify this with an example. The 'motor cortex' of our brain controls
movement, for instance pressing a button. The motor cortex, however, receives a
lot of information from other brain regions ('which button', 'using which
finger', 'when you have to press'). By examining which area is active just
before the motor cortex becomes active, we can investigate which areas provide
this information to the motor cortex.

In many diseases the effective communication between brain regions is
disturbed. In a stroke, for instance, a relay station between two brain regions
can be damaged, resulting in the impaired transfer of information between them.
It is therefore very important that we can quickly assess these communcations.
The research is part of a larger program aimed at further developing methods to
study the communication between brain areas.

To develop TMS-EEG as a technique to study the interaction between brain
regions. The specific experiments in this study are aimed at investigating the
effects of brief activations of specific brain regions using TMS on signals
recorded non-invasively using EEG.

The study consists of three different *Arms*. Each Arm contains a different
experiment, assessing a unique aspect of the TMS-evoked potential.

In Arm 1, stimulation will be targeted to the motor cortex. Participants will
engage in a motor preparation task. These manipulations are known to affect the
activity of the motor cortex. Hence, this arm allows us to assess how the
TMS-evoked potential over this brain region is differentially modulated by
changes in activity in this brain region.

In Arm 2, the effects of an earlier pulse over a region connected to the motor
cortex (the contralateral motor cortex and the ipsilateral frontal cortex) on
the TMS-evoked potential elicited by motor cortex stimulation will be assessed
in the absence of an explicit task for the participant. In other words, this
Arm presents a first test of whether this technique can be used to assess
interactions between different brain regions.

In Arm 3, we will combine these two manipulations and test whether long-range
cortical interactions as assessed using the TMS-evoked potential are modulated
by cognitive state. Participants will perform a grasping task while the
interaction between inferior parietal lobule and superior parietal lobule with
the motor cortex are assessed.

Participants will receive TMS pulses, the effects of which will be measured
using EEG. The number, frequency, and intensity of the TMS pulses will be
within published safety norms (Rosse et al., 2009, Clin Neurophysiol).

There is no direct benefit of this research for the participants. Transcranial
magnetic stimulation (TMS) is an often used, non-invasive technique based on
the principle of electromagnetic induction. During stimulation a participant
will probably hear a clock sound of the TMS pulses and experience stimulation
of nerves and muscles on the head. The most often reported side effect is a
mild and quickly passing headache (2-4%). A strong headache is very rare
(0.3-0.5%). In TMS studies of specific patient populations (e.g., those with
epilepsy) or in studies using protocols deviating from the norm (e.g., in
stimulation intensity of stimulation frequency) epilepsy has been reported in
exceptional cases. In this study we will only work with healthy participants
and use stimulation protocols in accordance with the standard safety norms. All
participants will be screened for relevant past medical events and other
TMS-related safety aspects (e.g., metal in or on the head) prior to the study.
There are no serious adverse events expected in this study, risk and burden to
the participants is considered minimal. MRI, used in Arm 3, is associated with
strong magnetic fields, requiring that participants do not have any metal in or
on their model. MRI is also very loud, requiring participants to wear ear
defenders.