Neural Correlates of Reward-Based Spatial Learning in Persons with Cocaine Dependence

Dysfunctional learning systems are thought to be central to the pathogenesis of and impair recovery from addictions. The functioning of the brain circuits for episodic memory or learning that support goal-directed behavior has not been studied previously in persons with cocaine dependence (CD). Thirteen abstinent CD and 13 healthy participants underwent MRI scanning while performing a task that requires the use of spatial cues to navigate a virtual-reality environment and find monetary rewards, allowing the functional assessment of the brain systems for spatial learning, a form of episodic memory. Whereas both groups performed similarly on the reward-based spatial learning task, we identified disturbances in brain regions involved in learning and reward in CD participants. In particular, CD was associated with impaired functioning of medial temporal lobe (MTL), a brain region that is crucial for spatial learning (and episodic memory) with concomitant recruitment of striatum (which normally participates in stimulus-response, or habit, learning), and prefrontal cortex. CD was also associated with enhanced sensitivity of the ventral striatum to unexpected rewards but not to expected rewards earned during spatial learning. We provide evidence that spatial learning in CD is characterized by disturbances in functioning of an MTL-based system for episodic memory and a striatum-based system for stimulus-response learning and reward. We have found additional abnormalities in distributed cortical regions. Consistent with findings from animal studies, we provide the first evidence in humans describing the disruptive effects of cocaine on the coordinated functioning of multiple neural systems for learning and memory.     

Neural evidence for an association between social proficiency and sensitivity to social reward

Data from developmental psychology suggests a link between the growth of socio-emotional competences and the infant''s sensitivity to the salience of social stimuli. The aim of the present study was to find evidence for this relationship in healthy adults. Thirty-five participants were recruited based on their score above the 85th or below the 15th percentile of the empathy quotient questionnaire (EQ, Baron-Cohen and Wheelwright, 2004). Functional magnetic resonance imaging (fMRI) was used to compare neural responses to cues of social and non-social (monetary) reward. When compared to the high-EQ group, the low-EQ group showed reduced activity of the brain s reward system, specifically the right nucleus accumbens, in response to cues predictive of social reward (videos showing gestures of approval)—but increased activation in this area for monetary incentives. Our data provide evidence for a link between self-reported deficits in social proficiency and reduced sensitivity to the motivational salience of positive social stimuli.     

Neural correlates of reward and loss sensitivity in psychopathy

Psychopathy is a personality disorder associated with callous and impulsive behavior and criminal recidivism. It has long been theorized that psychopaths have deficits in processing reward and punishment. Here, we use structural and functional magnetic resonance imaging to examine the neural correlates of reward and loss sensitivity in a group of criminal psychopaths. Forty-one adult male prison inmates (n = 18 psychopaths and n = 23 non-psychopaths) completed a functional magnetic resonance imaging task involving the gain or loss of money. Across the entire sample of participants, monetary gains elicited robust activation within the ventral striatum (VS). Although psychopaths and non-psychopaths did not significantly differ with respect to overall levels of VS response to reward vs loss, we observed significantly different correlations between VS responses and psychopathy severity within each group. Volumetric analyses of striatal subregions revealed a similar pattern of correlations, specifically for the right accumbens area within VS. In a separate sample of inmates (n = 93 psychopaths and n = 117 non-psychopaths) who completed a self-report measure of appetitive motivation, we again found that the correlation with psychopathy severity differed between groups. These convergent results offer novel insight into the neural substrates of reward and loss processing in psychopathy.     

Impaired inhibitory control in anorexia nervosa elicited by physical activity stimuli

Besides food restriction, hyperactivity is considered a key behavioral trait of anorexia nervosa (AN), playing a major role in the pathogenesis and progression of the disorder. However, the underlying neurophysiology remains poorly understood. We used functional magnetic resonance imaging during two affective go/no-go tasks to probe inhibitory control in response to stimuli depicting physical activity vs inactivity and food vs non-food in AN patients compared with 26 healthy athlete and non-athlete controls. We hypothesized that neural correlates of behavioral inhibition are biased by the emotional information of the stimuli in AN patients, leading to a differential neural inhibitory pattern during the two tasks. Indeed, we found reduced response inhibition for food and non-food images in the putamen, while stimuli depicting physical activity resulted in an exaggerated response of the prefrontal cortex (PFC) and cerebellum in AN patients. However, both AN patients and athletes revealed an increased response in the somatosensory cortex to physical activity stimuli. These results suggest that physical activity stimuli might place an increased demand on the inhibitory control system in AN patients. The resulting hyperactivity of the PFC and cerebellum may lead to altered executive function and motor control, sustaining increased physical activity in AN patients.     

Reward-related neural responses are dependent on the beneficiary

Prior studies have suggested that positive social interactions are experienced as rewarding. Yet, it is not well understood how social relationships influence neural responses to other persons’ gains. In this study, we investigated neural responses during a gambling task in which healthy participants (N = 31; 18 females) could win or lose money for themselves, their best friend or a disliked other (antagonist). At the moment of receiving outcome, person-related activity was observed in the dorsal medial prefrontal cortex (dmPFC), precuneus and temporal parietal junction (TPJ), showing higher activity for friends and antagonists than for self, and this activity was independent of outcome. The only region showing an interaction between the person-participants played for and outcome was the ventral striatum. Specifically, the striatum was more active following gains than losses for self and friends, whereas for the antagonist this pattern was reversed. Together, these results show that, in a context with social and reward information, social aspects are processed in brain regions associated with social cognition (mPFC, TPJ), and reward aspects are processed in primary reward areas (striatum). Furthermore, there is an interaction of social and reward information in the striatum, such that reward-related activity was dependent on social relationship.     

Job Demands,Job Resources,and Job Performance in Japanese Workers: A Cross-sectional Study

This study investigated the cross-sectional association of job demands (i.e., psychological demands) and job resources (i.e., decision latitude, supervisor support, co-worker support, and extrinsic reward) with job performance. A total of 1,198 workers (458 males and 740 females) from a manufacturing company in Japan completed a self-administered questionnaire that included the Job Content Questionnaire, Effort-Reward Imbalance Questionnaire, World Health Organization Health and Work Performance Questionnaire, and demographic survey. Hierarchical multiple regression analyses were conducted. After adjusting for demographic characteristics, decision latitude (β=0.107, p=0.001) and extrinsic reward (β=0.158, p<0.001) were positively and significantly associated with job performance while supervisor support (β=−0.102, p=0.002) was negatively and significantly associated with job performance. On the other hand, psychological demands or co-worker support was not significantly associated with job performance. These findings suggest that higher decision latitude and extrinsic reward enhance job performance among Japanese employees.     

Differential role of N‐methyl‐D‐aspartate receptor‐mediated glutamate transmission in the nucleus accumbens shell and core in nicotine seeking in rats

Nicotine, a major psychoactive component of tobacco smoke, increases glutamate transmission in the nucleus accumbens (NAcc). However, the role of the N‐methyl‐D‐aspartate (NMDA)‐mediated glutamatergic neurotransmission in the NAcc shell and core subdivisions in nicotine‐dependent behaviors has not been studied. The present study evaluated, in rats, the effects of bilateral administration of the competitive NMDA receptor antagonist LY235959 (0, 0.1, 1, and 10 ng/0.5 μL/side) into the NAcc shell or core on intravenous nicotine (fixed‐ and progressive‐ratio schedules) and food (fixed‐ratio schedule) self‐administration, and cue‐induced reinstatement of nicotine‐seeking behavior. In addition, the effects of LY235959 injections in the NAcc shell were evaluated on nicotine‐induced conditioned taste aversion, a procedure that assesses the aversive effects of nicotine. LY235959 injections into the NAcc shell significantly increased nicotine self‐administration under both fixed‐ and progressive‐ratio schedules, and decreased food self‐administration, but had no effect on nicotine‐induced conditioned taste aversion or cue‐induced nicotine seeking. Furthermore, injections of LY235959 in the lateral septal nucleus, originally intended as an anatomical control site for the NAcc shell, increased nicotine self‐administration and decreased food self‐administration under the fixed‐ratio schedule. In contrast, LY235959 injections into the NAcc core increased the cue‐induced reinstatement of nicotine seeking and decreased food self‐administration, but had no effect on nicotine self‐administration. The present data suggest that NMDA receptor‐mediated glutamatergic neurotransmission in the NAcc shell and core differentially regulates food‐ and nicotine‐maintained responding. Importantly, the data suggest an inhibitory role for NMDA‐mediated glutamatergic neurotransmission in the NAcc shell and core in nicotine self‐administration and the cue‐induced reinstatement of nicotine seeking, respectively.     

Rapid dopamine transmission within the nucleus accumbens: Dramatic difference between morphine and oxycodone delivery

While most drugs of abuse increase dopamine neurotransmission, rapid neurochemical measurements show that different drugs evoke distinct dopamine release patterns within the nucleus accumbens. Rapid changes in dopamine concentration following psychostimulant administration have been well studied; however, such changes have never been examined following opioid delivery. Here, we provide novel measures of rapid dopamine release following intravenous infusion of two opioids, morphine and oxycodone, in drug‐naïve rats using fast‐scan cyclic voltammetry and rapid (1 min) microdialysis coupled with high‐performance liquid chromatography ‐ tandem mass spectrometry (HPLC‐MS). In addition to measuring rapid dopamine transmission, microdialysis HPLC‐MS measures changes in GABA, glutamate, monoamines, monoamine metabolites and several other neurotransmitters. Although both opioids increased dopamine release in the nucleus accumbens, their patterns of drug‐evoked dopamine transmission differed dramatically. Oxycodone evoked a robust and stable increase in dopamine concentration and a robust increase in the frequency and amplitude of phasic dopamine release events. Conversely, morphine evoked a brief (~ 1 min) increase in dopamine that was coincident with a surge in GABA concentration and then both transmitters returned to baseline levels. Thus, by providing rapid measures of neurotransmission, this study reveals previously unknown differences in opioid‐induced neurotransmitter signaling. Investigating these differences may be essential for understanding how these two drugs of abuse could differentially usurp motivational circuitry and powerfully influence behavior.