The Role of brain area S1 in the perception of actions.
A combined TMS and fMRI study on the functional connectivity of the human mirror neuron system.

Mirror Neurons (MN) were discovered in the lab of Rizzolatti and col. (for an
overview see Rizzolatti and Craighero, 2004): these neurons, located in the
ventral premotor cortex and the rostral inferior parietal lobe of the monkey
respond while the monkey performs an action (e.g. grasping a peanut) and when
the monkey observes another individual performing a similar action - as if the
monkey were in the skin of the other individual. These neurons suggest, that
the brain of the monkey automatically transforms what it sees other agents do
into the motor representations necessary for performing a similar action.
These findings however raised a number of important questions. (a) Does a
similar system exist in the human brain? (b) What brain regions show such a
mirror phenomenon? (c)Given that the function of a neuron is determined by the
pattern of connections that links it to other neurons, what pattern of
connectivity between brain areas make mirroring possible?

The human Mirror Neuron System
Regarding question (a), although it is not normally possible to record the
activity of single neurons in humans, a number of techniques now converge to
suggest that humans have indeed a mirror system similar to that of monkeys (see
Rizzolatti and Craighero, 2004). Neuroimaging methods including positron
emission tomography and more recently functional magnetic resonance imaging
(fMRI) show that regions directly similar to those in which mirror neurons have
been found in the monkey (the ventral premotor cortex and rostral posterior
parietal cortex) are active both when participants perform certain actions and
while they see other individuals perform similar actions (e.g. Gazzola et al.,
2007).

Which Brain Areas are Involved?
Question (b) and (c) however remain a matter of controversy. In the monkey,
where single cell recordings are the main method for exploring mirror neurons,
an experimenter chooses where in the brain to look for mirror neurons. This has
so far only been done for the ventral premotor and posterior parietal cortex.
It is therefore unclear whether other brain areas have similar properties.
Neuroimaging studies in humans however show that other brain areas are indeed
also involved both during the observation of other people*s actions and the
execution of similar actions. This data extends the original finding of mirror
neurons in the monkey by suggesting that a whole network of brain regions is
common to both the observation and execution of actions. This *shared circuit*
involves the ventral and dorsal premotor cortex, the posteior parietal lobe,
the somatosensory cortex and high level visual cortex.

How does the sets of brain regions of the pMNS interact to enable us to grasp
so intuitively what is going on in other individuals?
The present projects aims at investigating the connectivity between the brain
areas identifyed as part of the human Mirror Neuron System, in particular the
connections between the S1 area and the rest of the MNS. To do so two
techniques are going to be used: Repetitive Transcranial Magnetic Stimulation
(rTMS) is going to be used to disrupt the functioning of the targeted brain
area and Functional Magnetic Resonance Imaging (fMRI) is going to be used to
access the activations in the brain while the subject is observing and
executing actions. Data is going to be collected with fMRI before, immediately
after the rTMS and after the effects of the rTMS have dissapeared. Data from
these three sessions is going to be compared. Analysis of the data is going to
include standard fMRI data analysis methods and also various methods of
effective connectivity.

The study combines rTMS with fMRI to compare the activation in the brain when
the S1 brain area is active and when its* function is impaired by the rTMS.
In this study three scanning sessions will be recorded. During the fMRI-scan
sessions subjects will observe actions and execute actions. Just before these
sessions rTMS will be applied on the S1 brain area of the subjects. Two of
these sessions will include sham TMS (no effect on the brain activity) and the
other one will include rTMS by means of Theta Bursts stimulation (TBS), in this
way the functioning of the brain area will be impaired for a short period. In
all cases scanning is done immediately after the stimulation. The sham sessions
serve as a control and enable the researcher to isolate the effects that are
due to the rTMS stimulation and the ones due to the experimental condition.
Between the fMRI sessions will be at least 24 hours.

fMRI and rTMS are both non-invasive techniques, so there is no need of special
preparation of the subject. There are no risks that have been associated with
the fMRI acquisition. Subjects will be exposed to a magnetic field of 3 Tesla
and rapidly alternating gradients and radio frequency fields. This field is
used on a routinely basis in fMRI and MRI research. No harmful side effects
have been reported. On rare occasions, a peripheral nerve (abdomen) is
stimulated by the changing magnet gradients. This might cause an etching
feeling but it is not harmful. The data collected during the fMRI and MRI scans
will be used for research purposes only. However, if severe abnormalities are
noticed a specialist (radiologist or psychiatrist) will be asked for advice,
upon decision of the research team. If it is confirmed by the specialist that
medical treatment is needed, then the General Practitioner indicated by the
subject will be notified.

The safety of the Tetha-Bursts Stimulation (TBS) has been demonstrated in
recent research by Huang and col. (2005) and Di Lazzaro and col. (2005). The
exclusion criteria and safety norms applied to the standard rTMS will be used
as well (see Gates, 1992; Pascual-Leone et al., 1993; Wassermann eta al., 1996;
Wassermann, 1998).

No harmful side effects have been reported when the international safety
guidelines are followed (Wassermann, 1998). The strong magnetic fields used by
both fMRI and rTMS can dislocate ferromagnetic particles inside the brain and
the eyes. In order to exclude subjects with metal particles inside their brain,
subjects will be required to complete a questionnaire and only if none of the
exclusion criteria is met the subject will be allowed to participate in our
experiment.
No immediate benefits for the subjects are expected from their participation in
this study. Results, however, will permit us to understand more fully the
functioning of the human brain.