Inhibitory Control Training Enhanced by Transcranial Direct Current Stimulation to Reduce Binge Eating Episodes: Findings from the Randomized Phase II ACCElect Trial.

INTRODUCTION: Binge eating disorder (BED) is characterized by recurrent binge eating (BE) episodes with loss of control. Inhibitory control impairments, including alterations in dorsolateral prefrontal cortex (dlPFC) functioning, have been described for BED. A targeted modulation of inhibitory control circuits by the combination of inhibitory control training and transcranial brain stimulation could be promising. OBJECTIVE: The aim of the study was to demonstrate feasibility and clinical effects of a transcranial direct current stimulation (tDCS)-enhanced inhibitory control training to reduce BE episodes and to generate an empirical basis for a confirmatory trial. METHODS: We performed a monocentric clinical phase II double-blind randomized trial with two parallel arms. Forty-one adult outpatients with full-syndrome BED according to DSM-5 received six sessions of food-related inhibitory control training, randomly combined with 2 mA verum or sham tDCS of the right dlPFC. The main outcome was BE frequency within a 4-week interval after treatment termination (T8; primary) and at 12-week follow-up (T9; secondary) as compared to baseline. RESULTS: BE frequency was reduced in the sham group from 15.5 to 5.9 (T8) and to 6.8 (T9); in the verum group, the reduction was 18.6 to 4.4 (T8) resp. 3.8 (T9). Poisson regression with the study arm as the factor and baseline BE frequency as the covariate revealed a p value of 0.34 for T8 and 0.026 for T9. Sham and real tDCS differed at T9 in BE frequency. CONCLUSIONS: Inhibitory control training enhanced by tDCS is safe in patients with BED and results in a substantial and sustainable reduction in BE frequency which unfolds over several weeks post-treatment. These results constitute the empirical basis for a confirmatory trial.

Behavioural biases in the interaction with food objects in virtual reality and its clinical implication for binge eating disorder.

Cognitive processes play a central role in the development, maintenance and remission in mental disorders, like in Binge Eating Disorder (BED). Insights into cognitive mechanisms reflected by embodied interaction with food and its connections to clinically relevant psychopathology offer new possibilities for translational diagnostics and interventions. We longitudinally investigated the manual interaction with food in a virtual reality (VR) in 31 patients with BED. Patients were assessed at baseline before participating in a randomized-controlled trial (RCT) investigating a computer-based inhibitory control training programme enhanced by transcranial direct current stimulation (tDCS) and at a 6-week follow-up. At both assessments, an experimental VR paradigm was conducted and patients were characterized concerning eating disorder psychopathology, eating behaviour, general impulsivity and food craving. In the experimental task, one of two simultaneously presented objects (food vs. office tools) had to be collected. Food was recognized faster than office tools and subsequent approach behaviour was initiated faster, whereas thereafter, food was collected slower than office tools. Exploratory, we could not find a modulatory effect of applied tDCS on the interaction with food. No relationship between behavioural biases and sample characterizations could be detected. Two different stages in the manual interaction with food were found: a faster first stage that comprises recognition and movement initiation and a slower second stage that comprises controlled handling and may reflect aversive motivational processes. As the behavioural patterns do not change with an ameliorated BED-psychopathology at the second assessment, the task seems insensitive in detecting translational interconnections between behavioural biases and BED-characteristics.Level of evidence: Level I, experimental study.

Combined antisaccade task and transcranial direct current stimulation to increase response inhibition in binge eating disorder.

Binge eating disorder (BED) is associated with deficient response inhibition. Malfunctioning response inhibition is linked to hypoactivation of the dorsolateral prefrontal cortex (dlPFC), where excitability could be increased by anodal transcranial direct current stimulation (tDCS). Response inhibition can be assessed using an antisaccade task which requires supressing a dominant response (i.e. saccade) towards a newly appearing picture in the visual field. We performed a double-blind, randomised, placebo-controlled proof-of-concept-study in which we combined a food-modified antisaccade task with tDCS in people with BED. We expected task learning and modulatory tDCS effects. Sixteen people were allocated to a 1 mA condition, 15 people to a 2 mA condition. Each participant underwent the food-modified antisaccade task at three measurement points: baseline without stimulation, anodal verum and sham stimulation at the right dlPFC in a crossover design. The error rate and the latencies of correct antisaccades decreased over time. No tDCS effect on the error rate could be observed. Compared to sham stimulation, 2 mA tDCS decreased the latencies of correct antisaccades, whereas 1 mA tDCS increased it. Self-reported binge eating episodes were reduced in the 2 mA condition, while there was no change in the 1 mA condition. Participants demonstrated increased response inhibition capacities by a task learning effect concerning the error rate and latencies of correct antisaccades over time as well as a nonlinear tDCS effect represented by ameliorated latencies in the 2 mA and impaired latencies in the 1 mA condition. The reduction of binge eating episodes might indicate a transfer effect to everyday life. Given that the reduction in binge eating was observed before tDCS administration, this effect could not be the result of neuromodulation. Randomized clinical trials are needed to fully understand this reduction, and to explore the efficacy of a combined antisaccade and tDCS training for BED.

Ameliorating cognitive control in patients with binge eating disorder by electrical brain stimulation: study protocol of the randomized controlled ACCElect pilot trial.

BACKGROUND: The current first-line treatment for binge eating disorder (BED), which is psychotherapy, is moderately effective in terms of abstinence from binge-eating. Neurobiological evidence suggests that people affected by BED show difficulties along the spectrum of impulsivity, including inhibitory control impairments and highlights the potential of novel treatment approaches directly targeting inhibitory control, including cognitive training approaches and non-invasive brain stimulation. METHODS: ACCElect is a prospective, randomized controlled pilot trial investigating a novel, food-related inhibitory control training combined with transcranial direct current stimulation (tDCS). 40 patients with BED will be randomly assigned to receive the training either combined with verum or with sham stimulation (control condition). The inhibitory control training is based on principles of the antisaccade paradigm and comprises six training sessions over two weeks. Core aims are the investigation of feasibility and clinically relevant effects of a tDCS-enhanced inhibitory control training in BED patients and the establishment of a data basis for a larger efficacy trial. The primary clinical endpoint is binge-eating (BE) frequency in terms of changes in BE episodes four weeks after treatment termination as compared to baseline. Key secondary outcomes comprise ED pathology and general psychopathology, inhibitory control capacities, quality of life as well as acceptability and satisfaction with the intervention. DISCUSSION: The results of the present trial will contribute to the development of novel neurobiologically informed treatment approaches for patients suffering from BED. Trial registration The ACCElect trial was prospectively registered on October 1, 2020, under the registration number NCT04572087 at ClinicalTrials.gov ( https://clinicaltrials.gov/ct2/show/NCT04572087 ).

A Pilot Event-Related Potentials Study on Mechanisms Underlying a tDCS-Enhanced Food-Specific Response Inhibition Task for Patients With Binge Eating Disorder.

Behavioural studies demonstrate alterations in cognitive functioning, particularly impaired response inhibition and increased attentional bias towards food in binge eating disorder (BED). This pilot study aimed to investigate the neurophysiological processing of a food-specific inhibition training combined with anodal transcranial direct current stimulation (tDCS) of the right dorsolateral prefrontal cortex (DLPFC) in 16 patients with BED (mean age = 38.6, mean BMI = 33.7 kg/m2). Patients performed a food-specific antisaccade task at baseline (T0) and in a cross-over design with verum vs. sham stimulation at T1 and T2. We investigated (i) event-related potentials (ERPs; N2, ERN and P3 amplitudes) while executing the task at baseline, (ii) whether baseline ERPs would predict task performance at T1 and T2 and (iii) associations between ERPs, eating disorder pathology and impulsivity at baseline. The mean amplitude of N2 was less pronounced in erroneous saccades (ES) than correct saccades (CS), whereas ERN and P3 mean amplitudes were more pronounced in ES. Moreover, the P3 mean amplitude of ES predicted the percentage of ES at both follow up-measurements irrespective of the applied stimulation (sham vs. verum). N2 in trials with correct saccades were negatively correlated with nonplanning trait impulsivity, while P3 in erroneous antisaccade trials was negatively correlated with food-related impulsivity. Overall, the findings of reduced ERN, enhanced P3 and N2 amplitude might be interpreted as difficulties in response inhibition towards food in individuals with BED. In particular, P3 predicts task outcome at follow-up and might represent a potential marker for inhibitory control processes.

Mind the food: behavioural characteristics and imaging signatures of the specific handling of food objects.

In our world with nearly omnipresent availability of attractive and palatable high-calorie food, the struggle against overweight and obesity is a major individual and public health challenge. Preference for unhealthy food and eating-related habits have a strong influence on health, suggesting that high-calorie food triggers fast and near-automatic reaching and grasping movements. Therefore, it is important to better understand the specific neural mechanisms that control the handling of food involving a coordinated interplay between sensoric, motoric, and cognitive subsystems. To this end, 30 healthy participants (Ø BMI: 22.86 kg/m2; BMI range: 19-30 kg/m2; 23 females) were instructed to collect one of two concurrently presented objects (food vs. office tools) by manual movement in virtual reality (VR) and on a touchscreen. Parallel to the task in VR, regional brain activity was measured by functional near-infrared spectroscopy (fNIRS). In the VR and on the touchscreen, stimulus recognition and selection were faster for food than for office tools. Yet, food was collected more slowly than office tools when measured in VR. On the background of increased brain activity in the right dorsolateral prefrontal cortex (dlPFC) during food trials, this suggests more behavioural control activity during handling foods. In sum, this study emphasizes the role of the right dlPFC in faster recognition and selection of food as part of a food-valuation network, more controlled handling of food in the VR which highlights the relevance of medium for modelling food-specific embodied cognitions.