Inhibitory Control Training and iTBS for Excess Weight: Behavioral and Brain Changes (InhibE).

Change in BMI: Weight and height will be combined to report BMI in kg/m^2. Weight will be obtained in kilograms with a digital scale (TANITA Corporation of America) and height in meters with a measuring rod (SECA Tape Measure 206).

Food Go/No-go task (Based on the FoodTrainer App; Lawrence et al., 2015): Pictures appear and afterwards a green (Go signal) or red (No-Go signal) circle appears around them. Participants are instructed to score points by answering with a knob if the image is surrounded by a green circle, but not to press when the image is surrounded by a red circle. The presentation of the images is the same as in the FoodTrainer application: 50% of the images are food, with 100% of the healthy ones being presented under the 'Go' condition and 100% of the unhealthy ones under the 'No-Go' condition. The remaining 50% are non-food images, with 50-50% paired with 'Go' and 'No-Go' cues. In addition, participants can choose which categories of unhealthy foods they want to train. Brain activation to Go vs. No-Go stimuli and food vs. non-food stimuli will be compared. The task will be analysed to assess the brain activity associated with the task, using a psychophysiological interaction analysis(PPI).

The Neveu et al. (2018) task will be used, which consists of three phases: two rating phases and one decision phase with 50 food images. Participants have to answer on a 5-point Likert scale how healthy they consider the food to be (block 1) and how much they like the taste of the food (block 2). In the third block, the participant decides whether they prefer to eat a neutral reference food (calculated from the previous two blocks) or an alternative food. These forced choices lead to cognitive conflict when the reference food is considered tastier and the alternative food healthier or vice versa. Among trials with cognitive conflict, the choice of the healthier food is defined as a controlled choice, and the choice of the tastier food as an uncontrolled choice. Activation will be compared between the controlled vs. uncontrolled choice conditions.

The task will be analysed to assess the brain activity associated with the task, using a psychophysiological interaction analyses (PPI).

Participants will be instructed to remain still, with their eyes closed, trying not to think about anything in particular for 9 minutes to obtain images to study the resting connectivity of different brain networks. On the one hand, an independent component analyses (ICA) will be performed, which will allow comparison of the different brain networks, as a whole, between the groups, with special interest in those that have been shown to be altered in the PD population. On the other hand, seed-based connectivity analyses will be performed, in which changes in functional connectivity between the CPFDL and the rest of the brain will be observed.

Participants will be asked to remain still for 10 minutes to obtain diffusion tensor imaging (DTI) which provides indirect measurements of the architecture and connectivity of white matter fibres. The study of the DTI images will be carried out with the FSL programme, which allows the integrity of the white matter of the different groups to be measured by evaluating the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) maps.

To take these measurements at home, participants should ask someone for help and follow our instructions. WHtR results from WC divided by the height measured standing with heels close together and trunk erect.

Change in Food Craving. Food Craving Questionnaire State-reduced (FCQ-S-r)consists of 15 items to be scored on a 5-point scale ranging from strongly disagree to strongly agree. A higher score indicates higher state of craving at the time of the assessment

Diet information during the last year (pre-treatment), two last weeks (post-treatment) and 3 last months (follow-up) will be collected through a 52-item Food frequency questionnaire (CFA). Participants must record quantities of all the foods and drinks consumed during those periods. Data are transformed into total calories and calories from fats, carbohydrates, and sugars

International Physical Activity Questionnaire (IPAQ; www.ipaq.ki.se): is a questionnaire with 7 questions on physical activity during the last week, as well as walking and sitting time.It evaluates physical activity related to work, activity at home and free time determines the degrees of activity based on the metabolic equivalents (MET) consumed.Higher scores indicate greater physical activity

The following question will be asked using a visual analogue scale (VAS): In the last 2 weeks or 3 months, to what extent did you follow the exercise guidelines given to you by the programme's physical trainer? (0 = I did not follow the exercise recommendations at all; 100 = I absolutely followed the exercise recommendations).

The following question will be asked using a visual analogue scale (VAS): In the last 2 weeks or 3 months, how well did you follow the dietary guidelines given by the nutritionist in the programme (0 = I did not follow the diet at all; 100 = I followed the diet absolutely).

Beck Depression Inventory will be administered to test depression symptoms.The scores range from 0 to 63 points. The higher the score, the greater the severity of depressive symptoms

The Depression Anxiety Stress Scale-21 (DASS-21) will be used, taking into account scores on the stress and anxiety subscales. The scores for both subscales range from 0 to 21, a higher score indicating higher anxiety or stress

Dutch Eating Behaviour Questionnaire (DEBQ) will be administered to assess restrictive eating behaviours related to external cues and emotional states. Higher scores in each subscale reflect higher level of restrained, emotional, and external eating, respectively.The DEBQ uses a 5-point Likert scale, ranging from never (1) to very often (5). The average score is calculated for each subscale by adding scores obtained from individual items and dividing them by the number of items included in a subscale (mean range: 1-5).

Reward-Based Eating Scale (RED) is a 13 items questionnaire that evaluates worries about foods, losing intake control and absence of satiety. Higher scores reflect higher reward-based eating drive.

Coping subscale of the Palatable Eating Motives Scale (PEMS) will be used to evaluate the intentionality for eating palatable foods to face negative emotions. The coping subscale includes items that are scored on a 5-point Likert-type scale, the total range being from 5 to 25 points. Low scores indicate that the person rarely resorts to the consumption of pleasant foods as a strategy to cope with negative emotions or stressful situations. High scores suggest that the person frequently uses palatable food as a strategy to cope with stress or negative emotions, which may be related to unhealthy eating habits or emotional eating patterns.

The Emotion Questionnaire (ERQ) consists of 10 items to examine cognitive reappraisal and expressive suppression strategies. In cognitive reappraisal the highest score (42) is associated with better emotional outcomes while in expressive suppression the highest score (28) is linked to poorer well-being. Each item is rated on a Likert scale from strongly disagree (1) to strongly agree (7).

Motor inhibition will be assessed using FoodT. In the FoodT app reaction time for the high-calorie and low-calorie foods paired with the go and the no-go signal. The average response time for go and no-go items will be calculated according to the type of images (appetizing and healthy foods), and commission errors will be recorded.

Using a Stroop task with food, the interference of food-related words on task performance can be measured as an assessment of cognitive inhibition.

Score on the Food Delay Discounting will be used to measure the sensitivity to immediate rewards vs higher value rewards delayed. The participant's choices are recorded for each trial. Each trial varies in terms of the amount of reward and the amount of time to wait. To model the decisions, a hyperbolic discounting function is generally used.

This will be assessed using the Punishment Sensitivity and Reward Sensitivity Questionnaire (PSRSQ) of 48 items. Responses in the scale are in a "yes/no" format. Higher punishment sensitivity scores are associated with lower number of punishable errors while higher reward sensitivity scores are linked to higher number of passive avoidance errors.

Self-reported impulsivity will be measured with Impulsive behaviour scale (UPPS-P). It consists of 20 items scored on a four point Likert scale, ranging from strongly agree (1) to strongly disagree (4). Higher scores mean worse outcome in impulsivity, while lower scores are related to better self-control and regulation

Working Memory will be assessed using N-back Task score based on accuracy and reaction times. Higher accuracy scores indicate stronger working memory and attention, while faster reaction times are linked to quicker processing speed and decision-making.

Wisconsin Card Sorting Test will be administered to measure shift strategy in response to changing contingencies. There are128 trials where more correct responses, fewer perseverative and non perseverative errors, and more completed categories (max 6) are related to better performance

Iowa Gambling Task will be used to assess decision-making using money rewards.

A socio-demographic questionnaire will be administered to examine age, education, gender, socio-economic variables and clinical variables to consider exclusion and inclusion criteria. All these variables are qualitative.

The Beck Depression Inventory (BDI-II) will also be used to rule out major depressive symptoms as an exclusion criteria. The scores range from 0 to 63 points. Participants with a score higher than 29, indicative of severe symptoms, will be excluded.

The anxiety subscale of the DASS-21 will also be used to rule out symptoms of major anxiety as an exclusion criterion. The scores for both subscales range from 0 to 21. Participants with a score higher than 8, indicative of severe symptoms, will be excluded from the study.

Questionnaire on Eating and Weight Patterns-5 (QEWP-5) is adapted to DSM-5 criteria and will be used to exclude people with binge eating problems and bulimia. The QEWP-5 is not scored on a traditional numerical scale like other psychological tests; instead, responses are used to identify the presence of eating disorder symptoms. Positive responses to key questions about the frequency of binge eating, compensatory behaviors, and emotional distress may indicate the presence of an eating disorder.

The Health Resources Questionnaire asks how often and why people have needed medical care and medicines in the last 3 month to measure the impact of the intervention in terms of health uses. Fewer visits to health professionals will be indicative of improvement.

Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) adapted to excess weight will be used to assess motivation to change habits. It has 18 items that score readiness to change in people with abusive food use with a five point Likert scale, ranging from strongly disagree (1) to strongly agree (5). Higher scores mean better outcome in relation to motivation to change, while higher scores on ambivalence suggest doubts about the motivation to change.

A yes/no question will be asked to record whether or not participants have experienced weight stigma in the past and a VAS scale from 0 to 100 where they can rate the degree to which they have experienced stigma.

History of previous treatment, from pharmacological or nutritional to psychological, should be recorded.

Biological samples will be collected and deep-frozen in the CIMCYC until mass analyses are performed at the end of the project.

Fasting blood tests will determine hormone levels (pg/ml) of estradiol, progesterone, cortisol, leptin, adiponectin, TSH, thyroxine, triiodothyronine, ghrelin, glucagon and GLP-1. A total of 10 ml of blood will be collected and centrifuged to separate the plasma from the rest and stored at -80ºC

Biological samples will be collected and deep-frozen in the CIMCYC until mass analyses are performed at the end of the project.

Fasting blood tests will glucose and triglycerides levels (mg/dl). A total of 10 ml of blood will be collected and centrifuged to separate the plasma from the rest and stored at -80ºC

Biological samples will be collected and deep-frozen in the CIMCYC until mass analyses are performed at the end of the project.

Fasting blood tests will determine concentration of insulin (U/ml). A total of 10 ml of blood will be collected and centrifuged to separate the plasma from the rest and stored at -80ºC

Biological samples will be collected and deep-frozen in the CIMCYC until mass analyses are performed at the end of the project.

Fasting blood tests will determine concentration of IL-6 (pg/ml), CRP (mg/L) and TNF-alpha (pg/ml). In addition, genetic analyses will be performed by sequencing candidate genes. A total of 10 ml of blood will be collected and centrifuged to separate the plasma from the rest and stored at -80ºC

Biological samples will be collected and deep-frozen in the CIMCYC until mass analyses are performed at the end of the project.

Fasting blood tests will determine PYY (3-36) levels (pg/ml). A total of 10 ml of blood will be collected and centrifuged to separate the plasma from the rest and stored at -80ºC

Biological samples will be collected and deep-frozen in the CIMCYC until mass analyses are performed at the end of the project.

Fasting blood tests will determine genetic analyses will be performed by sequencing candidate genes. Genome-wide association analysis is proposed to identify new genes and variants associated with PD such as ZFP36, GAD2 on chromosome 10p12, Neuromedin β with whole exome sequencing and methylation analysis.A total of 10 ml of blood will be collected and centrifuged to separate the plasma from the rest and stored at -80ºC

Biological samples will be collected and deep-frozen in the CIMCYC until mass analyses are performed at the end of the project.

Saliva sample tests will determine oral microbiota (microbial taxa). It will be collected using three swabs (right cheek, left cheek, tongue) that will be stored at -80ºC

Biological samples will be collected and deep-frozen in the CIMCYC until mass analyses are performed at the end of the project.

Participants will collect fecal samples and 1.5 g of the top layer will be stored in tubes at -80ºC. Testing of faecal samples will determine gut microbiota composition (microbial taxa).

Biological samples will be collected and deep-frozen in the CIMCYC until mass analyses are performed at the end of the project. Proteomics analyses will determine concentration of proteins (mg/mL).

Samples will be collected in plastic bottles, centrifuged and stored at -80ºC

The SF-36 (Short Form 36 Health Survey) is one of the most widely used questionnaires to measure health-related quality of life.

It consists of 36 questions assessing eight key dimensions: physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role and mental health. Each dimension is scored on a scale of 0 to 100, where 0 represents the worst health status and 100 the best.

Years of Life Adjusted for Quality (QALY) is a measure used in healthcare to assess the value of medical treatments or interventions, combining quantity and quality of life. One QALY is equivalent to one year of life in full health. If a person lives a year with a reduced quality of life (due to illness, for example), a value of less than 1 is assigned, depending on the degree of well-being. This metric allows the effectiveness of different interventions to be compared, helping in health decision-making and resource allocation. It combines life years and quality (from SF-36) used in economic evaluation and cost-utility analyses of the intervention

The BMI will be used to assess the success of the intervention in the cost-effectiveness calculations.

The FCQ-S-r will be used to assess the success of the intervention in the cost-effectiveness calculations.

The Health Resource Questionnaire will be used to assess the success of the intervention in the cost-effectiveness calculations.

The Cost of a Clinical Psychology Area Specialist (FEA) for 3 minutes per session over 10 days, based on Andalusian Health Service remuneration will be used to assess the success of the intervention in the cost-effectiveness calculations.

The Cost of a Clinical Psychology Area Specialist (FEA) for 10 minutes per session over 10 days, based on Andalusian Health Service remuneration will be used to assess the success of the intervention in the cost-effectiveness calculations.

The Cost of fMRI and iTBS equipment will be used to assess the success of the intervention in the cost-effectiveness calculations.