Compulsivity Across the Pathological Misuse of Drug and Non-Drug Rewards.

Behavioral adaptation is required for the successful navigation of a constantly changing environment. Impairments in behavioral flexibility are commonly observed in psychiatric disorders including those of addiction. This study investigates two distinct facets of compulsivity, namely reversal learning and attentional set shifting, implicating orbitofrontal and lateral prefrontal regions respectively, across disorders of primary and secondary rewards. Obese subjects with and without binge eating disorder (BED), individuals with compulsive sexual behaviors (CSB), alcohol dependence (AD) and pathological video-gaming (VG) were tested with two computerized tasks: the probabilistic reversal task (trials to criterion and win-stay/lose-shift errors) and the intra/extra-dimensional set shift task (IED). Individuals with AD and pathological VG were slower at reversal learning irrespective of valence, with AD subjects more likely to perseverate after losses. Compared to obese subjects without BED, BED subjects were worse at reversal learning to wins but better at losses highlighting valence effects as a function of binge eating. CSB subjects demonstrated enhanced sensitivity to reward outcomes with faster acquisition and greater perseveration with higher magnitude rewards. We further show an impairment in attentional set shifting in individuals with BED and AD relative to healthy volunteers (HV). This study provides evidence for commonalities and differences in two distinct dimensions of behavioral inflexibility across disorders of compulsivity. We summarize studies on compulsivity subtypes within this same patient population. We emphasize commonalities in AD and BED with impairments across a range of compulsivity indices, perhaps supporting pathological binge eating as a form of behavioral addiction. We further emphasize commonalities in reversal learning across disorders and the crucial role of valence effects. These findings highlight the role of behavioral inflexibility and compulsivity as a relevant domain in defining dimensional psychiatry and the identification of relevant cognitive endophenotypes as targets for therapeutic modulation.PB was supported by the Portuguese Foundation for Science and Technology (individual fellowship: SFRH/BD/33889/2009). VV and NAH are Wellcome Trust Intermediate Fellows. The study was funded by the Wellcome Trust (WT093705/Z/10/Z).This is the final version of the article. It first appeared from Frontiers via http://dx.doi.org/10.3389/fnbeh.2016.0015

A Mobile Phone App for the Generation and Characterization of Motor Habits.

Habits are a powerful route to efficiency; the ability to constantly shift between goal-directed and habitual strategies, as well as integrate them into behavioral output, is key to optimal performance in everyday life. When such ability is impaired, it may lead to loss of control and to compulsive behavior. Habits have successfully been induced and investigated in rats using methods such as overtraining stimulus-response associations and outcome devaluation, respectively. However, such methods have ineffectively measured habits in humans because (1) human habits usually involve more complex sequences of actions than in rats and (2) of pragmatic impediments posed by the extensive time (weeks or even months), it may take for routine habits to develop. We present here a novel behavioral paradigm-a mobile-phone app methodology-for inducing and measuring habits in humans during their everyday schedule and environment. It assumes that practice is key to achieve automaticity and proficiency and that the use of a hierarchical sequence of actions is the best strategy for capturing the cognitive mechanisms involved in habit formation (including "chunking") and consolidation. The task is a gamified self-instructed and self-paced app on a mobile phone that enables subjects to learn and practice two sequences of finger movements, composed of chords and single presses. It involves a step-wise learning procedure in which subjects begin responding to a visual and auditory cued sequence by generating responses on the screen using four fingers. Such cues progressively disappear throughout 1 month of training, enabling the subject ultimately to master the motor skill involved. We present preliminary data for the acquisition of motor sequence learning in 29 healthy individuals, each trained over a month period. We demonstrate an asymptotic improvement in performance, as well as its automatic nature. We also report how people integrate the task into their daily routine, the development of motor precision throughout training, and the effect of intermittent reinforcement and reward extinction in habit preservation. The findings help to validate this "real world" app for measuring human habits

Reflection impulsivity in binge drinking: behavioural and volumetric correlates.

The degree to which an individual accumulates evidence prior to making a decision, also known as reflection impulsivity, can be affected in psychiatric disorders. Here, we study decisional impulsivity in binge drinkers, a group at elevated risk for developing alcohol use disorders, comparing two tasks assessing reflection impulsivity and a delay discounting task, hypothesizing impairments in both subtypes of impulsivity. We also assess volumetric correlates of reflection impulsivity focusing on regions previously implicated in functional magnetic resonance imaging studies. Sixty binge drinkers and healthy volunteers were tested using two different information-gathering paradigms: the beads task and the Information Sampling Task (IST). The beads task was analysed using a behavioural approach and a Bayesian model of decision making. Delay discounting was assessed using the Monetary Choice Questionnaire. Regression analyses of primary outcomes were conducted with voxel-based morphometry analyses. Binge drinkers sought less evidence prior to decision in the beads task compared with healthy volunteers in both the behavioural and computational modelling analysis. There were no group differences in the IST or delay discounting task. Greater impulsivity as indexed by lower evidence accumulation in the beads task was associated with smaller dorsolateral prefrontal cortex and inferior parietal volumes. In contrast, greater impulsivity as indexed by lower evidence accumulation in the IST was associated with greater dorsal cingulate and precuneus volumes. Binge drinking is characterized by impaired reflection impulsivity suggesting a deficit in deciding on the basis of future outcomes that are more difficult to represent. These findings emphasize the role of possible therapeutic interventions targeting decision-making deficits.The study was supported by theWellcome Trust grant to VV (093705/10/Z) and to NA Harrison. PB is supported by the Portuguese Foundation for Science and Technology (individual fellowship to PB: SFRH/BD/33889/ 2009). YW is supported by the Fyssen Fondation. MM is supported by the Welcome Trust and the Biomedical Research Centre.Wewould also like to thank theWolfson Brain Imaging Center staff for their expertise with collecting the imaging data and all the participants for their involvement in this study. The Behavioural and Clinical Neuroscience Institute is supported by the Wellcome Trust and Medical Research Council.This is the final published version. It first appeared from Wiley via http://dx.doi.org/10.1111/adb.1222

Solubility and solid phase studies of isomeric phenolic acids in pure solvents

The solubilities of gallic, protocatechuic, gentisic or α-resorcylic acids were measured in nine pure solvents (water, methanol, ethanol, 1-propanol, 2-propanol, 2-butanone, ethyl acetate, acetonitrile and dimethylformamide) at 298.15 K and 313.15 K, using the analytical isothermal shake-flask method. Additionally, solid phase studies of the selected phenolic acids were carried out using differential scanning calorimetry (DSC) and X-ray diffraction (XRD), giving access to important data on melting properties as well as on the structure of the solid phase before and after the dissolution. The NRTL-SAC model coupled to the reference solvent approach (RSA) were applied to correlate the solubility data in a set of seven solvents and, after used to predict the solubility in 1-propanol and dimethylformamide. Average relative deviations (ARD) between 28 and 40% for the correlation and between 16 and 59% for the predictions were obtained. These values are within the order of magnitude usually found for such type of semi-predictive models, using a limited set of data.This work is supported by: Project “AIProcMat@N2020 - Advanced Industrial Processes and Materials for a Sustainable Northern Region of Portugal 2020”, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); Project POCI-01-0145-FEDER-006984 – Associate Laboratory LSRE-LCM funded by ERDF through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI); Project POCI-01-0145-FEDER-030463 financed by COMPETE and Portugal2020 and national funds through FCT - Fundação para a Ciência e a Tecnologia . We also acknowledge the support of CICECO – Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (Ref. FCT UID/CTM/50011/2013 ). Appendix Ainfo:eu-repo/semantics/publishedVersio

Enhanced attentional bias towards sexually explicit cues in individuals with and without compulsive sexual behaviours.

Compulsive sexual behaviour (CSB) is relatively common and has been associated with significant distress and psychosocial impairments. CSB has been conceptualized as either an impulse control disorder or a non-substance 'behavioural' addiction. Substance use disorders are commonly associated with attentional biases to drug cues which are believed to reflect processes of incentive salience. Here we assess male CSB subjects compared to age-matched male healthy controls using a dot probe task to assess attentional bias to sexually explicit cues. We show that compared to healthy volunteers, CSB subjects have enhanced attentional bias to explicit cues but not neutral cues particularly for early stimuli latency. Our findings suggest enhanced attentional bias to explicit cues possibly related to an early orienting attentional response. This finding dovetails with our recent observation that sexually explicit videos were associated with greater activity in a neural network similar to that observed in drug-cue-reactivity studies. Greater desire or wanting rather than liking was further associated with activity in this neural network. These studies together provide support for an incentive motivation theory of addiction underlying the aberrant response towards sexual cues in CSB.This is the published version of the manuscript. It is originally published by PLoS in PLoS ONE here: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0105476

Action-sequence learning, habits and automaticity in obsessive-compulsive disorder

Enhanced habit formation, greater automaticity and impaired goal/habit arbitration in obsessive-compulsive disorder (OCD) are key hypotheses from the goal/habit imbalance theory of compulsion which have not been directly investigated. This article tests these hypotheses using a combination of newly developed behavioral tasks. First, we trained patients with OCD and healthy controls, using a novel smartphone app, to perform chunked action sequences, previously shown to engage habit brain circuitry. The motor training was daily over one month period. There was equivalent procedural learning and attainment of habitual performance (measured with an objective criteria of automaticity) in both groups, despite greater subjective habitual tendencies in patients with OCD, self-reported via a recently developed questionnaire. We then used a combination of follow-up behavioral tasks to further assess the arbitration between previous automatic and new goal-directed action sequences. We found no evidence for impairments of goal/habit arbitration in OCD following re-evaluation based on monetary feedback, although there was a greater preference for engaging in the trained habitual sequence under certain conditions which may have derived from its intrinsic value. These findings may lead to a reformulation of the goal/habit imbalance hypothesis in OCD. Finally, OCD patients with higher compulsivity scores and habitual tendencies showed more engagement with the motor habit-training app and reported symptom alleviation, with implications for its potential use as a form of habit reversal therapy

Mapping Compulsivity in the DSM-5 Obsessive Compulsive and Related Disorders: Cognitive Domains, Neural Circuitry, and Treatment.

Compulsions are repetitive, stereotyped thoughts and behaviors designed to reduce harm. Growing evidence suggests that the neurocognitive mechanisms mediating behavioral inhibition (motor inhibition, cognitive inflexibility) reversal learning and habit formation (shift from goal-directed to habitual responding) contribute toward compulsive activity in a broad range of disorders. In obsessive compulsive disorder, distributed network perturbation appears focused around the prefrontal cortex, caudate, putamen, and associated neuro-circuitry. Obsessive compulsive disorder-related attentional set-shifting deficits correlated with reduced resting state functional connectivity between the dorsal caudate and the ventrolateral prefrontal cortex on neuroimaging. In contrast, experimental provocation of obsessive compulsive disorder symptoms reduced neural activation in brain regions implicated in goal-directed behavioral control (ventromedial prefrontal cortex, caudate) with concordant increased activation in regions implicated in habit learning (presupplementary motor area, putamen). The ventromedial prefrontal cortex plays a multifaceted role, integrating affective evaluative processes, flexible behavior, and fear learning. Findings from a neuroimaging study of Pavlovian fear reversal, in which obsessive compulsive disorder patients failed to flexibly update fear responses despite normal initial fear conditioning, suggest there is an absence of ventromedial prefrontal cortex safety signaling in obsessive compulsive disorder, which potentially undermines explicit contingency knowledge and may help to explain the link between cognitive inflexibility, fear, and anxiety processing in compulsive disorders such as obsessive compulsive disorder

Increased ventral striatal volume in college-aged binge drinkers

BACKGROUND Binge drinking is a serious public health issue associated with cognitive, physiological, and anatomical differences from healthy individuals. No studies, however, have reported subcortical grey matter differences in this population. To address this, we compared the grey matter volumes of college-age binge drinkers and healthy controls, focusing on the ventral striatum, hippocampus and amygdala. METHOD T1-weighted images of 19 binge drinkers and 19 healthy volunteers were analyzed using voxel-based morphometry. Structural data were also covaried with Alcohol Use Disorders Identification Test (AUDIT) scores. Cluster-extent threshold and small volume corrections were both used to analyze imaging data. RESULTS Binge drinkers had significantly larger ventral striatal grey matter volumes compared to controls. There were no between group differences in hippocampal or amygdalar volume. Ventral striatal, amygdalar, and hippocampal volumes were also negatively related to AUDIT scores across groups. CONCLUSIONS Our findings stand in contrast to the lower ventral striatal volume previously observed in more severe forms of alcohol use disorders, suggesting that college-age binge drinkers may represent a distinct population from those groups. These findings may instead represent early sequelae, compensatory effects of repeated binge and withdrawal, or an endophenotypic risk factor

Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions