Disgust proneness and associated neural substrates in obesity.

Defects in experiencing disgust may contribute to obesity by allowing for the overconsumption of food. However, the relationship of disgust proneness and its associated neural locus has yet to be explored in the context of obesity. Thirty-three participants (17 obese, 16 lean) completed the Disgust Propensity and Sensitivity Scale-Revised and a functional magnetic resonance imaging paradigm where images from 4 categories (food, contaminates, contaminated food or fixation) were randomly presented. Independent two-sample t-tests revealed significantly lower levels of Disgust Sensitivity for the obese group (mean score = 14.7) compared with the lean group (mean score = 17.6, P = 0.026). The obese group had less activation in the right insula than the lean group when viewing contaminated food images. Multiple regression with interaction analysis revealed one left insula region where the association of Disgust Sensitivity scores with activation differed by group when viewing contaminated food images. These interaction effects were driven by the negative correlation of Disgust Sensitivity scores with beta values extracted from the left insula in the obese group (r = -0.59) compared with a positive correlation in the lean group (r = 0.65). Given these body mass index-dependent differences in Disgust Sensitivity and neural responsiveness to disgusting food images, it is likely that altered Disgust Sensitivity may contribute to obesity.

Human ecstasy (MDMA) polydrug users have altered brain activation during semantic processing.

RATIONALE: Ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) polydrug users have verbal memory performance that is statistically significantly lower than that of control subjects. Studies have correlated long-term MDMA use with altered brain activation in regions that play a role in verbal memory. OBJECTIVES: The aim of our study was to examine the association of lifetime ecstasy use with semantic memory performance and brain activation in ecstasy polydrug users. METHODS: A total of 23 abstinent ecstasy polydrug users (age = 24.57 years) and 11 controls (age = 22.36 years) performed a two-part functional magnetic resonance imaging (fMRI) semantic encoding and recognition task. To isolate brain regions activated during each semantic task, we created statistical activation maps in which brain activation was greater for word stimuli than for non-word stimuli (corrected p < 0.05). RESULTS: During the encoding phase, ecstasy polydrug users had greater activation during semantic encoding bilaterally in language processing regions, including Brodmann areas 7, 39, and 40. Of this bilateral activation, signal intensity with a peak T in the right superior parietal lobe was correlated with lifetime ecstasy use (r s = 0.43, p = 0.042). Behavioral performance did not differ between groups. CONCLUSIONS: These findings demonstrate that ecstasy polydrug users have increased brain activation during semantic processing. This increase in brain activation in the absence of behavioral deficits suggests that ecstasy polydrug users have reduced cortical efficiency during semantic encoding, possibly secondary to MDMA-induced 5-HT neurotoxicity. Although pre-existing differences cannot be ruled out, this suggests the possibility of a compensatory mechanism allowing ecstasy polydrug users to perform equivalently to controls, providing additional support for an association of altered cerebral neurophysiology with MDMA exposure.

Cannabis cue-induced brain activation correlates with drug craving in limbic and visual salience regions: preliminary results.

Craving is a major motivator underlying drug use and relapse but the neural correlates of cannabis craving are not well understood. This study sought to determine whether visual cannabis cues increase cannabis craving and whether cue-induced craving is associated with regional brain activation in cannabis-dependent individuals. Cannabis craving was assessed in 16 cannabis-dependent adult volunteers while they viewed cannabis cues during a functional MRI (fMRI) scan. The Marijuana Craving Questionnaire was administered immediately before and after each of three cannabis cue-exposure fMRI runs. FMRI blood-oxygenation-level-dependent (BOLD) signal intensity was determined in regions activated by cannabis cues to examine the relationship of regional brain activation to cannabis craving. Craving scores increased significantly following exposure to visual cannabis cues. Visual cues activated multiple brain regions, including inferior orbital frontal cortex, posterior cingulate gyrus, parahippocampal gyrus, hippocampus, amygdala, superior temporal pole, and occipital cortex. Craving scores at baseline and at the end of all three runs were significantly correlated with brain activation during the first fMRI run only, in the limbic system (including amygdala and hippocampus) and paralimbic system (superior temporal pole), and visual regions (occipital cortex). Cannabis cues increased craving in cannabis-dependent individuals and this increase was associated with activation in the limbic, paralimbic, and visual systems during the first fMRI run, but not subsequent fMRI runs. These results suggest that these regions may mediate visually cued aspects of drug craving. This study provides preliminary evidence for the neural basis of cue-induced cannabis craving and suggests possible neural targets for interventions targeted at treating cannabis dependence.

Evidence for chronically altered serotonin function in the cerebral cortex of female 3,4-methylenedioxymethamphetamine polydrug users.

CONTEXT: MDMA (3,4-methylenedioxymethamphetamine, also popularly known as "ecstasy") is a popular recreational drug that produces loss of serotonin axons in animal models. Whether MDMA produces chronic reductions in serotonin signaling in humans remains controversial. OBJECTIVE: To determine whether MDMA use is associated with chronic reductions in serotonin signaling in the cerebral cortex of women as reflected by increased serotonin(2A) receptor levels. DESIGN: Cross-sectional case-control study comparing serotonin(2A) receptor levels in abstinent female MDMA polydrug users with those in women who did not use MDMA (within-group design assessing the association of lifetime MDMA use and serotonin(2A) receptors). Case participants were abstinent from MDMA use for at least 90 days as verified by analysis of hair samples. The serotonin(2A) receptor levels in the cerebral cortex were determined using serotonin(2A)-specific positron emission tomography with radioligand fluorine 18-labeled setoperone as the tracer. SETTING: Academic medical center research laboratory. PARTICIPANTS: A total of 14 female MDMA users and 10 women who did not use MDMA (controls). The main exclusion criteria were nondrug-related DSM-IV Axis I psychiatric disorders and general medical illness. MAIN OUTCOME MEASURES: Cortical serotonin(2A) receptor nondisplaceable binding potential (serotonin(2A)BP(ND)). RESULTS: MDMA users had increased serotonin(2A)BP(ND) in occipital-parietal (19.7%), temporal (20.5%), occipitotemporal-parietal (18.3%), frontal (16.6%), and frontoparietal (18.5%) regions (corrected P < .05). Lifetime MDMA use was positively associated with serotonin(2A)BP(ND) in frontoparietal (ß = 0.665; P = .007), occipitotemporal (ß = 0.798; P = .002), frontolimbic (ß = 0.634; P = .02), and frontal (ß = 0.691; P = .008) regions. In contrast, there were no regions in which MDMA use was inversely associated with receptor levels. There were no statistically significant effects of the duration of MDMA abstinence on serotonin(2A)BP(ND). CONCLUSIONS: The recreational use of MDMA is associated with long-lasting increases in serotonin(2A) receptor density. Serotonin(2A) receptor levels correlate positively with lifetime MDMA use and do not decrease with abstinence. These results suggest that MDMA use produces chronic serotonin neurotoxicity in humans. Given the broad role of serotonin in human brain function, the possibility for therapeutic MDMA use, and the widespread recreational popularity of this drug, these results have critical public health implications.

Human Ecstasy use is associated with increased cortical excitability: an fMRI study.

The serotonergic neurotoxin, 3,4-methylenedioxymethamphetamine (MDMA/Ecstasy), is a highly popular recreational drug. Human recreational MDMA users have neurocognitive and neuropsychiatric impairments, and human neuroimaging data are consistent with animal reports of serotonin neurotoxicity. However, functional neuroimaging studies have not found consistent effects of MDMA on brain neurophysiology in human users. Several lines of evidence suggest that studying MDMA effects in visual system might reveal the general cortical and subcortical neurophysiological consequences of MDMA use. We used 3 T functional magnetic resonance imaging during visual stimulation to compare visual system lateral geniculate nucleus (LGN) and Brodmann Area (BA) 17 and BA 18 activation in 20 long abstinent (479.95±580.65 days) MDMA users and 20 non-MDMA user controls. Lifetime quantity of MDMA use was strongly positively correlated with blood oxygenation level-dependent (BOLD) signal intensity in bilateral LGN (r(s)=0.59; p=0.007), BA 17 (r(s)=0.50; p=0.027), and BA 18 (r(s)=0.48; p=0.031), and with the spatial extent of activation in BA 17 (r(s)=0.059; p=0.007) and BA 18 (r(s)=0.55; p=0.013). There were no between-group differences in brain activation in any region, but the heaviest MDMA users showed a significantly greater spatial extent of activation than controls in BA 17 (p=0.031) and BA 18 (p=0.049). These results suggest that human recreational MDMA use may be associated with a long-lasting increase in cortical excitability, possibly through loss of serotonin input to cortical and subcortical regions. When considered in the context of previous results, cortical hyper-excitability may be a biomarker for MDMA-induced serotonin neurotoxicity.