Reward-related responses and tonic craving in cocaine addiction: an imaging study of the monetary incentive delay task

Background Cocaine addiction is associated with altered sensitivity to natural reinforcers and intense drug craving. However, previous findings on reward-related responses are mixed and few studies have examined whether reward responses relate to tonic cocaine craving. Methods We combined fMRI and a monetary incentive delay task to investigate these issues. Imaging data were processed with published routines and the results were evaluated with a corrected threshold. We compared reward responses of 50 cocaine dependent individuals (CDs) and 45 healthy controls (HCs) for the ventral striatum (VS) and the whole brain. We also examined the regional responses in association with tonic cocaine craving, as assessed by the Cocaine Craving Questionnaire (CCQ) in CDs. We performed mediation analyses to evaluate the relationship between regional responses, CCQ score, and recent cocaine use. Results The VS showed higher activation to large as compared to small or no wins but this reward-related activity did not differ between CDs and HCs. The precentral gyrus (PCG), anterior insula, and supplementary motor area showed higher activation during large vs. no wins in positive correlation with the CCQ score in CDs. Mediation analyses suggested that days of cocaine use in the prior month contributed to higher CCQ scores and, in turn, PCG reward responses. Conclusions The results highlight a unique relationship between reward responses of the primary motor cortex, tonic cocaine craving and recent cocaine use. The motor cortex may partake in the cognitive motor processes critical to drug seeking behavior in addicted individuals.

Der Effekt von Belohnungen auf die intraindividuelle Variabilität der Reaktionszeit bei erwachsenen ADHS-Patienten : eine Analyse anhand des Ex-Gauß’schen Verteilungsmodells

Increased intraindividual variability of reaction time is a main cognitive feature of Attention Deficit Hyperactivity Disorder. It is associated with deficits in sustained attention. While traditionally, mean and variance were used to characterize reaction time distributions, the ex-gaussian distributional model allows a more sophisticated analysis of reaction time series. Reaction time distributions are separated in a normal and an exponential component. The present study investigates the impact of incentives on reaction time variability in a sample of adult ADHD patients. ADHD is associated with increased Tau, the output parameter of the ex-gaussian model characterizing the exponential part of the distribution. Tau is linked to “lapses of attention”, which are more frequent in ADHD patients. It is known that tau can be modulated in ADHD Patients. It was therefore postulated that tau would be higher in ADHD Patients in a paradigm where quick answers were required but could be modulated by monetary incentives. In addition, the effect of “delay discounting”, which is more distinct in ADHD patients, on reaction time variability was investigated. Eventually, the association of variability measures with strength of ADHD symptoms was tested. To this end, reaction time distributions of 62 adult ADHD patients and 45 healthy controls from two different reaction time paradigms were analyzed. The monetary incentive delay task, by comprehending a control – and a win condition, allows an investigation of the effect of incentives on reaction times. Subjects had to react as fast as possible by keypress to a stimulus, after a cue signaled a possible monetary reward. During the Delay-Discounting-Task, subjects had to choose between sooner, but smaller, and higher delayed monetary rewards, during which they could use as much time for consideration as desired. Results show that an increased Tau in the control condition of the monetary- incentive-delay-task could be replicated, while a distinct influence of the win condition emerged. Subjects with ADHD showed an improvement of Tau in the win condition even below the level of healthy controls. However, they showed increased variability of the “regular” responses around the mean of the normal component of the distribution, represented by sigma. Moreover, it was indicated by trend a higher reaction time variability in ADHD patients during choices of delayed rewards. Tau was associated the current symptom strength as well as with the strength of ADHD-Symptoms during childhood, assessed by questionnaire. While the present results could have implications for etiological models of the disease, they may also contribute to the development of novel diagnostic methods. In advanced studies, neural correlates of sophisticated measures of reaction time variability should be investigated. Furthermore, they should be associated with genetic risk factors with regard to possible endophenotypes. Possible implications for clinical handling of patients should be explored.

Latent variables for region of interest activation during the Monetary Incentive Delay Task

Background: The Monetary Incentive Delay Task (MID) has been used extensively to probe anticipatory reward processes. However, individual differences evident during this task may relate to other constructs such as general arousal or valence processing (i.e., anticipation of negative versus positive outcomes). This investigation used a latent variable approach to parse activation patterns during the MID within a transdiagnostic clinical sample.Methods: Participants were drawn from the first 500 individuals recruited for the Tulsa-1000 (T1000), a naturalistic longitudinal study of 1000 participants aged 18-55 (n = 476 with MID data). We employed a multiview latent analysis method, group factor analysis, to characterize factors within and across variable sets consisting of: (1) region of interest (ROI)-based blood oxygenation level-dependent (BOLD) contrasts during reward and loss anticipation; and (2) self-report measures of positive and negative valence and related constructs.Results: Three factors comprised of ROI indicators emerged to accounted for >43% of variance and loaded on variables representing: (1) general arousal or general activation; (2) valence, with dissociable responses to anticipation of win versus loss; and (3) region-specific activation, with dissociable activation in salience versus perceptual brain networks. Two additional factors were comprised of self-report variables, which appeared to represent arousal and valence.Conclusions: Results indicate that multiview techniques to identify latent variables offer a novel approach for differentiating brain activation patterns during task engagement. Such approaches may offer insight into neural processing patterns through dimension reduction, be useful for probing individual differences, and aid in the development of optimal explanatory or predictive frameworks.

The acute effects of cannabidiol on the neural correlates of reward anticipation and feedback in healthy volunteers

Background: Cannabidiol has potential therapeutic benefits for people with psychiatric disorders characterised by reward function impairment. There is existing evidence that cannabidiol may influence some aspects of reward processing. However, it is unknown whether cannabidiol acutely affects brain function underpinning reward anticipation and feedback. Hypotheses: We predicted that cannabidiol would augment brain activity associated with reward anticipation and feedback. Methods: We administered a single 600 mg oral dose of cannabidiol and matched placebo to 23 healthy participants in a double-blind, placebo-controlled, repeated-measures design. We employed the monetary incentive delay task during functional magnetic resonance imaging to assay the neural correlates of reward anticipation and feedback. We conducted whole brain analyses and region-of-interest analyses in pre-specified reward-related brain regions. Results: The monetary incentive delay task elicited expected brain activity during reward anticipation and feedback, including in the insula, caudate, nucleus accumbens, anterior cingulate and orbitofrontal cortex. However, across the whole brain, we did not find any evidence that cannabidiol altered reward-related brain activity. Moreover, our Bayesian analyses showed that activity in our regions-of-interest was similar following cannabidiol and placebo. Additionally, our behavioural measures of motivation for reward did not show a significant difference between cannabidiol and placebo. Discussion: Cannabidiol did not acutely affect the neural correlates of reward anticipation and feedback in healthy participants. Future research should explore the effects of cannabidiol on different components of reward processing, employ different doses and administration regimens, and test its reward-related effects in people with psychiatric disorders.

Men Show Higher Neural Sensitivity to Wins – Large or Small – than Women in the Monetary Incentive Delay Task

Background Men and women show differences in sensitivity to reward and punishment, which may impact behavior in health and disease. However, the neural bases of these sex differences remain under-investigated. Here, by combining functional magnetic resonance imaging (fMRI) and a Monetary Incentive Delay Task (MIDT), we examined sex differences in the neural responses to monetary wins and losses and how these regional activities vary with individual reward and punishment sensitivity. Methods Sixty-three healthy adults (27 women) participated in the fMRI study with a 3-Tesla scanner. Sensitivity to punishment (SP) and sensitivity to reward (SR) were assessed with the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ). In the MIDT, participants pressed a button to collect either $1, 1¢, or nil, with the reaction time window titrated across trials to achieve ~67% success. Imaging data were processed with published routines and evaluated with a corrected threshold. Results The results showed higher SP score in women vs. men and higher SR score in men vs. women. Compared to women, men also showed higher response to the receipt of dollar or cent reward in the medial prefrontal cortex, in the area of the supplementary motor cortex. Regional responses to loss did not show sex differences. Further, in a whole-brain regression, activation of the caudate head during 1¢ loss was correlated positively with SR score in men but not in women, and the sex difference was confirmed by a slope test. Conclusions Together, men showed higher SR and neural sensitivity to the receipt of reward, big or small, than women. Individual differences in SR could be reflected by caudate response to a small loss in men. These findings highlight how men and women may differ in reward-related brain activations in the MIDT and add to the imaging literature of sex differences in cognitive and affective functions.