Noninvasive Neuromodulation of the Prefrontal Cortex in Subjects With Obesity

The hypothesis is that tDCS will successfully engage prefrontal-related neurobehavioral
cognitive control systems, resulting in decreased eating disinhibition and therefore
facilitation of weight loss and weight loss maintenance. To test this hypothesis, a 6-month
randomized, sham-controlled, double-blind, intervention study was designed. Subjects will
undergo an intervention with the following components/phases:

1. Phase 1 - Target engagement (one session) The purpose of this phase is to examine
whether tDCS can reach the brain target, the dorsolateral prefrontal cortex, and
influence performance in a neuropsychology tests that depends on the activity of this
region. Results from this component of the study will provide evidence for target
engagement. Genomic DNA will be extracted from whole blood for sequencing of
Catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF)
polymorphism genotypes.

2. Phase 2 - tDCS alone (two weeks) During this phase participants will receive daily tDCS
sessions over the course of two weeks (Monday to Friday; total=10 sessions). The purpose
of this phase is to examine the effect of modulating the activity of the prefrontal
cortex with tDCS on body weight under baseline/weight stable conditions. Also analyse
changes in appetite and eating behavior.

3. Phase 3 - tDCS plus hypocaloric diet (two weeks). During this phase participants will
undergo a hypocaloric diet intervention aimed at achieving a 5% body weight reduction at
3 months. The diet will be individualized on the basis of physical activity levels, age
for each participant. This intervention will be be conducted at an inpatient,
well-controlled setting to guarantee adherence to the diet. Here the diet intervention
will be administered in combination with tDCS. tDCS will be applied every other day
(Monday, Wednesday, Friday) over the course of these two weeks. The purpose of this
component is to examine acute changes in weight associated with tDCS in combination with
the diet. Also analyse changes in appetite and eating behavior.

4. Phase 4 - Follow up (6 months). During this phase (outpatient) changes in body weight
over time will be assessed to evaluate weight maintenance. Subjects will be asked to
come back to the laboratory at 1, 3 and 6 months. Also analyse changes in appetite and
eating behavior.

Inclusion Criteria:

- Women with obesity (BMI 30-35 kg/m2), with stable weight over the previous 3 months.

Exclusion Criteria:

- pregnancy

- diabetes

- acute and chronic kidney disease

- pancreatitis

- any active psychiatric or neurological condition at the time of joining the study

- intake of centrally-acting medications that could interfere with tDCS effects

- anemia (Hgb <12 g/dl)

- any other significant medical condition

- contraindications for tDCS, which includes damaged skin at the site of stimulation,
any electrically sensitive or metallic device and history of epilepsy