The role of the left and right frontal hemisphere on mood and behaviour:
A transcranial direct current stimulation study

There is evidence from the scientific literature to assume a relationship
between a frontal asymmetry in brain activity and cognitive emotional
information processes associated with mood. Transcranial direct current
stimulation (tDCS) is a non-invasive and safe method that applies weak
electrical currents to the scalp that can be used to modulate frontal brain
asymmetries to study this assumed relationship. This study will not only
broaden our understanding of the functional role of the left and right frontal
cortex, but may contribute to the development of alternative ways to treat mood
disorders such as depression by way of non-invasive neuromodulation also.

The aim of the present double blind cross-over sham controlled study is to
study the functional role of the left and right frontal cortex on mood and
behaviour in healthy volunteers by applying tDCS to the left and right frontal
hemispheres.

Placebo controlled double-blind cross-over design.
The experiment will consist of one intak (half an hour) and three test sessions
of one an a half hour each (total: 5 hours)

The experiment consists of on screening/intake and three experimental sessions.
During the first session safety issues and experimental procedures will be
explained to the subject and informed consent is obtained. A standard health
and safety-screening list is administered to check for contra-indications to
non-invasive brain stimulation. Right handedness will be assessed with the
Edinburgh handedness inventory (Oldfield, 1971) and subjects will fill out
standard lab digital personality questionnaires that include the BIS-BAS
(Carver & White, 1994) and BPA questionnaire (Buss & Perry, 1992). Individual
motor threshold (MT) from the left and right primary motor cortex using the
thumb movement visualization method will be measured to determine TMS intensity
(Schutter & Van Honk, 2006). On experimental days participants will be
instructed to refrain from taking psychotropic substances, including coffee,
tea and chocolate at least 2 hours prior to experimentation. During the test
session a mood questionnaire will be administered (5 min) and a four-minute
background EEG recording (15 min including preparation) will be made. Next,
participants will be seated in a comfortable chair en receive direct current
stimulation to the frontal lobes for 15 min. after which the mood questionnaire
(5 min) will be administered and a four-minute background EEG recording (15 min
including preparation) will be made for a second time. Then, the excitability
of the hemispheres will be measured using transcranial magnetic stimulation (20
min). During this measurement the volunteers has to squeeze his/her hands for a
short time prior to the pulse. Finally, an attention tasks will be administered
(10 min).

Schematic overview of the procedure:

Session 1: intake: screening, questionnaires, motor threshold determination
(TMS)
Session 2: testing day1: questionnaire, background EEG, tDCS1, questionnaire,
background EEG, cortical excitability and connectivity (TMS), attention task
Session 3: testng day 2: questionnaire, background EEG, tDCS2, questionnaire,
background EEG, cortical excitability and connectivity (TMS), attention task
Session 4: testingday 3: questionnaire, background EEG, tDCS3, questionnaire,
background EEG, cortical excitability and connectivity (TMS), attention task

MANIPULATION

Transcranial direct current stimulation (tDCS) will be delivered by a
battery-driven constant DC current stimulator (Eldith DC Stimulator (CE 0118),
Ilmenau) using a pair of electrodes in a 5-7 cm (35 cm2) saline-soaked
synthetic sponge at a current intensity of 1 mA for 15 minutes on three
separate sessions.

1- Cl-Ar tDCS: Cathodal electrode left frontal cortex - anodal electrode right
frontal cortex (1 mA/ 35 cm2, 15 min)

2- Al-Cr tDCS: Anodal electrode left frontal cortex - anodal electrode right
frontal cortex (1 mA/ 35 cm2, 15 min)

3- Placebo tDCS: Random montage (0 mA/ 35 cm2, 15 min)


READOUT

Transcranial magnetic stimulation (TMS) will be applied to measure cortical
excitability and connectivity between the hemispheres following tDCS. Using a
coil that will be placed on the head nerve cells can be activated through
magnetic pulses. Whenever the coil is held over the primary motor cortex the
magnetic pulse will cause a thumb twitch (MEP) that can be quantified with a
pair of electrodes fixed to the left and right thumb muscle. A series of 72
pulses to the left and 72 pulses to the right hemisphere (stimulatie interval:
5-7s) will provide insights in tDCS-related changes in cortical excitability
and connectivity between the hemispheres.

Transcranial direct current stimulation (tDCS) is a painless method that
applies weak electric currents to the scalp which are able to temporarily
modulate brain activity. In some cases tDCS causes an itching senstion under
the electrodes or (mild) headache. In rare cases tDCS cause nausea or
dizziness. This technique does not carry any other risks.

Transcranial magnetic stimulation (TMS) is a method that applies magnetic
pulses to scalp to excite neurons in the motor cortex. This neural excitation
causes small hand movements of the muscles that can be recorded using
electrodes attached to the hand. Some people report a (mild) headache during
stimulation. In rare cases TMS causes nausea and dizziness. In extremely rare
cases high frequency TMS (25 Hz or more)can cause an epileptic insult. TMS
safety guidelines as published by the journal of the Federation of Clinical
Neurophysiology (Wassermann EM Electroencephalography and Clinical
Neurophysiology Clinical Neurophysiology 1998 103 1-16). The TMS paramers in
the current research proposal are in the low frequency TMS range (0. 2 Hz or
less) .

Headache can be treated with standard analgesics, like paracetamol (200mg).

With EEG electric brain activity can be recorded from the scalp using a cap
containing electrodes. EEG technique is safe and utilizes gel (salt solution)
to make contacts between the scalp en electrode. Some people may experience the
cap and gel as a little bit uncomfortable.

Questionnaires and the short attention task will administered to monitor mood
and cognitive performance. Neither of these measures carry any significant risk

Procedure will be identical across test sessions (only the applied tDCS varies)
and each session will last for maximal 1 hour. Duration of total study is 4
hours.

Notably, volunteers can withdraw from the study at any given time for any given
reason or for no reason at all.