Capuchin Monkeys Exercise Self-control by Choosing Token Exchange Over an Immediate Reward

Self-control is a prerequisite for complex cognitive processes such as cooperation and planning. As such, comparative studies of self-control may help elucidate the evolutionary origin of these capacities. A variety of methods have been developed to test for self-control in non-human primates that include some variation of foregoing an immediate reward in order to gain a more favorable reward. We used a token exchange paradigm to test for self-control in capuchin monkeys (Cebus apella). Animals were trained that particular tokens could be exchanged for food items worth different values. To test for self-control, a monkey was provided with a token that was associated with a lower-value food. When the monkey exchanged the token, the experimenter provided the monkey with a choice between the lower-value food item associated with the token or another token that was associated with a higher-value food. If the monkey chose the token, they could then exchange it for the higher-value food. Of seven monkeys trained to exchange tokens, five demonstrated that they attributed value to the tokens by differentially selecting tokens for higher-value foods over tokens for lower-value foods. When provided with a choice between a food item or a token for a higher-value food, two monkeys selected the token significantly more than expected by chance. The ability of capuchin monkeys to forego an immediate food reward and select a token that could then be traded for a more preferred food demonstrated some degree of self-control. Thus, results suggest a token exchange paradigm could be a successful technique for assessing self-control in this New World species.

Dopaminergic modulation of the human reward system: a placebo-controlled dopamine depletion fMRI study

Reward related behaviour is linked to dopaminergic neurotransmission. Our aim was to gain insight into dopaminergic involvement in the human reward system. Combining functional magnetic resonance imaging with dopaminergic depletion by α-methylparatyrosine we measured dopamine-related brain activity in 10 healthy volunteers. In addition to blood-oxygen-level-dependent (BOLD) contrast we assessed the effect of dopaminergic depletion on prolactin response, peripheral markers for dopamine and norepinephrine. In the placebo condition we found increased activation in the left caudate and left cingulate gyrus during anticipation of reward. In the α-methylparatyrosine condition there was no significant brain activation during anticipation of reward or loss. In α-methylparatyrosine, anticipation of reward vs. loss increased activation in the right insula, left frontal, right parietal cortices and right cingulate gyrus. Comparing placebo versus α-methylparatyrosine showed increased activation in the left cingulate gyrus during anticipation of reward and the left medial frontal gyrus during anticipation of loss. α-methylparatyrosine reduced levels of dopamine in urine and homovanillic acid in plasma and increased prolactin. No significant effect of α-methylparatyrosine was found on norepinephrine markers. Our findings implicate distinct patterns of BOLD underlying reward processing following dopamine depletion, suggesting a role of dopaminergic neurotransmission for anticipation of monetary reward.

Dopamine-related deficit in reward learning after catecholamine depletion in unmedicated, remitted subjects with bulimia nervosa

Disturbances in reward processing have been implicated in bulimia nervosa (BN). Abnormalities in processing reward-related stimuli might be linked to dysfunctions of the catecholaminergic neurotransmitter system, but findings have been inconclusive. A powerful way to investigate the relationship between catecholaminergic function and behavior is to examine behavioral changes in response to experimental catecholamine depletion (CD). The purpose of this study was to uncover putative catecholaminergic dysfunction in remitted subjects with BN who performed a reinforcement-learning task after CD. CD was achieved by oral alpha-methyl-para-tyrosine (AMPT) in 19 unmedicated female subjects with remitted BN (rBN) and 28 demographically matched healthy female controls (HC). Sham depletion administered identical capsules containing diphenhydramine. The study design consisted of a randomized, double-blind, placebo-controlled crossover, single-site experimental trial. The main outcome measures were reward learning in a probabilistic reward task analyzed using signal-detection theory. Secondary outcome measures included self-report assessments, including the Eating Disorder Examination-Questionnaire. Relative to healthy controls, rBN subjects were characterized by blunted reward learning in the AMPT-but not in placebo-condition. Highlighting the specificity of these findings, groups did not differ in their ability to perceptually distinguish between stimuli. Increased CD-induced anhedonic (but not eating disorder) symptoms were associated with a reduced response bias toward a more frequently rewarded stimulus. In conclusion, under CD, rBN subjects showed reduced reward learning compared with healthy control subjects. These deficits uncover disturbance of the central reward processing systems in rBN related to altered brain catecholamine levels, which might reflect a trait-like deficit increasing vulnerability to BN.

Assessment of Alcohol Reward in Prairie Voles (Microtus ochrogaster)

The purpose of our study was to assess whether prairie voles find alcohol rewarding. Prairie voles have recently become a species of interest for alcohol studies, which have traditionally used other rodent model species including several different strains of mice and rats. The prairie vole is one of only two known rodent species that readily administers high levels of unsweetened alcohol, implicating it as a potentially effective animal model for studying alcohol abuse. However, voluntary consumption does not necessarily imply that prairie voles find it rewarding. Therefore the purpose of our study was to investigate if alcohol has rewarding properties for prairie voles using three different approaches: place conditioning, flavor conditioning, and immunohistochemistry. Furthermore, we sought to characterize their reward profile and compare it to other commonly used rodent models ¿ C57BL/6 mice, DBA/2J mice, and Sprague-Dawley rats. Place and flavor conditioning are behavioral methods that rely on the learned association between a stimulus and the effects of a drug; the drug of interest in these studies is alcohol. To assess whether prairie voles will demonstrate a conditioned preference for alcohol-paired stimuli, seven place conditioning studies were run that investigated a range of different doses, individual conditioning session durations, and trial durations. Video analysis revealed no difference in the amount of time spent on the alcohol-paired floor, suggesting no conditioned place preference for alcohol. Two flavor conditioning tests were conducted to assess whether voles would demonstrate a preference for an alcohol-paired flavored saccharin solution. Voles demonstrated reduced consumption of the alcohol-paired flavored saccharin solution, regardless of dose or flavor, when alcohol administration occurred after conditioning sessions (p=<0.001). When alcohol was administered before conditioning sessions, no difference in consumption of the alcohol-paired and saline-paired flavored saccharin solutions was seen (p=0.545). Previous studies that have documented similar behavior have hypothesized that this is an example of an anticipatory contrast effect. This theory proposes that prairie voles reduce their intake of a hedonic solution (flavored saccharin solution) in anticipation of later drug administration (alcohol). However, conditioning-based behavioral methods of studying alcohol reward are highly sensitive to the parameters of the conditioned stimulus, thus it is possible that voles will not show preference for alcohol-related stimuli, even if they do find alcohol rewarding. Immunohistochemical analysis supplemented this behavioral data by allowing us to identify specific neural regions that were directly activated in response to the acute administration of alcohol. No difference in the number of activated c-Fos neurons in the Nucleus Accumbens (NAc) core or shell was seen (p=0.3364; p=0.6698) in animals that received an acute injection of alcohol or saline. There was a significant increase in the number of activated c-Fos neurons in the Paraventricular Nucleus of the Hypothalamus (PVN) in alcohol-treated animals compared to saline-treated animals (p=0.0034). There was no difference in the pixel count of activated c-Fos neurons or in the % area activated in the Arcuate Nucleus between alcohol and saline-treated animals (p=0.4523; p=0.3304). In conclusion, the place conditioning studies that were conducted in this thesis suggest that prairie voles do not demonstrate preference or aversion towards alcohol-paired stimuli. The flavor conditioning studies suggest that prairie voles do not demonstrate aversion but rather avoidance of the alcohol-paired flavor in anticipation of future alcohol administration. The preliminary immunohistochemical data collected is inconclusive but cannot rule out the possibility of neuronal activation patterns indicative of reward. Taken together, our data indicate that prairie voles hav

Overcommitment but not effort-reward imbalance relates to stress-induced coagulation changes in teachers

BACKGROUND: Stress-related hypercoagulability might link job stress with atherosclerosis. PURPOSE: This paper aims to study whether overcommitment, effort-reward imbalance, and the overcommitment by effort-reward imbalance interaction relate to an exaggerated procoagulant stress response. METHODS: We assessed job stress in 52 healthy teachers (49 +/- 8 years, 63% women) at study entry and, after a mean follow-up of 21 +/- 4 months, when they underwent an acute psychosocial stressor and had coagulation measures determined in plasma. In order to increase the reliability of job stress measures, entry and follow-up scores of overcommitment and of effort-reward imbalance were added up to total scores. RESULTS: During recovery from stress, elevated overcommitment correlated with D-dimer increase and with smaller fibrinogen decrease. In contrast, overcommitment was not associated with coagulation changes from pre-stress to immediately post-stress. Effort-reward imbalance and the interaction between overcommitment and effort-reward imbalance did not correlate with stress-induced changes in coagulation measures. CONCLUSIONS: Overcommitment predicted acute stress-induced hypercoagulability, particularly during the recovery period.

White matter pathway organization of the reward system is related to positive and negative symptoms in schizophrenia

The reward systemin schizophrenia has been linked to the emergence of delusions on the one hand and to negative symptoms such as affective flattening on the other hand. Previous Diffusion Tensor Imaging (DTI) studies reported white matter microstructure alterations of regions related to the reward system. The present study aimed at extending these findings by specifically investigating connection pathways of the reward system in schizophrenia. Therefore, 24 patients with schizophrenia and 22 healthy controls matched for age and gender underwent DTI-scans. Using a probabilistic fiber tracking approachwe bilaterally extracted pathways connecting the ventral tegmental area (VTA) with the nucleus accumbens (NAcc), themedial and lateral orbitofrontal cortices (mOFC, lOFC), the dorsolateral prefrontal cortex (dlPFC) and the amygdala; as well as pathways connecting NAcc with mOFC, lOFC, dlPFC and amygdala resulting in a total of 18 connections. Probability indices forming part of a bundle of interest (PIBI) were compared between groups using independent t-tests. In 6 connection pathways PIBI-valueswere increased in schizophrenia. In 3 of these pathways the spatial extension of connection pathways was decreased. In schizophrenia patients, there was a negative correlation of PIBI-values and PANSS negative scores in the left VTA–amygdala and in the left NAcc–mOFC connection. A sum score of delusions and hallucinations correlated positively with PIBI-values of the left amygdala–NAcc connection. Structural organization of specific segments ofwhite matter pathways of the reward systemin schizophrenia may contribute to the emergence of delusions and negative symptoms in schizophrenia.

Dopaminergic modulation of the reward system in schizophrenia: A placebo-controlled dopamine depletion fMRI study

Background The brain reward circuitry innervated by dopamine is critically disturbed in schizophrenia. This study aims to investigate the role of dopamine-related brain activity during prediction of monetary reward and loss in first episode schizophrenia patients. Methods We measured blood–oxygen-level dependent (BOLD) activity in 10 patients with schizophrenia (SCH) and 12 healthy controls during dopamine depletion with α-methylparatyrosine (AMPT) and during a placebo condition (PLA). Results AMPT reduced the activation of striatal and cortical brain regions in SCH. In SCH vs. controls reduced activation was found in the AMPT condition in several regions during anticipation of reward and loss, including areas of the striatum and frontal cortex. In SCH vs. controls reduced activation of the superior temporal gyrus and posterior cingulate was observed in PLA during anticipation of rewarding stimuli. PLA patients had reduced activation in the ventral striatum, frontal and cingulate cortex in anticipation of loss. The findings of reduced dopamine-related brain activity during AMPT were verified by reduced levels of dopamine in urine, homovanillic-acid in plasma and increased prolactin levels. Conclusions Our results indicate that dopamine depletion affects functioning of the cortico-striatal reward circuitry in SCH. The findings also suggest that neuronal functions associated with dopamine neurotransmission and attribution of salience to reward predicting stimuli are altered in schizophrenia.

Learning reward timing in cortex through reward dependent expression of synaptic plasticity.

The ability to represent time is an essential component of cognition but its neural basis is unknown. Although extensively studied both behaviorally and electrophysiologically, a general theoretical framework describing the elementary neural mechanisms used by the brain to learn temporal representations is lacking. It is commonly believed that the underlying cellular mechanisms reside in high order cortical regions but recent studies show sustained neural activity in primary sensory cortices that can represent the timing of expected reward. Here, we show that local cortical networks can learn temporal representations through a simple framework predicated on reward dependent expression of synaptic plasticity. We assert that temporal representations are stored in the lateral synaptic connections between neurons and demonstrate that reward-modulated plasticity is sufficient to learn these representations. We implement our model numerically to explain reward-time learning in the primary visual cortex (V1), demonstrate experimental support, and suggest additional experimentally verifiable predictions.

Molecular mechanisms underlying a cellular analog of operant reward learning.

Operant conditioning is a ubiquitous but mechanistically poorly understood form of associative learning in which an animal learns the consequences of its behavior. Using a single-cell analog of operant conditioning in neuron B51 of Aplysia, we examined second-messenger pathways engaged by activity and reward and how they may provide a biochemical association underlying operant learning. Conditioning was blocked by Rp-cAMP, a peptide inhibitor of PKA, a PKC inhibitor, and by expressing a dominant-negative isoform of Ca2+-dependent PKC (apl-I). Thus, both PKA and PKC were necessary for operant conditioning. Injection of cAMP into B51 mimicked the effects of operant conditioning. Activation of PKC also mimicked conditioning but was dependent on both cAMP and PKA, suggesting that PKC acted at some point upstream of PKA activation. Our results demonstrate how these molecules can interact to mediate operant conditioning in an individual neuron important for the expression of the conditioned behavior.

The Role of BDNF, Leptin and Catecholamines in Reward Learning in Bulimia Nervosa

Background: A relationship between bulimia nervosa (BN) and reward-related behavior is supported by several lines of evidence. The dopaminergic dysfunctions in the processing of reward-related stimuli have been shown to be modulated by the neurotrophin brain derived neurotrophic factor (BDNF) and the hormone leptin. Methods: Using a randomized, double-blind, placebo-controlled, crossover design, a reward learning task was applied to study the behavior of 20 female subjects with remitted BN (rBN) and 27 female healthy controls under placebo and catecholamine depletion with alpha-methyl-para-tyrosine (AMPT). The plasma levels of BDNF and leptin were measured twice during the placebo and the AMPT condition, immediately before and 1 h after a standardized breakfast. Results: AMPT-induced differences in plasma BDNF levels were positively correlated with the AMPT-induced differences in reward learning in the whole sample (p = 0.05). Across conditions, plasma BDNF levels were higher in rBN subjects compared to controls (diagnosis effect; p = 0.001). Plasma BDNF and leptin levels were higher in the morning before compared to after a standardized breakfast across groups and conditions (time effect; p < 0.0001). The plasma leptin levels were higher under catecholamine depletion compared to placebo in the whole sample (treatment effect; p = 0.0004). Conclusions: This study reports on preliminary findings that suggest a catecholamine-dependent association of plasma BDNF and reward learning in subjects with rBN and controls. A role of leptin in reward learning is not supported by this study. However, leptin levels were sensitive to a depletion of catecholamine stores in both rBN and controls.

EEG marker of inhibitory brain activity correlates with resting-state cerebral blood flow in the reward system in major depression

Frontal alpha band asymmetry (FAA) is a marker of altered reward processing in major depressive disorder (MDD), associated with reduced approach behavior and withdrawal. However, its association with brain metabolism remains unclear. The aim of this study is to investigate FAA and its correlation with resting – state cerebral blood flow (rCBF). We hypothesized an association of FAA with regional rCBF in brain regions relevant for reward processing and motivated behavior, such as the striatum. We enrolled 20 patients and 19 healthy subjects. FAA scores and rCBF were quantified with the use of EEG and arterial spin labeling. Correlations of the two were evaluated, as well as the association with FAA and psychometric assessments of motivated behavior and anhedonia. Patients showed a left – lateralized pattern of frontal alpha activity and a correlation of FAA lateralization with subscores of Hamilton Depression Rating Scale linked to motivated behavior. An association of rCBF and FAA scores was found in clusters in the dorsolateral prefrontal cortex bilaterally (patients) and in the left medial frontal gyrus, in the right caudate head and in the right inferior parietal lobule (whole group). No correlations were found in healthy controls. Higher inhibitory right – lateralized alpha power was associated with lower rCBF values in prefrontal and striatal regions, predominantly in the right hemisphere, which are involved in the processing of motivated behavior and reward. Inhibitory brain activity in the reward system may contribute to some of the motivational problems observed in MDD.