Chantal Martin-Soelch

Reward mechanisms in the brain and their role in dependence: evidence from neurophysiological and neuroimaging studies

This article reviews neuronal activity related to reward processing in primate and human brains. In the primate brain, neurophysiological methods provide a differentiated view of reward processing in a limited number of brain structures. Dopamine neurons respond to unpredictable rewards and produce a global reinforcement signal. Some neurons in the striatum also react to the expectation and detection of reward. Other striatal neurons show reward-related activities related to the preparation, initiation and execution of movement. Orbitofrontal neurons discriminate among different rewards and code reward preferences. In the human brain, regions belonging to a meso-striatal and meso-corticolimbic loop respond to reinforcement stimuli in control subjects. These observations corroborate results obtained in primates. Additionally, reward induces activation in regions specific to task performance. Our results also show a similar pattern of reward-related activation in nicotine and opiate addicts. Thus, in contrast to healthy subjects, typical reward-related regions respond in addicts to monetary reward but not to nonmonetary reinforcement. Reduced activation in performance-related regions is also observed in both groups of dependent subjects. The results of animal and human studies suggest that dopamine and dopamine-related regions are associated with the integration of motivational information and movement execution. Dopamine-related pathological disorders can be associated with movement disorders, such as Parkinsons disease or with false motivational attributions such as drug dependence.

Appetitive conditioning: neural bases and implications for psychopathology

Appetitive conditioning is the process through which new rewards are learned and acquire their motivational salience. Although it has the same evolutionary survival significance as aversive conditioning, appetitive conditioning has rarely been studied in humans. This gap may be explained by the difficulty to find in humans suitable appetitive stimuli that can elicit physiological responses similar to those elicited by aversive stimuli. To help remedy this gap, we review the literature on conditioning, with emphasis on appetitive conditioning. This review comprises three parts. First, we examine the different forms of conditioning. Second, we review the neural basis of appetitive conditioning, particularly from a functional neuroimaging perspective. And third, we demonstrate how perturbations in processes involved in appetitive conditioning can contribute to implicated psychopathologies and suggest neurobiological models underlying these pathologies. The ultimate goal of this review is to stimulate new avenues of research that have direct links to molecular biology, and thus could prove to be invaluable to progress in the understanding and treatment of psychiatric disabilities.

Changes in reward-induced brain activation in opiate addicts

Many studies indicate a role of the cerebral dopaminergic reward system in addiction. Motivated by these findings, we examined in opiate addicts whether brain regions involved in the reward circuitry also react to human prototypical rewards. We measured regional cerebral blood flow (rCBF) with H215O positron emission tomography (PET) during a visuo‐spatial recognition task with delayed response in control subjects and in opiate addicts participating in a methadone program. Three conditions were defined by the types of feedback: nonsense feedback; nonmonetary reinforcement; or monetary reward, received by the subjects for a correct response. We found in the control subjects rCBF increases in regions associated with the meso‐striatal and meso‐corticolimbic circuits in response to both monetary reward and nonmonetary reinforcement. In opiate addicts, these regions were activated only in response to monetary reward. Furthermore, nonmonetary reinforcement elicited rCBF increases in limbic regions of the opiate addicts that were not activated in the control subjects. Because psychoactive drugs serve as rewards and directly affect regions of the dopaminergic system like the striatum, we conclude that the differences in rCBF increases between controls and addicts can be attributed to an adaptive consequence of the addiction process.

Is depression associated with dysfunction of the central reward system

The neural substrates of MDD (major depressive disorder) are complex and not yet fully understood. In the present review, I provide a short overview of the findings supporting the hypothesis of a dysfunctional dopamine system in the pathophysiology of depression. Because the mesocorticolimbic dopamine system is involved in reward processing, it has been hypothesized that a reduced function of this system could underlie the anhedonia and amotivation associated with depression. This hypothesis is supported by several observations providing indirect evidence for reduced central dopaminergic transmission in depression. However, some of the differences observed between controls and depressed patients in dopamine function seem to be specific to a subsample of patients, and influenced by the methods chosen. Studies that investigated the neural bases of some MDD behavioural symptoms showed that anhedonia, loss of motivation and the diminished ability to concentrate or make decisions could be associated with a blunted reaction to positive reinforcers and rewards on one side, and with a bias towards negative feedback on the other side. Only a few studies have investigated the neural basis of anhedonia and the responses to rewards in MDD subjects, mostly evidencing a blunted response to reward signals that was associated with reduced brain activation in regions associated with the brain reward system. In conclusion, there is evidence for a dysfunction of the dopamine system in depression and for blunted response to reward signals. However, the exact nature of this dysfunction is not yet clear and needs to be investigated in further studies.

Lateralization and gender differences in the dopaminergic response to unpredictable reward in the human ventral striatum

Electrophysiological studies have shown that mesostriatal dopamine (DA) neurons increase activity in response to unpredicted rewards. With respect to other functions of the mesostriatal dopaminergic system, dopamine’s actions show prominent laterality effects. Whether changes in DA transmission elicited by rewards also are lateralized, however, has not been investigated. Using [11C]raclopride‐PET to assess the striatal DA response to unpredictable monetary rewards, we hypothesized that such rewards would induce an asymmetric reduction in [11C]raclopride binding in the ventral striatum, reflecting lateralization of endogenous dopamine release. In 24 healthy volunteers, differences in the regional D2/3 receptor binding potential (ΔBP) between an unpredictable reward condition and a sensorimotor control condition were measured using the bolus‐plus‐constant‐infusion [11C]raclopride method. During the reward condition subjects randomly received monetary awards while performing a ‘slot‐machine’ task. The ΔBP between conditions was assessed in striatal regions‐of‐interest and compared between left and right sides. We found a significant condition × lateralization interaction in the ventral striatum. A significant reduction in binding potential (BPND) in the reward condition vs. the control condition was found only in the right ventral striatum, and the ΔBP was greater in the right than the left ventral striatum. Unexpectedly, these laterality effects appeared to be partly accounted for by gender differences, as our data showed a significant bilateral BPND reduction in women while in men the reduction reached significance only in the right ventral striatum. These data suggest that DA release in response to unpredictable reward is lateralized in the human ventral striatum, particularly in males.

Impact of emotion on cognition in trauma survivors: What is the role of posttraumatic stress disorder?

BACKGROUND Cognitive theories of anxiety disorders postulate an increased attentional bias to environmental cues associated with threat that underlies the exaggerated fear response. The role of trauma, which may represent strong competitive advantage for attention, remains unclear. We investigated the influence of trauma exposure and the presence of anxiety/stress disorders on the impact of emotional distractors on cognitive performance. METHODS Fourteen trauma-exposed subjects with PTSD, 12 trauma-exposed subjects with anxiety disorders other than PTSD, 12 trauma-exposed healthy subjects and 19 non-trauma-exposed healthy controls participated in this study. The impact of emotion on cognition was determined by the Affective Stroop task that measures the effect of irrelevant emotional distractors on the speed of operant responding. RESULTS The speed of cognitive performance was significantly reduced in the presence of negative distractors versus neutral or positive distractors in subjects with PTSD, while there was no significant influence of the distractor type on performance in the other diagnostic groups (diagnosis-by-distractor type interaction, p<0.001). While negative distractors induced the same levels of anxiety and depersonalization in subjects with PTSD and subjects with other anxiety disorders, distractor-induced depersonalization was associated with slowing of cognitive performance in PTSD (p=0.02) but not in other groups. LIMITATIONS Different types of anxiety disorders in the non-PTSD group might reduce the selectivity of the results; some subjects received medication possibly impacting on their cognitive functioning. CONCLUSIONS The cognitive impairments in the presence of negative distractors specifically found in PTSD call for research into novel psychotherapeutic approaches, e.g. attentional training, for PTSD.

The Functional DRD3 Ser9Gly Polymorphism (rs6280) Is Pleiotropic, Affecting Reward as Well as Movement

Abnormalities of motivation and behavior in the context of reward are a fundamental component of addiction and mood disorders. Here we test the effect of a functional missense mutation in the dopamine 3 receptor (DRD3) gene (ser9gly, rs6280) on reward-associated dopamine (DA) release in the striatum. Twenty-six healthy controls (HCs) and 10 unmedicated subjects with major depressive disorder (MDD) completed two positron emission tomography (PET) scans with [11C]raclopride using the bolus plus constant infusion method. On one occasion subjects completed a sensorimotor task (control condition) and on another occasion subjects completed a gambling task (reward condition). A linear regression analysis controlling for age, sex, diagnosis, and self-reported anhedonia indicated that during receipt of unpredictable monetary reward the glycine allele was associated with a greater reduction in D2/3 receptor binding (i.e., increased reward-related DA release) in the middle (anterior) caudate (p<0.01) and the ventral striatum (p<0.05). The possible functional effect of the ser9gly polymorphism on DA release is consistent with previous work demonstrating that the glycine allele yields D3 autoreceptors that have a higher affinity for DA and display more robust intracellular signaling. Preclinical evidence indicates that chronic stress and aversive stimulation induce activation of the DA system, raising the possibility that the glycine allele, by virtue of its facilitatory effect on striatal DA release, increases susceptibility to hyperdopaminergic responses that have previously been associated with stress, addiction, and psychosis.

DRD2/ANKK1 Taq1A polymorphism (rs1800497) has opposing effects on D2/3 receptor binding in healthy controls and patients with major depressive disorder.

The A1 allele of the DRD2/ANKK1 Taq1A polymorphism (rs1800497) is associated with reduced striatal D(2/3) receptor binding in healthy individuals (Con) as well as depression and addiction. However, the effect of rs1800497 on D(2/3) receptor binding in depressed patients as well as the SNPs effect on D(2/3) binding during reward-associated dopamine release is unknown. Twelve unmedicated patients with major depressive disorder (MDD) and 24 Con completed PET scans with [(11)C]raclopride, once without receiving monetary rewards (baseline) and once while winning money. In Con, the A1 allele was associated with reduced baseline binding potential (BP(ND)) in the middle caudate and ventral striatum. However, in MDD patients the A1 allele was associated with increased baseline BP(ND) in these regions. There were no significant associations between rs1800497 and change in BP(ND) during reward-associated dopamine release. Conceivably, the A1 allele predisposes to depression and addiction via its effect on the post-synaptic D(2) receptor.

The validity and reliability of the German version of the Somatoform Dissociation Questionnaire (SDQ-20).

The present study investigated the validity of the German version of the Somatoform Dissociation Questionnaire (SDQ-20), a scale designed to measure somatoform dissociative symptoms. Somatoform dissociation involves physical manifestations of a dissociation of the personality and is considered a unique entity in the phenomenological spectrum of dissociation. The validity and reliability of the German version of the SDQ-20 was examined using a sample of 225 patients with (n = 39) and without dissociative disorders who were recruited from several in- and outpatient psychiatric clinics. Patients were assessed using structured diagnostic interviews; diagnostic checklists; and self-rating scales for dissociation, and posttraumatic stress. Patients with dissociative disorders reported significantly more (p < .001) somatoform dissociative symptoms than patients without dissociative disorders (criterion validity). Significant correlations (p < .001) were found between scores of somatoform dissociation, psychoform dissociation, posttraumatic stress symptoms, and traumatic childhood experiences (construct validity). Reliability was corroborated by a Cronbachs alpha coefficient of .91 and a test–retest correlation of .89. A component factor analysis suggested unidimensionality of the SDQ-20. In conclusion, the psychometric properties and cross-cultural validity of the German version of the SDQ-20 are excellent. Our results form the basis for the further study of somatoform dissociation in German-speaking populations.

Reduced response to reward in smokers and cannabis users.

Background: Cannabis is one of the most commonly used illicit drugs. Reduced neural and behavioral reactions to reward have been demonstrated in other forms of addiction, as expressed by reduced mood reactivity and lack of striatal activation to rewards, but this effect has not yet been investigated in cannabis users. Methods: We hypothesized that cannabis users and tobacco smokers would evidence lower positive mood ratings in rewarded conditions than control participants and that this reduction would be greater in cannabis users than in smokers. We examined the influence of reward on mood and performance in a group of regular cannabis users, a group of tobacco smokers and a group of nonsmokers while they performed a spatial recognition task with delayed response that incorporated 3 levels of difficulty. Correct responses were either not reinforced or reinforced with money. We measured the accuracy of reactions, reaction times and mood ratings throughout the trials. Results: Cannabis users rated their mood as significantly worse than the smokers and nonsmokers during the easiest level of the rewarded condition. A significant positive correlation between mood ratings and monetary reward was found in the nonsmokers but not in the cannabis users and smokers. The groups did not differ with regard to task performance. Conclusions: Our results suggest that regular cannabis use affects certain aspects of motivation and that both tobacco smoking and cannabis use lead to similar motivational changes. However, the use of cannabis seems to affect motivation in a stronger way than does tobacco smoking alone.