Noninvasive neuromodulation of the prefrontal cortex in young women with obesity: a randomized clinical trial.

BACKGROUND/OBJECTIVES: Obesity is associated with reduced neurocognitive performance. Individuals with obesity show decreased activation in the left dorsolateral prefrontal cortex (DLPFC), a key brain region relevant to the regulation of eating behavior. Transcranial direct current stimulation (tDCS) has emerged as a potential technique to correct these abnormalities. However, there is limited information to date, particularly in clinical settings and regarding long-term effects of tDCS. This study aimed to investigate the effects of DLPFC-targeted tDCS in young women with obesity. SUBJECT/METHODS: Randomized, double-blind, sham-controlled parallel-design clinical trial conducted in 38 women, aged 20-40 years, with BMI 30-35 kg/m2. STUDY DESIGN: Phase I: target engagement (immediate effects of tDCS on working memory performance), Phase II: tDCS only (ten sessions, 2 weeks), Phase III: tDCS + hypocaloric diet (six sessions, 30% energy intake reduction, 2 weeks, inpatient), Phase IV: follow-up at 1, 3, and 6 months. PRIMARY OUTCOME: change in body weight. SECONDARY OUTCOMES: change in eating behavior and appetite. Additional analyses: effect of Catechol-O-methyl transferase (COMT) gene variability. Data were analyzed as linear mixed models. RESULTS: There was no group difference in change in body weight during the tDCS intervention. At follow-up, the active group lost less weight than the sham group. In addition, the active group regained weight at 6-month follow-up, compared with sham. Genetic analysis indicated that COMT Met noncarriers were the subgroup that accounted for this paradoxical response in the active group. CONCLUSION: Our results suggest that in young women with class I obesity, tDCS targeted to the DLPFC does not facilitate weight loss. Indeed, we found indications that tDCS could have a paradoxical effect in this population, possibly connected with individual differences in dopamine availability. Future studies are needed to confirm these findings.

Neuromodulation of the prefrontal cortex facilitates diet-induced weight loss in midlife women: a randomized, proof-of-concept clinical trial.

BACKGROUND: High body mass index (BMI) is associated with neurocognitive impairments that contribute to overeating and interfere with weight loss efforts. Overweight and obesity at midlife can accelerate neurodegenerative changes and increase the risk of late-life dementia. Noninvasive neuromodulation represents a novel, affordable and scalable approach to improve neurocognitive function in this context. The purpose of this proof-of-concept study was to examine whether transcranial direct current stimulation (tDCS) aimed at enhancing prefrontal cortex activity could enhance weight loss, in combination with a hypocaloric diet, and study underlying mechanisms. METHODS: Overall, 38 women with BMI 25-35 kg/m2 underwent a 4 week randomized, double-blinded, sham-controlled, and parallel-design intervention, during which they received eight sessions of tDCS (n = 18 sham, n = 20 active) in combination with a diet (caloric goal of 20 kcal/kg/day). We evaluated longitudinal changes in body weight, appetite and food craving. In addition, we examined the contribution of cognitive-executive processes via food-modified computerized tasks. RESULTS: We found that the active group had more reduction in body weight than the sham group throughout the study (p = 0.020) and significant weekly weight loss. At 4 weeks, the active group lost 2.32% of initial body weight (sham: 1.29%). Components of subjective appetite and food craving showed a trend toward more reduction in the active group. These changes were paralleled by significant improvements in task performance in the active group, particularly in a dual task that required inhibitory control and working memory (p = 0.007-0.031). Improvement in inhibitory control performance predicted reduction in lack of control overeating, explaining 43.5% of its variance at the end of the study (p = 0.003). No significant adverse effects were observed. CONCLUSIONS: Our results provide proof-of-concept validation of prefrontal-targeted tDCS, combined with a diet, in midlife women with excess body weight, paving the way for larger studies evaluating clinical efficacy and long-term effects of this intervention.

Prefronto-cerebellar neuromodulation affects appetite in obesity.

Human neuroimaging studies have consistently reported changes in cerebellar function and integrity in association with obesity. To date, however, the nature of this link has not been studied directly. Emerging evidence suggests a role for the cerebellum in higher cognitive functions through reciprocal connections with the prefrontal cortex. The purpose of this exploratory study was to examine appetite changes associated with noninvasive prefronto-cerebellar neuromodulation in obesity. Totally, 12 subjects with class I obesity (mean body mass index 32.9 kg/m2) underwent a randomized, single-blinded, sham-controlled, crossover study, during which they received transcranial direct current stimulation ((tDCS); active/sham) aimed at simultaneously enhancing the activity of the prefrontal cortex and decreasing the activity of the cerebellum. Changes in appetite (state and food-cue-triggered) and performance in a food-modified working memory task were evaluated. We found that active tDCS caused an increase in hunger and desire to eat following food-cue exposure. In line with these data, subjects also tended to make more errors during the working memory task. No changes in basic motor performance occurred. This study represents the first demonstration that prefronto-cerebellar neuromodulation can influence appetite in individuals with obesity. While preliminary, our findings support a potential role for prefronto-cerebellar pathways in the behavioral manifestations of obesity.

Appetite effects of prefrontal stimulation depend on COMT Val158Met polymorphism: A randomized clinical trial.

The regulation of appetite is supported by dopamine-modulated brain circuits. Recent studies have shown that transcranial direct current stimulation (tDCS) aimed at increasing the excitability of the dorsolateral prefrontal cortex can reduce appetite, but the underlying mechanisms remain unknown, and response variability is large. The aim of this study was to determine whether individual differences in Catechol-O-methyl transferase (COMT) Val158Met polymorphism can influence tDCS effects on appetite. Thirty-eight adult women with obesity, classified as carriers or non-carriers of the Met allele, underwent a randomized, double-blind, sham-controlled tDCS intervention involving three phases: Phase I, target engagement (immediate effects of tDCS on working memory performance), Phase II, tDCS only (10 sessions, two weeks), and Phase III, tDCS + hypocaloric diet: (6 sessions, two weeks, 30% energy intake reduction, inpatient). Data were analyzed using linear mixed-effects models and mixed ANCOVA. Appetite was evaluated using visual analogue scales. We found that Met-carriers receiving active tDCS were the only participants who experienced a significant reduction of appetite over time. Conversely, Met non-carriers maintained high levels of appetite during the intervention; this effect was driven by a delayed paradoxical rise in appetite after stimulation. Working memory task performance at phase I correlated with subsequent appetite change in a COMT-dependent manner: speed improvements during the task predicted appetite increase in Met carriers and appetite reduction in Met non-carriers. Our findings suggest that genotype differences impacting dopamine levels influence prefrontal tDCS effects on appetite. This source of variability should be considered in the design of future studies.

Improved food Go/No-Go scores after transcranial direct current stimulation (tDCS) to prefrontal cortex in a randomized trial.

OBJECTIVE: Reduced dorsolateral prefrontal cortex (dlPFC) activity and inhibitory control may contribute to obesity. The study objective was to assess effects of repeated transcranial direct current stimulation (tDCS) on food Go/No-Go (GNG), food Stroop performance, and snack food intake. METHODS: Twenty-nine individuals with obesity (12 male; mean [SD], age 42 [11] years; BMI 39 [8]) participated in a combined inpatient/outpatient randomized parallel-design trial and received 15 sessions of anodal or sham tDCS to the left dlPFC. Food-related inhibitory control (GNG), attentional bias (Stroop), and snack food intake were assessed at baseline, completion of inpatient sessions (day 7), and follow-up (day 31). RESULTS: GNG performance improved in the anodal group by day 31, compared with sham (p = 0.01), but Stroop scores did not differ by intervention. Greater snack food intake was associated with lower GNG scores (p = 0.01), driven by the sham group (p < 0.001) and higher food and palatable bias scores on the Stroop (all p = 0.02) across both groups. Changes on tasks were not associated with changes in intake. CONCLUSIONS: Anodal tDCS to the left dlPFC improved performance on a food-related inhibitory control task, providing evidence of potential for therapeutic benefit of neuromodulation in areas controlling executive function. Results showed that tDCS to the dlPFC reduced snack food intake and hunger; however, underlying neurocognitive mechanisms remain uncertain.

Neurocognitive effects of umami: association with eating behavior and food choice.

Free glutamate, a key substance underlying the umami taste of foods, fulfills a number of physiological functions related to energy balance. Previous experimental studies have shown that intake of a broth or soup supplemented with monosodium glutamate (MSG) prior to a meal can decrease appetite and food intake, particularly in women with propensity to overeat and gain weight. In this study, we examined potential neurocognitive mechanisms underlying this effect. We evaluated changes after intake of a chicken broth with or without MSG added (MSG+/MSG-) in a sample of healthy young women. Subjects were assessed with a food-modified computerized inhibitory control task, a buffet meal test with eye-tracking, and brain responses during a food choice paradigm evaluated with functional neuroimaging. We found evidence for improvement in key parameters related to inhibitory control following intake of the MSG+ broth, particularly in subjects with high levels of eating disinhibition, who also showed lower intake of saturated fat during the meal. Additionally, consumption of the MSG+ broth led to a reduction of the rate of fixation switches between plates at the meal, and increased engagement of a brain region in the left dorsolateral prefrontal cortex previously associated with successful self-control during dietary decisions. Altogether, these results, while preliminary, suggest potential facilitating effects of glutamate (MSG) on cognitive executive processes that are relevant for the support of healthy eating behaviors and food choice.

Functional neuroimaging in obesity.

PURPOSE OF REVIEW: This review examines recent advances in the use of functional neuroimaging to study human obesity, a field that is rapidly expanding and continues to be of paramount importance for a better understanding of the pathogenesis of this condition. With rising levels of obesity worldwide and limited therapeutic options, there is a great need for the development of new solutions that can benefit patients. RECENT FINDINGS: Studies that utilize functional neuroimaging are beginning to shed light on the nature of behavioral and neurocognitive dysfunctions previously identified in individuals with obesity. Significant progress has occurred in the study of reward-related processes, cognition-reward interactions, mechanisms of weight loss, genetic influences and the case of obesity in children and adolescents. Research findings confirm that obesity and its related overeating behaviors are strongly associated with the brain, both at a regional level and a large-scale network level. SUMMARY: Functional neuroimaging studies bring unprecedented levels of detail to examine the brain basis of obesity and show promise for the development of future brain-based biomarkers and interventions in this condition.

Functional neuroimaging in obesity.

PURPOSE OF REVIEW: The review examines recent advances in the use of functional neuroimaging to study human obesity, a field that is rapidly expanding and continues to be of paramount importance for a better understanding of the pathogenesis of this condition. With rising levels of obesity worldwide and limited therapeutic options, there is a great need for the development of new solutions that can benefit patients. RECENT FINDINGS: Studies that utilize functional neuroimaging are beginning to shed light on the nature of behavioral and neurocognitive dysfunctions previously identified in individuals with obesity. Significant progress has occurred in the study of reward-related processes, cognition-reward interactions, mechanisms of weight loss, genetic influences, and the case of obesity in children and adolescents. Research findings confirm that obesity and its related overeating behaviors are strongly associated with the brain, both at a regional level and a large-scale network level. SUMMARY: Functional neuroimaging studies bring unprecedented levels of detail to examine the brain basis of obesity, and show promise for the development of future brain-based biomarkers and interventions in this condition.

The "Smart Dining Table": Automatic Behavioral Tracking of a Meal with a Multi-Touch-Computer.

Studying how humans eat in the context of a meal is important to understanding basic mechanisms of food intake regulation and can help develop new interventions for the promotion of healthy eating and prevention of obesity and eating disorders. While there are a number of methodologies available for behavioral evaluation of a meal, there is a need for new tools that can simplify data collection through automatic and online analysis. Also, there are currently no methods that leverage technology to add a dimension of interactivity to the meal table. In this study, we examined the feasibility of a new technology for automatic detection and classification of bites during a laboratory meal. We used a SUR40 multi-touch tabletop computer, powered by an infrared camera behind the screen. Tags were attached to three plates, allowing their positions to be tracked, and the saturation (a measure of the infrared intensity) in the surrounding region was measured. A Kinect camera was used to record the meals for manual verification and provide gesture detection for when the bites were taken. Bite detections triggered classification of the source plate by the SUR40 based on saturation flux in the preceding time window. Five healthy subjects (aged 20-40 years, one female) were tested, providing a total sample of 320 bites. Sensitivity, defined as the number of correctly detected bites out of the number of actual bites, was 67.5%. Classification accuracy, defined as the number of correctly classified bites out of those detected, was 82.4%. Due to the poor sensitivity, a second experiment was designed using a single plate and a Myo armband containing a nine-axis accelerometer as an alternative method for bite detection. The same subjects were tested (sample: 195 bites). Using a simple threshold on the pitch reading of the magnetometer, the Myo data achieved 86.1% sensitivity vs. 60.5% with the Kinect. Further, the precision of positive predictive value was 72.1% for the Myo vs. 42.8% for the Kinect. We conclude that the SUR40 + Myo combination is feasible for automatic detection and classification of bites with adequate accuracy for a range of applications.

Computational modeling of transcranial direct current stimulation (tDCS) in obesity: Impact of head fat and dose guidelines.

Recent studies show that acute neuromodulation of the prefrontal cortex with transcranial direct current stimulation (tDCS) can decrease food craving, attentional bias to food, and actual food intake. These data suggest potential clinical applications for tDCS in the field of obesity. However, optimal stimulation parameters in obese individuals are uncertain. One fundamental concern is whether a thick, low-conductivity layer of subcutaneous fat around the head can affect current density distribution and require dose adjustments during tDCS administration. The aim of this study was to investigate the role of head fat on the distribution of current during tDCS and evaluate whether dosing standards for tDCS developed for adult individuals in general are adequate for the obese population. We used MRI-derived high-resolution computational models that delineated fat layers in five human heads from subjects with body mass index (BMI) ranging from "normal-lean" to "super-obese" (20.9 to 53.5 kg/m(2)). Data derived from these simulations suggest that head fat influences tDCS current density across the brain, but its relative contribution is small when other components of head anatomy are added. Current density variability between subjects does not appear to have a direct and/or simple link to BMI. These results indicate that guidelines for the use of tDCS can be extrapolated to obese subjects without sacrificing efficacy and/or treatment safety; the recommended standard parameters can lead to the delivery of adequate current flow to induce neuromodulation of brain activity in the obese population.

Finite Element study of skin and fat delineation in an obese subject for transcranial Direct Current Stimulation.

Because of pilot data suggesting the efficacy of transcranial Direct Current Stimulation (tDCS) in treating a range of neuropsychiatric disorders as well as in controlling cravings, there is interest to apply to obese subjects. The abnormal thickness of fat that exist in obese subjects may influence current delivery from scalp electrodes to the brain. MRI-derived Finite Element (FE) models of a morbidly obese subject were created with and without fat delineated. The inclusion of fat to the FE model reduced the effective volume of the relatively conductive skin. This led to greater current penetration to the cortical surface. Electric field was substantially greater (60%) in magnitude and a difference in the spatial profile was noted in the model with fat. Additional models testing the effect of varying fat conductivity revealed an inflection in current penetration as fat conductivity is varied. It was postulated that this may be due to a shunting effect both when the shell of fat surrounding the skull is too resistive for penetration and when the fat is so conductive as to lead current around rather than through the head. Precise FE tDCS model of obese patients requires the precise inclusion of fat.