The Use of Virtual Reality in Craving Assessment and Cue-Exposure Therapy in Substance Use Disorders

Craving is recognized as an important diagnosis criterion for substance use disorders (SUDs) and a predictive factor of relapse. Various methods to study craving exist; however, suppressing craving to successfully promote abstinence remains an unmet clinical need in SUDs. One reason is that social and environmental contexts recalling drug and alcohol consumption in the everyday life of patients suffering from SUDs often initiate craving and provoke relapse. Current behavioral therapies for SUDs use the cue-exposure approach to suppress salience of social and environmental contexts that may induce craving. They facilitate learning and cognitive reinforcement of new behavior and entrain craving suppression in the presence of cues related to drug and alcohol consumption. Unfortunately, craving often overweighs behavioral training especially in real social and environmental contexts with peer pressure encouraging the use of substance, such as parties and bars. In this perspective, virtual reality (VR) is gaining interest in the development of cue-reactivity paradigms and practices new skills in treatment. VR enhances ecological validity of traditional craving-induction measurement. In this review, we discuss results from (1) studies using VR and alternative virtual agents in the induction of craving and (2) studies combining cue-exposure therapy with VR in the promotion of abstinence from drugs and alcohol use. They used virtual environments, displaying alcohol and drugs to SUD patients. Moreover, some environments included avatars. Hence, some studies have focused on the social interactions that are associated with drug-seeking behaviors and peer pressure. Findings indicate that VR can successfully increase craving. Studies combining cue–exposure therapy with virtual environment, however, reported mitigated success so far

Études des mécanismes d'action de la stimulation cérébrale non-invasive avec l'imagerie par résonnance magnétique : une perspective d'utilisation dans le trouble lié aux substances

Introduction Le trouble lié aux substances est une condition neuropsychiatrique complexe particulièrement difficile à traiter avec les méthodes thérapeutiques actuelles et les rechutes sont fréquentes. Le craving, cette envie de consommer la substance, est un facteur critique dans la rechute. Les techniques de stimulation cérébrale non-invasive telles que la stimulation transcrânienne par courant continu (tDCS) et la stimulation magnétique transcrânienne répétée (rTMS) ont démontré des résultats intéressants dans plusieurs conditions psychiatriques, dont dans la réduction du craving chez les patients souffrant de troubles liés aux substances. Cela dit, les mécanismes d’action de ces techniques demeurent mal définis. Objectifs L’objectif de cette thèse est de déterminer les mécanismes d’action de la tDCS et rTMS, et de les mettre en perspective dans le trouble lié aux substances. Méthodes Nous avons effectué 3 études combinant la tDCS ou rTMS avec l’imagerie par résonance magnétique (IRM). Nous avons combiné la stimulation cérébrale avec la spectroscopie par résonance magnétique (MRS), qui permet de quantifier la concentration de métabolites cérébraux, et l’imagerie par résonance magnétique fonctionnelle (IRMf), qui permet de mesurer la connectivité fonctionnelle entre structures cérébrales. Résultats La première étude a combiné l’administration de la tDCS au cortex préfrontal et la MRS. Les résultats démontrent que la tDCS permet l’élévation de n-acétylaspartate (NAA) et glutamine+glutamate (Glx) dans le cortex préfrontal dorsolatéral (DLPFC) et le striatum. Ceci suggère que la tDCS a un effet excitateur rapide sur le DLPFC et facilite la transmission corticostriatale. La deuxième étude a combiné la tDCS avec l’IRMf, dans un devis expérimental calqué sur celui de l’étude 1. Les résultats indiquent que la tDCS administrée au DLPFC augmente la connectivité fonctionnelle entre le DLPFC et le striatum, ce qui suggère une augmentation de l’activité des voies corticostriatales. La troisième étude est une étude de cas clinique où nous avons administré la rTMS à un patient du trouble lié aux substances et obtenu des mesures en MRS avant puis après la rTMS. Les résultats cliniques démontrent une diminution du craving et des symptômes anxieux chez le patient. Les résultats neurophysiologiques démontrent que la rTMS a permis l’élévation de NAA et Glx dans le DLPFC, striatum et le cortex cingulaire. Ces résultats suggèrent que la rTMS a un effet excitateur sur le DLPFC et ses structures sous-jacentes, ce qui pourrait expliquer la diminution de symptômes. Conclusion Les résultats démontrent que la tDCS et la rTMS administrés au DLPFC ont des effets excitateurs locaux, sur le DLPFC, et distaux, suivant les voies corticostriatales. Ces résultats suggèrent que ces techniques peuvent moduler l’activité des voies glutamatergiques préfrontales. Ceci pourrait participer à diminuer le craving chez les patients de dépendances aux substances et suggère que la stimulation cérébrale non-invasive est une technique alternative à explorer dans cette perspective.Introduction Substance use disorders (SUD) is a complex neuropsychiatric disorder that is particularly difficult to treat with conventional treatment methods and relapse is frequent. Cravings are a critical factor in relapse and constitute an important target for abstinence. Noninvasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have demonstrated interesting clinical potential in a wide range of neuropsychiatric disorders, including the decrease of craving in patients of SUD, when administrated to the dorsolateral prefrontal cortex (DLPFC). However, neurophysiological mechanisms of action of tDCS and rTMS remain largely unknown. Objectives The objective of the thesis is to characterize some of these mechanisms of action and put them in perspective of its potential therapeutic effect in SUD. Methods To investigate this, we conducted 3 studies combining tDCS or rTMS and magnetic resonance imaging (MRI) techniques in healthy individuals and SUD patients. We combined brain stimulation with agnetic resonance spectroscopy (MRS), which allows to measure levels of brain metabolites within a voxel of interest, and functional MRI (fMRI), which allows to measure functional connectivity levels between cerebral structures. Results The first study combined prefrontal tDCS and MRS in healthy subjects. Results show that tDCS elevated brain metabolites n-acetylaspartate (NAA) and glutamine+glutamate (Glx) in the DLPFC and striatum. This suggests that tDCS has fast excitatory effects over the DLPFC and facilitates corticostriatal transmission. The second study replicated the same design as the first one, with tDCS combined with fMRI. Results show that tDCS elevated functional connectivity of the DLPFC with the striatal region, suggesting a fast excitatory effect of the corticostriatal pathways. The final study is a case report in which we administrated rTMS to the prefrontal cortex of a SUD patient. We gathered MRS measurements before and after the rTMS regimen. Clinical results show that rTMS decreased cravings for substances and anxiety symptoms. Neurophysiological results show that rTMS elevated levels of NAA and Glx in the DLPFC, striatum and cingulate cortex. These results suggest that rTMS has an excitatory effect over the DLPFC and its downstream targets, which may explain reduction of symptoms of SUD and anxiety. Conclusion Taken together, these findings suggest that tDCS and rTMS of the DLPFC have excitatory effects on the stimulation target and downstream structures. This suggests that tDCS and rTMS can modulate activity within prefrontal glutamatergic pathways. Such effects may explain reduction of craving in patients of SUD and support the idea that noninvasive brain stimulation has therapeutic potential in this condition

Modulation de la transmission dopaminergique par les récepteurs nucléaires orphelins NURR1 et NUR77 : rôles distincts et interactions

Les récepteurs nucléaires orphelins Nurrl et Nur77 sont des facteurs de transcription qui remplissent des fonctions différentes au sein des systèmes dopaminergiques adultes. Cela dit, ils sont tous deux impliqués dans les réponses comportementales imputables à ces systèmes. L'objectif de l'étude était de déterminer la possibilité d'une interaction fonctionnelle entre les deux récepteurs en comparant différentes souches de souris transgéniques. Nous avons observé que la suppression du gène Nur77 et la réduction partielle de Nurrl mènent à l'expression d'un phénotype particulier chez les animaux Double Knockout (Nurrl (+/-); Nur77 (-/-))dans divers protocoles expérimentaux évaluant l' activité locomotrice en conditions basales ou sous l' influence d' agents pharmacologiques. Nous avons également mesuré les niveaux d'expression de certaines neuropeptides, l' enképhaline et la dynorphine, qui sont également modulés différemment chez les animaux Double Knockout dans un contexte de stimulation et de blocage des récepteurs dopaminergiques. Nos résultats suggèrent qu'une interaction fonctionnelle et dépendante du contexte entre Nurrl et Nur77 existe

Food Addiction in a Spanish Sample of Eating Disorders: DSM‐5 Diagnostic Subtype Differentiation and Validation Data

Although the concept of ‘food addiction’ (FA) has raised growing interest because of evidence for similarities between substance dependence and excessive food intake, there is a lack of studies that explore this construct among the wide spectrum of eating disorders (EDs). Besides providing validation scores of a Spanish version of the Yale FA Scale (YFAS‐S), this study examined the prevalence of ‘FA’ among ED subtypes compared with healthy‐eating controls (HCs) and the association between ‘FA’ scores, eating symptomatology and general psychopathology. A sample of 125 adult women with ED, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders 5 criteria, and 82 healthy‐eating women participated in the study. All participants were assessed with the YFAS‐S, the ED Inventory‐2 and the Symptom Checklist‐Revised. Results showed that the internal structure of the one‐dimensional solution for the YFAS‐S was very good ( α  = 0.95). The YFAS‐S has a good discriminative capacity to differentiate between ED and controls (specificity = 97.6% and sensitivity (Se) = 72.8%; area under receiver operating characteristic curve = 0.90) and a good Se to screen for specific ED subtypes. YFAS‐S scores were associated with higher levels of negative affect and depression, higher general psychopathology, more severe eating pathology and greater body mass index. When comparing the prevalence of ‘FA’ between ED subtypes, the lowest prevalence of ‘FA’, measured with the YFAS‐S, was for the anorexia nervosa (AN) restrictive subtype with 50%, and the highest was for the AN binge–purging subtype (85.7%), followed by bulimia nervosa (81.5%) and binge eating disorder (76.9%). In conclusion, higher YFAS‐S scores are associated with bingeing ED‐subtype patients and with more eating severity and psychopathology. Although the ‘FA’ construct is able to differentiate between ED and HC, it needs to be further explored. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109343/1/erv2311.pd

Hippocampal and striatal responses during motor learning are modulated by prefrontal cortex stimulation

While it is widely accepted that motor sequence learning (MSL) is supported by a prefrontal-mediated interaction between hippocampal and striatal networks, it remains unknown whether the functional responses of these networks can be modulated in humans with targeted experimental interventions. The present proof-of-concept study employed a multimodal neuroimaging approach, including functional magnetic resonance (MR) imaging and MR spectroscopy, to investigate whether individually-tailored theta-burst stimulation of the dorsolateral prefrontal cortex can modulate responses in the hippocampus and the basal ganglia during motor learning. Our results indicate that while stimulation did not modulate motor performance nor task-related brain activity, it influenced connectivity patterns within hippocampo-frontal and striatal networks. Stimulation also altered the relationship between the levels of gamma-aminobutyric acid (GABA) in the stimulated prefrontal cortex and learning-related changes in both activity and connectivity in fronto-striato-hippocampal networks. This study provides the first experimental evidence, to the best of our knowledge, that brain stimulation can alter motor learning-related functional responses in the striatum and hippocampus.This work was supported by the Belgian Research Foundation Flanders (FWO; G099516N) and internal funds from KU Leuven. GA also received support from FWO (G0D7918N, G0B1419N, 1524218N) and Excellence of Science (EOS, 30446199, MEMODYN, with SPS and DM). MAG, ND and MPV received salary support from these grants. MAG is funded by a predoctoral fellowship from FWO (1141320N). Financial support for author BRK was provided by the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement (703490) and a postdoctoral fellowship from FWO (132635). This study applies tools developed under National Institutes of Health (NIH) Grants R01- EB-016089, R01-023963, and P41-EB015909; RAEE also receives salary support from these grants. NAJP receives salary support from NIH Grant R00-MH-107719. EMR received salary support from the Air Force Office of Scientific Research (AFOSR, Virginia, USA; FA9550-16-1-0191)

"Eating addiction", rather than "food addiction", better captures addictive-like eating behavior

Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved. This review has been compiled by scientists of the NeuroFAST consortium (The Integrated Neurobiology of Food Intake, Addiction and Stress; www.neurofast.eu), a research program that aims to reveal neurobiological and psychological mechanisms underlying habit-forming addictive processes related to the overconsumption of highly palatable food. The research leading to these results has received funding from the European Union's Seventh Framework programme for research, technological development and demonstration under grant agreement no. 245009.Peer reviewedPublisher PD

Abnormalities of the late positive potential during emotional processing in individuals with psychopathic traits: a meta-analysis

International audienceAbstract Background Individuals with psychopathic traits display deficits in emotional processing. A key event-related potential component involved in emotional processing is the late positive potential (LPP). In healthy controls, LPP amplitude is greater in response to negative stimuli than to positive or neutral stimuli. In the current study, we aimed to compare LPP amplitudes between individuals with psychopathic traits and control subjects when presented with negative, positive or neutral stimuli. We hypothesized that LPP amplitude evoked by emotional stimuli would be reduced in individuals with psychopathic traits compared to healthy controls. Methods After a systematic review of the literature, we conducted a meta-analysis to compare LPP amplitude elicited by emotional stimuli in individuals with psychopathic traits and healthy controls. Results Individuals with psychopathic traits showed significantly reduced LPP amplitude evoked by negative stimuli (mean effect size = −0.47; 95% CI −0.60 to −0.33; p < 0.005) compared to healthy controls. No significant differences between groups were observed for the processing of positive (mean effect size = −0.15; 95% CI −0.42 to 0.12; p = 0.28) and neutral stimuli (mean effect size = −0.12; 95% CI 0.31 to 0.07; p = 0.21). Conclusions Measured by LPP amplitude, individuals with psychopathic traits displayed abnormalities in the processing of emotional stimuli with negative valence whereas processing of stimuli with positive and neutral valence was unchanged as compared with healthy controls