Left prefrontal activity and the voluntary control of social emotional behaviour

The left ventrolateral prefrontal cortex (vlPFC) is found to be involved in the
control of social emotional behaviour. This social emotional behaviour could be
quantified by means of the approach-avoidance (AA) task, in which happy or
angry facial expressions should be either approached or avoided by pulling or
pushing a joystick, respectively. It is found that people are more likely to
approach positive and to avoid negative facial expressions (affect-congruent
condition). In the affect-incongruent condition (i.e. avoid positive and
approach negative faces), on the other hand, reaction times are found to be
longer because the automatic emotional tendencies have to be suppressed (the
so-called congruency effect). The aim of this project is to investigate whether
activity of the vlPFC is crucial for the control of social emotional behaviour.
In order to infer a causal relationship, Trancranial Magnetic Stimulation (TMS)
will be applied over the vlPFC. We hypothesize that the congruency effect will
increase after inhibition of the left vlPFC.

The aim of this study is to investigate whether the vlPFC is crucially involved
in the voluntary control of social emotional behaviour. Presumably, the
congruency effect will be larger (i.e. higher reaction times in the incongruent
condition) on the approach-avoidance task after inhibition of the left vlPFC by
TMS. This finding would indicate a crucial role for the vlPFC in overruling
automatic emotional tendencies.
In previous studies, endogenous testosterone and cortisol were found to
modulate social emotional behaviour. Therefore, hormonal measures will be taken
into account. We expect to find a positive correlation between cortisol and the
congruency effect and a negative correlation between testosterone and the
congruency effect.
Furthermore, to investigate (and control for) the influence of TMS on cerebral
blood flow, Arterial Spin Labeling (ASL) will be performed. By means of this
technique, it is possible to magnetically label the blood supply to the region
of interest (PFC), which gives an indication of the cerebral blood flow in the
specific region. We expect to measure less cerebral blood flow in the left
vlPFC after inhibition with TMS.

The study will consist of four sessions, each separated by approximately a
week. During the first session, the motor threshold (MT) will be determined (to
determine the stimulation intensity in the later TMS-sessions) and a structural
MRI-scan will be made (in order to localize the TMS coil on the left vlPFC in
the other TMS-sessions). Furthermore, during this first session, a short cTBS
protocol (20 sec.) will be applied on the vlPFC at a low intensity (80% of
aMT). By this means, subjects will be allowed to indicate whether they would
like to proceed with the experiment. In the other three sessions, an off-line
TMS-protocol will be used in which Theta Burst Stimulation (TBS) or repetitive
TMS (5 Hz.) will be administered. In order to control for the effects of TMS on
the cerebral blood flow, subjects will perform the AA-task during the
measurement of ASL. Moreover, because endogenous testosterone and cortisol were
found to influence approach-avoidance behaviour, these hormones will also be
taken into account.

All participants will receive two different theta-burst stimulations of 600
pulses and one repetitive TMS (5Hz.) of 200 pulses at 80% of active motor
threshold on three different sessions:
1. Continuous TBS (inhibition) over the vlPFC (experimental intervention).
2. Repetitive TMS (5Hz.) over the vlPFC (to control for stimulation).
3. Continuous TBS over the vertex (to control for site ).

All TMS protocols will take 40 sec.

TMS is not painful at the level of intensity used in this project (i.e. 80% of
active motor threshold). From the previous literature we know that, in rare
cases, subjects could report a (light) headache, which could be treated easily
with paracetamol. On the basis of incidental epileptic seizures triggered by
TMS in early 90*s, safety-guidelines were established to set up the maximum
duration of TMS stimulation (Wassermann, 1998). Therefore, our protocols will
follow these safety TMS guidelines. Furthermore, all subjects will be
pre-screened for relevant medical history, drug abuse, head trauma,
neurological or psychiatric illness, pregnancy, heart disease, cardiac
pacemakers, medication pumps, tricyclic antidepressants, neuroleptics, family
history of neurological illness, psychiatric illness or epilepsy. Because the
risk associated with participation can be considered negligible and the burden
can be considered minimal, we do not expect adverse events during the project.