Compulsive sexual behavior: Prefrontal and limbic volume and interactions.

$\textit{Background:}$ Compulsive sexual behaviors (CSB) are relatively common and associated with significant personal and social dysfunction. The underlying neurobiology is still poorly understood. The present study examines brain volumes and resting state functional connectivity in CSB compared with matched healthy volunteers (HV). $\textit{Methods:}$ Structural MRI (MPRAGE) data were collected in 92 subjects (23 CSB males and 69 age-matched male HV) and analyzed using voxel-based morphometry. Resting state functional MRI data using multi-echo planar sequence and independent components analysis (ME-ICA) were collected in 68 subjects (23 CSB subjects and 45 age-matched HV). $\textit{Results:}$ CSB subjects showed greater left amygdala gray matter volumes (small volume corrected, Bonferroni adjusted $P$ < 0.01) and reduced resting state functional connectivity between the left amygdala seed and bilateral dorsolateral prefrontal cortex (whole brain, cluster corrected FWE $P$ < 0.05) compared with HV. $\textit{Conclusions:}$ CSB is associated with elevated volumes in limbic regions relevant to motivational salience and emotion processing, and impaired functional connectivity between prefrontal control regulatory and limbic regions. Future studies should aim to assess longitudinal measures to investigate whether these findings are risk factors that predate the onset of the behaviors or are consequences of the behaviors

Pilot study: Improving attention bias modification of alcohol cues through concealed gaze-contingent feedback in alcohol dependence.

In an attempt to improve attention bias modification (ABM), we tested whether an attentional training protocol which featured monetary operant conditioning of eye-gaze to avoid alcohol stimuli in alcohol-dependent patients could reduce attention, craving and relapse to alcohol. We employed a pilot randomized control trial (RCT) with 21 detoxified alcohol dependent patients (48.9 ± 10 years of age, 9 male) from an inpatient and outpatient treatment centre. The novel concealed operant conditioning paradigm provided monetary reinforcements or punishments respective to eye-gaze patterns towards neutral or towards alcohol stimuli along with an 80% probability of a to-be-detected probe appearing following neutral stimuli (ET-ABM group). Patients in the control-group received random monetary feedback and a 50/50 ABM contingency. We compared AB on trained and untrained stimuli and addiction severity measures of obsessive thoughts and desires to alcohol following training. We further assessed addiction severity and relapse outcome at a 3-month follow-up. Results indicate that this attentional retraining only worked for the trained stimuli and did not generalize to untrained stimuli or to addiction severity measures or relapse outcome. Potential explanations for lack of generalization include the low sample size and imbalances on important prognostic variables between the active-group and control-group. We discuss progress and challenges for further research on cognitive training using gaze-contingent feedback

Compulsive sexual behavior: Prefrontal and limbic volume and interactions.

BACKGROUND: Compulsive sexual behaviors (CSB) are relatively common and associated with significant personal and social dysfunction. The underlying neurobiology is still poorly understood. The present study examines brain volumes and resting state functional connectivity in CSB compared with matched healthy volunteers (HV). METHODS: Structural MRI (MPRAGE) data were collected in 92 subjects (23 CSB males and 69 age-matched male HV) and analyzed using voxel-based morphometry. Resting state functional MRI data using multi-echo planar sequence and independent components analysis (ME-ICA) were collected in 68 subjects (23 CSB subjects and 45 age-matched HV). RESULTS: CSB subjects showed greater left amygdala gray matter volumes (small volume corrected, Bonferroni adjusted P < 0.01) and reduced resting state functional connectivity between the left amygdala seed and bilateral dorsolateral prefrontal cortex (whole brain, cluster corrected FWE P < 0.05) compared with HV. CONCLUSIONS: CSB is associated with elevated volumes in limbic regions relevant to motivational salience and emotion processing, and impaired functional connectivity between prefrontal control regulatory and limbic regions. Future studies should aim to assess longitudinal measures to investigate whether these findings are risk factors that predate the onset of the behaviors or are consequences of the behaviors. Hum Brain Mapp 38:1182-1190, 2017. © 2016 Wiley Periodicals, Inc

Sexually dimorphic brain volume interaction in college-aged binge drinkers.

BACKGROUND: Binge consumption of alcohol is a major societal problem associated with important cognitive, physiological and neurotoxic consequences. Converging evidence highlights the need to assess binge drinking (BD) and its effects on the developing brain while taking into account gender differences. Here, we compared the brain volumetric differences between genders in college-aged binge drinkers and healthy volunteers. METHOD: T1-weighted magnetic resonance imaging (MRI) images of 30 binge drinkers (18 males) and 46 matched healthy volunteers (23 males) were examined using voxel-based morphometry. The anatomical scans were covaried with Alcohol Use Disorders Identification Test (AUDIT) scores. Whole brain voxel-wise group comparisons were performed using a cluster extent threshold correction. RESULTS: Several large clusters qualified with group-by-gender interactions were observed in prefrontal, striatal and medial temporal areas, whereby BD females had more volume than non-BD females, while males showed the inverse pattern of decreased volume in BD males and increased volume in non-BD males. AUDIT scores negatively correlated with volume in the right superior frontal cortex and precentral gyrus. CONCLUSIONS: These findings dovetail with previous studies reporting that a state effect of BD in college-aged drinkers and the severity of alcohol use are associated with volumetric alterations in the cortical and subcortical areas of the brain. Our study indicates that these widespread volumetric changes vary differentially by gender, suggesting either sexual dimorphic endophenotypic risk factors, or differential neurotoxic sensitivities for males and females.The study was supported by the Wellcome Trust grant to VV (093705/10/Z). We would like to thank the WBIC staff for their expertise and assistance with collecting the imaging data, and our participants for their time and commitment. The Behavioural and Clinical Neuroscience Institute is supported by the Wellcome Trust and Medical Research Council.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.nicl.2015.12.00

Pilot study: Improving attention bias modification of alcohol cues through concealed gaze-contingent feedback in alcohol dependence.

In an attempt to improve attention bias modification (ABM), we tested whether an attentional training protocol which featured monetary operant conditioning of eye-gaze to avoid alcohol stimuli in alcohol-dependent patients could reduce attention, craving and relapse to alcohol. We employed a pilot randomized control trial (RCT) with 21 detoxified alcohol dependent patients (48.9 ± 10 years of age, 9 male) from an inpatient and outpatient treatment centre. The novel concealed operant conditioning paradigm provided monetary reinforcements or punishments respective to eye-gaze patterns towards neutral or towards alcohol stimuli along with an 80% probability of a to-be-detected probe appearing following neutral stimuli (ET-ABM group). Patients in the control-group received random monetary feedback and a 50/50 ABM contingency. We compared AB on trained and untrained stimuli and addiction severity measures of obsessive thoughts and desires to alcohol following training. We further assessed addiction severity and relapse outcome at a 3-month follow-up. Results indicate that this attentional retraining only worked for the trained stimuli and did not generalize to untrained stimuli or to addiction severity measures or relapse outcome. Potential explanations for lack of generalization include the low sample size and imbalances on important prognostic variables between the active-group and control-group. We discuss progress and challenges for further research on cognitive training using gaze-contingent feedback

MDMA-assisted psychotherapy for PTSD:Growing evidence for memory effects mediating treatment efficacy

The application of MDMA in conjunction with psychotherapy has in recent years seen a resurgence of clinical, scientific, and public interest in the treatment of posttraumatic stress disorder (PTSD). Clinical trials have shown promising safety and efficacy, but the mechanisms underlying this treatment form remain largely unestablished. This article explores recent preclinical and clinical evidence suggesting that the treatment's efficacy may be influenced by the mnemonic effects of MDMA. We review data on the effects of MDMA on fear extinction and fear reconsolidation and the utility of these processes for PTSD treatment. We corroborate our findings by incorporating research from cognitive psychology and psychopharmacology and offer recommendations for future research

Incentives and voluntary stopping: The intentional hand task.

Intentional inhibition, the endogenous decision to stop or cancel an action, is arguably a more ecologically valid process than automatized, reactive, inhibition which occurs in response to an external stop signal without active decision making at the moment of inhibition. Choosing to stop an act of opening the fridge door, or of reaching for a bottle of alcohol may therefore extend beyond a reactive inhibitory process, e.g. stopping at a red traffic light. Existing paradigms of intentional inhibition focus on the proportions of intentional stops. Here we developed the Intentional Hand Task, which provides stop response times for intentional and instructed trials. Participants move a cursor by initiating an arm movement, after which a Go, Stop or Choice trial occurs. In Go trials, participants are instructed to make a speeded continuation of their arm movement towards a target whereas in the Stop trials participants are instructed to rapidly stop the already initiated movement. In Choice trials, participants chose whether to continue or stop the movement. By comparing response times when movement was stopped, we found that intentionally stopping took significantly longer than externally instructed stopping. We further investigated the influence of reward incentives, by cueing trials with either the prospect of No, Low or High reward for correctly continuing in Go trials, stopping in Stop trials or achieving a random balance of intentional Go and Stops in Choice trials. Reward incentives led to greater approach behaviours, indicated by significantly higher Go accuracy in instructed Go trials and faster response times across both Go trial types. The presence of reward incentives led to significantly fewer intentional stop choices. Our findings suggest intentional inhibition of an ongoing action may require a further decisional process. Furthermore, monetary incentives may implicitly trigger an appetitive system thus facilitating approach rather than intentional inhibitory behaviour. These findings are particularly relevant to cue-related relapse in disorders of addiction where cues may facilitate approach behaviours to the detriment of intentional inhibitory control

Pupillary reactivity to alcohol cues as a predictive biomarker of alcohol relapse following treatment in a pilot study.

RATIONALE: Identifying the predictors of relapse in detoxified alcohol-dependent patients is crucial for effective surveillance procedures and the optimization of treatment. Physiological measures such as functional MRI activity and heart rate variability have been shown as potential markers of relapse prediction. OBJECTIVES: Our aim was to assess differential pupillary reactions to alcohol-related cues as an objective physiological candidate predictor of relapse. METHODS: We examined the relationship between cue-elicited pupillary reactions to alcohol stimuli and luminance-controlled neutral stimuli in 21 detoxified alcohol-dependent patients and subsequent relapse outcome at a 4-month follow-up. RESULTS: Differential pupillary dilation to alcohol stimuli as compared to neutral stimuli at 150 to 250 ms after stimulus onset substantially improved the model prediction of relapse outcome (additional 27% of variance) beyond that achieved from five standardized questionnaires on alcohol craving, alcohol use, problematic use severity, depressive tendencies, and duration of abstinence (47% of variance). In contrast, alcohol craving did not improve relapse model prediction. CONCLUSIONS: This pilot study shows that alcohol-dependent patients with greater pupillary dilation to alcohol stimuli are more vulnerable to relapse, and that pupillometry presents as an important tool for addiction science

A bias towards natural rewards away from gambling cues in gamblers undergoing active treatment.

BACKGROUND: Disorders of substance and behavioral addiction are believed to be associated with a myopic bias towards the incentive salience of addiction-related cues away from general rewards in the environment. In non-treatment seeking gambling disorder patients, neural activity to anticipation of monetary rewards is enhanced relative to erotic rewards. Here we focus on the balance between anticipation of reward types in active treatment gamblers relative to healthy volunteers. METHODS: Fifty-three (25 gambling disorder males, 28 age-matched male healthy volunteers) were scanned with fMRI performing a Monetary Incentive Delay task with monetary and erotic outcomes. RESULTS: During reward anticipation, gambling disorder was associated with greater left orbitofrontal cortex and ventral striatal activity to erotic relative to monetary reward anticipation compared to healthy volunteers. Lower impulsivity correlated with greater activity in the dorsal striatum and dorsal anterior cingulate cortex to erotic anticipation in gambling disorder subjects. In the outcome phase, gambling disorder subjects showed greater activity in the ventral striatum, ventromedial and dorsolateral prefrontal cortex and anterior cingulate cortex to both reward types relative to healthy volunteers. CONCLUSIONS: These findings contrast directly with previous findings in non-treatment seeking gambling disorder. Our observations highlight the role of treatment state in active treatment gambling disorder, emphasizing a potential influence of treatment status, gambling abstinence or cognitive behavioral therapy on increasing the salience of general rewards beyond that of gambling-related cues. These findings support a potential therapeutic role for targeting the salience of non-gambling related rewards and potential biomarkers for treatment efficacy