Combining cognitive bias modification with rTMS: Evidence from a single session intervention in a dysphoric student population

In recent years, a number of studies on the use of high frequency rTMS applied
to the left DLPFC have proven its favorable effect in reducing depressive
symptoms in a population suffering from recurrent major depressive disorder
(MDD). Next to this therapeutic effect, the stimulation of the left DLPFC has
been found to affect attention allocation towards negative pictorial stimuli
during a dot-probe task, an instrument measuring attentional biases. A second
line of research has tried to affect these attentional biases, as they have
been found to play a causal role in the development and maintenance of
emotional disorders. Studies on this attention bias modification (ABM) training
have proven its effectiveness in reducing an attentional bias towards negative
pictorial stimuli in depression, and even more important, its therapeutic
effects in reducing emotional vulnerability. ABM has been further suggested to
increase attentional control. Recently, a study has examined the neural
substrates underlying this form of ABM training, revealing that ABM modulates
the activity of the DLPFC. In sum, both techniques that are designed to
ultimately reduce depressive symptoms seem to affect neural activity of the
DLPFC as well as an attentional bias towards negative stimuli. Adding ABM to
the rTMS treatment thereby might amplify the beneficial effects on depressive
symptomatology and attentional processing.

The aim of this study is to test in a single session study in participants with
subclinical depressive symptoms, whether adding ABM to rTMS treatment might
maximize the beneficial effects on attentional bias, attentional control and
emotional vulnerability.

For this study, 188 participants will be randomly assigned to one of four
groups (each n=47). The first group will first receive an active rTMS treatment
followed by a computerized ABM training. The second group will receive the same
rTMS treatment followed by a sham ABM training whereas the third group will
receive a sham-rTMS treatment followed by a usual ABM training. The fourth
group will function as a control group and therefore receive a sham-rTMS
treatment followed by a sham ABM training.

We will administer offline high frequency TMS to the left DLPFC with an
intensity of 110%rMT, in 30 trains of 10Hz pulses with a duration of 5 seconds
and an inter-train interval of 25 seconds (50 pulses per train, 1500 pulses per
session).
Besides the TMS stimulation we will also make use of an attention bias
modification (ABM) training, in the form of a modified version of the dot-probe
task. Positive and negative pictures, equivalent in low-intensity will be
selected. Fifty percent of these pictures will exclusively contain faces (i.e.,
sad or happy expression) and the other half will depict scenes (e.g., puppies,
grave yard). During the training, always one positive and one negative picture
will be presented on the screen simultaneously, whereby only the positive
picture will get replaced by the probe. Participants are asked to react to the
probe as fast as possible by means of a button press.

Except for financial compensation or course credit points, possible benefit
resulting from the treatment cannot be guaranteed to participants. Transcranial
magnetic stimulation (TMS) is a widely used non-invasive brain stimulation
technique, based on the principle of electromagnetic induction and it will be
applied only once to half of the participants. 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
in studies that exceeded 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 participants are screened for their relevant medical
history and other TMS safety aspects (e.g. presence of metal parts in the
head). There are no risk factors related to the computerized ABM training. In
summary, because the risk and burden associated with participation can be
considered negligible-to-minimal, we do not expect any serious adverse events
during the project.