Due to its high ecological validity, virtual reality (VR) technology has emerged as a powerful tool for mental health research. Despite the wide use of VR simulations in research on mental illnesses, ...the study of addictive processes through the use of VR environments is still at its dawn. In a systematic literature search, we identified 38 reports of research projects using highly immersive head-mounted displays, goggles, or CAVE technologies to provide insight into treatment mechanisms of addictive behaviors. So far, VR research has mainly addressed the roles of craving, psychophysiology, affective states, cognition, and brain activity in addiction. The computer-generated VR environments offer very realistic, dynamic, interactive, and complex real-life simulations requesting active participation. They create a high sense of immersion in users by combining stereoscopic three-dimensional visual, auditory, olfactory, and tactile perceptions, tracking systems responding to user movements, and social interactions. VR is an emerging tool to study how proximal multi-sensorial cues, contextual environmental cues, as well as their interaction (complex cues) modulate addictive behaviors. VR allows for experimental designs under highly standardized, strictly controlled, predictable, and repeatable conditions. Moreover, VR simulations can be personalized. They are currently refined for psychotherapeutic interventions. Embodiment, eye-tracking, and neurobiological factors represent novel future directions. The progress of VR applications has bred auspicious ways to advance the understanding of treatment mechanisms underlying addictions, which researchers have only recently begun to exploit. VR methods promise to yield significant achievements to the addiction field. These are necessary to develop more efficacious and efficient preventive and therapeutic strategies.
This article explores the mechanisms of action and the potential responder profile of acamprosate, a compound efficacious in relapse prevention of alcoholism. New evidence at the molecular and ...cellular level suggests that acamprosate attenuates hyper‐glutamatergic states that occur during early abstinence and involves iono (NMDA)‐ and metabotrotropic (mGluR5) glutamate receptors along with augmented intracellular calcium release and electrophysiological changes. Thus mutant mice with enhanced glutamate levels exhibit higher alcohol consumption than wild type mice and respond better to acamprosate, demonstrating that acamprosate acts mainly on a hyper‐glutamatergic system. This mode of action further suggests that acamprosate exhibits neuroprotective properties. In rats, cue‐induced reinstatement behavior is significantly reduced by acamprosate treatment whereas cue‐induced craving responses in alcohol‐dependent patients seem not to be affected by this treatment. An ongoing study (“Project Predict”) defines specific responder profiles for an individualized use of acamprosate and naltrexone. Neurophysiological as well as psychometric data are used to define 2 groups of patients: “reward cravers” and “relief cravers”. While naltrexone should work better in the first group, acamprosate is hypothesized to be efficacious in the latter where withdrawal associated and/or cue induced hyper‐glutamatergic states are thought to trigger relapse. Further research should target the definition of subgroups applying endophenotypic approaches, e.g. by detecting a hyperglutamatergic syndrome using MR spectroscopy.
Recent studies on the pathophysiology of alcohol dependence suggest a link between peripheral calcium concentrations and alcohol craving. Here, we investigated the association between plasma calcium ...concentration, cue-induced brain activation, and alcohol craving. Plasma calcium concentrations were measured at the onset of inpatient detoxification in a sample of
N
= 115 alcohol-dependent patients. Alcohol cue-reactivity was assessed during early abstinence (mean 11.1 days) using a functional magnetic resonance imaging (fMRI) alcohol cue-reactivity task. Multiple regression analyses and bivariate correlations between plasma calcium concentrations, clinical craving measures and neural alcohol cue-reactivity (CR) were tested. Results show a significant negative correlation between plasma calcium concentrations and compulsive alcohol craving. Higher calcium levels predicted higher alcohol cue-induced brain response in a cluster of frontal brain areas, including the dorsolateral prefrontal cortex (dlPFC), the anterior prefrontal cortex (alPFC), and the inferior (IFG) and middle frontal gyri (MFG). In addition, functional brain activation in those areas correlated negatively with craving for alcohol during fMRI. Higher peripheral calcium concentrations during withdrawal predicted increased alcohol cue-induced brain activation in frontal brain areas, which are associated with craving inhibition and cognitive control functions. This might indicate that higher plasma calcium concentrations at onset of detoxification could modulate craving inhibition during early abstinence.
Trial registration number
: DRKS00003388; date of registration: 14.12.2011.
Rationale
Alcohol use disorder is a common and devastating mental illness for which satisfactory treatments are still lacking. Nalmefene, as an opioid receptor modulator, could pharmacologically ...support the reduction of drinking by reducing the (anticipated) rewarding effects of alcohol and expanding the range of treatment options. It has been hypothesized that nalmefene acts via an indirect modulation of the mesolimbic reward system. So far, only a few imaging findings on the neuronal response to nalmefene are available.
Objectives
We tested the effect of a single dose of 18 mg nalmefene on neuronal cue-reactivity in the ventral and dorsal striatum and subjective craving.
Methods
Eighteen non-treatment-seeking participants with alcohol use disorder (67% male,
M
= 50.3 ± 13.9 years) with a current high-risk drinking level (
M
= 76.9 ± 52 g of pure alcohol per day) were investigated using a cue-reactivity task during functional magnetic resonance imaging (fMRI) in a double-blind, placebo-controlled, cross-over study/design. In addition, self-reported craving was assessed before and after exposure to alcohol cues.
Results
An a priori defined region of interest (ROI) analysis of fMRI data from 15 participants revealed that nalmefene reduced alcohol cue-reactivity in the ventral, but not the dorsal striatum. Additionally, the subjective craving was significantly reduced after the cue-reactivity task under nalmefene compared to placebo.
Conclusion
In the present study, reduced craving and cue-reactivity to alcohol stimuli in the ventral striatum by nalmefene indicates a potential anti-craving effect of this drug via attenuation of neural alcohol cue-reactivity.
Obesity is highly prevalent worldwide and results in a high disease burden. The efforts to monitor and predict treatment outcome in participants with obesity using functional magnetic resonance ...imaging (fMRI) depends on the reliability of the investigated task-fMRI brain activation. To date, no study has investigated whole-brain reliability of neural food cue-reactivity. To close this gap, we analyzed the longitudinal reliability of an established food cue-reactivity task. Longitudinal reliability of neural food-cue-induced brain activation and subjective food craving ratings over three fMRI sessions (T0: 2 weeks before surgery, T1: 8 weeks and T2: 24 weeks after surgery) were investigated in
N
= 11 participants with obesity. We computed an array of established reliability estimates, including the intraclass correlation (ICC), the Dice and Jaccard coefficients and similarity of brain activation maps. The data indicated good reliability (ICC > 0.6) of subjective food craving ratings over 26 weeks and excellent reliability (ICC > 0.75) of brain activation signals for the contrast of interest (food > neutral) in the caudate, putamen, thalamus, middle cingulum, inferior, middle and superior occipital gyri, and middle and superior temporal gyri and cunei. Using similarity estimates, it was possible to re-identify individuals based on their neural activation maps (73%) with a fading degree of accuracy, when comparing fMRI sessions further apart. The results show excellent reliability of task-fMRI neural brain activation in several brain regions. Current data suggest that fMRI-based measures might indeed be suitable to monitor and predict treatment outcome in participants with obesity undergoing bariatric surgery.
There is increasing evidence that brain-derived neurotrophic factor (BDNF) impacts on the development of obesity. We are the first to test the hypothesis that BDNF levels might be associated with ...neural reactivity to food cues in patients suffering from obesity and healthy controls. We assessed visual food cue-induced neural response in 19 obese patients and 20 matched controls using functional magnetic resonance imaging and analyzed the associations between BDNF levels, food cue-reactivity and food craving. Whole-brain analysis in both groups revealed that food cues elicited higher neural activation in clusters of mesolimbic brain areas including the insula (food > neutral). Patients suffering from obesity showed a significant positive correlation between plasma BDNF levels and visual food cue-reactivity in the bilateral insulae. In addition, patients suffering from obesity with positive food cue-induced insula activation also reported significantly higher food craving than those with low cue-reactivity—an effect that was absent in normal weight participants. The present findings implicate that BDNF levels in patients suffering from obesity might be involved in food craving and obesity in humans. This highlights the importance to consider BDNF pathways when investigating obesity and obesity treatment.
Opioid-dependent patients frequently show deficits in multiple cognitive domains that might impact on their everyday life performance and interfere with therapeutic efforts. To date, the ...neurobiological underpinnings of those deficits remain to be determined. We investigated working memory performance and gray matter volume (GMV) differences in 17 patients on opioid maintenance treatment (OMT) and 17 healthy individuals using magnetic resonance imaging and voxel-based morphometry. In addition, we explored associations between substance intake, gray matter volume, and working memory task performance. Patients on OMT committed more errors during the working memory task than healthy individuals and showed smaller insula and putamen GMV. The duration of heroin use prior to OMT was associated with working memory performance and insula GMV in patients. Neither the substitution agent (methadone and buprenorphine) nor concurrent abuse of illegal substances during the 3 months prior to the experiment was significantly associated with GMV. Results indicate that impaired working memory performance and structural deficits in the insula of opioid-dependent patients are related to the duration of heroin use. This suggests that early inclusion into OMT or abstinence-oriented therapies that shorten the period of heroin abuse may limit the impairments to GMV and cognitive performance of opioid-dependent individuals.
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