Investigating the Impact of a Genome-Wide Supported Bipolar Risk Variant of MAD1L1 on the Human Reward System.

PubMed

Trost, Sarah; Diekhof, Esther K; Mohr, Holger; Vieker, Henning; Krämer, Bernd; Wolf, Claudia; Keil, Maria; Dechent, Peter; Binder, Elisabeth B; Gruber, Oliver

2016-10-01

Recent genome-wide association studies have identified MAD1L1 (mitotic arrest deficient-like 1) as a susceptibility gene for bipolar disorder and schizophrenia. The minor allele of the single-nucleotide polymorphism (SNP) rs11764590 in MAD1L1 was associated with bipolar disorder. Both diseases, bipolar disorder and schizophrenia, are linked to functional alterations in the reward system. We aimed at investigating possible effects of the MAD1L1 rs11764590 risk allele on reward systems functioning in healthy adults. A large homogenous sample of 224 young (aged 18-31 years) participants was genotyped and underwent functional magnetic resonance imaging (fMRI). All participants performed the 'Desire-Reason Dilemma' paradigm investigating the neural correlates that underlie reward processing and active reward dismissal in favor of a long-term goal. We found significant hypoactivations of the ventral tegmental area (VTA), the bilateral striatum and bilateral frontal and parietal cortices in response to conditioned reward stimuli in the risk allele carriers compared with major allele carriers. In the dilemma situation, functional connectivity between prefrontal brain regions and the ventral striatum was significantly diminished in the risk allele carriers. Healthy risk allele carriers showed a significant deficit of their bottom-up response to conditioned reward stimuli in the bilateral VTA and striatum. Furthermore, functional connectivity between the ventral striatum and prefrontal areas exerting top-down control on the mesolimbic reward system was reduced in this group. Similar alterations in reward processing and disturbances of prefrontal control mechanisms on mesolimbic brain circuits have also been reported in bipolar disorder and schizophrenia. Together, these findings suggest the existence of an intermediate phenotype associated with MAD1L1.

Activation of VTA GABA neurons disrupts reward consumption

PubMed Central

van Zessen, Ruud; Phillips, Jana L.; Budygin, Evgeny A.; Stuber, Garret D.

2012-01-01

The activity of Ventral Tegmental Area (VTA) dopamine (DA) neurons promotes behavioral responses to rewards and environmental stimuli that predict them. VTA GABA inputs synapse directly onto DA neurons and may regulate DA neuronal activity to alter reward-related behaviors, however, the functional consequences of selective activation of VTA GABA neurons remains unknown. Here, we show that in vivo optogenetic activation of VTA GABA neurons disrupts reward consummatory behavior, but not conditioned anticipatory behavior in response to reward-predictive cues. In addition, direct activation of VTA GABA projections to the nucleus accumbens (NAc) resulted in detectable GABA release, but did not alter reward consumption. Furthermore, optogenetic stimulation of VTA GABA neurons directly suppressed the activity and excitability of neighboring DA neurons, as well as the release of DA in the NAc, suggesting that the dynamic interplay between VTA DA and GABA neurons can control the initiation and termination of reward-related behaviors. PMID:22445345

Altered resting-state functional connectivity of the frontal-striatal reward system in social anxiety disorder.

PubMed

Manning, Joshua; Reynolds, Gretchen; Saygin, Zeynep M; Hofmann, Stefan G; Pollack, Mark; Gabrieli, John D E; Whitfield-Gabrieli, Susan

2015-01-01

We investigated differences in the intrinsic functional brain organization (functional connectivity) of the human reward system between healthy control participants and patients with social anxiety disorder. Functional connectivity was measured in the resting-state via functional magnetic resonance imaging (fMRI). 53 patients with social anxiety disorder and 33 healthy control participants underwent a 6-minute resting-state fMRI scan. Functional connectivity of the reward system was analyzed by calculating whole-brain temporal correlations with a bilateral nucleus accumbens seed and a ventromedial prefrontal cortex seed. Patients with social anxiety disorder, relative to the control group, had (1) decreased functional connectivity between the nucleus accumbens seed and other regions associated with reward, including ventromedial prefrontal cortex; (2) decreased functional connectivity between the ventromedial prefrontal cortex seed and lateral prefrontal regions, including the anterior and dorsolateral prefrontal cortices; and (3) increased functional connectivity between both the nucleus accumbens seed and the ventromedial prefrontal cortex seed with more posterior brain regions, including anterior cingulate cortex. Social anxiety disorder appears to be associated with widespread differences in the functional connectivity of the reward system, including markedly decreased functional connectivity between reward regions and between reward regions and lateral prefrontal cortices, and markedly increased functional connectivity between reward regions and posterior brain regions.

Independent functional connectivity networks underpin food and monetary reward sensitivity in excess weight.

PubMed

Verdejo-Román, Juan; Fornito, Alex; Soriano-Mas, Carles; Vilar-López, Raquel; Verdejo-García, Antonio

2017-02-01

Overvaluation of palatable food is a primary driver of obesity, and is associated with brain regions of the reward system. However, it remains unclear if this network is specialized in food reward, or generally involved in reward processing. We used functional magnetic resonance imaging (fMRI) to characterize functional connectivity during processing of food and monetary rewards. Thirty-nine adults with excess weight and 37 adults with normal weight performed the Willingness to Pay for Food task and the Monetary Incentive Delay task in the fMRI scanner. A data-driven graph approach was applied to compare whole-brain, task-related functional connectivity between groups. Excess weight was associated with decreased functional connectivity during the processing of food rewards in a network involving primarily frontal and striatal areas, and increased functional connectivity during the processing of monetary rewards in a network involving principally frontal and parietal areas. These two networks were topologically and anatomically distinct, and were independently associated with BMI. The processing of food and monetary rewards involve segregated neural networks, and both are altered in individuals with excess weight. Copyright © 2016 Elsevier Inc. All rights reserved.

Heterogeneity of reward mechanisms.

PubMed

Lajtha, A; Sershen, H

2010-06-01

The finding that many drugs that have abuse potential and other natural stimuli such as food or sexual activity cause similar chemical changes in the brain, an increase in extracellular dopamine (DA) in the shell of the nucleus accumbens (NAccS), indicated some time ago that the reward mechanism is at least very similar for all stimuli and that the mechanism is relatively simple. The presently available information shows that the mechanisms involved are more complex and have multiple elements. Multiple brain regions, multiple receptors, multiple distinct neurons, multiple transmitters, multiple transporters, circuits, peptides, proteins, metabolism of transmitters, and phosphorylation, all participate in reward mechanisms. The system is variable, is changed during development, is sex-dependent, and is influenced by genetic differences. Not all of the elements participate in the reward of all stimuli. Different set of mechanisms are involved in the reward of different drugs of abuse, yet different mechanisms in the reward of natural stimuli such as food or sexual activity; thus there are different systems that distinguish different stimuli. Separate functions of the reward system such as anticipation, evaluation, consummation and identification; all contain function-specific elements. The level of the stimulus also influences the participation of the elements of the reward system, there are possible reactions to even below threshold stimuli, and excessive stimuli can change reward to aversion involving parts of the system. Learning and memory of past reward is an important integral element of reward and addictive behavior. Many of the reward elements are altered by repeated or chronic stimuli, and chronic exposure to one drug is likely to alter the response to another stimulus. To evaluate and identify the reward stimulus thus requires heterogeneity of the reward components in the brain.

Pain and suicidality: Insights from reward and addiction neuroscience

PubMed Central

Elman, Igor; Borsook, David; Volkow, Nora D.

2016-01-01

Suicidality is exceedingly prevalent in pain patients. Although the pathophysiology of this link remains unclear, it may be potentially related to the partial congruence of physical and emotional pain systems. The latter system’s role in suicide is also conspicuous during setbacks and losses sustained in the context of social attachments. Here we propose a model based on the neural pathways mediating reward and anti-reward (i.e., allostatic adjustment to recurrent activation of the reward circuitry); both are relevant etiologic factors in pain, suicide and social attachments. A comprehensive literature search on neurobiology of pain and suicidality was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) physical and emotional pain, (2) emotional pain and social attachments, (3) pain-and suicide-related alterations of the reward and anti-reward circuits as compared to addiction, which is the premier probe for dysfunction of these circuits and (4) mechanistically informed treatments of co-occurring pain and suicidality. Pain-, stress- and analgesic drugs-induced opponent and proponent states of the mesolimbic dopaminergic pathways may render reward and anti-reward systems vulnerable to sensitization, cross-sensitization and aberrant learning of contents and contexts associated with suicidal acts and behaviors. These findings suggest that pain patients exhibit alterations in the brain circuits mediating reward (depressed function) and anti-reward (sensitized function) that may affect their proclivity for suicide and support pain and suicidality classification among other “reward deficiency syndromes” and a new proposal for “enhanced anti-reward syndromes”. We suggest that interventions aimed at restoring the balance between the reward and anti-reward networks in patients with chronic pain may help decreasing their suicide risk. PMID:23827972

Pain and suicidality: insights from reward and addiction neuroscience.

PubMed

Elman, Igor; Borsook, David; Volkow, Nora D

2013-10-01

Suicidality is exceedingly prevalent in pain patients. Although the pathophysiology of this link remains unclear, it may be potentially related to the partial congruence of physical and emotional pain systems. The latter system's role in suicide is also conspicuous during setbacks and losses sustained in the context of social attachments. Here we propose a model based on the neural pathways mediating reward and anti-reward (i.e., allostatic adjustment to recurrent activation of the reward circuitry); both are relevant etiologic factors in pain, suicide and social attachments. A comprehensive literature search on neurobiology of pain and suicidality was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) physical and emotional pain, (2) emotional pain and social attachments, (3) pain- and suicide-related alterations of the reward and anti-reward circuits as compared to addiction, which is the premier probe for dysfunction of these circuits and (4) mechanistically informed treatments of co-occurring pain and suicidality. Pain-, stress- and analgesic drugs-induced opponent and proponent states of the mesolimbic dopaminergic pathways may render reward and anti-reward systems vulnerable to sensitization, cross-sensitization and aberrant learning of contents and contexts associated with suicidal acts and behaviors. These findings suggest that pain patients exhibit alterations in the brain circuits mediating reward (depressed function) and anti-reward (sensitized function) that may affect their proclivity for suicide and support pain and suicidality classification among other "reward deficiency syndromes" and a new proposal for "enhanced anti-reward syndromes". We suggest that interventions aimed at restoring the balance between the reward and anti-reward networks in patients with chronic pain may help decreasing their suicide risk. Published by Elsevier Ltd.

Functional disconnection of the orbitofrontal cortex and basolateral amygdala impairs acquisition of a rat gambling task and disrupts animals' ability to alter decision-making behavior after reinforcer devaluation.

PubMed

Zeeb, Fiona D; Winstanley, Catharine A

2013-04-10

An inability to adjust choice preferences in response to changes in reward value may underlie key symptoms of many psychiatric disorders, including chemical and behavioral addictions. We developed the rat gambling task (rGT) to investigate the neurobiology underlying complex decision-making processes. As in the Iowa Gambling task, the optimal strategy is to avoid choosing larger, riskier rewards and to instead favor options associated with smaller rewards but less loss and, ultimately, greater long-term gain. Given the demonstrated importance of the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) in acquisition of the rGT and Iowa Gambling task, we used a contralateral disconnection lesion procedure to assess whether functional connectivity between these regions is necessary for optimal decision-making. Disrupting the OFC-BLA pathway retarded acquisition of the rGT. Devaluing the reinforcer by inducing sensory-specific satiety altered decision-making in control groups. In contrast, disconnected rats did not update their choice preference following reward devaluation, either when the devalued reward was still delivered or when animals needed to rely on stored representations of reward value (i.e., during extinction). However, all rats exhibited decreased premature responding and slower response latencies after satiety manipulations. Hence, disconnecting the OFC and BLA did not affect general behavioral changes caused by reduced motivation, but instead prevented alterations in the value of a specific reward from contributing appropriately to cost-benefit decision-making. These results highlight the role of the OFC-BLA pathway in the decision-making process and suggest that communication between these areas is vital for the appropriate assessment of reward value to influence choice.

fMRI of alterations in reward selection, anticipation, and feedback in major depressive disorder.

PubMed

Smoski, Moria J; Felder, Jennifer; Bizzell, Joshua; Green, Steven R; Ernst, Monique; Lynch, Thomas R; Dichter, Gabriel S

2009-11-01

The purpose of the present investigation was to evaluate reward processing in unipolar major depressive disorder (MDD). Specifically, we investigated whether adults with MDD demonstrated hyporesponsivity in striatal brain regions and/or hyperresponsivity in cortical brain regions involved in conflict monitoring using a Wheel of Fortune task designed to probe responses during reward selection, reward anticipation, and reward feedback. Functional magnetic resonance imaging (fMRI) data indicated that the MDD group was characterized by reduced activation of striatal reward regions during reward selection, reward anticipation, and reward feedback, supporting previous data indicating hyporesponsivity of reward systems in MDD. Support was not found for hyperresponsivity of cognitive control regions during reward selection or reward anticipation. Instead, MDD participants showed hyperresponsivity in orbitofrontal cortex, a region associated with assessment of risk and reward, during reward selection, as well as decreased activation of the middle frontal gyrus and the rostral cingulate gyrus during reward selection and anticipation. Finally, depression severity was predicted by activation in bilateral midfrontal gyrus during reward selection. Results indicate that MDD is characterized by striatal hyporesponsivity, and that future studies of MDD treatments that seek to improve responses to rewarding stimuli should assess striatal functioning.

Altered brain response to reward and punishment in adolescents with Anorexia Nervosa

PubMed Central

Bischoff-Grethe, Amanda; McCurdy, Danyale; Grenesko-Stevens, Emily; (Zoe) Irvine, Laura E.; Wagner, Angela; Yau, Wai-Ying Wendy; Fennema-Notestine, Christine; Wierenga, Christina E.; Fudge, Julie L.; Delgado, Mauricio R.; Kaye, Walter H.

2013-01-01

Adults recovered from anorexia nervosa (AN) have altered reward modulation within striatal limbic regions associated with the emotional significance of stimuli, and executive regions concerned with planning and consequences. We hypothesized that adolescents with AN would show similar disturbed reward modulation within the striatum and the anterior cingulate cortex, a region connected to the striatum and involved in reward-guided action selection. Using functional magnetic resonance imaging, twenty-two adolescent females (10 restricting-type AN, 12 healthy volunteers) performed a monetary guessing task. Time series data associated with monetary wins and losses within striatal and cingulate regions of interest were subjected to a linear mixed effects analysis. All participants responded more strongly to wins versus losses in limbic and anterior executive striatal territories. However, AN participants exhibited an exaggerated response to losses compared to wins in posterior executive and sensorimotor striatal regions, suggesting altered function in circuitry responsible for coding the affective context of stimuli and action selection based upon these valuations. As AN individuals are particularly sensitive to criticism, failure, and making mistakes, these findings may reflect the neural processes responsible for a bias in those with AN to exaggerate negative consequences. PMID:24148909

Altered brain response to reward and punishment in adolescents with Anorexia nervosa.

PubMed

Bischoff-Grethe, Amanda; McCurdy, Danyale; Grenesko-Stevens, Emily; Irvine, Laura E Zoe; Wagner, Angela; Yau, Wai-Ying Wendy; Fennema-Notestine, Christine; Wierenga, Christina E; Fudge, Julie L; Delgado, Mauricio R; Kaye, Walter H

2013-12-30

Adults recovered from Anorexia nervosa (AN) have altered reward modulation within striatal limbic regions associated with the emotional significance of stimuli, and executive regions concerned with planning and consequences. We hypothesized that adolescents with AN would show similar disturbed reward modulation within the striatum and the anterior cingulate cortex, a region connected to the striatum and involved in reward-guided action selection. Using functional magnetic resonance imaging, twenty-two adolescent females (10 restricting-type AN, 12 healthy volunteers) performed a monetary guessing task. Time series data associated with monetary wins and losses within striatal and cingulate regions of interest were subjected to a linear mixed effects analysis. All participants responded more strongly to wins versus losses in limbic and anterior executive striatal territories. However, AN participants exhibited an exaggerated response to losses compared to wins in posterior executive and sensorimotor striatal regions, suggesting altered function in circuitry responsible for coding the affective context of stimuli and action selection based upon these valuations. As AN individuals are particularly sensitive to criticism, failure, and making mistakes, these findings may reflect the neural processes responsible for a bias in those with AN to exaggerate negative consequences. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Dopamine Depletion Reduces Food-Related Reward Activity Independent of BMI

PubMed Central

Frank, Sabine; Veit, Ralf; Sauer, Helene; Enck, Paul; Friederich, Hans-Christoph; Unholzer, Theresa; Bauer, Ute-Maria; Linder, Katarzyna; Heni, Martin; Fritsche, Andreas; Preissl, Hubert

2016-01-01

Reward sensitivity and possible alterations in the dopaminergic-reward system are associated with obesity. We therefore aimed to investigate the influence of dopamine depletion on food-reward processing. We investigated 34 female subjects in a randomized placebo-controlled, within-subject design (body mass index (BMI)=27.0 kg/m2 ±4.79 SD; age=28 years ±4.97 SD) using an acute phenylalanine/tyrosine depletion drink representing dopamine depletion and a balanced amino acid drink as the control condition. Brain activity was measured with functional magnetic resonance imaging during a ‘wanting' and ‘liking' rating of food items. Eating behavior-related traits and states were assessed on the basis of questionnaires. Dopamine depletion resulted in reduced activation in the striatum and higher activation in the superior frontal gyrus independent of BMI. Brain activity during the wanting task activated a more distributed network than during the liking task. This network included gustatory, memory, visual, reward, and frontal regions. An interaction effect of dopamine depletion and the wanting/liking task was observed in the hippocampus. The interaction with the covariate BMI was significant in motor and control regions but not in the striatum. Our results support the notion of altered brain activity in the reward and prefrontal network with blunted dopaminergic action during food-reward processing. This effect is, however, independent of BMI, which contradicts the reward-deficiency hypothesis. This hints to the hypothesis suggesting a different or more complex mechanism underlying the dopaminergic reward function in obesity. PMID:26450814

Cocaine affects foraging behaviour and biogenic amine modulated behavioural reflexes in honey bees.

PubMed

Søvik, Eirik; Even, Naïla; Radford, Catherine W; Barron, Andrew B

2014-01-01

In humans and other mammals, drugs of abuse alter the function of biogenic amine pathways in the brain leading to the subjective experience of reward and euphoria. Biogenic amine pathways are involved in reward processing across diverse animal phyla, however whether cocaine acts on these neurochemical pathways to cause similar rewarding behavioural effects in animal phyla other than mammals is unclear. Previously, it has been shown that bees are more likely to dance (a signal of perceived reward) when returning from a sucrose feeder after cocaine treatment. Here we examined more broadly whether cocaine altered reward-related behaviour, and biogenic amine modulated behavioural responses in bees. Bees developed a preference for locations at which they received cocaine, and when foraging at low quality sucrose feeders increase their foraging rate in response to cocaine treatment. Cocaine also increased reflexive proboscis extension to sucrose, and sting extension to electric shock. Both of these simple reflexes are modulated by biogenic amines. This shows that systemic cocaine treatment alters behavioural responses that are modulated by biogenic amines in insects. Since insect reward responses involve both octopamine and dopamine signalling, we conclude that cocaine treatment altered diverse reward-related aspects of behaviour in bees. We discuss the implications of these results for understanding the ecology of cocaine as a plant defence compound. Our findings further validate the honey bee as a model system for understanding the behavioural impacts of cocaine, and potentially other drugs of abuse.

Altered neural processing of reward and punishment in adolescents with Major Depressive Disorder.

PubMed

Landes, I; Bakos, S; Kohls, G; Bartling, J; Schulte-Körne, G; Greimel, E

2018-05-01

Altered reward and punishment function has been suggested as an important vulnerability factor for the development of Major Depressive Disorder (MDD). Prior ERP studies found evidence for neurophysiological dysfunctions in reinforcement processes in adults with MDD. To date, only few ERP studies have examined the neural underpinnings of reinforcement processing in adolescents diagnosed with MDD. The present event-related potential (ERP) study aimed to investigate neurophysiological mechanisms of anticipation and consumption of reward and punishment in adolescents with MDD in one comprehensive paradigm. During ERP recording, 25 adolescents with MDD and 29 healthy controls (12-17 years) completed a Monetary Incentive Delay Task comprising both a monetary reward and a monetary punishment condition. During anticipation, the cue-P3 signaling attentional allocation was recorded. During consumption, the feedback-P3 and Reward Positivity (RewP) were recorded to capture attentional allocation and outcome evaluation, respectively. Compared to controls, adolescents with MDD showed prolonged cue-P3 latencies to reward cues. Furthermore, unlike controls, adolescents with MDD displayed shorter feedback-P3 latencies in the reward versus punishment condition. RewPs did not differ between groups. It remains unanswered whether the observed alterations in adolescent MDD represent a state or trait. Delayed neural processing of reward cues corresponds to the clinical presentation of adolescent MDD with reduced motivational tendencies to obtain rewards. Relatively shorter feedback-P3 latencies in the reward versus punishment condition could indicate a high salience of performance-contingent reward. Frequent exposure of negatively biased adolescents with MDD to performance-contingent rewards might constitute a promising intervention approach. Copyright © 2018 Elsevier B.V. All rights reserved.

Dopamine homeostasis: brain functional connectivity in reward deficiency syndrome.

PubMed

Febo, Marcelo; Blum, Kenneth; Badgaiyan, Rajendra D; Baron, David; Thanos, Panayotis K; Colon-Perez, Luis M; Demortrovics, Zsolt; Gold, Mark S

2017-01-01

Reward deficiency syndrome (RDS) was first proposed by Kenneth Blum in 1995 to provide a clinically relevant and predictive term for conditions involving deficits in mesocorticolimbic dopamine function. Genetic, molecular, and neuronal alterations in key components of this circuitry contribute to a reward deficit state that can drive drug-seeking, consumption, and relapse. Among the dysfunctions observed in RDS are dysregulated resting state networks, which recently have been assessed in detail in chronic drug users by, positron emission tomography, functional magnetic resonance imaging, and functional connectivity analysis. A growing number of studies are helping to determine the putative roles of dopamine and glutamatergic neurotransmission in the regulation of activity in resting state networks, particularly in brain reward circuitry affected in drug use disorders. Indeed, we hypothesize in the present review that loss of homeostasis of these systems may lead to 'unbalanced' functional networks that might be both cause and outcome of disrupted synaptic communication between cortical and subcortical systems essential for controlling reward, emotional control, sensation seeking, and chronic drug use.

Circadian misalignment, reward-related brain function, and adolescent alcohol involvement.

PubMed

Hasler, Brant P; Clark, Duncan B

2013-04-01

Developmental changes in sleep and circadian rhythms that occur during adolescence may contribute to reward-related brain dysfunction, and consequently increase the risk of alcohol use disorders (AUDs). This review (i) describes marked changes in circadian rhythms, reward-related behavior and brain function, and alcohol involvement that occur during adolescence, (ii) offers evidence that these parallel developmental changes are associated, and (iii) posits a conceptual model by which misalignment between sleep-wake timing and endogenous circadian timing may increase the risk of adolescent AUDs by altering reward-related brain function. The timing of sleep shifts later throughout adolescence, in part due to developmental changes in endogenous circadian rhythms, which tend to become more delayed. This tendency for delayed sleep and circadian rhythms is at odds with early school start times during secondary education, leading to misalignment between many adolescents' sleep-wake schedules and their internal circadian timing. Circadian misalignment is associated with increased alcohol use and other risk-taking behaviors, as well as sleep loss and sleep disturbance. Growing evidence indicates that circadian rhythms modulate the reward system, suggesting that circadian misalignment may impact adolescent alcohol involvement by altering reward-related brain function. Neurocognitive function is also subject to sleep and circadian influence, and thus circadian misalignment may also impair inhibitory control and other cognitive processes relevant to alcohol use. Specifically, circadian misalignment may further exacerbate the cortical-subcortical imbalance within the reward circuit, an imbalance thought to explain increased risk-taking and sensation-seeking during adolescence. Adolescent alcohol use is highly contextualized, however, and thus studies testing this model will also need to consider factors that may influence both circadian misalignment and alcohol use. This review highlights growing evidence supporting a path by which circadian misalignment may disrupt reward mechanisms, which may in turn accelerate the transition from alcohol use to AUDs in vulnerable adolescents. Copyright © 2013 by the Research Society on Alcoholism.

Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z

PubMed Central

Badgaiyan, Rajendra D.; Thanos, Panayotis K.; Kulkarni, Praveen; Giordano, John; Baron, David; Gold, Mark S.

2017-01-01

Dopaminergic reward dysfunction in addictive behaviors is well supported in the literature. There is evidence that alterations in synchronous neural activity between brain regions subserving reward and various cognitive functions may significantly contribute to substance-related disorders. This study presents the first evidence showing that a pro-dopaminergic nutraceutical (KB220Z) significantly enhances, above placebo, functional connectivity between reward and cognitive brain areas in the rat. These include the nucleus accumbens, anterior cingulate gyrus, anterior thalamic nuclei, hippocampus, prelimbic and infralimbic loci. Significant functional connectivity, increased brain connectivity volume recruitment (potentially neuroplasticity), and dopaminergic functionality were found across the brain reward circuitry. Increases in functional connectivity were specific to these regions and were not broadly distributed across the brain. While these initial findings have been observed in drug naïve rodents, this robust, yet selective response implies clinical relevance for addicted individuals at risk for relapse, who show reductions in functional connectivity after protracted withdrawal. Future studies will evaluate KB220Z in animal models of addiction. PMID:28445527

Altered neural reward and loss processing and prediction error signalling in depression

PubMed Central

Ubl, Bettina; Kuehner, Christine; Kirsch, Peter; Ruttorf, Michaela

2015-01-01

Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression. PMID:25567763

Altered neural correlates of reward and loss processing during simulated slot-machine fMRI in pathological gambling and cocaine dependence☆

PubMed Central

Worhunsky, Patrick D.; Malison, Robert T.; Rogers, Robert D.; Potenza, Marc N.

2014-01-01

Background Individuals with gambling or substance-use disorders exhibit similar functional alterations in reward circuitry suggestive of a shared underlying vulnerability in addictive disorders. Additional research into common and unique alterations in reward-processing in substance-related and non-substance-related addictions may identify neural factors that could be targeted in treatment development for these disorders. Methods To investigate contextual reward-processing in pathological gambling, a slot-machine fMRI task was performed by three groups (with pathological gambling, cocaine dependence and neither disorder; N=24 each) to determine the extent to which two groups with addictions (non-substance-related and substance-related) showed similarities and differences with respect to each other and a non-addicted group during anticipatory periods and following the delivery of winning, losing and ‘near-miss’ outcomes. Results Individuals with pathological gambling or cocaine dependence compared to those with neither disorder exhibited exaggerated anticipatory activity in mesolimbic and ventrocortical regions, with pathological-gambling participants displaying greater positive possible-reward anticipation and cocaine-dependent participants displaying more negative certain-loss anticipation. Neither clinical sample exhibited medial frontal or striatal responses that were observed following near-miss outcomes in healthy comparison participants. Conclusions Alterations in anticipatory processing may be sensitive to the valence of rewards and content-disorder-specific. Common and unique findings in pathological gambling and cocaine dependence with respect to anticipatory reward and near-miss loss processing suggest shared and unique elements that might be targeted through behavioral or pharmacological interventions in the treatment of addictions. PMID:25448081

Altered neural reward representations in pathological gamblers revealed by delay and probability discounting.

PubMed

Miedl, Stephan F; Peters, Jan; Büchel, Christian

2012-02-01

The neural basis of excessive delay discounting and reduced risk sensitivity of pathological gamblers with a particular focus on subjective neural reward representations has not been previously examined. To examine how pathological gamblers represent subjective reward value at a neural level and how this is affected by gambling severity. Model-based functional magnetic resonance imaging study with patients and control subjects. Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf. Participants were recruited from the local community by advertisement and through self-help groups. A sample of 16 pathological gamblers (according to the DSM-IV definition) was matched by age, sex, smoking status, income, educational level, and handedness to 16 healthy controls. Pathological gamblers showed increased discounting of delayed rewards and a trend toward decreased discounting of probabilistic rewards compared with matched controls. At the neural level, a significant group × condition interaction indicated that reward representations in the gamblers were modulated in a condition-specific manner, such that they exhibited increased (delay discounting) and decreased (probability discounting) neural value correlations in the reward system. In addition, throughout the reward system, neuronal value signals for delayed rewards were negatively correlated with gambling severity. The results extend previous reports of a generally hypoactive reward system in pathological gamblers by showing that, even when subjective reward valuation is accounted for, gamblers still show altered reward representations. Furthermore, results point toward a gradual degradation of mesolimbic reward representations for delayed rewards during the course of pathological gambling.

Chronic stress impairs spatial memory and motivation for reward without disrupting motor ability and motivation to explore.

PubMed

Kleen, Jonathan K; Sitomer, Matthew T; Killeen, Peter R; Conrad, Cheryl D

2006-08-01

This study uses an operant, behavioral model to assess the daily changes in the decay rate of short-term memory, motivation, and motor ability in rats exposed to chronic restraint. Restraint decreased reward-related motivation by 50% without altering memory decay rate or motor ability. Moreover, chronic restraint impaired hippocampal-dependent spatial memory on the Y maze (4-hr delay) and produced CA3 dendritic retraction without altering hippocampal-independent maze navigation (1-min delay) or locomotion. Thus, mechanisms underlying motivation for food reward differ from those underlying Y maze exploration, and neurobiological substrates of spatial memory, such as the hippocampus, differ from those that underlie short-term memory. Chronic restraint produces functional, neuromorphological, and physiological alterations that parallel symptoms of depression in humans. Copyright 2006 APA, all rights reserved.

Reward-related decision making in eating and weight disorders: A systematic review and meta-analysis of the evidence from neuropsychological studies.

PubMed

Wu, Mudan; Brockmeyer, Timo; Hartmann, Mechthild; Skunde, Mandy; Herzog, Wolfgang; Friederich, Hans-Christoph

2016-02-01

Eating disorders (EDs) and overweight/obesity (OW/OB) are serious public health concerns that share common neuropsychological features and patterns of disturbed eating. Reward-related decision making as a basic neurocognitive function may trans-diagnostically underlie both pathological overeating and restricted eating. The present meta-analysis synthesizes the evidence from N=82 neuropsychological studies for altered reward-related decision making in all ED subtypes, OW and OB. The overall effect sizes for the differences between currently-ill ED patients and OW/OB people and controls were Hedge's g=-0.49 [CI: -0.63; -0.35], and Hedge's g=-0.39 [CI: -0.53; -0.25], respectively. Decision making was found to be altered to similar degrees in all ED subtypes and OB. Effect sizes, however, diverged for the different measures of decision making. Adolescents appear to be less affected than adults. When foods were used as rewarding stimuli, decision making was found to be intact in OB. The findings support that altered general reward-related decision making is a salient neuropsychological factor across eating and weight disorders in adulthood. Copyright © 2015 Elsevier Ltd. All rights reserved.

The rat's not for turning: Dissociating the psychological components of cognitive inflexibility☆

PubMed Central

Nilsson, Simon R.O.; Alsiö, Johan; Somerville, Elizabeth M.; Clifton, Peter G.

2015-01-01

Executive function is commonly assessed by assays of cognitive flexibility such as reversal learning and attentional set-shifting. Disrupted performance in these assays, apparent in many neuropsychiatric disorders, is frequently interpreted as inability to overcome prior associations with reward. However, non-rewarded or irrelevant associations may be of considerable importance in both discrimination learning and cognitive flexibility. Non-rewarded associations can have greater influence on choice behaviour than rewarded associations in discrimination learning. Pathology-related deficits in cognitive flexibility can produce selective disruptions to both the processing of irrelevant associations and associations with reward. Genetic and pharmacological animal models demonstrate that modulation of reversal learning may result from alterations in either rewarded or non-rewarded associations. Successful performance in assays of cognitive flexibility can therefore depend on a combination of rewarded, non-rewarded, and irrelevant associations derived from previous learning, accounting for some inconsistencies observed in the literature. Taking this combination into account may increase the validity of animal models and may also reveal pathology-specific differences in problem solving and executive function. PMID:26112128

Post-learning hippocampal dynamics promote preferential retention of rewarding events

PubMed Central

Gruber, Matthias J.; Ritchey, Maureen; Wang, Shao-Fang; Doss, Manoj K.; Ranganath, Charan

2016-01-01

Reward motivation is known to modulate memory encoding, and this effect depends on interactions between the substantia nigra/ ventral tegmental area complex (SN/VTA) and the hippocampus. It is unknown, however, whether these interactions influence offline neural activity in the human brain that is thought to promote memory consolidation. Here, we used functional magnetic resonance imaging (fMRI) to test the effect of reward motivation on post-learning neural dynamics and subsequent memory for objects that were learned in high- or low-reward motivation contexts. We found that post-learning increases in resting-state functional connectivity between the SN/VTA and hippocampus predicted preferential retention of objects that were learned in high-reward contexts. In addition, multivariate pattern classification revealed that hippocampal representations of high-reward contexts were preferentially reactivated during post-learning rest, and the number of hippocampal reactivations was predictive of preferential retention of items learned in high-reward contexts. These findings indicate that reward motivation alters offline post-learning dynamics between the SN/VTA and hippocampus, providing novel evidence for a potential mechanism by which reward could influence memory consolidation. PMID:26875624

Abstinence duration modulates striatal functioning during monetary reward processing in cocaine patients.

PubMed

Bustamante, Juan-Carlos; Barrós-Loscertales, Alfonso; Costumero, Víctor; Fuentes-Claramonte, Paola; Rosell-Negre, Patricia; Ventura-Campos, Noelia; Llopis, Juan-José; Ávila, César

2014-09-01

Pre-clinical and clinical studies in cocaine addiction highlight alterations in the striatal dopaminergic reward system that subserve maintenance of cocaine use. Using an instrumental conditioning paradigm with monetary reinforcement, we studied striatal functional alterations in long-term abstinent cocaine-dependent patients and striatal functioning as a function of abstinence and treatment duration. Eighteen patients and 20 controls underwent functional magnetic resonance imaging during a Monetary Incentive Delay task. Region of interest analyses based on masks of the dorsal and ventral striatum were conducted to test between-group differences and the functional effects in the cocaine group of time (in months) with no more than two lapses from the first time patients visited the clinical service to seek treatment at the scanning time (duration of treatment), and the functional effects of the number of months with no lapses or relapses at the scanning session time (length of abstinence). We applied a voxel-wise and a cluster-wise FWE-corrected level (pFWE) at a threshold of P < 0.05. The patient group showed lower activation in the right caudate during reward anticipation than the control group. The regression analyses in the patients group revealed a positive correlation between duration of treatment and brain activity in the left caudate during reward anticipation. Likewise, length of abstinence negatively correlated with brain activity in the bilateral nucleus accumbens during monetary outcome processing. In conclusion, caudate and nucleus accumbens show a different brain response pattern to non-drug rewards during cocaine addiction, which can be modulated by treatment success. © 2013 The Authors, Addiction Biology © 2013 Society for the Study of Addiction.

The Behavioral Pharmacology of Effort-Related Choice Behavior: Dopamine, Adenosine and beyond

ERIC Educational Resources Information Center

Salamone, John D.; Correa, Merce; Nunes, Eric J.; Randall, Patrick A.; Pardo, Marta

2012-01-01

For many years, it has been suggested that drugs that interfere with dopamine (DA) transmission alter the "rewarding" impact of primary reinforcers such as food. Research and theory related to the functions of mesolimbic DA are undergoing a substantial conceptual restructuring, with the traditional emphasis on hedonia and primary reward yielding…

THC reduces the anticipatory nucleus accumbens response to reward in subjects with a nicotine addiction

PubMed Central

Jansma, J M; van Hell, H H; Vanderschuren, L J M J; Bossong, M G; Jager, G; Kahn, R S; Ramsey, N F

2013-01-01

Recent evidence has implicated the endocannabinoid (eCB) system in nicotine addiction. The eCB system also has an important role in reward mechanisms, and nicotine addiction has been associated with aberrant reward processing. Motivated by this evidence, we tested the hypothesis that eCB modulation of reward processing is altered in subjects with a nicotine addiction (NAD). For this purpose, we compared reward-related activity in NAD with healthy controls (HC) in a pharmacological magnetic resonance imaging (MRI) study using Δ9-tetrahydrocannabinol (THC) administration to challenge the eCB system. Eleven HC and 10 NAD participated in a 3-T functional MRI (fMRI) study with a double-blind, cross-over, placebo-controlled design, using a Monetary Incentive Delay (MID) paradigm with three reward levels. Reward activity in the nucleus accumbens (NAcc) and caudate putamen during anticipation and feedback of reward was compared after THC and placebo. fMRI results indicated a significant reduction of reward anticipation activity in the NAcc in NAD after THC administration, which was not present in HC. This is indicated by a significant group by drug by reward interaction. Our data show that THC significantly reduces the NAcc response to monetary reward anticipation in NAD. These results suggest that nicotine addiction is associated with altered eCB modulation of reward processing in the NAcc. This study adds important human data to existing evidence implicating the eCB system in nicotine addiction. PMID:23443360

Orbitofrontal overactivation in reward processing in borderline personality disorder: the role of non-suicidal self-injury.

PubMed

Vega, Daniel; Ripollés, Pablo; Soto, Àngel; Torrubia, Rafael; Ribas, Joan; Monreal, Jose Antonio; Pascual, Juan Carlos; Salvador, Raymond; Pomarol-Clotet, Edith; Rodríguez-Fornells, Antoni; Marco-Pallarés, Josep

2018-02-01

Borderline Personality Disorder (BPD) is a disabling and difficult-to-treat mental disease. One of its core features is a significant difficulty in affect regulation, which is often accompanied by Non-Suicidal Self-Injury (NSSI). It is suggested that this type of behavior elicits positive emotions and mitigates emotional distress, and therefore can ultimately be reinforced and promoted. In spite of the high prevalence of NSSI behaviors (also in non-BPD samples), their role in modulating reward-related processes has not yet been investigated in BPD patients. In the present study, this lack of research was addressed. A large sample of BPD patients (N = 40), divided into two groups depending on the presence of NSSI, and a group of matched healthy controls underwent functional Magnetic Resonance Imaging (fMRI) while performing a gambling task. Patients who committed NSSI acts exhibited enhanced activation of the orbitofrontal cortex following an unexpected reward, when compared with controls and BPD patients with no NSSI behavior. In addition, the NSSI group showed diminished functional connectivity between the left orbitofrontal cortex and the right parahippocampal gyrus. These findings might suggest impaired ability to update reward associations of potential choices when both BPD and NSSI are present. We propose that the presence of NSSI involves alterations in the reward system independently of BPD, and thus can be considered as a possible phenotype for reward-related alterations.

Social stress reactivity alters reward and punishment learning

PubMed Central

Frank, Michael J.; Allen, John J. B.

2011-01-01

To examine how stress affects cognitive functioning, individual differences in trait vulnerability (punishment sensitivity) and state reactivity (negative affect) to social evaluative threat were examined during concurrent reinforcement learning. Lower trait-level punishment sensitivity predicted better reward learning and poorer punishment learning; the opposite pattern was found in more punishment sensitive individuals. Increasing state-level negative affect was directly related to punishment learning accuracy in highly punishment sensitive individuals, but these measures were inversely related in less sensitive individuals. Combined electrophysiological measurement, performance accuracy and computational estimations of learning parameters suggest that trait and state vulnerability to stress alter cortico-striatal functioning during reinforcement learning, possibly mediated via medio-frontal cortical systems. PMID:20453038

Social stress reactivity alters reward and punishment learning.

PubMed

Cavanagh, James F; Frank, Michael J; Allen, John J B

2011-06-01

To examine how stress affects cognitive functioning, individual differences in trait vulnerability (punishment sensitivity) and state reactivity (negative affect) to social evaluative threat were examined during concurrent reinforcement learning. Lower trait-level punishment sensitivity predicted better reward learning and poorer punishment learning; the opposite pattern was found in more punishment sensitive individuals. Increasing state-level negative affect was directly related to punishment learning accuracy in highly punishment sensitive individuals, but these measures were inversely related in less sensitive individuals. Combined electrophysiological measurement, performance accuracy and computational estimations of learning parameters suggest that trait and state vulnerability to stress alter cortico-striatal functioning during reinforcement learning, possibly mediated via medio-frontal cortical systems.

Dietary triglycerides act on mesolimbic structures to regulate the rewarding and motivational aspects of feeding

PubMed Central

Cansell, Céline; Castel, Julien; Denis, Raphaël G. P.; Rouch, Claude; Delbes, Anne-Sophie; Martinez, Sarah; Mestivier, Denis; Finan, Brian; Maldonado-Aviles, Jaime G.; Rijnsburger, Merel; Tschöp, Matthias H.; DiLeone, Ralph J.; Eckel, Robert H.; la Fleur, Susanne E.; Magnan, Christophe; Hnasko, Thomas S.; Luquet, Serge

2014-01-01

Circulating triglycerides (TG) normally increase after a meal but are altered in pathophysiological conditions such as obesity. Although TG metabolism in the brain remains poorly understood, several brain structures express enzymes that process TG-enriched particles, including mesolimbic structures. For this reason, and because consumption of high fat diet alters dopamine signaling, we tested the hypothesis that TG might directly target mesolimbic reward circuits to control reward-seeking behaviors. We found that the delivery of small amounts of TG to the brain through the carotid artery rapidly reduced both spontaneous and amphetamine-induced locomotion, abolished preference for palatable food, and reduced the motivation to engage in food-seeking behavior. Conversely, targeted disruption of the TG-hydrolyzing enzyme lipoprotein lipase specifically in the nucleus accumbens increased palatable food preference and food seeking behavior. Finally, prolonged TG perfusion resulted in a return to normal palatable food preference despite continued locomotor suppression, suggesting that adaptive mechanisms occur. These findings reveal new mechanisms by which dietary fat may alter mesolimbic circuit function and reward seeking. PMID:24732670

Identity-Specific Reward Representations in Orbitofrontal Cortex Are Modulated by Selective Devaluation

PubMed Central

Howard, James D.

2017-01-01

Goal-directed behavior is sensitive to the current value of expected outcomes. This requires independent representations of specific rewards, which have been linked to orbitofrontal cortex (OFC) function. However, the mechanisms by which the human brain updates specific goals on the fly, and translates those updates into choices, have remained unknown. Here we implemented selective devaluation of appetizing food odors in combination with pattern-based neuroimaging and a decision-making task. We found that in a hungry state, participants chose to smell high-intensity versions of two value-matched food odor rewards. After eating a meal corresponding to one of the two odors, participants switched choices toward the low intensity of the sated odor but continued to choose the high intensity of the nonsated odor. This sensory-specific behavioral effect was mirrored by pattern-based changes in fMRI signal in lateral posterior OFC, where specific reward identity representations were altered after the meal for the sated food odor but retained for the nonsated counterpart. In addition, changes in functional connectivity between the OFC and general value coding in ventromedial prefrontal cortex (vmPFC) predicted individual differences in satiety-related choice behavior. These findings demonstrate how flexible representations of specific rewards in the OFC are updated by devaluation, and how functional connections to vmPFC reflect the current value of outcomes and guide goal-directed behavior. SIGNIFICANCE STATEMENT The orbitofrontal cortex (OFC) is critical for goal-directed behavior. A recent proposal is that OFC fulfills this function by representing a variety of state and task variables (“cognitive maps”), including a conjunction of expected reward identity and value. Here we tested how identity-specific representations of food odor reward are updated by satiety. We found that fMRI pattern-based signatures of reward identity in lateral posterior OFC were modulated after selective devaluation, and that connectivity between this region and general value coding ventromedial prefrontal cortex (vmPFC) predicted choice behavior. These results provide evidence for a mechanism by which devaluation modulates a cognitive map of expected reward in OFC and thereby alters general value signals in vmPFC to guide goal-directed behavior. PMID:28159906

Functional changes of the reward system underlie blunted response to social gaze in cocaine users

PubMed Central

Preller, Katrin H.; Herdener, Marcus; Schilbach, Leonhard; Stämpfli, Philipp; Hulka, Lea M.; Vonmoos, Matthias; Ingold, Nina; Vogeley, Kai; Tobler, Philippe N.; Seifritz, Erich; Quednow, Boris B.

2014-01-01

Social interaction deficits in drug users likely impede treatment, increase the burden of the affected families, and consequently contribute to the high costs for society associated with addiction. Despite its significance, the neural basis of altered social interaction in drug users is currently unknown. Therefore, we investigated basal social gaze behavior in cocaine users by applying behavioral, psychophysiological, and functional brain-imaging methods. In study I, 80 regular cocaine users and 63 healthy controls completed an interactive paradigm in which the participants’ gaze was recorded by an eye-tracking device that controlled the gaze of an anthropomorphic virtual character. Valence ratings of different eye-contact conditions revealed that cocaine users show diminished emotional engagement in social interaction, which was also supported by reduced pupil responses. Study II investigated the neural underpinnings of changes in social reward processing observed in study I. Sixteen cocaine users and 16 controls completed a similar interaction paradigm as used in study I while undergoing functional magnetic resonance imaging. In response to social interaction, cocaine users displayed decreased activation of the medial orbitofrontal cortex, a key region of reward processing. Moreover, blunted activation of the medial orbitofrontal cortex was significantly correlated with a decreased social network size, reflecting problems in real-life social behavior because of reduced social reward. In conclusion, basic social interaction deficits in cocaine users as observed here may arise from altered social reward processing. Consequently, these results point to the importance of reinstatement of social reward in the treatment of stimulant addiction. PMID:24449854

Altered frontal inter-hemispheric resting state functional connectivity is associated with bulimic symptoms among restrained eaters.

PubMed

Chen, Shuaiyu; Dong, Debo; Jackson, Todd; Su, Yanhua; Chen, Hong

2016-01-29

Theory and research have indicated that restrained eating (RE) increases risk for binge-eating and eating disorder symptoms. According to the goal conflict model, such risk may result from disrupted hedonic-feeding control and its interaction with reward-driven eating. However, RE-related alterations in functional interactions among associated underlying brain regions, especially between the cerebral hemispheres, have rarely been examined directly. Therefore, we investigated inter-hemispheric resting-state functional connectivity (RSFC) among female restrained eaters (REs) (n=23) and unrestrained eaters (UREs) (n=24) following food deprivation as well as its relation to overall bulimia nervosa (BN) symptoms using voxel-mirrored homotopic connectivity (VMHC). Seed-based RSFC associated with areas exhibiting significant VMHC differences was also assessed. Compared to UREs, REs showed reduced VMHC in the dorsal-lateral prefrontal cortex (DLPFC), an area involved in inhibiting hedonic overeating. REs also displayed decreased RSFC between the right DLPFC and regions associated with reward estimation--the ventromedial prefrontal cortex (VMPFC) and posterior cingulate cortex (PCC). Finally, bulimic tendencies had a negative correlation with VMHC in the DLPFC and a positive correlation with functional connectivity (DLPFC and VMPFC) among REs but not UREs. Findings suggested that reduced inter-hemispheric functional connectivity in appetite inhibition regions and altered functional connectivity in reward related regions may help to explain why some REs fail to control hedonically-motivated feeding and experience higher associated levels of BN symptomatology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Striatal activation and frontostriatal connectivity during non-drug reward anticipation in alcohol dependence.

PubMed

Becker, Alena; Kirsch, Martina; Gerchen, Martin Fungisai; Kiefer, Falk; Kirsch, Peter

2017-05-01

According to prevailing neurobiological theories of addiction, altered function in neural reward circuitry is a central mechanism of alcohol dependence. Growing evidence postulates that the ventral striatum (VS), as well as areas of the prefrontal cortex, contribute to the increased incentive salience of alcohol-associated cues, diminished motivation to pursue non-drug rewards and weakened strength of inhibitory cognitive control, which are central to addiction. The present study aims to investigate the neural response and functional connectivity underlying monetary, non-drug reward processing in alcohol dependence. We utilized a reward paradigm to investigate the anticipation of monetary reward in 32 alcohol-dependent inpatients and 35 healthy controls. Functional magnetic resonance imaging was used to measure task-related brain activation and connectivity. Alcohol-dependent patients showed increased activation of the VS during anticipation of monetary gain compared with healthy controls. Generalized psychophysiological interaction analyses revealed decreased functional connectivity between the VS and the dorsolateral prefrontal cortex in alcohol dependent patients relative to controls. Increased activation of the VS and reduced frontostriatal connectivity were associated with increased craving. These findings provide evidence that alcohol dependence is rather associated with disrupted integration of striatal and prefrontal processes than with a global reward anticipation deficit. © 2016 Society for the Study of Addiction.

Sleep and Circadian Contributions to Adolescent Alcohol Use Disorder

PubMed Central

Hasler, Brant P.; Soehner, Adriane M.; Clark, Duncan B.

2014-01-01

Adolescence is a time of marked changes across sleep, circadian rhythms, brain function, and alcohol use. Starting at puberty, adolescents’ endogenous circadian rhythms and preferred sleep times shift later, often leading to a mismatch with the schedules imposed by secondary education. This mismatch induces circadian misalignment and sleep loss, which have been associated with affect dysregulation, increased drug and alcohol use, and other risk-taking behaviors in adolescents and adults. In parallel to developmental changes in sleep, adolescent brains are undergoing structural and functional changes in the circuits subserving the pursuit and processing of rewards. These developmental changes in reward processing likely contribute to the initiation of alcohol use during adolescence. Abundant evidence indicates that sleep and circadian rhythms modulate reward function, suggesting that adolescent sleep and circadian disturbance may contribute to altered reward function, and in turn, alcohol involvement. In this review, we summarize the relevant evidence and propose that these parallel developmental changes in sleep, circadian rhythms, and neural processing of reward interact to increase risk for alcohol use disorder (AUD). PMID:25442171

Reward and aversion in a heterogeneous midbrain dopamine system.

PubMed

Lammel, Stephan; Lim, Byung Kook; Malenka, Robert C

2014-01-01

The ventral tegmental area (VTA) is a heterogeneous brain structure that serves a central role in motivation and reward processing. Abnormalities in the function of VTA dopamine (DA) neurons and the targets they influence are implicated in several prominent neuropsychiatric disorders including addiction and depression. Recent studies suggest that the midbrain DA system is composed of anatomically and functionally heterogeneous DA subpopulations with different axonal projections. These findings may explain a number of previously confusing observations that suggested a role for DA in processing both rewarding as well as aversive events. Here we will focus on recent advances in understanding the neural circuits mediating reward and aversion in the VTA and how stress as well as drugs of abuse, in particular cocaine, alter circuit function within a heterogeneous midbrain DA system. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Lighting up the brain's reward circuitry.

PubMed

Lobo, Mary Kay

2012-07-01

The brain's reward circuit is critical for mediating natural reward behaviors including food, sex, and social interaction. Drugs of abuse take over this circuit and produce persistent molecular and cellular alterations in the brain regions and their neural circuitry that make up the reward pathway. Recent use of optogenetic technologies has provided novel insights into the functional and molecular role of the circuitry and cell subtypes within these circuits that constitute this pathway. This perspective will address the current and future use of light-activated proteins, including those involved in modulating neuronal activity, cellular signaling, and molecular properties in the neural circuitry mediating rewarding stimuli and maladaptive responses to drugs of abuse. © 2012 New York Academy of Sciences.

The Brain Reward Circuitry in Mood Disorders

PubMed Central

Russo, Scott J.; Nestler, Eric J.

2013-01-01

Mood disorders are common and debilitating conditions characterized in part by profound deficits in reward-related behavioral domains. A recent literature has identified important structural and functional alterations within the brain’s reward circuitry —particularly in the ventral tegmental area to nucleus accumbens pathway — that are associated with symptoms such as anhedonia and aberrant reward-associated perception and memory. This review synthesizes recent data from human and rodent studies from which emerges a circuit-level framework for understanding reward deficits in depression. We also discuss some of the molecular and cellular underpinnings of this framework, ranging from adaptations in glutamatergic synapses and neurotrophic factors to transcriptional and epigenetic mechanisms. PMID:23942470

Altered cingulo-striatal function underlies reward drive deficits in schizophrenia.

PubMed

Park, Il Ho; Chun, Ji Won; Park, Hae-Jeong; Koo, Min-Seong; Park, Sunyoung; Kim, Seok-Hyeong; Kim, Jae-Jin

2015-02-01

Amotivation in schizophrenia is assumed to involve dysfunctional dopaminergic signaling of reward prediction or anticipation. It is unclear, however, whether the translation of neural representation of reward value to behavioral drive is affected in schizophrenia. In order to examine how abnormal neural processing of response valuation and initiation affects incentive motivation in schizophrenia, we conducted functional MRI using a deterministic reinforcement learning task with variable intervals of contingency reversals in 20 clinically stable patients with schizophrenia and 20 healthy controls. Behaviorally, the advantage of positive over negative reinforcer in reinforcement-related responsiveness was not observed in patients. Patients showed altered response valuation and initiation-related striatal activity and deficient rostro-ventral anterior cingulate cortex activation during reward approach initiation. Among these neural abnormalities, rostro-ventral anterior cingulate cortex activation was correlated with positive reinforcement-related responsiveness in controls and social anhedonia and social amotivation subdomain scores in patients. Our findings indicate that the central role of the anterior cingulate cortex is in translating action value into driving force of action, and underscore the role of the cingulo-striatal network in amotivation in schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia.

PubMed

Segarra, Nuria; Metastasio, Antonio; Ziauddeen, Hisham; Spencer, Jennifer; Reinders, Niels R; Dudas, Robert B; Arrondo, Gonzalo; Robbins, Trevor W; Clark, Luke; Fletcher, Paul C; Murray, Graham K

2016-07-01

Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.

Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia

PubMed Central

Segarra, Nuria; Metastasio, Antonio; Ziauddeen, Hisham; Spencer, Jennifer; Reinders, Niels R; Dudas, Robert B; Arrondo, Gonzalo; Robbins, Trevor W; Clark, Luke; Fletcher, Paul C; Murray, Graham K

2016-01-01

Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states. PMID:26708106

Medial reward and lateral non-reward orbitofrontal cortex circuits change in opposite directions in depression.

PubMed

Cheng, Wei; Rolls, Edmund T; Qiu, Jiang; Liu, Wei; Tang, Yanqing; Huang, Chu-Chung; Wang, XinFa; Zhang, Jie; Lin, Wei; Zheng, Lirong; Pu, JunCai; Tsai, Shih-Jen; Yang, Albert C; Lin, Ching-Po; Wang, Fei; Xie, Peng; Feng, Jianfeng

2016-12-01

The first brain-wide voxel-level resting state functional connectivity neuroimaging analysis of depression is reported, with 421 patients with major depressive disorder and 488 control subjects. Resting state functional connectivity between different voxels reflects correlations of activity between those voxels and is a fundamental tool in helping to understand the brain regions with altered connectivity and function in depression. One major circuit with altered functional connectivity involved the medial orbitofrontal cortex Brodmann area 13, which is implicated in reward, and which had reduced functional connectivity in depression with memory systems in the parahippocampal gyrus and medial temporal lobe, especially involving the perirhinal cortex Brodmann area 36 and entorhinal cortex Brodmann area 28. The Hamilton Depression Rating Scale scores were correlated with weakened functional connectivity of the medial orbitofrontal cortex Brodmann area 13. Thus in depression there is decreased reward-related and memory system functional connectivity, and this is related to the depressed symptoms. The lateral orbitofrontal cortex Brodmann area 47/12, involved in non-reward and punishing events, did not have this reduced functional connectivity with memory systems. Second, the lateral orbitofrontal cortex Brodmann area 47/12 had increased functional connectivity with the precuneus, the angular gyrus, and the temporal visual cortex Brodmann area 21. This enhanced functional connectivity of the non-reward/punishment system (Brodmann area 47/12) with the precuneus (involved in the sense of self and agency), and the angular gyrus (involved in language) is thus related to the explicit affectively negative sense of the self, and of self-esteem, in depression. A comparison of the functional connectivity in 185 depressed patients not receiving medication and 182 patients receiving medication showed that the functional connectivity of the lateral orbitofrontal cortex Brodmann area 47/12 with these three brain areas was lower in the medicated than the unmedicated patients. This is consistent with the hypothesis that the increased functional connectivity of the lateral orbitofrontal cortex Brodmann area 47/12 is related to depression. Relating the changes in cortical connectivity to our understanding of the functions of different parts of the orbitofrontal cortex in emotion helps to provide new insight into the brain changes related to depression. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Orbitofrontal reward sensitivity and impulsivity in adult attention deficit hyperactivity disorder.

PubMed

Wilbertz, Gregor; van Elst, Ludger Tebartz; Delgado, Mauricio R; Maier, Simon; Feige, Bernd; Philipsen, Alexandra; Blechert, Jens

2012-03-01

Impulsivity symptoms of adult attention deficit hyperactivity disorder (ADHD) such as increased risk taking have been linked with impaired reward processing. Previous studies have focused on reward anticipation or on rewarded executive functioning tasks and have described a striatal hyporesponsiveness and orbitofrontal alterations in adult and adolescent ADHD. Passive reward delivery and its link to behavioral impulsivity are less well understood. To study this crucial aspect of reward processing we used functional magnetic resonance imaging (fMRI) combined with electrodermal assessment in male and female adult ADHD patients (N=28) and matched healthy control participants (N=28) during delivery of monetary and non-monetary rewards. Further, two behavioral tasks assessed risky decision making (game of dice task) and delay discounting. Results indicated that both groups activated ventral and dorsal striatum and the medial orbitofrontal cortex (mOFC) in response to high-incentive (i.e. monetary) rewards. A similar, albeit less strong activation pattern was found for low-incentive (i.e. non-monetary) rewards. Group differences emerged when comparing high and low incentive rewards directly: activation in the mOFC coded for the motivational change in reward delivery in healthy controls, but not ADHD patients. Additionally, this dysfunctional mOFC activity in patients correlated with risky decision making and delay discounting and was paralleled by physiological arousal. Together, these results suggest that the mOFC codes reward value and type in healthy individuals whereas this function is deficient in ADHD. The brain-behavior correlations suggest that this deficit might be related to behavioral impulsivity. Reward value processing difficulties in ADHD should be considered when assessing reward anticipation and emotional learning in research and applied settings. Copyright © 2011 Elsevier Inc. All rights reserved.

Insulin, Central Dopamine D2 Receptors, and Monetary Reward Discounting in Obesity

PubMed Central

Eisenstein, Sarah A.; Gredysa, Danuta M.; Antenor–Dorsey, Jo Ann; Green, Leonard; Arbeláez, Ana Maria; Koller, Jonathan M.; Black, Kevin J.; Perlmutter, Joel S.; Moerlein, Stephen M.; Hershey, Tamara

2015-01-01

Animal research finds that insulin regulates dopamine signaling and reward behavior, but similar research in humans is lacking. We investigated whether individual differences in body mass index, percent body fat, pancreatic β-cell function, and dopamine D2 receptor binding were related to reward discounting in obese and non-obese adult men and women. Obese (n = 27; body mass index>30) and non-obese (n = 20; body mass index<30) adults were assessed for percent body fat with dual-energy X-ray absorptiometry and for β-cell function using disposition index. Choice of larger, but delayed or less certain, monetary rewards relative to immediate, certain smaller monetary rewards was measured using delayed and probabilistic reward discounting tasks. Positron emission tomography using a non-displaceable D2-specific radioligand, [11C](N-methyl)benperidol quantified striatal D2 receptor binding. Groups differed in body mass index, percent body fat, and disposition index, but not in striatal D2 receptor specific binding or reward discounting. Higher percent body fat in non-obese women related to preference for a smaller, certain reward over a larger, less likely one (greater probabilistic discounting). Lower β-cell function in the total sample and lower insulin sensitivity in obese related to stronger preference for an immediate and smaller monetary reward over delayed receipt of a larger one (greater delay discounting). In obese adults, higher striatal D2 receptor binding related to greater delay discounting. Interestingly, striatal D2 receptor binding was not significantly related to body mass index, percent body fat, or β-cell function in either group. Our findings indicate that individual differences in percent body fat, β-cell function, and striatal D2 receptor binding may each contribute to altered reward discounting behavior in non-obese and obese individuals. These results raise interesting questions about whether and how striatal D2 receptor binding and metabolic factors, including β-cell function, interact to affect reward discounting in humans. PMID:26192187

Insulin, Central Dopamine D2 Receptors, and Monetary Reward Discounting in Obesity.

PubMed

Eisenstein, Sarah A; Gredysa, Danuta M; Antenor-Dorsey, Jo Ann; Green, Leonard; Arbeláez, Ana Maria; Koller, Jonathan M; Black, Kevin J; Perlmutter, Joel S; Moerlein, Stephen M; Hershey, Tamara

2015-01-01

Animal research finds that insulin regulates dopamine signaling and reward behavior, but similar research in humans is lacking. We investigated whether individual differences in body mass index, percent body fat, pancreatic β-cell function, and dopamine D2 receptor binding were related to reward discounting in obese and non-obese adult men and women. Obese (n = 27; body mass index>30) and non-obese (n = 20; body mass index<30) adults were assessed for percent body fat with dual-energy X-ray absorptiometry and for β-cell function using disposition index. Choice of larger, but delayed or less certain, monetary rewards relative to immediate, certain smaller monetary rewards was measured using delayed and probabilistic reward discounting tasks. Positron emission tomography using a non-displaceable D2-specific radioligand, [11C](N-methyl)benperidol quantified striatal D2 receptor binding. Groups differed in body mass index, percent body fat, and disposition index, but not in striatal D2 receptor specific binding or reward discounting. Higher percent body fat in non-obese women related to preference for a smaller, certain reward over a larger, less likely one (greater probabilistic discounting). Lower β-cell function in the total sample and lower insulin sensitivity in obese related to stronger preference for an immediate and smaller monetary reward over delayed receipt of a larger one (greater delay discounting). In obese adults, higher striatal D2 receptor binding related to greater delay discounting. Interestingly, striatal D2 receptor binding was not significantly related to body mass index, percent body fat, or β-cell function in either group. Our findings indicate that individual differences in percent body fat, β-cell function, and striatal D2 receptor binding may each contribute to altered reward discounting behavior in non-obese and obese individuals. These results raise interesting questions about whether and how striatal D2 receptor binding and metabolic factors, including β-cell function, interact to affect reward discounting in humans.

A reward-centred model of anorexia nervosa: a focussed narrative review of the neurological and psychophysiological literature.

PubMed

O'Hara, Caitlin B; Campbell, Iain C; Schmidt, Ulrike

2015-05-01

This focussed narrative review examines neurobiological and psychophysiological evidence supporting a role for altered reward processes in the development and maintenance of anorexia nervosa (AN). In AN, there does not appear to be a generalised inability to experience reward. Rather, data suggest that a reluctance to gain weight leads to an aversive appraisal of food- and taste-related stimuli. As a result, cues compatible with this aberrant mode of thinking become rewarding for the individual. Evidence also suggests that attribution of motivational salience to such cues promotes anorectic behaviours. These findings are consistent with models in which interactions between cognition and reward are important in eliciting the anorectic "habit". A model is proposed which is consistent with elements of other theoretical frameworks, but differs in that its emphasis is towards neural overlaps between AN and addiction. It is consistent with AN being a reward-based learned behaviour in which aberrant cognitions related to eating and shape alter functioning of central reward systems. It proposes that the primary neural problem responsible for the development, maintenance, and treatment resistance is centred in the striatal reward system. This helps shift the emphasis of aetiological models towards reward processing, particularly in the context of illness-compatible cues. Furthermore, it suggests that continuing to explore the utility and valued nature of AN in the patient's life would be a useful inclusion in treatment and prevention models. Copyright © 2015. Published by Elsevier Ltd.

Altered resting state functional connectivity of fear and reward circuitry in comorbid PTSD and major depression.

PubMed

Zhu, Xi; Helpman, Liat; Papini, Santiago; Schneier, Franklin; Markowitz, John C; Van Meter, Page E; Lindquist, Martin A; Wager, Tor D; Neria, Yuval

2017-07-01

Individuals with comorbid posttraumatic stress disorder and major depressive disorder (PTSD-MDD) often exhibit greater functional impairment and poorer treatment response than individuals with PTSD alone. Research has not determined whether PTSD-MDD is associated with different network connectivity abnormalities than PTSD alone. We used functional magnetic resonance imaging (fMRI) to measure resting state functional connectivity (rs-FC) patterns of brain regions involved in fear and reward processing in three groups: patients with PTSD-alone (n = 27), PTSD-MDD (n = 21), and trauma-exposed healthy controls (TEHCs, n = 34). Based on previous research, seeds included basolateral amygdala (BLA), centromedial amygdala (CMA), and nucleus accumbens (NAcc). Regardless of MDD comorbidity, PTSD was associated with decreased connectivity of BLA-orbitalfrontal cortex (OFC) and CMA-thalamus pathways, key to fear processing, and fear expression, respectively. PTSD-MDD, compared to PTSD-alone and TEHC, was associated with decreased connectivity across multiple amygdala and striatal-subcortical pathways: BLA-OFC, NAcc-thalamus, and NAcc-hippocampus. Further, while both the BLA-OFC and the NAcc-thalamus pathways were correlated with MDD symptoms, PTSD symptoms correlated with the amygdala pathways (BLA-OFC; CMA-thalamus) only. Comorbid PTSD-MDD may be associated with multifaceted functional connectivity alterations in both fear and reward systems. Clinical implications are discussed. © 2016 Wiley Periodicals, Inc.

Preliminary investigation of the relationships between sleep duration, reward circuitry function, and mood dysregulation in youth offspring of parents with bipolar disorder.

PubMed

Soehner, Adriane M; Bertocci, Michele A; Manelis, Anna; Bebko, Genna; Ladouceur, Cecile D; Graur, Simona; Monk, Kelly; Bonar, Lisa K; Hickey, Mary Beth; Axelson, David; Goldstein, Benjamin I; Goldstein, Tina R; Birmaher, Boris; Phillips, Mary L

2016-11-15

Altered reward circuitry function is observed in individuals with bipolar disorder (BD) and their unaffected offspring (OBP). While OBP are at elevated risk for BD, modifiable risk factors that may exacerbate neural vulnerabilities in OBP remain under-characterized. As sleep loss is strongly linked to mania in BD, this study tested associations between sleep duration, reward circuitry function, and mood dysregulation in OBP. Two groups of youth unaffected with BD (9-17yr) completed a number-guessing fMRI reward paradigm: 25 OBP and 21 age-sex-IQ-matched offspring of control parents with non-BD psychopathology (OCP), to differentiate risk for BD from risk for psychopathology more broadly. Regressions tested effects of group status, self-reported past-week sleep duration, and their interaction on neural activity and bilateral ventral striatum (VS) functional connectivity to win>control. Correlations with parent-reported mood dysregulation were assessed. Group effects were observed for right posterior insula activity (OCP>OBP) and VS-left posterior insula connectivity (OBP>OCP). Group ⁎ sleep duration interactions were observed for left dorsal anterior-mid-cingulate (daMCC) activity and VS-left anterior insula/ventrolateral prefrontal cortex (VLPFC) connectivity. Specifically, sleep duration and daMCC activity were positively related in OBP, but negatively related in OCP and sleep duration and VS-left anterior insula/VLPFC connectivity were negatively related in OBP, but positively in OCP. Additionally, increased VS-left posterior insula connectivity and VS-left anterior insula/VLPFC connectivity were associated with greater mood dysregulation in OBP only. Cross-sectional design and small sample size. Altered reward-related VS-insula connectivity could represent a neural pathway underpinning mood dysregulation in OBP, and may be modulated by shortened sleep duration. Copyright © 2016 Elsevier B.V. All rights reserved.

Identity-Specific Reward Representations in Orbitofrontal Cortex Are Modulated by Selective Devaluation.

PubMed

Howard, James D; Kahnt, Thorsten

2017-03-08

Goal-directed behavior is sensitive to the current value of expected outcomes. This requires independent representations of specific rewards, which have been linked to orbitofrontal cortex (OFC) function. However, the mechanisms by which the human brain updates specific goals on the fly, and translates those updates into choices, have remained unknown. Here we implemented selective devaluation of appetizing food odors in combination with pattern-based neuroimaging and a decision-making task. We found that in a hungry state, participants chose to smell high-intensity versions of two value-matched food odor rewards. After eating a meal corresponding to one of the two odors, participants switched choices toward the low intensity of the sated odor but continued to choose the high intensity of the nonsated odor. This sensory-specific behavioral effect was mirrored by pattern-based changes in fMRI signal in lateral posterior OFC, where specific reward identity representations were altered after the meal for the sated food odor but retained for the nonsated counterpart. In addition, changes in functional connectivity between the OFC and general value coding in ventromedial prefrontal cortex (vmPFC) predicted individual differences in satiety-related choice behavior. These findings demonstrate how flexible representations of specific rewards in the OFC are updated by devaluation, and how functional connections to vmPFC reflect the current value of outcomes and guide goal-directed behavior. SIGNIFICANCE STATEMENT The orbitofrontal cortex (OFC) is critical for goal-directed behavior. A recent proposal is that OFC fulfills this function by representing a variety of state and task variables ("cognitive maps"), including a conjunction of expected reward identity and value. Here we tested how identity-specific representations of food odor reward are updated by satiety. We found that fMRI pattern-based signatures of reward identity in lateral posterior OFC were modulated after selective devaluation, and that connectivity between this region and general value coding ventromedial prefrontal cortex (vmPFC) predicted choice behavior. These results provide evidence for a mechanism by which devaluation modulates a cognitive map of expected reward in OFC and thereby alters general value signals in vmPFC to guide goal-directed behavior. Copyright © 2017 the authors 0270-6474/17/372627-12$15.00/0.

Functional magnetic resonance imaging in awake transgenic fragile X rats: evidence of dysregulation in reward processing in the mesolimbic/habenular neural circuit.

PubMed

Kenkel, W M; Yee, J R; Moore, K; Madularu, D; Kulkarni, P; Gamber, K; Nedelman, M; Ferris, C F

2016-03-22

Anxiety and social deficits, often involving communication impairment, are fundamental clinical features of fragile X syndrome. There is growing evidence that dysregulation in reward processing is a contributing factor to the social deficits observed in many psychiatric disorders. Hence, we hypothesized that transgenic fragile X mental retardation 1 gene (fmr1) KO (FX) rats would display alterations in reward processing. To this end, awake control and FX rats were imaged for changes in blood oxygen level dependent (BOLD) signal intensity in response to the odor of almond, a stimulus to elicit the innate reward response. Subjects were 'odor naive' to this evolutionarily conserved stimulus. The resulting changes in brain activity were registered to a three-dimensional segmented, annotated rat atlas delineating 171 brain regions. Both wild-type (WT) and FX rats showed robust brain activation to a rewarding almond odor, though FX rats showed an altered temporal pattern and tended to have a higher number of voxels with negative BOLD signal change from baseline. This pattern of greater negative BOLD was especially apparent in the Papez circuit, critical to emotional processing and the mesolimbic/habenular reward circuit. WT rats showed greater positive BOLD response in the supramammillary area, whereas FX rats showed greater positive BOLD response in the dorsal lateral striatum, and greater negative BOLD response in the retrosplenial cortices, the core of the accumbens and the lateral preoptic area. When tested in a freely behaving odor-investigation paradigm, FX rats failed to show the preference for almond odor which typifies WT rats. However, FX rats showed investigation profiles similar to WT when presented with social odors. These data speak to an altered processing of this highly salient novel odor in the FX phenotype and lend further support to the notion that altered reward systems in the brain may contribute to fragile X syndrome symptomology.

The anabolic steroid nandrolone alters cannabinoid self-administration and brain CB1 receptor density and function.

PubMed

Struik, Dicky; Fadda, Paola; Zara, Tamara; Zamberletti, Erica; Rubino, Tiziana; Parolaro, Daniela; Fratta, Walter; Fattore, Liana

2017-01-01

Clinical and pre-clinical observations indicate that anabolic-androgenic steroids can induce neurobiological changes that alter the rewarding effects of drugs of abuse. In this study, we investigated the effect of the anabolic steroid nandrolone on the rewarding properties of the cannabinoid CB 1 receptor agonist WIN55,212-2 (WIN) in rats. Lister Hooded male rats were treated intramuscularly with nandrolone (15mg/kg) or vehicle for 14 consecutive days, and then allowed to self-administer WIN (12.5μg/kg/infusion) intravenously. After reaching stable drug intake, self-administration behavior was extinguished to examine drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Other behavioral parameters presumed to influence drug-taking and drug-seeking behaviors were examined to gain more insight into the behavioral specificity of nandrolone treatment. Finally, animals were sacrificed for analysis of CB 1 receptor density and function in selected brain areas. We found that nandrolone-treated rats self-administered up to 2 times more cannabinoid than vehicle-treated rats, but behaved similarly to control rats when tested for drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Enhanced cannabinoid intake by nandrolone-treated rats was not accompanied by changes in locomotor activity, sensorimotor gating, or memory function. However, our molecular data show that after chronic WIN self-administration nandrolone-treated rats display altered CB 1 receptor density and function in selected brain areas. We hypothesize that increased cannabinoid self-administration in nandrolone-treated rats results from a nandrolone-induced decrease in reward function, which rats seem to compensate by voluntarily increasing their cannabinoid intake. Altogether, our findings corroborate the hypothesis that chronic exposure to anabolic-androgenic steroids induces dysfunction of the reward pathway in rats and might represent a potential risk factor for abuse of cannabis and other drugs in humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

Glutamatergic plasticity and alcohol dependence-induced alterations in reward, affect and cognition.

PubMed

Burnett, Elizabeth J; Chandler, L Judson; Trantham-Davidson, Heather

2016-02-04

Alcohol dependence is characterized by a reduction in reward threshold, development of a negative affective state, and significant cognitive impairments. Dependence-induced glutamatergic neuroadaptations in the neurocircuitry mediating reward, affect and cognitive function are thought to underlie the neural mechanism for these alterations. These changes serve to promote increased craving for alcohol and facilitate the development of maladaptive behaviors that promote relapse to alcohol drinking during periods of abstinence. To review the extant literature on the effects of chronic alcohol exposure on glutamatergic neurotransmission and its impact on reward, affect and cognition. Evidence from a diverse set of studies demonstrates significant enhancement of glutamatergic activity following chronic alcohol exposure. In particular, up-regulation of GluN2B-containing NMDA receptor expression and function is a commonly observed phenomenon that likely reflects activity-dependent adaptive homeostatic plasticity. However, this observation as well as other glutamatergic neuroadaptations are often circuit and cell-type specific. Dependence-induced alterations in glutamate signaling contribute to many of the symptoms experienced in addicted individuals and can persist well into abstinence. This suggests that they play an important role in the development of behaviors that increase the probability for relapse. As our understanding of the complexity of the neurocircuitry involved in the addictive process has advanced, it has become increasingly clear that investigations of cell-type and circuit-specific effects are required to gain a more comprehensive understanding of the glutamatergic adaptations and their functional consequences in alcohol addiction. While pharmacological treatments for alcohol dependence and relapse targeting the glutamatergic system have shown great promise in preclinical models, more research is needed to uncover novel, possibly circuit-specific, therapeutic targets that exhibit improved efficacy and reduced side effects. Copyright © 2015 Elsevier Inc. All rights reserved.

Mesolimbic Dopamine Signals the Value of Work

PubMed Central

Hamid, Arif A.; Pettibone, Jeffrey R.; Mabrouk, Omar S.; Hetrick, Vaughn L.; Schmidt, Robert; Vander Weele, Caitlin M.; Kennedy, Robert T.; Aragona, Brandon J.; Berke, Joshua D.

2015-01-01

Dopamine cell firing can encode errors in reward prediction, providing a learning signal to guide future behavior. Yet dopamine is also a key modulator of motivation, invigorating current behavior. Existing theories propose that fast (“phasic”) dopamine fluctuations support learning, while much slower (“tonic”) dopamine changes are involved in motivation. We examined dopamine release in the nucleus accumbens across multiple time scales, using complementary microdialysis and voltammetric methods during adaptive decision-making. We first show that minute-by-minute dopamine levels covary with reward rate and motivational vigor. We then show that second-by-second dopamine release encodes an estimate of temporally-discounted future reward (a value function). We demonstrate that changing dopamine immediately alters willingness to work, and reinforces preceding action choices by encoding temporal-difference reward prediction errors. Our results indicate that dopamine conveys a single, rapidly-evolving decision variable, the available reward for investment of effort, that is employed for both learning and motivational functions. PMID:26595651

Involvement of the endocannabinoid system in reward processing in the human brain.

PubMed

van Hell, Hendrika H; Jager, Gerry; Bossong, Matthijs G; Brouwer, Annelies; Jansma, J Martijn; Zuurman, Lineke; van Gerven, Joop; Kahn, René S; Ramsey, Nick F

2012-02-01

Disturbed reward processing in humans has been associated with a number of disorders, such as depression, addiction, and attention-deficit hyperactivity disorder. The endocannabinoid (eCB) system has been implicated in reward processing in animals, but in humans, the relation between eCB functioning and reward is less clear. The current study uses functional magnetic resonance imaging (fMRI) to investigate the role of the eCB system in reward processing in humans by examining the effect of the eCB agonist Δ(9)-tetrahydrocannabinol (THC) on reward-related brain activity. Eleven healthy males participated in a randomized placebo-controlled pharmacological fMRI study with administration of THC to challenge the eCB system. We compared anticipatory and feedback-related brain activity after placebo and THC, using a monetary incentive delay task. In this task, subjects are notified before each trial whether a correct response is rewarded ("reward trial") or not ("neutral trial"). Subjects showed faster reaction times during reward trials compared to neutral trials, and this effect was not altered by THC. THC induced a widespread attenuation of the brain response to feedback in reward trials but not in neutral trials. Anticipatory brain activity was not affected. These results suggest a role for the eCB system in the appreciation of rewards. The involvement of the eCB system in feedback processing may be relevant for disorders in which appreciation of natural rewards may be affected such as addiction.

Active and observational reward learning in adults with autism spectrum disorder: relationship with empathy in an atypical sample.

PubMed

Bellebaum, Christian; Brodmann, Katja; Thoma, Patrizia

2014-01-01

Autism spectrum disorders (ASDs) are characterised by disturbances in social behaviour. A prevailing hypothesis suggests that these problems are related to deficits in assigning rewarding value to social stimuli. The present study aimed to examine monetary reward processing in adults with ASDs by means of event-related potentials (ERPs). Ten individuals with mild ASDs (Asperger's syndrome and high-functioning autism) and 12 healthy control subjects performed an active and an observational probabilistic reward-learning task. Both groups showed similar overall learning performance. With respect to reward processing, subjects with ASDs exhibited a general reduction in feedback-related negativity (FRN) amplitude, irrespective of feedback valence and type of learning (active or observational). Individuals with ASDs showed lower scores for cognitive empathy, while affective empathy did not differ between groups. Correlation analyses revealed that higher empathy (both cognitive and affective) negatively affected performance in observational learning in controls and in active learning in ASDs (only cognitive empathy). No relationships were seen between empathy and ERPs. Reduced FRN amplitudes are discussed in terms of a deficit in fast reward processing in ASDs, which may indicate altered reward system functioning.

Offspring neuroimmune consequences of maternal malnutrition: Potential mechanism for behavioral impairments that underlie metabolic and neurodevelopmental disorders.

PubMed

Smith, B L; Reyes, T M

2017-10-01

Maternal malnutrition significantly increases offspring risk for both metabolic and neurodevelopmental disorders. Animal models of maternal malnutrition have identified behavioral changes in the adult offspring related to executive function and reward processing. Together, these changes in executive and reward-based behaviors likely contribute to the etiology of both metabolic and neurodevelopmental disorders associated with maternal malnutrition. Concomitant with the behavioral effects, maternal malnutrition alters offspring expression of reward-related molecules and inflammatory signals in brain pathways that control executive function and reward. Neuroimmune pathways and microglial interactions in these specific brain circuits, either in early development or later in adulthood, could directly contribute to the maternal malnutrition-induced behavioral phenotypes. Understanding these mechanisms will help advance treatment strategies for metabolic and neurodevelopmental disorders, especially noninvasive dietary supplementation interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

Reward Prediction Errors in Drug Addiction and Parkinson's Disease: from Neurophysiology to Neuroimaging.

PubMed

García-García, Isabel; Zeighami, Yashar; Dagher, Alain

2017-06-01

Surprises are important sources of learning. Cognitive scientists often refer to surprises as "reward prediction errors," a parameter that captures discrepancies between expectations and actual outcomes. Here, we integrate neurophysiological and functional magnetic resonance imaging (fMRI) results addressing the processing of reward prediction errors and how they might be altered in drug addiction and Parkinson's disease. By increasing phasic dopamine responses, drugs might accentuate prediction error signals, causing increases in fMRI activity in mesolimbic areas in response to drugs. Chronic substance dependence, by contrast, has been linked with compromised dopaminergic function, which might be associated with blunted fMRI responses to pleasant non-drug stimuli in mesocorticolimbic areas. In Parkinson's disease, dopamine replacement therapies seem to induce impairments in learning from negative outcomes. The present review provides a holistic overview of reward prediction errors across different pathologies and might inform future clinical strategies targeting impulsive/compulsive disorders.

Reward magnitude tracking by neural populations in ventral striatum

PubMed Central

Fiallos, Ana M.; Bricault, Sarah J.; Cai, Lili X.; Worku, Hermoon A.; Colonnese, Matthew T.; Westmeyer, Gil; Jasanoff, Alan

2017-01-01

Evaluation of the magnitudes of intrinsically rewarding stimuli is essential for assigning value and guiding behavior. By combining parametric manipulation of a primary reward, medial forebrain bundle (MFB) microstimulation, with functional magnetic imaging (fMRI) in rodents, we delineated a broad network of structures activated by behaviorally characterized levels of rewarding stimulation. Correlation of psychometric behavioral measurements with fMRI response magnitudes revealed regions whose activity corresponded closely to the subjective magnitude of rewards. The largest and most reliable focus of reward magnitude tracking was observed in the shell region of the nucleus accumbens (NAc). Although the nonlinear nature of neurovascular coupling complicates interpretation of fMRI findings in precise neurophysiological terms, reward magnitude tracking was not observed in vascular compartments and could not be explained by saturation of region-specific hemodynamic responses. In addition, local pharmacological inactivation of NAc changed the profile of animals’ responses to rewards of different magnitudes without altering mean reward response rates, further supporting a hypothesis that neural population activity in this region contributes to assessment of reward magnitudes. PMID:27789262

Aberrant mesolimbic dopamine-opiate interaction in obesity.

PubMed

Tuominen, Lauri; Tuulari, Jetro; Karlsson, Henry; Hirvonen, Jussi; Helin, Semi; Salminen, Paulina; Parkkola, Riitta; Hietala, Jarmo; Nuutila, Pirjo; Nummenmaa, Lauri

2015-11-15

Dopamine and opioid neurotransmitter systems share many functions such as regulation of reward and pleasure. μ-Opioid receptors (MOR) modulate the mesolimbic dopamine system in ventral tegmental area and striatum, key areas implicated in reward. We hypothesized that dopamine and opioid receptor availabilities correlate in vivo and that this correlation is altered in obesity, a disease with altered reward processing. Twenty lean females (mean BMI 22) and 25 non-binge eating morbidly obese females (mean BMI 41) underwent two positron emission tomography scans with [(11)C]carfentanil and [(11)C]raclopride to measure the MOR and dopamine D2 receptor (DRD2) availability, respectively. In lean subjects, the MOR and DRD2 availabilities were positively associated in the ventral striatum (r=0.62, p=0.003) and dorsal caudate nucleus (r=0.62, p=0.004). Moreover, DRD2 availability in the ventral striatum was associated with MOR availability in other regions of the reward circuitry, particularly in the ventral tegmental area. In morbidly obese subjects, this receptor interaction was significantly weaker in ventral striatum but unaltered in the caudate nucleus. Finally, the association between DRD2 availability in the ventral striatum and MOR availability in the ventral tegmental area was abolished in the morbidly obese. The study demonstrates a link between DRD2 and MOR availabilities in living human brain. This interaction is selectively disrupted in mesolimbic dopamine system in morbid obesity. We propose that interaction between the dopamine and opioid systems is a prerequisite for normal reward processing and that disrupted cross-talk may underlie altered reward processing in obesity. Copyright © 2015 Elsevier Inc. All rights reserved.

Noradrenergic modulation of risk/reward decision making.

PubMed

Montes, David R; Stopper, Colin M; Floresco, Stan B

2015-08-01

Catecholamine transmission modulates numerous cognitive and reward-related processes that can subserve more complex functions such as cost/benefit decision making. Dopamine has been shown to play an integral role in decisions involving reward uncertainty, yet there is a paucity of research investigating the contributions of noradrenaline (NA) transmission to these functions. The present study was designed to elucidate the contribution of NA to risk/reward decision making in rats, assessed with a probabilistic discounting task. We examined the effects of reducing noradrenergic transmission with the α2 agonist clonidine (10-100 μg/kg), and increasing activity at α2A receptor sites with the agonist guanfacine (0.1-1 mg/kg), the α2 antagonist yohimbine (1-3 mg/kg), and the noradrenaline transporter (NET) inhibitor atomoxetine (0.3-3 mg/kg) on probabilistic discounting. Rats chose between a small/certain reward and a larger/risky reward, wherein the probability of obtaining the larger reward either decreased (100-12.5 %) or increased (12.5-100 %) over a session. In well-trained rats, clonidine reduced risky choice by decreasing reward sensitivity, whereas guanfacine did not affect choice behavior. Yohimbine impaired adjustments in decision biases as reward probability changed within a session by altering negative feedback sensitivity. In a subset of rats that displayed prominent discounting of probabilistic rewards, the lowest dose of atomoxetine increased preference for the large/risky reward when this option had greater long-term utility. These data highlight an important and previously uncharacterized role for noradrenergic transmission in mediating different aspects of risk/reward decision making and mediating reward and negative feedback sensitivity.

Additive effects of oxytocin receptor gene polymorphisms on reward circuitry in youth with autism.

PubMed

Hernandez, L M; Krasileva, K; Green, S A; Sherman, L E; Ponting, C; McCarron, R; Lowe, J K; Geschwind, D H; Bookheimer, S Y; Dapretto, M

2017-08-01

Several common alleles in the oxytocin receptor gene (OXTR) are associated with altered brain function in reward circuitry in neurotypical adults and may increase risk for autism spectrum disorders (ASD). Yet, it is currently unknown how variation in the OXTR relates to brain functioning in individuals with ASD, and, critically, whether neural endophenotypes vary as a function of aggregate genetic risk. Here, for we believe the first time, we use a multi-locus approach to examine how genetic variation across several OXTR single-nucleotide polymorphisms (SNPs) affect functional connectivity of the brain's reward network. Using data from 41 children with ASD and 41 neurotypical children, we examined functional connectivity of the nucleus accumbens (NAcc) - a hub of the reward network - focusing on how connectivity varies with OXTR risk-allele dosage. Youth with ASD showed reduced NAcc connectivity with other areas in the reward circuit as a function of increased OXTR risk-allele dosage, as well as a positive association between risk-allele dosage and symptom severity, whereas neurotypical youth showed increased NAcc connectivity with frontal brain regions involved in mentalizing. In addition, we found that increased NAcc-frontal cortex connectivity in typically developing youth was related to better scores on a standardized measure of social functioning. Our results indicate that cumulative genetic variation on the OXTR impacts reward system connectivity in both youth with ASD and neurotypical controls. By showing differential genetic effects on neuroendophenotypes, these pathways elucidate mechanisms of vulnerability versus resilience in carriers of disease-associated risk alleles.

Association of Marijuana Use With Blunted Nucleus Accumbens Response to Reward Anticipation.

PubMed

Martz, Meghan E; Trucco, Elisa M; Cope, Lora M; Hardee, Jillian E; Jester, Jennifer M; Zucker, Robert A; Heitzeg, Mary M

2016-08-01

Marijuana use may alter ventral striatal response to reward, which might heighten susceptibility to substance use disorder. Longitudinal research is needed to determine the effects of marijuana use on neural function involved in reward response. To determine whether marijuana use among young adults prospectively affects nucleus accumbens (NAcc) activation during reward anticipation. One hundred eight young adults were recruited from the Michigan Longitudinal Study, an ongoing study of youth at high risk for substance use disorder and a contrast sample of control families. Participants underwent 3 consecutive functional magnetic resonance imaging scans at approximate ages of 20 (time 1), 22 (time 2), and 24 (time 3) years. Self-report data on marijuana and other drug use occasions were collected annually since age 11 years. Cross-lagged models were used to test the association of marijuana use with neural response in the NAcc to reward anticipation during a monetary incentive delay task controlling for sex, age, other substance use, and family history of substance use disorder. Of 108 participants, 39 (36.1%) were female and mean (SD) age at baseline was 20.1 (1.4) years. Greater marijuana use was associated with later blunted activation in the NAcc during reward anticipation (time 1 to time 2: β = -0.26, P = .04; time 2 to time 3: β = -0.25, P = .01). When the cross-lagged model was tested with the inclusion of previous and concurrent cigarette use, the effect of marijuana use from time 2 to time 3 remained significant (β = -0.29; P = .005) and the effect of cigarette use was nonsignificant. The findings of this study indicate that marijuana use is associated with decreased neural response in the NAcc during the anticipation of nondrug rewards. Over time, marijuana use may alter anticipatory reward processing in the NAcc, which may increase the risk for continued drug use and later addiction.

Comparing the neural basis of monetary reward and cognitive feedback during information-integration category learning.

PubMed

Daniel, Reka; Pollmann, Stefan

2010-01-06

The dopaminergic system is known to play a central role in reward-based learning (Schultz, 2006), yet it was also observed to be involved when only cognitive feedback is given (Aron et al., 2004). Within the domain of information-integration category learning, in which information from several stimulus dimensions has to be integrated predecisionally (Ashby and Maddox, 2005), the importance of contingent feedback is well established (Maddox et al., 2003). We examined the common neural correlates of reward anticipation and prediction error in this task. Sixteen subjects performed two parallel information-integration tasks within a single event-related functional magnetic resonance imaging session but received a monetary reward only for one of them. Similar functional areas including basal ganglia structures were activated in both task versions. In contrast, a single structure, the nucleus accumbens, showed higher activation during monetary reward anticipation compared with the anticipation of cognitive feedback in information-integration learning. Additionally, this activation was predicted by measures of intrinsic motivation in the cognitive feedback task and by measures of extrinsic motivation in the rewarded task. Our results indicate that, although all other structures implicated in category learning are not significantly affected by altering the type of reward, the nucleus accumbens responds to the positive incentive properties of an expected reward depending on the specific type of the reward.

Work Stress and Altered Biomarkers: A Synthesis of Findings Based on the Effort-Reward Imbalance Model.

PubMed

Siegrist, Johannes; Li, Jian

2017-11-10

While epidemiological studies provide statistical evidence on associations of exposures such as stressful work with elevated risks of stress-related disorders (e.g., coronary heart disease or depression), additional information on biological pathways and biomarkers underlying these associations is required. In this contribution, we summarize the current state of the art on research findings linking stressful work, in terms of an established theoretical model-effort-reward imbalance-with a broad range of biomarkers. Based on structured electronic literature search and recent available systematic reviews, our synthesis of findings indicates that associations of work stress with heart rate variability, altered blood lipids, and risk of metabolic syndrome are rather consistent and robust. Significant relationships with blood pressure, heart rate, altered immune function and inflammation, cortisol release, and haemostatic biomarkers were also observed, but due to conflicting findings additional data will be needed to reach a firm conclusion. This narrative review of empirical evidence supports the argument that the biomarkers under study can act as mediators of epidemiologically established associations of work stress, as measured by effort-reward imbalance, with incident stress-related disorders.

Reward-based spatial learning in unmedicated adults with obsessive-compulsive disorder.

PubMed

Marsh, Rachel; Tau, Gregory Z; Wang, Zhishun; Huo, Yuankai; Liu, Ge; Hao, Xuejun; Packard, Mark G; Peterson, Bradley S; Simpson, H Blair

2015-04-01

The authors assessed the functioning of mesolimbic and striatal areas involved in reward-based spatial learning in unmedicated adults with obsessive-compulsive disorder (OCD). Functional MRI blood-oxygen-level-dependent response was compared in 33 unmedicated adults with OCD and 33 healthy, age-matched comparison subjects during a reward-based learning task that required learning to use extramaze cues to navigate a virtual eight-arm radial maze to find hidden rewards. The groups were compared in their patterns of brain activation associated with reward-based spatial learning versus a control condition in which rewards were unexpected because they were allotted pseudorandomly to experimentally prevent learning. Both groups learned to navigate the maze to find hidden rewards, but group differences in neural activity during navigation and reward processing were detected in mesolimbic and striatal areas. During navigation, the OCD group, unlike the healthy comparison group, exhibited activation in the left posterior hippocampus. Unlike healthy subjects, participants in the OCD group did not show activation in the left ventral putamen and amygdala when anticipating rewards or in the left hippocampus, amygdala, and ventral putamen when receiving unexpected rewards (control condition). Signal in these regions decreased relative to baseline during unexpected reward receipt among those in the OCD group, and the degree of activation was inversely associated with doubt/checking symptoms. Participants in the OCD group displayed abnormal recruitment of mesolimbic and ventral striatal circuitry during reward-based spatial learning. Whereas healthy comparison subjects exhibited activation in this circuitry in response to the violation of reward expectations, unmedicated OCD participants did not and instead over-relied on the posterior hippocampus during learning. Thus, dopaminergic innervation of reward circuitry may be altered, and future study of anterior/posterior hippocampal dysfunction in OCD is warranted.

Marijuana and cannabinoid regulation of brain reward circuits.

PubMed

Lupica, Carl R; Riegel, Arthur C; Hoffman, Alexander F

2004-09-01

The reward circuitry of the brain consists of neurons that synaptically connect a wide variety of nuclei. Of these brain regions, the ventral tegmental area (VTA) and the nucleus accumbens (NAc) play central roles in the processing of rewarding environmental stimuli and in drug addiction. The psychoactive properties of marijuana are mediated by the active constituent, Delta(9)-THC, interacting primarily with CB1 cannabinoid receptors in a large number of brain areas. However, it is the activation of these receptors located within the central brain reward circuits that is thought to play an important role in sustaining the self-administration of marijuana in humans, and in mediating the anxiolytic and pleasurable effects of the drug. Here we describe the cellular circuitry of the VTA and the NAc, define the sites within these areas at which cannabinoids alter synaptic processes, and discuss the relevance of these actions to the regulation of reinforcement and reward. In addition, we compare the effects of Delta(9)-THC with those of other commonly abused drugs on these reward circuits, and we discuss the roles that endogenous cannabinoids may play within these brain pathways, and their possible involvement in regulating ongoing brain function, independently of marijuana consumption. We conclude that, whereas Delta(9)-THC alters the activity of these central reward pathways in a manner that is consistent with other abused drugs, the cellular mechanism through which this occurs is likely different, relying upon the combined regulation of several afferent pathways to the VTA.

How humans integrate the prospects of pain and reward during choice

PubMed Central

Talmi, Deborah; Dayan, Peter; Kiebel, Stefan J.; Frith, Chris D.; Dolan, Raymond J.

2010-01-01

The maxim “no pain, no gain” summarises scenarios where an action leading to reward also entails a cost. Although we know a substantial amount about how the brain represents pain and reward separately, we know little about how they are integrated during goal directed behaviour. Two theoretical models might account for the integration of reward and pain. An additive model specifies that the disutility of costs is summed linearly with the utility of benefits, while an interactive model suggests that cost and benefit utilities interact so that the sensitivity to benefits is attenuated as costs become increasingly aversive. Using a novel task that required integration of physical pain and monetary reward, we examined the mechanism underlying cost-benefit integration in humans. We provide evidence in support of an interactive model in behavioural choice. Using functional neuroimaging we identify a neural signature for this interaction such that when the consequences of actions embody a mixture of reward and pain, there is an attenuation of a predictive reward-signal in both ventral anterior cingulate cortex and ventral striatum. We conclude that these regions subserve integration of action costs and benefits in humans, a finding that suggests a cross-species similarity in neural substrates that implement this function and illuminates mechanisms that underlie altered decision making under aversive conditions. PMID:19923294

Menthol Alone Upregulates Midbrain nAChRs, Alters nAChR Subtype Stoichiometry, Alters Dopamine Neuron Firing Frequency, and Prevents Nicotine Reward

PubMed Central

Henderson, Brandon J.; Wall, Teagan R.; Henley, Beverley M.; Kim, Charlene H.; Nichols, Weston A.; Moaddel, Ruin; Xiao, Cheng

2016-01-01

Upregulation of β2 subunit-containing (β2*) nicotinic acetylcholine receptors (nAChRs) is implicated in several aspects of nicotine addiction, and menthol cigarette smokers tend to upregulate β2* nAChRs more than nonmenthol cigarette smokers. We investigated the effect of long-term menthol alone on midbrain neurons containing nAChRs. In midbrain dopaminergic (DA) neurons from mice containing fluorescent nAChR subunits, menthol alone increased the number of α4 and α6 nAChR subunits, but this upregulation did not occur in midbrain GABAergic neurons. Thus, chronic menthol produces a cell-type-selective upregulation of α4* nAChRs, complementing that of chronic nicotine alone, which upregulates α4 subunit-containing (α4*) nAChRs in GABAergic but not DA neurons. In mouse brain slices and cultured midbrain neurons, menthol reduced DA neuron firing frequency and altered DA neuron excitability following nAChR activation. Furthermore, menthol exposure before nicotine abolished nicotine reward-related behavior in mice. In neuroblastoma cells transfected with fluorescent nAChR subunits, exposure to 500 nm menthol alone also increased nAChR number and favored the formation of (α4)3(β2)2 nAChRs; this contrasts with the action of nicotine itself, which favors (α4)2(β2)3 nAChRs. Menthol alone also increases the number of α6β2 receptors that exclude the β3 subunit. Thus, menthol stabilizes lower-sensitivity α4* and α6 subunit-containing nAChRs, possibly by acting as a chemical chaperone. The abolition of nicotine reward-related behavior may be mediated through menthol's ability to stabilize lower-sensitivity nAChRs and alter DA neuron excitability. We conclude that menthol is more than a tobacco flavorant: administered alone chronically, it alters midbrain DA neurons of the nicotine reward-related pathway. SIGNIFICANCE STATEMENT Menthol, the most popular flavorant for tobacco products, has been considered simply a benign flavor additive. However, as we show here, menthol alone exerts several neurobiological changes. We are among the first to show that menthol, by itself, increases the number of nicotinic acetylcholine receptors (nAChRs) in the mouse brain. It does so at a dose that matches nicotine in its ability to increase nAChR number. At this same dose, menthol also alters midbrain dopamine neuron function and prevents nicotine reward-related behavior. Together, our data show that menthol is more than an “inert” flavor additive and is able to change the function of midbrain dopamine neurons that are part of the mesolimbic reward pathway. PMID:26961950

Neuroimaging meta-analysis of cannabis use studies reveals convergent functional alterations in brain regions supporting cognitive control and reward processing.

PubMed

Yanes, Julio A; Riedel, Michael C; Ray, Kimberly L; Kirkland, Anna E; Bird, Ryan T; Boeving, Emily R; Reid, Meredith A; Gonzalez, Raul; Robinson, Jennifer L; Laird, Angela R; Sutherland, Matthew T

2018-03-01

Lagging behind rapid changes to state laws, societal views, and medical practice is the scientific investigation of cannabis's impact on the human brain. While several brain imaging studies have contributed important insight into neurobiological alterations linked with cannabis use, our understanding remains limited. Here, we sought to delineate those brain regions that consistently demonstrate functional alterations among cannabis users versus non-users across neuroimaging studies using the activation likelihood estimation meta-analysis framework. In ancillary analyses, we characterized task-related brain networks that co-activate with cannabis-affected regions using data archived in a large neuroimaging repository, and then determined which psychological processes may be disrupted via functional decoding techniques. When considering convergent alterations among users, decreased activation was observed in the anterior cingulate cortex, which co-activated with frontal, parietal, and limbic areas and was linked with cognitive control processes. Similarly, decreased activation was observed in the dorsolateral prefrontal cortex, which co-activated with frontal and occipital areas and linked with attention-related processes. Conversely, increased activation among users was observed in the striatum, which co-activated with frontal, parietal, and other limbic areas and linked with reward processing. These meta-analytic outcomes indicate that cannabis use is linked with differential, region-specific effects across the brain.

Food reward, hyperphagia, and obesity

PubMed Central

Lenard, Natalie R.; Shin, Andrew C.

2011-01-01

Given the unabated obesity problem, there is increasing appreciation of expressions like “my eyes are bigger than my stomach,” and recent studies in rodents and humans suggest that dysregulated brain reward pathways may be contributing not only to drug addiction but also to increased intake of palatable foods and ultimately obesity. After describing recent progress in revealing the neural pathways and mechanisms underlying food reward and the attribution of incentive salience by internal state signals, we analyze the potentially circular relationship between palatable food intake, hyperphagia, and obesity. Are there preexisting individual differences in reward functions at an early age, and could they be responsible for development of obesity later in life? Does repeated exposure to palatable foods set off a cascade of sensitization as in drug and alcohol addiction? Are reward functions altered by secondary effects of the obese state, such as increased signaling through inflammatory, oxidative, and mitochondrial stress pathways? Answering these questions will significantly impact prevention and treatment of obesity and its ensuing comorbidities as well as eating disorders and drug and alcohol addiction. PMID:21411768

Neuroimaging of the Dopamine/Reward System in Adolescent Drug Use

PubMed Central

Ernst, Monique; Luciana, Monica

2015-01-01

Adolescence is characterized by heightened risk-taking, including substance misuse. These behavioral patterns are influenced by ontogenic changes in neurotransmitter systems, particularly the dopamine system, which is fundamentally involved in the neural coding of reward and motivated approach behavior. During adolescence, this system evidences a peak in activity. At the same time, the dopamine system is neuroplastically altered by substance abuse, impacting subsequent function. Here, we describe properties of the dopamine system that change with typical adolescent development and that are altered with substance abuse. Much of this work has been gleaned from animal models due to limitations in measuring dopamine in pediatric samples. Structural and functional neuroimaging techniques have been used to examine structures that are heavily DA-innervated; they measure morphological and functional changes with age and with drug exposure. Presenting marijuana abuse as an exemplar, we consider recent findings that support an adolescent peak in DA-driven reward-seeking behavior and related deviations in motivational systems that are associated with marijuana abuse/dependence. Clinicians are advised that (1) chronic adolescent marijuana use may lead to deficiencies in incentive motivation, (2) that this state is due to marijuana’s interactions with the developing DA system, and (3) that treatment strategies should be directed to remediating resultant deficiencies in goal-directed activity. PMID:26095977

Hormonal contraceptives suppress oxytocin-induced brain reward responses to the partner's face.

PubMed

Scheele, Dirk; Plota, Jessica; Stoffel-Wagner, Birgit; Maier, Wolfgang; Hurlemann, René

2016-05-01

The hypothalamic peptide oxytocin (OXT) has been identified as a key modulator of pair-bonding in men, but its effects in women are still elusive. Moreover, there is substantial evidence that hormonal contraception (HC) influences partner preferences and sexual satisfaction, which constitute core domains of OXT function. We thus hypothesized that OXT effects on partner-related behavioral and neural responses could be significantly altered in women using HC. In this functional magnetic resonance imaging study involving 40 pair-bonded women, 21 of whom were using HC, we investigated whether a 24-IU nasal dose of OXT would modulate brain reward responses evoked by the romantic partner's face relative to the faces of familiar and unfamiliar people. Treatment with OXT increased the perceived attractiveness of the partner relative to other men, which was paralleled by elevated responses in reward-associated regions, including the nucleus accumbens. These effects of OXT were absent in women using HC. Our results confirm and extend previous findings in men that OXT interacts with the brain reward system to reinforce partner value representations, indicating a common OXT-dependent mechanism underlying partner attraction in both sexes. This mechanism may be disturbed in women using HC, suggesting that gonadal steroids could alter partner-specific OXT effects. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Amygdala Contributions to Stimulus-Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning.

PubMed

Rudebeck, Peter H; Ripple, Joshua A; Mitz, Andrew R; Averbeck, Bruno B; Murray, Elisabeth A

2017-02-22

Orbitofrontal cortex (OFC), medial frontal cortex (MFC), and amygdala mediate stimulus-reward learning, but the mechanisms through which they interact are unclear. Here, we investigated how neurons in macaque OFC and MFC signaled rewards and the stimuli that predicted them during learning with and without amygdala input. Macaques performed a task that required them to evaluate two stimuli and then choose one to receive the reward associated with that option. Four main findings emerged. First, amygdala lesions slowed the acquisition and use of stimulus-reward associations. Further analyses indicated that this impairment was due, at least in part, to ineffective use of negative feedback to guide subsequent decisions. Second, the activity of neurons in OFC and MFC rapidly evolved to encode the amount of reward associated with each stimulus. Third, amygdalectomy reduced encoding of stimulus-reward associations during the evaluation of different stimuli. Reward encoding of anticipated and received reward after choices were made was not altered. Fourth, amygdala lesions led to an increase in the proportion of neurons in MFC, but not OFC, that encoded the instrumental response that monkeys made on each trial. These correlated changes in behavior and neural activity after amygdala lesions strongly suggest that the amygdala contributes to the ability to learn stimulus-reward associations rapidly by shaping encoding within OFC and MFC. SIGNIFICANCE STATEMENT Altered functional interactions among orbital frontal cortex (OFC), medial frontal cortex (MFC), and amygdala are thought to underlie several psychiatric conditions, many related to reward learning. Here, we investigated the causal contribution of the amygdala to the development of neuronal activity in macaque OFC and MFC related to rewards and the stimuli that predict them during learning. Without amygdala inputs, neurons in both OFC and MFC showed decreased encoding of stimulus-reward associations. MFC also showed increased encoding of the instrumental responses that monkeys made on each trial. Behaviorally, changes in neural activity were accompanied by slower stimulus-reward learning. The findings suggest that interactions among amygdala, OFC, and MFC contribute to learning about stimuli that predict rewards. Copyright © 2017 the authors 0270-6474/17/372186-17$15.00/0.

Amygdala Contributions to Stimulus–Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning

PubMed Central

Averbeck, Bruno B.

2017-01-01

Orbitofrontal cortex (OFC), medial frontal cortex (MFC), and amygdala mediate stimulus–reward learning, but the mechanisms through which they interact are unclear. Here, we investigated how neurons in macaque OFC and MFC signaled rewards and the stimuli that predicted them during learning with and without amygdala input. Macaques performed a task that required them to evaluate two stimuli and then choose one to receive the reward associated with that option. Four main findings emerged. First, amygdala lesions slowed the acquisition and use of stimulus–reward associations. Further analyses indicated that this impairment was due, at least in part, to ineffective use of negative feedback to guide subsequent decisions. Second, the activity of neurons in OFC and MFC rapidly evolved to encode the amount of reward associated with each stimulus. Third, amygdalectomy reduced encoding of stimulus–reward associations during the evaluation of different stimuli. Reward encoding of anticipated and received reward after choices were made was not altered. Fourth, amygdala lesions led to an increase in the proportion of neurons in MFC, but not OFC, that encoded the instrumental response that monkeys made on each trial. These correlated changes in behavior and neural activity after amygdala lesions strongly suggest that the amygdala contributes to the ability to learn stimulus–reward associations rapidly by shaping encoding within OFC and MFC. SIGNIFICANCE STATEMENT Altered functional interactions among orbital frontal cortex (OFC), medial frontal cortex (MFC), and amygdala are thought to underlie several psychiatric conditions, many related to reward learning. Here, we investigated the causal contribution of the amygdala to the development of neuronal activity in macaque OFC and MFC related to rewards and the stimuli that predict them during learning. Without amygdala inputs, neurons in both OFC and MFC showed decreased encoding of stimulus–reward associations. MFC also showed increased encoding of the instrumental responses that monkeys made on each trial. Behaviorally, changes in neural activity were accompanied by slower stimulus–reward learning. The findings suggest that interactions among amygdala, OFC, and MFC contribute to learning about stimuli that predict rewards. PMID:28123082

Reduced cerebellar brain activity during reward processing in adolescent binge drinkers

PubMed Central

Cservenka, Anita; Jonesb, Scott A.; Nagel, Bonnie J.

2015-01-01

Due to ongoing development, adolescence may be a period of heightened vulnerability to the neurotoxic effects of alcohol. Binge drinking may alter reward-driven behavior and neurocircuitry, thereby increasing risk for escalating alcohol use. Therefore, we compared reward processing in adolescents with and without a history of recent binge drinking. At their baseline study visit, all participants (age = 14.86 ± 0.88) were free of heavy alcohol use and completed a modified version of the Wheel of Fortune (WOF) functional magnetic resonance imaging task. Following this visit, 17 youth reported binge drinking on ≥3 occasions within a 90 day period and were matched to 17 youth who remained alcohol and substance-naïve. All participants repeated the WOF task during a second visit (age = 16.83 ± 1.22). No significant effects were found in a region of interest analysis of the ventral striatum, but whole-brain analyses showed significant group differences in reward response at the second study visit in the left cerebellum, controlling for baseline visit brain activity (p/α<0.05), which was negatively correlated with mean number of drinks consumed/drinking day in the last 90 days. These findings suggest that binge drinking during adolescence may alter brain activity during reward processing in a dose-dependent manner. PMID:26190276

Reward Circuitry in Addiction.

PubMed

Cooper, Sarah; Robison, A J; Mazei-Robison, Michelle S

2017-07-01

Understanding the brain circuitry that underlies reward is critical to improve treatment for many common health issues, including obesity, depression, and addiction. Here we focus on insights into the organization and function of reward circuitry and its synaptic and structural adaptations in response to cocaine exposure. While the importance of certain circuits, such as the mesocorticolimbic dopamine pathway, are well established in drug reward, recent studies using genetics-based tools have revealed functional changes throughout the reward circuitry that contribute to different facets of addiction, such as relapse and craving. The ability to observe and manipulate neuronal activity within specific cell types and circuits has led to new insight into not only the basic connections between brain regions, but also the molecular changes within these specific microcircuits, such as neurotrophic factor and GTPase signaling or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor function, that underlie synaptic and structural plasticity evoked by drugs of abuse. Excitingly, these insights from preclinical rodent work are now being translated into the clinic, where transcranial magnetic simulation and deep brain stimulation therapies are being piloted in human cocaine dependence. Thus, this review seeks to summarize current understanding of the major brain regions implicated in drug-related behaviors and the molecular mechanisms that contribute to altered connectivity between these regions, with the postulation that increased knowledge of the plasticity within the drug reward circuit will lead to new and improved treatments for addiction.

Maternal interpersonal affiliation is associated with adolescents' brain structure and reward processing

PubMed Central

Schneider, S; Brassen, S; Bromberg, U; Banaschewski, T; Conrod, P; Flor, H; Gallinat, J; Garavan, Hugh; Heinz, A; Martinot, J-L; Nees, F; Rietschel, M; Smolka, M N; Ströhle, A; Struve, M; Schumann, G; Büchel, C

2012-01-01

Considerable animal and human research has been dedicated to the effects of parenting on structural brain development, focusing on hippocampal and prefrontal areas. Conversely, although functional imaging studies suggest that the neural reward circuitry is involved in parental affection, little is known about mothers' interpersonal qualities in relation to their children's brain structure and function. Moreover, gender differences concerning the effect of maternal qualities have rarely been investigated systematically. In 63 adolescents, we assessed structural and functional magnetic resonance imaging as well as interpersonal affiliation in their mothers. This allowed us to associate maternal affiliation with gray matter density and neural responses during different phases of the well-established Monetary Incentive Delay task. Maternal affiliation was positively associated with hippocampal and orbitofrontal gray matter density. Moreover, in the feedback of reward hit as compared with reward miss, an association with caudate activation was found. Although no significant gender effects were observed in these associations, during reward feedback as compared with baseline, maternal affiliation was significantly associated with ventral striatal and caudate activation only in females. Our findings demonstrate that maternal interpersonal affiliation is related to alterations in both the brain structure and reward-related activation in healthy adolescents. Importantly, the pattern is in line with typical findings in depression and post-traumatic stress disorder, suggesting that a lack of maternal affiliation might have a role in the genesis of mental disorders. PMID:23149446

Cannabinoid modulation of drug reward and the implications of marijuana legalization.

PubMed

Covey, Dan P; Wenzel, Jennifer M; Cheer, Joseph F

2015-12-02

Marijuana is the most popular illegal drug worldwide. Recent trends indicate that this may soon change; not due to decreased marijuana use, but to an amendment in marijuana's illegal status. The cannabinoid type 1 (CB1) receptor mediates marijuana's psychoactive and reinforcing properties. CB1 receptors are also part of the brain endocannabinoid (eCB) system and support numerous forms of learning and memory, including the conditioned reinforcing properties of cues predicting reward or punishment. This is accomplished via eCB-dependent alterations in mesolimbic dopamine function, which plays an obligatory role in reward learning and motivation. Presynaptic CB1 receptors control midbrain dopamine neuron activity and thereby shape phasic dopamine release in target regions, particularly the nucleus accumbens (NAc). By also regulating synaptic input to the NAc, CB1 receptors modulate NAc output onto downstream neurons of the basal ganglia motor circuit, and thereby support goal-directed behaviors. Abused drugs promote short- and long-term adaptations in eCB-regulation of mesolimbic dopamine function, and thereby hijack neural systems related to the pursuit of rewards to promote drug abuse. By pharmacologically targeting the CB1 receptors, marijuana has preferential access to this neuronal system and can potently alter eCB-dependent processing of reward-related stimuli. As marijuana legalization progresses, greater access to this drug should increase the utility of marijuana as a research tool to better understand the eCB system, which has the potential to advance cannabinoid-based treatments for drug addiction. Copyright © 2014 Elsevier B.V. All rights reserved.

Reward acts on the pFC to enhance distractor resistance of working memory representations.

PubMed

Fallon, Sean James; Cools, Roshan

2014-12-01

Working memory and reward processing are often thought to be separate, unrelated processes. However, most daily activities involve integrating these two types of information, and the two processes rarely, if ever, occur in isolation. Here, we show that working memory and reward interact in a task-dependent manner and that this task-dependent interaction involves modulation of the pFC by the ventral striatum. Specifically, BOLD signal during gains relative to losses in the ventral striatum and pFC was associated not only with enhanced distractor resistance but also with impairment in the ability to update working memory representations. Furthermore, the effect of reward on working memory was accompanied by differential coupling between the ventral striatum and ignore-related regions in the pFC. Together, these data demonstrate that reward-related signals modulate the balance between cognitive stability and cognitive flexibility by altering functional coupling between the ventral striatum and the pFC.

Reward Processing, Neuroeconomics, and Psychopathology.

PubMed

Zald, David H; Treadway, Michael T

2017-05-08

Abnormal reward processing is a prominent transdiagnostic feature of psychopathology. The present review provides a framework for considering the different aspects of reward processing and their assessment, and highlights recent insights from the field of neuroeconomics that may aid in understanding these processes. Although altered reward processing in psychopathology has often been treated as a general hypo- or hyperresponsivity to reward, increasing data indicate that a comprehensive understanding of reward dysfunction requires characterization within more specific reward-processing domains, including subjective valuation, discounting, hedonics, reward anticipation and facilitation, and reinforcement learning. As such, more nuanced models of the nature of these abnormalities are needed. We describe several processing abnormalities capable of producing the types of selective alterations in reward-related behavior observed in different forms of psychopathology, including (mal)adaptive scaling and anchoring, dysfunctional weighting of reward and cost variables, competition between valuation systems, and reward prediction error signaling.

Alterations of Brain Functional Architecture Associated with Psychopathic Traits in Male Adolescents with Conduct Disorder.

PubMed

Pu, Weidan; Luo, Qiang; Jiang, Yali; Gao, Yidian; Ming, Qingsen; Yao, Shuqiao

2017-09-12

Psychopathic traits of conduct disorder (CD) have a core callous-unemotional (CU) component and an impulsive-antisocial component. Previous task-driven fMRI studies have suggested that psychopathic traits are associated with dysfunction of several brain areas involved in different cognitive functions (e.g., empathy, reward, and response inhibition etc.), but the relationship between psychopathic traits and intrinsic brain functional architecture has not yet been explored in CD. Using a holistic brain-wide functional connectivity analysis, this study delineated the alterations in brain functional networks in patients with conduct disorder. Compared with matched healthy controls, we found decreased anti-synchronization between the fronto-parietal network (FPN) and default mode network (DMN), and increased intra-network synchronization within the frontothalamic-basal ganglia, right frontoparietal, and temporal/limbic/visual networks in CD patients. Correlation analysis showed that the weakened FPN-DMN interaction was associated with CU traits, while the heightened intra-network functional connectivity was related to impulsivity traits in CD patients. Our findings suggest that decoupling of cognitive control (FPN) with social understanding of others (DMN) is associated with the CU traits, and hyper-functions of the reward and motor inhibition systems elevate impulsiveness in CD.

A review of reward processing and motivational impairment in schizophrenia.

PubMed

Strauss, Gregory P; Waltz, James A; Gold, James M

2014-03-01

This article reviews and synthesizes research on reward processing in schizophrenia, which has begun to provide important insights into the cognitive and neural mechanisms associated with motivational impairments. Aberrant cortical-striatal interactions may be involved with multiple reward processing abnormalities, including: (1) dopamine-mediated basal ganglia systems that support reinforcement learning and the ability to predict cues that lead to rewarding outcomes; (2) orbitofrontal cortex-driven deficits in generating, updating, and maintaining value representations; (3) aberrant effort-value computations, which may be mediated by disrupted anterior cingulate cortex and midbrain dopamine functioning; and (4) altered activation of the prefrontal cortex, which is important for generating exploratory behaviors in environments where reward outcomes are uncertain. It will be important for psychosocial interventions targeting negative symptoms to account for abnormalities in each of these reward processes, which may also have important interactions; suggestions for novel behavioral intervention strategies that make use of external cues, reinforcers, and mobile technology are discussed.

Effects of alexithymia and empathy on the neural processing of social and monetary rewards.

PubMed

Goerlich, Katharina Sophia; Votinov, Mikhail; Lammertz, Sarah E; Winkler, Lina; Spreckelmeyer, Katja N; Habel, Ute; Gründer, Gerhard; Gossen, Anna

2017-07-01

Empathy has been found to affect the neural processing of social and monetary rewards. Alexithymia, a subclinical condition showing a close inverse relationship with empathy is linked to dysfunctions of socio-emotional processing in the brain. Whether alexithymia alters the neural processing of rewards, which is currently unknown. Here, we investigated the influence of both alexithymia and empathy on reward processing using a social incentive delay (SID) task and a monetary incentive delay (MID) task in 45 healthy men undergoing functional magnetic resonance imaging. Controlling for temperament-character dimensions and rejection sensitivity, the relationship of alexithymia and empathy with neural activity in several a priori regions of interest (ROIs) was examined by means of partial correlations, while participants anticipated and received social and monetary rewards. Results were considered significant if they survived Holm-Bonferroni correction for multiple comparisons. Alexithymia modulated neural activity in several ROIs of the emotion and reward network, both during the anticipation of social and monetary rewards and in response to the receipt of monetary rewards. In contrast, empathy did not affect reward anticipation and modulated ROI activity only in response to the receipt of social rewards. These results indicate a significant influence of alexithymia on the processing of social and monetary rewards in the healthy brain.

Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach

PubMed Central

Tschernegg, Melanie; Crone, Julia S.; Eigenberger, Tina; Schwartenbeck, Philipp; Fauth-Bühler, Mira; Lemènager, Tagrid; Mann, Karl; Thon, Natasha; Wurst, Friedrich M.; Kronbichler, Martin

2013-01-01

Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders. PMID:24098282

Distinct alterations in motor & reward seeking behavior are dependent on the gestational age of exposure to LPS-induced maternal immune activation.

PubMed

Straley, Megan E; Van Oeffelen, Wesley; Theze, Sarah; Sullivan, Aideen M; O'Mahony, Siobhain M; Cryan, John F; O'Keeffe, Gerard W

2017-07-01

The dopaminergic system is involved in motivation, reward and the associated motor activities. Mesodiencephalic dopaminergic neurons in the ventral tegmental area (VTA) regulate motivation and reward, whereas those in the substantia nigra (SN) are essential for motor control. Defective VTA dopaminergic transmission has been implicated in schizophrenia, drug addiction and depression whereas dopaminergic neurons in the SN are lost in Parkinson's disease. Maternal immune activation (MIA) leading to in utero inflammation has been proposed to be a risk factor for these disorders, yet it is unclear how this stimulus can lead to the diverse disturbances in dopaminergic-driven behaviors that emerge at different stages of life in affected offspring. Here we report that gestational age is a critical determinant of the subsequent alterations in dopaminergic-driven behavior in rat offspring exposed to lipopolysaccharide (LPS)-induced MIA. Behavioral analysis revealed that MIA on gestational day 16 but not gestational day 12 resulted in biphasic impairments in motor behavior. Specifically, motor impairments were evident in early life, which were resolved by adolescence, but subsequently re-emerged in adulthood. In contrast, reward seeking behaviors were altered in offspring exposed MIA on gestational day 12. These changes were not due to a loss of dopaminergic neurons per se in the postnatal period, suggesting that they reflect functional changes in dopaminergic systems. This highlights that gestational age may be a key determinant of how MIA leads to distinct alterations in dopaminergic-driven behavior across the lifespan of affected offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

Reward Processing, Neuroeconomics, and Psychopathology

PubMed Central

Zald, David H.; Treadway, Michael

2018-01-01

Abnormal reward processing is a prominent transdiagnostic feature of psychopathology. The present review provides a framework for considering the different aspects of reward processing and their assessment and highlight recent insights from the field of neuroeconomics that may aid in understanding these processes. Although altered reward processing in psychopathology has often been treated as a general hypo- or hyper-responsivity to reward, increasing data indicate that a comprehensive understanding of reward dysfunction requires characterization within more specific reward processing domains, including subjective valuation, discounting, hedonics, reward anticipation and facilitation, and reinforcement learning. As such, more nuanced models of the nature of these abnormalities are needed. We describe several processing abnormalities capable of producing the types of selective alterations in reward related behavior observed in different forms of psychopathology, including (mal)adaptive scaling and anchoring, dysfunctional weighting of reward and cost variables, completion between valuation systems, and positive prediction error signaling. PMID:28301764

The impact of junk foods on the adolescent brain.

PubMed

Reichelt, Amy C; Rank, Michelle M

2017-12-01

Adolescence is a significant period of physical, social, and emotional development, and is characterized by prominent neurobiological changes in the brain. The maturational processes that occur in brain regions responsible for cognitive control and reward seeking may underpin excessive consumption of palatable high fat and high sugar "junk" foods during adolescence. Recent studies have highlighted the negative impact of these foods on brain function, resulting in cognitive impairments and altered reward processing. The increased neuroplasticity during adolescence may render the brain vulnerable to the negative effects of these foods on cognition and behavior. In this review, we describe the mechanisms by which junk food diets influence neurodevelopment during adolescence. Diet can lead to alterations in dopamine-mediated reward signaling, and inhibitory neurotransmission controlled by γ-aminobutyric acid (GABA), two major neurotransmitter systems that are under construction across adolescence. We propose that poor dietary choices may derail the normal adolescent maturation process and influence neurodevelopmental trajectories, which can predispose individuals to dysregulated eating and impulsive behaviors. © 2017 Wiley Periodicals, Inc.

Work Stress and Altered Biomarkers: A Synthesis of Findings Based on the Effort–Reward Imbalance Model

PubMed Central

Siegrist, Johannes; Li, Jian

2017-01-01

While epidemiological studies provide statistical evidence on associations of exposures such as stressful work with elevated risks of stress-related disorders (e.g., coronary heart disease or depression), additional information on biological pathways and biomarkers underlying these associations is required. In this contribution, we summarize the current state of the art on research findings linking stressful work, in terms of an established theoretical model—effort-reward imbalance—with a broad range of biomarkers. Based on structured electronic literature search and recent available systematic reviews, our synthesis of findings indicates that associations of work stress with heart rate variability, altered blood lipids, and risk of metabolic syndrome are rather consistent and robust. Significant relationships with blood pressure, heart rate, altered immune function and inflammation, cortisol release, and haemostatic biomarkers were also observed, but due to conflicting findings additional data will be needed to reach a firm conclusion. This narrative review of empirical evidence supports the argument that the biomarkers under study can act as mediators of epidemiologically established associations of work stress, as measured by effort–reward imbalance, with incident stress-related disorders. PMID:29125555

The effects of AMPA receptor blockade in the prelimbic cortex on systemic and ventral tegmental area opiate reward sensitivity.

PubMed

De Jaeger, Xavier; Bishop, Stephanie F; Ahmad, Tasha; Lyons, Danika; Ng, Garye Ami; Laviolette, Steven R

2013-02-01

The medial prefrontal cortex (mPFC) is a key neural region involved in opiate-related reward memory processing. AMPA receptor transmission in the mPFC modulates opiate-related reward memory processing, and chronic opiate exposure is associated with alterations in intra-mPFC AMPA receptor function. The objectives of this study were to examine how pharmacological blockade of AMPA receptor transmission in the prelimbic (PLC) division of the mPFC may modulate opiate reward memory acquisition and whether opiate exposure state may modulate the functional role of intra-PLC AMPA receptor transmission during opiate reward learning. Using an unbiased conditioned place preference (CPP) procedure in rats, we performed discrete, bilateral intra-PLC microinfusions of the AMPA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione, prior to behavioral morphine CPP conditioning, using sub-reward threshold conditioning doses of either systemic (0.05 mg/kg; i.p.) or intra-ventral tegmental area (VTA) morphine (250 ng/0.5 μl). We show that, in both opiate-naïve and opiate-dependent states, intra-PLC blockade of AMPA receptor transmission, but not the infralimbic cortex, increases the behavioral reward magnitude of systemic or intra-VTA morphine. This effect is dependent on dopamine (DA)ergic signaling because pre-administration of cis-(Z)-flupenthixol-dihydrochloride (α-flu), a broad-spectrum dopamine receptor antagonist, blocked the morphine-reward potentiating effects of AMPA receptor blockade. These findings suggest a critical role for intra-PLC AMPA receptor transmission in the processing of opiate reward signaling. Furthermore, blockade of AMPA transmission specifically within the PLC is capable of switching opiate reward processing to a DA-dependent reward system, independently of previous opiate exposure history.

Feedback associated with expectation for larger-reward improves visuospatial working memory performances in children with ADHD.

PubMed

Hammer, Rubi; Tennekoon, Michael; Cooke, Gillian E; Gayda, Jessica; Stein, Mark A; Booth, James R

2015-08-01

We tested the interactive effect of feedback and reward on visuospatial working memory in children with ADHD. Seventeen boys with ADHD and 17 Normal Control (NC) boys underwent functional magnetic resonance imaging (fMRI) while performing four visuospatial 2-back tasks that required monitoring the spatial location of letters presented on a display. Tasks varied in reward size (large; small) and feedback availability (no-feedback; feedback). While the performance of NC boys was high in all conditions, boys with ADHD exhibited higher performance (similar to those of NC boys) only when they received feedback associated with large-reward. Performance pattern in both groups was mirrored by neural activity in an executive function neural network comprised of few distinct frontal brain regions. Specifically, neural activity in the left and right middle frontal gyri of boys with ADHD became normal-like only when feedback was available, mainly when feedback was associated with large-reward. When feedback was associated with small-reward, or when large-reward was expected but feedback was not available, boys with ADHD exhibited altered neural activity in the medial orbitofrontal cortex and anterior insula. This suggests that contextual support normalizes activity in executive brain regions in children with ADHD, which results in improved working memory. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Striatal response to reward anticipation: evidence for a systems-level intermediate phenotype for schizophrenia.

PubMed

Grimm, Oliver; Heinz, Andreas; Walter, Henrik; Kirsch, Peter; Erk, Susanne; Haddad, Leila; Plichta, Michael M; Romanczuk-Seiferth, Nina; Pöhland, Lydia; Mohnke, Sebastian; Mühleisen, Thomas W; Mattheisen, Manuel; Witt, Stephanie H; Schäfer, Axel; Cichon, Sven; Nöthen, Markus; Rietschel, Marcella; Tost, Heike; Meyer-Lindenberg, Andreas

2014-05-01

Attenuated ventral striatal response during reward anticipation is a core feature of schizophrenia that is seen in prodromal, drug-naive, and chronic schizophrenic patients. Schizophrenia is highly heritable, raising the possibility that this phenotype is related to the genetic risk for the disorder. To examine a large sample of healthy first-degree relatives of schizophrenic patients and compare their neural responses to reward anticipation with those of carefully matched controls without a family psychiatric history. To further support the utility of this phenotype, we studied its test-retest reliability, its potential brain structural contributions, and the effects of a protective missense variant in neuregulin 1 (NRG1) linked to schizophrenia by meta-analysis (ie, rs10503929). Examination of a well-established monetary reward anticipation paradigm during functional magnetic resonance imaging at a university hospital; voxel-based morphometry; test-retest reliability analysis of striatal activations in an independent sample of 25 healthy participants scanned twice with the same task; and imaging genetics analysis of the control group. A total of 54 healthy first-degree relatives of schizophrenic patients and 80 controls matched for demographic, psychological, clinical, and task performance characteristics were studied. Blood oxygen level-dependent response during reward anticipation, analysis of intraclass correlations of functional contrasts, and associations between striatal gray matter volume and NRG1 genotype. Compared with controls, healthy first-degree relatives showed a highly significant decrease in ventral striatal activation during reward anticipation (familywise error-corrected P < .03 for multiple comparisons across the whole brain). Supplemental analyses confirmed that the identified systems-level functional phenotype is reliable (with intraclass correlation coefficients of 0.59-0.73), independent of local gray matter volume (with no corresponding group differences and no correlation to function, and with all uncorrected P values >.05), and affected by the NRG1 genotype (higher striatal responses in controls with the protective rs10503929 C allele; familywise error-corrected P < .03 for ventral striatal response). Healthy first-degree relatives of schizophrenic patients show altered striatal activation during reward anticipation in a directionality and localization consistent with prior patient findings. This provides evidence for a functional neural system mechanism related to familial risk. The phenotype can be assessed reliably, is independent of alterations in striatal structure, and is influenced by a schizophrenia candidate gene variant in NRG1. These data encourage us to further investigate the genetic and molecular contributions to this phenotype.

Neuroendocrinology and brain imaging of reward in eating disorders: A possible key to the treatment of anorexia nervosa and bulimia nervosa.

PubMed

Monteleone, Alessio Maria; Castellini, Giovanni; Volpe, Umberto; Ricca, Valdo; Lelli, Lorenzo; Monteleone, Palmiero; Maj, Mario

2018-01-03

Anorexia nervosa and bulimia nervosa are severe eating disorders whose etiopathogenesis is still unknown. Clinical features suggest that eating disorders may develop as reward-dependent syndromes, since eating less food is perceived as rewarding in anorexia nervosa while consumption of large amounts of food during binge episodes in bulimia nervosa aims at reducing the patient's negative emotional states. Therefore, brain reward mechanisms have been a major focus of research in the attempt to contribute to the comprehension of the pathophysiology of these disorders. Structural brain imaging data provided the evidence that brain reward circuits may be altered in patients with anorexia or bulimia nervosa. Similarly, functional brain imaging studies exploring the activation of brain reward circuits by food stimuli as well as by stimuli recognized to be potentially rewarding for eating disordered patients, such as body image cues or stimuli related to food deprivation and physical hyperactivity, showed several dysfunctions in ED patients. Moreover, very recently, it has been demonstrated that some of the biochemical homeostatic modulators of eating behavior are also implicated in the regulation of food-related and non-food-related reward, representing a possible link between the aberrant behaviors of ED subjects and their hypothesized deranged reward processes. In particular, changes in leptin and ghrelin occur in patients with anorexia or bulimia nervosa and have been suggested to represent not only homeostatic adaptations to an altered energy balance but to contribute also to the acquisition and/or maintenance of persistent starvation, binge eating and physical hyperactivity, which are potentially rewarding for ED patients. On the basis of such findings new pathogenetic models of EDs have been proposed, and these models may provide new theoretical basis for the development of innovative treatment strategies, either psychological and pharmacological, with the aim to improve the outcomes of so severe disabling disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Disambiguating ventral striatum fMRI-related bold signal during reward prediction in schizophrenia

PubMed Central

Morris, R W; Vercammen, A; Lenroot, R; Moore, L; Langton, J M; Short, B; Kulkarni, J; Curtis, J; O'Donnell, M; Weickert, C S; Weickert, T W

2012-01-01

Reward detection, surprise detection and prediction-error signaling have all been proposed as roles for the ventral striatum (vStr). Previous neuroimaging studies of striatal function in schizophrenia have found attenuated neural responses to reward-related prediction errors; however, as prediction errors represent a discrepancy in mesolimbic neural activity between expected and actual events, it is critical to examine responses to both expected and unexpected rewards (URs) in conjunction with expected and UR omissions in order to clarify the nature of ventral striatal dysfunction in schizophrenia. In the present study, healthy adults and people with schizophrenia were tested with a reward-related prediction-error task during functional magnetic resonance imaging to determine whether schizophrenia is associated with altered neural responses in the vStr to rewards, surprise prediction errors or all three factors. In healthy adults, we found neural responses in the vStr were correlated more specifically with prediction errors than to surprising events or reward stimuli alone. People with schizophrenia did not display the normal differential activation between expected and URs, which was partially due to exaggerated ventral striatal responses to expected rewards (right vStr) but also included blunted responses to unexpected outcomes (left vStr). This finding shows that neural responses, which typically are elicited by surprise, can also occur to well-predicted events in schizophrenia and identifies aberrant activity in the vStr as a key node of dysfunction in the neural circuitry used to differentiate expected and unexpected feedback in schizophrenia. PMID:21709684

Reward Improves Cancellation and Restraint Inhibition Across Childhood and Adolescence

PubMed Central

Sinopoli, Katia J.; Schachar, Russell; Dennis, Maureen

2011-01-01

Inhibitory control allows for the regulation of thought and action, and interacts with motivational variables, such as reward, to modify behavior adaptively as environments change. We examined the effects of reward on two distinct forms of inhibitory control, cancellation and restraint. Typically developing children and adolescents completed two versions of the stop signal task (cancellation and restraint) under three reward conditions (neutral, low reward, and high reward), where rewards were earned for successful inhibitory control. Rewards improved both cancellation and restraint inhibition, with similar effects of reward on each form of inhibitory control. Rewards did not alter the speed of response execution in either task, suggesting that rewards specifically altered inhibition processes without influencing processes related to response execution. Adolescents were faster and less variable than children when executing and inhibiting their responses. There were similar developmental effects of reward on the speed of inhibitory control, but group differences were found in terms of accuracy of inhibition in the restraint task. These results clarify how reward modulates two different forms of regulatory behavior in children and adolescents. PMID:21744952

Taste Reward Circuitry Related Brain Structures Characterize Ill and Recovered Anorexia Nervosa and Bulimia Nervosa

PubMed Central

Frank, Guido K.; Shott, Megan E.; Hagman, Jennifer O.; Mittal, Vijay A.

2013-01-01

Objective The pathophysiology of the eating disorder anorexia nervosa remains obscure, but structural brain alterations could be functionally important biomarkers. Here we assessed taste pleasantness and reward sensitivity in relation to brain structure, which might be related to food avoidance commonly seen in eating disorders. Method We used structural magnetic resonance brain imaging to study gray and white matter volumes in individuals with restricting type currently ill (n = 19) or recovered-anorexia nervosa (n = 24), bulimia nervosa (n= 19) and healthy control women (n=24). Results All eating disorder groups showed increased gray matter volume of the medial orbitofrontal cortex (gyrus rectus). Manually tracing confirmed larger gyrus rectus volume, and predicted taste pleasantness across all groups. The analyses also indicated other morphological differences between diagnostic categories: Ill and recovered-anorexia nervosa had increased right, while bulimia nervosa had increased left antero-ventral insula gray matter volumes compared to controls. Furthermore, dorsal striatum volumes were reduced in recovered-anorexia and bulimia nervosa, and predicted sensitivity to reward in the eating disorder groups. The eating disorder groups also showed reduced white matter in right temporal and parietal areas when compared to healthy controls. Notably, the results held when controlling for a range of covariates (e.g., age, depression, anxiety, medications). Conclusion Brain structure in medial orbitofrontal cortex, insula and striatum is altered in eating disorders and suggests altered brain circuitry that has been associated with taste pleasantness and reward value. PMID:23680873

Mesolimbic recruitment by nondrug rewards in detoxified alcoholics: effort anticipation, reward anticipation, and reward delivery.

PubMed

Bjork, James M; Smith, Ashley R; Chen, Gang; Hommer, Daniel W

2012-09-01

Aberrant sensitivity of incentive neurocircuitry to nondrug rewards has been suggested as either a risk factor for or consequence of drug addiction. Using functional magnetic resonance imaging, we tested whether alcohol-dependent patients (ADP: n = 29) showed altered recruitment of ventral striatal (VS) incentive neurocircuitry compared to controls (n = 23) by: (1) cues to respond for monetary rewards, (2) post-response anticipation of rewards, or (3) delivery of rewards. Using an instrumental task with two-stage presentation of reward-predictive information, subjects saw cues signaling opportunities to win $0, $1, or $10 for responding to a target. Following this response, subjects were notified whether their success would be indicated by a lexical notification (“Hit?”) or by delivery of a monetary reward (“Win?”). After a variable interval, subjects then viewed the trial outcome. We found no significant group differences in voxelwise activation by task contrasts, or in signal change extracted from VS. Both ADP and controls showed significant VS and other limbic recruitment by pre-response reward anticipation. In addition, controls also showed VS recruitment by post-response reward-anticipation, and ADP had appreciable subthreshold VS activation. Both groups also showed similar mesolimbic responses to reward deliveries. Across all subjects, a questionnaire measure of “hot” impulsivity correlated with VS recruitment by post-response anticipation of low rewards and with VS recruitment by delivery of low rewards. These findings indicate that incentive-motivational processing of nondrug rewards is substantially maintained in recovering alcoholics, and that reward-elicited VS recruitment correlates more with individual differences in trait impulsivity irrespective of addiction.

Impaired Feedback Processing for Symbolic Reward in Individuals with Internet Game Overuse

PubMed Central

Kim, Jinhee; Kim, Hackjin; Kang, Eunjoo

2017-01-01

Reward processing, which plays a critical role in adaptive behavior, is impaired in addiction disorders, which are accompanied by functional abnormalities in brain reward circuits. Internet gaming disorder, like substance addiction, is thought to be associated with impaired reward processing, but little is known about how it affects learning, especially when feedback is conveyed by less-salient motivational events. Here, using both monetary (±500 KRW) and symbolic (Chinese characters “right” or “wrong”) rewards and penalties, we investigated whether behavioral performance and feedback-related neural responses are altered in Internet game overuse (IGO) group. Using functional MRI, brain responses for these two types of reward/penalty feedback were compared between young males with problems of IGO (IGOs, n = 18, mean age = 22.2 ± 2.0 years) and age-matched control subjects (Controls, n = 20, mean age = 21.2 ± 2.1) during a visuomotor association task where associations were learned between English letters and one of four responses. No group difference was found in adjustment of error responses following the penalty or in brain responses to penalty, for either monetary or symbolic penalties. The IGO individuals, however, were more likely to fail to choose the response previously reinforced by symbolic (but not monetary) reward. A whole brain two-way ANOVA analysis for reward revealed reduced activations in the IGO group in the rostral anterior cingulate cortex/ventromedial prefrontal cortex (vmPFC) in response to both reward types, suggesting impaired reward processing. However, the responses to reward in the inferior parietal region and medial orbitofrontal cortex/vmPFC were affected by the types of reward in the IGO group. Unlike the control group, in the IGO group the reward response was reduced only for symbolic reward, suggesting lower attentional and value processing specific to symbolic reward. Furthermore, the more severe the Internet gaming overuse symptoms in the IGO group, the greater the activations of the ventral striatum for monetary relative to symbolic reward. These findings suggest that IGO is associated with bias toward motivationally salient reward, which would lead to poor goal-directed behavior in everyday life. PMID:29051739

Ghrelin-Derived Peptides: A Link between Appetite/Reward, GH Axis, and Psychiatric Disorders?

PubMed Central

Labarthe, Alexandra; Fiquet, Oriane; Hassouna, Rim; Zizzari, Philippe; Lanfumey, Laurence; Ramoz, Nicolas; Grouselle, Dominique; Epelbaum, Jacques; Tolle, Virginie

2014-01-01

Psychiatric disorders are often associated with metabolic and hormonal alterations, including obesity, diabetes, metabolic syndrome as well as modifications in several biological rhythms including appetite, stress, sleep–wake cycles, and secretion of their corresponding endocrine regulators. Among the gastrointestinal hormones that regulate appetite and adapt the metabolism in response to nutritional, hedonic, and emotional dysfunctions, at the interface between endocrine, metabolic, and psychiatric disorders, ghrelin plays a unique role as the only one increasing appetite. The secretion of ghrelin is altered in several psychiatric disorders (anorexia, schizophrenia) as well as in metabolic disorders (obesity) and in animal models in response to emotional triggers (psychological stress …) but the relationship between these modifications and the physiopathology of psychiatric disorders remains unclear. Recently, a large literature showed that this key metabolic/endocrine regulator is involved in stress and reward-oriented behaviors and regulates anxiety and mood. In addition, preproghrelin is a complex prohormone but the roles of the other ghrelin-derived peptides, thought to act as functional ghrelin antagonists, are largely unknown. Altered ghrelin secretion and/or signaling in psychiatric diseases are thought to participate in altered appetite, hedonic response and reward. Whether this can contribute to the mechanism responsible for the development of the disease or can help to minimize some symptoms associated with these psychiatric disorders is discussed in the present review. We will thus describe (1) the biological actions of ghrelin and ghrelin-derived peptides on food and drugs reward, anxiety and depression, and the physiological consequences of ghrelin invalidation on these parameters, (2) how ghrelin and ghrelin-derived peptides are regulated in animal models of psychiatric diseases and in human psychiatric disorders in relation with the GH axis. PMID:25386163

Caloric primary rewards systematically alter time perception.

PubMed

Fung, Bowen J; Murawski, Carsten; Bode, Stefan

2017-11-01

Human time perception can be influenced by contextual factors, such as the presence of reward. Yet, the exact nature of the relationship between time perception and reward has not been conclusively characterized. We implemented a novel experimental paradigm to measure estimations of time across a range of suprasecond intervals, during the anticipation and after the consumption of fruit juice, a physiologically relevant primary reward. We show that average time estimations were systematically affected by the consumption of reward, but not by the anticipation of reward. Compared with baseline estimations of time, reward consumption was associated with subsequent overproductions of time, and this effect increased for larger magnitudes of reward. Additional experiments demonstrated that the effect of consumption did not extend to a secondary reward (money), a tasteless, noncaloric primary reward (water), or a sweet, noncaloric reward (aspartame). However, a tasteless caloric reward (maltodexrin) did induce overproductions of time, although this effect did not scale with reward magnitude. These results suggest that the consumption of caloric primary rewards can alter time perception, which may be a psychophysiological mechanism by which organisms regulate homeostatic balance. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Altered brain activation in a reversal learning task unmasks adaptive changes in cognitive control in writer's cramp.

PubMed

Zeuner, Kirsten E; Knutzen, Arne; Granert, Oliver; Sablowsky, Simone; Götz, Julia; Wolff, Stephan; Jansen, Olav; Dressler, Dirk; Schneider, Susanne A; Klein, Christine; Deuschl, Günther; van Eimeren, Thilo; Witt, Karsten

2016-01-01

Previous receptor binding studies suggest dopamine function is altered in the basal ganglia circuitry in task-specific dystonia, a condition characterized by contraction of agonist and antagonist muscles while performing specific tasks. Dopamine plays a role in reward-based learning. Using fMRI, this study compared 31 right-handed writer's cramp patients to 35 controls in reward-based learning of a probabilistic reversal-learning task. All subjects chose between two stimuli and indicated their response with their left or right index finger. One stimulus response was rewarded 80%, the other 20%. After contingencies reversal, the second stimulus response was rewarded in 80%. We further linked the DRD2/ANKK1-TaqIa polymorphism, which is associated with 30% reduction of the striatal dopamine receptor density with reward-based learning and assumed impaired reversal learning in A + subjects. Feedback learning in patients was normal. Blood-oxygen level dependent (BOLD) signal in controls increased with negative feedback in the insula, rostral cingulate cortex, middle frontal gyrus and parietal cortex (pFWE < 0.05). In comparison to controls, patients showed greater increase in BOLD activity following negative feedback in the dorsal anterior cingulate cortex (BA32). The genetic status was not correlated with the BOLD activity. The Brodmann area 32 (BA32) is part of the dorsal anterior cingulate cortex (dACC) that plays an important role in coordinating and integrating information to guide behavior and in reward-based learning. The dACC is connected with the basal ganglia-thalamo-loop modulated by dopaminergic signaling. This finding suggests disturbed integration of reinforcement history in decision making and implicate that the reward system might contribute to the pathogenesis in writer's cramp.

Mechanisms Underlying Motivational Deficits in Psychopathology: Similarities and Differences in Depression and Schizophrenia.

PubMed

Barch, Deanna M; Pagliaccio, David; Luking, Katherine

2016-01-01

Motivational and hedonic impairments are core aspects of a variety of types of psychopathology. These impairments cut across diagnostic categories and may be critical to understanding major aspects of the functional impairments accompanying psychopathology. Given the centrality of motivational and hedonic systems to psychopathology, the Research Domain Criteria (RDoC) initiative includes a "positive valence" systems domain that outlines a number of constructs that may be key to understanding the nature and mechanisms of motivational and hedonic impairments in psychopathology. These component constructs include initial responsiveness to reward, reward anticipation or expectancy, incentive or reinforcement learning, effort valuation, and action selection. Here, we review behavioral and neuroimaging studies providing evidence for impairments in these constructs in individuals with psychosis versus in individuals with depressive pathology. There are important differences in the nature of reward-related and hedonic deficits associated with psychosis versus depression that have major implications for our understanding of etiology and treatment development. In particular, the literature strongly suggests the presence of impairments in in-the-moment hedonics or "liking" in individuals with depressive pathology, particularly among those who experience anhedonia. Such deficits may propagate forward and contribute to impairments in other constructs that are dependent on hedonic responses, such as anticipation, learning, effort, and action selection. Such hedonic impairments could reflect alterations in dopamine and/or opioid signaling in the striatum related to depression or specifically to anhedonia in depressed populations. In contrast, the literature points to relatively intact in-the-moment hedonic processing in psychosis, but provides much evidence for impairments in other components involved in translating reward to action selection. Particularly, individuals with schizophrenia exhibit altered reward prediction and associated striatal and prefrontal activation, impaired reward learning, and impaired reward-modulated action selection.

Dopaminergic control of cognitive flexibility in humans and animals

PubMed Central

Klanker, Marianne; Feenstra, Matthijs; Denys, Damiaan

2013-01-01

Striatal dopamine (DA) is thought to code for learned associations between cues and reinforcers and to mediate approach behavior toward a reward. Less is known about the contribution of DA to cognitive flexibility—the ability to adapt behavior in response to changes in the environment. Altered reward processing and impairments in cognitive flexibility are observed in psychiatric disorders such as obsessive compulsive disorder (OCD). Patients with this disorder show a disruption of functioning in the frontostriatal circuit and alterations in DA signaling. In this review we summarize findings from animal and human studies that have investigated the involvement of striatal DA in cognitive flexibility. These findings may provide a better understanding of the role of dopaminergic dysfunction in cognitive inflexibility in psychiatric disorders, such as OCD. PMID:24204329

The basolateral amygdala in reward learning and addiction

PubMed Central

Wassum, Kate M.; Izquierdo, Alicia

2015-01-01

Sophisticated behavioral paradigms partnered with the emergence of increasingly selective techniques to target the basolateral amygdala (BLA) have resulted in an enhanced understanding of the role of this nucleus in learning and using reward information. Due to the wide variety of behavioral approaches many questions remain on the circumscribed role of BLA in appetitive behavior. In this review, we integrate conclusions of BLA function in reward-related behavior using traditional interference techniques (lesion, pharmacological inactivation) with those using newer methodological approaches in experimental animals that allow in vivo manipulation of cell type-specific populations and neural recordings. Secondly, from a review of appetitive behavioral tasks in rodents and monkeys and recent computational models of reward procurement, we derive evidence for BLA as a neural integrator of reward value, history, and cost parameters. Taken together, BLA codes specific and temporally dynamic outcome representations in a distributed network to orchestrate adaptive responses. We provide evidence that experiences with opiates and psychostimulants alter these outcome representations in BLA, resulting in long-term modified action. PMID:26341938

Executive function and decision-making in women with fibromyalgia.

PubMed

Verdejo-García, Antonio; López-Torrecillas, Francisca; Calandre, Elena Pita; Delgado-Rodríguez, Antonia; Bechara, Antoine

2009-02-01

Patients with fibromyalgia (FM) typically report cognitive problems, and they state that these deficits are disturbing in everyday life. Despite these substantial subjective complaints by FM patients, very few studies have addressed objectively the effect of such aversive states on neuropsychological performance. In this study we aimed to examine possible impairment of executive function and decision-making in a sample of 36 women diagnosed with FM and 36 healthy women matched in age, education, and socio-economic status. We contrasted performance of both groups on two measures of executive functioning: the Wisconsin Card Sorting Test (WCST), which assesses cognitive flexibility skills, and the Iowa Gambling Tasks (IGT; original and variant versions), which assess emotion-based decision-making. We also examined the relationship between executive function performance and pain experience, and between executive function and personality traits of novelty-seeking, harm avoidance, reward dependence, and persistence (measured by the Temperament and Character Inventory-Revised). Results showed that on the WCST, FM women showed poorer performance than healthy comparison women on the number of categories and non-perseverative errors, but not on perseverative errors. FM patients also showed altered learning curve in the original IGT (where reward is immediate and punishment is delayed), suggesting compromised emotion-based decision-making; but not in the variant IGT (where punishment is immediate but reward is delayed), suggesting hypersensitivity to reward. Personality variables were very mildly associated with cognitive performance in FM women.

Modulation of frontostriatal interaction aligns with reduced primary reward processing under serotonergic drugs.

PubMed

Abler, Birgit; Grön, Georg; Hartmann, Antonie; Metzger, Coraline; Walter, Martin

2012-01-25

Recently, functional interactions between anteroventral prefrontal cortex and nucleus accumbens (NAcc) have been shown to relate to behavior counteracting reward-desiring (Diekhof and Gruber, 2010). Downregulation of the reward system by serotonin has also been suggested as the mode of action accounting for unsatisfactory effects of serotonin reuptake inhibitors (SSRIs) such as insufficient alleviation or even increase of anhedonia, and loss of interest. However, understanding of the in vivo mechanisms of SSRI-related alteration of the human reward system is still incomplete. Using functional magnetic resonance imaging (fMRI) within a double-blind cross-over within-subjects study design and administering the SSRI paroxetine, the dopamine/norepinephrine reuptake inhibitor bupropione, and placebo for 7 d each, we investigated a group of 18 healthy male subjects. Under paroxetine, subjects showed significantly decreased activation of the bilateral NAcc during processing of primary rewards (erotic videos), but not under bupropion. Similar to the previous study, analysis of psychophysiological interactions revealed that this downregulation relied on negative interactions between left and right NAcc fMRI signals and the bilateral anteroventral prefrontal cortex that now were significantly enhanced under paroxetine and reduced under bupropion. Individual drug-dependent modulations of interacting brain regions were significantly associated with individual expressions of impulsivity as a personality trait. Our results corroborate and extend previous insights on interregional crosstalk from secondary to primary rewards and demonstrate parallels between active inhibitory control of and serotonergic effects on the dopaminergic reward system's activity.

Neural network alterations across eating disorders: a narrative review of fMRI studies.

PubMed

Steward, Trevor; Menchón, José M; Jiménez-Murcia, Susana; Soriano-Mas, Carles; Fernández-Aranda, Fernando

2017-10-17

Functional magnetic resonance imaging (fMRI) has provided insight on how neural abnormalities are related to the symptomatology of the eating disorders (EDs): anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). More specifically, an increasingly growing number of brain imaging studies has shed light on how functionally connected brain networks contribute not only to disturbed eating behavior, but also to transdiagnostic alterations in body/interoceptive perception, reward processing and executive functions. This narrative review aims to summarize recent advances in fMRI studies of patients with EDs by highlighting studies investigating network alterations that are shared across EDs. Findings on reward processing in both AN and BN patients point to the presence of altered sensitivity to salient food stimuli in striatal regions and to the possibility of hypothalamic inputs being overridden by top-down cognitive control regions. Additionally, innovative new lines of research suggest that increased activations in fronto-striatal circuits are strongly associated with the maintenance of restrictive eating habits in AN patients. Although significantly fewer studies have been carried out in patients with BN and BED, aberrant neural responses to both food cues and anticipated food receipt appear to occur in these populations. These altered responses, coupled with diminished recruitment of prefrontal cognitive control circuitry, are believed to contribute to the binge eating of palatable foods. Results from functional network connectivity studies are diverse, but findings tend to converge on indicating disrupted resting-state connectivity in executive networks, the default-mode network and the salience network across EDs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Neural response to reward anticipation in those with depression with and without panic disorder.

PubMed

Gorka, Stephanie M; Huggins, Ashley A; Fitzgerald, Daniel A; Nelson, Brady D; Phan, K Luan; Shankman, Stewart A

2014-08-01

One of the hallmark features of major depressive disorder (MDD) is reduced reward anticipation. There have been mixed findings in the literature as to whether reward anticipation deficits in MDD are related to diminished mesolimbic activation and/or enhanced dorsal anterior cingulate activation (dACC). One of the reasons for these mixed findings is that these studies have typically not addressed the role of comorbid anxiety, a class of disorders which frequently co-occur with depression and have a common neurobiology. The aim of the current study was to examine group differences in neural responses to reward anticipation in 40 adults with either: (1) current MDD with no lifetime diagnosis of an anxiety disorder (MDD-only), (2) current MDD with comorbid panic disorder (MDD-PD), or (3) no lifetime diagnosis of psychopathology. All participants completed a passive slot machine task during a functional magnetic resonance imaging (fMRI) scan. Analyses indicated that there were no group differences in activation of mesolimbic reward regions; however, the MDD-only group exhibited greater dACC activation during the anticipation of rewards compared with the healthy controls and the comorbid MDD-PD group (who did not differ from each other). The sample size was small which limits generalizability. These findings provide preliminary support for the role of hyperactive dACC functioning in reduced reward anticipation in MDD. They also indicate that comorbid anxiety may alter the association between MDD and neural responding to reward anticipation. Copyright © 2014 Elsevier B.V. All rights reserved.

REWARD/PUNISHMENT REVERSAL LEARNING IN OLDER SUICIDE ATTEMPTERS

PubMed Central

Dombrovski, Alexandre Y.; Clark, Luke; Siegle, Greg J.; Butters, Meryl A.; Ichikawa, Naho; Sahakian, Barbara; Szanto, Katalin

2011-01-01

Objective Suicide rates are very high in old age, and the contribution of cognitive risk factors remains poorly understood. Suicide may be viewed as an outcome of an altered decision process. We hypothesized that impairment in a component of affective decision-making – reward/punishment-based learning – is associated with attempted suicide in late-life depression. We expected that suicide attempters would discount past reward/punishment history, focusing excessively on the most recent rewards and punishments. Further, we hypothesized that this impairment could be dissociated from executive abilities such as forward planning. Method We assessed reward/punishment-based learning using the Probabilistic Reversal Learning task in 65 individuals aged 60 and older: suicide attempters, suicide ideators, non-suicidal depressed elderly, and non-depressed controls. We used a reinforcement learning computational model to decompose reward/punishment processing over time. The Stockings of Cambridge test served as a control measure of executive function. Results Suicide attempters but not suicide ideators showed impaired probabilistic reversal learning compared to both non-suicidal depressed elderly and to non-depressed controls, after controlling for effects of education, global cognitive function, and substance use. Model-based analyses revealed that suicide attempters discounted previous history to a higher degree, compared to controls, basing their choice largely on reward/punishment received on the last trial. Groups did not differ in their performance on the Stockings of Cambridge. Conclusions Older suicide attempters display impaired reward/punishment-based learning. We propose a hypothesis that older suicide attempters make overly present-focused decisions, ignoring past experiences. Modification of this ‘myopia for the past’ may have therapeutic potential. PMID:20231320

Neural Reward Processing Mediates the Relationship between Insomnia Symptoms and Depression in Adolescence.

PubMed

Casement, Melynda D; Keenan, Kate E; Hipwell, Alison E; Guyer, Amanda E; Forbes, Erika E

2016-02-01

Emerging evidence suggests that insomnia may disrupt reward-related brain function-a potentially important factor in the development of depressive disorder. Adolescence may be a period during which such disruption is especially problematic given the rise in the incidence of insomnia and ongoing development of neural systems that support reward processing. The present study uses longitudinal data to test the hypothesis that disruption of neural reward processing is a mechanism by which insomnia symptoms-including nocturnal insomnia symptoms (NIS) and nonrestorative sleep (NRS)-contribute to depressive symptoms in adolescent girls. Participants were 123 adolescent girls and their caregivers from an ongoing longitudinal study of precursors to depression across adolescent development. NIS and NRS were assessed annually from ages 9 to 13 years. Girls completed a monetary reward task during a functional MRI scan at age 16 years. Depressive symptoms were assessed at ages 16 and 17 years. Multivariable regression tested the prospective associations between NIS and NRS, neural response during reward anticipation, and the mean number of depressive symptoms (omitting sleep problems). NRS, but not NIS, during early adolescence was positively associated with late adolescent dorsal medial prefrontal cortex (dmPFC) response to reward anticipation and depressive symptoms. DMPFC response mediated the relationship between early adolescent NRS and late adolescent depressive symptoms. These results suggest that NRS may contribute to depression by disrupting reward processing via altered activity in a region of prefrontal cortex involved in affective control. The results also support the mechanistic differentiation of NIS and NRS. © 2016 Associated Professional Sleep Societies, LLC.

Role of contingency in striatal response to incentive in adolescents with anxiety.

PubMed

Benson, Brenda E; Guyer, Amanda E; Nelson, Eric E; Pine, Daniel S; Ernst, Monique

2015-03-01

This study examines the effect of contingency on reward function in anxiety. We define contingency as the aspect of a situation in which the outcome is determined by one's action-that is, when there is a direct link between one's action and the outcome of the action. Past findings in adolescents with anxiety or at risk for anxiety have revealed hypersensitive behavioral and neural responses to higher value rewards with correct performance. This hypersensitivity to highly valued (salient) actions suggests that the value of actions is determined not only by outcome magnitude, but also by the degree to which the outcome is contingent on correct performance. Thus, contingency and incentive value might each modulate reward responses in unique ways in anxiety. Using fMRI with a monetary reward task, striatal response to cue anticipation is compared in 18 clinically anxious and 20 healthy adolescents. This task manipulates orthogonally reward contingency and incentive value. Findings suggest that contingency modulates the neural response to incentive magnitude differently in the two groups. Specifically, during the contingent condition, right-striatal response tracks incentive value in anxious, but not healthy, adolescents. During the noncontingent condition, striatal response is bilaterally stronger to low than to high incentive in anxious adolescents, while healthy adolescents exhibit the expected opposite pattern. Both contingency and reward magnitude differentiate striatal activation in anxious versus healthy adolescents. These findings may reflect exaggerated concern about performance and/or alterations of striatal coding of reward value in anxious adolescents. Abnormalities in reward function in anxiety may have treatment implications.

Effects of selective serotonin reuptake inhibition on neural activity related to risky decisions and monetary rewards in healthy males.

PubMed

Macoveanu, Julian; Fisher, Patrick M; Haahr, Mette E; Frokjaer, Vibe G; Knudsen, Gitte M; Siebner, Hartwig R

2014-10-01

Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are commonly prescribed antidepressant drugs targeting the dysfunctional serotonin (5-HT) system, yet little is known about the functional effects of prolonged serotonin reuptake inhibition in healthy individuals. Here we used functional MRI (fMRI) to investigate how a three-week fluoxetine intervention influences neural activity related to risk taking and reward processing. Employing a double-blinded parallel-group design, 29 healthy young males were randomly assigned to receive 3 weeks of a daily dose of 40 mg fluoxetine or placebo. Participants underwent task-related fMRI prior to and after the three-week intervention while performing a card gambling task. The task required participants to choose between two decks of cards. Choices were associated with different risk levels and potential reward magnitudes. Relative to placebo, the SSRI intervention did not alter individual risk-choice preferences, but modified neural activity during decision-making and reward processing: During the choice phase, SSRI reduced the neural response to increasing risk in lateral orbitofrontal cortex, a key structure for value-based decision-making. During the outcome phase, a midbrain region showed an independent decrease in the responsiveness to rewarding outcomes. This midbrain cluster included the raphe nuclei from which serotonergic modulatory projections originate to both cortical and subcortical regions. The findings corroborate the involvement of the normally functioning 5HT-system in decision-making under risk and processing of monetary rewards. The data suggest that prolonged SSRI treatment might reduce emotional engagement by reducing the impact of risk during decision-making or the impact of reward during outcome evaluation. Copyright © 2014 Elsevier Inc. All rights reserved.

Neural correlates of reward processing in healthy siblings of patients with schizophrenia

PubMed Central

Hanssen, Esther; van der Velde, Jorien; Gromann, Paula M.; Shergill, Sukhi S.; de Haan, Lieuwe; Bruggeman, Richard; Krabbendam, Lydia; Aleman, André; van Atteveldt, Nienke

2015-01-01

Deficits in motivational behavior and psychotic symptoms often observed in schizophrenia (SZ) may be driven by dysfunctional reward processing (RP). RP can be divided in two different stages; reward anticipation and reward consumption. Aberrant processing during reward anticipation seems to be related to SZ. Studies in patients with SZ have found less activation in the ventral striatum (VS) during anticipation of reward, but these findings do not provide information on effect of the genetic load on reward processing. Therefore, this study investigated RP in healthy first-degree relatives of SZ patients. The sample consisted of 94 healthy siblings of SZ patients and 57 healthy controls. Participants completed a classic RP task, the Monetary Incentive Delay task, during functional magnetic resonance imaging (fMRI). As expected, there were no behavioral differences between groups. In contrast to our expectations, we found no differences in any of the anticipatory reward related brain areas (region of interest analyses). Whole-brain analyses did reveal group differences during both reward anticipation and reward consumption; during reward anticipation siblings showed less deactivation in the insula, posterior cingulate cortex (PCC) and medial frontal gyrus (MFG) than controls. During reward consumption siblings showed less deactivation in the PCC and the right MFG compared to controls and activation in contrast to deactivation in controls in the precuneus and the left MFG. Exclusively in siblings, MFG activity correlated positively with subclinical negative symptoms. These regions are typically associated with the default mode network (DMN), which normally shows decreases in activation during task-related cognitive processes. Thus, in contrast to prior literature in patients with SZ, the results do not point to altered brain activity in classical RP brain areas, such as the VS. However, the weaker deactivation found outside the reward-related network in siblings could indicate reduced task-related suppression (i.e., hyperactivation) of the DMN. The presence of DMN hyperactivation during reward anticipation and reward consumption might indicate that siblings of patients with SZ have a higher baseline level of DMN activation and possible abnormal network functioning. PMID:26441601

Altered intrinsic hippocmapus declarative memory network and its association with impulsivity in abstinent heroin dependent subjects.

PubMed

Zhai, Tian-Ye; Shao, Yong-Cong; Xie, Chun-Ming; Ye, En-Mao; Zou, Feng; Fu, Li-Ping; Li, Wen-Jun; Chen, Gang; Chen, Guang-Yu; Zhang, Zheng-Guo; Li, Shi-Jiang; Yang, Zheng

2014-10-01

Converging evidence suggests that addiction can be considered a disease of aberrant learning and memory with impulsive decision-making. In the past decades, numerous studies have demonstrated that drug addiction is involved in multiple memory systems such as classical conditioned drug memory, instrumental learning memory and the habitual learning memory. However, most of these studies have focused on the contributions of non-declarative memory, and declarative memory has largely been neglected in the research of addiction. Based on a recent finding that hippocampus, as a core functioning region of declarative memory, was proved biased the decision-making process based on past experiences by spreading associated reward values throughout memory. Our present study focused on the hippocampus. By utilizing seed-based network analysis on the resting-state functional MRI datasets with the seed hippocampus we tested how the intrinsic hippocampal memory network altered toward drug addiction, and examined how the functional connectivity strength within the altered hippocampal network correlated with behavioral index 'impulsivity'. Our results demonstrated that HD group showed enhanced coherence between hippocampus which represents declarative memory system and non-declarative reward-guided learning memory system, and also showed attenuated intrinsic functional link between hippocampus and top-down control system, compared to the CN group. This alteration was furthered found to have behavioral significance over the behavioral index 'impulsivity' measured with Barratt Impulsiveness Scale (BIS). These results provide insights into the mechanism of declarative memory underlying the impulsive behavior in drug addiction. Copyright © 2014 Elsevier B.V. All rights reserved.

Impaired flexible decision-making in Major Depressive Disorder.

PubMed

Cella, Matteo; Dymond, Simon; Cooper, Andy

2010-07-01

Depression is associated with dysfunctional affective states, neuropsychological impairment and altered sensitivity to reward and punishment. These impairments can influence complex decision-making in changing environments. The contingency shifting variant Iowa Gambling Task (IGT) was used to assess flexible decision-making performance in a group of medicated unipolar Major Depressive Disorder (MDD) patients (n=19) and a group of healthy control volunteers (n=20). The task comprised the standard IGT followed by a contingency-shift phase where decks progressively changed reward and punishment schedule. Patients with MDD showed impaired performance compared to controls during both the standard and the contingency-shift phases of the IGT. Analysis of the contingency-shift phase demonstrated that individuals with depression had difficulties perceiving when a previously bad contingency became good. The present findings have several limitations including small sample size, the possible confounding role of medication and absence of other neuropsychological tests (i.e., executive function). Depressed patients show impaired decision-making behaviour in static and dynamic environments. Altered sensitivity to reward and punishment is proposed as the mechanism responsible for the lack of advantageous choices and poor adjustment to a changing environment.

Common Alterations in Sensitivity to Type but Not Amount of Reward in ADHD and Autism Spectrum Disorders

ERIC Educational Resources Information Center

Demurie, Ellen; Roeyers, Herbert; Baeyens, Dieter; Sonuga-Barke, Edmund

2011-01-01

Background: Children with attention deficit/hyperactivity disorder (ADHD) display abnormalities in reward processing. Most reward studies have focused on the effects of material or monetary rewards. Studies with autism spectrum disorder (ASD) have focused on social rewards. In this study we compared the effects of amount and type of reward in…

Mesolimbic recruitment by nondrug rewards in detoxified alcoholics: effort anticipation, reward anticipation and reward delivery

PubMed Central

Bjork, James M.; Smith, Ashley R.; Chen, Gang; Hommer, Daniel W.

2011-01-01

Aberrant sensitivity of incentive neurocircuitry to nondrug rewards has been suggested as either a risk factor for or consequence of drug addiction. Using functional magnetic resonance imaging, we tested whether alcohol-dependent patients (ADP: n = 29) showed altered recruitment of ventral striatal (VS) incentive neurocircuitry compared to controls (n = 23) by: 1) cues to respond for monetary rewards, 2) post-response anticipation of rewards, or 3) delivery of rewards. Using an instrumental task with two-stage presentation of reward-predictive information, subjects saw cues signaling opportunities to win $0, $1, or $10 for responding to a target. Following this response, subjects were notified whether their success would be indicated by a lexical notification (“Hit?”) or by delivery of a monetary reward (“Win?”). After a variable interval, subjects then viewed the trial outcome. We found no significant group differences in voxelwise activation by task contrasts, or in signal change extracted from VS. Both ADP and controls showed significant VS and other limbic recruitment by pre-response reward anticipation. In addition, controls also showed VS recruitment by post-response reward-anticipation, and ADP had appreciable subthreshold VS activation. Both groups also showed similar mesolimbic responses to reward deliveries. Across all subjects, a questionnaire measure of “hot” impulsivity correlated with VS recruitment by post-response anticipation of low rewards and with VS recruitment by delivery of low rewards. These findings indicate that incentive-motivational processing of nondrug rewards is substantially maintained in recovering alcoholics, and that reward-elicited VS recruitment correlates more with individual differences in trait impulsivity irrespective of addiction. PMID:22281932

Adolescent cannabinoid exposure effects on natural reward seeking and learning in rats.

PubMed

Schoch, H; Huerta, M Y; Ruiz, C M; Farrell, M R; Jung, K M; Huang, J J; Campbell, R R; Piomelli, D; Mahler, S V

2018-01-01

Adolescence is characterized by endocannabinoid (ECB)-dependent refinement of neural circuits underlying emotion, learning, and motivation. As a result, adolescent cannabinoid receptor stimulation (ACRS) with phytocannabinoids or synthetic agonists like "Spice" cause robust and persistent changes in both behavior and circuit architecture in rodents, including in reward-related regions like medial prefrontal cortex and nucleus accumbens (NAc). Here, we examine persistent effects of ACRS with the cannabinoid receptor 1/2 specific agonist WIN55-212,2 (WIN; 1.2 mg/kg/day, postnatal day (PD) 30-43), on natural reward-seeking behaviors and ECB system function in adult male Long Evans rats (PD 60+). WIN ACRS increased palatable food intake, and altered attribution of incentive salience to food cues in a sign-/goal-tracking paradigm. ACRS also blunted hunger-induced sucrose intake, and resulted in increased anandamide and oleoylethanolamide levels in NAc after acute food restriction not seen in controls. ACRS did not affect food neophobia or locomotor response to a novel environment, but did increase preference for exploring a novel environment. These results demonstrate that ACRS causes long-term increases in natural reward-seeking behaviors and ECB system function that persist into adulthood, potentially increasing liability to excessive natural reward seeking later in life.

The alcoholic brain: neural bases of impaired reward-based decision-making in alcohol use disorders.

PubMed

Galandra, Caterina; Basso, Gianpaolo; Cappa, Stefano; Canessa, Nicola

2018-03-01

Neuroeconomics is providing insights into the neural bases of decision-making in normal and pathological conditions. In the neuropsychiatric domain, this discipline investigates how abnormal functioning of neural systems associated with reward processing and cognitive control promotes different disorders, and whether such evidence may inform treatments. This endeavor is crucial when studying different types of addiction, which share a core promoting mechanism in the imbalance between impulsive subcortical neural signals associated with immediate pleasurable outcomes and inhibitory signals mediated by a prefrontal reflective system. The resulting impairment in behavioral control represents a hallmark of alcohol use disorders (AUDs), a chronic relapsing disorder characterized by excessive alcohol consumption despite devastating consequences. This review aims to summarize available magnetic resonance imaging (MRI) evidence on reward-related decision-making alterations in AUDs, and to envision possible future research directions. We review functional MRI (fMRI) studies using tasks involving monetary rewards, as well as MRI studies relating decision-making parameters to neurostructural gray- or white-matter metrics. The available data suggest that excessive alcohol exposure affects neural signaling within brain networks underlying adaptive behavioral learning via the implementation of prediction errors. Namely, weaker ventromedial prefrontal cortex activity and altered connectivity between ventral striatum and dorsolateral prefrontal cortex likely underpin a shift from goal-directed to habitual actions which, in turn, might underpin compulsive alcohol consumption and relapsing episodes despite adverse consequences. Overall, these data highlight abnormal fronto-striatal connectivity as a candidate neurobiological marker of impaired choice in AUDs. Further studies are needed, however, to unveil its implications in the multiple facets of decision-making.

Long-term alterations in vulnerability to addiction to drugs of abuse and in brain gene expression after early life ethanol exposure.

PubMed

Barbier, Estelle; Pierrefiche, Olivier; Vaudry, David; Vaudry, Hubert; Daoust, Martine; Naassila, Mickaël

2008-12-01

Exposure to ethanol early in life can have long-lasting implications on brain function and drug of abuse response later in life. The present study investigated in rats, the long-term consequences of pre- and postnatal (early life) ethanol exposure on drug consumption/reward and the molecular targets potentially associated with these behavioral alterations. Since a relationship has been demonstrated between heightened drugs intake and susceptibility to drugs-induced locomotor activity/sensitization, anxiolysis, we tested these behavioral responses, depending on the drug, in control and early life ethanol-exposed animals. Our results show that progeny exposed to early life ethanol displayed increased consumption of ethanol solutions and increased sensitivity to cocaine rewarding effects assessed in the conditioned place preference test. Offspring exposed to ethanol were more sensitive to the anxiolytic effect of ethanol and the increased sensitivity could, at least in part, explain the alteration in the consumption of ethanol for its anxiolytic effects. In addition, the sensitivity to hypothermic effects of ethanol and ethanol metabolism were not altered by early life ethanol exposure. The sensitization to cocaine (20 mg/kg) and to amphetamine (1.2 mg/kg) was increased after early life ethanol exposure and, could partly explain, an increase in the rewarding properties of psychostimulants. Gene expression analysis revealed that expression of a large number of genes was altered in brain regions involved in the reinforcing effects of drugs of abuse. Dopaminergic receptors and transporter binding sites were also down-regulated in the striatum of ethanol-exposed offspring. Such long-term neurochemical alterations in transmitter systems and in the behavioral responses to ethanol and other drugs of abuse may confer an increased liability for addiction in exposed offspring.

Neural and personality correlates of individual differences related to the effects of acute tryptophan depletion on future reward evaluation.

PubMed

Demoto, Yoshihiko; Okada, Go; Okamoto, Yasumasa; Kunisato, Yoshihiko; Aoyama, Shiori; Onoda, Keiichi; Munakata, Ayumi; Nomura, Michio; Tanaka, Saori C; Schweighofer, Nicolas; Doya, Kenji; Yamawaki, Shigeto

2012-01-01

In general, humans tend to discount the value of delayed reward. An increase in the rate of discounting leads to an inability to select a delayed reward over a smaller immediate reward (reward-delay impulsivity). Although deficits in the serotonergic system are implicated in this reward-delay impulsivity, there is individual variation in response to serotonin depletion. The aim of the present study was to investigate whether the effects of serotonin depletion on the ability to evaluate future reward are affected by individual personality traits or brain activation. Personality traits were assessed using the NEO-Five Factor Inventory and Temperament and Character Inventory. The central serotonergic levels of 16 healthy volunteers were manipulated by dietary tryptophan depletion. Subjects performed a delayed reward choice task that required the continuous estimation of reward value during functional magnetic resonance imaging scanning. Discounting rates were increased in 9 participants, but were unchanged or decreased in 7 participants in response to tryptophan depletion. Participants whose discounting rate was increased by tryptophan depletion had significantly higher neuroticism and lower self-directedness. Furthermore, tryptophan depletion differentially affected the groups in terms of hemodynamic responses to the value of predicted future reward in the right insula. These results suggest that individuals who have high neuroticism and low self-directedness as personality traits are particularly vulnerable to the effect of low serotonin on future reward evaluation accompanied by altered brain activation patterns. Copyright © 2012 S. Karger AG, Basel.

Brain reward responses to food stimuli among female monozygotic twins discordant for BMI.

PubMed

Doornweerd, Stieneke; De Geus, Eco J; Barkhof, Frederik; Van Bloemendaal, Liselotte; Boomsma, Dorret I; Van Dongen, Jenny; Drent, Madeleine L; Willemsen, Gonneke; Veltman, Dick J; IJzerman, Richard G

2017-06-08

Obese individuals are characterized by altered brain reward responses to food. Despite the latest discovery of obesity-associated genes, the contribution of environmental and genetic factors to brain reward responsiveness to food remains largely unclear. Sixteen female monozygotic twin pairs with a mean BMI discordance of 3.96 ± 2.1 kg/m 2 were selected from the Netherlands Twin Register to undergo functional MRI scanning while watching high- and low-calorie food and non-food pictures and during the anticipation and receipt of chocolate milk. In addition, appetite ratings, eating behavior and food intake were assessed using visual analog scales, validated questionnaires and an ad libitum lunch. In the overall group, visual and taste stimuli elicited significant activation in regions of interest (ROIs) implicated in reward, i.e. amygdala, insula, striatum and orbitofrontal cortex. However, when comparing leaner and heavier co-twins no statistically significant differences in ROI-activations were observed after family wise error correction. Heavier versus leaner co-twins reported higher feelings of hunger (P = 0.02), cravings for sweet food (P = 0.04), body dissatisfaction (P < 0.05) and a trend towards more emotional eating (P = 0.1), whereas caloric intake was not significantly different between groups (P = 0.3). Our results suggest that inherited rather than environmental factors are largely responsible for the obesity-related altered brain responsiveness to food. Future studies should elucidate the genetic variants underlying the susceptibility to reward dysfunction and obesity. NCT02025595.

Self-reported impulsivity in Huntington's disease patients and relationship to executive dysfunction and reward responsiveness.

PubMed

Johnson, Patricia L; Potts, Geoffrey F; Sanchez-Ramos, Juan; Cimino, Cynthia R

2017-09-01

Few studies have directly investigated impulsivity in Huntington's disease (HD) despite known changes in dopaminergic and frontal functioning, changes that have been associated with impulsivity in other disorders and in the normal population. This study sought to further categorize impulsivity in HD through examining differences in self-reported impulsivity between community controls and HD patients, the relationship between executive dysfunction and impulsivity, and the relationship of a reward/punishment behavioral inhibition task in relation to these self-report measures. It was expected that HD patients would report higher impulsivity and executive dysfunction and that these measures would relate to a reward/punishment behavioral inhibition task. The Barratt Impulsivity Scale (BIS-11) and Behavioral Inhibition/Behavioral Activation Scale (BIS/BAS) were completed, and the Mini-Mental State Examination (MMSE) and a reward-based flanker task with punishing and rewarding conditions were administered to 22 HD patients and 14 control participants. HD patients reported higher trait impulsivity (BIS-11) and executive dysfunction (Frontal Systems Behavior Scale, FrSBE) but not increased impulsivity on the BIS/BAS relative to controls. Higher BIS-11 scores were related to increased self-reported executive dysfunction and the attention/working memory factor of the MMSE. On a reward/punishment behavioral inhibition task, BAS was uniquely related to increased accuracy on rewarding trials of the flanker task, but was not related to punishing trials in HD patients. The relationships found suggest that trait impulsivity is reported higher in HD and may not be driven by altered reward evaluation and the appetitive nature of stimuli but rather by increased executive dysfunction and lack of sensitivity to punishment. Impulsivity in HD may represent a combination of trait impulsivity, altered dopaminergic circuitry, and executive dysfunction. Understanding impulsivity in HD is important as it is related to increased risk to the patient and difficult behaviors for the caregiver, and sheds light on the disease process.

Impairments in learning by monetary rewards and alcohol-associated rewards in detoxified alcoholic patients.

PubMed

Jokisch, Daniel; Roser, Patrik; Juckel, Georg; Daum, Irene; Bellebaum, Christian

2014-07-01

Excessive alcohol consumption has been linked to structural and functional brain changes associated with cognitive, emotional, and behavioral impairments. It has been suggested that neural processing in the reward system is also affected by alcoholism. The present study aimed at further investigating reward-based associative learning and reversal learning in detoxified alcohol-dependent patients. Twenty-one detoxified alcohol-dependent patients and 26 healthy control subjects participated in a probabilistic learning task using monetary and alcohol-associated rewards as feedback stimuli indicating correct responses. Performance during acquisition and reversal learning in the different feedback conditions was analyzed. Alcohol-dependent patients and healthy control subjects showed an increase in learning performance over learning blocks during acquisition, with learning performance being significantly lower in alcohol-dependent patients. After changing the contingencies, alcohol-dependent patients exhibited impaired reversal learning and showed, in contrast to healthy controls, different learning curves for different types of rewards with no increase in performance for high monetary and alcohol-associated feedback. The present findings provide evidence that dysfunctional processing in the reward system in alcohol-dependent patients leads to alterations in reward-based learning resulting in a generally reduced performance. In addition, the results suggest that alcohol-dependent patients are, in particular, more impaired in changing an established behavior originally reinforced by high rewards. Copyright © 2014 by the Research Society on Alcoholism.

Mapping brain functional alterations in betel-quid chewers using resting-state fMRI and network analysis.

PubMed

Weng, Jun-Cheng; Chou, Yu-Syuan; Huang, Guo-Joe; Tyan, Yeu-Sheng; Ho, Ming-Chou

2018-04-01

The World Health Organization regards betel quid (BQ) as a human carcinogen, and DSM-IV and ICD-10 dependence symptoms may develop with its heavy use. BQ's possible effects of an enhanced reward system and disrupted inhibitory control may increase the likelihood of habitual substance use. The current study aimed to employ resting-state fMRI to examine the hypothesized enhanced reward system (e.g., the basal forebrain system) and disrupted inhibitory control (e.g., the prefrontal system) in BQ chewers. The current study recruited three groups of 48 male participants: 16 BQ chewers, 15 tobacco- and alcohol-user controls, and 17 healthy controls. We used functional connectivity (FC), mean fractional amplitude of low-frequency fluctuations (mfALFF), and mean regional homogeneity (mReHo) to evaluate functional alternations in BQ chewers. Graph theoretical analysis (GTA) and network-based statistical (NBS) analysis were also performed to identify the functional network differences among the three groups. Our hypothesis was partially supported: the enhanced reward system for the BQ chewers (e.g., habitual drug-seeking behavior) was supported; however, their inhibitory control was relatively preserved. In addition, we reported that the BQ chewers may have enhanced visuospatial processing and decreased local segregation. The current results (showing an enhanced reward system in the chewers) provided the clinicians with important insight for the future development of an effective abstinence treatment.

Perturbations in Effort-Related Decision-Making Driven by Acute Stress and Corticotropin-Releasing Factor.

PubMed

Bryce, Courtney A; Floresco, Stan B

2016-07-01

Acute stress activates numerous systems in a coordinated effort to promote homeostasis, and can exert differential effects on mnemonic and cognitive functions depending on a myriad of factors. Stress can alter different forms of cost/benefit decision-making, yet the mechanisms that drive these effects, remain unclear. In the present study, we probed how corticotropin-releasing factor (CRF) may contribute to stress-induced alterations in cost/benefit decision-making, using an task where well-trained rats chose between a low effort/low reward lever (LR; two pellets) and a high effort/high reward lever (HR; four pellets), with the effort requirement increasing over a session (2, 5, 10, and 20 presses). One-hour restraint stress markedly reduced preference for the HR option, but this effect was attenuated by infusions of the CRF antagonist, alpha-helical CRF. Conversely, central CRF infusion mimicked the effect of stress on decision-making, as well as increased decision latencies and reduced response vigor. CRF infusions did not alter preference for larger vs smaller rewards, but did reduce responding for food delivered on a progressive ratio, suggesting that these treatments may amplify perceived effort costs that may be required to obtain rewards. CRF infusions into the ventral tegmental area recapitulated the effect of central CRF treatment and restraint on choice behavior, suggesting that these effects may be mediated by perturbations in dopamine transmission. These findings highlight the involvement of CRF in regulating effort-related decisions and suggest that increased CRF activity may contribute to motivational impairments and abnormal decision-making associated with stress-related psychiatric disorders such as depression.

Perturbations in Effort-Related Decision-Making Driven by Acute Stress and Corticotropin-Releasing Factor

PubMed Central

Bryce, Courtney A; Floresco, Stan B

2016-01-01

Acute stress activates numerous systems in a coordinated effort to promote homeostasis, and can exert differential effects on mnemonic and cognitive functions depending on a myriad of factors. Stress can alter different forms of cost/benefit decision-making, yet the mechanisms that drive these effects, remain unclear. In the present study, we probed how corticotropin-releasing factor (CRF) may contribute to stress-induced alterations in cost/benefit decision-making, using an task where well-trained rats chose between a low effort/low reward lever (LR; two pellets) and a high effort/high reward lever (HR; four pellets), with the effort requirement increasing over a session (2, 5, 10, and 20 presses). One-hour restraint stress markedly reduced preference for the HR option, but this effect was attenuated by infusions of the CRF antagonist, alpha-helical CRF. Conversely, central CRF infusion mimicked the effect of stress on decision-making, as well as increased decision latencies and reduced response vigor. CRF infusions did not alter preference for larger vs smaller rewards, but did reduce responding for food delivered on a progressive ratio, suggesting that these treatments may amplify perceived effort costs that may be required to obtain rewards. CRF infusions into the ventral tegmental area recapitulated the effect of central CRF treatment and restraint on choice behavior, suggesting that these effects may be mediated by perturbations in dopamine transmission. These findings highlight the involvement of CRF in regulating effort-related decisions and suggest that increased CRF activity may contribute to motivational impairments and abnormal decision-making associated with stress-related psychiatric disorders such as depression. PMID:26830960

Dynamic risk control by human nucleus accumbens

PubMed Central

Lopez-Sosa, Fernando; Gonzalez-Rosa, Javier Jesus; Galarza, Ana; Avecillas, Josue; Pineda-Pardo, Jose Angel; Lopez-Ibor, Juan José; Reneses, Blanca; Barcia, Juan Antonio

2015-01-01

Real-world decisions about reward often involve a complex counterbalance of risk and value. Although the nucleus accumbens has been implicated in the underlying neural substrate, its criticality to human behaviour remains an open question, best addressed with interventional methodology that probes the behavioural consequences of focal neural modulation. Combining a psychometric index of risky decision-making with transient electrical modulation of the nucleus accumbens, here we reveal profound, highly dynamic alteration of the relation between probability of reward and choice during therapeutic deep brain stimulation in four patients with treatment-resistant psychiatric disease. Short-lived phasic electrical stimulation of the region of the nucleus accumbens dynamically altered risk behaviour, transiently shifting the psychometric function towards more risky decisions only for the duration of stimulation. A critical, on-line role of human nucleus accumbens in dynamic risk control is thereby established. PMID:26428667

Abnormal Temporal Difference Reward-Learning Signals in Major Depression

ERIC Educational Resources Information Center

Kumar, P.; Waiter, G.; Ahearn, T.; Milders, M.; Reid, I.; Steele, J. D.

2008-01-01

Anhedonia is a core symptom of major depressive disorder (MDD), long thought to be associated with reduced dopaminergic function. However, most antidepressants do not act directly on the dopamine system and all antidepressants have a delayed full therapeutic effect. Recently, it has been proposed that antidepressants fail to alter dopamine…

Behavioral and Electrophysiological Alterations for Reinforcement Learning in Manic and Euthymic Patients with Bipolar Disorder.

PubMed

Ryu, Vin; Ha, Ra Yeon; Lee, Su Jin; Ha, Kyooseob; Cho, Hyun-Sang

2017-03-01

Bipolar disorder is characterized by behavioral changes such as risk-taking and increasing goal-directed activities, which may result from altered reward processing. Patients with bipolar disorder show impaired reward learning in situations that require the integration of reinforced feedback over time. In this study, we examined the behavioral and electrophysiological characteristics of reward learning in manic and euthymic patients with bipolar disorder using a probabilistic reward task. Twenty-four manic and 20 euthymic patients with bipolar I disorder and 24 healthy control subjects performed the probabilistic reward task. We assessed response bias (RB) as a preference for the stimulus paired with the more frequent reward and feedback-related negativity (FRN) to correct identification of the rich stimulus. Both manic and euthymic patients showed significantly lower RB scores in the early learning stage (block 1) in comparison with the late learning stage (block 2 or block 3) of the task, as well as significantly lower RB scores in the early stage compared to healthy subjects. Relatively more negative FRN amplitude is elicited by no presentation of an expected reward, compared to that elicited by presentation of expected feedback. The FRN became significantly more negative from the early (block 1) to the later stages (blocks 2 and 3) in both manic and euthymic patients, but not in healthy subjects. Changes in RB scores and FRN amplitudes between blocks 2 and 3 and block 1 correlated positively in healthy controls, but correlated negatively in manic and euthymic patients. The severity of manic symptoms correlated positively with reward learning scores and negatively with the FRN. These findings suggest that patients with bipolar disorder during euthymic or manic states have behavioral and electrophysiological alterations in reward learning compared to healthy subjects. This dysfunctional reward processing may be related to the abnormal decision-making or altered goal-directed activities frequently seen in patients with bipolar disorder. © 2017 John Wiley & Sons Ltd.

Continuous, but not intermittent, antipsychotic drug delivery intensifies the pursuit of reward cues.

PubMed

Bédard, Anne-Marie; Maheux, Jérôme; Lévesque, Daniel; Samaha, Anne-Noël

2011-05-01

Chronic exposure to antipsychotic medications can persistently change brain dopamine systems. Most studies on the functional significance of these neural changes have focused on motor behavior and few have addressed how long-term antipsychotic treatment might influence dopamine-mediated reward function. We asked, therefore, whether a clinically relevant antipsychotic treatment regimen would alter the incentive motivational properties of a reward cue. We assessed the ability of a Pavlovian-conditioned stimulus to function as a conditioned reward, as well as to elicit approach behavior in rats treated with haloperidol, either continuously (achieved via subcutaneous osmotic minipump) or intermittently (achieved via daily subcutaneous injections). Continuous, but not intermittent, treatment enhanced the ability of amphetamine to potentiate the conditioned reinforcing effects of a cue associated with water. This effect was not related to differences in the ability to attribute predictive value to a conditioned stimulus (as measured by conditioned approach behavior), but was potentially linked to the development of behavioral supersensitivity to amphetamine and to augmented amphetamine-induced immediate early-gene expression (c-fos and Nur77) in dorsal striatopallidal and striatonigral cells. By enhancing the ability of reward cues to control behavior and by intensifying dopamine-mediated striatopallidal and striatonigral cell activity, standard (ie, continuous) antipsychotic treatment regimens might exacerbate drug-seeking and drug-taking behavior in schizophrenia. Achieving regular but transiently high antipsychotic levels in the brain (as modeled in the intermittent condition) might be a viable option to prevent these changes. This possibility should be explored in the clinic.

Effects of dopamine D1 receptor blockade in the prelimbic prefrontal cortex or lateral dorsal striatum on frontostriatal function in Wistar and Spontaneously Hypertensive Rats.

PubMed

Gauthier, Jamie M; Tassin, David H; Dwoskin, Linda P; Kantak, Kathleen M

2014-07-15

Attention Deficit Hyperactivity Disorder (ADHD) is associated with dysfunctional prefrontal and striatal circuitry and dysregulated dopamine neurotransmission. Spontaneously Hypertensive Rats (SHR), a heuristically useful animal model of ADHD, were evaluated against normotensive Wistar (WIS) controls to determine whether dopamine D1 receptor blockade of either prelimbic prefrontal cortex (plPFC) or lateral dorsal striatum (lDST) altered learning functions of both interconnected sites. A strategy set shifting task measured plPFC function (behavioral flexibility/executive function) and a reward devaluation task measured lDST function (habitual responding). Prior to tests, rats received bilateral infusions of SCH 23390 (1.0 μg/side) or vehicle into plPFC or lDST. Following vehicle, SHR exhibited longer lever press reaction times, more trial omissions, and fewer completed trials during the set shift test compared to WIS, indicating slower decision-making and attentional/motivational impairment in SHR. After reward devaluation, vehicle-treated SHR responded less than WIS, indicating relatively less habitual responding in SHR. After SCH 23390 infusions into plPFC, WIS expressed the same behavioral phenotype as vehicle-treated SHR during set shift and reward devaluation tests. In SHR, SCH 23390 infusions into plPFC exacerbated behavioral deficits in the set shift test and maintained the lower rate of responding in the reward devaluation test. SCH 23390 infusions into lDST did not modify set shifting in either strain, but produced lower rates of responding than vehicle infusions after reward devaluation in WIS. This research provides pharmacological evidence for unidirectional interactions between prefrontal and striatal brain regions, which has implications for the neurological basis of ADHD and its treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Obesity is marked by distinct functional connectivity in brain networks involved in food reward and salience.

PubMed

Wijngaarden, M A; Veer, I M; Rombouts, S A R B; van Buchem, M A; Willems van Dijk, K; Pijl, H; van der Grond, J

2015-01-01

We hypothesized that brain circuits involved in reward and salience respond differently to fasting in obese versus lean individuals. We compared functional connectivity networks related to food reward and saliency after an overnight fast (baseline) and after a prolonged fast of 48 h in lean versus obese subjects. We included 13 obese (2 males, 11 females, BMI 35.4 ± 1.2 kg/m(2), age 31 ± 3 years) and 11 lean subjects (2 males, 9 females, BMI 23.2 ± 0.5 kg/m(2), age 28 ± 3 years). Resting-state functional magnetic resonance imaging scans were made after an overnight fast (baseline) and after a prolonged 48 h fast. Functional connectivity of the amygdala, hypothalamus and posterior cingulate cortex (default-mode) networks was assessed using seed-based correlations. At baseline, we found a stronger connectivity between hypothalamus and left insula in the obese subjects. This effect diminished upon the prolonged fast. After prolonged fasting, connectivity of the hypothalamus with the dorsal anterior cingulate cortex (dACC) increased in lean subjects and decreased in obese subjects. Amygdala connectivity with the ventromedial prefrontal cortex was stronger in lean subjects at baseline, which did not change upon the prolonged fast. No differences in posterior cingulate cortex connectivity were observed. In conclusion, obesity is marked by alterations in functional connectivity networks involved in food reward and salience. Prolonged fasting differentially affected hypothalamic connections with the dACC and the insula between obese and lean subjects. Our data support the idea that food reward and nutrient deprivation are differently perceived and/or processed in obesity. Copyright © 2015 Elsevier B.V. All rights reserved.

Morphine and MK-801 administration leads to alternative NMDAR1 splicing and associated changes in reward seeking behavior and nociception on an operant orofacial assay

PubMed Central

Anderson, Ethan M.; Del Valle-Pinero, Arseima Y.; Suckow, Shelby K.; Nolan, Todd A.; Neubert, John K.; Caudle, Robert M.

2012-01-01

The NMDA receptor plays a large role in opioid-induced plastic changes in the nervous system. The expression levels of its NR1 subunit are altered dramatically by morphine but no changes in its alternative splicing have been reported. Changes in the splicing of the N1, C1, C2, and C2’ cassettes can alter the pharmacology and regulation of this receptor. Western blots run on brain tissue from rats made tolerant to morphine revealed altered splicing of the N1 cassettes in the accumbens and amygdala, and the C1 cassette in the amygdala and the dorsal hippocampus. After three days of withdrawal C2’-containing NR1 subunits were down-regulated in each of these areas. These were not due to acute doses of morphine and may represent long term alterations in drug-induced neuroplasticity. We also examined the effects of morphine tolerance on an operant orofacial nociception assay which forces an animal to endure an aversive heat stimulus in order to receive a sweet milk reward. Morphine decreased pain sensitivity as expected but also increased motivational reward seeking in this task. NMDAR antagonism potentiated this reward seeking behavior suggesting that instead of attenuating tolerance, MK-801 may actually alter the rewarding and/or motivational properties of morphine. When combined, MK-801 and morphine had an additive effect which led to altered splicing in the accumbens, amygdala, and the dorsal hippocampus. In conclusion, NR1 splicing may play a major role in the cognitive behavioral aspects especially in motivational reward seeking behaviors. PMID:22531378

Robust changes in reward circuitry during reward loss in current and former cocaine users during performance of a monetary incentive delay task.

PubMed

Patel, Krishna T; Stevens, Michael C; Meda, Shashwath A; Muska, Christine; Thomas, Andre D; Potenza, Marc N; Pearlson, Godfrey D

2013-10-01

Abnormal function in reward circuitry in cocaine addiction could predate drug use as a risk factor, follow drug use as a consequence of substance-induced alterations, or both. We used a functional magnetic resonance imaging monetary incentive delay task (MIDT) to investigate reward-loss neural response differences among 42 current cocaine users, 35 former cocaine users, and 47 healthy subjects who also completed psychological measures and tasks related to impulsivity and reward. We found various reward processing-related group differences in several MIDT phases. Across task phases we found a control > current user > former user activation pattern, except for loss outcome, where former compared with current cocaine users activated ventral tegmental area more robustly. We also found regional prefrontal activation differences during loss anticipation between cocaine-using groups. Both groups of cocaine users scored higher than control subjects on impulsivity, compulsivity and reward-punishment sensitivity factors. In addition, impulsivity-related factors correlated positively with activation in amygdala and negatively with anterior cingulate activation during loss anticipation. Compared with healthy subjects, both former and current users displayed abnormal brain activation patterns during MIDT performance. Both cocaine groups differed similarly from healthy subjects, but differences between former and current users were localized to the ventral tegmental area during loss outcome and to prefrontal regions during loss anticipation, suggesting that long-term cocaine abstinence does not normalize most reward circuit abnormalities. Elevated impulsivity-related factors that relate to loss processing in current and former users suggest that these tendencies and relationships may pre-exist cocaine addiction. © 2013 Society of Biological Psychiatry.

Menthol Enhances Nicotine Reward-Related Behavior by Potentiating Nicotine-Induced Changes in nAChR Function, nAChR Upregulation, and DA Neuron Excitability.

PubMed

Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; McKinney, Sheri; Lester, Henry A

2017-11-01

Understanding why the quit rate among smokers of menthol cigarettes is lower than non-menthol smokers requires identifying the neurons that are altered by nicotine, menthol, and acetylcholine. Dopaminergic (DA) neurons in the ventral tegmental area (VTA) mediate the positive reinforcing effects of nicotine. Using mouse models, we show that menthol enhances nicotine-induced changes in nicotinic acetylcholine receptors (nAChRs) expressed on midbrain DA neurons. Menthol plus nicotine upregulates nAChR number and function on midbrain DA neurons more than nicotine alone. Menthol also enhances nicotine-induced changes in DA neuron excitability. In a conditioned place preference (CPP) assay, we observed that menthol plus nicotine produces greater reward-related behavior than nicotine alone. Our results connect changes in midbrain DA neurons to menthol-induced enhancements of nicotine reward-related behavior and may help explain how smokers of menthol cigarettes exhibit reduced cessation rates.

Menthol Enhances Nicotine Reward-Related Behavior by Potentiating Nicotine-Induced Changes in nAChR Function, nAChR Upregulation, and DA Neuron Excitability

PubMed Central

Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; McKinney, Sheri; Lester, Henry A

2017-01-01

Understanding why the quit rate among smokers of menthol cigarettes is lower than non-menthol smokers requires identifying the neurons that are altered by nicotine, menthol, and acetylcholine. Dopaminergic (DA) neurons in the ventral tegmental area (VTA) mediate the positive reinforcing effects of nicotine. Using mouse models, we show that menthol enhances nicotine-induced changes in nicotinic acetylcholine receptors (nAChRs) expressed on midbrain DA neurons. Menthol plus nicotine upregulates nAChR number and function on midbrain DA neurons more than nicotine alone. Menthol also enhances nicotine-induced changes in DA neuron excitability. In a conditioned place preference (CPP) assay, we observed that menthol plus nicotine produces greater reward-related behavior than nicotine alone. Our results connect changes in midbrain DA neurons to menthol-induced enhancements of nicotine reward-related behavior and may help explain how smokers of menthol cigarettes exhibit reduced cessation rates. PMID:28401925

New developments in brain research of internet and gaming disorder.

PubMed

Weinstein, Aviv; Livny, Abigail; Weizman, Abraham

2017-04-01

There is evidence that the neural mechanisms underlying Internet Gaming Disorder (IGD) resemble those of drug addiction. Functional Magnetic Resonance Imaging (fMRI) studies of the resting state and measures of gray matter volume have shown that Internet game playing was associated with changes to brain regions responsible for attention and control, impulse control, motor function, emotional regulation, sensory-motor coordination. Furthermore, Internet game playing was associated with lower white matter density in brain regions that are involved in decision-making, behavioral inhibition and emotional regulation. Videogame playing involved changes in reward inhibitory mechanisms and loss of control. Structural brain imaging studies showed alterations in the volume of the ventral striatum that is an important part of the brain's reward mechanisms. Finally, videogame playing was associated with dopamine release similar in magnitude to those of drugs of abuse and lower dopamine transporter and dopamine receptor D 2 occupancy indicating sub-sensitivity of dopamine reward mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rationale and design of REWARD (revving-up exercise for sustained weight loss by altering neurological reward and drive): a randomized trial in obese endometrial cancer survivors.

PubMed

Nock, Nora L; Dimitropoulos, Anastasia; Rao, Stephen M; Flask, Chris A; Schluchter, Mark; Zanotti, Kristine M; Rose, Peter G; Kirwan, John P; Alberts, Jay

2014-11-01

Obesity is a leading risk factor for endometrial cancer (EC), particularly Type I forms, which are increasing in the U.S. Although death rates from most cancers have been decreasing, overall mortality in EC is increasing in the U.S. EC survivors' poor fitness combined with their surgical treatments may make weight loss particularly challenging. High intensity exercise increases neurotrophins and neurological reward via altered striatal dopamine in animals, and, in humans, chronic high intensity exercise enhances meal-induced satiety and may reduce hedonic eating. "Assisted" exercise, a mode of exercise whereby a patient's voluntary exercise rate is augmented mechanically, may modulate brain dopamine levels in Parkinson's Disease patients but has not been previously evaluated as a treatment for obesity. We describe the rationale and design of the REWARD trial, which has the overarching goal of randomizing 120 obese EC survivors to "assisted" or voluntary rate cycling to evaluate the efficacy of "assisted" exercise in enhancing and sustaining weight loss. Patients in both arms will receive 3 days/week of supervised exercise and 1 day/week of a group dietary behavioral intervention for 16 weeks and, then, will be followed for 6 months. The primary outcome is weight loss. Secondary outcomes include measures for body composition, fitness, eating behavior, exercise motivation and, quality of life as well as cognition and food reward and motivation as assessed by functional magnetic resonance imaging (fMRI) tasks. If successful, the REWARD program could be extended to help sustain weight loss in obese cancer and non-cancer patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Ventral striatum dysfunction in children and adolescents with reactive attachment disorder: functional MRI study

PubMed Central

Takiguchi, Shinichiro; Fujisawa, Takashi X.; Mizushima, Sakae; Saito, Daisuke N.; Okamoto, Yuko; Shimada, Koji; Koizumi, Michiko; Kumazaki, Hirokazu; Jung, Minyoung; Kosaka, Hirotaka; Hiratani, Michio; Ohshima, Yusei; Teicher, Martin H.

2015-01-01

Background Child maltreatment is a major risk factor for psychopathology, including reactive attachment disorder (RAD). Aims To examine whether neural activity during reward processing was altered in children and adolescents with RAD. Method Sixteen children and adolescents with RAD and 20 typically developing (TD) individuals performed tasks with high and low monetary rewards while undergoing functional magnetic resonance imaging. Results Significantly reduced activity in the caudate and nucleus accumbens was observed during the high monetary reward condition in the RAD group compared with the TD group (P=0.015, family-wise error-corrected cluster level). Significant negative correlations between bilateral striatal activity and avoidant attachment were observed in the RAD and TD groups. Conclusions Striatal neural reward activity in the RAD group was markedly decreased. The present results suggest that dopaminergic dysfunction occurs in the striatum of children and adolescents with RAD, leading towards potential future risks for psychopathology. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703736

Delay Discounting of Reward in ADHD: Application in Young Children

ERIC Educational Resources Information Center

Wilson, Vanessa B.; Mitchell, Suzanne H.; Musser, Erica D.; Schmitt, Colleen F.; Nigg, Joel T.

2011-01-01

Background: A key underlying process that may contribute to attention-deficit/hyperactivity disorder (ADHD) involves alterations in reward evaluation, including assessing the relative value of immediate over delayed rewards. This study examines whether children with ADHD discount the value of delayed rewards to a greater degree than typically…

The basolateral amygdala in reward learning and addiction.

PubMed

Wassum, Kate M; Izquierdo, Alicia

2015-10-01

Sophisticated behavioral paradigms partnered with the emergence of increasingly selective techniques to target the basolateral amygdala (BLA) have resulted in an enhanced understanding of the role of this nucleus in learning and using reward information. Due to the wide variety of behavioral approaches many questions remain on the circumscribed role of BLA in appetitive behavior. In this review, we integrate conclusions of BLA function in reward-related behavior using traditional interference techniques (lesion, pharmacological inactivation) with those using newer methodological approaches in experimental animals that allow in vivo manipulation of cell type-specific populations and neural recordings. Secondly, from a review of appetitive behavioral tasks in rodents and monkeys and recent computational models of reward procurement, we derive evidence for BLA as a neural integrator of reward value, history, and cost parameters. Taken together, BLA codes specific and temporally dynamic outcome representations in a distributed network to orchestrate adaptive responses. We provide evidence that experiences with opiates and psychostimulants alter these outcome representations in BLA, resulting in long-term modified action. Copyright © 2015 Elsevier Ltd. All rights reserved.

Altered reward processing in adolescents with prenatal exposure to maternal cigarette smoking.

PubMed

Müller, Kathrin U; Mennigen, Eva; Ripke, Stephan; Banaschewski, Tobias; Barker, Gareth J; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Flor, Herta; Garavan, Hugh; Heinz, Andreas; Lawrence, Claire; Loth, Eva; Mann, Karl; Martinot, Jean-Luc; Pausova, Zdenka; Rietschel, Marcella; Ströhle, Andreas; Struve, Maren; Walaszek, Bernadeta; Schumann, Gunter; Paus, Tomáš; Smolka, Michael N

2013-08-01

Higher rates of substance use and dependence have been observed in the offspring of mothers who smoked during pregnancy. Animal studies indicate that prenatal exposure to nicotine alters the development of brain areas related to reward processing, which might be a risk factor for substance use and addiction later in life. However, no study has examined the effect of maternal smoking on the offspring's brain response during reward processing. To determine whether adolescents with prenatal exposure to maternal cigarette smoking differ from their nonexposed peers in the response of the ventral striatum to the anticipation or the receipt of a reward. An observational case-control study. Data were obtained from the IMAGEN Study, a European multicenter study of impulsivity, reinforcement sensitivity, and emotional reactivity in adolescents. The IMAGEN sample consists of 2078 healthy adolescents (age range, 13-15 years) recruited from March 1, 2008, through December 31, 2011, in local schools. We assessed an IMAGEN subsample of 177 adolescents with prenatal exposure to maternal cigarette smoking and 177 nonexposed peers (age range, 13-15 years) matched by sex, maternal educational level, and imaging site. Response to reward in the ventral striatum measured with functional magnetic resonance imaging. In prenatally exposed adolescents, we observed a weaker response in the ventral striatum during reward anticipation (left side, F = 14.98 [P < .001]; right side, F = 15.95 [P < .001]) compared with their nonexposed peers. No differences were found regarding the responsivity of the ventral striatum to the receipt of a reward (left side, F = 0.21 [P = .65]; right side, F = 0.47 [P = .49]). The weaker responsivity of the ventral striatum to reward anticipation in prenatally exposed adolescents may represent a risk factor for substance use and development of addiction later in life. This result highlights the need for education and preventive measures to reduce smoking during pregnancy. Future analyses should assess whether prenatally exposed adolescents develop an increased risk for substance use and addiction and which role the reported neuronal differences during reward anticipation plays in this development.

The effects of HIV-1 regulatory TAT protein expression on brain reward function, response to psychostimulants and delay-dependent memory in mice.

PubMed

Kesby, James P; Markou, Athina; Semenova, Svetlana

2016-10-01

Depression and psychostimulant abuse are common comorbidities among humans with immunodeficiency virus (HIV) disease. The HIV regulatory protein TAT is one of multiple HIV-related proteins associated with HIV-induced neurotoxicity. TAT-induced dysfunction of dopamine and serotonin systems in corticolimbic brain areas may result in impaired reward function, thus, contributing to depressive symptoms and psychostimulant abuse. Transgenic mice with doxycycline-induced TAT protein expression in the brain (TAT+, TAT- control) show neuropathology resembling brain abnormalities in HIV+ humans. We evaluated brain reward function in response to TAT expression, nicotine and methamphetamine administration in TAT+ and TAT- mice using the intracranial self-stimulation procedure. We evaluated the brain dopamine and serotonin systems with high-performance liquid chromatography. The effects of TAT expression on delay-dependent working memory in TAT+ and TAT- mice using the operant delayed nonmatch-to-position task were also assessed. During doxycycline administration, reward thresholds were elevated by 20% in TAT+ mice compared with TAT- mice. After the termination of doxycycline treatment, thresholds of TAT+ mice remained significantly higher than those of TAT- mice and this was associated with changes in mesolimbic serotonin and dopamine levels. TAT+ mice showed a greater methamphetamine-induced threshold lowering compared with TAT- mice. TAT expression did not alter delay-dependent working memory. These results indicate that TAT expression in mice leads to reward deficits, a core symptom of depression, and a greater sensitivity to methamphetamine-induced reward enhancement. Our findings suggest that the TAT protein may contribute to increased depressive-like symptoms and continued methamphetamine use in HIV-positive individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Punishment sensitivity modulates the processing of negative feedback but not error-induced learning.

PubMed

Unger, Kerstin; Heintz, Sonja; Kray, Jutta

2012-01-01

Accumulating evidence suggests that individual differences in punishment and reward sensitivity are associated with functional alterations in neural systems underlying error and feedback processing. In particular, individuals highly sensitive to punishment have been found to be characterized by larger mediofrontal error signals as reflected in the error negativity/error-related negativity (Ne/ERN) and the feedback-related negativity (FRN). By contrast, reward sensitivity has been shown to relate to the error positivity (Pe). Given that Ne/ERN, FRN, and Pe have been functionally linked to flexible behavioral adaptation, the aim of the present research was to examine how these electrophysiological reflections of error and feedback processing vary as a function of punishment and reward sensitivity during reinforcement learning. We applied a probabilistic learning task that involved three different conditions of feedback validity (100%, 80%, and 50%). In contrast to prior studies using response competition tasks, we did not find reliable correlations between punishment sensitivity and the Ne/ERN. Instead, higher punishment sensitivity predicted larger FRN amplitudes, irrespective of feedback validity. Moreover, higher reward sensitivity was associated with a larger Pe. However, only reward sensitivity was related to better overall learning performance and higher post-error accuracy, whereas highly punishment sensitive participants showed impaired learning performance, suggesting that larger negative feedback-related error signals were not beneficial for learning or even reflected maladaptive information processing in these individuals. Thus, although our findings indicate that individual differences in reward and punishment sensitivity are related to electrophysiological correlates of error and feedback processing, we found less evidence for influences of these personality characteristics on the relation between performance monitoring and feedback-based learning.

A longitudinal examination of event-related potentials sensitive to monetary reward and loss feedback from late childhood to middle adolescence.

PubMed

Kujawa, Autumn; Carroll, Ashley; Mumper, Emma; Mukherjee, Dahlia; Kessel, Ellen M; Olino, Thomas; Hajcak, Greg; Klein, Daniel N

2017-11-04

Brain regions involved in reward processing undergo developmental changes from childhood to adolescence, and alterations in reward-related brain function are thought to contribute to the development of psychopathology. Event-related potentials (ERPs), such as the reward positivity (RewP) component, are valid measures of reward responsiveness that are easily assessed across development and provide insight into temporal dynamics of reward processing. Little work has systematically examined developmental changes in ERPs sensitive to reward. In this longitudinal study of 75 youth assessed 3 times across 6years, we used principal components analyses (PCA) to differentiate ERPs sensitive to monetary reward and loss feedback in late childhood, early adolescence, and middle adolescence. We then tested reliability of, and developmental changes in, ERPs. A greater number of ERP components differentiated reward and loss feedback in late childhood compared to adolescence, but components in childhood accounted for only a small proportion of variance. A component consistent with RewP was the only one to consistently emerge at each of the 3 assessments. RewP demonstrated acceptable reliability, particularly from early to middle adolescence, though reliability estimates varied depending on scoring approach and developmental period. The magnitude of the RewP component did not significantly change across time. Results provide insight into developmental changes in the structure of ERPs sensitive to reward, and indicate that RewP is a consistently observed and relatively stable measure of reward responsiveness, particularly across adolescence. Copyright © 2017. Published by Elsevier B.V.

Evidence of Altered Brain Responses to Nicotine in an Animal Model of Attention Deficit/Hyperactivity Disorder.

PubMed

Poirier, Guillaume L; Huang, Wei; Tam, Kelly; DiFranza, Joseph R; King, Jean A

2017-09-01

Individuals with attention deficit/hyperactivity disorder (ADHD) are susceptible to earlier and more severe nicotine addiction. To shed light on the relationship between nicotine and ADHD, we examined nicotine's effects on functional brain networks in an animal model of ADHD. Awake magnetic resonance imaging was used to compare functional connectivity in adolescent (post-natal day 44 ± 2) males of the spontaneously hypertensive rat (SHR) strain and two control strains, Wistar-Kyoto and Sprague-Dawley (n = 16 each). We analyzed functional connectivity immediately before and after nicotine exposure (0.4 mg/kg base) in naïve animals, using a region-of-interest approach focussing on 16 regions previously implicated in reward and addiction. Relative to the control groups, the SHR strain demonstrated increased functional connectivity between the ventral tegmental area (VTA) and retrosplenial cortex in response to nicotine, suggesting an aberrant response to nicotine. In contrast, increased VTA-substantia nigra connectivity in response to a saline injection in the SHR was absent following a nicotine injection, suggesting that nicotine normalized function in this circuit. In the SHR, nicotine triggered an atypical response in one VTA circuit while normalizing activity in another. The VTA has been widely implicated in drug reward. Our data suggest that increased susceptibility to nicotine addiction in individuals with ADHD may involve altered responses to nicotine involving VTA circuits. Nicotine addiction is more common among individuals with ADHD. We found that two circuits involving the VTA responded differently to nicotine in animals that model ADHD in comparison to two control strains. In one circuit, nicotine normalized activity that was abnormal in the ADHD animals, while in the other circuit nicotine caused an atypical brain response in the ADHD animals. The VTA has been implicated in drug reward. Our results would be consistent with an interpretation that nicotine may normalize abnormal brain activity in ADHD, and that nicotine may be more rewarding for individuals with ADHD. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Natural Rewards, Neuroplasticity, and Non-Drug Addictions

PubMed Central

Olsen, Christopher M.

2011-01-01

There is a high degree of overlap between brain regions involved in processing natural rewards and drugs of abuse. “Non-drug” or “behavioral” addictions have become increasingly documented in the clinic, and pathologies include compulsive activities such as shopping, eating, exercising, sexual behavior, and gambling. Like drug addiction, non-drug addictions manifest in symptoms including craving, impaired control over the behavior, tolerance, withdrawal, and high rates of relapse. These alterations in behavior suggest that plasticity may be occurring in brain regions associated with drug addiction. In this review, I summarize data demonstrating that exposure to non-drug rewards can alter neural plasticity in regions of the brain that are affected by drugs of abuse. Research suggests that there are several similarities between neuroplasticity induced by natural and drug rewards and that, depending on the reward, repeated exposure to natural rewards might induce neuroplasticity that either promotes or counteracts addictive behavior. PMID:21459101

Altered insula response to sweet taste processing after recovery from anorexia and bulimia nervosa.

PubMed

Oberndorfer, Tyson A; Frank, Guido K W; Simmons, Alan N; Wagner, Angela; McCurdy, Danyale; Fudge, Julie L; Yang, Tony T; Paulus, Martin P; Kaye, Walter H

2013-10-01

Recent studies suggest that altered function of higher-order appetitive neural circuitry may contribute to restricted eating in anorexia nervosa and overeating in bulimia nervosa. This study used sweet tastes to interrogate gustatory neurocircuitry involving the anterior insula and related regions that modulate sensory-interoceptive-reward signals in response to palatable foods. Participants who had recovered from anorexia nervosa and bulimia nervosa were studied to avoid confounding effects of altered nutritional state. Functional MRI measured brain response to repeated tastes of sucrose and sucralose to disentangle neural processing of caloric and noncaloric sweet tastes. Whole-brain functional analysis was constrained to anatomical regions of interest. Relative to matched comparison women (N=14), women recovered from anorexia nervosa (N=14) had significantly diminished and women recovered from bulimia nervosa (N=14) had significantly elevated hemodynamic response to tastes of sucrose in the right anterior insula. Anterior insula response to sucrose compared with sucralose was exaggerated in the recovered group (lower in women recovered from anorexia nervosa and higher in women recovered from bulimia nervosa). The anterior insula integrates sensory reward aspects of taste in the service of nutritional homeostasis. One possibility is that restricted eating and weight loss occur in anorexia nervosa because of a failure to accurately recognize hunger signals, whereas overeating in bulimia nervosa could represent an exaggerated perception of hunger signals. This response may reflect the altered calibration of signals related to sweet taste and the caloric content of food and may offer a pathway to novel and more effective treatments.

Reduced Vglut2/Slc17a6 Gene Expression Levels throughout the Mouse Subthalamic Nucleus Cause Cell Loss and Structural Disorganization Followed by Increased Motor Activity and Decreased Sugar Consumption

PubMed Central

Smith-Anttila, Casey J.A.; Nordenankar, Karin; Arvidsson, Emma; Mahmoudi, Souha; Zampera, André; Wärner Jonsson, Hanna; Bergquist, Jonas; Lévesque, Daniel; Andersson, Malin; Dumas, Sylvie

2016-01-01

The subthalamic nucleus (STN) plays a central role in motor, cognitive, and affective behavior. Deep brain stimulation (DBS) of the STN is the most common surgical intervention for advanced Parkinson’s disease (PD), and STN has lately gained attention as target for DBS in neuropsychiatric disorders, including obsessive compulsive disorder, eating disorders, and addiction. Animal studies using STN-DBS, lesioning, or inactivation of STN neurons have been used extensively alongside clinical studies to unravel the structural organization, circuitry, and function of the STN. Recent studies in rodent STN models have exposed different roles for STN neurons in reward-related functions. We have previously shown that the majority of STN neurons express the vesicular glutamate transporter 2 gene (Vglut2/Slc17a6) and that reduction of Vglut2 mRNA levels within the STN of mice [conditional knockout (cKO)] causes reduced postsynaptic activity and behavioral hyperlocomotion. The cKO mice showed less interest in fatty rewards, which motivated analysis of reward-response. The current results demonstrate decreased sugar consumption and strong rearing behavior, whereas biochemical analyses show altered dopaminergic and peptidergic activity in the striatum. The behavioral alterations were in fact correlated with opposite effects in the dorsal versus the ventral striatum. Significant cell loss and disorganization of the STN structure was identified, which likely accounts for the observed alterations. Rare genetic variants of the human VGLUT2 gene exist, and this study shows that reduced Vglut2/Slc17a6 gene expression levels exclusively within the STN of mice is sufficient to cause strong modifications in both the STN and the mesostriatal dopamine system. PMID:27699212

Reduced Vglut2/Slc17a6 Gene Expression Levels throughout the Mouse Subthalamic Nucleus Cause Cell Loss and Structural Disorganization Followed by Increased Motor Activity and Decreased Sugar Consumption.

PubMed

Schweizer, Nadine; Viereckel, Thomas; Smith-Anttila, Casey J A; Nordenankar, Karin; Arvidsson, Emma; Mahmoudi, Souha; Zampera, André; Wärner Jonsson, Hanna; Bergquist, Jonas; Lévesque, Daniel; Konradsson-Geuken, Åsa; Andersson, Malin; Dumas, Sylvie; Wallén-Mackenzie, Åsa

2016-01-01

The subthalamic nucleus (STN) plays a central role in motor, cognitive, and affective behavior. Deep brain stimulation (DBS) of the STN is the most common surgical intervention for advanced Parkinson's disease (PD), and STN has lately gained attention as target for DBS in neuropsychiatric disorders, including obsessive compulsive disorder, eating disorders, and addiction. Animal studies using STN-DBS, lesioning, or inactivation of STN neurons have been used extensively alongside clinical studies to unravel the structural organization, circuitry, and function of the STN. Recent studies in rodent STN models have exposed different roles for STN neurons in reward-related functions. We have previously shown that the majority of STN neurons express the vesicular glutamate transporter 2 gene ( Vglut2/Slc17a6 ) and that reduction of Vglut2 mRNA levels within the STN of mice [conditional knockout (cKO)] causes reduced postsynaptic activity and behavioral hyperlocomotion. The cKO mice showed less interest in fatty rewards, which motivated analysis of reward-response. The current results demonstrate decreased sugar consumption and strong rearing behavior, whereas biochemical analyses show altered dopaminergic and peptidergic activity in the striatum. The behavioral alterations were in fact correlated with opposite effects in the dorsal versus the ventral striatum. Significant cell loss and disorganization of the STN structure was identified, which likely accounts for the observed alterations. Rare genetic variants of the human VGLUT2 gene exist, and this study shows that reduced Vglut2/Slc17a6 gene expression levels exclusively within the STN of mice is sufficient to cause strong modifications in both the STN and the mesostriatal dopamine system.

Abnormal Social Reward Responses in Anorexia Nervosa: An fMRI Study.

PubMed

Via, Esther; Soriano-Mas, Carles; Sánchez, Isabel; Forcano, Laura; Harrison, Ben J; Davey, Christopher G; Pujol, Jesús; Martínez-Zalacaín, Ignacio; Menchón, José M; Fernández-Aranda, Fernando; Cardoner, Narcís

2015-01-01

Patients with anorexia nervosa (AN) display impaired social interactions, implicated in the development and prognosis of the disorder. Importantly, social behavior is modulated by reward-based processes, and dysfunctional at-brain-level reward responses have been involved in AN neurobiological models. However, no prior evidence exists of whether these neural alterations would be equally present in social contexts. In this study, we conducted a cross-sectional social-judgment functional magnetic resonance imaging (fMRI) study of 20 restrictive-subtype AN patients and 20 matched healthy controls. Brain activity during acceptance and rejection was investigated and correlated with severity measures (Eating Disorder Inventory -EDI-2) and with personality traits of interest known to modulate social behavior (The Sensitivity to Punishment and Sensitivity to Reward Questionnaire). Patients showed hypoactivation of the dorsomedial prefrontal cortex (DMPFC) during social acceptance and hyperactivation of visual areas during social rejection. Ventral striatum activation during rejection was positively correlated in patients with clinical severity scores. During acceptance, activation of the frontal opercula-anterior insula and dorsomedial/dorsolateral prefrontal cortices was differentially associated with reward sensitivity between groups. These results suggest an abnormal motivational drive for social stimuli, and involve overlapping social cognition and reward systems leading to a disruption of adaptive responses in the processing of social reward. The specific association of reward-related regions with clinical and psychometric measures suggests the putative involvement of reward structures in the maintenance of pathological behaviors in AN.

Impaired decision making in oppositional defiant disorder related to altered psychophysiological responses to reinforcement.

PubMed

Luman, Marjolein; Sergeant, Joseph A; Knol, Dirk L; Oosterlaan, Jaap

2010-08-15

When making decisions, children with oppositional defiant disorder (ODD) are thought to focus on reward and ignore penalty. This is suggested to be associated with a state of low psychophysiological arousal. This study investigates decision making in 18 children with oppositional defiant disorder and 24 typically developing control subjects. Children were required to choose between three alternatives that carried either frequent small rewards and occasional small penalties (advantageous), frequent large rewards and increasing penalties (seductive), or frequent small rewards and increasing penalties (disadvantageous). Penalties in the seductive and disadvantageous alternatives increased either in frequency or magnitude in two conditions. Heart rate (HR) and skin conductance responses to reinforcement were obtained. In the magnitude condition, children with ODD showed an increased preference for the seductive alternative (carrying large rewards); this was not observed in the frequency condition. Children with ODD, compared with typically developing children, displayed greater HR reactivity to reward (more HR deceleration) and smaller HR reactivity to penalty. Correlation analyses showed that decreased HR responses to penalty were related to an increased preference for large rewards. No group differences were observed in skin conductance responses to reward or penalty. The findings suggest that an increased preference for large rewards in children with ODD is related to a reduced cardiac reactivity to aversive stimuli. This confirms notions of impaired decision making and altered reinforcement sensitivity in children with ODD and adds to the literature linking altered autonomic control to antisocial behavior. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Mu opioid receptors in GABAergic forebrain neurons moderate motivation for heroin and palatable food

PubMed Central

Charbogne, Pauline; Gardon, Olivier; Martín-García, Elena; Keyworth, Helen L.; Matsui, Aya; Mechling, Anna E.; Bienert, Thomas; Nasseef, Taufiq; Robé, Anne; Moquin, Luc; Darcq, Emmanuel; Ben Hamida, Sami; Robledo, Patricia; Matifas, Audrey; Befort, Katia; Gavériaux-Ruff, Claire; Harsan, Laura-Adela; Von Everfeldt, Dominik; Hennig, Jurgen; Gratton, Alain; Kitchen, Ian; Bailey, Alexis; Alvarez, Veronica A.; Maldonado, Rafael; Kieffer, Brigitte L.

2016-01-01

BACKGROUND Mu opioid receptors (MORs) are central to pain control, drug reward and addictive behaviors, but underlying circuit mechanisms have been poorly explored by genetic approaches. Here we investigate the contribution of MORs expressed in GABAergic forebrain neurons to major biological effects of opiates, and also challenge the canonical disinhibition model of opiate reward. METHODS We used Dlx5/6-mediated recombination to create conditional Oprm1 mice in GABAergic forebrain neurons. We characterized the genetic deletion by histology, electrophysiology and microdialysis, probed neuronal activation by c-Fos immunohistochemistry and resting state-functional magnetic resonance imaging, and investigated main behavioral responses to opiates, including motivation to obtain heroin and palatable food. RESULTS Mutant mice showed MOR transcript deletion mainly in the striatum. In the ventral tegmental area (VTA), local MOR activity was intact, and reduced activity was only observed at the level of striatonigral afferents. Heroin-induced neuronal activation was modified at both sites, and whole-brain functional networks were altered in live animals. Morphine analgesia was not altered, neither was physical dependence to chronic morphine. In contrast, locomotor effects of heroin were abolished, and heroin-induced catalepsy was increased. Place preference to heroin was not modified, but remarkably, motivation to obtain heroin and palatable food was enhanced in operant self-administration procedures. CONCLUSIONS Our study reveals dissociable MOR functions across mesocorticolimbic networks. Thus beyond a well-established role in reward processing, operating at the level of local VTA neurons, MORs also moderate motivation for appetitive stimuli within forebrain circuits that drive motivated behaviors. PMID:28185645

Cocaine addiction is associated with abnormal prefrontal function, increased striatal connectivity and sensitivity to monetary incentives, and decreased connectivity outside the human reward circuit.

PubMed

Vaquero, Lucía; Cámara, Estela; Sampedro, Frederic; Pérez de Los Cobos, José; Batlle, Francesca; Fabregas, Josep Maria; Sales, Joan Artur; Cervantes, Mercè; Ferrer, Xavier; Lazcano, Gerardo; Rodríguez-Fornells, Antoni; Riba, Jordi

2017-05-01

Cocaine addiction has been associated with increased sensitivity of the human reward circuit to drug-related stimuli. However, the capacity of non-drug incentives to engage this network is poorly understood. Here, we characterized the functional sensitivity to monetary incentives and the structural integrity of the human reward circuit in abstinent cocaine-dependent (CD) patients and their matched controls. We assessed the BOLD response to monetary gains and losses in 30 CD patients and 30 healthy controls performing a lottery task in a magnetic resonance imaging scanner. We measured brain gray matter volume (GMV) using voxel-based morphometry and white matter microstructure using voxel-based fractional anisotropy (FA). Functional data showed that, after monetary incentives, CD patients exhibited higher activation in the ventral striatum than controls. Furthermore, we observed an inverted BOLD response pattern in the prefrontal cortex, with activity being highest after unexpected high gains and lowest after losses. Patients showed increased GMV in the caudate and the orbitofrontal cortex, increased white matter FA in the orbito-striatal pathway but decreased FA in antero-posterior association bundles. Abnormal activation in the prefrontal cortex correlated with GMV and FA increases in the orbitofrontal cortex. While functional abnormalities in the ventral striatum were inversely correlated with abstinence duration, structural alterations were not. In conclusion, results suggest abnormal incentive processing in CD patients with high salience for rewards and punishments in subcortical structures but diminished prefrontal control after adverse outcomes. They further suggest that hypertrophy and hyper-connectivity within the reward circuit, to the expense of connectivity outside this network, characterize cocaine addiction. © 2016 Society for the Study of Addiction.

Impact of Early Life Adversity on Reward Processing in Young Adults: EEG-fMRI Results from a Prospective Study over 25 Years

PubMed Central

Boecker, Regina; Holz, Nathalie E.; Buchmann, Arlette F.; Blomeyer, Dorothea; Plichta, Michael M.; Wolf, Isabella; Baumeister, Sarah; Meyer-Lindenberg, Andreas; Banaschewski, Tobias

2014-01-01

Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy young adults (mean age = 24.4 years; 58% female) from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus), indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV), with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway. PMID:25118701

Problematic internet use is associated with structural alterations in the brain reward system in females.

PubMed

Altbäcker, Anna; Plózer, Enikő; Darnai, Gergely; Perlaki, Gábor; Horváth, Réka; Orsi, Gergely; Nagy, Szilvia Anett; Bogner, Péter; Schwarcz, Attila; Kovács, Norbert; Komoly, Sámuel; Clemens, Zsófia; Janszky, József

2016-12-01

Neuroimaging findings suggest that excessive Internet use shows functional and structural brain changes similar to substance addiction. Even though it is still under debate whether there are gender differences in case of problematic use, previous studies by-passed this question by focusing on males only or by using gender matched approach without controlling for potential gender effects. We designed our study to find out whether there are structural correlates in the brain reward system of problematic Internet use in habitual Internet user females. T1-weighted Magnetic Resonance (MR) images were collected in 82 healthy habitual Internet user females. Structural brain measures were investigated using both automated MR volumetry and voxel based morphometry (VBM). Self-reported measures of problematic Internet use and hours spent online were also assessed. According to MR volumetry, problematic Internet use was associated with increased grey matter volume of bilateral putamen and right nucleus accumbens while decreased grey matter volume of orbitofrontal cortex (OFC). Similarly, VBM analysis revealed a significant negative association between the absolute amount of grey matter OFC and problematic Internet use. Our findings suggest structural brain alterations in the reward system usually related to addictions are present in problematic Internet use.

Developmental Ethanol Exposure Causes Reduced Feeding and Reveals a Critical Role for Neuropeptide F in Survival

PubMed Central

Guevara, Amanda; Gates, Hillary; Urbina, Brianna; French, Rachael

2018-01-01

Food intake is necessary for survival, and natural reward circuitry has evolved to help ensure that animals ingest sufficient food to maintain development, growth, and survival. Drugs of abuse, including alcohol, co-opt the natural reward circuitry in the brain, and this is a major factor in the reinforcement of drug behaviors leading to addiction. At the junction of these two aspects of reward are alterations in feeding behavior due to alcohol consumption. In particular, developmental alcohol exposure (DAE) results in a collection of physical and neurobehavioral disorders collectively referred to as Fetal Alcohol Spectrum Disorder (FASD). The deleterious effects of DAE include intellectual disabilities and other neurobehavioral changes, including altered feeding behaviors. Here we use Drosophila melanogaster as a genetic model organism to study the effects of DAE on feeding behavior and the expression and function of Neuropeptide F. We show that addition of a defined concentration of ethanol to food leads to reduced feeding at all stages of development. Further, genetic conditions that reduce or eliminate NPF signaling combine with ethanol exposure to further reduce feeding, and the distribution of NPF is altered in the brains of ethanol-supplemented larvae. Most strikingly, we find that the vast majority of flies with a null mutation in the NPF receptor die early in larval development when reared in ethanol, and provide evidence that this lethality is due to voluntary starvation. Collectively, we find a critical role for NPF signaling in protecting against altered feeding behavior induced by developmental ethanol exposure. PMID:29623043

Opiate exposure state controls dopamine D3 receptor and cdk5/calcineurin signaling in the basolateral amygdala during reward and withdrawal aversion memory formation.

PubMed

Rosen, Laura G; Rushlow, Walter J; Laviolette, Steven R

2017-10-03

The dopamine (DA) D3 receptor (D3R) is highly expressed in the basolateral nucleus of the amygdala (BLA), a neural region critical for processing opiate-related reward and withdrawal aversion-related memories. Functionally, D3R transmission is linked to downstream Cdk5 and calcineurin signaling, both of which regulate D3R activity states and play critical roles in memory-related synaptic plasticity. Previous evidence links D3R transmission to opiate-related memory processing, however little is known regarding how chronic opiate exposure may alter D3R-dependent memory mechanisms. Using conditioned place preference (CPP) and withdrawal aversion (conditioned place aversion; CPA) procedures in rats, combined with molecular analyses of BLA protein expression, we examined the effects of chronic opiate exposure on the functional role of intra-BLA D3R transmission during the acquisition of opiate reward or withdrawal aversion memories. Remarkably, we report that the state of opiate exposure during behavioural conditioning (opiate-naïve/non-dependent vs. chronically exposed and in withdrawal) controlled the functional role of intra-BLA D3R transmission during the acquisition of both opiate reward memories and withdrawal-aversion associative memories. Thus, whereas intra-BLA D3R blockade had no effect on opiate reward memory formation in the non-dependent state, blockade of intra-BLA D3R transmission prevented the formation of opiate reward and withdrawal aversion memory in the chronically exposed state. This switch in the functional role of D3R transmission corresponded to significant increases in Cdk5 phosphorylation and total expression levels of calcineurin, and a corresponding decrease in intra-BLA D3R expression. Inhibition of either intra-BLA Cdk5 or calcineurin reversed these effects, switching intra-BLA associative memory formation back to a D3R-independent mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

Imaging genetics and the neurobiological basis of individual differences in vulnerability to addiction.

PubMed

Sweitzer, Maggie M; Donny, Eric C; Hariri, Ahmad R

2012-06-01

Addictive disorders are heritable, but the search for candidate functional polymorphisms playing an etiological role in addiction is hindered by complexity of the phenotype and the variety of factors interacting to impact behavior. Advances in human genome sequencing and neuroimaging technology provide an unprecedented opportunity to explore the impact of functional genetic variants on variability in behaviorally relevant neural circuitry. Here, we present a model for merging these technologies to trace the links between genes, brain, and addictive behavior. We describe imaging genetics and discuss the utility of its application to addiction. We then review data pertaining to impulsivity and reward circuitry as an example of how genetic variation may lead to variation in behavioral phenotype. Finally, we present preliminary data relating the neural basis of reward processing to individual differences in nicotine dependence. Complex human behaviors such as addiction can be traced to their basic genetic building blocks by identifying intermediate behavioral phenotypes, associated neural circuitry, and underlying molecular signaling pathways. Impulsivity has been linked with variation in reward-related activation in the ventral striatum (VS), altered dopamine signaling, and functional polymorphisms of DRD2 and DAT1 genes. In smokers, changes in reward-related VS activation induced by smoking abstinence may be associated with severity of nicotine dependence. Variation in genes related to dopamine signaling may contribute to heterogeneity in VS sensitivity to reward and, ultimately, to addiction. These findings illustrate the utility of the imaging genetics approach for investigating the neurobiological basis for vulnerability to addiction. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Diminished fronto-striatal activity during processing of monetary rewards and losses in pathological gambling

PubMed Central

Balodis, Iris M.; Kober, Hedy; Worhunsky, Patrick D.; Stevens, Michael C.; Pearlson, Godfrey D.; Potenza, Marc N.

2012-01-01

Background Mesocorticolimbic neurocircuitry and impulsivity have both been implicated in pathological gambling (PG) and in reward processing. However, the neural underpinnings of specific phases of reward and loss processing in PG and their relationships to impulsivity remain only partially understood. The present functional magnetic resonance imaging study examined brain activity associated with different phases of reward and loss processing in PG. Given an inverse relationship between ventral striatal recruitment during anticipation of monetary rewards and impulsivity in alcohol dependence, the current study explored whether a similar association might also be present in PG. Methods Fourteen adults with PG and 14 control comparison (CC) participants performed the Monetary Incentive Delay Task (MIDT) to identify brain activation changes associated with reward/loss prospect, reward/loss anticipation and reward/loss notification. Impulsivity was assessed separately using the Barratt Impulsiveness Scale. Results Relative to the CC group, the PG group exhibited significantly reduced activity in the ventromedial prefrontal cortex, insula and ventral striatum during several phases, including the prospect and anticipation phases of both gain and losses. Activity in the ventral striatum correlated inversely with levels of impulsivity in PG participants, consistent with prior findings in alcohol dependence. Conclusions Relatively decreased activity in cortico-striatal neurocircuitry during multiple phases of reward processing suggests consistent alterations in neurocircuitry underlying incentive valuation and loss prediction. Together with findings in alcohol dependence, these results suggest that impulsive tendencies in addictions may be reflected in diminished ventral striatal activations to reward anticipation and may represent targets for treatment development in addictions. PMID:22336565

Diminished frontostriatal activity during processing of monetary rewards and losses in pathological gambling.

PubMed

Balodis, Iris M; Kober, Hedy; Worhunsky, Patrick D; Stevens, Michael C; Pearlson, Godfrey D; Potenza, Marc N

2012-04-15

Mesocorticolimbic neurocircuitry and impulsivity have both been implicated in pathological gambling (PG) and in reward processing. However, the neural underpinnings of specific phases of reward and loss processing in PG and their relationships to impulsivity remain only partially understood. The present functional magnetic resonance imaging study examined brain activity associated with different phases of reward and loss processing in PG. Given an inverse relationship between ventral striatal recruitment during anticipation of monetary rewards and impulsivity in alcohol dependence, the current study explored whether a similar association might also be present in PG. Fourteen adults with PG and 14 control comparison participants performed the Monetary Incentive Delay Task to identify brain activation changes associated with reward/loss prospect, reward/loss anticipation, and reward/loss notification. Impulsivity was assessed separately using the Barratt Impulsiveness Scale. Relative to the control comparison group, the PG group exhibited significantly reduced activity in the ventromedial prefrontal cortex, insula, and ventral striatum during several phases, including the prospect and anticipation phases of both gains and losses. Activity in the ventral striatum correlated inversely with levels of impulsivity in PG participants, consistent with prior findings in alcohol dependence. Relatively decreased activity in corticostriatal neurocircuitry during multiple phases of reward processing suggests consistent alterations in neurocircuitry underlying incentive valuation and loss prediction. Together with findings in alcohol dependence, these results suggest that impulsive tendencies in addictions may be reflected in diminished ventral striatal activations to reward anticipation and may represent targets for treatment development in addictions. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Link Between Increased Satiety Gut Hormones and Reduced Food Reward After Gastric Bypass Surgery for Obesity.

PubMed

Goldstone, Anthony P; Miras, Alexander D; Scholtz, Samantha; Jackson, Sabrina; Neff, Karl J; Pénicaud, Luc; Geoghegan, Justin; Chhina, Navpreet; Durighel, Giuliana; Bell, Jimmy D; Meillon, Sophie; le Roux, Carel W

2016-02-01

Roux-en-Y gastric bypass (RYGB) surgery is an effective long-term intervention for weight loss maintenance, reducing appetite, and also food reward, via unclear mechanisms. To investigate the role of elevated satiety gut hormones after RYGB, we examined food hedonic-reward responses after their acute post-prandial suppression. These were randomized, placebo-controlled, double-blind, crossover experimental medicine studies. Two groups, more than 5 months after RYGB for obesity (n = 7-11), compared with nonobese controls (n = 10), or patients after gastric banding (BAND) surgery (n = 9) participated in the studies. Studies were performed after acute administration of the somatostatin analog octreotide or saline. In one study, patients after RYGB, and nonobese controls, performed a behavioral progressive ratio task for chocolate sweets. In another study, patients after RYGB, and controls after BAND surgery, performed a functional magnetic resonance imaging food picture evaluation task. Octreotide increased both appetitive food reward (breakpoint) in the progressive ratio task (n = 9), and food appeal (n = 9) and reward system blood oxygen level-dependent signal (n = 7) in the functional magnetic resonance imaging task, in the RYGB group, but not in the control groups. Octreotide suppressed postprandial plasma peptide YY, glucagon-like peptide-1, and fibroblast growth factor-19 after RYGB. The reduction in plasma peptide YY with octreotide positively correlated with the increase in brain reward system blood oxygen level-dependent signal in RYGB/BAND subjects, with a similar trend for glucagon-like peptide-1. Enhanced satiety gut hormone responses after RYGB may be a causative mechanism by which anatomical alterations of the gut in obesity surgery modify behavioral and brain reward responses to food.

Cocaine Self-Administration Experience Induces Pathological Phasic Accumbens Dopamine Signals and Abnormal Incentive Behaviors in Drug-Abstinent Rats

PubMed Central

Wang, Xuefei; Sugam, Jonathan A.; Carelli, Regina M.

2016-01-01

Chronic exposure to drugs of abuse is linked to long-lasting alterations in the function of limbic system structures, including the nucleus accumbens (NAc). Although cocaine acts via dopaminergic mechanisms within the NAc, less is known about whether phasic dopamine (DA) signaling in the NAc is altered in animals with cocaine self-administration experience or if these animals learn and interact normally with stimuli in their environment. Here, separate groups of rats self-administered either intravenous cocaine or water to a receptacle (controls), followed by 30 d of enforced abstinence. Next, all rats learned an appetitive Pavlovian discrimination and voltammetric recordings of real-time DA release were taken in either the NAc core or shell of cocaine and control subjects. Cocaine experience differentially impaired DA signaling in the core and shell relative to controls. Although phasic DA signals in the shell were essentially abolished for all stimuli, in the core, DA did not distinguish between cues and was abnormally biased toward reward delivery. Further, cocaine rats were unable to learn higher-order associations and even altered simple conditioned approach behaviors, displaying enhanced preoccupation with cue-associated stimuli (sign-tracking; ST) but diminished time at the food cup awaiting reward delivery (goal-tracking). Critically, whereas control DA signaling correlated with ST behaviors, cocaine experience abolished this relationship. These findings show that cocaine has persistent, differential, and pathological effects on both DA signaling and DA-dependent behaviors and suggest that psychostimulant experience may remodel the very circuits that bias organisms toward repeated relapse. SIGNIFICANCE STATEMENT Relapsing to drug abuse despite periods of abstinence and sincere attempts to quit is one of the most pernicious facets of addiction. Unfortunately, little is known about how the dopamine (DA) system functions after periods of drug abstinence, particularly its role in behavior in nondrug situations. Here, rats learned about food-paired stimuli after prolonged abstinence from cocaine self-administration. Using voltammetry, we found that real-time DA signals in cocaine-experienced rats were strikingly altered relative to controls. Further, cocaine-experienced animals found reward-predictive stimuli abnormally salient and spent more time interacting with cues. Therefore, cocaine induces neuroplastic changes in the DA system that biases animals toward salient stimuli (including reward-associated cues), putting addicts at increasing risk to relapse as addiction increases in severity. PMID:26740664

Basolateral Amygdala, Nicotinic Cholinergic Receptors, and Nicotine: pharmacological effects and addiction in animal models and humans.

PubMed

Sharp, B M

2018-05-26

The amygdala is involved in processing incoming information about rewarding stimuli and emotions that denote danger such as anxiety and fear. Bi-directional neural connections between basolateral amygdala (BLA) and brain regions such as nucleus accumbens, prefrontal cortex, hippocampus and hindbrain regions regulate motivation, cognition, and responses to stress. Altered local regulation of BLA excitability is pivotal to the behavioral disturbances characteristic of posttraumatic stress disorder (PTSD), and relapse to drug use induced by stress. Herein, we review the physiological regulation of BLA by cholinergic inputs, emphasizing the role of BLA nicotinic receptors. We review BLA-dependent effects of nicotine on cognition, motivated behaviors and emotional states, including memory, taking and seeking drugs, and anxiety and fear in humans and animal models. The alterations in BLA activity observed in animal studies inform human behavioral and brain imaging research by enabling a more exact understanding of altered BLA function. Converging evidence indicates that cholinergic signaling from basal forebrain projections to local nicotinic receptors is an important physiological regulator of BLA and that nicotine alters BLA function. In essence, BLA is necessary for: behavioral responses to stimuli that evoke anxiety and fear; reinstatement of cue-induced drug seeking; responding to second-order cues conditioned to abused drugs; reacquisition of amplified nicotine self-administration due to chronic stress during abstinence; and to promote responding for natural reward. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Perceived Chronic Stress Exposure Modulates Reward-Related Medial Prefrontal Cortex Responses to Acute Stress in Depression

PubMed Central

Kumar, Poornima; Slavich, George M.; Berghorst, Lisa H.; Treadway, Michael T.; Brooks, Nancy H.; Dutra, Sunny J.; Greve, Douglas N.; O'Donovan, Aoife; Bleil, Maria E.; Maninger, Nicole; Pizzagalli, Diego A.

2015-01-01

Introduction Major depressive disorder (MDD) is often precipitated by life stress and growing evidence suggests that stress-induced alterations in reward processing may contribute to such risk. However, no human imaging studies have examined how recent life stress exposure modulates the neural systems that underlie reward processing in depressed and healthy individuals. Methods In this proof-of-concept study, 12 MDD and 10 psychiatrically healthy individuals were interviewed using the Life Events and Difficulties Schedule (LEDS) to assess their perceived levels of recent acute and chronic life stress exposure. Additionally, each participant performed a monetary incentive delay task under baseline (no-stress) and stress (social-evaluative) conditions during functional MRI. Results Across groups, medial prefrontal cortex (mPFC) activation to reward feedback was greater during acute stress versus no-stress conditions in individuals with greater perceived stressor severity. Under acute stress, depressed individuals showed a positive correlation between perceived stressor severity levels and reward-related mPFC activation (r = 0.79, p = 0.004), whereas no effect was found in healthy controls. Moreover, for depressed (but not healthy) individuals, the correlations between the stress (r = 0.79) and no-stress (r = −0.48) conditions were significantly different. Finally, relative to controls, depressed participants showed significantly reduced mPFC grey matter, but functional findings remained when accounting for structural differences. Limitation Small sample size, which warrants replication. Conclusion Depressed individuals experiencing greater recent life stress recruited the mPFC more under stress when processing rewards. Our results represent an initial step toward elucidating mechanisms underlying stress sensitization and recurrence in depression. PMID:25898329

Pro-Dopamine Regulator – (KB220) to Balance Brain Reward Circuitry in Reward Deficiency Syndrome (RDS)

PubMed Central

Blum, Kenneth; Febo, Marcelo; Fried, Lyle; Baron, David; Braverman, Eric R.; Dushaj, Kristina; Li, Mona; Demetrovics, Zsolt; Badgaiyan, Rajendra D.

2017-01-01

We are faced with a worldwide opiate/opioid epidemic that is devastating. According to the Centers for Disease Control and Prevention (CDC), at least 127 people, young and old, are dying every day in America due to narcotic overdose. The Food and Drug Administration (FDA) has approved Medication-Assisted Treatments (MATs) for opiate/opioids as well as alcohol and nicotine. The mechanism of action of most MATS favors either blocking of dopaminergic function or a form of Opiate Substitution Therapy (OST). These treatment options are adequate for short-term treatment of the symptoms of addiction and harm reduction but fail long-term to deal with the cause or lead to recovery. There is a need to continue to seek better treatment options. This mini-review is the history of the development of one such treatment; a glutaminergic-dopaminergic optimization complex called KB220. Growing evidence indicates that brain reward circuitry controls drug addiction, in conjunction with “anti-reward systems” as the “anti-reward systems” can be affected by both glutaminergic and dopaminergic transmission. KB220 may likely alter the function of these regions and provide for the possible eventual balancing the brain reward system and the induction of “dopamine homeostasis.” Many of these concepts have been reported elsewhere and have become an integral part of the addiction science literature. However, the concise review may encourage readership to reconsider these facts and stimulate further research focused on the impact that the induction of “dopamine homeostasis” may have on recovery and relapse prevention. PMID:28804788

Moderation of the Relationship Between Reward Expectancy and Prediction Error-Related Ventral Striatal Reactivity by Anhedonia in Unmedicated Major Depressive Disorder: Findings From the EMBARC Study

PubMed Central

Greenberg, Tsafrir; Chase, Henry W.; Almeida, Jorge R.; Stiffler, Richelle; Zevallos, Carlos R.; Aslam, Haris A.; Deckersbach, Thilo; Weyandt, Sarah; Cooper, Crystal; Toups, Marisa; Carmody, Thomas; Kurian, Benji; Peltier, Scott; Adams, Phillip; McInnis, Melvin G.; Oquendo, Maria A.; McGrath, Patrick J.; Fava, Maurizio; Weissman, Myrna; Parsey, Ramin; Trivedi, Madhukar H.; Phillips, Mary L.

2016-01-01

Objective Anhedonia, disrupted reward processing, is a core symptom of major depressive disorder. Recent findings demonstrate altered reward-related ventral striatal reactivity in depressed individuals, but the extent to which this is specific to anhedonia remains poorly understood. The authors examined the effect of anhedonia on reward expectancy (expected outcome value) and prediction error-(discrepancy between expected and actual outcome) related ventral striatal reactivity, as well as the relationship between these measures. Method A total of 148 unmedicated individuals with major depressive disorder and 31 healthy comparison individuals recruited for the multisite EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study underwent functional MRI during a well-validated reward task. Region of interest and whole-brain data were examined in the first- (N=78) and second- (N=70) recruited cohorts, as well as the total sample, of depressed individuals, and in healthy individuals. Results Healthy, but not depressed, individuals showed a significant inverse relationship between reward expectancy and prediction error-related right ventral striatal reactivity. Across all participants, and in depressed individuals only, greater anhedonia severity was associated with a reduced reward expectancy-prediction error inverse relationship, even after controlling for other symptoms. Conclusions The normal reward expectancy and prediction error-related ventral striatal reactivity inverse relationship concords with conditioning models, predicting a shift in ventral striatal responding from reward outcomes to reward cues. This study shows, for the first time, an absence of this relationship in two cohorts of unmedicated depressed individuals and a moderation of this relationship by anhedonia, suggesting reduced reward-contingency learning with greater anhedonia. These findings help elucidate neural mechanisms of anhedonia, as a step toward identifying potential biosignatures of treatment response. PMID:26183698

Moderation of the Relationship Between Reward Expectancy and Prediction Error-Related Ventral Striatal Reactivity by Anhedonia in Unmedicated Major Depressive Disorder: Findings From the EMBARC Study.

PubMed

Greenberg, Tsafrir; Chase, Henry W; Almeida, Jorge R; Stiffler, Richelle; Zevallos, Carlos R; Aslam, Haris A; Deckersbach, Thilo; Weyandt, Sarah; Cooper, Crystal; Toups, Marisa; Carmody, Thomas; Kurian, Benji; Peltier, Scott; Adams, Phillip; McInnis, Melvin G; Oquendo, Maria A; McGrath, Patrick J; Fava, Maurizio; Weissman, Myrna; Parsey, Ramin; Trivedi, Madhukar H; Phillips, Mary L

2015-09-01

Anhedonia, disrupted reward processing, is a core symptom of major depressive disorder. Recent findings demonstrate altered reward-related ventral striatal reactivity in depressed individuals, but the extent to which this is specific to anhedonia remains poorly understood. The authors examined the effect of anhedonia on reward expectancy (expected outcome value) and prediction error- (discrepancy between expected and actual outcome) related ventral striatal reactivity, as well as the relationship between these measures. A total of 148 unmedicated individuals with major depressive disorder and 31 healthy comparison individuals recruited for the multisite EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study underwent functional MRI during a well-validated reward task. Region of interest and whole-brain data were examined in the first- (N=78) and second- (N=70) recruited cohorts, as well as the total sample, of depressed individuals, and in healthy individuals. Healthy, but not depressed, individuals showed a significant inverse relationship between reward expectancy and prediction error-related right ventral striatal reactivity. Across all participants, and in depressed individuals only, greater anhedonia severity was associated with a reduced reward expectancy-prediction error inverse relationship, even after controlling for other symptoms. The normal reward expectancy and prediction error-related ventral striatal reactivity inverse relationship concords with conditioning models, predicting a shift in ventral striatal responding from reward outcomes to reward cues. This study shows, for the first time, an absence of this relationship in two cohorts of unmedicated depressed individuals and a moderation of this relationship by anhedonia, suggesting reduced reward-contingency learning with greater anhedonia. These findings help elucidate neural mechanisms of anhedonia, as a step toward identifying potential biosignatures of treatment response.

Neural substrates of reward magnitude, probability, and risk during a wheel of fortune decision-making task.

PubMed

Smith, Bruce W; Mitchell, Derek G V; Hardin, Michael G; Jazbec, Sandra; Fridberg, Daniel; Blair, R James R; Ernst, Monique

2009-01-15

Economic decision-making involves the weighting of magnitude and probability of potential gains/losses. While previous work has examined the neural systems involved in decision-making, there is a need to understand how the parameters associated with decision-making (e.g., magnitude of expected reward, probability of expected reward and risk) modulate activation within these neural systems. In the current fMRI study, we modified the monetary wheel of fortune (WOF) task [Ernst, M., Nelson, E.E., McClure, E.B., Monk, C.S., Munson, S., Eshel, N., et al. (2004). Choice selection and reward anticipation: an fMRI study. Neuropsychologia 42(12), 1585-1597.] to examine in 25 healthy young adults the neural responses to selections of different reward magnitudes, probabilities, or risks. Selection of high, relative to low, reward magnitude increased activity in insula, amygdala, middle and posterior cingulate cortex, and basal ganglia. Selection of low-probability, as opposed to high-probability reward, increased activity in anterior cingulate cortex, as did selection of risky, relative to safe reward. In summary, decision-making that did not involve conflict, as in the magnitude contrast, recruited structures known to support the coding of reward values, and those that integrate motivational and perceptual information for behavioral responses. In contrast, decision-making under conflict, as in the probability and risk contrasts, engaged the dorsal anterior cingulate cortex whose role in conflict monitoring is well established. However, decision-making under conflict failed to activate the structures that track reward values per se. Thus, the presence of conflict in decision-making seemed to significantly alter the pattern of neural responses to simple rewards. In addition, this paradigm further clarifies the functional specialization of the cingulate cortex in processes of decision-making.

Altered reward system reactivity for personalized circumscribed interests in autism.

PubMed

Kohls, Gregor; Antezana, Ligia; Mosner, Maya G; Schultz, Robert T; Yerys, Benjamin E

2018-01-01

Neurobiological research in autism spectrum disorders (ASD) has paid little attention on brain mechanisms that cause and maintain restricted and repetitive behaviors and interests (RRBIs). Evidence indicates an imbalance in the brain's reward system responsiveness to social and non-social stimuli may contribute to both social deficits and RRBIs. Thus, this study's central aim was to compare brain responsiveness to individual RRBI (i.e., circumscribed interests), with social rewards (i.e., social approval), in youth with ASD relative to typically developing controls (TDCs). We conducted a 3T functional magnetic resonance imaging (fMRI) study to investigate the blood-oxygenation-level-dependent effect of personalized circumscribed interest rewards versus social rewards in 39 youth with ASD relative to 22 TDC. To probe the reward system, we employed short video clips as reinforcement in an instrumental incentive delay task. This optimization increased the task's ecological validity compared to still pictures that are often used in this line of research. Compared to TDCs, youth with ASD had stronger reward system responses for CIs mostly within the non-social realm (e.g., video games) than social rewards (e.g., approval). Additionally, this imbalance within the caudate nucleus' responsiveness was related to greater social impairment. The current data support the idea of reward system dysfunction that may contribute to enhanced motivation for RRBIs in ASD, accompanied by diminished motivation for social engagement. If a dysregulated reward system indeed supports the emergence and maintenance of social and non-social symptoms of ASD, then strategically targeting the reward system in future treatment endeavors may allow for more efficacious treatment practices that help improve outcomes for individuals with ASD and their families.

Blunted responses to reward in remitted post-traumatic stress disorder

PubMed Central

Kalebasi, Nilufer; Kuelen, Eveline; Schnyder, Ulrich; Schumacher, Sonja; Mueller-Pfeiffer, Christoph; Wilhelm, Frank H; Athilingam, Jegath; Moergeli, Hanspeter; Martin-Soelch, Chantal

2015-01-01

Background Recent evidence suggests blunted responses to rewarding stimuli in patients with post-traumatic stress disorder (PTSD). However, it is not clear whether these alterations in reward processing normalize in remitted PTSD patients. Methods We tested behavioral and physiological responses to monetary reward in a spatial memory task in 13 accident survivors with remitted PTSD, 14 accident survivors who never had PTSD, and 16 nontrauma-exposed subjects. All accident survivors were recruited from two samples of severely physically injured patients, who had participated in previous prospective studies on the incidence of PTSD after accidental injury approximately 10 years ago. Reaction time, accuracy, skin conductance responses, and self-reported mood were assessed during the task. Results Accident survivors who never had PTSD and nontrauma exposed controls reported significantly higher positive mood in the reinforced versus nonreinforced condition (P < 0.045 and P < 0.001, respectively), while there was no effect of reinforcement in remitted PTSD subjects. Conclusions Our findings suggest an alteration of the reward system in remitted PTSD. Further research is needed to investigate whether altered reward processing is a residual characteristic in PTSD after remission of symptoms or, alternatively, a preexisting risk factor for the development of PTSD after a traumatic event. PMID:26357590

Oxytocin curbs calorie intake via food-specific increases in the activity of brain areas that process reward and establish cognitive control.

PubMed

Spetter, Maartje S; Feld, Gordon B; Thienel, Matthias; Preissl, Hubert; Hege, Maike A; Hallschmid, Manfred

2018-02-09

The hypothalamic neurohormone oxytocin decreases food intake via largely unexplored mechanisms. We investigated the central nervous mediation of oxytocin's hypophagic effect in comparison to its impact on the processing of generalized rewards. Fifteen fasted normal-weight, young men received intranasal oxytocin (24 IU) or placebo before functional magnetic resonance imaging (fMRI) measurements of brain activity during exposure to food stimuli and a monetary incentive delay task (MID). Subsequently, ad-libitum breakfast intake was assessed. Oxytocin compared to placebo increased activity in the ventromedial prefrontal cortex, supplementary motor area, anterior cingulate, and ventrolateral prefrontal cortices in response to high- vs. low-calorie food images in the fasted state, and reduced calorie intake by 12%. During anticipation of monetary rewards, oxytocin compared to placebo augmented striatal, orbitofrontal and insular activity without altering MID performance. We conclude that during the anticipation of generalized rewards, oxytocin stimulates dopaminergic reward-processing circuits. In contrast, oxytocin restrains food intake by enhancing the activity of brain regions that exert cognitive control, while concomitantly increasing the activity of structures that process food reward value. This pattern points towards a specific role of oxytocin in the regulation of eating behaviour in humans that might be of relevance for potential clinical applications.

Spared internal but impaired external reward prediction error signals in major depressive disorder during reinforcement learning.

PubMed

Bakic, Jasmina; Pourtois, Gilles; Jepma, Marieke; Duprat, Romain; De Raedt, Rudi; Baeken, Chris

2017-01-01

Major depressive disorder (MDD) creates debilitating effects on a wide range of cognitive functions, including reinforcement learning (RL). In this study, we sought to assess whether reward processing as such, or alternatively the complex interplay between motivation and reward might potentially account for the abnormal reward-based learning in MDD. A total of 35 treatment resistant MDD patients and 44 age matched healthy controls (HCs) performed a standard probabilistic learning task. RL was titrated using behavioral, computational modeling and event-related brain potentials (ERPs) data. MDD patients showed comparable learning rate compared to HCs. However, they showed decreased lose-shift responses as well as blunted subjective evaluations of the reinforcers used during the task, relative to HCs. Moreover, MDD patients showed normal internal (at the level of error-related negativity, ERN) but abnormal external (at the level of feedback-related negativity, FRN) reward prediction error (RPE) signals during RL, selectively when additional efforts had to be made to establish learning. Collectively, these results lend support to the assumption that MDD does not impair reward processing per se during RL. Instead, it seems to alter the processing of the emotional value of (external) reinforcers during RL, when additional intrinsic motivational processes have to be engaged. © 2016 Wiley Periodicals, Inc.

Altered subjective reward valuation among female heavy marijuana users.

PubMed

Hefner, Kathryn R; Starr, Mark J

2017-02-01

Maladaptive decision-making is a cardinal feature of drug use, contributing to ongoing use, and reflecting alterations in how drug users assess uncertain reward value. Accumulating evidence indicates the consequences of heavy marijuana use are worse for female versus male animals and humans, but research assessing sex differences in reward-related decision-making among marijuana users remains scarce. We examined sex differences in the subjective valuation of certain and uncertain rewards among heavy marijuana users (52; 26 male and 26 female) and controls (52; 26 male and 26 female). We offered male and female heavy marijuana users and controls monetary rewards of certain and uncertain (probabilistic) values. We measured how preferences for uncertain rewards varied by the objective value of those rewards, moderators of reward uncertainty, Marijuana Group and Sex. Men were more sensitive to changes in the objective value of uncertain rewards than women. However, this effect of Sex differed by Marijuana Group. Female heavy marijuana users were more sensitive to changes in uncertain reward value, particularly when the "stakes" were high (i.e., greater difference between potential uncertain rewards), than female controls. Female heavy marijuana users' sensitivity to changes in the value of high stakes uncertain rewards was comparable to male marijuana users and controls. In contrast, male marijuana users' sensitivity to changes in the value of high stakes uncertain rewards did not differ from male controls. These results suggest sex differences in sensitivity to high risk rewards may be one pathway contributing to severer consequences of heavy marijuana use among women. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Altered subjective reward valuation among female heavy marijuana users

PubMed Central

Hefner, Kathryn R.; Starr, Mark. J.

2016-01-01

Maladaptive decision-making is a cardinal feature of drug use, contributing to ongoing use, and reflecting alterations in how drug users assess uncertain reward value. Accumulating evidence indicates the consequences of heavy marijuana use are worse for female versus male animals and humans, but research assessing sex differences in reward-related decision-making among marijuana users remains scarce. We examined sex differences in the subjective valuation of certain and uncertain rewards among heavy marijuana users (52; 26 male and 26 female) and controls (52; 26 male and 26 female). We offered male and female heavy marijuana users and controls monetary rewards of certain and uncertain (probabilistic) values. We measured how preferences for uncertain rewards varied by the objective value of those rewards, moderators of reward uncertainty, marijuana use, and sex. Men were more sensitive to changes in the objective value of uncertain rewards than women. However, this effect of sex differed by marijuana group. Female heavy marijuana users were more sensitive to changes in uncertain reward value, particularly when the ‘stakes’ were high (i.e., greater difference between potential uncertain rewards), than female controls. Female heavy marijuana users’ sensitivity to changes in the value of high stakes uncertain rewards was comparable to male marijuana users and controls. In contrast, male marijuana users’ sensitivity to changes in the value of high stakes uncertain rewards did not differ from male controls. These results suggest sex differences in sensitivity to high risk rewards may be one pathway contributing to severer consequences of heavy marijuana use among women. PMID:27936816

Adolescence and Reward: Making Sense of Neural and Behavioral Changes Amid the Chaos

PubMed Central

Walker, Deena M.; Willing, Jari

2017-01-01

Adolescence is a time of significant neural and behavioral change with remarkable development in social, emotional, and cognitive skills. It is also a time of increased exploration and risk-taking (e.g., drug use). Many of these changes are thought to be the result of increased reward-value coupled with an underdeveloped inhibitory control, and thus a hypersensitivity to reward. Perturbations during adolescence can alter the developmental trajectory of the brain, resulting in long-term alterations in reward-associated behaviors. This review highlights recent developments in our understanding of how neural circuits, pubertal hormones, and environmental factors contribute to adolescent-typical reward-associated behaviors with a particular focus on sex differences, the medial prefrontal cortex, social reward, social isolation, and drug use. We then introduce a new approach that makes use of natural adaptations of seasonally breeding species to investigate the role of pubertal hormones in adolescent development. This research has only begun to parse out contributions of the many neural, endocrine, and environmental changes to the heightened reward sensitivity and increased vulnerability to mental health disorders that characterize this life stage. PMID:29118215

Amphetamine sensitization alters reward processing in the human striatum and amygdala.

PubMed

O'Daly, Owen G; Joyce, Daniel; Tracy, Derek K; Azim, Adnan; Stephan, Klaas E; Murray, Robin M; Shergill, Sukhwinder S

2014-01-01

Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS) has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD) signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders.

No Evidence for Inhibitory Deficits or Altered Reward Processing in ADHD: Data From a New Integrated Monetary Incentive Delay Go/No-Go Task.

PubMed

Demurie, Ellen; Roeyers, Herbert; Wiersema, Jan R; Sonuga-Barke, Edmund

2016-04-01

Cognitive and motivational factors differentially affect individuals with mental health problems such as ADHD. Here we introduce a new task to disentangle the relative contribution of inhibitory control and reward anticipation on task performance in children with ADHD and/or autism spectrum disorders (ASD). Typically developing children, children with ADHD,  ASD, or both disorders worked during separate sessions for monetary or social rewards in go/no-go tasks with varying inhibitory load levels. Participants also completed a monetary temporal discounting (TD) task. As predicted, task performance was sensitive to both the effects of anticipated reward amount and inhibitory load. Reward amount had different effects depending on inhibitory load level. TD correlated with inhibitory control in the ADHD group. The integration of the monetary incentive delay and go/no-go paradigms was successful. Surprisingly, there was no evidence of inhibitory control deficits or altered reward anticipation in the clinical groups. © The Author(s) 2013.

Altered functioning of reward circuitry in youth offspring of parents with bipolar disorder.

PubMed

Manelis, A; Ladouceur, C D; Graur, S; Monk, K; Bonar, L K; Hickey, M B; Dwojak, A C; Axelson, D; Goldstein, B I; Goldstein, T R; Bebko, G; Bertocci, M A; Gill, M K; Birmaher, B; Phillips, M L

2016-01-01

Offspring of parents with bipolar disorder (BD) (BO) are at higher risk of BD than offspring of parents with non-BD psychopathology (NBO), although both groups are at higher risk than offspring of psychiatrically healthy parents (HC) for other affective and psychiatric disorders. Abnormal functioning in reward circuitry has been demonstrated previously in individuals with BD. We aimed to determine whether activation and functional connectivity in this circuitry during risky decision-making differentiated BO, NBO and HC. BO (n = 29; mean age = 13.8 years; 14 female), NBO (n = 28; mean age = 13.9 years; 12 female) and HC (n = 23; mean age = 13.7 years; 11 female) were scanned while performing a number-guessing reward task. Of the participants, 11 BO and 12 NBO had current non-BD psychopathology; five BO and four NBO were taking psychotropic medications. A 3 (group) × 2 (conditions: win-control/loss-control) analysis of variance revealed a main effect of group on right frontal pole activation: BO showed significantly greater activation than HC. There was a significant main effect of group on functional connectivity between the bilateral ventral striatum and the right ventrolateral prefrontal cortex (Z > 3.09, cluster-p < 0.05): BO showed significantly greater negative functional connectivity than other participants. These between-group differences remained after removing youth with psychiatric disorders and psychotropic medications from analyses. This is the first study to demonstrate that reward circuitry activation and functional connectivity distinguish BO from NBO and HC. The fact that the pattern of findings remained when comparing healthy BO v. healthy NBO v. HC suggests that these neuroimaging measures may represent trait-level neurobiological markers conferring either risk for, or protection against, BD in youth.

Sex Differences in Drug-Related Stress-System Changes: Implications for Treatment in Substance-Abusing Women

PubMed Central

Fox, Helen C.; Sinha, Rajita

2009-01-01

Extensive research indicates that chronic substance abuse disrupts stress and reward systems of the brain. Gender variation within these stress-system alterations, including the impact of sex hormones on these changes, may influence sex-specific differences in both the development of, and recovery from, dependency. As such, gender variations in stress-system function may also provide a viable explanation for why women are markedly more vulnerable than men to the negative consequences of drug use. This article therefore initially reviews studies that have examined gender differences in emotional and biophysiological changes to the stress and reward system following the acute administration of drugs, including cocaine, alcohol, and nicotine. The article then reviews studies that have examined gender differences in response to various types of stress in both healthy and drug-abusing populations. Studies examining the impact of sex hormones on these gender-related responses are also reported. The implications of these sex-specific variations in stress and reward system function are discussed in terms of both comorbid psychopathology and treatment outcome. PMID:19373619

NEURAL REACTIVITY TO REWARD AS A PREDICTOR OF COGNITIVE BEHAVIORAL THERAPY RESPONSE IN ANXIETY AND DEPRESSION.

PubMed

Burkhouse, Katie L; Kujawa, Autumn; Kennedy, Amy E; Shankman, Stewart A; Langenecker, Scott A; Phan, K Luan; Klumpp, Heide

2016-04-01

Cognitive behavioral therapy (CBT) is a well-established treatment for anxiety and depression; however, response to CBT is heterogeneous across patients and many remain symptomatic after therapy, raising the need to identify prospective predictors for treatment planning. Altered neural processing of reward has been implicated in both depression and anxiety, and improving hedonic capacity is a goal of CBT. However, little is known about how neural response to reward relates to CBT outcomes in depression and anxiety. The current study used the reward positivity (RewP) event-related potential (ERP) component to examine whether neural reactivity to reward would predict CBT response in a sample of patients with anxiety without depression (n = 30) and comorbid anxiety and depression (CAD, n = 22). Participants completed a guessing reward ERP paradigm before completing 12 weeks of standard CBT. The majority of the sample (68%; 35 out of 52 patients) responded to treatment, and those with a reduced RewP at baseline were more likely to respond to treatment. A reduced RewP was also associated with a greater pre-to-post CBT reduction in depressive symptoms among individuals with CAD, but not among individuals with pure anxiety. CBT may be most beneficial in reducing depressive symptoms for individuals who demonstrate decreased reward reactivity prior to treatment. CBT may target reward brain function, leading to greater improvement in symptoms. These effects may be strongest, and therefore most meaningful, for individuals with reward-processing deficits prior to treatment. © 2016 Wiley Periodicals, Inc.

Neural Reactivity to Reward as a Predictor of Cognitive Behavioral Therapy Response in Anxiety and Depression

PubMed Central

Burkhouse, Katie L.; Kujawa, Autumn; Kennedy, Amy E.; Shankman, Stewart A.; Langenecker, Scott A.; Phan, K. Luan; Klumpp, Heide

2016-01-01

Background Cognitive behavioral therapy (CBT) is a well-established treatment for anxiety and depression; however, response to CBT is heterogeneous across patients and many remain symptomatic after therapy, raising the need to identify prospective predictors for treatment planning. Altered neural processing of reward has been implicated in both depression and anxiety, and improving hedonic capacity is a goal of CBT. However, little is known about how neural response to reward relates to CBT outcomes in depression and anxiety. The current study used the reward positivity (RewP) event-related potential (ERP) component to examine whether neural reactivity to reward would predict CBT response in a sample of patients with anxiety without depression (n = 30) and comorbid anxiety and depression (CAD, n = 22). Methods Participants completed a guessing reward ERP paradigm before completing 12 weeks of standard CBT. Results The majority of the sample (68%; 35 of 52 patients) responded to treatment, and those with a reduced RewP at baseline were more likely to respond to treatment. A reduced RewP was also associated with a greater pre-to-post CBT reduction in depressive symptoms among individuals with CAD, but not among individuals with pure anxiety. Conclusions CBT may be most beneficial in reducing depressive symptoms for individuals who demonstrate decreased reward reactivity prior to treatment. CBT may target reward brain function, leading to greater improvement in symptoms. These effects may be strongest, and therefore most meaningful, for individuals with reward processing deficits prior to treatment. PMID:27038409

Sex-Steroid Hormone Manipulation Reduces Brain Response to Reward.

PubMed

Macoveanu, Julian; Henningsson, Susanne; Pinborg, Anja; Jensen, Peter; Knudsen, Gitte M; Frokjaer, Vibe G; Siebner, Hartwig R

2016-03-01

Mood disorders are twice as frequent in women than in men. Risk mechanisms for major depression include adverse responses to acute changes in sex-steroid hormone levels, eg, postpartum in women. Such adverse responses may involve an altered processing of rewards. Here, we examine how women's vulnerability for mood disorders is linked to sex-steroid dynamics by investigating the effects of a pharmacologically induced fluctuation in ovarian sex steroids on the brain response to monetary rewards. In a double-blinded placebo controlled study, healthy women were randomized to receive either placebo or the gonadotropin-releasing hormone agonist (GnRHa) goserelin, which causes a net decrease in sex-steroid levels. Fifty-eight women performed a gambling task while undergoing functional MRI at baseline, during the mid-follicular phase, and again following the intervention. The gambling task enabled us to map regional brain activity related to the magnitude of risk during choice and to monetary reward. The GnRHa intervention caused a net reduction in ovarian sex steroids (estradiol and testosterone) and increased depression symptoms. Compared with placebo, GnRHa reduced amygdala's reactivity to high monetary rewards. There was a positive association between the individual changes in testosterone and changes in bilateral insula response to monetary rewards. Our data provide evidence for the involvement of sex-steroid hormones in reward processing. A blunted amygdala response to rewarding stimuli following a rapid decline in sex-steroid hormones may reflect a reduced engagement in positive experiences. Abnormal reward processing may constitute a neurobiological mechanism by which sex-steroid fluctuations provoke mood disorders in susceptible women.

Altered insula response to sweet taste processing after recovery from anorexia and bulimia nervosa

PubMed Central

Oberndorfer, Tyson A.; Frank, Guido K.W.; Simmons, Alan N.; Wagner, Angela; McCurdy, Danyale; Fudge, Julie L.; Yang, Tony T.; Paulus, Martin P.; Kaye, Walter H.

2014-01-01

Objective Recent studies suggest that altered function of higher-order appetitive neural circuitry may contribute to restricted eating in anorexia nervosa and overeating in bulimia nervosa. This study used sweet tastes to interrogate gustatory neurocircuitry involving the anterior insula and related regions that modulate sensory-interoceptive-reward signals in response to palatable foods. Method Subjects recovered from anorexia and bulimia were studied to avoid confounding effects of altered nutritional state. Functional magnetic resonance imaging measured brain response to repeated tastes of sucrose and sucralose to disentangle neural processing of caloric and non-caloric sweet tastes. Whole-brain functional analysis was constrained to anatomical regions of interest. Results Compared to matched control women (n=14), women recovered from anorexia (n=14) had diminished (F(1,27)=7.79, p=0.01) and women recovered from bulimia (n=14) had exaggerated (F(1,27)=6.12, p=0.02) right anterior insula hemodynamic response to tastes of sucrose. Furthermore, anterior insula responses to sucrose compared to sucralose was exaggerated in recovered subjects (lower in women recovered from anorexia and higher in women recovered from bulimia). Conclusions The anterior insula integrates sensory/reward aspects of taste in the service of nutritional homeostasis. For example, one possibility is that restricted eating and weight loss occur in anorexia nervosa because of a failure to accurately recognize hunger signals, whereas overeating in bulimia nervosa could represent an exaggerated perception of hunger signals. This response may reflect the altered calibration of signals related to sweet taste and the caloric content of food and may offer a pathway to novel and more effective treatments. PMID:23732817

Incentive relativity in middle aged rats.

PubMed

Justel, N; Mustaca, A; Boccia, M; Ruetti, E

2014-01-24

Response to a reinforcer is affected by prior experience with different reward values of that reward, a phenomenon known as incentive relativity. Two different procedures to study this phenomenon are the incentive downshift (ID) and the consummatory anticipatory negative contrast (cANC), the former is an emotional-cognitive protocol and the latter cognitive one. Aged rodents, as also well described in aged humans, exhibit alterations in cognitive functions. The main goal of this work was to evaluate the effect of age in the incentive' assessment using these two procedures. The results indicated that aged rats had an adequate assessment of the rewards but their performance is not completely comparable to that of young subjects. They recover faster from the ID and they had a cognitive impairment in the cANC. The results are discussed in relation to age-related changes in memory and emotion. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Ventral striatum response during reward and punishment reversal learning in unmedicated major depressive disorder.

PubMed

Robinson, Oliver J; Cools, Roshan; Carlisi, Christina O; Sahakian, Barbara J; Drevets, Wayne C

2012-02-01

Affective biases may underlie many of the key symptoms of major depressive disorder, from anhedonia to altered cognitive performance. Understanding the cause of these biases is therefore critical in the quest for improved treatments. Depression is associated, for example, with a negative affective bias in reversal learning. However, despite the fact that reversal learning is associated with striatal response in healthy individuals and depressed individuals exhibit attenuated striatal function on multiple tasks, studies to date have not demonstrated striatal involvement in the negative bias in reversal learning in depression. In this study, the authors sought to determine whether this may be because reversal learning tasks conventionally used to study behavior examine reversals only on the basis of unexpected punishment and therefore do not adequately separate reward- and punishment-based behavior. The authors used functional MRI to compare the hemodynamic response to a reversal learning task with mixed reward- and punishment-based reversal stages between individuals with unmedicated major depressive disorder (N=13) and healthy comparison subjects (N=14). Impaired reward (but not punishment) reversal accuracy was found alongside attenuated anteroventral striatal response to unexpected reward in depression. Attenuated neurophysiological response of the anteroventral striatum may reflect dysfunction in circuits involving afferent projections from the orbitofrontal, limbic, and/or mesostriatal dopaminergic pathways, which conceivably may, together with the ventral striatum, underlie anhedonia in depression. Learning to appreciate and enjoy positive life experiences is critical for recovery from depression. This study pinpoints a neural target for such recovery.

Brain reward system's alterations in response to food and monetary stimuli in overweight and obese individuals.

PubMed

Verdejo-Román, Juan; Vilar-López, Raquel; Navas, Juan F; Soriano-Mas, Carles; Verdejo-García, Antonio

2017-02-01

The brain's reward system is crucial to understand obesity in modern society, as increased neural responsivity to reward can fuel the unhealthy food choices that are driving the growing obesity epidemic. Brain's reward system responsivity to food and monetary rewards in individuals with excessive weight (overweight and obese) versus normal weight controls, along with the relationship between this responsivity and body mass index (BMI) were tested. The sample comprised 21 adults with obesity (BMI > 30), 21 with overweight (BMI between 25 and 30), and 39 with normal weight (BMI < 25). Participants underwent a functional magnetic resonance imaging (fMRI) session while performing two tasks that involve the processing of food (Willing to Pay) and monetary rewards (Monetary Incentive Delay). Neural activations within the brain reward system were compared across the three groups. Curve fit analyses were conducted to establish the association between BMI and brain reward system's response. Individuals with obesity had greater food-evoked responsivity in the dorsal and ventral striatum compared with overweight and normal weight groups. There was an inverted U-shape association between BMI and monetary-evoked responsivity in the ventral striatum, medial frontal cortex, and amygdala; that is, individuals with BMIs between 27 and 32 had greater responsivity to monetary stimuli. Obesity is associated with greater food-evoked responsivity in the ventral and dorsal striatum, and overweight is associated with greater monetary-evoked responsivity in the ventral striatum, the amygdala, and the medial frontal cortex. Findings suggest differential reactivity of the brain's reward system to food versus monetary rewards in obesity and overweight. Hum Brain Mapp 38:666-677, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Mu Opioid Receptors in Gamma-Aminobutyric Acidergic Forebrain Neurons Moderate Motivation for Heroin and Palatable Food.

PubMed

Charbogne, Pauline; Gardon, Olivier; Martín-García, Elena; Keyworth, Helen L; Matsui, Aya; Mechling, Anna E; Bienert, Thomas; Nasseef, Taufiq; Robé, Anne; Moquin, Luc; Darcq, Emmanuel; Ben Hamida, Sami; Robledo, Patricia; Matifas, Audrey; Befort, Katia; Gavériaux-Ruff, Claire; Harsan, Laura-Adela; von Elverfeldt, Dominik; Hennig, Jurgen; Gratton, Alain; Kitchen, Ian; Bailey, Alexis; Alvarez, Veronica A; Maldonado, Rafael; Kieffer, Brigitte L

2017-05-01

Mu opioid receptors (MORs) are central to pain control, drug reward, and addictive behaviors, but underlying circuit mechanisms have been poorly explored by genetic approaches. Here we investigate the contribution of MORs expressed in gamma-aminobutyric acidergic forebrain neurons to major biological effects of opiates, and also challenge the canonical disinhibition model of opiate reward. We used Dlx5/6-mediated recombination to create conditional Oprm1 mice in gamma-aminobutyric acidergic forebrain neurons. We characterized the genetic deletion by histology, electrophysiology, and microdialysis; probed neuronal activation by c-Fos immunohistochemistry and resting-state functional magnetic resonance imaging; and investigated main behavioral responses to opiates, including motivation to obtain heroin and palatable food. Mutant mice showed MOR transcript deletion mainly in the striatum. In the ventral tegmental area, local MOR activity was intact, and reduced activity was only observed at the level of striatonigral afferents. Heroin-induced neuronal activation was modified at both sites, and whole-brain functional networks were altered in live animals. Morphine analgesia was not altered, and neither was physical dependence to chronic morphine. In contrast, locomotor effects of heroin were abolished, and heroin-induced catalepsy was increased. Place preference to heroin was not modified, but remarkably, motivation to obtain heroin and palatable food was enhanced in operant self-administration procedures. Our study reveals dissociable MOR functions across mesocorticolimbic networks. Thus, beyond a well-established role in reward processing, operating at the level of local ventral tegmental area neurons, MORs also moderate motivation for appetitive stimuli within forebrain circuits that drive motivated behaviors. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Altered striatal intrinsic functional connectivity in pediatric anxiety

PubMed Central

Dorfman, Julia; Benson, Brenda; Farber, Madeline; Pine, Daniel; Ernst, Monique

2016-01-01

Anxiety disorders are among the most common psychiatric disorders of adolescence. Behavioral and task-based imaging studies implicate altered reward system function, including striatal dysfunction, in adolescent anxiety. However, no study has yet examined alterations of the striatal intrinsic functional connectivity in adolescent anxiety disorders. The current study examines striatal intrinsic functional connectivity (iFC), using six bilateral striatal seeds, among 35 adolescents with anxiety disorders and 36 healthy comparisons. Anxiety is associated with abnormally low iFC within the striatum (e.g., between nucleus accumbens and caudate nucleus), and between the striatum and prefrontal regions, including subgenual anterior cingulate cortex, posterior insula and supplementary motor area. The current findings extend prior behavioral and task-based imaging research, and provide novel data implicating decreased striatal iFC in adolescent anxiety. Alterations of striatal neurocircuitry identified in this study may contribute to the perturbations in the processing of motivational, emotional, interoceptive, and motor information seen in pediatric anxiety disorders. This pattern of the striatal iFC perturbations can guide future research on specific mechanisms underlying anxiety. PMID:27004799

Neural responses to visual food stimuli after a normal vs. higher protein breakfast in breakfast-skipping teens: a pilot fMRI study.

PubMed

Leidy, Heather J; Lepping, Rebecca J; Savage, Cary R; Harris, Corey T

2011-10-01

This functional magnetic resonance imaging (fMRI) pilot study identified whether breakfast consumption would alter the neural activity in brain regions associated with food motivation and reward in overweight "breakfast skipping" (BS) adolescent girls and examined whether increased protein at breakfast would lead to additional alterations. Ten girls (Age: 15 ± 1 years; BMI percentile 93 ± 1%; BS 5 ± 1×/week) completed 3 testing days. Following the BS day, the participants were provided with, in randomized order, normal protein (NP; 18 ± 1 g protein) or higher protein (HP; 50 ± 1 g protein) breakfast meals to consume at home for 6 days. On day 7 of each pattern, the participants came to the laboratory to consume their respective breakfast followed by appetite questionnaires and an fMRI brain scan to identify brain activation responses to viewing food vs. nonfood images prior to lunch. Breakfast consumption led to enduring (i.e., 3-h post breakfast) reductions in neural activation in the hippocampus, amygdala, cingulate, and parahippocampus vs. BS. HP led to enduring reductions in insula and middle prefrontal cortex activation vs. NP. Hippocampal, amygdala, cingulate, and insular activations were correlated with appetite and inversely correlated with satiety. In summary, the addition of breakfast led to alterations in brain activation in regions previously associated with food motivation and reward with additional alterations following the higher-protein breakfast. These data suggest that increased dietary protein at breakfast might be a beneficial strategy to reduce reward-driven eating behavior in overweight teen girls. Due to the small sample size, caution is warranted when interpreting these preliminary findings.

Subliminal and supraliminal processing of reward-related stimuli in anorexia nervosa.

PubMed

Boehm, I; King, J A; Bernardoni, F; Geisler, D; Seidel, M; Ritschel, F; Goschke, T; Haynes, J-D; Roessner, V; Ehrlich, S

2018-04-01

Previous studies have highlighted the role of the brain reward and cognitive control systems in the etiology of anorexia nervosa (AN). In an attempt to disentangle the relative contribution of these systems to the disorder, we used functional magnetic resonance imaging (fMRI) to investigate hemodynamic responses to reward-related stimuli presented both subliminally and supraliminally in acutely underweight AN patients and age-matched healthy controls (HC). fMRI data were collected from a total of 35 AN patients and 35 HC, while they passively viewed subliminally and supraliminally presented streams of food, positive social, and neutral stimuli. Activation patterns of the group × stimulation condition × stimulus type interaction were interrogated to investigate potential group differences in processing different stimulus types under the two stimulation conditions. Moreover, changes in functional connectivity were investigated using generalized psychophysiological interaction analysis. AN patients showed a generally increased response to supraliminally presented stimuli in the inferior frontal junction (IFJ), but no alterations within the reward system. Increased activation during supraliminal stimulation with food stimuli was observed in the AN group in visual regions including superior occipital gyrus and the fusiform gyrus/parahippocampal gyrus. No group difference was found with respect to the subliminal stimulation condition and functional connectivity. Increased IFJ activation in AN during supraliminal stimulation may indicate hyperactive cognitive control, which resonates with clinical presentation of excessive self-control in AN patients. Increased activation to food stimuli in visual regions may be interpreted in light of an attentional food bias in AN.

FNDC5/irisin, a molecular target for boosting reward-related learning and motivation.

PubMed

Zsuga, Judit; Tajti, Gabor; Papp, Csaba; Juhasz, Bela; Gesztelyi, Rudolf

2016-05-01

Interventions focusing on the prevention and treatment of chronic non-communicable diseases are on rise. In the current article, we propose that dysfunction of the mesocortico-limbic reward system contributes to the emergence of the WHO-identified risk behaviors (tobacco use, unhealthy diet, physical inactivity and harmful use of alcohol), behaviors that underlie the evolution of major non-communicable diseases (e.g. cardiovascular diseases, cancer, diabetes and chronic respiratory diseases). Given that dopaminergic neurons of the mesocortico-limbic system are tightly associated with reward-related processes and motivation, their dysfunction may fundamentally influence behavior. While nicotine and alcohol alter dopamine neuron function by influencing some receptors, mesocortico-limbic system dysfunction was associated with elevation of metabolic set-point leading to hedonic over-eating. Although there is some empirical evidence, precise molecular mechanism for linking physical inactivity and mesocortico-limbic dysfunction per se seems to be missing; identification of which may contribute to higher success rates for interventions targeting lifestyle changes pertaining to physical activity. In the current article, we compile evidence in support of a link between exercise and the mesocortico-limbic system by elucidating interactions on the axis of muscle - irisin - brain derived neurotrophic factor (BDNF) - and dopaminergic function of the midbrain. Irisin is a contraction-regulated myokine formed primarily in skeletal muscle but also in the brain. Irisin stirred considerable interest, when its ability to induce browning of white adipose tissue parallel to increasing thermogenesis was discovered. Furthermore, it may also play a role in the regulation of behavior given it readily enters the central nervous system, where it induces BDNF expression in several brain areas linked to reward processing, e.g. the ventral tegmental area and the hippocampus. BDNF is a neurotropic factor that increases neuronal dopamine content, modulates dopamine release relevant for neuronal plasticity and increased neuronal survival as well as learning and memory. Further linking BDNF to dopaminergic function is BDNF's ability to activate tropomyosin-related kinase B receptor that shares signalization with presynaptic dopamine-3 receptors in the ventral tegmental area. Summarizing, we propose that the skeletal muscle derived irisin may be the link between physical activity and reward-related processes and motivation. Moreover alteration of this axis may contribute to sedentary lifestyle and subsequent non-communicable diseases. Preclinical and clinical experimental models to test this hypothesis are also proposed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Perceived stress predicts altered reward and loss feedback processing in medial prefrontal cortex

PubMed Central

Treadway, Michael T.; Buckholtz, Joshua W.; Zald, David H.

2013-01-01

Stress is a significant risk factor for the development of psychopathology, particularly symptoms related to reward processing. Importantly, individuals display marked variation in how they perceive and cope with stressful events, and such differences are strongly linked to risk for developing psychiatric symptoms following stress exposure. However, many questions remain regarding the neural architecture that underlies inter-subject variability in perceptions of stressors. Using functional magnetic resonance imaging (fMRI) during a Monetary Incentive Delay (MID) paradigm, we examined the effects of self-reported perceived stress levels on neural activity during reward anticipation and feedback in a sample of healthy individuals. We found that subjects reporting more uncontrollable and overwhelming stressors displayed blunted neural responses in medial prefrontal cortex (mPFC) following feedback related to monetary gains as well monetary losses. This is consistent with preclinical models that implicate the mPFC as a key site of vulnerability to the noxious effects of uncontrollable stressors. Our data help translate these findings to humans, and elucidate some of the neural mechanisms that may underlie stress-linked risk for developing reward-related psychiatric symptoms. PMID:23730277

Distinct Roles of Opioid and Dopamine Systems in Lateral Hypothalamic Intracranial Self-Stimulation.

PubMed

Ide, Soichiro; Takahashi, Takehiro; Takamatsu, Yukio; Uhl, George R; Niki, Hiroaki; Sora, Ichiro; Ikeda, Kazutaka

2017-05-01

Opioid and dopamine systems play crucial roles in reward. Similarities and differences in the neural mechanisms of reward that are mediated by these 2 systems have remained largely unknown. Thus, in the present study, we investigated the differences in reward function in both µ-opioid receptor knockout mice and dopamine transporter knockout mice, important molecules in the opioid and dopamine systems. Mice were implanted with electrodes into the right lateral hypothalamus (l hour). Mice were then trained to put their muzzle into the hole in the head-dipping chamber for intracranial electrical stimulation, and the influences of gene knockout were assessed. Significant differences are observed between opioid and dopamine systems in reward function. µ-Opioid receptor knockout mice exhibited enhanced intracranial electrical stimulation, which induced dopamine release. They also exhibited greater motility under conditions of "despair" in both the tail suspension test and water wheel test. In contrast, dopamine transporter knockout mice maintained intracranial electrical stimulation responding even when more active efforts were required to obtain the reward. The absence of µ-opioid receptor or dopamine transporter did not lead to the absence of intracranial electrical stimulation responsiveness but rather differentially altered it. The present results in µ-opioid receptor knockout mice are consistent with the suppressive involvement of µ-opioid receptors in both positive incentive motivation associated with intracranial electrical stimulation and negative incentive motivation associated with depressive states. In contrast, the results in dopamine transporter knockout mice are consistent with the involvement of dopamine transporters in positive incentive motivation, especially its persistence. Differences in intracranial electrical stimulation in µ-opioid receptor and dopamine transporter knockout mice underscore the multidimensional nature of reward. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Effects of striatal ΔFosB overexpression and ketamine on social defeat stress-induced anhedonia in mice.

PubMed

Donahue, Rachel J; Muschamp, John W; Russo, Scott J; Nestler, Eric J; Carlezon, William A

2014-10-01

Chronic social defeat stress (CSDS) produces persistent behavioral adaptations in mice. In many behavioral assays, it can be difficult to determine if these adaptations reflect core signs of depression. We designed studies to characterize the effects of CSDS on sensitivity to reward because anhedonia (reduced sensitivity to reward) is a defining characteristic of depressive disorders in humans. We also examined the effects of striatal ΔFosB overexpression and the N-methyl-D-aspartate receptor antagonist ketamine, both of which promote resilience, on CSDS-induced alterations in reward function and social interaction. Intracranial self-stimulation (ICSS) was used to quantify CSDS-induced changes in reward function. Mice were implanted with lateral hypothalamic electrodes, and ICSS thresholds were measured after each of 10 daily CSDS sessions and during a 5-day recovery period. We also examined if acute intraperitoneal administration of ketamine (2.5-20 mg/kg) reverses CSDS-induced effects on reward or, in separate mice, social interaction. ICSS thresholds were increased by CSDS, indicating decreases in the rewarding impact of lateral hypothalamic stimulation (anhedonia). This effect was attenuated in mice overexpressing ∆FosB in striatum, consistent with pro-resilient actions of this transcription factor. High, but not low, doses of ketamine administered after completion of the CSDS regimen attenuated social avoidance in defeated mice, although this effect was transient. Ketamine did not block CSDS-induced anhedonia in the ICSS test. This study found that CSDS triggers persistent anhedonia and confirms that ΔFosB overexpression produces stress resilience. The findings of this study also indicate that acute administration of ketamine fails to attenuate CSDS-induced anhedonia despite reducing other depression-related behavioral abnormalities. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Perceived life stress exposure modulates reward-related medial prefrontal cortex responses to acute stress in depression.

PubMed

Kumar, Poornima; Slavich, George M; Berghorst, Lisa H; Treadway, Michael T; Brooks, Nancy H; Dutra, Sunny J; Greve, Douglas N; O'Donovan, Aoife; Bleil, Maria E; Maninger, Nicole; Pizzagalli, Diego A

2015-07-15

Major depressive disorder (MDD) is often precipitated by life stress and growing evidence suggests that stress-induced alterations in reward processing may contribute to such risk. However, no human imaging studies have examined how recent life stress exposure modulates the neural systems that underlie reward processing in depressed and healthy individuals. In this proof-of-concept study, 12 MDD and 10 psychiatrically healthy individuals were interviewed using the Life Events and Difficulties Schedule (LEDS) to assess their perceived levels of recent acute and chronic life stress exposure. Additionally, each participant performed a monetary incentive delay task under baseline (no-stress) and stress (social-evaluative) conditions during functional MRI. Across groups, medial prefrontal cortex (mPFC) activation to reward feedback was greater during acute stress versus no-stress conditions in individuals with greater perceived stressor severity. Under acute stress, depressed individuals showed a positive correlation between perceived stressor severity levels and reward-related mPFC activation (r=0.79, p=0.004), whereas no effect was found in healthy controls. Moreover, for depressed (but not healthy) individuals, the correlations between the stress (r=0.79) and no-stress (r=-0.48) conditions were significantly different. Finally, relative to controls, depressed participants showed significantly reduced mPFC gray matter, but functional findings remained robust while accounting for structural differences. Small sample size, which warrants replication. Depressed individuals experiencing greater recent life stress recruited the mPFC more under stress when processing rewards. Our results represent an initial step toward elucidating mechanisms underlying stress sensitization and recurrence in depression. Copyright © 2015 Elsevier B.V. All rights reserved.

Adolescence and Reward: Making Sense of Neural and Behavioral Changes Amid the Chaos.

PubMed

Walker, Deena M; Bell, Margaret R; Flores, Cecilia; Gulley, Joshua M; Willing, Jari; Paul, Matthew J

2017-11-08

Adolescence is a time of significant neural and behavioral change with remarkable development in social, emotional, and cognitive skills. It is also a time of increased exploration and risk-taking (e.g., drug use). Many of these changes are thought to be the result of increased reward-value coupled with an underdeveloped inhibitory control, and thus a hypersensitivity to reward. Perturbations during adolescence can alter the developmental trajectory of the brain, resulting in long-term alterations in reward-associated behaviors. This review highlights recent developments in our understanding of how neural circuits, pubertal hormones, and environmental factors contribute to adolescent-typical reward-associated behaviors with a particular focus on sex differences, the medial prefrontal cortex, social reward, social isolation, and drug use. We then introduce a new approach that makes use of natural adaptations of seasonally breeding species to investigate the role of pubertal hormones in adolescent development. This research has only begun to parse out contributions of the many neural, endocrine, and environmental changes to the heightened reward sensitivity and increased vulnerability to mental health disorders that characterize this life stage. Copyright © 2017 the authors 0270-6474/17/3710855-12$15.00/0.

Lipopolysaccharide Alters Motivated Behavior in a Monetary Reward Task: a Randomized Trial.

PubMed

Lasselin, Julie; Treadway, Michael T; Lacourt, Tamara E; Soop, Anne; Olsson, Mats J; Karshikoff, Bianka; Paues-Göranson, Sofie; Axelsson, John; Dantzer, Robert; Lekander, Mats

2017-03-01

Inflammation-induced sickness is associated with a large set of behavioral alterations; however, its motivational aspects remain poorly explored in humans. The present study assessed the effect of lipopolysaccharide (LPS) administration at a dose of 2 ng/kg of body weight on motivation in 21 healthy human subjects in a double-blinded, placebo (saline)-controlled, cross-over design. Incentive motivation and reward sensitivity were measured using the Effort Expenditure for Rewards Task (EEfRT), in which motivation for high-effort/high-reward trials vs low-effort/low-reward trials are manipulated by variations in reward magnitude and probability to win. Because of the strong interactions between sleepiness and motivation, the role of sleepiness was also determined. As expected, the probability to win predicted the choice to engage in high-effort/high-reward trials; however, this occurred at a greater extent after LPS than after saline administration. This effect was related to the level of sleepiness. Sleepiness increased motivation to choose the high-effort/high-reward mode of response, but only when the probability to win was the highest. LPS had no effect on reward sensitivity either directly or via sleepiness. These results indicate that systemic inflammation induced by LPS administration causes motivational changes in young healthy subjects, which are associated with sleepiness. Thus, despite its association with energy-saving behaviors, sickness allows increased incentive motivation when the effort is deemed worthwhile.

Neural reactivity to monetary rewards and losses differentiates social from generalized anxiety in children.

PubMed

Kessel, Ellen M; Kujawa, Autumn; Hajcak Proudfit, Greg; Klein, Daniel N

2015-07-01

The relationship between reward sensitivity and pediatric anxiety is poorly understood. Evidence suggests that alterations in reward processing are more characteristic of depressive than anxiety disorders. However, some studies have reported that anxiety disorders are also associated with perturbations in reward processing. Heterogeneity in the forms of anxiety studied may account for the differences between studies. We used the feedback-negativity, an event-related potential sensitive to monetary gains versus losses (ΔFN), to examine whether different forms of youth anxiety symptoms were uniquely associated with reward sensitivity as indexed by neural reactivity to the receipt of positive and negative monetary outcomes. Participants were 390, eight- to ten-year-old children (175 females) from a large community sample. The ΔFN was measured during a monetary reward task. Self-reports of child anxiety and depression symptoms and temperamental positive emotionality (PE) were obtained. Multiple regression analysis revealed that social anxiety and generalized anxiety symptoms were unique predictors of reward sensitivity after accounting for concurrent depressive symptoms and PE. While social anxiety was associated with a greater ΔFN, generalized anxiety was associated with a reduced ΔFN. Different symptom dimensions of child anxiety are differentially related to alterations in reward sensitivity. This may, in part, explain inconsistent findings in the literature regarding reward processing in anxiety. © 2014 Association for Child and Adolescent Mental Health.

Lipopolysaccharide Alters Motivated Behavior in a Monetary Reward Task: a Randomized Trial

PubMed Central

Lasselin, Julie; Treadway, Michael T; Lacourt, Tamara E; Soop, Anne; Olsson, Mats J; Karshikoff, Bianka; Paues-Göranson, Sofie; Axelsson, John; Dantzer, Robert; Lekander, Mats

2017-01-01

Inflammation-induced sickness is associated with a large set of behavioral alterations; however, its motivational aspects remain poorly explored in humans. The present study assessed the effect of lipopolysaccharide (LPS) administration at a dose of 2 ng/kg of body weight on motivation in 21 healthy human subjects in a double-blinded, placebo (saline)-controlled, cross-over design. Incentive motivation and reward sensitivity were measured using the Effort Expenditure for Rewards Task (EEfRT), in which motivation for high-effort/high-reward trials vs low-effort/low-reward trials are manipulated by variations in reward magnitude and probability to win. Because of the strong interactions between sleepiness and motivation, the role of sleepiness was also determined. As expected, the probability to win predicted the choice to engage in high-effort/high-reward trials; however, this occurred at a greater extent after LPS than after saline administration. This effect was related to the level of sleepiness. Sleepiness increased motivation to choose the high-effort/high-reward mode of response, but only when the probability to win was the highest. LPS had no effect on reward sensitivity either directly or via sleepiness. These results indicate that systemic inflammation induced by LPS administration causes motivational changes in young healthy subjects, which are associated with sleepiness. Thus, despite its association with energy-saving behaviors, sickness allows increased incentive motivation when the effort is deemed worthwhile. PMID:27620550

A longitudinal high-risk study of adolescent anxiety, depression and parent-severity on the developmental course of risk-adjustment.

PubMed

Rawal, Adhip; Riglin, Lucy; Ng-Knight, Terry; Collishaw, Stephan; Thapar, Anita; Rice, Frances

2014-11-01

Adolescence is associated with developments in the reward system and increased rates of emotional disorders. Familial risk for depression may be associated with disruptions in the reward system. However, it is unclear how symptoms of depression and anxiety influence the development of reward-processing over adolescence and whether variation in the severity of parental depression is associated with hyposensitivity to reward in a high-risk sample. We focused on risk-adjustment (adjusting decisions about reward according to the probability of obtaining reward) as this was hypothesized to improve over adolescence. In a one-year longitudinal sample (N = 197) of adolescent offspring of depressed parents, we examined how symptoms of depression and anxiety (generalized anxiety and social anxiety) influenced the development of risk-adjustment. We also examined how parental depression severity influenced adolescent risk-adjustment. Risk-adjustment improved over the course of the study indicating improved adjustment of reward-seeking to shifting contingencies. Depressive symptoms were associated with decreases in risk-adjustment over time while social anxiety symptoms were associated with increases in risk-adjustment over time. Specifically, depression was associated with reductions in reward-seeking at favourable reward probabilities only, whereas social anxiety (but not generalized anxiety) led to reductions in reward-seeking at low reward probabilities only. Parent depression severity was associated with lowered risk-adjustment in offspring and also influenced the longitudinal relationship between risk-adjustment and offspring depression. Anxiety and depression distinctly alter the pattern of longitudinal change in reward-processing. Severity of parent depression was associated with alterations in adolescent offspring reward-processing in a high-risk sample. © 2014 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

Repeated cocaine exposure facilitates the expression of incentive motivation and induces habitual control in rats.

PubMed

LeBlanc, Kimberly H; Maidment, Nigel T; Ostlund, Sean B

2013-01-01

There is growing evidence that mere exposure to drugs can induce long-term alterations in the neural systems that mediate reward processing, motivation, and behavioral control, potentially causing the pathological pursuit of drugs that characterizes the addicted state. The incentive sensitization theory proposes that drug exposure potentiates the influence of reward-paired cues on behavior. It has also been suggested that drug exposure biases action selection towards the automatic execution of habits and away from more deliberate goal-directed control. The current study investigated whether rats given repeated exposure to peripherally administered cocaine would show alterations in incentive motivation (assayed using the Pavlovian-to-instrumental transfer (PIT) paradigm) or habit formation (assayed using sensitivity to reward devaluation). After instrumental and Pavlovian training for food pellet rewards, rats were given 6 daily injections of cocaine (15 mg/kg, IP) or saline, followed by a 10-d period of rest. Consistent with the incentive sensitization theory, cocaine-treated rats showed stronger cue-evoked lever pressing than saline-treated rats during the PIT test. The same rats were then trained on a new instrumental action with a new food pellet reward before undergoing a reward devaluation testing. Although saline-treated rats exhibited sensitivity to reward devaluation, indicative of goal-directed performance, cocaine-treated rats were insensitive to this treatment, suggesting a reliance on habitual processes. These findings, when taken together, indicate that repeated exposure to cocaine can cause broad alterations in behavioral control, spanning both motivational and action selection processes, and could therefore help explain aberrations of decision-making that underlie drug addiction.

Repeated Cocaine Exposure Facilitates the Expression of Incentive Motivation and Induces Habitual Control in Rats

PubMed Central

LeBlanc, Kimberly H.; Maidment, Nigel T.; Ostlund, Sean B.

2013-01-01

There is growing evidence that mere exposure to drugs can induce long-term alterations in the neural systems that mediate reward processing, motivation, and behavioral control, potentially causing the pathological pursuit of drugs that characterizes the addicted state. The incentive sensitization theory proposes that drug exposure potentiates the influence of reward-paired cues on behavior. It has also been suggested that drug exposure biases action selection towards the automatic execution of habits and away from more deliberate goal-directed control. The current study investigated whether rats given repeated exposure to peripherally administered cocaine would show alterations in incentive motivation (assayed using the Pavlovian-to-instrumental transfer (PIT) paradigm) or habit formation (assayed using sensitivity to reward devaluation). After instrumental and Pavlovian training for food pellet rewards, rats were given 6 daily injections of cocaine (15 mg/kg, IP) or saline, followed by a 10-d period of rest. Consistent with the incentive sensitization theory, cocaine-treated rats showed stronger cue-evoked lever pressing than saline-treated rats during the PIT test. The same rats were then trained on a new instrumental action with a new food pellet reward before undergoing a reward devaluation testing. Although saline-treated rats exhibited sensitivity to reward devaluation, indicative of goal-directed performance, cocaine-treated rats were insensitive to this treatment, suggesting a reliance on habitual processes. These findings, when taken together, indicate that repeated exposure to cocaine can cause broad alterations in behavioral control, spanning both motivational and action selection processes, and could therefore help explain aberrations of decision-making that underlie drug addiction. PMID:23646106

A Mechanism for Reducing Delay Discounting by Altering Temporal Attention

ERIC Educational Resources Information Center

Radu, Peter T.; Yi, Richard; Bickel, Warren K.; Gross, James J.; McClure, Samuel M.

2011-01-01

Rewards that are not immediately available are discounted compared to rewards that are immediately available. The more a person discounts a delayed reward, the more likely that person is to have a range of behavioral problems, including clinical disorders. This latter observation has motivated the search for ions that reduce discounting. One…

Decision making with uncertain reinforcement in children with attention deficit/hyperactivity disorder (ADHD).

PubMed

Drechsler, Renate; Rizzo, Patrizia; Steinhausen, Hans-Christoph

2010-01-01

Reward-related processes are impaired in children with ADHD. Whether these deficits can be ascribed to an aversion to delay or to an altered responsiveness to magnitude, frequency, valence, or the probability of rewards still needs to be explored. In the present study, children with ADHD and normal controls aged 7 to 10 years performed a simple probabilistic discounting task. They had to choose between alternatives where the magnitude of rewards was inversely related to the probability of outcomes. As a result, children with ADHD opted more frequently for less likely but larger rewards than normal controls. Shifts of the response category after positive or negative feedback, however, occurred as often in children with ADHD as in control children. In children with ADHD, the frequency of risky choices was correlated with neuropsychological measures of response time variability but unrelated to measures of inhibitory control. It is concluded that the tendency to select less likely but larger rewards possibly represents a separate facet of dysfunctional reward processing, independent of delay aversion or altered responsiveness to feedback.

A neurocomputational account of reward and novelty processing and effects of psychostimulants in attention deficit hyperactivity disorder.

PubMed

Sethi, Arjun; Voon, Valerie; Critchley, Hugo D; Cercignani, Mara; Harrison, Neil A

2018-05-01

Computational models of reinforcement learning have helped dissect discrete components of reward-related function and characterize neurocognitive deficits in psychiatric illnesses. Stimulus novelty biases decision-making, even when unrelated to choice outcome, acting as if possessing intrinsic reward value to guide decisions toward uncertain options. Heightened novelty seeking is characteristic of attention deficit hyperactivity disorder, yet how this influences reward-related decision-making is computationally encoded, or is altered by stimulant medication, is currently uncertain. Here we used an established reinforcement-learning task to model effects of novelty on reward-related behaviour during functional MRI in 30 adults with attention deficit hyperactivity disorder and 30 age-, sex- and IQ-matched control subjects. Each participant was tested on two separate occasions, once ON and once OFF stimulant medication. OFF medication, patients with attention deficit hyperactivity disorder showed significantly impaired task performance (P = 0.027), and greater selection of novel options (P = 0.004). Moreover, persistence in selecting novel options predicted impaired task performance (P = 0.025). These behavioural deficits were accompanied by a significantly lower learning rate (P = 0.011) and heightened novelty signalling within the substantia nigra/ventral tegmental area (family-wise error corrected P < 0.05). Compared to effects in controls, stimulant medication improved attention deficit hyperactivity disorder participants' overall task performance (P = 0.011), increased reward-learning rates (P = 0.046) and enhanced their ability to differentiate optimal from non-optimal novel choices (P = 0.032). It also reduced substantia nigra/ventral tegmental area responses to novelty. Preliminary cross-sectional evidence additionally suggested an association between long-term stimulant treatment and a reduction in the rewarding value of novelty. These data suggest that aberrant substantia nigra/ventral tegmental area novelty processing plays an important role in the suboptimal reward-related decision-making characteristic of attention deficit hyperactivity disorder. Compared to effects in controls, abnormalities in novelty processing and reward-related learning were improved by stimulant medication, suggesting that they may be disorder-specific targets for the pharmacological management of attention deficit hyperactivity disorder symptoms.

Neural correlates of specific musical anhedonia

PubMed Central

Martínez-Molina, Noelia; Mas-Herrero, Ernest; Rodríguez-Fornells, Antoni; Zatorre, Robert J.

2016-01-01

Although music is ubiquitous in human societies, there are some people for whom music holds no reward value despite normal perceptual ability and preserved reward-related responses in other domains. The study of these individuals with specific musical anhedonia may be crucial to understand better the neural correlates underlying musical reward. Previous neuroimaging studies have shown that musically induced pleasure may arise from the interaction between auditory cortical networks and mesolimbic reward networks. If such interaction is critical for music-induced pleasure to emerge, then those individuals who do not experience it should show alterations in the cortical-mesolimbic response. In the current study, we addressed this question using fMRI in three groups of 15 participants, each with different sensitivity to music reward. We demonstrate that the music anhedonic participants showed selective reduction of activity for music in the nucleus accumbens (NAcc), but normal activation levels for a monetary gambling task. Furthermore, this group also exhibited decreased functional connectivity between the right auditory cortex and ventral striatum (including the NAcc). In contrast, individuals with greater than average response to music showed enhanced connectivity between these structures. Thus, our results suggest that specific musical anhedonia may be associated with a reduction in the interplay between the auditory cortex and the subcortical reward network, indicating a pivotal role of this interaction for the enjoyment of music. PMID:27799544

Neural processing of reward and punishment in young people at increased familial risk of depression.

PubMed

McCabe, Ciara; Woffindale, Caroline; Harmer, Catherine J; Cowen, Philip J

2012-10-01

Abnormalities in the neural representation of rewarding and aversive stimuli have been well-described in patients with acute depression, and we previously found abnormal neural responses to rewarding and aversive sight and taste stimuli in recovered depressed patients. The aim of the present study was to determine whether similar abnormalities might be present in young people at increased familial risk of depression but with no personal history of mood disorder. We therefore used functional magnetic resonance imaging to examine the neural responses to pleasant and aversive sights and tastes in 25 young people (16-21 years of age) with a biological parent with depression and 25 age- and gender-matched control subjects. We found that, relative to the control subjects, participants with a parental history of depression showed diminished responses in the orbitofrontal cortex to rewarding stimuli, whereas activations to aversive stimuli were increased in the lateral orbitofrontal cortex and insula. In anterior cingulate cortex the at-risk group showed blunted neural responses to both rewarding and aversive stimuli. Our findings suggest that young people at increased familial risk of depression have altered neural representation of reward and punishment, particularly in cortical regions linked to the use of positive and negative feedback to guide adaptive behavior. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Neural Reward Processing Mediates the Relationship between Insomnia Symptoms and Depression in Adolescence

PubMed Central

Casement, Melynda D.; Keenan, Kate E.; Hipwell, Alison E.; Guyer, Amanda E.; Forbes, Erika E.

2016-01-01

Study Objectives: Emerging evidence suggests that insomnia may disrupt reward-related brain function—a potentially important factor in the development of depressive disorder. Adolescence may be a period during which such disruption is especially problematic given the rise in the incidence of insomnia and ongoing development of neural systems that support reward processing. The present study uses longitudinal data to test the hypothesis that disruption of neural reward processing is a mechanism by which insomnia symptoms—including nocturnal insomnia symptoms (NIS) and nonrestorative sleep (NRS)—contribute to depressive symptoms in adolescent girls. Method: Participants were 123 adolescent girls and their caregivers from an ongoing longitudinal study of precursors to depression across adolescent development. NIS and NRS were assessed annually from ages 9 to 13 years. Girls completed a monetary reward task during a functional MRI scan at age 16 years. Depressive symptoms were assessed at ages 16 and 17 years. Multivariable regression tested the prospective associations between NIS and NRS, neural response during reward anticipation, and the mean number of depressive symptoms (omitting sleep problems). Results: NRS, but not NIS, during early adolescence was positively associated with late adolescent dorsal medial prefrontal cortex (dmPFC) response to reward anticipation and depressive symptoms. DMPFC response mediated the relationship between early adolescent NRS and late adolescent depressive symptoms. Conclusions: These results suggest that NRS may contribute to depression by disrupting reward processing via altered activity in a region of prefrontal cortex involved in affective control. The results also support the mechanistic differentiation of NIS and NRS. Citation: Casement MD, Keenan KE, Hipwell AE, Guyer AE, Forbes EE. Neural reward processing mediates the relationship between insomnia symptoms and depression in adolescence. SLEEP 2016;39(2):439–447. PMID:26350468

Estradiol is a critical regulator of food-reward behavior.

PubMed

Richard, Jennifer E; López-Ferreras, Lorena; Anderberg, Rozita H; Olandersson, Kajsa; Skibicka, Karolina P

2017-04-01

Food intake is reduced by estrogenic hormones, levels of which vary throughout life and fluctuate throughout the ovarian cycle in females. However, estrogens have also been shown to increase reward derived from drugs of abuse, where motivational properties of drugs and progression to addiction are potentiated by estrogens. Whether reward derived from food, and specifically motivational properties of food, are altered by estrogens remains unknown. Here we investigated the effect of the estrous cycle on food reward behavior and show estrous cycle dictated variability in food motivation, measured by progressive ratio operant conditioning, in female rats. Reward behavior was lowest on days associated with high estrogen signaling. We therefore also examined the actions of subcutaneously administered β-estradiol on food reward and found that β-estradiol reduced food reward behavior. The ventral tegmental area (VTA) is a crucial node of the neurocircuitry underlying motivated behavior and estrogen receptors are expressed in this nucleus. Thus, we examined whether the effects of estrogens on reward were exerted directly at the level of the VTA. Intra-VTA microinjection of β-estradiol led to a significant reduction in food-motivated behavior. Interestingly, this effect was not accompanied by a reduction in chow intake or body weight, nor did it alter locomotor activity. Importantly, removal of the ovaries produced a potent and lasting elevation in food reward and food-seeking behavior, suggesting that ovarian sex steroids are critical for maintenance of normal food reward behavior. These data reveal a novel role for estrogens in the control of food reward behavior.​. Copyright © 2017 Elsevier Ltd. All rights reserved.

Decision making and executive function in male adolescents with early-onset or adolescence-onset conduct disorder and control subjects.

PubMed

Fairchild, Graeme; van Goozen, Stephanie H M; Stollery, Sarah J; Aitken, Michael R F; Savage, Justin; Moore, Simon C; Goodyer, Ian M

2009-07-15

Although conduct disorder (CD) is associated with an increased susceptibility to substance use disorders, little is known about decision-making processes or reward mechanisms in CD. This study investigated decision making under varying motivational conditions in CD. Performances on the Risky Choice Task (RCT) and the Wisconsin Card Sorting Test (WCST) were assessed in 156 adolescents (84 control subjects, 34 with adolescence-onset CD, and 38 with early-onset CD). The RCT was performed twice, once under normal motivational conditions and once under conditions of increased motivation and psychosocial stress. Increased motivation and stress led to more cautious decision making and changes in framing effects on the RCT in all groups, although such effects were least pronounced in the early-onset CD group. Participants from both CD subgroups selected the risky choice more frequently than control subjects. Under normal motivational conditions, early-onset CD participants chose the risky choice more frequently in trials occurring after small gains, relative to control subjects and adolescence-onset CD participants. Following adjustment for IQ differences, the groups did not differ significantly in terms of WCST performance. Differences in decision making between control subjects and individuals with CD suggest that the balance between sensitivity to reward and punishment is shifted in this disorder, particularly the early-onset form. Our data on modulation of decision making according to previous outcomes suggest altered reward mechanisms in early-onset CD. The WCST data suggest that impairments in global executive function do not underlie altered decision making in CD.

Effects of Chronic Consumption of Sugar-Enriched Diets on Brain Metabolism and Insulin Sensitivity in Adult Yucatan Minipigs.

PubMed

Ochoa, Melissa; Malbert, Charles-Henri; Meurice, Paul; Val-Laillet, David

2016-01-01

Excessive sugar intake might increase the risk to develop eating disorders via an altered reward circuitry, but it remains unknown whether different sugar sources induce different neural effects and whether these effects are dependent from body weight. Therefore, we compared the effects of three high-fat and isocaloric diets varying only in their carbohydrate sources on brain activity of reward-related regions, and assessed whether brain activity is dependent on insulin sensitivity. Twenty-four minipigs underwent 18FDG PET brain imaging following 7-month intake of high-fat diets of which 20% in dry matter weight (36.3% of metabolisable energy) was provided by starch, glucose or fructose (n = 8 per diet). Animals were then subjected to a euglycemic hyperinsulinemic clamp to determine peripheral insulin sensitivity. After a 7-month diet treatment, all groups had substantial increases in body weight (from 36.02±0.85 to 63.33±0.81 kg; P<0.0001), regardless of the diet. All groups presented similar insulin sensitivity index (ISI = 1.39±0.10 mL·min-1·μUI·kg). Compared to starch, chronic exposure to fructose and glucose induced bilateral brain activations, i.e. increased basal cerebral glucose metabolism, in several reward-related brain regions including the anterior and dorsolateral prefrontal cortex, the orbitofrontal cortex, the anterior cingulate cortex, the caudate and putamen. The lack of differences in insulin sensitivity index and body weight suggests that the observed differences in basal brain glucose metabolism are not related to differences in peripheral insulin sensitivity and weight gain. The differences in basal brain metabolism in reward-related brain areas suggest the onset of cerebral functional alterations induced by chronic consumption of dietary sugars. Further studies should explore the underlying mechanisms, such as the availability of intestinal and brain sugar transporter, or the appearance of addictive-like behavioral correlates of these brain functional characteristics.

Cocaine Self-Administration Experience Induces Pathological Phasic Accumbens Dopamine Signals and Abnormal Incentive Behaviors in Drug-Abstinent Rats.

PubMed

Saddoris, Michael P; Wang, Xuefei; Sugam, Jonathan A; Carelli, Regina M

2016-01-06

Chronic exposure to drugs of abuse is linked to long-lasting alterations in the function of limbic system structures, including the nucleus accumbens (NAc). Although cocaine acts via dopaminergic mechanisms within the NAc, less is known about whether phasic dopamine (DA) signaling in the NAc is altered in animals with cocaine self-administration experience or if these animals learn and interact normally with stimuli in their environment. Here, separate groups of rats self-administered either intravenous cocaine or water to a receptacle (controls), followed by 30 d of enforced abstinence. Next, all rats learned an appetitive Pavlovian discrimination and voltammetric recordings of real-time DA release were taken in either the NAc core or shell of cocaine and control subjects. Cocaine experience differentially impaired DA signaling in the core and shell relative to controls. Although phasic DA signals in the shell were essentially abolished for all stimuli, in the core, DA did not distinguish between cues and was abnormally biased toward reward delivery. Further, cocaine rats were unable to learn higher-order associations and even altered simple conditioned approach behaviors, displaying enhanced preoccupation with cue-associated stimuli (sign-tracking; ST) but diminished time at the food cup awaiting reward delivery (goal-tracking). Critically, whereas control DA signaling correlated with ST behaviors, cocaine experience abolished this relationship. These findings show that cocaine has persistent, differential, and pathological effects on both DA signaling and DA-dependent behaviors and suggest that psychostimulant experience may remodel the very circuits that bias organisms toward repeated relapse. Relapsing to drug abuse despite periods of abstinence and sincere attempts to quit is one of the most pernicious facets of addiction. Unfortunately, little is known about how the dopamine (DA) system functions after periods of drug abstinence, particularly its role in behavior in nondrug situations. Here, rats learned about food-paired stimuli after prolonged abstinence from cocaine self-administration. Using voltammetry, we found that real-time DA signals in cocaine-experienced rats were strikingly altered relative to controls. Further, cocaine-experienced animals found reward-predictive stimuli abnormally salient and spent more time interacting with cues. Therefore, cocaine induces neuroplastic changes in the DA system that biases animals toward salient stimuli (including reward-associated cues), putting addicts at increasing risk to relapse as addiction increases in severity. Copyright © 2016 the authors 0270-6474/16/360235-16$15.00/0.

Coupling Neurogenetics (GARS™) and a Nutrigenomic Based Dopaminergic Agonist to Treat Reward Deficiency Syndrome (RDS): Targeting Polymorphic Reward Genes for Carbohydrate Addiction Algorithms

PubMed Central

Blum, Kenneth; Simpatico, Thomas; Badgaiyan, Rajendra D.; Demetrovics, Zsolt; Fratantonio, James; Agan, Gozde; Febo, Marcelo; Gold, Mark S.

2016-01-01

Earlier work from our laboratory, showing anti-addiction activity of a nutraceutical consisting of amino-acid precursors and enkephalinase inhibition properties and our discovery of the first polymorphic gene (Dopamine D2 Receptor Gene [DRD2]) to associate with severe alcoholism serves as a blue-print for the development of “Personalized Medicine” in addiction. Prior to the later genetic finding, we developed the concept of Brain Reward Cascade, which continues to act as an important component for stratification of addiction risk through neurogenetics. In 1996 our laboratory also coined the term “Reward Deficiency Syndrome (RDS)” to define a common genetic rubric for both substance and non-substance related addictive behaviors. Following many reiterations we utilized polymorphic targets of a number of reward genes (serotonergic, Opioidergic, GABAergic and Dopaminergic) to customize KB220 [Neuroadaptogen- amino-acid therapy (NAAT)] by specific algorithms. Identifying 1,000 obese subjects in the Netherlands a subsequent small subset was administered various KB220Z formulae customized according to respective DNA polymorphisms individualized that translated to significant decreases in both Body Mass Index (BMI) and weight in pounds. Following these experiments, we have been successfully developing a panel of genes known as “Genetic Addiction Risk Score” (GARSpDX)™. Selection of 10 genes with appropriate variants, a statistically significant association between the ASI-Media Version-alcohol and drug severity scores and GARSpDx was found A variant of KB220Z in abstinent heroin addicts increased resting state functional connectivity in a putative network including: dorsal anterior cingulate, medial frontal gyrus, nucleus accumbens, posterior cingulate, occipital cortical areas, and cerebellum. In addition, we show that KB220Z significantly activates, above placebo, seed regions of interest including the left nucleus accumbens, cingulate gyrus, anterior thalamic nuclei, hippocampus, pre-limbic and infra-limbic loci. KB220Z demonstrates significant functional connectivity, increased brain volume recruitment and enhanced dopaminergic functionality across the brain reward circuitry. We propose a Reward Deficiency System Solution that promotes early identification and stratification of risk alleles by utilizing GARSDx, allowing for customized nutrigenomic targeting of these risk alleles by altering KB220Z ingredients as an algorithmic function of carrying these polymorphic DNA–SNPS, potentially yielding the first ever nutrigenomic solution for addiction and pain. PMID:27617300

Abuse Pattern of Toluene Exposure Alters Mouse Behavior in a Waiting-for-Reward Operant Task

PubMed Central

Bowen, Scott E.; McDonald, Phillip

2009-01-01

Inhaling solvents for recreational purposes continues to be a world-wide public health concern. Toluene, a volatile solvent in many abused products, adversely affects the central nervous system. However, the long-term neurobehavioral effects of exposure to high-concentration, binge patterns typical of toluene abuse remain understudied. We studied the behavioral effects of repeated toluene exposure on cognitive function following binge toluene exposure on behavioral impulse control in Swiss Webster mice using a “wait-for-reward” operant task. Mice were trained on a fixed-ratio (FR) schedule using sweetened milk as a reward. Upon achieving FR15, a wait component was added which delivered free rewards in the absence of responses at increasing time intervals (2 sec, 4 sec, 6 sec, etc…). Mice continued to receive free rewards until they pressed a lever that reinstated the FR component (FR Reset). Once proficient in the FR-Wait task, mice were exposed to either 1,000 ppm, 3,600 ppm or 6,000 ppm toluene, or 0 ppm (air controls) for 30 min per day for 40 days. To avoid acute effects of toluene exposure, behavior was assessed 23 hours later. Repeated toluene exposure decreased response rates, the number of FR resets, and increased mean wait time, resulting in a higher response-to-reinforcer ratio than exhibited by controls. Mice receiving the higher exposure level (6,000 ppm) showed a dramatic decrease in the number of rewards received, which was reversed when toluene exposure ceased. Mice receiving the lower exposure level (1,000 ppm) showed little change in the number of rewards. These results indicate that repeated binge exposures to high concentrations of toluene can significantly interfere with performance as measured by a waiting-for-reward task, suggesting a significant impact on cognitive and/or psychomotor function. PMID:18832024

Altered reward processing in women recovered from anorexia nervosa.

PubMed

Wagner, Angela; Aizenstein, Howard; Venkatraman, Vijay K; Fudge, Julie; May, J Christopher; Mazurkewicz, Laura; Frank, Guido K; Bailer, Ursula F; Fischer, Lorie; Nguyen, Van; Carter, Cameron; Putnam, Karen; Kaye, Walter H

2007-12-01

Individuals with anorexia nervosa are known to be ascetic and able to sustain self-denial of food as well as most comforts and pleasures in life. Building on previous findings of altered striatal dopamine binding in anorexia nervosa, the authors sought to assess the response of the anterior ventral striatum to reward and loss in this disorder. Striatal responses to a simple monetary reward task were investigated using event-related functional magnetic resonance imaging. To avoid the confounding effects of malnutrition, the authors compared 13 healthy comparison women and 13 women who had recovered from restricting-type anorexia nervosa and had 1 year of normal weight and regular menstrual cycles, without binge eating or purging. Recovered women showed greater hemodynamic activation in the caudate than comparison women. Only the recovered women showed a significant positive relationship between trait anxiety and the percentage change in hemodynamic signal in the caudate during either wins or losses. In contrast, in the anterior ventral striatum, comparison women distinguished positive and negative feedback, whereas recovered women had similar responses to both conditions. Individuals who have recovered from anorexia nervosa may have difficulties in differentiating positive and negative feedback. The exaggerated activation of the caudate, a region involved in linking action to outcome, may constitute an attempt at "strategic" (as opposed to hedonic) means of responding to reward stimuli. The authors hypothesize that individuals with anorexia nervosa have an imbalance in information processing, with impaired ability to identify the emotional significance of a stimulus but increased traffic in neurocircuits concerned with planning and consequences.

Ventral Striatum Response During Reward and Punishment Reversal Learning in Unmedicated Major Depressive Disorder

PubMed Central

Robinson, Oliver J.; Cools, Roshan; Carlisi, Christina O.; Sahakian, Barbara J.; Drevets, Wayne C.

2017-01-01

Objective Affective biases may underlie many of the key symptoms of major depressive disorder, from anhedonia to altered cognitive performance. Understanding the cause of these biases is therefore critical in the quest for improved treatments. Depression is associated, for example, with a negative affective bias in reversal learning. However, despite the fact that reversal learning is associated with striatal response in healthy individuals and depressed individuals exhibit attenuated striatal function on multiple tasks, studies to date have not demonstrated striatal involvement in the negative bias in reversal learning in depression. In this study, the authors sought to determine whether this may be because reversal learning tasks conventionally used to study behavior examine reversals only on the basis of unexpected punishment and therefore do not adequately separate reward- and punishment-based behavior. Method The authors used functional MRI to com pare the hemodynamic response to a reversal learning task with mixed reward- and punishment-based reversal stages between individuals with unmedicated major depressive disorder (N=13) and healthy comparison subjects (N=14). Results Impaired reward (but not punishment) reversal accuracy was found alongside attenuated anteroventral striatal response to unexpected reward in depression. Conclusions Attenuated neurophysiological response of the anteroventral striatum may reflect dysfunction in circuits involving afferent projections from the orbitofrontal, limbic, and/or mesostriatal dopaminergic pathways, which conceivably may, together with the ventral striatum, underlie anhedonia in depression. Learning to appreciate and enjoy positive life experiences is critical for recovery from depression. This study pinpoints a neural target for such recovery. PMID:22420038

Are Extremes of Consumption in Eating Disorders Related to an Altered Balance between Reward and Inhibition?

PubMed

Wierenga, Christina E; Ely, Alice; Bischoff-Grethe, Amanda; Bailer, Ursula F; Simmons, Alan N; Kaye, Walter H

2014-01-01

The primary defining characteristic of a diagnosis of an eating disorder (ED) is the "disturbance of eating or eating-related behavior that results in the altered consumption or absorption of food" (DSM V; American Psychiatric Association, 2013). There is a spectrum, ranging from those who severely restrict eating and become emaciated on one end to those who binge and overconsume, usually accompanied by some form of compensatory behaviors, on the other. How can we understand reasons for such extremes of food consummatory behaviors? Recent work on obesity and substance use disorders has identified behaviors and neural pathways that play a powerful role in human consummatory behaviors. That is, corticostriatal limbic and dorsal cognitive neural circuitry can make drugs and food rewarding, but also engage self-control mechanisms that may inhibit their use. Importantly, there is considerable evidence that alterations of these systems also occur in ED. This paper explores the hypothesis that an altered balance of reward and inhibition contributes to altered extremes of response to salient stimuli, such as food. We will review recent studies that show altered sensitivity to reward and punishment in ED, with evidence of altered activity in corticostriatal and insula processes with respect to monetary gains or losses, and tastes of palatable foods. We will also discuss evidence for a spectrum of extremes of inhibition and dysregulation behaviors in ED supported by studies suggesting that this is related to top-down self-control mechanisms. The lack of a mechanistic understanding of ED has thwarted efforts for evidence-based approaches to develop interventions. Understanding how ED behavior is encoded in neural circuits would provide a foundation for developing more specific and effective treatment approaches.

How the Brain Wants What the Body Needs: The Neural Basis of Positive Alliesthesia.

PubMed

Avery, Jason A; Burrows, Kaiping; Kerr, Kara L; Bodurka, Jerzy; Khalsa, Sahib S; Paulus, Martin P; Simmons, W Kyle

2017-03-01

Discontinuing unhealthy behaviors, such as overeating or drug use, depends upon an individual's ability to overcome the influence of environmental reward cues. The strength of that influence, however, varies greatly depending upon the internal state of the body. Characterizing the relationship between interoceptive signaling and shifting drug cue valuation provides an opportunity for understanding the neural bases of how changing internal states alter reward processing more generally. A total of 17 cigarette smokers rated the pleasantness of cigarette pictures when they were nicotine sated or nicotine abstinent. On both occasions, smokers also underwent functional magnetic resonance imaging (fMRI) scanning while performing a visceral interoceptive attention task and a resting-state functional connectivity scan. Hemodynamic, physiological, and behavioral parameters were compared between sated and abstinent scans. The relationships between changes in these parameters across scan sessions were also examined. Smokers rated cigarette pictures as significantly more pleasant while nicotine abstinent than while nicotine sated. Comparing abstinent with sated scans, smokers also exhibited significantly decreased mid-insula, amygdala, and orbitofrontal activity while attending to interoceptive signals from the body. Change in interoceptive activity within the left mid-insula predicted the increase in smoker's pleasantness ratings of cigarette cues. This increase in pleasantness ratings was also correlated with an increase in resting-state functional connectivity between the mid-insula and the ventral striatum and ventral pallidum. These findings support a model wherein interoceptive processing in the mid-insula of withdrawal signals from the body potentiates the motivational salience of reward cues through the recruitment of hedonic 'hot spots' within the brain's reward circuitry.

Mirtazapine and ketanserin alter preference for gambling-like schedules of reinforcement in rats.

PubMed

Persons, Amanda L; Tedford, Stephanie E; Celeste Napier, T

2017-07-03

Drug and behavioral addictions have overlapping features, e.g., both manifest preference for larger, albeit costlier, reinforcement options in cost/benefit decision-making tasks. Our prior work revealed that the mixed-function serotonergic compound, mirtazapine, attenuates behaviors by rats motivated by abused drugs. To extend this work to behavioral addictions, here we determined if mirtazapine and/or ketanserin, another mixed-function serotonin-acting compound, can alter decision-making in rats that is independent of drug (or food)-motivated reward. Accordingly, we developed a novel variable-ratio task in rats wherein intracranial self-stimulation was used as the positive reinforcer. Using lever pressing for various levels of brain stimulation, the operant task provided choices between a small brain stimulation current delivered on a fixed-ratio schedule (i.e., a predictable reward) and a large brain stimulation delivered following an unpredictable number of responses (i.e., a variable-ratio schedule). This task allowed for demonstration of individualized preference and detection of shifts in motivational influences during a pharmacological treatment. Once baseline preference was established, we determined that pretreatment with mirtazapine or ketanserin significantly decreased preference for the large reinforcer presented after gambling-like schedules of reinforcement. When the rats were tested the next day without drug, preference for the unpredictable large reinforcer option was restored. These data demonstrate that mirtazapine and ketanserin can reduce preference for larger, costlier reinforcement options, and illustrate the potential for these drugs to alter behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

Distinct patterns of outcome valuation and amygdala-prefrontal cortex synaptic remodeling in adolescence and adulthood

PubMed Central

Stolyarova, Alexandra; Izquierdo, Alicia

2015-01-01

Adolescent behavior is typified by increased risk-taking, reward- and novelty-seeking, as well as an augmented need for social and environmental stimulation. This behavioral phenotype may result from alterations in outcome valuation or reward learning. In the present set of experiments, we directly compared adult and adolescent animals on tasks measuring both of these processes. Additionally, we examined developmental differences in dopamine D1-like receptor (D1R), dopamine D2-like receptor (D2R), and polysialylated neural cell adhesion molecule (PSA-NCAM) expression in animals that were trained on an effortful reward valuation task, given that these proteins play an important role in the functional development of the amygdala-prefrontocortical (PFC) circuit and mesocorticolimbic dopamine system. We found that adolescent animals were not different from adults in appetitive associative learning, but exhibited distinct pattern of responses to differences in outcome values, which was paralleled by an enhanced motivation to invest effort to obtain larger rewards. There were no differences in D2 receptor expression, but D1 receptor expression was significantly reduced in the striatum of animals that had experiences with reward learning during adolescence compared to animals that went through the same experiences in adulthood. We observed increased levels of PSA-NCAM expression in both PFC and amygdala of late adolescents compared to adults that were previously trained on an effortful reward valuation task. PSA-NCAM levels in PFC were strongly and positively associated with high effort/reward (HER) choices in adolescents, but not in adult animals. Increased levels of PSA-NCAM expression in adolescents may index increased structural plasticity and represent a neural correlate of a reward sensitive endophenotype. PMID:25999830

Dopaminergic dysfunction in schizophrenia: salience attribution revisited.

PubMed

Heinz, Andreas; Schlagenhauf, Florian

2010-05-01

A dysregulation of the mesolimbic dopamine system in schizophrenia patients may lead to aberrant attribution of incentive salience and contribute to the emergence of psychopathological symptoms like delusions. The dopaminergic signal has been conceptualized to represent a prediction error that indicates the difference between received and predicted reward. The incentive salience hypothesis states that dopamine mediates the attribution of "incentive salience" to conditioned cues that predict reward. This hypothesis was initially applied in the context of drug addiction and then transferred to schizophrenic psychosis. It was hypothesized that increased firing (chaotic or stress associated) of dopaminergic neurons in the striatum of schizophrenia patients attributes incentive salience to otherwise irrelevant stimuli. Here, we review recent neuroimaging studies directly addressing this hypothesis. They suggest that neuronal functions associated with dopaminergic signaling, such as the attribution of salience to reward-predicting stimuli and the computation of prediction errors, are indeed altered in schizophrenia patients and that this impairment appears to contribute to delusion formation.

Deficient neural activity subserving decision-making during reward waiting time in intertemporal choice in adult attention-deficit hyperactivity disorder.

PubMed

Todokoro, Ayako; Tanaka, Saori C; Kawakubo, Yuki; Yahata, Noriaki; Ishii-Takahashi, Ayaka; Nishimura, Yukika; Kano, Yukiko; Ohtake, Fumio; Kasai, Kiyoto

2018-04-24

Impulsivity, which significantly affects social adaptation, is an important target behavioral characteristic in interventions for attention-deficit hyperactivity disorder (ADHD). Typically, people are willing to wait longer to acquire greater rewards. Impulsivity in ADHD may be associated with brain dysfunction in decision-making involving waiting behavior under such situations. We tested the hypothesis that brain circuitry during a period of waiting (i.e., prior to the acquisition of reward) is altered in adults with ADHD. The participants included 14 medication-free adults with ADHD and 16 healthy controls matched for age, sex, IQ, and handedness. The behavioral task had participants choose between a delayed, larger monetary reward and an immediate, smaller monetary reward, where the reward waiting time actually occurred during functional magnetic resonance imaging measurement. We tested for group differences in the contrast values of blood-oxygen-level dependent signals associated with the length of waiting time, calculated using the parametric modulation method. While the two groups did not differ in the time discounting rate, the delay-sensitive contrast values were significantly lower in the caudate and visual cortex in individuals with ADHD. The higher impulsivity scores were significantly associated with lower delay-sensitive contrast values in the caudate and visual cortex. These results suggest that deficient neural activity affects decision-making involving reward waiting time during intertemporal choice tasks, and provide an explanation for the basis of impulsivity in adult ADHD. © 2018 The Author. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology.

Reward Contingencies Improve Goal-Directed Behavior by Enhancing Posterior Brain Attentional Regions and Increasing Corticostriatal Connectivity in Cocaine Addicts.

PubMed

Rosell-Negre, Patricia; Bustamante, Juan-Carlos; Fuentes-Claramonte, Paola; Costumero, Víctor; Llopis-Llacer, Juan-José; Barrós-Loscertales, Alfonso

2016-01-01

The dopaminergic system provides the basis for the interaction between motivation and cognition. It is triggered by the possibility of obtaining rewards to initiate the neurobehavioral adaptations necessary to achieve them by directing the information from motivational circuits to cognitive and action circuits. In drug addiction, the altered dopamine (DA) modulation of the meso-cortico-limbic reward circuitry, such as the prefrontal cortex (PFC), underlies the disproportionate motivational value of drug use at the expense of other non-drug reinforcers and the user's loss of control over his/her drug intake. We examine how the magnitude of the reward affects goal-directed processes in healthy control (HC) subjects and abstinent cocaine dependent (ACD) patients by using functional magnetic resonance imaging (fMRI) during a counting Stroop task with blocked levels of monetary incentives of different magnitudes (€0, €0.01, €0.5, €1 or €1.5). Our results showed that increasing reward magnitude enhances (1) performance facilitation in both groups; (2) left dorsolateral prefrontal cortex (DLPFC) activity in HC and left superior occipital cortex activity in ACD; and (3) left DLPFC and left putamen connectivity in ACD compared to HC. Moreover, we observed that (4) dorsal striatal and pallidum activity was associated with craving and addiction severity during the parametric increases in the monetary reward. In conclusion, the brain response to gradients in monetary value was different in HC and ACD, but both groups showed improved task performance due to the possibility of obtaining greater monetary rewards.

Reward Contingencies Improve Goal-Directed Behavior by Enhancing Posterior Brain Attentional Regions and Increasing Corticostriatal Connectivity in Cocaine Addicts

PubMed Central

Rosell-Negre, Patricia; Bustamante, Juan-Carlos; Fuentes-Claramonte, Paola; Costumero, Víctor; Llopis-Llacer, Juan-José; Barrós-Loscertales, Alfonso

2016-01-01

The dopaminergic system provides the basis for the interaction between motivation and cognition. It is triggered by the possibility of obtaining rewards to initiate the neurobehavioral adaptations necessary to achieve them by directing the information from motivational circuits to cognitive and action circuits. In drug addiction, the altered dopamine (DA) modulation of the meso-cortico-limbic reward circuitry, such as the prefrontal cortex (PFC), underlies the disproportionate motivational value of drug use at the expense of other non-drug reinforcers and the user’s loss of control over his/her drug intake. We examine how the magnitude of the reward affects goal-directed processes in healthy control (HC) subjects and abstinent cocaine dependent (ACD) patients by using functional magnetic resonance imaging (fMRI) during a counting Stroop task with blocked levels of monetary incentives of different magnitudes (€0, €0.01, €0.5, €1 or €1.5). Our results showed that increasing reward magnitude enhances (1) performance facilitation in both groups; (2) left dorsolateral prefrontal cortex (DLPFC) activity in HC and left superior occipital cortex activity in ACD; and (3) left DLPFC and left putamen connectivity in ACD compared to HC. Moreover, we observed that (4) dorsal striatal and pallidum activity was associated with craving and addiction severity during the parametric increases in the monetary reward. In conclusion, the brain response to gradients in monetary value was different in HC and ACD, but both groups showed improved task performance due to the possibility of obtaining greater monetary rewards. PMID:27907134

Dopamine modulates striatal response to reward and punishment in patients with Parkinson's disease: a pharmacological challenge fMRI study.

PubMed

Argyelan, Miklos; Herzallah, Mohammad; Sako, Wataru; DeLucia, Ivana; Sarpal, Deepak; Vo, An; Fitzpatrick, Toni; Moustafa, Ahmed A; Eidelberg, David; Gluck, Mark

2018-05-02

It is well established that Parkinson's disease leads to impaired learning from reward and enhanced learning from punishment. The administration of dopaminergic medications reverses this learning pattern. However, few studies have investigated the neural underpinnings of these cognitive processes. In this study, using fMRI, we tested a group of Parkinson's disease patients on and off dopaminergic medications and matched healthy individuals. All individuals completed an fMRI cognitive task that dissociates feedback learning from reward versus punishment. The administration of dopaminergic medications attenuated blood oxygen level dependent (BOLD) responses to punishment in the bilateral putamen, in bilateral dorsolateral prefrontal cortex and the left premotor cortex. Further, the administration of dopaminergic medications resulted in a higher ratio of BOLD activity between reward and punishment trials in these brain areas. BOLD activity in these brain areas was significantly correlated with learning from punishment, but not from reward trials. Furthermore, the administration of dopaminergic medications altered BOLD activity in the right insula and ventromedial prefrontal cortex when Parkinson's disease patients were anticipating feedback. These findings are in agreement with a large body of literature indicating that Parkinson's disease is associated with enhanced learning from punishment. However, it was surprising that dopaminergic medications modulated punishment learning as opposed to reward learning, although reward learning has been directly linked to dopaminergic function. We argue that these results might be attributed to both a change in the balance between direct and indirect pathway activation in the basal ganglia as well as the differential activity of D1 versus D2 dopamine receptors.

The risk variant in ODZ4 for bipolar disorder impacts on amygdala activation during reward processing.

PubMed

Heinrich, Angela; Lourdusamy, Anbarasu; Tzschoppe, Jelka; Vollstädt-Klein, Sabine; Bühler, Mira; Steiner, Sabina; Bach, Christiane; Poustka, Luise; Banaschewski, Tobias; Barker, Gareth; Büchel, Christian; Conrod, Patricia; Garavan, Hugh; Gallinat, Jürgen; Heinz, Andreas; Ittermann, Bernd; Loth, Eva; Mann, Karl; Martinot, Jean-Luc; Paus, Tomáš; Pausova, Zdenka; Smolka, Michael; Ströhle, Andreas; Struve, Maren; Witt, Stephanie; Flor, Herta; Schumann, Gunter; Rietschel, Marcella; Nees, Frauke

2013-06-01

Bipolar disorder is a severe mood disorder, which normally begins during adolescence or early adulthood and has a heritability of up to 80%. The largest genome-wide association analysis of bipolar disorder recently identified a new genome-wide associated variant in OZD4 (rs12576775). The aim of the present study was to further elucidate the role of this risk variant in the disease process using an imaging genetics approach. As increased amygdala and striatal responses during the processing of reward and emotion are characteristic for bipolar disorder patients, it was tested whether the risk variant has an influence on this endophenotype in healthy adolescents. We examined the impact of the risk variant rs12576775 on functional magnetic resonance imaging data in an adolescent sample (N = 485). Differential activation between carriers of the risk allele (G-allele) and homozygous A-allele carriers in the amygdala and the striatum during a modification of the monetary incentive delay task (examining reward) and a face task (examining emotion) was analyzed. Carriers of the risk allele showed an increased blood oxygen level-dependent response in the amygdala during reward sensitivity (p = 0.05) and reward expectation (p < 0.05) but not during the face task. No significant group differences were found in the striatum during both reward and emotion processing. Our results indicate that the ODZ4 risk variant influences reward processing in the amygdala. Alterations in the processing of emotion may have different underlying mechanisms and need to be further examined. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Emotional Eating Phenotype is Associated with Central Dopamine D2 Receptor Binding Independent of Body Mass Index

PubMed Central

Eisenstein, Sarah A.; Bischoff, Allison N.; Gredysa, Danuta M.; Antenor-Dorsey, Jo Ann V.; Koller, Jonathan M.; Al-Lozi, Amal; Pepino, Marta Y.; Klein, Samuel; Perlmutter, Joel S.; Moerlein, Stephen M.; Black, Kevin J.; Hershey, Tamara

2015-01-01

PET studies have provided mixed evidence regarding central D2/D3 dopamine receptor binding and its relationship with obesity as measured by body mass index (BMI). Other aspects of obesity may be more tightly coupled to the dopaminergic system. We characterized obesity-associated behaviors and determined if these related to central D2 receptor (D2R) specific binding independent of BMI. Twenty-two obese and 17 normal-weight participants completed eating- and reward-related questionnaires and underwent PET scans using the D2R-selective and nondisplaceable radioligand (N-[11C]methyl)benperidol. Questionnaires were grouped by domain (eating related to emotion, eating related to reward, non-eating behavior motivated by reward or sensitivity to punishment). Normalized, summed scores for each domain were compared between obese and normal-weight groups and correlated with striatal and midbrain D2R binding. Compared to normal-weight individuals, the obese group self-reported higher rates of eating related to both emotion and reward (p < 0.001), greater sensitivity to punishment (p = 0.06), and lower non-food reward behavior (p < 0.01). Across normal-weight and obese participants, self-reported emotional eating and non-food reward behavior positively correlated with striatal (p < 0.05) and midbrain (p < 0.05) D2R binding, respectively. In conclusion, an emotional eating phenotype may reflect altered central D2R function better than other commonly used obesity-related measures such as BMI. PMID:26066863

Insula and striatum activity in effort-related monetary reward processing in gambling disorder: the role of depressive symptomatology.

PubMed

Fauth-Bühler, Mira; Zois, Evangelos; Vollstädt-Klein, Sabine; Lemenager, Tagrid; Beutel, Martin; Mann, Karl

2014-01-01

The neurobiological underpinnings of effort-related monetary reward processing of gambling disorder have not been previously studied. To date neuroimaging studies lack in large sample sizes and as a consequence less attention has been given to brain reward processing that could potentially be attributed to comorbid conditions such as depressive mood state. We assessed monetary reward processing using an effort-dependent task during 3 tesla functional magnetic resonance imaging. We investigated a large sample of male, right-handed, slot-machine-playing disordered gamblers (DGs; N = 80) as well as age- and smoking-matched male healthy controls (HCs; N = 89). Depressive symptoms were assessed using the Beck Depression Inventory (BDI). DGs and HCs were divided into subgroups ("high" and "low") based on their BDI scores. Effort-related monetary reward processing did not differ between the complete groups of HCs and DGs. Brain activation during receipt of monetary reward though revealed a significant Group × BDI interaction: DGs with higher BDI scores compared to DGs with lower BDI scores showed greater brain activity in the right insula cortex and dorsal striatum while no differences were observed for HCs with higher versus lower BDI scores. Our results suggest that effort-related aspects of monetary motivation, i.e. when monetary output is tied to performance, are not altered in DG. Additionally, our findings strengthen the need for subgroup comparisons in future investigations of the disorder as part of a personalized medicine approach.

Romantic Love vs. Drug Addiction May Inspire a New Treatment for Addiction

PubMed Central

Zou, Zhiling; Song, Hongwen; Zhang, Yuting; Zhang, Xiaochu

2016-01-01

Drug addiction is a complex neurological dysfunction induced by recurring drug intoxication. Strategies to prevent and treat drug addiction constitute a topic of research interest. Early-stage romantic love is characterized by some characteristics of addiction, which gradually disappear as the love relationship progresses. Therefore, comparison of the concordance and discordance between romantic love and drug addiction may elucidate potential treatments for addiction. This focused review uses the evidences from our recent studies to compare the neural alterations between romantic love and drug addiction, moreover we also compare the behavioral and neurochemical alterations between romantic love and drug addiction. From the behavioral comparisons we find that there are many similarities between the early stage of romantic love and drug addiction, and this stage romantic love is considered as a behavioral addiction, while significant differences exist between the later stage of romantic love and drug addiction, and this stage of romantic love eventually developed into a prosocial behavior. The neuroimaging comparisons suggest that romantic love and drug addiction both display the functional enhancement in reward and emotion regulation network. Except the similar neural changes, romantic love display special function enhancement in social cognition network, while drug addiction display special dysfunction in cognitive control network. The neurochemical comparisons show that there are many similarities in the dopamine (DA) system, while significant differences in oxytocin (OT) system for romantic love and drug addiction. These findings indicate that the functional alterations in reward and emotion regulation network and the DA system may be the neurophysiological basis of romantic love as a behavioral addiction, and the functional alterations in social cognition network and the OT system may be the neurophysiological basis of romantic love as a prosocial behavior. It seems that the OT system is a critical factor for the development of addiction. So we then discuss strategies to treat drug addiction with OT, and suggest that future research should further investigate OT system interventions aiming to improve cognitive control and/or social cognition functions, in order to develop strategies designed to more effectively treat drug addiction. PMID:27713720

Romantic Love vs. Drug Addiction May Inspire a New Treatment for Addiction.

PubMed

Zou, Zhiling; Song, Hongwen; Zhang, Yuting; Zhang, Xiaochu

2016-01-01

Drug addiction is a complex neurological dysfunction induced by recurring drug intoxication. Strategies to prevent and treat drug addiction constitute a topic of research interest. Early-stage romantic love is characterized by some characteristics of addiction, which gradually disappear as the love relationship progresses. Therefore, comparison of the concordance and discordance between romantic love and drug addiction may elucidate potential treatments for addiction. This focused review uses the evidences from our recent studies to compare the neural alterations between romantic love and drug addiction, moreover we also compare the behavioral and neurochemical alterations between romantic love and drug addiction. From the behavioral comparisons we find that there are many similarities between the early stage of romantic love and drug addiction, and this stage romantic love is considered as a behavioral addiction, while significant differences exist between the later stage of romantic love and drug addiction, and this stage of romantic love eventually developed into a prosocial behavior. The neuroimaging comparisons suggest that romantic love and drug addiction both display the functional enhancement in reward and emotion regulation network. Except the similar neural changes, romantic love display special function enhancement in social cognition network, while drug addiction display special dysfunction in cognitive control network. The neurochemical comparisons show that there are many similarities in the dopamine (DA) system, while significant differences in oxytocin (OT) system for romantic love and drug addiction. These findings indicate that the functional alterations in reward and emotion regulation network and the DA system may be the neurophysiological basis of romantic love as a behavioral addiction, and the functional alterations in social cognition network and the OT system may be the neurophysiological basis of romantic love as a prosocial behavior. It seems that the OT system is a critical factor for the development of addiction. So we then discuss strategies to treat drug addiction with OT, and suggest that future research should further investigate OT system interventions aiming to improve cognitive control and/or social cognition functions, in order to develop strategies designed to more effectively treat drug addiction.

Translational Rodent Paradigms to Investigate Neuromechanisms Underlying Behaviors Relevant to Amotivation and Altered Reward Processing in Schizophrenia

PubMed Central

Young, Jared W.; Markou, Athina

2015-01-01

Amotivation and reward-processing deficits have long been described in patients with schizophrenia and considered large contributors to patients’ inability to integrate well in society. No effective treatments exist for these symptoms, partly because the neuromechanisms mediating such symptoms are poorly understood. Here, we propose a translational neuroscientific approach that can be used to assess reward/motivational deficits related to the negative symptoms of schizophrenia using behavioral paradigms that can also be conducted in experimental animals. By designing and using objective laboratory behavioral tools that are parallel in their parameters in rodents and humans, the neuromechanisms underlying behaviors with relevance to these symptoms of schizophrenia can be investigated. We describe tasks that measure the motivation of rodents to expend physical and cognitive effort to gain rewards, as well as probabilistic learning tasks that assess both reward learning and feedback-based decision making. The latter tasks are relevant because of demonstrated links of performance deficits correlating with negative symptoms in patients with schizophrenia. These tasks utilize operant techniques in order to investigate neural circuits targeting a specific domain across species. These tasks therefore enable the development of insights into altered mechanisms leading to negative symptom-relevant behaviors in patients with schizophrenia. Such findings will then enable the development of targeted treatments for these altered neuromechanisms and behaviors seen in schizophrenia. PMID:26194891

“Liking” and “wanting” of sweet and oily food stimuli as affected by high-fat diet-induced obesity, weight loss, leptin, and genetic predisposition

PubMed Central

Shin, Andrew C.; Townsend, R. Leigh; Patterson, Laurel M.

2011-01-01

Cross-sectional studies in both humans and animals have demonstrated associations between obesity and altered reward functions at the behavioral and neural level, but it is unclear whether these alterations are cause or consequence of the obese state. Reward behaviors were quantified in male, outbred Sprague-Dawley (SD) and selected line obesity-prone (OP) and obesity-resistant (OR) rats after induction of obesity by high-fat diet feeding and after subsequent loss of excess body weight by chronic calorie restriction. As measured by the brief access lick and taste-reactivity paradigms, both obese SD and OP rats “liked” low concentrations of sucrose and corn oil less, but “liked” the highest concentrations more, compared with lean rats, and this effect was fully reversed by weight loss in SD rats. Acute food deprivation was unable to change decreased responsiveness to low concentrations but eliminated increased responsiveness to high concentrations in obese SD rats, and leptin administration in weight-reduced SD rats shifted concentration-response curves toward that seen in the obese state in the brief access lick test. “Wanting” and reinforcement learning as assessed in the incentive runway and progressive ratio lever-pressing paradigms was paradoxically decreased in both obese (compared with lean SD rats) and OP (compared with OR rats). Thus, reversible, obesity-associated, reduced “liking” and “wanting” of low-calorie foods in SD rats suggest a role for secondary effects of the obese state on reward functions, while similar differences between select lines of OP and OR rats before induction of obesity indicate a genetic component. PMID:21849633

Maternal “junk-food” feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring

PubMed Central

Ong, Z. Y.; Muhlhausler, B. S.

2011-01-01

Individuals exposed to high-fat, high-sugar diets before birth have an increased risk of obesity in later life. Recent studies have shown that these offspring exhibit increased preference for fat, leading to suggestions that perinatal exposure to high-fat, high-sugar foods results in permanent changes within the central reward system that increase the subsequent drive to overconsume palatable foods. The present study has determined the effect of a maternal “junk-food” diet on the expression of key components of the mesolimbic reward pathway in the offspring of rat dams at 6 wk and 3 mo of age. We show that offspring of junk-food-fed (JF) dams exhibit higher fat intake from weaning until at least 3 mo of age (males: 16±0.6 vs. 11±0.8 g/kg/d; females: 19±1.3 vs. 13±0.4 g/kg/d; P<0.01). mRNA expression of μ-opioid receptor (Mu) was 1.6-fold higher (P<0.01) and dopamine active transporter (DAT) was 2-fold lower (P<0.05) in JF offspring at 6 wk of age. By 3 mo, these differences were reversed, and Mu mRNA expression was 2.8-fold lower (P<0.01) and DAT mRNA expression was 1.9-fold higher (P<0.01) in the JF offspring. These findings suggest that perinatal exposure to high-fat, high-sugar diets results in altered development of the central reward system, resulting in increased fat intake and altered response of the reward system to excessive junk-food intake in postnatal life.—Ong, Z. Y., Muhlhausler, B. S. Maternal “junk-food” feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring. PMID:21427213

Nectar quality perception by honey bees (Apis mellifera ligustica).

PubMed

Sanderson, Charlotte E; Cook, Peyton; Hill, Peggy S M; Orozco, Benjamin S; Abramson, Charles I; Wells, Harrington

2013-11-01

In exploring how foragers perceive rewards, we often find that well-motivated individuals are not too choosy and unmotivated individuals are unreliable and inconsistent. Nevertheless, when given a choice we see that individuals can clearly distinguish between rewards. Here we develop the logic of using responses to two-choice problems as a derivative function of perceived reward, and utilize this model to examine honey bee perception of nectar quality. Measuring the derivative allows us to deduce the perceived reward function. The derivative function of the perceived reward equation gives the rate of change of the reward perceived for each reward value. This approach depends on presenting free-flying foragers with a series of two different rewards presented simultaneously (i.e., two-choice, binomial tests). We also examine how honey bees integrate information from a range of reward qualities to formulate a functional response. Results suggest that honey bees overestimate higher quality rewards and that direct comparison is an important step in the integration of information from a range of rewards.

Impaired Flexible Reward-Based Decision-Making in Binge Eating Disorder: Evidence from Computational Modeling and Functional Neuroimaging.

PubMed

Reiter, Andrea M F; Heinze, Hans-Jochen; Schlagenhauf, Florian; Deserno, Lorenz

2017-02-01

Despite its clinical relevance and the recent recognition as a diagnostic category in the DSM-5, binge eating disorder (BED) has rarely been investigated from a cognitive neuroscientific perspective targeting a more precise neurocognitive profiling of the disorder. BED patients suffer from a lack of behavioral control during recurrent binge eating episodes and thus fail to adapt their behavior in the face of negative consequences, eg, high risk for obesity. To examine impairments in flexible reward-based decision-making, we exposed BED patients (n=22) and matched healthy individuals (n=22) to a reward-guided decision-making task during functional resonance imaging (fMRI). Performing fMRI analysis informed via computational modeling of choice behavior, we were able to identify specific signatures of altered decision-making in BED. On the behavioral level, we observed impaired behavioral adaptation in BED, which was due to enhanced switching behavior, a putative deficit in striking a balance between exploration and exploitation appropriately. This was accompanied by diminished activation related to exploratory decisions in the anterior insula/ventro-lateral prefrontal cortex. Moreover, although so-called model-free reward prediction errors remained intact, representation of ventro-medial prefrontal learning signatures, incorporating inference on unchosen options, was reduced in BED, which was associated with successful decision-making in the task. On the basis of a computational psychiatry account, the presented findings contribute to defining a neurocognitive phenotype of BED.

Impaired Flexible Reward-Based Decision-Making in Binge Eating Disorder: Evidence from Computational Modeling and Functional Neuroimaging

PubMed Central

Reiter, Andrea M F; Heinze, Hans-Jochen; Schlagenhauf, Florian; Deserno, Lorenz

2017-01-01

Despite its clinical relevance and the recent recognition as a diagnostic category in the DSM-5, binge eating disorder (BED) has rarely been investigated from a cognitive neuroscientific perspective targeting a more precise neurocognitive profiling of the disorder. BED patients suffer from a lack of behavioral control during recurrent binge eating episodes and thus fail to adapt their behavior in the face of negative consequences, eg, high risk for obesity. To examine impairments in flexible reward-based decision-making, we exposed BED patients (n=22) and matched healthy individuals (n=22) to a reward-guided decision-making task during functional resonance imaging (fMRI). Performing fMRI analysis informed via computational modeling of choice behavior, we were able to identify specific signatures of altered decision-making in BED. On the behavioral level, we observed impaired behavioral adaptation in BED, which was due to enhanced switching behavior, a putative deficit in striking a balance between exploration and exploitation appropriately. This was accompanied by diminished activation related to exploratory decisions in the anterior insula/ventro-lateral prefrontal cortex. Moreover, although so-called model-free reward prediction errors remained intact, representation of ventro–medial prefrontal learning signatures, incorporating inference on unchosen options, was reduced in BED, which was associated with successful decision-making in the task. On the basis of a computational psychiatry account, the presented findings contribute to defining a neurocognitive phenotype of BED. PMID:27301429

Pathological gambling and alcohol dependence: neural disturbances in reward and loss avoidance processing.

PubMed

Romanczuk-Seiferth, Nina; Koehler, Saskia; Dreesen, Caspar; Wüstenberg, Torsten; Heinz, Andreas

2015-05-01

Pathological gambling (PG) shares clinical characteristics such as craving and loss of control with substance use disorders and is thus considered a behavioral addiction. While functional alterations in the mesolimbic reward system have been correlated with craving and relapse in substance use disorders, only a few studies have examined this brain circuit in PG, and no direct comparison has been conducted so far. Thus, we investigated the neuronal correlates of reward processing in PG in contrast to alcohol-dependent (AD) patients and healthy subjects. Eighteen PG patients, 15 AD patients and 17 controls were investigated with a monetary incentive delay task, in which visual cues predict the consequence (monetary gain, avoidance of loss, none) of a fast response to a subsequent target stimulus. Functional magnetic resonance imaging data were analyzed to account for possible confounding factors such as local gray matter volume. Activity in the right ventral striatum during loss anticipation was increased in PG patients compared with controls and AD patients. Moreover, PG patients showed decreased activation in the right ventral striatum and right medial prefrontal cortex during successful loss avoidance compared with controls, which was inversely associated with severity of gambling behavior. Thus, despite neurobiological similarities to substance use disorders in reward processing, as reported by previous studies, we found relevant differences with respect to the anticipation of loss as well as its avoidance (negative reinforcement), which further contributes to the understanding of PG. © 2014 Society for the Study of Addiction.

Attenuating GABAA Receptor Signaling in Dopamine Neurons Selectively Enhances Reward Learning and Alters Risk Preference in Mice

PubMed Central

Parker, Jones G.; Wanat, Matthew J.; Soden, Marta E.; Ahmad, Kinza; Zweifel, Larry S.; Bamford, Nigel S.; Palmiter, Richard D.

2011-01-01

Phasic dopamine transmission encodes the value of reward-predictive stimuli and influences both learning and decision-making. Altered dopamine signaling is associated with psychiatric conditions characterized by risky choices such as pathological gambling. These observations highlight the importance of understanding how dopamine neuron activity is modulated. While excitatory drive onto dopamine neurons is critical for generating phasic dopamine responses, emerging evidence suggests that inhibitory signaling also modulates these responses. To address the functional importance of inhibitory signaling in dopamine neurons, we generated mice lacking the β3 subunit of the GABAA receptor specifically in dopamine neurons (β3-KO mice) and examined their behavior in tasks that assessed appetitive learning, aversive learning, and risk preference. Dopamine neurons in midbrain slices from β3-KO mice exhibited attenuated GABA-evoked inhibitory post-synaptic currents. Furthermore, electrical stimulation of excitatory afferents to dopamine neurons elicited more dopamine release in the nucleus accumbens of β3-KO mice as measured by fast-scan cyclic voltammetry. β3-KO mice were more active than controls when given morphine, which correlated with potential compensatory upregulation of GABAergic tone onto dopamine neurons. β3-KO mice learned faster in two food-reinforced learning paradigms, but extinguished their learned behavior normally. Enhanced learning was specific for appetitive tasks, as aversive learning was unaffected in β3-KO mice. Finally, we found that β3-KO mice had enhanced risk preference in a probabilistic selection task that required mice to choose between a small certain reward and a larger uncertain reward. Collectively, these findings identify a selective role for GABAA signaling in dopamine neurons in appetitive learning and decision-making. PMID:22114279

Leptin is associated with exaggerated brain reward and emotion responses to food images in adolescent obesity.

PubMed

Jastreboff, Ania M; Lacadie, Cheryl; Seo, Dongju; Kubat, Jessica; Van Name, Michelle A; Giannini, Cosimo; Savoye, Mary; Constable, R Todd; Sherwin, Robert S; Caprio, Sonia; Sinha, Rajita

2014-11-01

In the U.S., an astonishing 12.5 million children and adolescents are now obese, predisposing 17% of our nation's youth to metabolic complications of obesity, such as type 2 diabetes (T2D). Adolescent obesity has tripled over the last three decades in the setting of food advertising directed at children. Obese adults exhibit increased brain responses to food images in motivation-reward pathways. These neural alterations may be attributed to obesity-related metabolic changes, which promote food craving and high-calorie food (HCF) consumption. It is not known whether these metabolic changes affect neural responses in the adolescent brain during a crucial period for establishing healthy eating behaviors. Twenty-five obese (BMI 34.4 kg/m2, age 15.7 years) and fifteen lean (BMI 20.96 kg/m2, age 15.5 years) adolescents underwent functional MRI during exposure to HCF, low-calorie food (LCF), and nonfood (NF) visual stimuli 2 h after isocaloric meal consumption. Brain responses to HCF relative to NF cues increased in obese versus lean adolescents in striatal-limbic regions (i.e., putamen/caudate, insula, amygdala) (P < 0.05, family-wise error [FWE]), involved in motivation-reward and emotion processing. Higher endogenous leptin levels correlated with increased neural activation to HCF images in all subjects (P < 0.05, FWE). This significant association between higher circulating leptin and hyperresponsiveness of brain motivation-reward regions to HCF images suggests that dysfunctional leptin signaling may contribute to the risk of overconsumption of these foods, thus further predisposing adolescents to the development of obesity and T2D. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

The habenula as a novel link between the homeostatic and hedonic pathways in cancer-associated weight loss: a pilot study.

PubMed

Maldonado, Maria; Molfese, David L; Viswanath, Humsini; Curtis, Kaylah; Jones, Ashley; Hayes, Teresa G; Marcelli, Marco; Mediwala, Sanjay; Baldwin, Philip; Garcia, Jose M; Salas, Ramiro

2018-06-01

Little is known about the brain mechanisms underlying cancer-associated weight loss (C-WL) in humans despite this condition negatively affecting their quality of life and survival. We tested the hypothesis that patients with C-WL have abnormal connectivity in homeostatic and hedonic brain pathways together with altered brain activity during food reward. In 12 patients with cancer and 12 healthy controls, resting-state functional connectivity (RSFC, resting brain activity observed through changes in blood flow in the brain which creates a blood oxygen level-dependent signal that can be measured using functional magnetic resonance imaging) was used to compare three brain regions hypothesized to play a role in C-WL: the hypothalamus (homeostatic), the nucleus accumbens (hedonic), and the habenula (an important regulator of reward). In addition, the brain reward response to juice was studied. Participants included 12 patients with histological diagnosis of incurable cancer (solid tumours), a European Cooperative Oncology Group performance status of 0-2, and a ≥5% involuntary body weight loss from pre-illness over the previous 6 months and 12 non-cancer controls matched for age, sex, and race. RSFC between the hypothalamus, nucleus accumbens, and habenula and brain striatum activity as measured by functional MRI during juice reward delivery events were the main outcome measures. After adjusting for BMI and compared with matched controls, patients with C-WL were found to have reduced RSFC between the habenula and hypothalamus (P = 0.04) and between the habenula and nucleus accumbens (P = 0.014). Patients with C-WL also had reduced juice reward responses in the striatum compared with controls. In patients with C-WL, reduced connectivity between both homeostatic and hedonic brain regions and the habenula and reduced juice reward were observed. Further research is needed to establish the relevance of the habenula and striatum in C-WL. Published 2018. This article is a U.S. Government work and is in the public domain in the USA. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Overexpression of Neuronal RNA-binding protein HuD increases reward induced reinstatement of an instrumental response.

PubMed

Oliver, Robert J; Kenton, Johnny A; Stevens, Wennonah; Perrone-Bizzozero, Nora I; Brigman, Jonathan L

2018-06-22

The neuronal RNA-binding protein HuD is involved in synaptic plasticity and the molecular mechanisms of learning and memory. Previously, we have shown that HuD is upregulated after both spatial and addiction-associated forms of learning, such as conditioned place preference. However, what role HuD plays in non-drug dependent learning and memory is not fully understood. In order to elucidate the role that HuD plays in non-drug appetitive behavior, we assessed mice over-expressing HuD (HuD OE ) throughout the forebrain on the acquisition of an instrumental response for a non-sucrose food reward utilizing a touch-screen paradigm. Next, we examined whether HuD level would alter the extinction or reward-induced reinstatement of responding. We found that HuD OE acquired and extinguished the instrumental response at rates similar to control littermates with no significant alterations in secondary measures of motor behavior or motivation. However, HuD OE reinstated their responding for food reward at rates significantly higher than control animals after a brief presentation of reward. These results suggest that HuD positively regulates the reinstatement of natural reward seeking and supports the role of HuD in forms of learning and memory associated with seeking of appetitive rewards. Copyright © 2018. Published by Elsevier B.V.

Region specific up-regulation of oxytocin receptors in the opioid oprm1 (-/-) mouse model of autism.

PubMed

Gigliucci, Valentina; Leonzino, Marianna; Busnelli, Marta; Luchetti, Alessandra; Palladino, Viola Stella; D'Amato, Francesca R; Chini, Bice

2014-01-01

Autism spectrum disorders (ASDs) are characterized by impaired communication, social impairments, and restricted and repetitive behaviors and interests. Recently, altered motivation and reward processes have been suggested to participate in the physiopathology of ASDs, and μ-opioid receptors (MORs) have been investigated in relation to social reward due to their involvement in the neural circuitry of reward. Mice lacking a functional MOR gene (Oprm1 (-/-) mice) display abnormal social behavior and major autistic-like core symptoms, making them an animal model of autism. The oxytocin (OXT) system is a key regulator of social behavior and co-operates with the opioidergic system in the modulation of social behavior. To better understand the opioid-OXT interplay in the central nervous system, we first determined the expression of the oxytocin receptor (OXTR) in the brain of WT C57BL6/J mice by quantitative autoradiography; we then evaluated OXTR regional alterations in Oprm1 (-/-) mice. Moreover, we tested these mice in a paradigm of social behavior, the male-female social interaction test, and analyzed the effects of acute intranasal OXT treatment on their performance. In autoradiography, Oprm1 (-/-) mice selectively displayed increased OXTR expression in the Medial Anterior Olfactory Nucleus, the Central and Medial Amygdaloid nuclei, and the Nucleus Accumbens. Our behavioral results confirmed that Oprm1 (-/-) male mice displayed social impairments, as indicated by reduced ultrasonic calls, and that these were rescued by a single intranasal administration of OXT. Taken together, our results provide evidence of an interaction between OXT and opioids in socially relevant brain areas and in the modulation of social behavior. Moreover, they suggest that the oxytocinergic system may act as a compensative mechanism to bypass and/or restore alterations in circuits linked to impaired social behavior.

Brain reward-system activation in response to anticipation and consumption of palatable food is altered by glucagon-like peptide-1 receptor activation in humans.

PubMed

van Bloemendaal, L; Veltman, D J; Ten Kulve, J S; Groot, P F C; Ruhé, H G; Barkhof, F; Sloan, J H; Diamant, M; Ijzerman, R G

2015-09-01

To test the hypothesis that food intake reduction after glucagon-like peptide-1 (GLP-1) receptor activation is mediated through brain areas regulating anticipatory and consummatory food reward. As part of a larger study, we determined the effects of GLP-1 receptor activation on brain responses to anticipation and receipt of chocolate milk versus a tasteless solution, using functional MRI (fMRI). Obese subjects with type 2 diabetes, and obese and lean subjects with normoglycaemia (n = 48) underwent three fMRI sessions at separate visits with intravenous infusion of the GLP-1 receptor agonist exenatide, exenatide with prior GLP-1 receptor blockade by exendin-9-39 or placebo, during somatostatin pituitary-pancreatic clamps. Body mass index negatively correlated with brain responses to receipt of chocolate milk and positively correlated with anticipation of receipt of chocolate milk in brain areas regulating reward, appetite and motivation. Exenatide increased brain responses to receipt of chocolate milk and decreased anticipation of receipt of chocolate milk compared with placebo, paralleled by reductions in food intake. Exendin-9-39 largely prevented these effects. Our findings show that GLP-1 receptor activation decreases anticipatory food reward, which may reduce cravings for food and increases consummatory food reward, which may prevent overeating. © 2015 John Wiley & Sons Ltd.

Dopaminergic modulation of the trade-off between probability and time in economic decision-making.

PubMed

Arrondo, Gonzalo; Aznárez-Sanado, Maite; Fernández-Seara, Maria A; Goñi, Joaquín; Loayza, Francis R; Salamon-Klobut, Ewa; Heukamp, Franz H; Pastor, Maria A

2015-06-01

Studies on animals and humans have demonstrated the importance of dopamine in modulating decision-making processes. In this work, we have tested dopaminergic modulation of economic decision-making and its neural correlates by administering either placebo or metoclopramide, a dopamine D2-receptor antagonist, to healthy subjects, during a functional MRI study. The decision-making task combined probability and time delay with a fixed monetary reward. For individual behavioral characterization, we used the Probability Time Trade-off (PTT) economic model, which integrates the traditional trade-offs of reward magnitude-time and reward magnitude-probability into a single measurement, thereby quantifying the subjective value of a delayed and probabilistic outcome. A regression analysis between BOLD signal and the PTT model index permitted to identify the neural substrate encoding the subjective reward-value. Behaviorally, medication reduced the rate of temporal discounting over probability, reflected in medicated subjects being more prone to postpone the reward in order to increase the outcome probability. In addition, medicated subjects showed less activity during the task in the postcentral gyrus as well as frontomedian areas, whereas there were no differences in the ventromedial orbitofrontal cortex (VMOFC) between groups when coding the subjective value. The present study demonstrates by means of behavior and imaging that dopamine modulation alters the probability-time trade-off in human economic decision-making. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Sir2/Sirt1 Links Acute Inebriation to Presynaptic Changes and the Development of Alcohol Tolerance, Preference, and Reward.

PubMed

Engel, Gregory L; Marella, Sunanda; Kaun, Karla R; Wu, Julia; Adhikari, Pratik; Kong, Eric C; Wolf, Fred W

2016-05-11

Acute ethanol inebriation causes neuroadaptive changes in behavior that favor increased intake. Ethanol-induced alterations in gene expression, through epigenetic and other means, are likely to change cellular and neural circuit function. Ethanol markedly changes histone acetylation, and the sirtuin Sir2/SIRT1 that deacetylates histones and transcription factors is essential for the rewarding effects of long-term drug use. The molecular transformations leading from short-term to long-term ethanol responses mostly remain to be discovered. We find that Sir2 in the mushroom bodies of the fruit fly Drosophila promotes short-term ethanol-induced behavioral plasticity by allowing changes in the expression of presynaptic molecules. Acute inebriation strongly reduces Sir2 levels and increases histone H3 acetylation in the brain. Flies lacking Sir2 globally, in the adult nervous system, or specifically in the mushroom body α/β-lobes show reduced ethanol sensitivity and tolerance. Sir2-dependent ethanol reward is also localized to the mushroom bodies, and Sir2 mutants prefer ethanol even without a priming ethanol pre-exposure. Transcriptomic analysis reveals that specific presynaptic molecules, including the synaptic vesicle pool regulator Synapsin, depend on Sir2 to be regulated by ethanol. Synapsin is required for ethanol sensitivity and tolerance. We propose that the regulation of Sir2/SIRT1 by acute inebriation forms part of a transcriptional program in mushroom body neurons to alter presynaptic properties and neural responses to favor the development of ethanol tolerance, preference, and reward. We identify a mechanism by which acute ethanol inebriation leads to changes in nervous system function that may be an important basis for increasing ethanol intake and addiction liability. The findings are significant because they identify ethanol-driven transcriptional events that target presynaptic properties and direct behavioral plasticity. They also demonstrate that multiple forms of ethanol behavioral plasticity that are relevant to alcoholism are initiated by a shared mechanism. Finally, they link these events to the Drosophila brain region that associates context with innate approach and avoidance responses to code for reward and other higher-order behavior, similar in aspects to the role of the vertebrate mesolimbic system. Copyright © 2016 the authors 0270-6474/16/365241-11$15.00/0.

Altered motivation masks appetitive learning potential of obese mice

PubMed Central

Harb, Mazen R.; Almeida, Osborne F. X.

2014-01-01

Eating depends strongly on learning processes which, in turn, depend on motivation. Conditioned learning, where individuals associate environmental cues with receipt of a reward, forms an important part of hedonic mechanisms; the latter contribute to the development of human overweight and obesity by driving excessive eating in what may become a vicious cycle. Although mice are commonly used to explore the regulation of human appetite, it is not known whether their conditioned learning of food rewards varies as a function of body mass. To address this, groups of adult male mice of differing body weights were tested two appetitive conditioning paradigms (pavlovian and operant) as well as in food retrieval and hedonic preference tests in an attempt to dissect the respective roles of learning/motivation and energy state in the regulation of feeding behavior. We found that (i) the rate of pavlovian conditioning to an appetitive reward develops as an inverse function of body weight; (ii) higher body weight associates with increased latency to collect food reward; and (iii) mice with lower body weights are more motivated to work for a food reward, as compared to animals with higher body weights. Interestingly, as compared to controls, overweight and obese mice consumed smaller amounts of palatable foods (isocaloric milk or sucrose, in either the presence or absence of their respective maintenance diets: standard, low fat-high carbohydrate or high fat-high carbohydrate). Notably, however, all groups adjusted their consumption of the different food types, such that their body weight-corrected daily intake of calories remained constant. Thus, overeating in mice does not reflect a reward deficiency syndrome and, in contrast to humans, mice regulate their caloric intake according to metabolic status rather than to the hedonic properties of a particular food. Together, these observations demonstrate that excess weight masks the capacity for appetitive learning in the mouse. PMID:25400563

Altered Brain Activity during Reward Anticipation in Pathological Gambling and Obsessive-Compulsive Disorder

PubMed Central

Choi, Jung-Seok; Shin, Young-Chul; Jung, Wi Hoon; Jang, Joon Hwan; Kang, Do-Hyung; Choi, Chi-Hoon; Choi, Sam-Wook; Lee, Jun-Young; Hwang, Jae Yeon; Kwon, Jun Soo

2012-01-01

Background Pathological gambling (PG) and obsessive-compulsive disorder (OCD) are conceptualized as a behavioral addiction, with a dependency on repetitive gambling behavior and rewarding effects following compulsive behavior, respectively. However, no neuroimaging studies to date have examined reward circuitry during the anticipation phase of reward in PG compared with in OCD while considering repetitive gambling and compulsion as addictive behaviors. Methods/Principal Findings To elucidate the neural activities specific to the anticipation phase of reward, we performed event-related functional magnetic resonance imaging (fMRI) in young adults with PG and compared them with those in patients with OCD and healthy controls. Fifteen male patients with PG, 13 patients with OCD, and 15 healthy controls, group-matched for age, gender, and IQ, participated in a monetary incentive delay task during fMRI scanning. Neural activation in the ventromedial caudate nucleus during anticipation of both gain and loss decreased in patients with PG compared with that in patients with OCD and healthy controls. Additionally, reduced activation in the anterior insula during anticipation of loss was observed in patients with PG compared with that in patients with OCD which was intermediate between that in OCD and healthy controls (healthy controls < PG < OCD), and a significant positive correlation between activity in the anterior insula and South Oaks Gambling Screen score was found in patients with PG. Conclusions Decreased neural activity in the ventromedial caudate nucleus during anticipation may be a specific neurobiological feature for the pathophysiology of PG, distinguishing it from OCD and healthy controls. Correlation of anterior insular activity during loss anticipation with PG symptoms suggests that patients with PG fit the features of OCD associated with harm avoidance as PG symptoms deteriorate. Our findings have identified functional disparities and similarities between patients with PG and OCD related to the neural responses associated with reward anticipation. PMID:23029329

Ventral striatal network connectivity reflects reward learning and behavior in patients with Parkinson's disease.

PubMed

Petersen, Kalen; Van Wouwe, Nelleke; Stark, Adam; Lin, Ya-Chen; Kang, Hakmook; Trujillo-Diaz, Paula; Kessler, Robert; Zald, David; Donahue, Manus J; Claassen, Daniel O

2018-01-01

A subgroup of Parkinson's disease (PD) patients treated with dopaminergic therapy develop compulsive reward-driven behaviors, which can result in life-altering morbidity. The mesocorticolimbic dopamine network guides reward-motivated behavior; however, its role in this treatment-related behavioral phenotype is incompletely understood. Here, mesocorticolimbic network function in PD patients who develop impulsive and compulsive behaviors (ICB) in response to dopamine agonists was assessed using BOLD fMRI. The tested hypothesis was that network connectivity between the ventral striatum and the limbic cortex is elevated in patients with ICB and that reward-learning proficiency reflects the extent of mesocorticolimbic network connectivity. To evaluate this hypothesis, 3.0T BOLD-fMRI was applied to measure baseline functional connectivity on and off dopamine agonist therapy in age and sex-matched PD patients with (n = 19) or without (n = 18) ICB. An incentive-based task was administered to a subset of patients (n = 20) to quantify positively or negatively reinforced learning. Whole-brain voxelwise analyses and region-of-interest-based mixed linear effects modeling were performed. Elevated ventral striatal connectivity to the anterior cingulate gyrus (P = 0.013), orbitofrontal cortex (P = 0.034), insula (P = 0.044), putamen (P = 0.014), globus pallidus (P < 0.01), and thalamus (P < 0.01) was observed in patients with ICB. A strong trend for elevated amygdala-to-midbrain connectivity was found in ICB patients on dopamine agonist. Ventral striatum-to-subgenual cingulate connectivity correlated with reward learning (P < 0.01), but not with punishment-avoidance learning. These data indicate that PD-ICB patients have elevated network connectivity in the mesocorticolimbic network. Behaviorally, proficient reward-based learning is related to this enhanced limbic and ventral striatal connectivity. Hum Brain Mapp 39:509-521, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: role of the ventral tegmental area and central nucleus of the amygdala.

PubMed

Kenny, Paul J; Chartoff, Elena; Roberto, Marisa; Carlezon, William A; Markou, Athina

2009-01-01

Nicotine is considered an important component of tobacco responsible for the smoking habit in humans. Nicotine increases glutamate-mediated transmission throughout brain reward circuitries. This action of nicotine could potentially contribute to its intrinsic rewarding and reward-enhancing properties, which motivate consumption of the drug. Here we show that the competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0.5-2.5 mg per kg) abolished nicotine-enhanced brain reward function, reflected in blockade of the lowering of intracranial self-stimulation (ICSS) thresholds usually observed after experimenter-administered (0.25 mg per kg) or intravenously self-administered (0.03 mg per kg per infusion) nicotine injections. The highest LY235959 dose (5 mg per kg) tested reversed the hedonic valence of nicotine from positive to negative, reflected in nicotine-induced elevations of ICSS thresholds. LY235959 doses that reversed nicotine-induced lowering of ICSS thresholds also markedly decreased nicotine self-administration without altering responding for food reinforcement, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist NBQX had no effects on nicotine intake. In addition, nicotine self-administration upregulated NMDA receptor subunit expression in the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA), suggesting important interactions between nicotine and the NMDA receptor. Furthermore, nicotine (1 microM) increased NMDA receptor-mediated excitatory postsynaptic currents in rat CeA slices, similar to its previously described effects in the VTA. Finally, infusion of LY235959 (0.1-10 ng per side) into the CeA or VTA decreased nicotine self-administration. Taken together, these data suggest that NMDA receptors, including those in the CeA and VTA, gate the magnitude and valence of the effects of nicotine on brain reward systems, thereby regulating motivation to consume the drug.

Reward signals, attempted suicide, and impulsivity in late-life depression.

PubMed

Dombrovski, Alexandre Y; Szanto, Katalin; Clark, Luke; Reynolds, Charles F; Siegle, Greg J

2013-10-01

IMPORTANCE—Suicide can be viewed as an escape from unendurable punishment at the cost of any future rewards. Could faulty estimation of these outcomes predispose to suicidal behavior? In behavioral studies, many of those who have attempted suicide misestimate expected rewards on gambling and probabilistic learning tasks.OBJECTIVES—To describe the neural circuit abnormalities that underlie disadvantageous choices in people at risk for suicide and to relate these abnormalities to impulsivity, which is one of the components of vulnerability to suicide.DESIGN—Case-control functional magnetic resonance imaging study of reward learning using are inforcement learning model.SETTING—University hospital and outpatient clinic.PATIENTS—Fifty-three participants 60 years or older, including 15 depressed patients who had attempted suicide, 18 depressed patients who had never attempted suicide (depressed control subjects), and 20 psychiatrically healthy controls.MAIN OUTCOMES AND MEASURES—Components of the cortical blood oxygenation level–dependent response tracking expected and unpredicted rewards.RESULTS—Depressed elderly participants displayed 2 distinct disruptions of control over reward-guided behavior. First, impulsivity and a history of suicide attempts (particularly poorly planned ones) were associated with a weakened expected reward signal in the paralimbic cortex,which in turn predicted the behavioral insensitivity to contingency change. Second, depression was associated with disrupted corticostriatothalamic encoding of unpredicted rewards, which in turn predicted the behavioral over sensitivity to punishment. These results were robust to the effects of possible brain damage from suicide attempts, depressive severity, co-occurring substance use and anxiety disorders, antidepressant and anticholinergic exposure, lifetime exposure to electroconvulsive therapy, vascular illness, and incipient dementia.CONCLUSIONS AND RELEVANCE—Altered paralimbic reward signals and impulsivity and/or carelessness may facilitate unplanned suicidal acts. This pattern, also seen in gambling and cocaine use, may reflect a primary deficit in the paralimbic cortex or in its mesolimbic input. The over reactivity to punishment in depression may be caused in part by a disruption of appetitive learning in the corticostriatothalamic circuits.

Reward Signals, Attempted Suicide, and Impulsivity in Late-Life Depression

PubMed Central

Dombrovski, Alexandre Y.; Szanto, Katalin; Clark, Luke; Reynolds, Charles F.; Siegle, Greg J.

2013-01-01

IMPORTANCE Suicide can be viewed as an escape from unendurable punishment at the cost of any future rewards. Could faulty estimation of these outcomes predispose to suicidal behavior? In behavioral studies, many of those who have attempted suicide misestimate expected rewards on gambling and probabilistic learning tasks. OBJECTIVES To describe the neural circuit abnormalities that underlie disadvantageous choices in people at risk for suicide and to relate these abnormalities to impulsivity, which is one of the components of vulnerability to suicide. DESIGN Case-control functional magnetic resonance imaging study of reward learning using a reinforcement learning model. SETTING University hospital and outpatient clinic. PATIENTS Fifty-three participants 60 years or older, including 15 depressed patients who had attempted suicide, 18 depressed patients who had never attempted suicide (depressed control subjects), and 20 psychiatrically healthy controls. MAIN OUTCOMES AND MEASURES Components of the cortical blood oxygenation level–dependent response tracking expected and unpredicted rewards. RESULTS Depressed elderly participants displayed 2 distinct disruptions of control over reward-guided behavior. First, impulsivity and a history of suicide attempts (particularly poorly planned ones) were associated with a weakened expected reward signal in the paralimbic cortex, which in turn predicted the behavioral insensitivity to contingency change. Second, depression was associated with disrupted corticostriatothalamic encoding of unpredicted rewards, which in turn predicted the behavioral oversensitivity to punishment. These results were robust to the effects of possible brain damage from suicide attempts, depressive severity, co-occurring substance use and anxiety disorders, antidepressant and anticholinergic exposure, lifetime exposure to electroconvulsive therapy, vascular illness, and incipient dementia. CONCLUSIONS AND RELEVANCE Altered paralimbic reward signals and impulsivity and/or carelessness may facilitate unplanned suicidal acts. This pattern, also seen in gambling and cocaine use, may reflect a primary deficit in the paralimbic cortex or in its mesolimbic input. The overreactivity to punishment in depression may be caused in part by a disruption of appetitive learning in the corticostriatothalamic circuits. PMID:23925710

Cytokine effects on the basal ganglia and dopamine function: the subcortical source of inflammatory malaise.

PubMed

Felger, Jennifer C; Miller, Andrew H

2012-08-01

Data suggest that cytokines released during the inflammatory response target subcortical structures including the basal ganglia as well as dopamine function to acutely induce behavioral changes that support fighting infection and wound healing. However, chronic inflammation and exposure to inflammatory cytokines appears to lead to persisting alterations in the basal ganglia and dopamine function reflected by anhedonia, fatigue, and psychomotor slowing. Moreover, reduced neural responses to hedonic reward, decreased dopamine metabolites in the cerebrospinal fluid and increased presynaptic dopamine uptake and decreased turnover have been described. This multiplicity of changes in the basal ganglia and dopamine function suggest fundamental effects of inflammatory cytokines on dopamine synthesis, packaging, release and/or reuptake, which may sabotage and circumvent the efficacy of current treatment approaches. Thus, examination of the mechanisms by which cytokines alter the basal ganglia and dopamine function will yield novel insights into the treatment of cytokine-induced behavioral changes and inflammatory malaise. Copyright © 2012 Elsevier Inc. All rights reserved.

Reward alters the perception of time.

PubMed

Failing, Michel; Theeuwes, Jan

2016-03-01

Recent findings indicate that monetary rewards have a powerful effect on cognitive performance. In order to maximize overall gain, the prospect of earning reward biases visual attention to specific locations or stimulus features improving perceptual sensitivity and processing. The question we addressed in this study is whether the prospect of reward also affects the subjective perception of time. Here, participants performed a prospective timing task using temporal oddballs. The results show that temporal oddballs, displayed for varying durations, presented in a sequence of standard stimuli were perceived to last longer when they signaled a relatively high reward compared to when they signaled no or low reward. When instead of the oddball the standards signaled reward, the perception of the temporal oddball remained unaffected. We argue that by signaling reward, a stimulus becomes subjectively more salient thereby modulating its attentional deployment and distorting how it is perceived in time. Copyright © 2015 Elsevier B.V. All rights reserved.

Neural Correlates of Reward Processing in Depressed and Healthy Preschool-Age Children.

PubMed

Belden, Andy C; Irvin, Kelsey; Hajcak, Greg; Kappenman, Emily S; Kelly, Danielle; Karlow, Samantha; Luby, Joan L; Barch, Deanna M

2016-12-01

Adults and adolescents with major depressive disorder (MDD) show a blunted neural response to rewards. Depression has been validated in children as young as age 3; however, it remains unclear whether blunted response to reward is also a core feature of preschool-onset depression. If so, this would provide further validation for the continuity of the neural correlates of depression across the life span and would identify a potential target for treatment in young children. Fifty-three 4- to 7-year-old children with depression and 25 psychiatrically healthy 4- to 7-year-old children completed a simple guessing task in which points could be won or lost on each trial while event-related potentials (ERPs) were recorded. Psychiatric diagnosis was established using a preschool version of the Kiddie Schedule for Affective Disorders and Depression. Young children with depression showed a reduced differentiation between response to gains and losses, and this finding was driven by a blunted response to reward (i.e., the reward positivity [RewP]). These findings held even when controlling for co-occurring attention-deficit/hyperactivity disorder, oppositional defiant disorder, and generalized anxiety disorder. The RewP did not vary as a function of depression severity within the group with depression. Similar to adults and adolescents with depression, preschoolers with depression display reductions in responsivity to rewards as indexed by the RewP. These findings provide further evidence for continuity in the neural mechanisms associated with depression across the lifespan, and point to altered reward sensitivity as an early-emerging potential target for intervention in preschool-onset depression. Clinical trial registration information-A Randomized Controlled Trial of PCIT-ED for Preschool Depression; http://clinicaltrials.gov/; NCT02076425. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Differential effects of natural rewards and pain on vesicular glutamate transporter expression in the nucleus accumbens.

PubMed

Tukey, David S; Lee, Michelle; Xu, Duo; Eberle, Sarah E; Goffer, Yossef; Manders, Toby R; Ziff, Edward B; Wang, Jing

2013-07-09

Pain and natural rewards such as food elicit different behavioral effects. Both pain and rewards, however, have been shown to alter synaptic activities in the nucleus accumbens (NAc), a key component of the brain reward system. Mechanisms by which external stimuli regulate plasticity at NAc synapses are largely unexplored. Medium spiny neurons (MSNs) from the NAc receive excitatory glutamatergic inputs and modulatory dopaminergic and cholinergic inputs from a variety of cortical and subcortical structures. Glutamate inputs to the NAc arise primarily from prefrontal cortex, thalamus, amygdala, and hippocampus, and different glutamate projections provide distinct synaptic and ultimately behavioral functions. The family of vesicular glutamate transporters (VGLUTs 1-3) plays a key role in the uploading of glutamate into synaptic vesicles. VGLUT1-3 isoforms have distinct expression patterns in the brain, but the effects of external stimuli on their expression patterns have not been studied. In this study, we use a sucrose self-administration paradigm for natural rewards, and spared nerve injury (SNI) model for chronic pain. We examine the levels of VGLUTs (1-3) in synaptoneurosomes of the NAc in these two behavioral models. We find that chronic pain leads to a decrease of VGLUT1, likely reflecting decreased projections from the cortex. Pain also decreases VGLUT3 levels, likely representing a decrease in projections from GABAergic, serotonergic, and/or cholinergic interneurons. In contrast, chronic consumption of sucrose increases VGLUT3 in the NAc, possibly reflecting an increase from these interneuron projections. Our study shows that natural rewards and pain have distinct effects on the VGLUT expression pattern in the NAc, indicating that glutamate inputs to the NAc are differentially modulated by rewards and pain.

Sleep and meal-time misalignment alters functional connectivity: a pilot resting-state study.

PubMed

Yoncheva, Y N; Castellanos, F X; Pizinger, T; Kovtun, K; St-Onge, M-P

2016-11-01

Delayed sleep and meal times promote metabolic dysregulation and obesity. Altered coordination of sleeping and eating times may impact food-reward valuation and interoception in the brain, yet the independent and collective contributions of sleep and meal times are unknown. This randomized, in-patient crossover study experimentally manipulates sleep and meal times while preserving sleep duration (7.05±0.44 h for 5 nights). Resting-state functional magnetic resonance imaging scans (2 × 5-minute runs) were obtained for four participants (three males; 25.3±4.6 years), each completing all study phases (normal sleep/normal meal; late sleep/normal meal; normal sleep/late meal; and late sleep/late meal). Normal mealtimes were 1, 5, 11 and 12.5 h after awakening; late mealtimes were 4.5, 8.5, 14.5 and 16 h after awakening. Seed-based resting-state functional connectivity (RSFC) was computed for a priori regions-of-interest (seeds) and contrasted across conditions. Statistically significant (P<0.05, whole-brain corrected) regionally specific effects were found for multiple seeds. The strongest effects were linked to the amygdala: increased RSFC for late versus normal mealtimes (equivalent to skipping breakfast). A main effect of sleep and interaction with meal time were also observed. Preliminary findings support the feasibility of examining the effects of sleep and meal-time misalignment, independent of sleep duration, on RSFC in regions relevant to food reward and interoception.

Altered reward expectancy in individuals with recent methamphetamine dependence.

PubMed

Bischoff-Grethe, Amanda; Connolly, Colm G; Jordan, Stephan J; Brown, Gregory G; Paulus, Martin P; Tapert, Susan F; Heaton, Robert K; Woods, Steven P; Grant, Igor

2017-01-01

Chronic methamphetamine use may lead to changes in reward-related function of the ventral striatum and caudate nucleus. Whether methamphetamine-dependent individuals show heightened reactivity to positively valenced stimuli (i.e. positive reinforcement mechanisms), or an exaggerated response to negatively valenced stimuli (i.e. driven by negative reinforcement mechanisms) remains unclear. This study investigated neural functioning of expectancy and receipt for gains and losses in adults with (METH+) and without (METH-) histories of methamphetamine dependence. Participants (17 METH+; 23 METH-) performed a probabilistic feedback expectancy task during blood-oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). Participants were given visual cues probabilistically associated with monetary gain, loss, or neutral outcomes. General linear models examined the BOLD response to: (1) anticipation of gains and losses, and (2) gain and loss monetary outcomes. METH+ had less BOLD response to loss anticipation than METH- in the ventral striatum and posterior caudate. METH+ also showed more BOLD response to loss outcomes than to gain outcomes in the anterior and posterior caudate, whereas METH- did not show differential responses to the valence of outcomes. METH+ individuals showed attenuated neural response to anticipated gains and losses, but their response to loss outcomes was greater than to gain outcomes. A decreased response to loss anticipation, along with a greater response to loss outcomes, suggests an altered ability to evaluate future risks and benefits based upon prior experience, which may underlie suboptimal decision-making in METH+ individuals that increases the likelihood of risky behavior.

Altered reward expectancy in individuals with recent methamphetamine dependence

PubMed Central

Bischoff-Grethe, Amanda; Connolly, Colm G; Jordan, Stephan J; Brown, Gregory G; Paulus, Martin P; Tapert, Susan F; Heaton, Robert K; Woods, Steven P; Grant, Igor

2016-01-01

Background Chronic methamphetamine use may lead to changes in reward-related function of the ventral striatum and caudate nucleus. Whether methamphetamine dependent individuals show heightened reactivity to positively valenced stimuli (i.e., positive reinforcement mechanisms), or an exaggerated response to negatively valenced stimuli (i.e., driven by negative reinforcement mechanisms) remains unclear. This study investigated neural functioning of expectancy and receipt for gains and losses in adults with (METH+) and without (METH−) histories of methamphetamine dependence. Methods Participants (17 METH+; 23 METH−) performed a probabilistic feedback expectancy task during blood-oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). Participants were given visual cues probabilistically associated with monetary gain, loss, or neutral outcomes. General linear models examined the BOLD response to: (1) anticipation of gains and losses, and (2) gain and loss monetary outcomes. Results METH+ had less BOLD response to loss anticipation than METH− in the ventral striatum and posterior caudate. METH+ also showed more BOLD response to loss outcomes than to gain outcomes in the anterior and posterior caudate, whereas METH− did not show differential responses to the valence of outcomes. Discussion METH+ individuals showed attenuated neural response to anticipated gains and losses, but their response to loss outcomes was greater than to gain outcomes. A decreased response to loss anticipation, along with a greater response to loss outcomes, suggests an altered ability to evaluate future risks and benefits based upon prior experience, which may underlie suboptimal decision-making in METH+ individuals that increases the likelihood of risky behavior. PMID:27649775

Dissociable roles for the basolateral amygdala and orbitofrontal cortex in decision-making under risk of punishment.

PubMed

Orsini, Caitlin A; Trotta, Rose T; Bizon, Jennifer L; Setlow, Barry

2015-01-28

Several neuropsychiatric disorders are associated with abnormal decision-making involving risk of punishment, but the neural basis of this association remains poorly understood. Altered activity in brain systems including the basolateral amygdala (BLA) and orbitofrontal cortex (OFC) can accompany these same disorders, and these structures are implicated in some forms of decision-making. The current study investigated the role of the BLA and OFC in decision-making under risk of explicit punishment. Rats were trained in the risky decision-making task (RDT), in which they chose between two levers, one that delivered a small safe reward, and the other that delivered a large reward accompanied by varying risks of footshock punishment. Following training, they received sham or neurotoxic lesions of BLA or OFC, followed by RDT retesting. BLA lesions increased choice of the large risky reward (greater risk-taking) compared to both prelesion performance and sham controls. When reward magnitudes were equated, both BLA lesion and control groups shifted their choice to the safe (no shock) reward lever, indicating that the lesions did not impair punishment sensitivity. In contrast to BLA lesions, OFC lesions significantly decreased risk-taking compared with sham controls, but did not impair discrimination between different reward magnitudes or alter baseline levels of anxiety. Finally, neither lesion significantly affected food-motivated lever pressing under various fixed ratio schedules, indicating that lesion-induced alterations in risk-taking were not secondary to changes in appetitive motivation. Together, these findings indicate distinct roles for the BLA and OFC in decision-making under risk of explicit punishment. Copyright © 2015 the authors 0270-6474/15/351368-12$15.00/0.

Alcoholism: genes and mechanisms.

PubMed

Oroszi, Gabor; Goldman, David

2004-12-01

Alcoholism is a chronic relapsing/remitting disease that is frequently unrecognized and untreated, in part because of the partial efficacy of treatment. Only approximately one-third of patients remain abstinent and one-third have fully relapsed 1 year after withdrawal from alcohol, with treated patients doing substantially better than untreated [1]. The partial effectiveness of strategies for prevention and treatment, and variation in clinical course and side effects, represent a challenge and an opportunity to better understand the neurobiology of addiction. The strong heritability of alcoholism suggests the existence of inherited functional variants of genes that alter the metabolism of alcohol and variants of other genes that alter the neurobiologies of reward, executive cognitive function, anxiety/dysphoria, and neuronal plasticity. Each of these neurobiologies has been identified as a critical domain in the addictions. Functional alleles that alter alcoholism-related intermediate phenotypes include common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met leading to differences in three aspects of neurobiology: executive cognitive function, stress/anxiety response, and opioid function; opioid receptor micro1 (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters serotonin transporter function and appears to affect stress response and anxiety/dysphoria, which are factors relevant to initial vulnerability, the process of addiction, and relapse.

An essential role of acetylcholine-glutamate synergy at habenular synapses in nicotine dependence

PubMed Central

Frahm, Silke; Antolin-Fontes, Beatriz; Görlich, Andreas; Zander, Johannes-Friedrich; Ahnert-Hilger, Gudrun; Ibañez-Tallon, Ines

2015-01-01

A great deal of interest has been focused recently on the habenula and its critical role in aversion, negative-reward and drug dependence. Using a conditional mouse model of the ACh-synthesizing enzyme choline acetyltransferase (Chat), we report that local elimination of acetylcholine (ACh) in medial habenula (MHb) neurons alters glutamate corelease and presynaptic facilitation. Electron microscopy and immuno-isolation analyses revealed colocalization of ACh and glutamate vesicular transporters in synaptic vesicles (SVs) in the central IPN. Glutamate reuptake in SVs prepared from the IPN was increased by ACh, indicating vesicular synergy. Mice lacking CHAT in habenular neurons were insensitive to nicotine-conditioned reward and withdrawal. These data demonstrate that ACh controls the quantal size and release frequency of glutamate at habenular synapses, and suggest that the synergistic functions of ACh and glutamate may be generally important for modulation of cholinergic circuit function and behavior. DOI: http://dx.doi.org/10.7554/eLife.11396.001 PMID:26623516

Adolescent Cannabis Use: What is the Evidence for Functional Brain Alteration?

PubMed

Lorenzetti, Valentina; Alonso-Lana, Silvia; Youssef, George J; Verdejo-Garcia, Antonio; Suo, Chao; Cousijn, Janna; Takagi, Michael; Yücel, Murat; Solowij, Nadia

2016-01-01

Cannabis use typically commences during adolescence, a period during which the brain undergoes profound remodeling in areas that are high in cannabinoid receptors and that mediate cognitive control and emotion regulation. It is therefore important to determine the impact of adolescent cannabis use on brain function. We investigate the impact of adolescent cannabis use on brain function by reviewing the functional magnetic resonance imaging studies in adolescent samples. We systematically reviewed the literature and identified 13 functional neuroimaging studies in adolescent cannabis users (aged 13 to 18 years) performing working memory, inhibition and reward processing tasks. The majority of the studies found altered brain function, but intact behavioural task performance in adolescent cannabis users versus controls. The most consistently reported differences were in the frontal-parietal network, which mediates cognitive control. Heavier use was associated with abnormal brain function in most samples. A minority of studies controlled for the influence of confounders that can also undermine brain function, such as tobacco and alcohol use, psychopathology symptoms, family history of psychiatric disorders and substance use. Emerging evidence shows abnormal frontal-parietal network activity in adolescent cannabis users, particularly in heavier users. Brain functional alterations may reflect a compensatory neural mechanism that enables normal behavioural performance. It remains unclear if cannabis exposure drives these alterations, as substance use and mental health confounders have not been systematically examined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Microstimulation of the Human Substantia Nigra Alters Reinforcement Learning

PubMed Central

Ramayya, Ashwin G.; Misra, Amrit

2014-01-01

Animal studies have shown that substantia nigra (SN) dopaminergic (DA) neurons strengthen action–reward associations during reinforcement learning, but their role in human learning is not known. Here, we applied microstimulation in the SN of 11 patients undergoing deep brain stimulation surgery for the treatment of Parkinson's disease as they performed a two-alternative probability learning task in which rewards were contingent on stimuli, rather than actions. Subjects demonstrated decreased learning from reward trials that were accompanied by phasic SN microstimulation compared with reward trials without stimulation. Subjects who showed large decreases in learning also showed an increased bias toward repeating actions after stimulation trials; therefore, stimulation may have decreased learning by strengthening action–reward associations rather than stimulus–reward associations. Our findings build on previous studies implicating SN DA neurons in preferentially strengthening action–reward associations during reinforcement learning. PMID:24828643

Basolateral amygdala rapid glutamate release encodes an outcome-specific representation vital for reward-predictive cues to selectively invigorate reward-seeking actions

PubMed Central

Malvaez, Melissa; Greenfield, Venuz Y.; Wang, Alice S.; Yorita, Allison M.; Feng, Lili; Linker, Kay E.; Monbouquette, Harold G.; Wassum, Kate M.

2015-01-01

Environmental stimuli have the ability to generate specific representations of the rewards they predict and in so doing alter the selection and performance of reward-seeking actions. The basolateral amygdala participates in this process, but precisely how is unknown. To rectify this, we monitored, in near-real time, basolateral amygdala glutamate concentration changes during a test of the ability of reward-predictive cues to influence reward-seeking actions (Pavlovian-instrumental transfer). Glutamate concentration was found to be transiently elevated around instrumental reward seeking. During the Pavlovian-instrumental transfer test these glutamate transients were time-locked to and correlated with only those actions invigorated by outcome-specific motivational information provided by the reward-predictive stimulus (i.e., actions earning the same specific outcome as predicted by the presented CS). In addition, basolateral amygdala AMPA, but not NMDA glutamate receptor inactivation abolished the selective excitatory influence of reward-predictive cues over reward seeking. These data the hypothesis that transient glutamate release in the BLA can encode the outcome-specific motivational information provided by reward-predictive stimuli. PMID:26212790

Subjective perception of cocaine reward in mice assessed by a single exposure place preference (sePP) paradigm.

PubMed

Runegaard, Annika H; Jensen, Kathrine Louise; Dencker, Ditte; Wörtwein, Gitta; Gether, Ulrik

2017-09-01

The potential of abused drugs to induce addiction and compulsive drug-related behavior is associated with their ability to alter dopamine signaling. Dopamine plays a key role in reward signaling and it has been of great interest to investigate how various drugs of abuse alter reward-related behavior. In rodents, the rewarding effects of drugs have often been assessed in self-administration or place preference paradigms; both involving repeated drug exposure and weeks of training and testing. Our investigation describes a valid approach to assess the initial rewarding effects of cocaine in mice with a single exposure place preference (sePP) paradigm, avoiding repeated drug injections. We present the sePP paradigm with a 3-day protocol to assess the initial rewarding effects of cocaine. Interestingly, only male mice exhibit sePP to cocaine. To assess subsequent drug-related behavior, the protocol was extended by 3days of extinction followed by reinstatement on day 10. The sePP paradigm provides a reliable and convenient approach to assess the initial rewarding effects of cocaine, circumventing the need for repeated drug injections. The sePP protocol allows further dissection of the mechanism and influence of initial cocaine exposure on subsequent drug-related behaviors by including extinction and reinstatement. The lack of sePP in female mice may reflect a biologically relevant sex difference in the initial subjective perception of cocaine-induced reward. This could relate to and explain why males and females have been reported to respond differently to cocaine and cocaine-associated cues. Copyright © 2017 Elsevier B.V. All rights reserved.

The Rewarding and Locomotor-Sensitizing Effects of Repeated Cocaine Administration are Distinct and Separable in Mice

PubMed Central

Riday, Thorfinn T.; Kosofsky, Barry E.; Malanga, C.J.

2011-01-01

Repeated psychostimulant exposure progressively increases their potency to stimulate motor activity in rodents. This behavioral or locomotor sensitization is considered a model for some aspects of drug addiction in humans, particularly drug craving during abstinence. However, the role of increased motor behavior in drug reward remains incompletely understood. Intracranial self-stimulation (ICSS) was measured concurrently with locomotor activity to determine if acute intermittent cocaine administration had distinguishable effects on motor behavior and perception of brain stimulation-reward (BSR) in the same mice. Sensitization is associated with changes in neuronal activity and glutamatergic neurotransmission in brain reward circuitry. Expression of AMPA receptor subunits (GluR1 and GluR2) and CRE binding protein (CREB) was measured in the ventral tegmental area (VTA), dorsolateral striatum (STR) and nucleus accumbens (NAc) before and after a sensitizing regimen of cocaine, with and without ICSS. Repeated cocaine administration sensitized mice to its locomotor stimulating effects but not its ability to potentiate BSR. ICSS increased GluR1 in the VTA but not NAc or STR, demonstrating selective changes in protein expression with electrical stimulation of discrete brain structures. Repeated cocaine reduced GluR1, GluR2 and CREB expression in the NAc, and reductions of GluR1 and GluR2 but not CREB were further enhanced by ICSS. These data suggest that the effects of repeated cocaine exposure on reward and motor processes are dissociable in mice, and that reduction of excitatory neurotransmission in the NAc may predict altered motor function independently from changes in reward perception. PMID:22197517

Insula and striatum activity in effort-related monetary reward processing in gambling disorder: The role of depressive symptomatology

PubMed Central

Fauth-Bühler, Mira; Zois, Evangelos; Vollstädt-Klein, Sabine; Lemenager, Tagrid; Beutel, Martin; Mann, Karl

2014-01-01

The neurobiological underpinnings of effort-related monetary reward processing of gambling disorder have not been previously studied. To date neuroimaging studies lack in large sample sizes and as a consequence less attention has been given to brain reward processing that could potentially be attributed to comorbid conditions such as depressive mood state. We assessed monetary reward processing using an effort-dependent task during 3 tesla functional magnetic resonance imaging. We investigated a large sample of male, right-handed, slot-machine-playing disordered gamblers (DGs; N = 80) as well as age- and smoking-matched male healthy controls (HCs; N = 89). Depressive symptoms were assessed using the Beck Depression Inventory (BDI). DGs and HCs were divided into subgroups (“high” and “low”) based on their BDI scores. Effort-related monetary reward processing did not differ between the complete groups of HCs and DGs. Brain activation during receipt of monetary reward though revealed a significant Group × BDI interaction: DGs with higher BDI scores compared to DGs with lower BDI scores showed greater brain activity in the right insula cortex and dorsal striatum while no differences were observed for HCs with higher versus lower BDI scores. Our results suggest that effort-related aspects of monetary motivation, i.e. when monetary output is tied to performance, are not altered in DG. Additionally, our findings strengthen the need for subgroup comparisons in future investigations of the disorder as part of a personalized medicine approach. PMID:25379437

Distinct effects of ASD and ADHD symptoms on reward anticipation in participants with ADHD, their unaffected siblings and healthy controls: a cross-sectional study.

PubMed

van Dongen, Eelco V; von Rhein, Daniel; O'Dwyer, Laurence; Franke, Barbara; Hartman, Catharina A; Heslenfeld, Dirk J; Hoekstra, Pieter J; Oosterlaan, Jaap; Rommelse, Nanda; Buitelaar, Jan

2015-01-01

Autism spectrum disorder (ASD) traits are continuously distributed throughout the population, and ASD symptoms are also frequently observed in patients with attention-deficit/hyperactivity disorder (ADHD). Both ASD and ADHD have been linked to alterations in reward-related neural processing. However, whether both symptom domains interact and/or have distinct effects on reward processing in healthy and ADHD populations is currently unknown. We examined how variance in ASD and ADHD symptoms in individuals with ADHD and healthy participants was related to the behavioural and neural response to reward during a monetary incentive delay (MID) task. Participants (mean age: 17.7 years, range: 10-28 years) from the NeuroIMAGE study with a confirmed diagnosis of ADHD (n = 136), their unaffected siblings (n = 83), as well as healthy controls (n = 105) performed an MID task in a magnetic resonance imaging (MRI) scanner. ASD and ADHD symptom scores were used as predictors of the neural response to reward anticipation and reward receipt. Behavioural responses were modeled using linear mixed models; neural responses were analysed using FMRIB's Software Library (FSL) proprietary mixed effects analysis (FLAMEO). ASD and ADHD symptoms were associated with alterations in BOLD activity during reward anticipation, but not reward receipt. Specifically, ASD scores were related to increased insular activity during reward anticipation across the sample. No interaction was found between this effect and the presence of ADHD, suggesting that ASD symptoms had no differential effect in ADHD and healthy populations. ADHD symptom scores were associated with reduced dorsolateral prefrontal activity during reward anticipation. No interactions were found between the effects of ASD and ADHD symptoms on reward processing. Variance in ASD and ADHD symptoms separately influence neural processing during reward anticipation in both individuals with (an increased risk of) ADHD and healthy participants. Our findings therefore suggest that both symptom domains affect reward processing through distinct mechanisms, underscoring the importance of multidimensional and multimodal assessment in psychiatry.

The neurobiological basis of binge-eating disorder.

PubMed

Kessler, Robert M; Hutson, Peter H; Herman, Barry K; Potenza, Marc N

2016-04-01

Relatively little is known about the neuropathophysiology of binge-eating disorder (BED). Here, the evidence from neuroimaging, neurocognitive, genetics, and animal studies are reviewed to synthesize our current understanding of the pathophysiology of BED. Binge-eating disorder may be conceptualized as an impulsive/compulsive disorder, with altered reward sensitivity and food-related attentional biases. Neuroimaging studies suggest there are corticostriatal circuitry alterations in BED similar to those observed in substance abuse, including altered function of prefrontal, insular, and orbitofrontal cortices and the striatum. Human genetics and animal studies suggest that there are changes in neurotransmitter networks, including dopaminergic and opioidergic systems, associated with binge-eating behaviors. Overall, the current evidence suggests that BED may be related to maladaptation of the corticostriatal circuitry regulating motivation and impulse control similar to that found in other impulsive/compulsive disorders. Further studies are needed to understand the genetics of BED and how neurotransmitter activity and neurocircuitry function are altered in BED and how pharmacotherapies may influence these systems to reduce BED symptoms. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Brain structure and functional connectivity associated with pornography consumption: the brain on porn.

PubMed

Kühn, Simone; Gallinat, Jürgen

2014-07-01

Since pornography appeared on the Internet, the accessibility, affordability, and anonymity of consuming visual sexual stimuli have increased and attracted millions of users. Based on the assumption that pornography consumption bears resemblance with reward-seeking behavior, novelty-seeking behavior, and addictive behavior, we hypothesized alterations of the frontostriatal network in frequent users. To determine whether frequent pornography consumption is associated with the frontostriatal network. In a study conducted at the Max Planck Institute for Human Development in Berlin, Germany, 64 healthy male adults covering a wide range of pornography consumption reported hours of pornography consumption per week. Pornography consumption was associated with neural structure, task-related activation, and functional resting-state connectivity. Gray matter volume of the brain was measured by voxel-based morphometry and resting state functional connectivity was measured on 3-T magnetic resonance imaging scans. We found a significant negative association between reported pornography hours per week and gray matter volume in the right caudate (P < .001, corrected for multiple comparisons) as well as with functional activity during a sexual cue-reactivity paradigm in the left putamen (P < .001). Functional connectivity of the right caudate to the left dorsolateral prefrontal cortex was negatively associated with hours of pornography consumption. The negative association of self-reported pornography consumption with the right striatum (caudate) volume, left striatum (putamen) activation during cue reactivity, and lower functional connectivity of the right caudate to the left dorsolateral prefrontal cortex could reflect change in neural plasticity as a consequence of an intense stimulation of the reward system, together with a lower top-down modulation of prefrontal cortical areas. Alternatively, it could be a precondition that makes pornography consumption more rewarding.

Epigenetic dysregulation of the dopamine system in diet-induced obesity.

PubMed

Vucetic, Zivjena; Carlin, Jesse Lea; Totoki, Kathy; Reyes, Teresa M

2012-03-01

Chronic intake of high-fat (HF) diet is known to alter brain neurotransmitter systems that participate in the central regulation of food intake. Dopamine (DA) system changes in response to HF diet have been observed in the hypothalamus, important in the homeostatic control of food intake, as well as within the central reward circuitry [ventral tegmental area (VTA), nucleus accumbens (NAc), and pre-frontal cortex (PFC)], critical for coding the rewarding properties of palatable food and important in hedonically driven feeding behavior. Using a mouse model of diet-induced obesity (DIO), significant alterations in the expression of DA-related genes were documented in adult animals, and the general pattern of gene expression changes was opposite within the hypothalamus versus the reward circuitry (increased vs. decreased, respectively). Differential DNA methylation was identified within the promoter regions of tyrosine hydroxylase (TH) and dopamine transporter (DAT), and the pattern of this response was consistent with the pattern of gene expression. Behaviors consistent with increased hypothalamic DA and decreased reward circuitry DA were observed. These data identify differential DNA methylation as an epigenetic mechanism linking the chronic intake of HF diet with altered DA-related gene expression, and this response varies by brain region and DNA sequence. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Olanzapine treatment of adolescent rats alters adult reward behaviour and nucleus accumbens function

PubMed Central

Vinish, Monika; Elnabawi, Ahmed; Milstein, Jean A.; Burke, Jesse S.; Kallevang, Jonathan K.; Turek, Kevin C.; Lansink, Carien S.; Merchenthaler, Istvan; Bailey, Aileen M.; Kolb, Bryan; Cheer, Joseph F.; Frost, Douglas O.

2018-01-01

Antipsychotic drugs are increasingly used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of early life antipsychotic drug (APD) treatment. Most APDs are potent antagonists or partial agonists of dopamine (DA) D2 receptors ; atypical APDs also have multiple serotonergic activities. DA and serotonin regulate many neurodevelopmental processes. Thus, early life APD treatment can, potentially, perturb these processes, causing long-term behavioural and neurobiological sequelae. We treated adolescent, male rats with olanzapine (Ola) on post-natal days 28–49, under dosing conditions that approximate those employed therapeutically in humans. As adults, they exhibited enhanced conditioned place preference for amphetamine, as compared to vehicle-treated rats. In the nucleus accumbens core, DA D1 receptor binding was reduced, D2 binding was increased and DA release evoked by electrical stimulation of the ventral tegmental area was reduced. Thus, adolescent Ola treatment enduringly alters a key behavioural response to rewarding stimuli and modifies DAergic neurotransmission in the nucleus accumbens. The persistence of these changes suggests that even limited periods of early life Ola treatment may induce enduring changes in other reward-related behaviours and in behavioural and neurobiological responses to therapeutic and illicit psychotropic drugs. These results underscore the importance of improved understanding of the enduring sequelae of paediatric APD treatment as a basis for weighing the benefits and risks of adolescent APD therapy, especially prophylactic treatment in high-risk, asymptomatic patients. PMID:23351612

Alterations of reward mechanisms in bulbectomised rats.

PubMed

Grecksch, Gisela; Becker, Axel

2015-06-01

The positive association between alcoholism and depression is a common clinical observation. We investigated the relationship between depression and reward mechanisms using a validated animal model for depressive-like behaviour, the olfactory bulbectomy in rats. The effects of bilateral olfactory bulbectomy on reward mechanisms were studied in two different experimental paradigms - the voluntary self-administration of ethanol and the conditioned place preference to alcohol injection and compared to the effects of ethanol on locomotor activity and body core temperature. The voluntary ethanol intake was increased significantly in bulbectomised rats in a drinking experiment and also after a period of abstinence. Conditioned place preference (CPP) was induced in all animals. However, bulbectomised rats needed a higher dose of alcohol to produce CPP. The sedative effect of ethanol on locomotor activity was reduced in bulbectomised animals. Measurement of body temperature revealed a dose-dependent hypothermic effect of ethanol in both groups. These results suggest that the reward mechanisms may be altered in this animal model as a common phenomenon associated with depression. Furthermore, they support the hypothesis that the addictive and/or rewarding properties of some drugs of abuse may be modified in depression. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of anabolic-androgens on brain reward function

PubMed Central

Mhillaj, Emanuela; Morgese, Maria G.; Tucci, Paolo; Bove, Maria; Schiavone, Stefania; Trabace, Luigia

2015-01-01

Androgens are mainly prescribed to treat several diseases caused by testosterone deficiency. However, athletes try to promote muscle growth by manipulating testosterone levels or assuming androgen anabolic steroids (AAS). These substances were originally synthesized to obtain anabolic effects greater than testosterone. Although AAS are rarely prescribed compared to testosterone, their off-label utilization is very wide. Furthermore, combinations of different steroids and doses generally higher than those used in therapy are common. Symptoms of the chronic use of supra-therapeutic doses of AAS include anxiety, depression, aggression, paranoia, distractibility, confusion, amnesia. Interestingly, some studies have shown that AAS elicited electroencephalographic changes similar to those observed with amphetamine abuse. The frequency of side effects is higher among AAS abusers, with psychiatric complications such as labile mood, lack of impulse control and high violence. On the other hand, AAS addiction studies are complex because data collection is very difficult due to the subjects' reticence and can be biased by many variables, including physical exercise, that alter the reward system. Moreover, it has been reported that AAS may imbalance neurotransmitter systems involved in the reward process, leading to increased sensitivity toward opioid narcotics and central stimulants. The goal of this article is to review the literature on steroid abuse and changes to the reward system in preclinical and clinical studies. PMID:26379484

Effects of anabolic-androgens on brain reward function.

PubMed

Mhillaj, Emanuela; Morgese, Maria G; Tucci, Paolo; Bove, Maria; Schiavone, Stefania; Trabace, Luigia

2015-01-01

Androgens are mainly prescribed to treat several diseases caused by testosterone deficiency. However, athletes try to promote muscle growth by manipulating testosterone levels or assuming androgen anabolic steroids (AAS). These substances were originally synthesized to obtain anabolic effects greater than testosterone. Although AAS are rarely prescribed compared to testosterone, their off-label utilization is very wide. Furthermore, combinations of different steroids and doses generally higher than those used in therapy are common. Symptoms of the chronic use of supra-therapeutic doses of AAS include anxiety, depression, aggression, paranoia, distractibility, confusion, amnesia. Interestingly, some studies have shown that AAS elicited electroencephalographic changes similar to those observed with amphetamine abuse. The frequency of side effects is higher among AAS abusers, with psychiatric complications such as labile mood, lack of impulse control and high violence. On the other hand, AAS addiction studies are complex because data collection is very difficult due to the subjects' reticence and can be biased by many variables, including physical exercise, that alter the reward system. Moreover, it has been reported that AAS may imbalance neurotransmitter systems involved in the reward process, leading to increased sensitivity toward opioid narcotics and central stimulants. The goal of this article is to review the literature on steroid abuse and changes to the reward system in preclinical and clinical studies.

Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder

PubMed Central

Boecker-Schlier, Regina; Buchmann, Arlette F.; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Plichta, Michael M.; Cattrell, Anna; Schumann, Gunter; Esser, Günter; Schmidt, Martin; Buitelaar, Jan; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

2017-01-01

Abstract Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2–19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years). CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors. PMID:27694318

Neural mechanisms of social decision-making in the primate amygdala.

PubMed

Chang, Steve W C; Fagan, Nicholas A; Toda, Koji; Utevsky, Amanda V; Pearson, John M; Platt, Michael L

2015-12-29

Social decisions require evaluation of costs and benefits to oneself and others. Long associated with emotion and vigilance, the amygdala has recently been implicated in both decision-making and social behavior. The amygdala signals reward and punishment, as well as facial expressions and the gaze of others. Amygdala damage impairs social interactions, and the social neuropeptide oxytocin (OT) influences human social decisions, in part, by altering amygdala function. Here we show in monkeys playing a modified dictator game, in which one individual can donate or withhold rewards from another, that basolateral amygdala (BLA) neurons signaled social preferences both across trials and across days. BLA neurons mirrored the value of rewards delivered to self and others when monkeys were free to choose but not when the computer made choices for them. We also found that focal infusion of OT unilaterally into BLA weakly but significantly increased both the frequency of prosocial decisions and attention to recipients for context-specific prosocial decisions, endorsing the hypothesis that OT regulates social behavior, in part, via amygdala neuromodulation. Our findings demonstrate both neurophysiological and neuroendocrinological connections between primate amygdala and social decisions.

Neural mechanisms of social decision-making in the primate amygdala

PubMed Central

Chang, Steve W. C.; Fagan, Nicholas A.; Toda, Koji; Utevsky, Amanda V.; Pearson, John M.; Platt, Michael L.

2015-01-01

Social decisions require evaluation of costs and benefits to oneself and others. Long associated with emotion and vigilance, the amygdala has recently been implicated in both decision-making and social behavior. The amygdala signals reward and punishment, as well as facial expressions and the gaze of others. Amygdala damage impairs social interactions, and the social neuropeptide oxytocin (OT) influences human social decisions, in part, by altering amygdala function. Here we show in monkeys playing a modified dictator game, in which one individual can donate or withhold rewards from another, that basolateral amygdala (BLA) neurons signaled social preferences both across trials and across days. BLA neurons mirrored the value of rewards delivered to self and others when monkeys were free to choose but not when the computer made choices for them. We also found that focal infusion of OT unilaterally into BLA weakly but significantly increased both the frequency of prosocial decisions and attention to recipients for context-specific prosocial decisions, endorsing the hypothesis that OT regulates social behavior, in part, via amygdala neuromodulation. Our findings demonstrate both neurophysiological and neuroendocrinological connections between primate amygdala and social decisions. PMID:26668400

Reward-centricity and attenuated aversions: An adolescent phenotype emerging from studies in laboratory animals

PubMed Central

Doremus-Fitzwater, Tamara L.; Spear, Linda P.

2016-01-01

Adolescence is an evolutionarily conserved developmental period, with neural circuits and behaviors contributing to the detection, procurement, and receipt of rewards bearing similarity across species. Studies with laboratory animals suggest that adolescence is typified by a “reward-centric” phenotype—an increased sensitivity to rewards relative to adults. In contrast, adolescent rodents are reportedly less sensitive to the aversive properties of many drugs and naturally aversive stimuli. Alterations within the mesocorticolimbic dopamine and endocannabinoid systems likely contribute to an adolescent reward-sensitive, yet aversion-resistant, phenotype. Although early hypotheses postulated that developmental changes in dopaminergic circuitry would result in a “reward deficiency” syndrome, evidence now suggests the opposite: that adolescents are uniquely poised to seek out hedonic stimuli, experience greater “pleasure” from rewards, and consume rewarding stimuli in excess. Future studies that more clearly define the role of specific brain regions and neurotransmitter systems in the expression of behaviors toward reward- and aversive-related cues and stimuli are necessary to more fully understand an adolescent-proclivity for and vulnerability to rewards and drugs of potential abuse. PMID:27524639

Reward-centricity and attenuated aversions: An adolescent phenotype emerging from studies in laboratory animals.

PubMed

Doremus-Fitzwater, Tamara L; Spear, Linda P

2016-11-01

Adolescence is an evolutionarily conserved developmental period, with neural circuits and behaviors contributing to the detection, procurement, and receipt of rewards bearing similarity across species. Studies with laboratory animals suggest that adolescence is typified by a "reward-centric" phenotype-an increased sensitivity to rewards relative to adults. In contrast, adolescent rodents are reportedly less sensitive to the aversive properties of many drugs and naturally aversive stimuli. Alterations within the mesocorticolimbic dopamine and endocannabinoid systems likely contribute to an adolescent reward-sensitive, yet aversion-resistant, phenotype. Although early hypotheses postulated that developmental changes in dopaminergic circuitry would result in a "reward deficiency" syndrome, evidence now suggests the opposite: that adolescents are uniquely poised to seek out hedonic stimuli, experience greater "pleasure" from rewards, and consume rewarding stimuli in excess. Future studies that more clearly define the role of specific brain regions and neurotransmitter systems in the expression of behaviors toward reward- and aversive-related cues and stimuli are necessary to more fully understand an adolescent-proclivity for and vulnerability to rewards and drugs of potential abuse. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantifying familial influences on brain activation during the monetary incentive delay task: an adolescent monozygotic twin study.

PubMed

Silverman, Merav H; Krueger, Robert F; Iacono, William G; Malone, Stephen M; Hunt, Ruskin H; Thomas, Kathleen M

2014-12-01

Although altered brain activation during reward tasks has been found in a number of heritable psychiatric disorders and health outcomes, the familial nature of reward-related brain activation remains unexplored. In this study, we investigated the degree to which the magnitude of mesocorticolimbic reward system signal intensities in anticipation of reward during the monetary incentive delay (MID) task was similar within 46 pairs of adolescent, monozygotic twins. Significant within-pair correlations in brain activation during anticipation of gain were found in one third of the 18 reward-related regions investigated. These regions were the right nucleus accumbens, left and right posterior caudate, right anterior caudate, left insula, and anterior cingulate cortex. This serves as evidence for a shared familial contribution to individual differences in reward related brain activity in certain key reward processing regions. Copyright © 2014 Elsevier B.V. All rights reserved.

Microstimulation of the human substantia nigra alters reinforcement learning.

PubMed

Ramayya, Ashwin G; Misra, Amrit; Baltuch, Gordon H; Kahana, Michael J

2014-05-14

Animal studies have shown that substantia nigra (SN) dopaminergic (DA) neurons strengthen action-reward associations during reinforcement learning, but their role in human learning is not known. Here, we applied microstimulation in the SN of 11 patients undergoing deep brain stimulation surgery for the treatment of Parkinson's disease as they performed a two-alternative probability learning task in which rewards were contingent on stimuli, rather than actions. Subjects demonstrated decreased learning from reward trials that were accompanied by phasic SN microstimulation compared with reward trials without stimulation. Subjects who showed large decreases in learning also showed an increased bias toward repeating actions after stimulation trials; therefore, stimulation may have decreased learning by strengthening action-reward associations rather than stimulus-reward associations. Our findings build on previous studies implicating SN DA neurons in preferentially strengthening action-reward associations during reinforcement learning. Copyright © 2014 the authors 0270-6474/14/346887-09$15.00/0.

Reward-based plasticity of spatial priority maps: Exploiting inter-subject variability to probe the underlying neurobiology.

PubMed

Della Libera, Chiara; Calletti, Riccardo; Eštočinová, Jana; Chelazzi, Leonardo; Santandrea, Elisa

2017-04-01

Recent evidence indicates that the attentional priority of objects and locations is altered by the controlled delivery of reward, reflecting reward-based attentional learning. Here, we take an approach hinging on intersubject variability to probe the neurobiological bases of the reward-driven plasticity of spatial priority maps. Specifically, we ask whether an individual's susceptibility to the reward-based treatment can be accounted for by specific predictors, notably personality traits that are linked to reward processing (along with more general personality traits), but also gender. Using a visual search protocol, we show that when different target locations are associated with unequal reward probability, different priorities are acquired by the more rewarded relative to the less rewarded locations. However, while males exhibit the expected pattern of results, with greater priority for locations associated with higher reward, females show an opposite trend. Critically, both the extent and the direction of reward-based adjustments are further predicted by personality traits indexing reward sensitivity, indicating that not only male and female brains are differentially sensitive to reward, but also that specific personality traits further contribute to shaping their learning-dependent attentional plasticity. These results contribute to a better understanding of the neurobiology underlying reward-dependent attentional learning and cross-subject variability in this domain.

Acute stress-induced cortisol elevations mediate reward system activity during subconscious processing of sexual stimuli.

PubMed

Oei, Nicole Y L; Both, Stephanie; van Heemst, Diana; van der Grond, Jeroen

2014-01-01

Stress is thought to alter motivational processes by increasing dopamine (DA) secretion in the brain's "reward system", and its key region, the nucleus accumbens (NAcc). However, stress studies using functional magnetic resonance imaging (fMRI), mainly found evidence for stress-induced decreases in NAcc responsiveness toward reward cues. Results from both animal and human PET studies indicate that the stress hormone cortisol may be crucial in the interaction between stress and dopaminergic actions. In the present study we therefore investigated whether cortisol mediated the effect of stress on DA-related responses to -subliminal-presentation of reward cues using the Trier Social Stress Test (TSST), which is known to reliably enhance cortisol levels. Young healthy males (n = 37) were randomly assigned to the TSST or control condition. After stress induction, brain activation was assessed using fMRI during a backward-masking paradigm in which potentially rewarding (sexual), emotionally negative and neutral stimuli were presented subliminally, masked by pictures of inanimate objects. A region of interest analysis showed that stress decreased activation in the NAcc in response to masked sexual cues (voxel-corrected, p<05). Furthermore, with mediation analysis it was found that high cortisol levels were related to stronger NAcc activation, showing that cortisol acted as a suppressor variable in the negative relation between stress and NAcc activation. The present findings indicate that cortisol is crucially involved in the relation between stress and the responsiveness of the reward system. Although generally stress decreases activation in the NAcc in response to rewarding stimuli, high stress-induced cortisol levels suppress this relation, and are associated with stronger NAcc activation. Individuals with a high cortisol response to stress might on one hand be protected against reductions in reward sensitivity, which has been linked to anhedonia and depression, but they may ultimately be more vulnerable to increased reward sensitivity, and addictions. Future studies investigating effects of stress on reward sensitivity should take into account the severity of the stressor and the individual cortisol response to stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

Establishing a probabilistic reversal learning test in mice: evidence for the processes mediating reward-stay and punishment-shift behaviour and for their modulation by serotonin.

PubMed

Ineichen, Christian; Sigrist, Hannes; Spinelli, Simona; Lesch, Klaus-Peter; Sautter, Eva; Seifritz, Erich; Pryce, Christopher R

2012-11-01

Valid animal models of psychopathology need to include behavioural readouts informed by human findings. In the probabilistic reversal learning (PRL) task, human subjects are confronted with serial reversal of the contingency between two operant stimuli and reward/punishment and, superimposed on this, a low probability (0.2) of punished correct responses/rewarded incorrect responses. In depression, reward-stay and reversals completed are unaffected but response-shift following punished correct response trials, referred to as negative feedback sensitivity (NFS), is increased. The aims of this study were to: establish an operant spatial PRL test appropriate for mice; obtain evidence for the processes mediating reward-stay and punishment-shift responding; and assess effects thereon of genetically- and pharmacologically-altered serotonin (5-HT) function. The study was conducted with wildtype (WT) and heterozygous mutant (HET) mice from a 5-HT transporter (5-HTT) null mutant strain. Mice were mildly food deprived and reward was sugar pellet and punishment was 5-s time out. Mice exhibited high motivation and adaptive reversal performance. Increased probability of punished correct response (PCR) trials per session (p = 0.1, 0.2 or 0.3) led to monotonic decrease in reward-stay and reversals completed, suggesting accurate reward prediction. NFS differed from chance-level at p PCR = 0.1, suggesting accurate punishment prediction, whereas NFS was at chance-level at p = 0.2-0.3. At p PCR = 0.1, HET mice exhibited lower NFS than WT mice. The 5-HTT blocker escitalopram was studied acutely at p PCR = 0.2: a low dose (0.5-1.5 mg/kg) resulted in decreased NFS, increased reward-stay and increased reversals completed, and similarly in WT and HET mice. This study demonstrates that testing PRL in mice can provide evidence on the regulation of reward and punishment processing that is, albeit within certain limits, of relevance to human emotional-cognitive processing, its dysfunction and treatment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Nalmefene Reduces Reward Anticipation in Alcohol Dependence: An Experimental Functional Magnetic Resonance Imaging Study.

PubMed

Quelch, Darren R; Mick, Inge; McGonigle, John; Ramos, Anna C; Flechais, Remy S A; Bolstridge, Mark; Rabiner, Eugenii; Wall, Matthew B; Newbould, Rexford D; Steiniger-Brach, Björn; van den Berg, Franz; Boyce, Malcolm; Østergaard Nilausen, Dorrit; Breuning Sluth, Lasse; Meulien, Didier; von der Goltz, Christoph; Nutt, David; Lingford-Hughes, Anne

2017-06-01

Nalmefene is a µ and δ opioid receptor antagonist, κ opioid receptor partial agonist that has recently been approved in Europe for treating alcohol dependence. It offers a treatment approach for alcohol-dependent individuals with "high-risk drinking levels" to reduce their alcohol consumption. However, the neurobiological mechanism underpinning its effects on alcohol consumption remains to be determined. Using a randomized, double-blind, placebo-controlled, within-subject crossover design we aimed to determine the effect of a single dose of nalmefene on striatal blood oxygen level-dependent (BOLD) signal change during anticipation of monetary reward using the monetary incentive delay task following alcohol challenge. Twenty-two currently heavy-drinking, non-treatment-seeking alcohol-dependent males were recruited. The effect of single dose nalmefene (18 mg) on changes in a priori defined striatal region of interest BOLD signal change during reward anticipation compared with placebo was investigated using functional magnetic resonance imaging. Both conditions were performed under intravenous alcohol administration (6% vol/vol infusion to achieve a target level of 80 mg/dL). Datasets from 18 participants were available and showed that in the presence of the alcohol infusion, nalmefene significantly reduced the BOLD response in the striatal region of interest compared with placebo. Nalmefene did not alter brain perfusion. Nalmefene blunts BOLD response in the mesolimbic system during anticipation of monetary reward and an alcohol infusion. This is consistent with nalmefene's actions on opioid receptors, which modulate the mesolimbic dopaminergic system, and provides a neurobiological basis for its efficacy. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Diagnostic Classification of Schizophrenia Patients on the Basis of Regional Reward-Related fMRI Signal Patterns

PubMed Central

Koch, Stefan P.; Hägele, Claudia; Haynes, John-Dylan; Heinz, Andreas; Schlagenhauf, Florian; Sterzer, Philipp

2015-01-01

Functional neuroimaging has provided evidence for altered function of mesolimbic circuits implicated in reward processing, first and foremost the ventral striatum, in patients with schizophrenia. While such findings based on significant group differences in brain activations can provide important insights into the pathomechanisms of mental disorders, the use of neuroimaging results from standard univariate statistical analysis for individual diagnosis has proven difficult. In this proof of concept study, we tested whether the predictive accuracy for the diagnostic classification of schizophrenia patients vs. healthy controls could be improved using multivariate pattern analysis (MVPA) of regional functional magnetic resonance imaging (fMRI) activation patterns for the anticipation of monetary reward. With a searchlight MVPA approach using support vector machine classification, we found that the diagnostic category could be predicted from local activation patterns in frontal, temporal, occipital and midbrain regions, with a maximal cluster peak classification accuracy of 93% for the right pallidum. Region-of-interest based MVPA for the ventral striatum achieved a maximal cluster peak accuracy of 88%, whereas the classification accuracy on the basis of standard univariate analysis reached only 75%. Moreover, using support vector regression we could additionally predict the severity of negative symptoms from ventral striatal activation patterns. These results show that MVPA can be used to substantially increase the accuracy of diagnostic classification on the basis of task-related fMRI signal patterns in a regionally specific way. PMID:25799236

Sexual Experience in Female Rodents: Cellular Mechanisms and Functional Consequences

PubMed Central

Meisel, Robert L.; Mullins, Amanda J.

2007-01-01

The neurobiology of female sexual behavior has largely focused on mechanisms of hormone action on nerve cells and how these effects translate into the display of copulatory motor patterns. Of equal importance, though less studied, are some of the consequences of engaging in sexual behavior, including the rewarding properties of sexual interactions and how sexual experience alters copulatory efficiency. This review summarizes the effects of sexual experience on reward processes and copulation in female Syrian hamsters. Neural correlates of these sexual interactions include long-term cellular changes in dopamine transmission and postsynaptic signaling pathways related to neuronal plasticity (e.g., dendritic spine formation). Taken together, these studies suggest that sexual experience enhances the reinforcing properties of sexual behavior, which has the coincident outcome of increasing copulatory efficiency in a way that can increase reproductive success. PMID:16978593

Behavioral Flexibility and Response Selection Are Impaired after Limited Exposure to Oxycodone

ERIC Educational Resources Information Center

Seip-Cammack, Katharine M.; Shapiro, Matthew L.

2014-01-01

Behavioral flexibility allows individuals to adapt to situations in which rewards and goals change. Potentially addictive drugs may impair flexible decision-making by altering brain mechanisms that compute reward expectancies, thereby facilitating maladaptive drug use. To investigate this hypothesis, we tested the effects of oxycodone exposure on…

Fuel not fun: Reinterpreting attenuated brain responses to reward in obesity.

PubMed

Kroemer, Nils B; Small, Dana M

2016-08-01

There is a well-established literature linking obesity to altered dopamine signaling and brain response to food-related stimuli. Neuroimaging studies frequently report enhanced responses in dopaminergic regions during food anticipation and decreased responses during reward receipt. This has been interpreted as reflecting anticipatory "reward surfeit", and consummatory "reward deficiency". In particular, attenuated response in the dorsal striatum to primary food rewards is proposed to reflect anhedonia, which leads to overeating in an attempt to compensate for the reward deficit. In this paper, we propose an alternative view. We consider brain response to food-related stimuli in a reinforcement-learning framework, which can be employed to separate the contributions of reward sensitivity and reward-related learning that are typically entangled in the brain response to reward. Consequently, we posit that decreased striatal responses to milkshake receipt reflect reduced reward-related learning rather than reward deficiency or anhedonia because reduced reward sensitivity would translate uniformly into reduced anticipatory and consummatory responses to reward. By re-conceptualizing reward deficiency as a shift in learning about subjective value of rewards, we attempt to reconcile neuroimaging findings with the putative role of dopamine in effort, energy expenditure and exploration and suggest that attenuated brain responses to energy dense foods reflect the "fuel", not the fun entailed by the reward. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of reward motivation on human declarative memory.

PubMed

Miendlarzewska, Ewa A; Bavelier, Daphne; Schwartz, Sophie

2016-02-01

Motivational relevance can prioritize information for memory encoding and consolidation based on reward value. In this review, we pinpoint the possible psychological and neural mechanisms by which reward promotes learning, from guiding attention to enhancing memory consolidation. We then discuss how reward value can spill-over from one conditioned stimulus to a non-conditioned stimulus. Such generalization can occur across perceptually similar items or through more complex relations, such as associative or logical inferences. Existing evidence suggests that the neurotransmitter dopamine boosts the formation of declarative memory for rewarded information and may also control the generalization of reward values. In particular, temporally-correlated activity in the hippocampus and in regions of the dopaminergic circuit may mediate value-based decisions and facilitate cross-item integration. Given the importance of generalization in learning, our review points to the need to study not only how reward affects later memory but how learned reward values may generalize to related representations and ultimately alter memory structure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Translational Rodent Paradigms to Investigate Neuromechanisms Underlying Behaviors Relevant to Amotivation and Altered Reward Processing in Schizophrenia.

PubMed

Young, Jared W; Markou, Athina

2015-09-01

Amotivation and reward-processing deficits have long been described in patients with schizophrenia and considered large contributors to patients' inability to integrate well in society. No effective treatments exist for these symptoms, partly because the neuromechanisms mediating such symptoms are poorly understood. Here, we propose a translational neuroscientific approach that can be used to assess reward/motivational deficits related to the negative symptoms of schizophrenia using behavioral paradigms that can also be conducted in experimental animals. By designing and using objective laboratory behavioral tools that are parallel in their parameters in rodents and humans, the neuromechanisms underlying behaviors with relevance to these symptoms of schizophrenia can be investigated. We describe tasks that measure the motivation of rodents to expend physical and cognitive effort to gain rewards, as well as probabilistic learning tasks that assess both reward learning and feedback-based decision making. The latter tasks are relevant because of demonstrated links of performance deficits correlating with negative symptoms in patients with schizophrenia. These tasks utilize operant techniques in order to investigate neural circuits targeting a specific domain across species. These tasks therefore enable the development of insights into altered mechanisms leading to negative symptom-relevant behaviors in patients with schizophrenia. Such findings will then enable the development of targeted treatments for these altered neuromechanisms and behaviors seen in schizophrenia. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Common alterations in sensitivity to type but not amount of reward in ADHD and autism spectrum disorders.

PubMed

Demurie, Ellen; Roeyers, Herbert; Baeyens, Dieter; Sonuga-Barke, Edmund

2011-11-01

Children with attention deficit/hyperactivity disorder (ADHD) display abnormalities in reward processing. Most reward studies have focused on the effects of material or monetary rewards. Studies with autism spectrum disorder (ASD) have focused on social rewards. In this study we compared the effects of amount and type of reward in children with ADHD and those with ASD. Two adapted versions of the Monetary Incentive Delay Task were used to study the effects of monetary and social reward anticipation on performance in 40 typically developing (TD) children and adolescents (8-16y), 35 children and adolescents with ADHD and 31 children and adolescents with ASD. Monetary and social reward improved accuracy and response time (RT) in all groups. The higher the anticipated reward, the more accurate and faster were responses. Independent of these effects, there was a differential effect of reward type. Both clinical groups, but not TD, responded faster for monetary than social rewards. The results, while not supporting hyposensitivity to changes in reward amount in ADHD and ASD, do suggest that both groups are generally less motivated in settings where social as opposed to monetary rewards can be earned. © 2011 The Authors. Journal of Child Psychology and Psychiatry. © 2011 Association for Child and Adolescent Mental Health.

Addiction and brain reward and antireward pathways.

PubMed

Gardner, Eliot L

2011-01-01

Addictive drugs have in common that they are voluntarily self-administered by laboratory animals (usually avidly), and that they enhance the functioning of the reward circuitry of the brain (producing the 'high' that the drug user seeks). The core reward circuitry consists of an 'in-series' circuit linking the ventral tegmental area, nucleus accumbens and ventral pallidum via the medial forebrain bundle. Although originally believed to simply encode the set point of hedonic tone, these circuits are now believed to be functionally far more complex, also encoding attention, expectancy of reward, disconfirmation of reward expectancy, and incentive motivation. 'Hedonic dysregulation' within these circuits may lead to addiction. The 'second-stage' dopaminergic component in this reward circuitry is the crucial addictive-drug-sensitive component. All addictive drugs have in common that they enhance (directly or indirectly or even transsynaptically) dop-aminergic reward synaptic function in the nucleus accumbens. Drug self-administration is regulated by nucleus accumbens dopamine levels, and is done to keep nucleus accumbens dopamine within a specific elevated range (to maintain a desired hedonic level). For some classes of addictive drugs (e.g. opiates), tolerance to the euphoric effects develops with chronic use. Postuse dysphoria then comes to dominate reward circuit hedonic tone, and addicts no longer use drugs to get high, but simply to get back to normal ('get straight'). The brain circuits mediating the pleasurable effects of addictive drugs are anatomically, neurophysiologically and neurochemically different from those mediating physical dependence, and from those mediating craving and relapse. There are important genetic variations in vulnerability to drug addiction, yet environmental factors such as stress and social defeat also alter brain-reward mechanisms in such a manner as to impart vulnerability to addiction. In short, the 'bio-psycho-social' model of etiology holds very well for addiction. Addiction appears to correlate with a hypodopaminergic dysfunctional state within the reward circuitry of the brain. Neuroimaging studies in humans add credence to this hypothesis. Credible evidence also implicates serotonergic, opioid, endocannabinoid, GABAergic and glutamatergic mechanisms in addiction. Critically, drug addiction progresses from occasional recreational use to impulsive use to habitual compulsive use. This correlates with a progression from reward-driven to habit-driven drug-seeking behavior. This behavioral progression correlates with a neuroanatomical progression from ventral striatal (nucleus accumbens) to dorsal striatal control over drug-seeking behavior. The three classical sets of craving and relapse triggers are (a) reexposure to addictive drugs, (b) stress, and (c) reexposure to environmental cues (people, places, things) previously associated with drug-taking behavior. Drug-triggered relapse involves the nucleus accumbens and the neurotransmitter dopamine. Stress-triggered relapse involves (a) the central nucleus of the amygdala, the bed nucleus of the stria terminalis, and the neurotransmitter corticotrophin-releasing factor, and (b) the lateral tegmental noradrenergic nuclei of the brain stem and the neurotransmitter norepinephrine. Cue-triggered relapse involves the basolateral nucleus of the amygdala, the hippocampus and the neurotransmitter glutamate. Knowledge of the neuroanatomy, neurophysiology, neurochemistry and neuropharmacology of addictive drug action in the brain is currently producing a variety of strategies for pharmacotherapeutic treatment of drug addiction, some of which appear promising. Copyright © 2011 S. Karger AG, Basel.

Adolescent Stimulation of D2 Receptors Alters the Maturation of Dopamine-dependent Goal-Directed Behavior

PubMed Central

Naneix, Fabien; Marchand, Alain R; Pichon, Anaïs; Pape, Jean- Rémi; Coutureau, Etienne

2013-01-01

Adolescence is a period of high sensitivity to drugs and rewards, characterized by the immaturity of decision-making abilities. A chronic stimulation of reward systems during this period might constitute a factor of vulnerability to the development of psychiatric disorders. However, the long-term consequences of such an exposure have seldom been explored. Here, we investigate at the adult age the effects of chronic dopamine (DA) stimulation during adolescence on both the maturation of DA systems and the cognitive processes underlying goal-directed actions. We first demonstrate that chronic stimulation of D2 receptors by quinpirole during adolescence alters the development of DA systems. This treatment has particularly prominent effects on the mesocortical DA pathway where it decreases DA fibers density, DA concentration, and DA receptors expression. Furthermore, we show that quinpirole-treated rats exhibit specific impairments in instrumental goal-directed behavior, as they fail to adapt their action when action–outcome relationships change in a contingency degradation procedure. These results therefore highlight the vulnerability of DA system and prefrontal areas to prolonged stimulation during adolescence, and its potential long-term impact on cognitive functions. PMID:23443719

Dissociable Effects of Cocaine Dependence on Reward Processes: The Role of Acute Cocaine and Craving.

PubMed

Rose, Emma Jane; Salmeron, Betty Jo; Ross, Thomas J; Waltz, James; Schweitzer, Julie B; Stein, Elliot A

2017-02-01

The relative impact of chronic vs acute cocaine on dependence-related variability in reward processing in cocaine-dependent individuals (CD) is not well understood, despite the relevance of such effects to long-term outcomes. To dissociate these effects, CD (N=15) and healthy controls (HC; N=15) underwent MRI two times while performing a monetary incentive delay task. Both scans were identical across subjects/groups, except that, in a single-blind, counterbalanced design, CD received intravenous cocaine (30 mg/70 kg) before one session (CD+cocaine) and saline in another (CD+saline). Imaging analyses focused on activity related to anticipatory valence (gain/loss), anticipatory magnitude (small/medium/large), and reinforcing outcomes (successful/unsuccessful). Drug condition (cocaine vs saline) and group (HC vs CD+cocaine or CD+saline) did not influence valence-related activity. However, compared with HC, magnitude-related activity for gains was reduced in CD in the left cingulate gyrus post-cocaine and in the left putamen in the abstinence/saline condition. In contrast, magnitude-dependent activity for losses increased in CD vs HC in the right inferior parietal lobe post-cocaine and in the left superior frontal gyrus post-saline. Across outcomes (ie, successful and unsuccessful) activity in the right habenula decreased in CD in the abstinence/saline condition vs acute cocaine and HC. Cocaine-dependent variability in outcome- and loss-magnitude activity correlated negatively with ratings of cocaine craving and positively with how high subjects felt during the scanning session. Collectively, these data suggest dissociable effects of acute cocaine on non-drug reward processes, with cocaine consumption partially ameliorating dependence-related insensitivity to reinforcing outcomes/'liking', but having no discernible effect on dependence-related alterations in incentive salience/'wanting'. The relationship of drug-related affective sequelae to non-drug reward processing suggests that CD experience a general alteration of reward function and may be motivated to continue using cocaine for reasons beyond desired drug-related effects. This may have implications for individual differences in treatment efficacy for approaches that rely on reinforcement strategies (eg, contingency management) and for the long-term success of treatment.

Medial prefrontal brain activation to anticipated reward and loss in obsessive–compulsive disorder☆

PubMed Central

Kaufmann, C.; Beucke, J.C.; Preuße, F.; Endrass, T.; Schlagenhauf, F.; Heinz, A.; Juckel, G.; Kathmann, N.

2013-01-01

Obsessive–compulsive disorder (OCD) is associated with dysfunctional brain activity in several regions which are also involved in the processing of motivational stimuli. Processing of reward and punishment appears to be of special importance to understand clinical symptoms. There is evidence for higher sensitivity to punishment in patients with OCD which raises the question how avoidance of punishment relates to activity within the brain's reward circuitry. We employed the monetary incentive delay task paradigm optimized for modeling the anticipation phase of immediate reward and punishment, in the context of a cross-sectional event-related FMRI study comparing OCD patients and healthy control participants (n = 19 in each group). While overall behavioral performance was similar in both groups, patients showed increased activation upon anticipated losses in a medial and superior frontal cortex region extending into the cingulate cortex, and decreased activation upon anticipated rewards. No evidence was found for altered activation of dorsal or ventral striatal regions. Patients also showed more delayed responses for anticipated rewards than for anticipated losses whereas the reverse was true in healthy participants. The medial prefrontal cortex has been shown to implement a domain-general process comprising negative affect, pain and cognitive control. This process uses information about punishment to control aversively motivated actions by integrating signals arriving from subcortical regions. Our results support the notion that OCD is associated with altered sensitivity to anticipated rewards and losses in a medial prefrontal region whereas there is no significant aberrant activation in ventral or dorsal striatal brain regions during processing of reinforcement anticipation. PMID:24179774

Medial prefrontal brain activation to anticipated reward and loss in obsessive-compulsive disorder.

PubMed

Kaufmann, C; Beucke, J C; Preuße, F; Endrass, T; Schlagenhauf, F; Heinz, A; Juckel, G; Kathmann, N

2013-01-01

Obsessive-compulsive disorder (OCD) is associated with dysfunctional brain activity in several regions which are also involved in the processing of motivational stimuli. Processing of reward and punishment appears to be of special importance to understand clinical symptoms. There is evidence for higher sensitivity to punishment in patients with OCD which raises the question how avoidance of punishment relates to activity within the brain's reward circuitry. We employed the monetary incentive delay task paradigm optimized for modeling the anticipation phase of immediate reward and punishment, in the context of a cross-sectional event-related FMRI study comparing OCD patients and healthy control participants (n = 19 in each group). While overall behavioral performance was similar in both groups, patients showed increased activation upon anticipated losses in a medial and superior frontal cortex region extending into the cingulate cortex, and decreased activation upon anticipated rewards. No evidence was found for altered activation of dorsal or ventral striatal regions. Patients also showed more delayed responses for anticipated rewards than for anticipated losses whereas the reverse was true in healthy participants. The medial prefrontal cortex has been shown to implement a domain-general process comprising negative affect, pain and cognitive control. This process uses information about punishment to control aversively motivated actions by integrating signals arriving from subcortical regions. Our results support the notion that OCD is associated with altered sensitivity to anticipated rewards and losses in a medial prefrontal region whereas there is no significant aberrant activation in ventral or dorsal striatal brain regions during processing of reinforcement anticipation.

Dopamine Reward Prediction Error Responses Reflect Marginal Utility

PubMed Central

Stauffer, William R.; Lak, Armin; Schultz, Wolfram

2014-01-01

Summary Background Optimal choices require an accurate neuronal representation of economic value. In economics, utility functions are mathematical representations of subjective value that can be constructed from choices under risk. Utility usually exhibits a nonlinear relationship to physical reward value that corresponds to risk attitudes and reflects the increasing or decreasing marginal utility obtained with each additional unit of reward. Accordingly, neuronal reward responses coding utility should robustly reflect this nonlinearity. Results In two monkeys, we measured utility as a function of physical reward value from meaningful choices under risk (that adhered to first- and second-order stochastic dominance). The resulting nonlinear utility functions predicted the certainty equivalents for new gambles, indicating that the functions’ shapes were meaningful. The monkeys were risk seeking (convex utility function) for low reward and risk avoiding (concave utility function) with higher amounts. Critically, the dopamine prediction error responses at the time of reward itself reflected the nonlinear utility functions measured at the time of choices. In particular, the reward response magnitude depended on the first derivative of the utility function and thus reflected the marginal utility. Furthermore, dopamine responses recorded outside of the task reflected the marginal utility of unpredicted reward. Accordingly, these responses were sufficient to train reinforcement learning models to predict the behaviorally defined expected utility of gambles. Conclusions These data suggest a neuronal manifestation of marginal utility in dopamine neurons and indicate a common neuronal basis for fundamental explanatory constructs in animal learning theory (prediction error) and economic decision theory (marginal utility). PMID:25283778

Reward-Related Decision-Making in Pediatric Major Depressive Disorder: An fMRI Study

ERIC Educational Resources Information Center

Forbes, Erika E.; Christopher May, J.; Siegle, Greg J.; Ladouceur, Cecile D.; Ryan, Neal D.; Carter, Cameron S.; Birmaher, Boris; Axelson, David A.; Dahl, Ronald E.

2006-01-01

Background: Although reward processing is considered an important part of affective functioning, few studies have investigated reward-related decisions or responses in young people with affective disorders. Depression is postulated to involve decreased activity in reward-related affective systems. Methods: Using functional magnetic resonance…

Reduced Functional Connectivity within the Mesocorticolimbic System in Substance Use Disorders: An fMRI Study of Puerto Rican Young Adults

PubMed Central

Posner, Jonathan; Amira, Leora; Algaze, Antonio; Canino, Glorisa; Duarte, Cristiane S.

2016-01-01

Studies of the mesocorticolimbic reward system (MCLS) and its relationship with impulsivity and substance use disorders (SUD) have largely focused on individuals from non-minority backgrounds. This represents a significant gap in the literature particularly for minority populations who are disproportionately affected by the consequences of SUD. Using resting-state functional MRI (fMRI), we examined the coherence of neural activity, or functional connectivity, within the brain’s MCLS in 28 young adult Puerto Ricans (ages 25–27) who were part of a population-based cohort study. Half of the sample lived in San Juan, Puerto Rico; the other half lived in the South Bronx, New York. At each of the two sites, half of the sample had a history of a SUD. Relative to those without SUD, individuals with SUD had decreased connectivity between the nucleus accumbens (NAcc) and several regions within the MCLS. This finding was true irrespective of study site (i.e., San Juan or South Bronx). Reduced connectivity within the MCLS was also associated with higher self-reported levels of impulsivity. Path analysis suggested a potential mechanism linking impulsivity, the MCLS, and SUD: impulsivity, potentially by chronically promoting reward seeking behaviors, may contribute to decreased MCLS connectivity, which in turn, may confer vulnerability for SUD. Expanding upon prior studies suggesting that alterations within the MCLS underlie SUD, our findings suggest that such alterations are also related to impulsivity and are present in a high-risk young minority population. PMID:27252633

Dopamine reward prediction error responses reflect marginal utility.

PubMed

Stauffer, William R; Lak, Armin; Schultz, Wolfram

2014-11-03

Optimal choices require an accurate neuronal representation of economic value. In economics, utility functions are mathematical representations of subjective value that can be constructed from choices under risk. Utility usually exhibits a nonlinear relationship to physical reward value that corresponds to risk attitudes and reflects the increasing or decreasing marginal utility obtained with each additional unit of reward. Accordingly, neuronal reward responses coding utility should robustly reflect this nonlinearity. In two monkeys, we measured utility as a function of physical reward value from meaningful choices under risk (that adhered to first- and second-order stochastic dominance). The resulting nonlinear utility functions predicted the certainty equivalents for new gambles, indicating that the functions' shapes were meaningful. The monkeys were risk seeking (convex utility function) for low reward and risk avoiding (concave utility function) with higher amounts. Critically, the dopamine prediction error responses at the time of reward itself reflected the nonlinear utility functions measured at the time of choices. In particular, the reward response magnitude depended on the first derivative of the utility function and thus reflected the marginal utility. Furthermore, dopamine responses recorded outside of the task reflected the marginal utility of unpredicted reward. Accordingly, these responses were sufficient to train reinforcement learning models to predict the behaviorally defined expected utility of gambles. These data suggest a neuronal manifestation of marginal utility in dopamine neurons and indicate a common neuronal basis for fundamental explanatory constructs in animal learning theory (prediction error) and economic decision theory (marginal utility). Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Ethanol Exposure History and Alcoholic Reward Differentially Alter Dopamine Release in the Nucleus Accumbens to a Reward-Predictive Cue.

PubMed

Fiorenza, Amanda M; Shnitko, Tatiana A; Sullivan, Kaitlin M; Vemuru, Sudheer R; Gomez-A, Alexander; Esaki, Julie Y; Boettiger, Charlotte A; Da Cunha, Claudio; Robinson, Donita L

2018-06-01

Conditioned stimuli (CS) that predict reward delivery acquire the ability to induce phasic dopamine release in the nucleus accumbens (NAc). This dopamine release may facilitate conditioned approach behavior, which often manifests as approach to the site of reward delivery (called "goal-tracking") or to the CS itself (called "sign-tracking"). Previous research has linked sign-tracking in particular to impulsivity and drug self-administration, and addictive drugs may promote the expression of sign-tracking. Ethanol (EtOH) acutely promotes phasic release of dopamine in the accumbens, but it is unknown whether an alcoholic reward alters dopamine release to a CS. We hypothesized that Pavlovian conditioning with an alcoholic reward would increase dopamine release triggered by the CS and subsequent sign-tracking behavior. Moreover, we predicted that chronic intermittent EtOH (CIE) exposure would promote sign-tracking while acute administration of naltrexone (NTX) would reduce it. Rats received 14 doses of EtOH (3 to 5 g/kg, intragastric) or water followed by 6 days of Pavlovian conditioning training. Rewards were a chocolate solution with or without 10% (w/v) alcohol. We used fast-scan cyclic voltammetry to measure phasic dopamine release in the NAc core in response to the CS and the rewards. We also determined the effect of NTX (1 mg/kg, subcutaneous) on conditioned approach. Both CIE and alcoholic reward, individually but not together, associated with greater dopamine to the CS than control conditions. However, this increase in dopamine release was not linked to greater sign-tracking, as both CIE and alcoholic reward shifted conditioned approach from sign-tracking behavior to goal-tracking behavior. However, they both also increased sensitivity to NTX, which reduced goal-tracking behavior. While a history of EtOH exposure or alcoholic reward enhanced dopamine release to a CS, they did not promote sign-tracking under the current conditions. These findings are consistent with the interpretation that EtOH can stimulate conditioned approach, but indicate that the conditioned response may manifest as goal-tracking. Copyright © 2018 by the Research Society on Alcoholism.

Role of expected reward in frontal eye field during natural scene search

PubMed Central

Lawlor, Patrick N.; Ramkumar, Pavan; Kording, Konrad P.; Segraves, Mark A.

2016-01-01

When a saccade is expected to result in a reward, both neural activity in oculomotor areas and the saccade itself (e.g., its vigor and latency) are altered (compared with when no reward is expected). As such, it is unclear whether the correlations of neural activity with reward indicate a representation of reward beyond a movement representation; the modulated neural activity may simply represent the differences in motor output due to expected reward. Here, to distinguish between these possibilities, we trained monkeys to perform a natural scene search task while we recorded from the frontal eye field (FEF). Indeed, when reward was expected (i.e., saccades to the target), FEF neurons showed enhanced responses. Moreover, when monkeys accidentally made eye movements to the target, firing rates were lower than when they purposively moved to the target. Thus, neurons were modulated by expected reward rather than simply the presence of the target. We then fit a model that simultaneously included components related to expected reward and saccade parameters. While expected reward led to shorter latency and higher velocity saccades, these behavioral changes could not fully explain the increased FEF firing rates. Thus, FEF neurons appear to encode motivational factors such as reward expectation, above and beyond the kinematic and behavioral consequences of imminent reward. PMID:27169506

EEG to Primary Rewards: Predictive Utility and Malleability by Brain Stimulation

PubMed Central

Prause, Nicole; Siegle, Greg J.; Deblieck, Choi; Wu, Allan; Iacoboni, Marco

2016-01-01

Theta burst stimulation (TBS) is thought to affect reward processing mechanisms, which may increase and decrease reward sensitivity. To test the ability of TBS to modulate response to strong primary rewards, participants hypersensitive to primary rewards were recruited. Twenty men and women with at least two opposite-sex, sexual partners in the last year received two forms of TBS. Stimulations were randomized to avoid order effects and separated by 2 hours to reduce carryover. The two TBS forms have been demonstrated to inhibit (continuous) or excite (intermittent) the left dorsolateral prefrontal cortex using different pulse patterns, which links to brain areas associated with reward conditioning. After each TBS, participants completed tasks assessing their reward responsiveness to monetary and sexual rewards. Electroencephalography (EEG) was recorded. They also reported their number of orgasms in the weekend following stimulation. This signal was malleable by TBS, where excitatory TBS resulted in lower EEG alpha relative to inhibitory TBS to primary rewards. EEG responses to sexual rewards in the lab (following both forms of TBS) predicted the number of orgasms experienced over the forthcoming weekend. TBS may be useful in modifying hypersensitivity or hyposensitivity to primary rewards that predict sexual behaviors. Since TBS altered the anticipation of a sexual reward, TBS may offer a novel treatment for sexual desire problems. PMID:27902711

EEG to Primary Rewards: Predictive Utility and Malleability by Brain Stimulation.

PubMed

Prause, Nicole; Siegle, Greg J; Deblieck, Choi; Wu, Allan; Iacoboni, Marco

2016-01-01

Theta burst stimulation (TBS) is thought to affect reward processing mechanisms, which may increase and decrease reward sensitivity. To test the ability of TBS to modulate response to strong primary rewards, participants hypersensitive to primary rewards were recruited. Twenty men and women with at least two opposite-sex, sexual partners in the last year received two forms of TBS. Stimulations were randomized to avoid order effects and separated by 2 hours to reduce carryover. The two TBS forms have been demonstrated to inhibit (continuous) or excite (intermittent) the left dorsolateral prefrontal cortex using different pulse patterns, which links to brain areas associated with reward conditioning. After each TBS, participants completed tasks assessing their reward responsiveness to monetary and sexual rewards. Electroencephalography (EEG) was recorded. They also reported their number of orgasms in the weekend following stimulation. This signal was malleable by TBS, where excitatory TBS resulted in lower EEG alpha relative to inhibitory TBS to primary rewards. EEG responses to sexual rewards in the lab (following both forms of TBS) predicted the number of orgasms experienced over the forthcoming weekend. TBS may be useful in modifying hypersensitivity or hyposensitivity to primary rewards that predict sexual behaviors. Since TBS altered the anticipation of a sexual reward, TBS may offer a novel treatment for sexual desire problems.

Do Economic Rewards Work?

ERIC Educational Resources Information Center

Wallace, Brian D.

2009-01-01

The love of learning--that intrinsic desire to gain knowledge and insight into new subjects--was once its own reward. That was altered decades ago when parents started using the proverbial "stick and carrot" to motivate their children to do well in school, or even just show up. Today, educators across the country have taken hold of this…

Mood, food, and obesity.

PubMed

Singh, Minati

2014-01-01

Food is a potent natural reward and food intake is a complex process. Reward and gratification associated with food consumption leads to dopamine (DA) production, which in turn activates reward and pleasure centers in the brain. An individual will repeatedly eat a particular food to experience this positive feeling of gratification. This type of repetitive behavior of food intake leads to the activation of brain reward pathways that eventually overrides other signals of satiety and hunger. Thus, a gratification habit through a favorable food leads to overeating and morbid obesity. Overeating and obesity stems from many biological factors engaging both central and peripheral systems in a bi-directional manner involving mood and emotions. Emotional eating and altered mood can also lead to altered food choice and intake leading to overeating and obesity. Research findings from human and animal studies support a two-way link between three concepts, mood, food, and obesity. The focus of this article is to provide an overview of complex nature of food intake where various biological factors link mood, food intake, and brain signaling that engages both peripheral and central nervous system signaling pathways in a bi-directional manner in obesity.

The Function of Verbal Rewards in the Science Classroom.

ERIC Educational Resources Information Center

Lawlor, Francis Xavier

Contained is a review of the research done on the use of verbal rewards in the classroom. Some verbal rewards are tasks rewards, other rewards are more personal; and still other verbal rewards are impersonal. Verbal rewards, therefore, have both intellectual and emotional implications. Research literature indicates that "verbal reward"…

Do dorsal raphe 5-HT neurons encode "beneficialness"?

PubMed

Luo, Minmin; Li, Yi; Zhong, Weixin

2016-11-01

The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) affects numerous behavioral and physiological processes. Drugs that alter 5-HT signaling treat several major psychiatric disorders and may lead to widespread abuse. The dorsal raphe nucleus (DRN) in the midbrain provides a majority of 5-HT for the forebrain. The importance of 5-HT signaling propels the search for a general theoretical framework under which the diverse functions of the DRN 5-HT neurons can be interpreted and additional therapeutic solutions may be developed. However, experimental data so far support several seeming irreconcilable theories, suggesting that 5-HT neurons mediate behavioral inhibition, aversive processing, or reward signaling. Here, we review recent progresses and propose that DRN 5-HT neurons encode "beneficialness" - how beneficial the current environmental context represents for an individual. Specifically, we speculate that the activity of these neurons reflects the possible net benefit of the current context as determined by p·R-C, in which p indicates reward probability, R the reward value, and C the cost. Through the widespread projections of these neurons to the forebrain, the beneficialness signal may reconfigure neural circuits to bias perception, boost positive emotions, and switch behavioral choices. The "beneficialness" hypothesis can explain many conflicting observations, and at the same time raises new questions. We suggest additional experiments that will help elucidate the exact computational functions of the DRN 5-HT neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis.

PubMed

Frank, G K W; Shott, M E; Riederer, J; Pryor, T L

2016-11-01

Anorexia and bulimia nervosa are severe eating disorders that share many behaviors. Structural and functional brain circuits could provide biological links that those disorders have in common. We recruited 77 young adult women, 26 healthy controls, 26 women with anorexia and 25 women with bulimia nervosa. Probabilistic tractography was used to map white matter connectivity strength across taste and food intake regulating brain circuits. An independent multisample greedy equivalence search algorithm tested effective connectivity between those regions during sucrose tasting. Anorexia and bulimia nervosa had greater structural connectivity in pathways between insula, orbitofrontal cortex and ventral striatum, but lower connectivity from orbitofrontal cortex and amygdala to the hypothalamus (P<0.05, corrected for comorbidity, medication and multiple comparisons). Functionally, in controls the hypothalamus drove ventral striatal activity, but in anorexia and bulimia nervosa effective connectivity was directed from anterior cingulate via ventral striatum to the hypothalamus. Across all groups, sweetness perception was predicted by connectivity strength in pathways connecting to the middle orbitofrontal cortex. This study provides evidence that white matter structural as well as effective connectivity within the energy-homeostasis and food reward-regulating circuitry is fundamentally different in anorexia and bulimia nervosa compared with that in controls. In eating disorders, anterior cingulate cognitive-emotional top down control could affect food reward and eating drive, override hypothalamic inputs to the ventral striatum and enable prolonged food restriction.

Introduction: Addiction and Brain Reward and Anti-Reward Pathways

PubMed Central

Gardner, Eliot L.

2013-01-01

Addictive drugs have in common that they are voluntarily self-administered by laboratory animals (usually avidly) and that they enhance the functioning of the reward circuitry of the brain (producing the “high” that the drug-user seeks). The core reward circuitry consists of an “in series” circuit linking the ventral tegmental area, nucleus accumbens, and ventral pallidum - via the medial forebrain bundle. Although originally believed to encode simply the set-point of hedonic tone, these circuits are now believed to be functionally far more complex - also encoding attention, expectancy of reward, disconfirmation of reward expectancy, and incentive motivation. “Hedonic dysregulation” within these circuits may lead to addiction. The “second-stage” dopaminergic component in this reward circuitry is the crucial addictive-drug-sensitive component. All addictive drugs have in common that they enhance (directly or indirectly or even transsynaptically) dopaminergic reward synaptic function in the nucleus accumbens. Drug self-administration is regulated by nucleus accumbens dopamine levels, and is done to keep nucleus accumbens dopamine within a specific elevated range (to maintain a desired hedonic level). For some classes of addictive drugs (e.g., opiates), tolerance to the euphoric effects develops with chronic use. Post-use dysphoria then comes to dominate reward circuit hedonic tone, and addicts no longer use drugs to get “high,” but simply to get back to normal (“get straight”). The brain circuits mediating the pleasurable effects of addictive drugs are anatomically, neurophysiologically, and neurochemically different from those mediating physical dependence, and from those mediating craving and relapse. There are important genetic variations in vulnerability to drug addiction, yet environmental factors such as stress and social defeat also alter brain-reward mechanisms in such a manner as to impart vulnerability to addiction. In short, the “bio-psycho-social” model of etiology holds very well for addiction. Addiction appears to correlate with a hypo-dopaminergic dysfunctional state within the reward circuitry of the brain. Neuroimaging studies in humans add credence to this hypothesis. Credible evidence also implicates serotonergic, opioid, endocannabinoid, GABAergic, and glutamatergic mechanisms in addiction. Critically, drug addiction progresses from occasional recreational use to impulsive use to habitual compulsive use. This correlates with a progression from reward-driven to habit-driven drug-seeking behavior. This behavioral progression correlates with a neuroanatomical progression from ventral striatal (nucleus accumbens) to dorsal striatal control over drug-seeking behavior. The three classical sets of craving and relapse triggers are a) re-exposure to addictive drugs, b) stress, and c) re-exposure to environmental cues (“people, places, things”) previously associated with drug-taking behavior. Drug-triggered relapse involves the nucleus accumbens and the neurotransmitter dopamine. Stress-triggered relapse involves a) the central nucleus of the amygdala, the bed nucleus of the stria terminalis, and the neurotransmitter CRF; and b) the lateral tegmental noradrenergic nuclei of the brain stem and the neurotransmitter norepinephrine. Cue-triggered relapse involves the basolateral nucleus of the amygdala, the hippocampus, and the neurotransmitter glutamate. Knowledge of the neuroanatomy, neurophysiology, neurochemistry, and neuropharmacology of addictive drug action in the brain is currently producing a variety of strategies for pharmacotherapeutic treatment of drug addiction, some of which appear promising. PMID:21508625

Neural signal during immediate reward anticipation in schizophrenia: Relationship to real-world motivation and function.

PubMed

Subramaniam, Karuna; Hooker, Christine I; Biagianti, Bruno; Fisher, Melissa; Nagarajan, Srikantan; Vinogradov, Sophia

2015-01-01

Amotivation in schizophrenia is a central predictor of poor functioning, and is thought to occur due to deficits in anticipating future rewards, suggesting that impairments in anticipating pleasure can contribute to functional disability in schizophrenia. In healthy comparison (HC) participants, reward anticipation is associated with activity in frontal-striatal networks. By contrast, schizophrenia (SZ) participants show hypoactivation within these frontal-striatal networks during this motivated anticipatory brain state. Here, we examined neural activation in SZ and HC participants during the anticipatory phase of stimuli that predicted immediate upcoming reward and punishment, and during the feedback/outcome phase, in relation to trait measures of hedonic pleasure and real-world functional capacity. SZ patients showed hypoactivation in ventral striatum during reward anticipation. Additionally, we found distinct differences between HC and SZ groups in their association between reward-related immediate anticipatory neural activity and their reported experience of pleasure. HC participants recruited reward-related regions in striatum that significantly correlated with subjective consummatory pleasure, while SZ patients revealed activation in attention-related regions, such as the IPL, which correlated with consummatory pleasure and functional capacity. These findings may suggest that SZ patients activate compensatory attention processes during anticipation of immediate upcoming rewards, which likely contribute to their functional capacity in daily life.

Neural signal during immediate reward anticipation in schizophrenia: Relationship to real-world motivation and function

PubMed Central

Subramaniam, Karuna; Hooker, Christine I.; Biagianti, Bruno; Fisher, Melissa; Nagarajan, Srikantan; Vinogradov, Sophia

2015-01-01

Amotivation in schizophrenia is a central predictor of poor functioning, and is thought to occur due to deficits in anticipating future rewards, suggesting that impairments in anticipating pleasure can contribute to functional disability in schizophrenia. In healthy comparison (HC) participants, reward anticipation is associated with activity in frontal–striatal networks. By contrast, schizophrenia (SZ) participants show hypoactivation within these frontal–striatal networks during this motivated anticipatory brain state. Here, we examined neural activation in SZ and HC participants during the anticipatory phase of stimuli that predicted immediate upcoming reward and punishment, and during the feedback/outcome phase, in relation to trait measures of hedonic pleasure and real-world functional capacity. SZ patients showed hypoactivation in ventral striatum during reward anticipation. Additionally, we found distinct differences between HC and SZ groups in their association between reward-related immediate anticipatory neural activity and their reported experience of pleasure. HC participants recruited reward-related regions in striatum that significantly correlated with subjective consummatory pleasure, while SZ patients revealed activation in attention-related regions, such as the IPL, which correlated with consummatory pleasure and functional capacity. These findings may suggest that SZ patients activate compensatory attention processes during anticipation of immediate upcoming rewards, which likely contribute to their functional capacity in daily life. PMID:26413478

"Liking" and "wanting" linked to Reward Deficiency Syndrome (RDS): hypothesizing differential responsivity in brain reward circuitry.

PubMed

Blum, Kenneth; Gardner, Eliot; Oscar-Berman, Marlene; Gold, Mark

2012-01-01

In an attempt to resolve controversy regarding the causal contributions of mesolimbic dopamine (DA) systems to reward, we evaluate the three main competing explanatory categories: "liking,"learning," and "wanting" [1]. That is, DA may mediate (a) the hedonic impact of reward (liking), (b) learned predictions about rewarding effects (learning), or (c) the pursuit of rewards by attributing incentive salience to reward-related stimuli (wanting). We evaluate these hypotheses, especially as they relate to the Reward Deficiency Syndrome (RDS), and we find that the incentive salience or "wanting" hypothesis of DA function is supported by a majority of the evidence. Neuroimaging studies have shown that drugs of abuse, palatable foods, and anticipated behaviors such as sex and gaming affect brain regions involving reward circuitry, and may not be unidirectional. Drugs of abuse enhance DA signaling and sensitize mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Addictive drugs have in common that they are voluntarily selfadministered, they enhance (directly or indirectly) dopaminergic synaptic function in the nucleus accumbens (NAC), and they stimulate the functioning of brain reward circuitry (producing the "high" that drug users seek). Although originally believed simply to encode the set point of hedonic tone, these circuits now are believed to be functionally more complex, also encoding attention, reward expectancy, disconfirmation of reward expectancy, and incentive motivation. Elevated stress levels, together with polymorphisms of dopaminergic genes and other neurotransmitter genetic variants, may have a cumulative effect on vulnerability to addiction. The RDS model of etiology holds very well for a variety of chemical and behavioral addictions.

Decision-making under risk and ambiguity in low-birth-weight pigs.

PubMed

Murphy, Eimear; Kraak, Lynn; van den Broek, Jan; Nordquist, Rebecca E; van der Staay, Franz Josef

2015-03-01

Low birth weight (LBW) in humans is a risk factor for later cognitive, behavioural and emotional problems. In pigs, LBW is associated with higher mortality, but little is known about consequences for surviving piglets. Alteration in hypothalamic-pituitary-adrenal axis function in LBW pigs suggests altered emotionality, but no behavioural indicators have been studied. Decision-making under uncertain conditions, e.g., risk or ambiguity, is susceptible to emotional influences and may provide a means of assessing long-term effects of LBW in piglets. We tested LBW (N = 8) and normal-birth-weight (NBW; N = 8) male pigs in two decision-making tasks. For decision-making under risk, we developed a simple two-choice probabilistic task, the Pig Gambling Task (PGT), where an 'advantageous' option offered small but frequent rewards and a 'disadvantageous' option offered large but infrequent rewards. The advantageous option offered greater overall gain. For decision-making under ambiguity, we used a Judgement Bias Task (JBT) where pigs were trained to make an active response to 'positive' and 'negative' tone cues (signalling large and small rewards, respectively). Responses to ambiguous tone cues were rated as more or less optimistic. LBW pigs chose the advantageous option more often in later blocks of the PGT, and were scored as less optimistic in the JBT, than NBW pigs. Our findings demonstrate that LBW pigs have developed different behavioural strategies with respect to decision-making. We propose that this is guided by changes in emotionality in LBW piglets, and we provide behavioural evidence of increased negative affect in LBW piglets.

Caffeine in floral nectar enhances a pollinator's memory of reward.

PubMed

Wright, G A; Baker, D D; Palmer, M J; Stabler, D; Mustard, J A; Power, E F; Borland, A M; Stevenson, P C

2013-03-08

Plant defense compounds occur in floral nectar, but their ecological role is not well understood. We provide evidence that plant compounds pharmacologically alter pollinator behavior by enhancing their memory of reward. Honeybees rewarded with caffeine, which occurs naturally in nectar of Coffea and Citrus species, were three times as likely to remember a learned floral scent as were honeybees rewarded with sucrose alone. Caffeine potentiated responses of mushroom body neurons involved in olfactory learning and memory by acting as an adenosine receptor antagonist. Caffeine concentrations in nectar did not exceed the bees' bitter taste threshold, implying that pollinators impose selection for nectar that is pharmacologically active but not repellent. By using a drug to enhance memories of reward, plants secure pollinator fidelity and improve reproductive success.

Caffeine in floral nectar enhances a pollinator’s memory of reward

PubMed Central

Wright, G. A.; Baker, D. D.; Palmer, M. J.; Stabler, D.; Mustard, J. A.; Power, E. F.; Borland, A. M.; Stevenson, P. C.

2015-01-01

Plant defence compounds occur in floral nectar, but their ecological role is not well-understood. We provide the first evidence that plant compounds pharmacologically alter pollinator behaviour by enhancing their memory of reward. Honeybees rewarded with caffeine, which occurs naturally in nectar of Coffea and Citrus species, were three times more likely to remember a learned floral scent than those rewarded with sucrose alone. Caffeine potentiated responses of mushroom body neurons involved in olfactory learning and memory by acting as an adenosine receptor antagonist. Caffeine concentrations in nectar never exceeded the bees’ bitter taste threshold, implying that pollinators impose selection for nectar that is pharmacologically active but not repellent. By using a drug to enhance memories of reward, plants secure pollinator fidelity and improve reproductive success. PMID:23471406

Effort, anhedonia, and function in schizophrenia: reduced effort allocation predicts amotivation and functional impairment.

PubMed

Barch, Deanna M; Treadway, Michael T; Schoen, Nathan

2014-05-01

One of the most debilitating aspects of schizophrenia is an apparent interest in or ability to exert effort for rewards. Such "negative symptoms" may prevent individuals from obtaining potentially beneficial outcomes in educational, occupational, or social domains. In animal models, dopamine abnormalities decrease willingness to work for rewards, implicating dopamine (DA) function as a candidate substrate for negative symptoms given that schizophrenia involves dysregulation of the dopamine system. We used the effort-expenditure for rewards task (EEfRT) to assess the degree to which individuals with schizophrenia were wiling to exert increased effort for either larger magnitude rewards or for rewards that were more probable. Fifty-nine individuals with schizophrenia and 39 demographically similar controls performed the EEfRT task, which involves making choices between "easy" and "hard" tasks to earn potential rewards. Individuals with schizophrenia showed less of an increase in effort allocation as either reward magnitude or probability increased. In controls, the frequency of choosing the hard task in high reward magnitude and probability conditions was negatively correlated with depression severity and anhedonia. In schizophrenia, fewer hard task choices were associated with more severe negative symptoms and worse community and work function as assessed by a caretaker. Consistent with patterns of disrupted dopamine functioning observed in animal models of schizophrenia, these results suggest that 1 mechanism contributing to impaired function and motivational drive in schizophrenia may be a reduced allocation of greater effort for higher magnitude or higher probability rewards.

Atypical valuation of monetary and cigarette rewards in substance dependent smokers.

PubMed

Baker, Travis E; Wood, Jonathan M A; Holroyd, Clay B

2016-02-01

Substance dependent (SD) relative to non-dependent (ND) individuals exhibit an attenuated reward positivity, an electrophysiological signal believed to index sensitivity of anterior cingulate cortex (ACC) to rewards. Here we asked whether this altered neural response reflects a specific devaluation of monetary rewards relative to drug-related rewards by ACC. We recorded the reward positivity from SD and ND individuals who currently smoke, following an overnight period of abstinence, while they engaged in two feedback tasks. In a money condition the feedback indicated either a monetary reward or no reward, and in a cigarette condition the feedback indicated either a drug-related reward or no reward. Overall, cigarette relative to monetary rewards elicited a larger reward positivity. Further, for the subjects who engaged in the money condition first, the reward positivity was smaller for the SD compared to the ND participants, but for the subjects who engaged in the cigarette condition first, the reward positivity was larger for the SD compared to the ND participants. Our results suggest that the initial category of feedback "primed" the response of the ACC to the alternative feedback type on subsequent trials, and that SD and ND individuals responded differently to this priming effect. We propose that for people who misuse addictive substances, the prospect of obtaining drug-related rewards engages the ACC to exert control over extended behaviors. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Molecular imaging and neural networks in impulse control disorders in Parkinson's disease.

PubMed

Aracil-Bolaños, I; Strafella, A P

2016-01-01

Impulse control disorders (ICDs) may arise in Parkinson's disease (PD) in relation to the use of dopamine agonists (DA). A dysfunction of reward circuits is considered the main underlying mechanism. Neuroimaging has been largely used in this setting to understand the structure of the reward system and its abnormalities brought by exogenous stimulation in PD. Dopaminergic changes, such as increased dopamine release, reduced dopamine transporter activity and other changes, have been shown to be a consistent feature of ICDs in PD. Beyond the striatum, alterations of prefrontal cortical function may also impact an individuals' propensity for impulsivity. Neuroimaging is advancing our knowledge of the mechanisms involved in the development of these behavioral addictions. An increased understanding of these disorders may lead to the discovery of new therapeutic targets, or the identification of risk factors for the development of these disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Age associations with neural processing of reward anticipation in adolescents with bipolar disorders

PubMed Central

Urošević, Snežana; Luciana, Monica; Jensen, Jonathan B.; Youngstrom, Eric A.; Thomas, Kathleen M.

2016-01-01

Reward/behavioral approach system hypersensitivity is implicated in bipolar disorders (BD) and in normative development during adolescence. Pediatric onset of BD is associated with a more severe illness course. However, little is known about neural processing of rewards in adolescents with BD or developmental (i.e., age) associations with activation of these neural systems. The present study aims to address this knowledge gap. The present sample included 21 adolescents with BD and 26 healthy adolescents, ages 13 to 19. Participants completed a functional magnetic resonance imaging (fMRI) protocol using the Monetary Incentive Delay (MID) task. Behavioral performance was similar between groups. Group differences in BOLD activation during target anticipation and feedback anticipation periods of the task were examined using whole-brain analyses, as were group differences in age effects. During both target anticipation and feedback anticipation, adolescents with BD, compared to adolescents without psychopathology, exhibited decreased engagement of frontal regions involved in cognitive control (i.e., dorsolateral prefrontal cortex). Healthy adolescents exhibited age-related decreases, while adolescents with BD exhibited age-related increases, in activity of other cognitive control frontal areas (i.e., right inferior frontal gyrus), suggesting altered development in the BD group. Longitudinal research is needed to examine potentially abnormal development of cognitive control during reward pursuit in adolescent BD and whether early therapeutic interventions can prevent these potential deviations from normative development. PMID:27114896

Age associations with neural processing of reward anticipation in adolescents with bipolar disorders.

PubMed

Urošević, Snežana; Luciana, Monica; Jensen, Jonathan B; Youngstrom, Eric A; Thomas, Kathleen M

2016-01-01

Reward/behavioral approach system hypersensitivity is implicated in bipolar disorders (BD) and in normative development during adolescence. Pediatric onset of BD is associated with a more severe illness course. However, little is known about neural processing of rewards in adolescents with BD or developmental (i.e., age) associations with activation of these neural systems. The present study aims to address this knowledge gap. The present sample included 21 adolescents with BD and 26 healthy adolescents, ages 13 to 19. Participants completed a functional magnetic resonance imaging (fMRI) protocol using the Monetary Incentive Delay (MID) task. Behavioral performance was similar between groups. Group differences in BOLD activation during target anticipation and feedback anticipation periods of the task were examined using whole-brain analyses, as were group differences in age effects. During both target anticipation and feedback anticipation, adolescents with BD, compared to adolescents without psychopathology, exhibited decreased engagement of frontal regions involved in cognitive control (i.e., dorsolateral prefrontal cortex). Healthy adolescents exhibited age-related decreases, while adolescents with BD exhibited age-related increases, in activity of other cognitive control frontal areas (i.e., right inferior frontal gyrus), suggesting altered development in the BD group. Longitudinal research is needed to examine potentially abnormal development of cognitive control during reward pursuit in adolescent BD and whether early therapeutic interventions can prevent these potential deviations from normative development.

Maternal "junk-food" feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring.

PubMed

Ong, Z Y; Muhlhausler, B S

2011-07-01

Individuals exposed to high-fat, high-sugar diets before birth have an increased risk of obesity in later life. Recent studies have shown that these offspring exhibit increased preference for fat, leading to suggestions that perinatal exposure to high-fat, high-sugar foods results in permanent changes within the central reward system that increase the subsequent drive to overconsume palatable foods. The present study has determined the effect of a maternal "junk-food" diet on the expression of key components of the mesolimbic reward pathway in the offspring of rat dams at 6 wk and 3 mo of age. We show that offspring of junk-food-fed (JF) dams exhibit higher fat intake from weaning until at least 3 mo of age (males: 16 ± 0.6 vs. 11 ± 0.8 g/kg/d; females: 19 ± 1.3 vs. 13 ± 0.4 g/kg/d; P<0.01). mRNA expression of μ-opioid receptor (Mu) was 1.6-fold higher (P<0.01) and dopamine active transporter (DAT) was 2-fold lower (P<0.05) in JF offspring at 6 wk of age. By 3 mo, these differences were reversed, and Mu mRNA expression was 2.8-fold lower (P<0.01) and DAT mRNA expression was 1.9-fold higher (P<0.01) in the JF offspring. These findings suggest that perinatal exposure to high-fat, high-sugar diets results in altered development of the central reward system, resulting in increased fat intake and altered response of the reward system to excessive junk-food intake in postnatal life.

Comprehensive Behavioral Analysis of Male Ox1r (-/-) Mice Showed Implication of Orexin Receptor-1 in Mood, Anxiety, and Social Behavior.

PubMed

Abbas, Md G; Shoji, Hirotaka; Soya, Shingo; Hondo, Mari; Miyakawa, Tsuyoshi; Sakurai, Takeshi

2015-01-01

Neuropeptides orexin A and orexin B, which are exclusively produced by neurons in the lateral hypothalamic area, play an important role in the regulation of a wide range of behaviors and homeostatic processes, including regulation of sleep/wakefulness states and energy homeostasis. The orexin system has close anatomical and functional relationships with systems that regulate the autonomic nervous system, emotion, mood, the reward system, and sleep/wakefulness states. Recent pharmacological studies using selective antagonists have suggested that orexin receptor-1 (OX1R) is involved in physiological processes that regulate emotion, the reward system, and autonomic nervous system. Here, we examined Ox1r (-/-) mice with a comprehensive behavioral test battery to screen additional OX1R functions. Ox1r (-/-) mice showed increased anxiety-like behavior, altered depression-like behavior, slightly decreased spontaneous locomotor activity, reduced social interaction, increased startle response, and decreased prepulse inhibition. These results suggest that OX1R plays roles in social behavior and sensory motor gating in addition to roles in mood and anxiety.

Comprehensive Behavioral Analysis of Male Ox1r−/− Mice Showed Implication of Orexin Receptor-1 in Mood, Anxiety, and Social Behavior

PubMed Central

Abbas, Md. G.; Shoji, Hirotaka; Soya, Shingo; Hondo, Mari; Miyakawa, Tsuyoshi; Sakurai, Takeshi

2015-01-01

Neuropeptides orexin A and orexin B, which are exclusively produced by neurons in the lateral hypothalamic area, play an important role in the regulation of a wide range of behaviors and homeostatic processes, including regulation of sleep/wakefulness states and energy homeostasis. The orexin system has close anatomical and functional relationships with systems that regulate the autonomic nervous system, emotion, mood, the reward system, and sleep/wakefulness states. Recent pharmacological studies using selective antagonists have suggested that orexin receptor-1 (OX1R) is involved in physiological processes that regulate emotion, the reward system, and autonomic nervous system. Here, we examined Ox1r−/− mice with a comprehensive behavioral test battery to screen additional OX1R functions. Ox1r−/− mice showed increased anxiety-like behavior, altered depression-like behavior, slightly decreased spontaneous locomotor activity, reduced social interaction, increased startle response, and decreased prepulse inhibition. These results suggest that OX1R plays roles in social behavior and sensory motor gating in addition to roles in mood and anxiety. PMID:26696848

The amount effect and marginal value.

PubMed

Rachlin, Howard; Arfer, Kodi B; Safin, Vasiliy; Yen, Ming

2015-07-01

The amount effect of delay discounting (by which the value of larger reward amounts is discounted by delay at a lower rate than that of smaller amounts) strictly implies that value functions (value as a function of amount) are steeper at greater delays than they are at lesser delays. That is, the amount effect and the difference in value functions at different delays are actually a single empirical finding. Amount effects of delay discounting are typically found with choice experiments. Value functions for immediate rewards have been empirically obtained by direct judgment. (Value functions for delayed rewards have not been previously obtained.) The present experiment obtained value functions for both immediate and delayed rewards by direct judgment and found them to be steeper when the rewards were delayed--hence, finding an amount effect with delay discounting. © Society for the Experimental Analysis of Behavior.

Cigarette craving is associated with blunted reward processing in nicotine-dependent smokers.

PubMed

Peechatka, Alyssa L; Whitton, Alexis E; Farmer, Stacey L; Pizzagalli, Diego A; Janes, Amy C

2015-10-01

Dysfunctional reward processing leading to the undervaluation of non-drug rewards is hypothesized to play a crucial role in nicotine dependence. However, it is unclear if blunted reward responsivity and the desire to use nicotine are directly linked after a brief period of abstinence. Such an association would suggest that individuals with reduced reward responsivity may be at increased risk to experience nicotine craving. Reward function was evaluated with a probabilistic reward task (PRT), which measures reward responsivity to monetary incentives. To identify whether smoking status influenced reward function, PRT performance was compared between non-depressed, nicotine-dependent smokers and non-smokers. Within smokers, correlations were conducted to determine if blunted reward responsivity on the PRT was associated with increased nicotine craving. Time since last nicotine exposure was standardized to 4h for all smokers. Smokers and non-smokers did not differ in reward responsivity on the PRT. However, within smokers, a significant negative correlation was found between reward responsivity and intensity of nicotine craving. The current findings show that, among smokers, the intensity of nicotine craving is linked to lower sensitivity to non-drug rewards. This finding is in line with prior theories that suggest reward dysfunction in some clinical populations (e.g., depressive disorders, schizophrenia) may facilitate nicotine use. The current study expands on such theories by indicating that sub-clinical variations in reward function are related to motivation for nicotine use. Identifying smokers who show blunted sensitivity to non-drug rewards may help guide treatments aimed at mitigating the motivation to smoke. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Differential impairments underlying decision making in anorexia nervosa and bulimia nervosa: a cognitive modeling analysis.

PubMed

Chan, Trista Wai Sze; Ahn, Woo-Young; Bates, John E; Busemeyer, Jerome R; Guillaume, Sebastien; Redgrave, Graham W; Danner, Unna N; Courtet, Philippe

2014-03-01

This study examined the underlying processes of decision-making impairments in individuals with anorexia nervosa (AN) and bulimia nervosa (BN). We deconstructed their performance on the widely used decision task, the Iowa Gambling Task (IGT) into cognitive, motivational, and response processes using cognitive modeling analysis. We hypothesized that IGT performance would be characterized by impaired memory functions and heightened punishment sensitivity in AN, and by elevated sensitivity to reward as opposed to punishment in BN. We analyzed trial-by-trial data of IGT obtained from 224 individuals: 94 individuals with AN, 63 with BN, and 67 healthy comparison individuals (HC). The prospect valence learning model was used to assess cognitive, motivational, and response processes underlying IGT performance. Individuals with AN showed marginally impaired IGT performance compared to HC. Their performance was characterized by impairments in memory functions. Individuals with BN showed significantly impaired IGT performance compared to HC. They showed greater relative sensitivity to gains as opposed to losses than HC. Memory functions in AN were positively correlated with body mass index. This study identified differential impairments underlying IGT performance in AN and BN. Findings suggest that impaired decision making in AN might involve impaired memory functions. Impaired decision making in BN might involve altered reward and punishment sensitivity. Copyright © 2013 Wiley Periodicals, Inc.

The importance of context: When relative relief renders pain pleasant

PubMed Central

Leknes, Siri; Berna, Chantal; Lee, Michael C.; Snyder, Gregory D.; Biele, Guido; Tracey, Irene

2013-01-01

Context can influence the experience of any event. For instance, the thought that “it could be worse” can improve feelings towards a present misfortune. In this study we measured hedonic feelings, skin conductance, and brain activation patterns in 16 healthy volunteers who experienced moderate pain in two different contexts. In the “relative relief context,” moderate pain represented the best outcome, since the alternative outcome was intense pain. However, in the control context, moderate pain represented the worst outcome and elicited negative hedonic feelings. The context manipulation resulted in a “hedonic flip,” such that moderate pain elicited positive hedonics in the relative relief context. Somewhat surprisingly, moderate pain was even rated as pleasant in this context, despite being reported as painful in the control context. This “hedonic flip” was corroborated by physiological and functional neuroimaging data. When moderate pain was perceived as pleasant, skin conductance and activity in insula and dorsal anterior cingulate were significantly attenuated relative to the control moderate stimulus. “Pleasant pain” also increased activity in reward and valuation circuitry, including the medial orbitofrontal and ventromedial prefrontal cortices. Furthermore, the change in outcome hedonics correlated with activity in the periacqueductal grey (PAG) of the descending pain modulatory system (DPMS). The context manipulation also significantly increased functional connectivity between reward circuitry and the PAG, consistent with a functional change of the DPMS due to the altered motivational state. The findings of this study point to a role for brainstem and reward circuitry in a context-induced “hedonic flip” of pain. PMID:23352758

Diet-Induced Obesity and Diet-Resistant rats: differences in the rewarding and anorectic effects of D-amphetamine

PubMed Central

Valenza, Marta; Steardo, Luca; Cottone, Pietro; Sabino, Valentina

2015-01-01

Rationale Obesity is a leading public health problem worldwide. Multiple lines of evidence associate deficits in the brain reward circuit with obesity. Objective Whether alterations in brain reward sensitivity precede or are a consequence of obesity is unknown. This study aimed to investigate both innate and obesity-induced differences in the sensitivity to the effects of an indirect dopaminergic agonist. Methods Rats genetically prone to diet-induced obesity (DIO) and their counterpart diet-resistant (DR) were fed a chow diet and their response to D-amphetamine on intracranial self-stimulation and food intake were assessed. The same variables were then evaluated after exposing the rats to a high-fat diet, after DIO rats selectively developed obesity. Finally, gene expression levels of dopamine receptor 1 and 2 as well as tyrosine hydroxylase were measured in reward-related brain regions. Results In a pre-obesity state, DIO rats showed innate decreased sensitivity to the reward-enhancing and anorectic effects of D-amphetamine, as compared to DR rats. In a diet-induced obese state, the insensitivity to the potentiating effects of D-amphetamine on ICSS threshold persisted and became more marked in DIO rats, while the anorectic effects were comparable between genotypes. Finally, innate and obesity-induced differences in the gene expression of dopamine receptors were observed. Conclusions Our results demonstrate that brain reward deficits antedate the development of obesity and worsen after obesity is fully developed, suggesting that these alterations represent vulnerability factors for its development. Moreover, our data suggests that the reward-enhancing and anorectic effects of D-amphetamine are dissociable in the context of obesity. PMID:26047964

Association between pubertal stage at first drink and neural reward processing in early adulthood.

PubMed

Boecker-Schlier, Regina; Holz, Nathalie E; Hohm, Erika; Zohsel, Katrin; Blomeyer, Dorothea; Buchmann, Arlette F; Baumeister, Sarah; Wolf, Isabella; Esser, Günter; Schmidt, Martin H; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

2017-09-01

Puberty is a critical time period during human development. It is characterized by high levels of risk-taking behavior, such as increased alcohol consumption, and is accompanied by various neurobiological changes. Recent studies in animals and humans have revealed that the pubertal stage at first drink (PSFD) significantly impacts drinking behavior in adulthood. Moreover, neuronal alterations of the dopaminergic reward system have been associated with alcohol abuse or addiction. This study aimed to clarify the impact of PSFD on neuronal characteristics of reward processing linked to alcohol-related problems. One hundred sixty-eight healthy young adults from a prospective study covering 25 years participated in a monetary incentive delay task measured with simultaneous EEG-fMRI. PSFD was determined according to the age at menarche or Tanner stage of pubertal development, respectively. Alcohol-related problems in early adulthood were assessed with the Alcohol Use Disorder Identification Test (AUDIT). During reward anticipation, decreased fMRI activation of the frontal cortex and increased preparatory EEG activity (contingent negative variation) occurred with pubertal compared to postpubertal first alcohol intake. Moreover, alcohol-related problems during early adulthood were increased in pubertal compared to postpubertal beginners, which was mediated by neuronal activation of the right medial frontal gyrus. At reward delivery, increased fMRI activation of the left caudate and higher feedback-related EEG negativity were detected in pubertal compared to postpubertal beginners. Together with animal findings, these results implicate PSFD as a potential modulator of psychopathology, involving altered reward anticipation. Both PSFD timing and reward processing might thus be potential targets for early prevention and intervention. © 2016 Society for the Study of Addiction.

Evaluators' Perceptions of Teachers' Use of Behavior Alteration Techniques.

ERIC Educational Resources Information Center

Allen, Terre; Edwards, Renee

1988-01-01

Examines which message-based behavior alteration techniques (BATs) teacher evaluators perceive as commonly used by good, average, and poor teachers. Reports that principals equate reward-type messages with effective teaching and punishment-type messages with ineffective teaching. (MM)

“Liking” and “Wanting” Linked to Reward Deficiency Syndrome (RDS): Hypothesizing Differential Responsivity in Brain Reward Circuitry

PubMed Central

Blum, Kenneth; Gardner, Eliot; Oscar-Berman, Marlene; Gold, Mark

2013-01-01

In an attempt to resolve controversy regarding the causal contributions of mesolimbic dopamine (DA) systems to reward, we evaluate the three main competing explanatory categories: “liking,” “learning,” and “wanting” [1]. That is, DA may mediate (a) the hedonic impact of reward (liking), (b) learned predictions about rewarding effects (learning), or (c) the pursuit of rewards by attributing incentive salience to reward-related stimuli (wanting). We evaluate these hypotheses, especially as they relate to the Reward Deficiency Syndrome (RDS), and we find that the incentive salience or “wanting” hypothesis of DA function is supported by a majority of the evidence. Neuroimaging studies have shown that drugs of abuse, palatable foods, and anticipated behaviors such as sex and gaming affect brain regions involving reward circuitry, and may not be unidirectional. Drugs of abuse enhance DA signaling and sensitize mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Addictive drugs have in common that they are voluntarily self-administered, they enhance (directly or indirectly) dopaminergic synaptic function in the nucleus accumbens, and they stimulate the functioning of brain reward circuitry (producing the “high” that drug users seek). Although originally believed simply to encode the set point of hedonic tone, these circuits now are believed to be functionally more complex, also encoding attention, reward expectancy, disconfirmation of reward expectancy, and incentive motivation. Elevated stress levels, together with polymorphisms of dopaminergic genes and other neurotransmitter genetic variants, may have a cumulative effect on vulnerability to addiction. The RDS model of etiology holds very well for a variety of chemical and behavioral addictions. PMID:22236117

Negative reinforcement impairs overnight memory consolidation.

PubMed

Stamm, Andrew W; Nguyen, Nam D; Seicol, Benjamin J; Fagan, Abigail; Oh, Angela; Drumm, Michael; Lundt, Maureen; Stickgold, Robert; Wamsley, Erin J

2014-11-01

Post-learning sleep is beneficial for human memory. However, it may be that not all memories benefit equally from sleep. Here, we manipulated a spatial learning task using monetary reward and performance feedback, asking whether enhancing the salience of the task would augment overnight memory consolidation and alter its incorporation into dreaming. Contrary to our hypothesis, we found that the addition of reward impaired overnight consolidation of spatial memory. Our findings seemingly contradict prior reports that enhancing the reward value of learned information augments sleep-dependent memory processing. Given that the reward followed a negative reinforcement paradigm, consolidation may have been impaired via a stress-related mechanism. © 2014 Stamm et al.; Published by Cold Spring Harbor Laboratory Press.

Reward from bugs to bipeds: a comparative approach to understanding how reward circuits function

PubMed Central

Scaplen, Kristin M.; Kaun, Karla R.

2016-01-01

Abstract In a complex environment, animals learn from their responses to stimuli and events. Appropriate response to reward and punishment can promote survival, reproduction and increase evolutionary fitness. Interestingly, the neural processes underlying these responses are remarkably similar across phyla. In all species, dopamine is central to encoding reward and directing motivated behaviors, however, a comprehensive understanding of how circuits encode reward and direct motivated behaviors is still lacking. In part, this is a result of the sheer diversity of neurons, the heterogeneity of their responses and the complexity of neural circuits within which they are found. We argue that general features of reward circuitry are common across model organisms, and thus principles learned from invertebrate model organisms can inform research across species. In particular, we discuss circuit motifs that appear to be functionally equivalent from flies to primates. We argue that a comparative approach to studying and understanding reward circuit function provides a more comprehensive understanding of reward circuitry, and informs disorders that affect the brain’s reward circuitry. PMID:27328845

Valence-dependent influence of serotonin depletion on model-based choice strategy

PubMed Central

Worbe, Y; Palminteri, S; Savulich, G; Daw, N D; Fernandez-Egea, E; Robbins, T W; Voon, V

2016-01-01

Human decision-making arises from both reflective and reflexive mechanisms, which underpin goal-directed and habitual behavioural control. Computationally, these two systems of behavioural control have been described by different learning algorithms, model-based and model-free learning, respectively. Here, we investigated the effect of diminished serotonin (5-hydroxytryptamine) neurotransmission using dietary tryptophan depletion (TD) in healthy volunteers on the performance of a two-stage decision-making task, which allows discrimination between model-free and model-based behavioural strategies. A novel version of the task was used, which not only examined choice balance for monetary reward but also for punishment (monetary loss). TD impaired goal-directed (model-based) behaviour in the reward condition, but promoted it under punishment. This effect on appetitive and aversive goal-directed behaviour is likely mediated by alteration of the average reward representation produced by TD, which is consistent with previous studies. Overall, the major implication of this study is that serotonin differentially affects goal-directed learning as a function of affective valence. These findings are relevant for a further understanding of psychiatric disorders associated with breakdown of goal-directed behavioural control such as obsessive-compulsive disorders or addictions. PMID:25869808

Looking for reward in all the wrong places: dopamine receptor gene polymorphisms indirectly affect aggression through sensation-seeking.

PubMed

Chester, David S; DeWall, C Nathan; Derefinko, Karen J; Estus, Steven; Lynam, Donald R; Peters, Jessica R; Jiang, Yang

2016-10-01

Individuals with genotypes that code for reduced dopaminergic brain activity often exhibit a predisposition toward aggression. However, it remains largely unknown how dopaminergic genotypes may increase aggression. Lower-functioning dopamine systems motivate individuals to seek reward from external sources such as illicit drugs and other risky experiences. Based on emerging evidence that aggression is a rewarding experience, we predicted that the effect of lower-functioning dopaminergic functioning on aggression would be mediated by tendencies to seek the environment for rewards. Caucasian female and male undergraduates (N = 277) were genotyped for five polymorphisms of the dopamine D2 receptor (DRD2) gene; they reported their previous history of aggression and their dispositional reward-seeking. Lower-functioning DRD2 profiles were associated with greater sensation-seeking, which then predicted greater aggression. Our findings suggest that lower-functioning dopaminergic activity puts individuals at risk for violence because it motivates them to experience aggression's hedonically rewarding qualities.

Life stress in adolescence predicts early adult reward-related brain function and alcohol dependence

PubMed Central

Shaw, Daniel S.; Sitnick, Stephanie L.; Musselman, Samuel C.; Forbes, Erika E.

2015-01-01

Stressful life events increase vulnerability to problematic alcohol use, and they may do this by disrupting reward-related neural circuitry. This is particularly relevant for adolescents because alcohol use rises sharply after mid-adolescence and alcohol abuse peaks at age 20. Adolescents also report more stressors compared with children, and neural reward circuitry may be especially vulnerable to stressors during adolescence because of prefrontal cortex remodeling. Using a large sample of male participants in a longitudinal functional magnetic resonance imaging study (N = 157), we evaluated whether cumulative stressful life events between the ages of 15 and 18 were associated with reward-related brain function and problematic alcohol use at age 20 years. Higher cumulative stressful life events during adolescence were associated with decreased response in the medial prefrontal cortex (mPFC) during monetary reward anticipation and following the receipt of monetary rewards. Stress-related decreases in mPFC response during reward anticipation and following rewarding outcomes were associated with the severity of alcohol dependence. Furthermore, mPFC response mediated the association between stressful life events and later symptoms of alcohol dependence. These data are consistent with neurobiological models of addiction that propose that stressors during adolescence increase risk for problematic alcohol use by disrupting reward circuit function. PMID:24795442

Diurnal rhythms in psychological reward functioning in healthy young men: 'Wanting', liking, and learning.

PubMed

Byrne, Jamie E M; Murray, Greg

2017-01-01

A range of evidence suggests that human reward functioning is partly driven by the endogenous circadian system, generating 24-hour rhythms in behavioural measures of reward activation. Reward functioning is multifaceted but literature to date is largely limited to measures of self-reported positive mood states. The aim of this study was to advance the field by testing for hypothesised diurnal variation in previously unexplored components of psychological reward: 'wanting', liking, and learning using subjective and behavioural measures. Risky decision making (automatic Balloon Analogue Risk Task), affective responsivity to positive images (International Affective Pictures System), uncued self-reported discrete emotions, and learning-contingent reward (Iowa Gambling Task) were measured at 10.00 hours, 14.00 hours, and 19.00 hours in a counterbalanced repeated measures design with 50 healthy male participants (aged 18-30). As hypothesised, risky decision making (unconscious 'wanting') and ratings of arousal towards positive images (conscious wanting) exhibited a diurnal waveform with indices highest at 14.00 hours. No diurnal rhythm was observed for liking (pleasure ratings to positive images, discrete uncued positive emotions) or in a learning-contingent reward task. Findings reaffirm that diurnal variation in human reward functioning is most pronounced in the motivational 'wanting' components of reward.

Motor Cortex-Evoked Activity in Reciprocal Muscles Is Modulated by Reward Probability

PubMed Central

Suzuki, Makoto; Kirimoto, Hikari; Sugawara, Kazuhiro; Oyama, Mineo; Yamada, Sumio; Yamamoto, Jun-ichi; Matsunaga, Atsuhiko; Fukuda, Michinari; Onishi, Hideaki

2014-01-01

Horizontal intracortical projections for agonist and antagonist muscles exist in the primary motor cortex (M1), and reward may induce a reinforcement of transmission efficiency of intracortical circuits. We investigated reward-induced change in M1 excitability for agonist and antagonist muscles. Participants were 8 healthy volunteers. Probabilistic reward tasks comprised 3 conditions of 30 trials each: 30 trials contained 10% reward, 30 trials contained 50% reward, and 30 trials contained 90% reward. Each trial began with a cue (red fixation cross), followed by blue circle for 1 s. The subjects were instructed to perform wrist flexion and press a button with the dorsal aspect of middle finger phalanx as quickly as possible in response to disappearance of the blue circle without looking at their hand or the button. Two seconds after the button press, reward/non-reward stimulus was randomly presented for 2-s duration. The reward stimulus was a picture of Japanese 10-yen coin, and each subject received monetary reward at the end of experiment. Subjects were not informed of the reward probabilities. We delivered transcranial magnetic stimulation of the left M1 at the midpoint between center of gravities of agonist flexor carpi radialis (FCR) and antagonist extensor carpi radialis (ECR) muscles at 2 s after the red fixation cross and 1 s after the reward/non-reward stimuli. Relative motor evoked potential (MEP) amplitudes at 2 s after the red fixation cross were significantly higher for 10% reward probability than for 90% reward probability, whereas relative MEP amplitudes at 1 s after reward/non-reward stimuli were significantly higher for 90% reward probability than for 10% and 50% reward probabilities. These results implied that reward could affect the horizontal intracortical projections in M1 for agonist and antagonist muscles, and M1 excitability including the reward-related circuit before and after reward stimulus could be differently altered by reward probability. PMID:24603644

Neural correlates of reward processing in adults with 22q11 deletion syndrome.

PubMed

van Duin, Esther D A; Goossens, Liesbet; Hernaus, Dennis; da Silva Alves, Fabiana; Schmitz, Nicole; Schruers, Koen; van Amelsvoort, Therese

2016-01-01

22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is located at the deleted region, resulting in disrupted dopaminergic neurotransmission in 22q11DS, which may contribute to the increased vulnerability for psychosis. A dysfunctional motivational reward system is considered one of the salient features in psychosis and thought to be related to abnormal dopaminergic neurotransmission. The functional anatomy of the brain reward circuitry has not yet been investigated in 22q11DS. This study aims to investigate neural activity during anticipation of reward and loss in adult patients with 22q11DS. We measured blood-oxygen-level dependent (BOLD) activity in 16 patients with 22q11DS and 12 healthy controls during a monetary incentive delay task using a 3T Philips Intera MRI system. Data were analysed using SPM8. During anticipation of reward, the 22q11DS group alone displayed significant activation in bilateral middle frontal and temporal brain regions. Compared to healthy controls, significantly less activation in bilateral cingulate gyrus extending to premotor, primary motor and somatosensory areas was found. During anticipation of loss, the 22q11DS group displayed activity in the left middle frontal gyrus and anterior cingulate cortex, and relative to controls, they showed reduced brain activation in bilateral (pre)cuneus and left posterior cingulate. Within the 22q11DS group, COMT Val hemizygotes displayed more activation compared to Met hemizygotes in right posterior cingulate and bilateral parietal regions during anticipation of reward. During anticipation of loss, COMT Met hemizygotes compared to Val hemizygotes showed more activation in bilateral insula, striatum and left anterior cingulate. This is the first study to investigate reward processing in 22q11DS. Our preliminary results suggest that people with 22q11DS engage a fronto-temporal neural network. Compared to healthy controls, people with 22q11DS primarily displayed reduced activity in medial frontal regions during reward anticipation. COMT hemizygosity affects responsivity of the reward system in this condition. Alterations in reward processing partly underlain by the dopamine system may play a role in susceptibility for psychosis in 22q11DS.

Reward loss and the basolateral amygdala: A function in reward comparisons.

PubMed

Kawasaki, Katsuyoshi; Annicchiarico, Iván; Glueck, Amanda C; Morón, Ignacio; Papini, Mauricio R

2017-07-28

The neural circuitry underlying behavior in reward loss situations is poorly understood. We considered two such situations: reward devaluation (from large to small rewards) and reward omission (from large rewards to no rewards). There is evidence that the central nucleus of the amygdala (CeA) plays a role in the negative emotion accompanying reward loss. However, little is known about the function of the basolateral nucleus (BLA) in reward loss. Two hypotheses of BLA function in reward loss, negative emotion and reward comparisons, were tested in an experiment involving pretraining excitotoxic BLA lesions followed by training in four tasks: consummatory successive negative contrast (cSNC), autoshaping (AS) acquisition and extinction, anticipatory negative contrast (ANC), and open field testing (OF). Cell counts in the BLA (but not in the CeA) were significantly lower in animals with lesions vs. shams. BLA lesions eliminated cSNC and ANC, and accelerated extinction of lever pressing in AS. BLA lesions had no effect on OF testing: higher activity in the periphery than in the central area. This pattern of results provides support for the hypothesis that BLA neurons are important for reward comparison. The three affected tasks (cSNC, ANC, and AS extinction) involve reward comparisons. However, ANC does not seem to involve negative emotions and it was affected, whereas OF activity is known to involve negative emotion, but it was not affected. It is hypothesized that a circuit involving the thalamus, insular cortex, and BLA is critically involved in the mechanism comparing current and expected rewards. Copyright © 2017 Elsevier B.V. All rights reserved.

Discrete coding of stimulus value, reward expectation, and reward prediction error in the dorsal striatum.

PubMed

Oyama, Kei; Tateyama, Yukina; Hernádi, István; Tobler, Philippe N; Iijima, Toshio; Tsutsui, Ken-Ichiro

2015-11-01

To investigate how the striatum integrates sensory information with reward information for behavioral guidance, we recorded single-unit activity in the dorsal striatum of head-fixed rats participating in a probabilistic Pavlovian conditioning task with auditory conditioned stimuli (CSs) in which reward probability was fixed for each CS but parametrically varied across CSs. We found that the activity of many neurons was linearly correlated with the reward probability indicated by the CSs. The recorded neurons could be classified according to their firing patterns into functional subtypes coding reward probability in different forms such as stimulus value, reward expectation, and reward prediction error. These results suggest that several functional subgroups of dorsal striatal neurons represent different kinds of information formed through extensive prior exposure to CS-reward contingencies. Copyright © 2015 the American Physiological Society.

Discrete coding of stimulus value, reward expectation, and reward prediction error in the dorsal striatum

PubMed Central

Oyama, Kei; Tateyama, Yukina; Hernádi, István; Tobler, Philippe N.; Iijima, Toshio

2015-01-01

To investigate how the striatum integrates sensory information with reward information for behavioral guidance, we recorded single-unit activity in the dorsal striatum of head-fixed rats participating in a probabilistic Pavlovian conditioning task with auditory conditioned stimuli (CSs) in which reward probability was fixed for each CS but parametrically varied across CSs. We found that the activity of many neurons was linearly correlated with the reward probability indicated by the CSs. The recorded neurons could be classified according to their firing patterns into functional subtypes coding reward probability in different forms such as stimulus value, reward expectation, and reward prediction error. These results suggest that several functional subgroups of dorsal striatal neurons represent different kinds of information formed through extensive prior exposure to CS-reward contingencies. PMID:26378201

Oxytocin increases VTA activation to infant and sexual stimuli in nulliparous and postpartum women

PubMed Central

Gregory, Rebecca; Cheng, Hu; Rupp, Heather A.; Sengelaub, Dale R.; Heiman, Julia R.

2015-01-01

After giving birth, women typically experience decreased sexual desire and increased responsiveness to infant stimuli. These postpartum changes may be viewed as a trade-off in reproductive interests, which could be due to alterations in brain activity including areas associated with reward. The goal of this study was to describe the roles of oxytocin and parity on reward area activation in response to reproductive stimuli, specifically infant and sexual images. Because they have been shown to be associated with reward, the ventral tegmental area (VTA) and nucleus accumbens (NAc) were targeted as areas of expected alterations in activity. Oxytocin was chosen as a potential mediator of reproductive trade-offs because of its relationship to both mother–infant interactions, including breastfeeding and bonding, and sexual responses. We predicted that postpartum women would show higher reward area activation to infant stimuli and nulliparous women would show higher activation to sexual stimuli and that oxytocin would increase activation to infant stimuli in nulliparous women. To test this, we measured VTA and NAc activation using fMRI in response to infant photos, sexual photos, and neutral photos in 29 postpartum and 30 nulliparous women. Participants completed the Sexual Inhibition (SIS) and Sexual Excitation (SES) Scales and the Brief Index of Sexual Function for Women (BISF-W), which includes a sexual desire dimension, and received either oxytocin or placebo nasal spray before viewing crying and smiling infant and sexual images in an fMRI scanner. For both groups of women, intranasal oxytocin administration increased VTA activation to both crying infant and sexual images but not to smiling infant images. We found that postpartum women showed lower SES, higher SIS, and lower sexual desire compared to nulliparous women. Across parity groups, SES scores were correlated with VTA activation and subjective arousal ratings to sexual images. In postpartum women, sexual desire was positively correlated with VTA activation to sexual images and with SES. Our findings show that postpartum decreases in sexual desire may in part be mediated by VTA activation, and oxytocin increased activation of the VTA but not NAc in response to sexual and infant stimuli. Oxytocin may contribute to the altered reproductive priorities in postpartum women by increasing VTA activation to salient infant stimuli. PMID:25562711

Effects of motivation on reward and attentional networks: an fMRI study.

PubMed

Ivanov, Iliyan; Liu, Xun; Clerkin, Suzanne; Schulz, Kurt; Friston, Karl; Newcorn, Jeffrey H; Fan, Jin

2012-11-01

Existing evidence suggests that reward and attentional networks function in concert and that activation in one system influences the other in a reciprocal fashion; however, the nature of these influences remains poorly understood. We therefore developed a three-component task to assess the interaction effects of reward anticipation and conflict resolution on the behavioral performance and the activation of brain reward and attentional systems. Sixteen healthy adult volunteers aged 21-45 years were scanned with functional magnetic resonance imaging (fMRI) while performing the task. A two-way repeated measures analysis of variance (ANOVA) with cue (reward vs. non-reward) and target (congruent vs. incongruent) as within-subjects factors was used to test for main and interaction effects. Neural responses to anticipation, conflict, and reward outcomes were tested. Behaviorally there were main effects of both reward cue and target congruency on reaction time. Neuroimaging results showed that reward anticipation and expected reward outcomes activated components of the attentional networks, including the inferior parietal and occipital cortices, whereas surprising non-rewards activated the frontoinsular cortex bilaterally and deactivated the ventral striatum. In turn, conflict activated a broad network associated with cognitive control and motor functions. Interaction effects showed decreased activity in the thalamus, anterior cingulated gyrus, and middle frontal gyrus bilaterally when difficult conflict trials (e.g., incongruent targets) were preceded by reward cues; in contrast, the ventral striatum and orbitofrontal cortex showed greater activation during congruent targets preceded by reward cues. These results suggest that reward anticipation is associated with lower activation in attentional networks, possibly due to increased processing efficiency, whereas more difficult, conflict trials are associated with lower activity in regions of the reward system, possibly because such trials are experienced as less rewarding.

Altering spatial priority maps via reward-based learning.

PubMed

Chelazzi, Leonardo; Eštočinová, Jana; Calletti, Riccardo; Lo Gerfo, Emanuele; Sani, Ilaria; Della Libera, Chiara; Santandrea, Elisa

2014-06-18

Spatial priority maps are real-time representations of the behavioral salience of locations in the visual field, resulting from the combined influence of stimulus driven activity and top-down signals related to the current goals of the individual. They arbitrate which of a number of (potential) targets in the visual scene will win the competition for attentional resources. As a result, deployment of visual attention to a specific spatial location is determined by the current peak of activation (corresponding to the highest behavioral salience) across the map. Here we report a behavioral study performed on healthy human volunteers, where we demonstrate that spatial priority maps can be shaped via reward-based learning, reflecting long-lasting alterations (biases) in the behavioral salience of specific spatial locations. These biases exert an especially strong influence on performance under conditions where multiple potential targets compete for selection, conferring competitive advantage to targets presented in spatial locations associated with greater reward during learning relative to targets presented in locations associated with lesser reward. Such acquired biases of spatial attention are persistent, are nonstrategic in nature, and generalize across stimuli and task contexts. These results suggest that reward-based attentional learning can induce plastic changes in spatial priority maps, endowing these representations with the "intelligent" capacity to learn from experience. Copyright © 2014 the authors 0270-6474/14/348594-11$15.00/0.

Peripheral temperature drop in response to anticipation and consumption of a signaled palatable reward in laying hens (Gallus domesticus).

PubMed

Moe, Randi Oppermann; Stubsjøen, Solveig Marie; Bohlin, Jon; Flø, Andreas; Bakken, Morten

2012-06-25

The present study describes effects of anticipation and consumption of a palatable reward on comb surface temperature. The purpose was to investigate temperature responses as a potential physiological indicator of positive emotional states in laying hens. A rise in body temperature in response to stimuli predictive of or during exposure to unpleasant events has been interpreted as evidence of emotions in mammals and avians. However, this phenomenon has so far only been studied during anticipation of or exposure to negative events; i.e., emotions of a negative valence. Infrared thermography was used to record potential alterations in comb surface temperature to a conditioned cue signaling a reward (mealworms) and during reward delivery. On average, comb temperature dropped 1.5 °C (95% CI: +/-1.2 °C) after exposure to CS and consumption of reward (p~0.0014) when initial comb temperature was above 30 °C. Such temperature drop indicates a peripheral vasoconstriction and has clear resemblances to emotional fever as seen during negative emotional states. Thus, we propose that a drop in peripheral temperature reflects emotional arousal more than emotional valence. Substantial temperature responses due to diet-induced thermogenesis were found, further emphasizing a cautious interpretation of altered comb temperature in studies of animal welfare. Copyright © 2012 Elsevier Inc. All rights reserved.

The endocannabinoid system in brain reward processes.

PubMed

Solinas, M; Goldberg, S R; Piomelli, D

2008-05-01

Food, drugs and brain stimulation can serve as strong rewarding stimuli and are all believed to activate common brain circuits that evolved in mammals to favour fitness and survival. For decades, endogenous dopaminergic and opioid systems have been considered the most important systems in mediating brain reward processes. Recent evidence suggests that the endogenous cannabinoid (endocannabinoid) system also has an important role in signalling of rewarding events. First, CB(1) receptors are found in brain areas involved in reward processes, such as the dopaminergic mesolimbic system. Second, activation of CB(1) receptors by plant-derived, synthetic or endogenous CB(1) receptor agonists stimulates dopaminergic neurotransmission, produces rewarding effects and increases rewarding effects of abused drugs and food. Third, pharmacological or genetic blockade of CB(1) receptors prevents activation of dopaminergic neurotransmission by several addictive drugs and reduces rewarding effects of food and these drugs. Fourth, brain levels of the endocannabinoids anandamide and 2-arachidonoylglycerol are altered by activation of reward processes. However, the intrinsic activity of the endocannabinoid system does not appear to play a facilitatory role in brain stimulation reward and some evidence suggests it may even oppose it. The influence of the endocannabinoid system on brain reward processes may depend on the degree of activation of the different brain areas involved and might represent a mechanism for fine-tuning dopaminergic activity. Although involvement of the various components of the endocannabinoid system may differ depending on the type of rewarding event investigated, this system appears to play a major role in modulating reward processes.

Self-administration of the synthetic cathinone MPDV enhances reward function via a nicotinic receptor dependent mechanism.

PubMed

Geste, Jean R; Pompilus, Marjory; Febo, Marcelo; Bruijnzeel, Adriaan W

2018-05-09

Methylenedioxypyrovalerone (MDPV) is an addictive synthetic drug with severe side effects. Previous studies have shown that MDPV has positive reinforcing properties. However, little is known about the effect of MDPV self-administration on the state of the brain reward system and the neuronal mechanisms by which MDPV mediates its effects. The goal of the present studies was to determine the effect of MDPV self-administration on reward function and the role of cholinergic neurotransmission in the reinforcing effects of MDPV. To study the effect of MDPV self-administration on the brain reward system, rats were prepared with intravenous catheters and intracranial self-stimulation electrodes (ICSS). For 10 days, the reward thresholds were assessed immediately before (23 h post prior session) and after 1 h of MDPV self-administration. The reward thresholds were decreased immediately after MDPV self-administration, which is indicative of a potentiation of brain reward function. The reward thresholds 23 h after MDPV intake gradually increased over time, which is indicative of anhedonia. Pretreatment with the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine decreased the self-administration of MDPV and completely prevented the decrease in reward thresholds. A control study with palatable chocolate pellets showed that responding for a natural reinforcer does not affect the state of the brain reward system. Furthermore, mecamylamine did not affect responding for food pellets. In conclusion, the self-administration of MDPV potentiates reward function and nAChR blockade prevents the reward enhancing effects of MDPV self-administration. Preventing the MDPV-induced increase in cholinergic neurotransmission might be a safe approach to diminish MDPV abuse. Copyright © 2018. Published by Elsevier Ltd.

Repeated nicotine exposure enhances reward-related learning in the rat.

PubMed

Olausson, Peter; Jentsch, J David; Taylor, Jane R

2003-07-01

Repeated exposure to addictive drugs causes neuroadaptive changes in cortico-limbic-striatal circuits that may underlie alterations in incentive-motivational processes and reward-related learning. Such drug-induced alterations may be relevant to drug addiction because enhanced incentive motivation and increased control over behavior by drug-associated stimuli may contribute to aspects of compulsive drug-seeking and drug-taking behaviors. This study investigated the consequences of repeated nicotine treatment on the acquisition and performance of Pavlovian discriminative approach behavior, a measure of reward-related learning, in male rats. Water-restricted rats were trained to associate a compound conditioned stimulus (tone+light) with the availability of water (the unconditioned stimulus) in 15 consecutive daily sessions. In separate experiments, rats were repeatedly treated with nicotine (0.35 mg/kg, s.c.) either (1) prior to the onset of training, (2) after each daily training session was completed (ie postsession injections), or (3) received nicotine both before the onset of training as well as after each daily training session. In this study, all nicotine treatment schedules increased Pavlovian discriminative approach behavior and, thus, prior repeated exposure to nicotine, repeated postsession nicotine injections, or both, facilitated reward-related learning.

Altered Reward Reactivity as a Behavioural Endophenotype in Eating Disorders: A Pilot Investigation in Twins.

PubMed

Kanakam, Natalie; Krug, Isabel; Collier, David; Treasure, Janet

2017-05-01

Altered reward reactivity is a potential risk endophenotype for eating disorders (EDs). The aim of this study was to examine reward reactivity in female twins with EDs and compare it with a twin control group. A sample of 112 twins [n = 51 met lifetime DSM-IV ED criteria (anorexia nervosa n = 26; bulimic disorders n = 24), n = 19 unaffected cotwins and n = 42 control twins] was administered measures assessing reward reactivity, including the Game of Dice Task, the Behavioural Inhibition/Activation (BIS/BAS) Scales and the Appetitive Motivation Scale (AMS). Within pair, correlations for monozygotic and dizygotic twins were calculated and generalised estimating equations compared probands with non-ED cotwins and controls. The BAS and the AMS were reduced in EDs and negatively associated with restrictive symptoms. In addition, monozygotic twins pairs demonstrated significant within pair similarity for the BAS and AMS. Conversely, there was less evidence to support the BIS or risky decision-making as measured by the Game of Dice Task as an endophenotype in EDs. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Altered reward anticipation: Potential explanation for weight gain in schizophrenia?

PubMed

Grimm, Oliver; Kaiser, Stefan; Plichta, Michael M; Tobler, Philippe N

2017-04-01

Obesity and weight gain are severe complications of mental illness, especially schizophrenia. They result from changes in lifestyle and nutrition, side effects of medication and other, less well-understood factors. Recent studies suggest that obesity and weight gain are linked to psychopathology. Specifically, severe psychopathology is associated with greater weight dysregulation, typically weight gain. However, our knowledge about the neuroscientific basis of weight gain in schizophrenia is currently limited. We propose that altered reward anticipation, which in turn is related to striatal dopaminergic dysregulation, may explain why obesity is more prevalent in individuals with mental illness. We review evidence that reward anticipation and weight change are linked by a core deficit in dopaminergic striatal circuits. Several lines of evidence, running from animal studies to preclinical and clinical studies, suggest that striatal dopaminergic neurotransmission is a major hub for the regulation of eating behavior and that dopamine links eating behavior to other motivated behavior. From this perspective, the present review outlines a unifying perspective on dopaminergic reward anticipation as a theoretical frame to link weight gain, medication effects and psychopathology. We derive important but open empirical questions and present perspectives for new therapeutic concepts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mood, food, and obesity

PubMed Central

Singh, Minati

2014-01-01

Food is a potent natural reward and food intake is a complex process. Reward and gratification associated with food consumption leads to dopamine (DA) production, which in turn activates reward and pleasure centers in the brain. An individual will repeatedly eat a particular food to experience this positive feeling of gratification. This type of repetitive behavior of food intake leads to the activation of brain reward pathways that eventually overrides other signals of satiety and hunger. Thus, a gratification habit through a favorable food leads to overeating and morbid obesity. Overeating and obesity stems from many biological factors engaging both central and peripheral systems in a bi-directional manner involving mood and emotions. Emotional eating and altered mood can also lead to altered food choice and intake leading to overeating and obesity. Research findings from human and animal studies support a two-way link between three concepts, mood, food, and obesity. The focus of this article is to provide an overview of complex nature of food intake where various biological factors link mood, food intake, and brain signaling that engages both peripheral and central nervous system signaling pathways in a bi-directional manner in obesity. PMID:25225489

Altered spatial learning and delay discounting in a rat model of human third trimester binge ethanol exposure

PubMed Central

Bañuelos, Cristina; Gilbert, Ryan J.; Montgomery, Karienn S.; Fincher, Annette S.; Wang, Haiying; Frye, Gerald D.; Setlow, Barry; Bizon, Jennifer L.

2012-01-01

Ethanol exposure during perinatal development can cause cognitive abnormalities including difficulties in learning, attention, and memory, as well as heightened impulsivity. The purpose of this study was to assess performance in spatial learning and impulsive choice tasks in rats subjected to an intragastric intubation model of binge ethanol exposure during human third trimester-equivalent brain development. Male and female Sprague–Dawley rat pups were intubated with ethanol (5.25 g/kg/day) on postnatal days 4–9. At adolescence (between postnatal days 35–38), these rats and sham intubated within-litter controls were trained in both spatial and cued versions of the Morris water maze. A subset of the male rats was subsequently tested on a delay-discounting task to assess impulsive choice. Ethanol-exposed rats were spatially impaired relative to controls, but performed comparably to controls on the cued version of the water maze. Ethanol-exposed rats also showed greater preference for large delayed rewards on the delay discounting task, but no evidence for altered reward sensitivity or perseverative behavior. These data demonstrate that early postnatal intermittent binge-like ethanol exposure has prolonged, detrimental, but selective effects on cognition, suggesting that even relatively brief ethanol exposure late in human pregnancy can be deleterious for cognitive function. PMID:22129556

Medial orbitofrontal cortex codes relative rather than absolute value of financial rewards in humans.

PubMed

Elliott, R; Agnew, Z; Deakin, J F W

2008-05-01

Functional imaging studies in recent years have confirmed the involvement of orbitofrontal cortex (OFC) in human reward processing and have suggested that OFC responses are context-dependent. A seminal electrophysiological experiment in primates taught animals to associate abstract visual stimuli with differently valuable food rewards. Subsequently, pairs of these learned abstract stimuli were presented and firing of OFC neurons to the medium-value stimulus was measured. OFC firing was shown to depend on the relative value context. In this study, we developed a human analogue of this paradigm and scanned subjects using functional magnetic resonance imaging. The analysis compared neuronal responses to two superficially identical events, which differed only in terms of the preceding context. Medial OFC response to the same perceptual stimulus was greater when the stimulus predicted the more valuable of two rewards than when it predicted the less valuable. Additional responses were observed in other components of reward circuitry, the amygdala and ventral striatum. The central finding is consistent with the primate results and suggests that OFC neurons code relative rather than absolute reward value. Amygdala and striatal involvement in coding reward value is also consistent with recent functional imaging data. By using a simpler and less confounded paradigm than many functional imaging studies, we are able to demonstrate that relative financial reward value per se is coded in distinct subregions of an extended reward and decision-making network.

Time-of-day differences and short-term stability of the neural response to monetary reward: a pilot study.

PubMed

Hasler, Brant P; Forbes, Erika E; Franzen, Peter L

2014-10-30

Human and animal studies indicate that reward function is modulated by the circadian clock that governs our daily sleep/wake rhythm. For example, a robust circadian rhythm exists in positive affect, which is lower in the morning hours and peaks in the afternoon. A handful of functional neuroimaging studies suggest that systematic diurnal variation exists in brain activity related to other functions, but no published human studies have examined daily variation in the neural processing of reward. In the present study, we attempt to advance this literature by using functional neuroimaging methods to examine time-of-day changes in the responsivity of the reward circuit. Using a within-person design and a functional magnetic resonance imaging (fMRI) monetary reward task, we compared morning and afternoon reward-related brain activation in a sample of healthy young adults within 24h. Region of interest analyses focused on the striatum, and we hypothesized greater reward activation in the afternoon, concordant with the circadian peak in positive affect. Results were consistent with our hypothesis. In addition, we counterbalanced the order of morning and afternoon scans in order to explore the short-term stability of the neural response. Whole-brain analyses showed a markedly higher reactivity to reward throughout the brain in the first scan relative to the second scan, consistent with habituation to the monetary reward stimuli. However, these effects did not appear to explain the time-of-day findings. In summary, we report the first preliminary evidence of circadian variation in the neural processing of reward. These findings have both methodological and theoretical implications. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A functional variant of the serotonin transporter gene (SLC6A4) moderates impulsive choice in attention-deficit/hyperactivity disorder boys and siblings.

PubMed

Sonuga-Barke, Edmund J S; Kumsta, Robert; Schlotz, Wolff; Lasky-Su, Jessica; Marco, Rafaela; Miranda, Ana; Mulas, Fernando; Oades, Robert D; Banaschewski, Tobias; Mueller, Ueli; Andreou, Penny; Christiansen, Hanna; Gabriels, Isabel; Uebel, Henrik; Kuntsi, Jonna; Franke, Barbara; Buitelaar, Jan; Ebstein, Richard; Gill, Michael; Anney, Richard; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph; Steinhausen, Hans Christoph; Asherson, Philip; Faraone, Stephen V

2011-08-01

Impulsive drive for immediate reward (IDIR) and delay aversion are dissociable elements of the preference for immediate over delayed rewards seen in attention-deficit/hyperactivity disorder (ADHD). We hypothesized that IDIR would be associated with dopamine regulating genes and delay aversion would be associated with serotonin-regulating genes. Impulsive drive for immediate reward and delay aversion were measured in 459 male children and adolescents (328 ADHD and 131 unaffected siblings) with a laboratory choice task. The sample was genotyped for the 5HTT (SLC6A4) promoter serotonin-transporter-linked polymorphic region polymorphism and a DAT1 (SLC6A3) 40-base pair variable number tandem repeat located in the 3'-untranslated region of the gene. There was no effect of dopamine transporter (DAT)1 on IDIR. As predicted, serotonin-transporter-linked polymorphic region s-allele carriers were more delay averse. This effect was driven by the s/l genotype in the ADHD group. These results were not altered by taking account of the rs25531 A/G single nucleotide polymorphism and were independent of age, IQ, and oppositional defiant disorder symptoms. The results support the genetic distinctiveness of IDIR and delay aversion in ADHD and implicate serotonin function in delay aversion. Possible explanations of the heterosis effect in the ADHD cases are presented. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis

PubMed Central

Frank, G K W; Shott, M E; Riederer, J; Pryor, T L

2016-01-01

Anorexia and bulimia nervosa are severe eating disorders that share many behaviors. Structural and functional brain circuits could provide biological links that those disorders have in common. We recruited 77 young adult women, 26 healthy controls, 26 women with anorexia and 25 women with bulimia nervosa. Probabilistic tractography was used to map white matter connectivity strength across taste and food intake regulating brain circuits. An independent multisample greedy equivalence search algorithm tested effective connectivity between those regions during sucrose tasting. Anorexia and bulimia nervosa had greater structural connectivity in pathways between insula, orbitofrontal cortex and ventral striatum, but lower connectivity from orbitofrontal cortex and amygdala to the hypothalamus (P<0.05, corrected for comorbidity, medication and multiple comparisons). Functionally, in controls the hypothalamus drove ventral striatal activity, but in anorexia and bulimia nervosa effective connectivity was directed from anterior cingulate via ventral striatum to the hypothalamus. Across all groups, sweetness perception was predicted by connectivity strength in pathways connecting to the middle orbitofrontal cortex. This study provides evidence that white matter structural as well as effective connectivity within the energy-homeostasis and food reward-regulating circuitry is fundamentally different in anorexia and bulimia nervosa compared with that in controls. In eating disorders, anterior cingulate cognitive–emotional top down control could affect food reward and eating drive, override hypothalamic inputs to the ventral striatum and enable prolonged food restriction. PMID:27801897

Chronic stress exposure may affect the brain's response to high calorie food cues and predispose to obesogenic eating habits.

PubMed

Tryon, Matthew S; Carter, Cameron S; Decant, Rashel; Laugero, Kevin D

2013-08-15

Exaggerated reactivity to food cues involving calorically-dense foods may significantly contribute to food consumption beyond caloric need. Chronic stress, which can induce palatable "comfort" food consumption, may trigger or reinforce neural pathways leading to stronger reactions to highly rewarding foods. We implemented functional magnetic resonance imaging (fMRI) to assess whether chronic stress influences activation in reward, motivation and executive brain regions in response to pictures of high calorie and low calorie foods in thirty women. On separate lab visits, we also assessed food intake from a snack food buffet and circulating cortisol. In women reporting higher chronic stress (HCS), pictures of high calorie foods elicited exaggerated activity in regions of the brain involving reward, motivation, and habitual decision-making. In response to pictures of high calorie food, higher chronic stress was also associated with significant deactivation in frontal regions (BA10; BA46) linked to strategic planning and emotional control. In functional connectivity analysis, HCS strengthened connectivity between amygdala and the putamen, while LCS enhanced connectivity between amygdala and the anterior cingulate and anterior prefrontal cortex (BA10). A hypocortisolemic signature and more consumption of high calorie foods from the snack buffet were observed in the HCS group. These results suggest that persistent stress exposure may alter the brain's response to food in ways that predispose individuals to poor eating habits which, if sustained, may increase risk for obesity. © 2013.

Role stress, role reward, and mental health in a multiethnic sample of midlife women: results from the Study of Women's Health Across the Nation (SWAN).

PubMed

Lanza di Scalea, Teresa; Matthews, Karen A; Avis, Nancy E; Thurston, Rebecca C; Brown, Charlotte; Harlow, Sioban; Bromberger, Joyce T

2012-05-01

Little is known about the independent associations of reward and stress within specific roles with multiple measures of mental health in an ethnically diverse community sample of midlife women. The objective of this study is to examine if (1) role reward (within each role and across roles) contributes directly to mental health and buffers the negative impact of role stress and (2) associations among role occupancy, role stress, and role reward and mental health vary by race/ethnicity. With separate logistic regression analysis, we investigated cross-sectional relationships between role stress and role reward with presence/absence of high depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D≥16]), anxiety symptoms (feeling tense or nervous, irritable or grouchy, fearful for no reason, and heart pounding or racing total score≥4), or low social functioning (bottom 25th percentile of the Short-Form-36 [SF-36] social functioning subscale) in 2549 women participating in the third visit of the Study of Women's Health Across the Nation (SWAN), a longitudinal population-based study of menopause. High reward across roles attenuated the negative impact of role stress on social functioning but not on anxiety or depression. High reward marriage buffered the impact of marital stress on depression, and high reward mothering buffered the effect of maternal stress on depression and social functioning. Compared to Caucasians, Hispanics and Chinese with high stress across roles had better social functioning, and African American mothers had lower odds of high depressive symptoms. Role reward buffers the negative impact of stress on social functioning and depression, but not on anxiety. Minorities may respond to role stress by seeking social support.

Role Stress, Role Reward, and Mental Health in a Multiethnic Sample of Midlife Women: Results from the Study of Women's Health Across the Nation (SWAN)

PubMed Central

Lanza di Scalea, Teresa; Matthews, Karen A.; Avis, Nancy E.; Thurston, Rebecca C.; Brown, Charlotte; Harlow, Sioban

2012-01-01

Abstract Background Little is known about the independent associations of reward and stress within specific roles with multiple measures of mental health in an ethnically diverse community sample of midlife women. The objective of this study is to examine if (1) role reward (within each role and across roles) contributes directly to mental health and buffers the negative impact of role stress and (2) associations among role occupancy, role stress, and role reward and mental health vary by race/ethnicity. Methods With separate logistic regression analysis, we investigated cross-sectional relationships between role stress and role reward with presence/absence of high depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D≥16]), anxiety symptoms (feeling tense or nervous, irritable or grouchy, fearful for no reason, and heart pounding or racing total score≥4), or low social functioning (bottom 25th percentile of the Short-Form-36 [SF-36] social functioning subscale) in 2549 women participating in the third visit of the Study of Women's Health Across the Nation (SWAN), a longitudinal population-based study of menopause. Results High reward across roles attenuated the negative impact of role stress on social functioning but not on anxiety or depression. High reward marriage buffered the impact of marital stress on depression, and high reward mothering buffered the effect of maternal stress on depression and social functioning. Compared to Caucasians, Hispanics and Chinese with high stress across roles had better social functioning, and African American mothers had lower odds of high depressive symptoms. Conclusions Role reward buffers the negative impact of stress on social functioning and depression, but not on anxiety. Minorities may respond to role stress by seeking social support. PMID:22360697

Motivation and timing: Clues for modeling the reward system

PubMed Central

Galtress, Tiffany; Marshall, Andrew T.; Kirkpatrick, Kimberly

2012-01-01

There is growing evidence that a change in reward magnitude or value alters interval timing, indicating that motivation and timing are not independent processes as was previously believed. The present paper reviews several recent studies, as well as presenting some new evidence with further manipulations of reward value during training vs. testing on a peak procedure. The combined results cannot be accounted for by any of the current psychological timing theories. However, in examining the neural circuitry of the reward system, it is not surprising that motivation has an impact on timing because the motivation/valuation system directly interfaces with the timing system. A new approach is proposed for the development of the next generation of timing models, which utilizes knowledge of the neuroanatomy and neurophysiology of the reward system to guide the development of a neurocomputational model of the reward system. The initial foundation along with heuristics for proceeding with developing such a model is unveiled in an attempt to stimulate new theoretical approaches in the field. PMID:22421220

Altered Intrinsic Hippocmapus Declarative Memory Network and Its Association with Impulsivity in Abstinent Heroin Dependent Subjects

PubMed Central

Zhai, Tian-Ye; Shao, Yong-Cong; Xie, Chun-Ming; Ye, En-Mao; Zou, Feng; Fu, Li-Ping; Li, Wen-Jun; Chen, Gang; Chen, Guang-Yu; Zhang, Zheng-Guo; Li, Shi-Jiang; Yang, Zheng

2014-01-01

Converging evidence suggests that addiction can be considered a disease of aberrant learning and memory with impulsive decision-making. In the past decades, numerous studies have demonstrated that drug addiction is involved in multiple memory systems such as classical conditioned drug memory, instrumental learning memory and the habitual learning memory. However, most of these studies have focused on the contributions of non-declarative memory, and declarative memory has largely been neglected in the research of addiction. Based on a recent finding that hippocampus, as a core functioning region of declarative memory, was proved biased the decision-making process based on past experiences by spreading associated reward values throughout memory. Our present study focused on the hippocampus. By utilizing seed-based network analysis on the resting-state functional MRI datasets with the seed hippocampus we tested how the intrinsic hippocampal memory network altered towards drug addiction, and examined how the functional connectivity strength within the altered hippocampal network correlated with behavioral index ‘impulsivity’. Our results demonstrated that HD group showed enhanced coherence between hippocampus which represents declarative memory system and non-declarative rewardguided learning memory system, and also showed attenuated intrinsic functional link between hippocampus and top-down control system, compared to the CN group. This alteration was furthered found to have behavioral significance over the behavioral index ‘impulsivity’ measured with Barratt Impulsiveness Scale (BIS). These results provide insights into the mechanism of declarative memory underlying the impulsive behavior in drug addiction. PMID:25008351

Ventral pallidum roles in reward and motivation.

PubMed

Smith, Kyle S; Tindell, Amy J; Aldridge, J Wayne; Berridge, Kent C

2009-01-23

In recent years the ventral pallidum has become a focus of great research interest as a mechanism of reward and incentive motivation. As a major output for limbic signals, the ventral pallidum was once associated primarily with motor functions rather than regarded as a reward structure in its own right. However, ample evidence now suggests that ventral pallidum function is a major mechanism of reward in the brain. We review data indicating that (1) an intact ventral pallidum is necessary for normal reward and motivation, (2) stimulated activation of ventral pallidum is sufficient to cause reward and motivation enhancements, and (3) activation patterns in ventral pallidum neurons specifically encode reward and motivation signals via phasic bursts of excitation to incentive and hedonic stimuli. We conclude that the ventral pallidum may serve as an important 'limbic final common pathway' for mesocorticolimbic processing of many rewards.

Differential reward network functional connectivity in cannabis dependent and non-dependent users☆

PubMed Central

Filbey, Francesca M.; Dunlop, Joseph

2015-01-01

Background Emergent studies show that similar to other substances of abuse, cue-reactivity to cannabis is also associated with neural response in the brain’s reward pathway (Filbey et al., 2009). However, the inter-relatedness of brain regions during cue-reactivity in cannabis users remains unknown. Methods In this study, we conducted a series of investigations to determine functional connectivity during cue-reactivity in 71 cannabis users. First, we used psychophysiological interaction (PPI) analysis to examine coherent neural response to cannabis cues. Second, we evaluated whether these patterns of network functional connectivity differentiated dependent and non-dependent users. Finally, as an exploratory analysis, we determined the directionality of these connections via Granger connectivity analyses. Results PPI analyses showed reward network functional connectivity with the nucleus accumbens (NAc) seed region during cue exposure. Between-group contrasts found differential effects of dependence status. Dependent users (N = 31) had greater functional connectivity with amygdala and anterior cingulate gyrus (ACG) seeds while the non-dependent users (N = 24) had greater functional connectivity with the NAc, orbitofrontal cortex (OFC) and hippocampus seeds. Granger analyses showed that hippocampal and ACG activation preceded neural response in reward areas. Conclusions Both PPI and Granger analyses demonstrated strong functional coherence in reward regions during exposure to cannabis cues in current cannabis users. Functional connectivity (but not regional activation) in the reward network differentiated dependent from non-dependent cannabis users. Our findings suggest that repeated cannabis exposure causes observable changes in functional connectivity in the reward network and should be considered in intervention strategies. PMID:24838032

Exposure to opiates in female adolescents alters mu opiate receptor expression and increases the rewarding effects of morphine in future offspring.

PubMed

Vassoler, Fair M; Wright, Siobhan J; Byrnes, Elizabeth M

2016-04-01

Prescription opiate use and abuse has increased dramatically over the past two decades, including increased use in adolescent populations. Recently, it has been proposed that use during this critical period may affect future offspring even when use is discontinued prior to conception. Here, we utilize a rodent model to examine the effects of adolescent morphine exposure on the reward functioning of the offspring. Female Sprague Dawley rats were administered morphine for 10 days during early adolescence (post-natal day 30-39) using an escalating dosing regimen. Animals then remained drug free until adulthood at which point they were mated with naïve males. Adult offspring (F1 animals) were tested for their response to morphine-induced (0, 1, 2.5, 5, and 10 mg/kg, s.c.) conditioned place preference (CPP) and context-independent morphine-induced sensitization. Naïve littermates were used to examine mu opiate receptor expression in the nucleus accumbens and ventral tegmental area. Results indicate that F1 females whose mothers were exposed to morphine during adolescence (Mor-F1) demonstrate significantly enhanced CPP to the lowest doses of morphine compared with Sal-F1 females. There were no differences in context-independent sensitization between maternal treatment groups. Protein expression analysis showed significantly increased levels of accumbal mu opiate receptor in Mor-F1 offspring and decreased levels in the VTA. Taken together, these findings demonstrate a shift in the dose response curve with regard to the rewarding effects of morphine in Mor-F1 females which may in part be due to altered mu opiate receptor expression in the nucleus accumbens and VTA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Exposure to Opiates in Female Adolescents Alters Mu Opiate Receptor Expression and Increases the Rewarding Effects of Morphine in Future Offspring

PubMed Central

Vassoler, Fair M.; Wright, Siobhan J.; Byrnes, Elizabeth M.

2016-01-01

Prescription opiate use and abuse has increased dramatically over the past two decades, including increased use in adolescent populations. Recently, it has been proposed that use during this critical period may affect future offspring even when use is discontinued prior to conception. Here, we utilize a rodent model to examine the effects of adolescent morphine exposure on the reward functioning of the offspring. Female Sprague Dawley rats were administered morphine for 10 days during early adolescence (post-natal day 30–39) using an escalating dosing regimen. Animals then remained drug free until adulthood at which point they were mated with naïve males. Adult offspring (F1 animals) were tested for their response to morphine-induced (0, 1, 2.5, 5, and 10 mg/kg, s.c.) conditioned place preference (CPP) and context-independent morphine-induced sensitization. Naïve littermates were used to examine mu opiate receptor expression in the nucleus accumbens and ventral tegmental area. Results indicate that F1 females whose mothers were exposed to morphine during adolescence (Mor-F1) demonstrate significantly enhanced CPP to the lowest doses of morphine compared with Sal-F1 females. There were no differences in context-independent sensitization between maternal treatment groups. Protein expression analysis showed significantly increased levels of accumbal mu opiate receptor in Mor-F1 offspring and decreased levels in the VTA. Taken together, these findings demonstrate a shift in the dose response curve with regard to the rewarding effects of morphine in Mor-F1 females which may in part be due to altered mu opiate receptor expression in the nucleus accumbens and VTA. PMID:26700246

Saturation of subjective reward magnitude as a function of current and pulse frequency.

PubMed

Simmons, J M; Gallistel, C R

1994-02-01

In rats with electrodes in the medial forebrain bundle, the upper portion of the function relating the experienced magnitude of the reward to pulse frequency was determined at currents ranging from 100 to 1,000 microA. The pulse frequency required to produce an asymptotic level of reward was inversely proportional to current except at the lowest currents and highest pulse frequencies. At a given current, the subjective reward magnitude functions decelerated to an asymptote over an interval in which the pulse frequency doubled or tripled. The asymptotic level of reward was approximately constant for currents between 200 and 1,000 microA but declined substantially at currents at or below 100 microA and pulse frequencies at or above 250 to 400 pulses per second. The results are consistent with the hypothesis that the magnitude of the experienced reward depends only on the number of action potentials generated by the train of pulses in the bundle of reward-relevant axons.

Examining the interaction between cognitive control and reward sensitivity in substance use dependence.

PubMed

Charles-Walsh, Kathleen; Upton, Daniel J; Hester, Robert

2016-09-01

Drug dependence is characterized by altered reward processing and poor cognitive control, expressed as a preference for immediate rewards and impaired inhibitory control, respectively. To examine the interaction between reward processing (via the presence or absence of reward) and mechanisms of inhibitory control in drug dependence, the current study used the Monetary Incentive Control Task (MICT) to examine whether a group of opiate dependent persons demonstrated greater difficulty exerting control over immediate rewards compared to neutral stimuli. The MICT is a Go/Stop paradigm that examines inhibitory control over immediate rewards. Performance of 32 opiate dependent individuals was compared to 29 healthy controls. Opiate users demonstrated poorer inhibitory performance than controls, irrespective of cues signaling immediate reward. Whereas control participants' responses were modulated by probability cues, the opiate group did not show a capacity to up-regulate their cognitive control performance. The present results suggest a general decrease in cognitive control in opiate dependence, accompanied by a reduced ability to optimally modulate behavior in accordance with external cues. Opiate users and controls did not differ in the interaction between cognitive control and reward. The study highlights important issues for future research to consider when further examining this interaction in drug dependence. Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.

Impact of dietary protein and gender on food reinforcement

USDA-ARS?s Scientific Manuscript database

Recent evidence suggests that increasing dietary protein may alter reward-driven eating behavior. However, the link between protein and food reinforcement is not known. We sought to determine the extent to which increasing dietary protein alters food reinforcement in healthy adults. In a randomized ...

A Monetary Reward Alters Pacing but Not Performance in Competitive Cyclists.

PubMed

Skorski, Sabrina; Thompson, Kevin G; Keegan, Richard J; Meyer, Tim; Abbiss, Chris R

2017-01-01

Money has frequently been used as an extrinsic motivator since it is assumed that humans are willing to invest more effort for financial reward. However, the influence of a monetary reward on pacing and performance in trained athletes is not well-understood. Therefore, the aim of this study was to analyse the influence of a monetary reward in well-trained cyclists on their pacing and performance during short and long cycling time trials (TT). Twentythree cyclists (6 ♀, 17 ♂) completed 4 self-paced time trials (TTs, 2 short: 4 km and 6 min; 2 long: 20 km and 30 min); in a randomized order. Participants were separated into parallel, non-randomized "rewarded" and "non-rewarded" groups. Cyclists in the rewarded group received a monetary reward based on highest mean power output across all TTs. Cyclists in the non-rewarded group did not receive a monetary reward. Overall performance was not significantly different between groups in short or long TTs ( p > 0.48). Power output showed moderatly lower effect sizes at comencement of the short TTs ( P meandiff = 36.6 W; d > 0.44) and the 20 km TT ( P meandiff = 22.6 W; d = 0.44) in the rewarded group. No difference was observed in pacing during the 30 min TT ( p = 0.95). An external reward seems to have influenced pacing at the commencement of time trials. Participants in the non-rewarded group adopted a typical parabolic shaped pattern, whereas participants in the rewarded group started trials more conservatively. Results raise the possibility that using money as an extrinsic reward may interfere with regulatory processes required for effective pacing.

Differences in neural responses to reward and punishment processing between anorexia nervosa subtypes: An fMRI study.

PubMed

Murao, Ema; Sugihara, Genichi; Isobe, Masanori; Noda, Tomomi; Kawabata, Michiko; Matsukawa, Noriko; Takahashi, Hidehiko; Murai, Toshiya; Noma, Shun'ichi

2017-09-01

Anorexia nervosa (AN) includes the restricting (AN-r) and binge-eating/purging (AN-bp) subtypes, which have been reported to differ regarding their underlying pathophysiologies as well as their behavioral patterns. However, the differences in neural mechanisms of reward systems between AN subtypes remain unclear. The aim of the present study was to explore differences in the neural processing of reward and punishment between AN subtypes. Twenty-three female patients with AN (11 AN-r and 12 AN-bp) and 20 healthy women underwent functional magnetic resonance imaging while performing a monetary incentive delay task. Whole-brain one-way analysis of variance was conducted to test between-group differences. There were significant group differences in brain activation in the rostral anterior cingulate cortex and right posterior insula during loss anticipation, with increased brain activation in the AN-bp group relative to the AN-r and healthy women groups. No significant differences were found during gain anticipation. AN-bp patients showed altered neural responses to punishment in brain regions implicated in emotional arousal. Our findings suggest that individuals with AN-bp are more sensitive to potential punishment than individuals with AN-r and healthy individuals at the neural level. The present study provides preliminary evidence that there are neurobiological differences between AN subtypes with regard to the reward system, especially punishment processing. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

Central administration of the anorexigenic peptide neuromedin U decreases alcohol intake and attenuates alcohol-induced reward in rodents.

PubMed

Vallöf, Daniel; Ulenius, Lisa; Egecioglu, Emil; Engel, Jörgen A; Jerlhag, Elisabet

2017-05-01

By investigating the neurochemical mechanisms through which alcohol activates the brain reward systems, novel treatment strategies for alcohol use disorder (AUD), a chronic relapsing disease, can be developed. In contrast to the common view of the function of gut-brain peptides, such as neuromedin U (NMU), to regulate food intake and appetite, a novel role in reinforcement mediation has been implied. The anorexigenic effects of NMU are mediated via NMU2 receptors, preferably in the arcuate nucleus and paraventricular nucleus. The expression of NMU2 receptors is also expressed in several reward-related areas in the brain, suggesting a role in reward regulation. The present experiments were therefore set up to investigate the effect of intracerebroventricular administration of NMU on alcohol-mediated behaviors in rodents. We found that central administration of NMU attenuated alcohol-induced locomotor stimulation, accumbal dopamine release and the expression of conditioned place preference in mice. In addition, NMU dose dependently decreased alcohol intake in high, but not in low, alcohol-consuming rats. Central NMU administration did not alter the blood alcohol concentrations nor change the corticosterone levels in rodents. Given that AUD is a major health-care challenge causing an enormous cost to society and novel treatment strategies are warranted, our data suggest that NMU analogues deserve to be evaluated as novel treatment of AUD in humans. © 2016 The Authors Addiction Biology published by John Wiley & Sons Ltd.

Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer's disease

PubMed Central

Nobili, Annalisa; Latagliata, Emanuele Claudio; Viscomi, Maria Teresa; Cavallucci, Virve; Cutuli, Debora; Giacovazzo, Giacomo; Krashia, Paraskevi; Rizzo, Francesca Romana; Marino, Ramona; Federici, Mauro; De Bartolo, Paola; Aversa, Daniela; Dell'Acqua, Maria Concetta; Cordella, Alberto; Sancandi, Marco; Keller, Flavio; Petrosini, Laura; Puglisi-Allegra, Stefano; Mercuri, Nicola Biagio; Coccurello, Roberto; Berretta, Nicola; D'Amelio, Marcello

2017-01-01

Alterations of the dopaminergic (DAergic) system are frequently reported in Alzheimer's disease (AD) patients and are commonly linked to cognitive and non-cognitive symptoms. However, the cause of DAergic system dysfunction in AD remains to be elucidated. We investigated alterations of the midbrain DAergic system in the Tg2576 mouse model of AD, overexpressing a mutated human amyloid precursor protein (APPswe). Here, we found an age-dependent DAergic neuron loss in the ventral tegmental area (VTA) at pre-plaque stages, although substantia nigra pars compacta (SNpc) DAergic neurons were intact. The selective VTA DAergic neuron degeneration results in lower DA outflow in the hippocampus and nucleus accumbens (NAc) shell. The progression of DAergic cell death correlates with impairments in CA1 synaptic plasticity, memory performance and food reward processing. We conclude that in this mouse model of AD, degeneration of VTA DAergic neurons at pre-plaque stages contributes to memory deficits and dysfunction of reward processing. PMID:28367951

Ventral Pallidum Roles in Reward and Motivation

PubMed Central

Smith, Kyle S.; Tindell, Amy J.; Aldridge, J. Wayne; Berridge, Kent C.

2008-01-01

In recent years the ventral pallidum has become a focus of great research interest as a mechanism of reward and incentive motivation. As a major output for limbic signals, the ventral pallidum was once associated primarily with motor functions rather than regarded as a reward structure in its own right. However, ample evidence now suggests that ventral pallidum function is a major mechanism of reward in the brain. We review data indicating that 1) an intact ventral pallidum is necessary for normal reward and motivation, 2) stimulated activation of ventral pallidum is sufficient to cause reward and motivation enhancements, and 3) activation patterns in ventral pallidum neurons specifically encode reward and motivation signals via phasic bursts of excitation to incentive and hedonic stimuli. We conclude that the ventral pallidum may serve as an important ‘limbic final common pathway’ for mesocorticolimbic processing of many rewards. PMID:18955088

Response effort discounts the subjective value of rewards.

PubMed

Nishiyama, Ryoji

2014-09-01

Factors associated with obtaining a reward, such as a temporal delay in receiving the reward, can influence the subjective value of the reward. Cognitive as well as physical response effort is also known to influence choice behaviors. The present study used hypothetical situations to assess whether response effort affects the subjective value of rewards. The results demonstrated that increasing response effort increases the amount of money that participants are willing to forgo to avoid engaging in work. An exponential as well as hyperbolic function provided a good fit for such discounting. The findings suggest that response effort discounts the subjective value of a reward as a function of its amount. Copyright © 2014 Elsevier B.V. All rights reserved.

Influence of ventral tegmental area input on cortico-subcortical networks underlying action control and decision making.

PubMed

Richter, Anja; Gruber, Oliver

2018-02-01

It is argued that the mesolimbic system has a more general function in processing all salient events, including and extending beyond rewards. Saliency was defined as an event that is unexpected due to its frequency of occurrence and elicits an attentional-behavioral switch. Using functional magnetic resonance imaging (fMRI), signals were measured in response to the modulation of salience of rewarding and nonrewarding events during a reward-based decision making task, the so called desire-reason dilemma paradigm (DRD). Replicating previous findings, both frequent and infrequent, and therefore salient, reward stimuli elicited reliable activation of the ventral tegmental area (VTA) and ventral striatum (vStr). When immediate reward desiring contradicted the superordinate task-goal, we found an increased activation of the VTA and vStr when the salient reward stimuli were presented compared to the nonsalient reward stimuli, indicating a boosting of activation in these brain regions. Furthermore, we found a significantly increased functional connectivity between the VTA and vStr, confirming the boosting of vStr activation via VTA input. Moreover, saliency per se without a reward association led to an increased activation of brain regions in the mesolimbic reward system as well as the orbitofrontal cortex (OFC), inferior frontal gyrus (IFG), and anterior cingulate cortex (ACC). Finally, findings uncovered multiple increased functional interactions between cortical saliency-processing brain areas and the VTA and vStr underlying detection and processing of salient events and adaptive decision making. © 2017 Wiley Periodicals, Inc.

Behavioral and Neural Manifestations of Reward Memory in Carriers of Low-Expressing versus High-Expressing Genetic Variants of the Dopamine D2 Receptor

PubMed Central

Richter, Anni; Barman, Adriana; Wüstenberg, Torsten; Soch, Joram; Schanze, Denny; Deibele, Anna; Behnisch, Gusalija; Assmann, Anne; Klein, Marieke; Zenker, Martin; Seidenbecher, Constanze; Schott, Björn H.

2017-01-01

Dopamine is critically important in the neural manifestation of motivated behavior, and alterations in the human dopaminergic system have been implicated in the etiology of motivation-related psychiatric disorders, most prominently addiction. Patients with chronic addiction exhibit reduced dopamine D2 receptor (DRD2) availability in the striatum, and the DRD2 TaqIA (rs1800497) and C957T (rs6277) genetic polymorphisms have previously been linked to individual differences in striatal dopamine metabolism and clinical risk for alcohol and nicotine dependence. Here, we investigated the hypothesis that the variants of these polymorphisms would show increased reward-related memory formation, which has previously been shown to jointly engage the mesolimbic dopaminergic system and the hippocampus, as a potential intermediate phenotype for addiction memory. To this end, we performed functional magnetic resonance imaging (fMRI) in 62 young, healthy individuals genotyped for DRD2 TaqIA and C957T variants. Participants performed an incentive delay task, followed by a recognition memory task 24 h later. We observed effects of both genotypes on the overall recognition performance with carriers of low-expressing variants, namely TaqIA A1 carriers and C957T C homozygotes, showing better performance than the other genotype groups. In addition to the better memory performance, C957T C homozygotes also exhibited a response bias for cues predicting monetary reward. At the neural level, the C957T polymorphism was associated with a genotype-related modulation of right hippocampal and striatal fMRI responses predictive of subsequent recognition confidence for reward-predicting items. Our results indicate that genetic variations associated with DRD2 expression affect explicit memory, specifically for rewarded stimuli. We suggest that the relatively better memory for rewarded stimuli in carriers of low-expressing DRD2 variants may reflect an intermediate phenotype of addiction memory. PMID:28507526

Immaturities in Reward Processing and Its Influence on Inhibitory Control in Adolescence

PubMed Central

Terwilliger, R.; Teslovich, T.; Velanova, K.; Luna, B.

2010-01-01

The nature of immature reward processing and the influence of rewards on basic elements of cognitive control during adolescence are currently not well understood. Here, during functional magnetic resonance imaging, healthy adolescents and adults performed a modified antisaccade task in which trial-by-trial reward contingencies were manipulated. The use of a novel fast, event-related design enabled developmental differences in brain function underlying temporally distinct stages of reward processing and response inhibition to be assessed. Reward trials compared with neutral trials resulted in faster correct inhibitory responses across ages and in fewer inhibitory errors in adolescents. During reward trials, the blood oxygen level–dependent signal was attenuated in the ventral striatum in adolescents during cue assessment, then overactive during response preparation, suggesting limitations during adolescence in reward assessment and heightened reactivity in anticipation of reward compared with adults. Importantly, heightened activity in the frontal cortex along the precentral sulcus was also observed in adolescents during reward-trial response preparation, suggesting reward modulation of oculomotor control regions supporting correct inhibitory responding. Collectively, this work characterizes specific immaturities in adolescent brain systems that support reward processing and describes the influence of reward on inhibitory control. In sum, our findings suggest mechanisms that may underlie adolescents’ vulnerability to poor decision-making and risk-taking behavior. PMID:19875675

Tentative Evidence for Striatal Hyperactivity in Adolescent Cannabis Using Boys: A Cross-Sectional Multicenter fMRI Study

PubMed Central

Jager, Gerry; Block, Robert I.; Luijten, Maartje; Ramsey, Nick F.

2013-01-01

Adolescents' risk-taking behavior has been linked to a maturational imbalance between reward (“go”) and inhibitory-control (“stop”) related brain circuitry. This may drive adolescent drug-taking, such as cannabis use. In this study we assessed the non-acute effects of adolescent cannabis use on reward-related brain function. We performed a two-site (United States and Netherlands; pooled data) functional magnetic resonance imaging (fMRI) study with a cross-sectional design. Twenty-one abstinent but frequent cannabis-using boys were compared with 24 non-using peers on reward-related brain function, using a monetary incentive delay task with fMRI. Focus was on anticipatory and response stages of reward and brain areas critically involved in reward processing like the striatum. Performance in users was normal. Region-of-interest analysis indicated striatal hyperactivity during anticipatory stages of reward in users. Intriguingly, this effect was most pronounced during non-rewarding events. Striatal hyperactivity in adolescent cannabis users may signify an overly sensitive motivational brain circuitry. Frequent cannabis use during adolescence may induce diminished ability to disengage the motivational circuit when no reward can be obtained. This could strengthen the search for reinforcements like drugs of abuse, even when facing the negative (non-rewarding) consequences. PMID:23909003

Video game training and the reward system.

PubMed

Lorenz, Robert C; Gleich, Tobias; Gallinat, Jürgen; Kühn, Simone

2015-01-01

Video games contain elaborate reinforcement and reward schedules that have the potential to maximize motivation. Neuroimaging studies suggest that video games might have an influence on the reward system. However, it is not clear whether reward-related properties represent a precondition, which biases an individual toward playing video games, or if these changes are the result of playing video games. Therefore, we conducted a longitudinal study to explore reward-related functional predictors in relation to video gaming experience as well as functional changes in the brain in response to video game training. Fifty healthy participants were randomly assigned to a video game training (TG) or control group (CG). Before and after training/control period, functional magnetic resonance imaging (fMRI) was conducted using a non-video game related reward task. At pretest, both groups showed strongest activation in ventral striatum (VS) during reward anticipation. At posttest, the TG showed very similar VS activity compared to pretest. In the CG, the VS activity was significantly attenuated. This longitudinal study revealed that video game training may preserve reward responsiveness in the VS in a retest situation over time. We suggest that video games are able to keep striatal responses to reward flexible, a mechanism which might be of critical value for applications such as therapeutic cognitive training.

Video game training and the reward system

PubMed Central

Lorenz, Robert C.; Gleich, Tobias; Gallinat, Jürgen; Kühn, Simone

2015-01-01

Video games contain elaborate reinforcement and reward schedules that have the potential to maximize motivation. Neuroimaging studies suggest that video games might have an influence on the reward system. However, it is not clear whether reward-related properties represent a precondition, which biases an individual toward playing video games, or if these changes are the result of playing video games. Therefore, we conducted a longitudinal study to explore reward-related functional predictors in relation to video gaming experience as well as functional changes in the brain in response to video game training. Fifty healthy participants were randomly assigned to a video game training (TG) or control group (CG). Before and after training/control period, functional magnetic resonance imaging (fMRI) was conducted using a non-video game related reward task. At pretest, both groups showed strongest activation in ventral striatum (VS) during reward anticipation. At posttest, the TG showed very similar VS activity compared to pretest. In the CG, the VS activity was significantly attenuated. This longitudinal study revealed that video game training may preserve reward responsiveness in the VS in a retest situation over time. We suggest that video games are able to keep striatal responses to reward flexible, a mechanism which might be of critical value for applications such as therapeutic cognitive training. PMID:25698962

Suboptimal choice in rats: incentive salience attribution promotes maladaptive decision-making

PubMed Central

Chow, Jonathan J; Smith, Aaron P; Wilson, A George; Zentall, Thomas R; Beckmann, Joshua S

2016-01-01

Stimuli that are more predictive of subsequent reward also function as better conditioned reinforcers. Moreover, stimuli attributed with incentive salience function as more robust conditioned reinforcers. Some theories have suggested that conditioned reinforcement plays an important role in promoting suboptimal choice behavior, like gambling. The present experiments examined how different stimuli, those attributed with incentive salience versus those without, can function in tandem with stimulus-reward predictive utility to promote maladaptive decision-making in rats. One group of rats had lights associated with goal-tracking as the reward-predictive stimuli and another had levers associated with sign-tracking as the reward-predictive stimuli. All rats were first trained on a choice procedure in which the expected value across both alternatives was equivalent but differed in their stimulus-reward predictive utility. Next, the expected value across both alternatives was systematically changed so that the alternative with greater stimulus-reward predictive utility was suboptimal in regard to primary reinforcement. The results demonstrate that in order to obtain suboptimal choice behavior, incentive salience alongside strong stimulus-reward predictive utility may be necessary; thus, maladaptive decision-making can be driven more by the value attributed to stimuli imbued with incentive salience that reliably predict a reward rather than the reward itself. PMID:27993692

Suboptimal choice in rats: Incentive salience attribution promotes maladaptive decision-making.

PubMed

Chow, Jonathan J; Smith, Aaron P; Wilson, A George; Zentall, Thomas R; Beckmann, Joshua S

2017-03-01

Stimuli that are more predictive of subsequent reward also function as better conditioned reinforcers. Moreover, stimuli attributed with incentive salience function as more robust conditioned reinforcers. Some theories have suggested that conditioned reinforcement plays an important role in promoting suboptimal choice behavior, like gambling. The present experiments examined how different stimuli, those attributed with incentive salience versus those without, can function in tandem with stimulus-reward predictive utility to promote maladaptive decision-making in rats. One group of rats had lights associated with goal-tracking as the reward-predictive stimuli and another had levers associated with sign-tracking as the reward-predictive stimuli. All rats were first trained on a choice procedure in which the expected value across both alternatives was equivalent but differed in their stimulus-reward predictive utility. Next, the expected value across both alternatives was systematically changed so that the alternative with greater stimulus-reward predictive utility was suboptimal in regard to primary reinforcement. The results demonstrate that in order to obtain suboptimal choice behavior, incentive salience alongside strong stimulus-reward predictive utility may be necessary; thus, maladaptive decision-making can be driven more by the value attributed to stimuli imbued with incentive salience that reliably predict a reward rather than the reward itself. Copyright © 2016 Elsevier B.V. All rights reserved.

Tentative evidence for striatal hyperactivity in adolescent cannabis-using boys: a cross-sectional multicenter fMRI study.

PubMed

Jager, Gerry; Block, Robert I; Luijten, Maartje; Ramsey, Nick F

2013-01-01

Adolescents' risk-taking behavior has been linked to a maturational imbalance between reward ("go") and inhibitory-control ("stop")-related brain circuitry. This may drive adolescent drug-taking, such as cannabis use. In this study, we assessed the non-acute effects of adolescent cannabis use on reward-related brain function. We performed a two-site (United States and Netherlands; pooled data) functional magnetic resonance imaging (fMRI) study with a cross-sectional design. Twenty-one abstinent but frequent cannabis-using boys were compared with 24 non-using peers on reward-related brain function, using a monetary incentive delay task with fMRI. Focus was on anticipatory and response stages of reward and brain areas critically involved in reward processing like the striatum. Performance in users was normal. Region-of-interest analysis indicated striatal hyperactivity during anticipatory stages of reward in users. Intriguingly, this effect was most pronounced during non-rewarding events. Striatal hyperactivity in adolescent cannabis users may signify an overly sensitive motivational brain circuitry. Frequent cannabis use during adolescence may induce diminished ability to disengage the motivational circuit when no reward can be obtained. This could strengthen the search for reinforcements like drugs of abuse, even when facing the negative (non-rewarding) consequences.

Dissociated effects of anticipating smoking versus monetary reward in the caudate as a function of smoking abstinence.

PubMed

Sweitzer, Maggie M; Geier, Charles F; Joel, Danielle L; McGurrin, Patrick; Denlinger, Rachel L; Forbes, Erika E; Donny, Eric C

2014-11-01

Theories of addiction suggest that chronic smoking may be associated with both hypersensitivity to smoking and related cues and hyposensitivity to alternative reinforcers. However, neural responses to smoking and nonsmoking rewards are rarely evaluated within the same paradigm, leaving the extent to which both processes operate simultaneously uncertain. Behavioral evidence and theoretical models suggest that dysregulated reward processing may be more pronounced during deprivation from nicotine, but neuroimaging evidence on the effects of deprivation on reward processing is limited. The current study examined the impact of deprivation from smoking on neural processing of both smoking and monetary rewards. Two separate functional magnetic resonance imaging scans were performed in 38 daily smokers, one after smoking without restriction and one following 24 hours of abstinence. A rewarded guessing task was conducted during each scan to evaluate striatal blood oxygen level-dependent response during anticipation of both smoking and monetary rewards. A significant reward type by abstinence interaction was observed in the bilateral caudate and medial prefrontal cortex during reward anticipation. The blood oxygen level-dependent response to anticipation of smoking reward was significantly higher and anticipation of monetary rewards was significantly lower during abstinence compared with nonabstinence. Attenuation of monetary reward-related activation during abstinence was significantly correlated with abstinence-induced increases in craving and withdrawal. These results provide the first direct evidence of dissociated effects of smoking versus monetary rewards as a function of abstinence. The findings suggest an important neural pathway that may underlie the choice to smoke in lieu of alternative reinforcement during a quit attempt. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

Neural Sensitivity to Absolute and Relative Anticipated Reward in Adolescents

PubMed Central

Vaidya, Jatin G.; Knutson, Brian; O'Leary, Daniel S.; Block, Robert I.; Magnotta, Vincent

2013-01-01

Adolescence is associated with a dramatic increase in risky and impulsive behaviors that have been attributed to developmental differences in neural processing of rewards. In the present study, we sought to identify age differences in anticipation of absolute and relative rewards. To do so, we modified a commonly used monetary incentive delay (MID) task in order to examine brain activity to relative anticipated reward value (neural sensitivity to the value of a reward as a function of other available rewards). This design also made it possible to examine developmental differences in brain activation to absolute anticipated reward magnitude (the degree to which neural activity increases with increasing reward magnitude). While undergoing fMRI, 18 adolescents and 18 adult participants were presented with cues associated with different reward magnitudes. After the cue, participants responded to a target to win money on that trial. Presentation of cues was blocked such that two reward cues associated with $.20, $1.00, or $5.00 were in play on a given block. Thus, the relative value of the $1.00 reward varied depending on whether it was paired with a smaller or larger reward. Reflecting age differences in neural responses to relative anticipated reward (i.e., reference dependent processing), adults, but not adolescents, demonstrated greater activity to a $1 reward when it was the larger of the two available rewards. Adults also demonstrated a more linear increase in ventral striatal activity as a function of increasing absolute reward magnitude compared to adolescents. Additionally, reduced ventral striatal sensitivity to absolute anticipated reward (i.e., the difference in activity to medium versus small rewards) correlated with higher levels of trait Impulsivity. Thus, ventral striatal activity in anticipation of absolute and relative rewards develops with age. Absolute reward processing is also linked to individual differences in Impulsivity. PMID:23544046

Modeling the effect of reward amount on probability discounting.

PubMed

Myerson, Joel; Green, Leonard; Morris, Joshua

2011-03-01

The present study with college students examined the effect of amount on the discounting of probabilistic monetary rewards. A hyperboloid function accurately described the discounting of hypothetical rewards ranging in amount from $20 to $10,000,000. The degree of discounting increased continuously with amount of probabilistic reward. This effect of amount was not due to changes in the rate parameter of the discounting function, but rather was due to increases in the exponent. These results stand in contrast to those observed with the discounting of delayed monetary rewards, in which the degree of discounting decreases with reward amount due to amount-dependent decreases in the rate parameter. Taken together, this pattern of results suggests that delay and probability discounting reflect different underlying mechanisms. That is, the fact that the exponent in the delay discounting function is independent of amount is consistent with a psychophysical scaling interpretation, whereas the finding that the exponent of the probability-discounting function is amount-dependent is inconsistent with such an interpretation. Instead, the present results are consistent with the idea that the probability-discounting function is itself the product of a value function and a weighting function. This idea was first suggested by Kahneman and Tversky (1979), although their prospect theory does not predict amount effects like those observed. The effect of amount on probability discounting was parsimoniously incorporated into our hyperboloid discounting function by assuming that the exponent was proportional to the amount raised to a power. The amount-dependent exponent of the probability-discounting function may be viewed as reflecting the effect of amount on the weighting of the probability with which the reward will be received.

Early-Life Seizures Produce Lasting Alterations in the Structure and Function of the Prefrontal Cortex

PubMed Central

Kleen, Jonathan K.; Sesqué, Alexandre; Wu, Edie X.; Miller, Forrest A.; Hernan, Amanda E.; Holmes, Gregory L.; Scott, Rod C.

2011-01-01

Early-life seizures (ELS) are associated with long-term behavioral disorders including autism and ADHD, suggesting that frontal lobe structures may be permanently affected. We tested whether ELS produce structural alterations in the prefrontal cortex (PFC) and impair PFC-mediated function using an operant task of behavioral flexibility in rats. Adult rats that had been exposed to 75 flurothyl seizures during postnatal days 1–10 showed decreased behavioral flexibility in the task compared to controls over multiple behavioral sessions, measured as a lever preference asymmetry (p<0.001) and a decreased efficiency of attaining food rewards (p<0.05). ELS rats also showed an increased thickness of the PFC (p<0.01), primarily attributed to layer V (p<0.01) with no differences in cell density. These structural changes correlated with lever preference behavioral impairments (p<0.05). This study demonstrates that the consequences of ELS extend to the PFC, which may help explain the high prevalence of comorbid behavioral disorders following ELS. PMID:21873119

A Free-Choice High-Fat High-Sugar Diet Alters Day-Night Per2 Gene Expression in Reward-Related Brain Areas in Rats.

PubMed

Blancas-Velazquez, Aurea Susana; Unmehopa, Unga A; Eggels, Leslie; Koekkoek, Laura; Kalsbeek, Andries; Mendoza, Jorge; la Fleur, Susanne E

2018-01-01

Under normal light-dark conditions, nocturnal rodents consume most of their food during the dark period. Diets high in fat and sugar, however, may affect the day-night feeding rhythm resulting in a higher light phase intake. In vitro and in vivo studies showed that nutrients affect clock-gene expression. We therefore hypothesized that overconsuming fat and sugar alters clock-gene expression in brain structures important for feeding behavior. We determined the effects of a free-choice high-fat high-sugar (fcHFHS) diet on clock-gene expression in rat brain areas related to feeding and reward and compared them with chow-fed rats. Consuming a fcHFHS diet for 6 weeks disrupted day-night differences in Per2 mRNA expression in the nucleus accumbens (NAc) and lateral hypothalamus but not in the suprachiasmatic nucleus, habenula, and ventral tegmental area. Furthermore, short-term sugar drinking, but not fat feeding, upregulates Per2 mRNA expression in the NAc. The disruptions in day-night differences in NAc Per2 gene expression were not accompanied by altered day-night differences in the mRNA expression of peptides related to food intake. We conclude that the fcHFHS diet and acute sugar drinking affect Per2 gene expression in areas involved in food reward; however, this is not sufficient to alter the day-night pattern of food intake.

A Free-Choice High-Fat High-Sugar Diet Alters Day–Night Per2 Gene Expression in Reward-Related Brain Areas in Rats

PubMed Central

Blancas-Velazquez, Aurea Susana; Unmehopa, Unga A.; Eggels, Leslie; Koekkoek, Laura; Kalsbeek, Andries; Mendoza, Jorge; la Fleur, Susanne E.

2018-01-01

Under normal light–dark conditions, nocturnal rodents consume most of their food during the dark period. Diets high in fat and sugar, however, may affect the day–night feeding rhythm resulting in a higher light phase intake. In vitro and in vivo studies showed that nutrients affect clock-gene expression. We therefore hypothesized that overconsuming fat and sugar alters clock-gene expression in brain structures important for feeding behavior. We determined the effects of a free-choice high-fat high-sugar (fcHFHS) diet on clock-gene expression in rat brain areas related to feeding and reward and compared them with chow-fed rats. Consuming a fcHFHS diet for 6 weeks disrupted day–night differences in Per2 mRNA expression in the nucleus accumbens (NAc) and lateral hypothalamus but not in the suprachiasmatic nucleus, habenula, and ventral tegmental area. Furthermore, short-term sugar drinking, but not fat feeding, upregulates Per2 mRNA expression in the NAc. The disruptions in day–night differences in NAc Per2 gene expression were not accompanied by altered day–night differences in the mRNA expression of peptides related to food intake. We conclude that the fcHFHS diet and acute sugar drinking affect Per2 gene expression in areas involved in food reward; however, this is not sufficient to alter the day–night pattern of food intake. PMID:29686649

Probing reward function in posttraumatic stress disorder: expectancy and satisfaction with monetary gains and losses.

PubMed

Hopper, James W; Pitman, Roger K; Su, Zhaohui; Heyman, Gene M; Lasko, Natasha B; Macklin, Michael L; Orr, Scott P; Lukas, Scott E; Elman, Igor

2008-08-01

Posttraumatic stress disorder (PTSD) may be associated with dysfunctional reward processing. The present study assessed for such dysfunction in both the expectancy and outcome phases of reward processing. Male Vietnam veterans with (n=15) and without (n=11) combat-related PTSD were administered a wheel of fortune-type gambling task. Self-reported ratings of expectancy and satisfaction were collected respectively before and after each experience of monetary gain or loss. PTSD participants reported both lower expectancy of reward and lower satisfaction with reward when it was received. The latter result was manifest in a failure of PTSD participants to show the greater satisfaction that normally accompanies rewards received under conditions of low expectancy. These results suggest reward function impairment in PTSD related to expectancy, satisfaction, and the expectancy-satisfaction relationship.

Ventral Striatum Functional Connectivity as a Predictor of Adolescent Depressive Disorder in a Longitudinal Community-Based Sample.

PubMed

Pan, Pedro Mario; Sato, João R; Salum, Giovanni A; Rohde, Luis A; Gadelha, Ary; Zugman, Andre; Mari, Jair; Jackowski, Andrea; Picon, Felipe; Miguel, Eurípedes C; Pine, Daniel S; Leibenluft, Ellen; Bressan, Rodrigo A; Stringaris, Argyris

2017-11-01

Previous studies have implicated aberrant reward processing in the pathogenesis of adolescent depression. However, no study has used functional connectivity within a distributed reward network, assessed using resting-state functional MRI (fMRI), to predict the onset of depression in adolescents. This study used reward network-based functional connectivity at baseline to predict depressive disorder at follow-up in a community sample of adolescents. A total of 637 children 6-12 years old underwent resting-state fMRI. Discovery and replication analyses tested intrinsic functional connectivity (iFC) among nodes of a putative reward network. Logistic regression tested whether striatal node strength, a measure of reward-related iFC, predicted onset of a depressive disorder at 3-year follow-up. Further analyses investigated the specificity of this prediction. Increased left ventral striatum node strength predicted increased risk for future depressive disorder (odds ratio=1.54, 95% CI=1.09-2.18), even after excluding participants who had depressive disorders at baseline (odds ratio=1.52, 95% CI=1.05-2.20). Among 11 reward-network nodes, only the left ventral striatum significantly predicted depression. Striatal node strength did not predict other common adolescent psychopathology, such as anxiety, attention deficit hyperactivity disorder, and substance use. Aberrant ventral striatum functional connectivity specifically predicts future risk for depressive disorder. This finding further emphasizes the need to understand how brain reward networks contribute to youth depression.

Cocaine decreases saccharin preference without altering sweet taste sensitivity.

PubMed

Roebber, Jennifer K; Izenwasser, Sari; Chaudhari, Nirupa

2015-06-01

In rodents, saccharin consumption is suppressed when the sweet taste stimulus is paired with moderate doses of cocaine. Several hypotheses have been used to explain the seemingly contradictory effect of decreased consumption of a normally preferred substance following a highly rewarding drug. A common theme across these hypotheses is that saccharin is interpreted as less rewarding after cocaine pairing. We considered the alternative possibility that suppression is caused not by a change in reward circuitry, but rather by a change in taste detection, for instance by altering the afferent taste response and decreasing sensitivity to sweet taste stimuli. To evaluate this possibility, we measured saccharin taste sensitivity of mice before and after a standard cocaine-pairing paradigm. We measured taste sensitivity using a brief-access lickometer equipped with multiple concentrations of saccharin solution and established concentration-response curves before and after saccharin-cocaine pairing. Our results indicate that the EC50 for saccharin was unaltered following pairing. Instead, the avidity of licking saccharin, an indicator of motivation, was depressed. Latency to first-lick, a negative indicator of motivation, was also dramatically increased. Thus, our findings are consistent with the interpretation that saccharin-cocaine pairing results in devaluing of the sweet taste reward. Copyright © 2015 Elsevier Inc. All rights reserved.

Reward-related genes and personality traits in alcohol-dependent individuals: a pilot case control study.

PubMed

Landgren, Sara; Berglund, Kristina; Jerlhag, Elisabet; Fahlke, Claudia; Balldin, Jan; Berggren, Ulf; Zetterberg, Henrik; Blennow, Kaj; Engel, Jörgen A

2011-01-01

Components of the brain reward system, i.e. the mesolimbic dopamine, laterodorsal cholinergic and ghrelin signaling systems, have been implicated in alcohol reward in preclinical studies. Genetic variants of these systems have previously been linked to alcohol dependence. Here, we genotyped 31 single nucleotide polymorphisms (SNPs): 1 SNP in the dopamine D₂ receptor (DRD2) gene, 20 SNPs in 5 different nicotinic acetylcholine receptor subunit (CHRN*) genes, and 10 SNPs in the genes encoding pro-ghrelin (GHRL) and its receptor (GHSR), in a pilot study of type 1 alcoholics (n = 84) and healthy controls (n = 32). These individuals were characterized using the Temperament and Character Inventory. None of the SNPs were associated with risk of alcohol dependence in this population. The GG genotype of SNP rs13261190 in the CHRNB3 was associated with increased novelty seeking, while SNPs of the ghrelin signaling system were associated with decreased self-directedness (AA of rs495225, GHSR) and alterations in self-transcendence (AA of both rs42451 and rs35680, GHRL). In conclusion, this pilot study suggests that reward-related genes are associated with altered personality scores in type 1 alcohol dependence, which warrants future studies of these associations in larger study samples. Copyright © 2011 S. Karger AG, Basel.

Reward components of feeding behavior are preserved during mouse aging

PubMed Central

Harb, Mazen R.; Sousa, Nuno; Zihl, Joseph; Almeida, Osborne F. X.

2014-01-01

Eating behavior depends on associations between the sensory and energetic properties of foods. Healthful balance of these factors is a challenge for industrialized societies that have an abundance of food, food choices and food-related cues. Here, we were interested in whether appetitive conditioning changes as a function of age. Operant and pavlovian conditioning experiments (rewarding stimulus was a palatable food) in male mice (aged 3, 6, and 15 months) showed that implicit (non-declarative) memory remains intact during aging. Two other essential components of eating behavior, motivation and hedonic preference for rewarding foods, were also found not to be altered in aging mice. Specifically, hedonic responding by satiated mice to isocaloric foods of differing sensory properties (sucrose, milk) was similar in all age groups; importantly, however, this paradigm disclosed that older animals adjust their energy intake according to energetic need. Based on the assumption that the mechanisms that control feeding are conserved across species, it would appear that overeating and obesity in humans reflects a mismatch between ancient physiological mechanisms and today's cue-laden environment. The implication of the present results showing that aging does not impair the ability to learn stimulus-food associations is that the risk of overeating in response to food cues is maintained through to old age. PMID:25278876

Differential mesolimbic and prefrontal alterations during reward anticipation and consummation in positive and negative schizotypy.

PubMed

Yan, Chao; Wang, Yi; Su, Li; Xu, Ting; Yin, Da-Zhi; Fan, Ming-Xia; Deng, Ci-Ping; Wang, Zhao-Xin; Lui, Simon S Y; Cheung, Eric F C; Chan, Raymond C K

2016-08-30

Schizotypy is associated with anhedonia. However, previous findings on the neural substrates of anhedonia in schizotypy are mixed. In the present study, we measured the neural substrates associated with reward anticipation and consummation in positive and negative schizotypy using functional MRI. The Monetary Incentive Delay task was administered to 33 individuals with schizotypy (18 positive schizotypy (PS),15 negative schizotypy (NS)) and 22 healthy controls. Comparison between schizotypy individuals and controls were performed using two-sample T tests for contrast images involving gain versus non-gain anticipation condition and gain versus non-gain consummation condition. Multiple comparisons were corrected using Monte Carlo Simulation correction of p<.05. The results showed no significant difference in brain activity between controls and schizotypy individuals as a whole during gain anticipation or consummation. However, during the consummatory phase, NS individuals rather than PS individuals showed diminished left amygdala and left putamen activity compared with controls. We observed significantly weaker activation at the left ventral striatum during gain anticipation in NS individuals compared with controls. PS individuals, however, exhibited enhanced right ventral lateral prefrontal activity. These findings suggest that different dimensions of schizotypy may be underlied by different neural dysfunctions in reward anticipation and consummation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Continuous theta-burst stimulation (cTBS) over the lateral prefrontal cortex alters reinforcement learning bias.

PubMed

Ott, Derek V M; Ullsperger, Markus; Jocham, Gerhard; Neumann, Jane; Klein, Tilmann A

2011-07-15

The prefrontal cortex is known to play a key role in higher-order cognitive functions. Recently, we showed that this brain region is active in reinforcement learning, during which subjects constantly have to integrate trial outcomes in order to optimize performance. To further elucidate the role of the dorsolateral prefrontal cortex (DLPFC) in reinforcement learning, we applied continuous theta-burst stimulation (cTBS) either to the left or right DLPFC, or to the vertex as a control region, respectively, prior to the performance of a probabilistic learning task in an fMRI environment. While there was no influence of cTBS on learning performance per se, we observed a stimulation-dependent modulation of reward vs. punishment sensitivity: Left-hemispherical DLPFC stimulation led to a more reward-guided performance, while right-hemispherical cTBS induced a more avoidance-guided behavior. FMRI results showed enhanced prediction error coding in the ventral striatum in subjects stimulated over the left as compared to the right DLPFC. Both behavioral and imaging results are in line with recent findings that left, but not right-hemispherical stimulation can trigger a release of dopamine in the ventral striatum, which has been suggested to increase the relative impact of rewards rather than punishment on behavior. Copyright © 2011 Elsevier Inc. All rights reserved.

Reward components of feeding behavior are preserved during mouse aging.

PubMed

Harb, Mazen R; Sousa, Nuno; Zihl, Joseph; Almeida, Osborne F X

2014-01-01

Eating behavior depends on associations between the sensory and energetic properties of foods. Healthful balance of these factors is a challenge for industrialized societies that have an abundance of food, food choices and food-related cues. Here, we were interested in whether appetitive conditioning changes as a function of age. Operant and pavlovian conditioning experiments (rewarding stimulus was a palatable food) in male mice (aged 3, 6, and 15 months) showed that implicit (non-declarative) memory remains intact during aging. Two other essential components of eating behavior, motivation and hedonic preference for rewarding foods, were also found not to be altered in aging mice. Specifically, hedonic responding by satiated mice to isocaloric foods of differing sensory properties (sucrose, milk) was similar in all age groups; importantly, however, this paradigm disclosed that older animals adjust their energy intake according to energetic need. Based on the assumption that the mechanisms that control feeding are conserved across species, it would appear that overeating and obesity in humans reflects a mismatch between ancient physiological mechanisms and today's cue-laden environment. The implication of the present results showing that aging does not impair the ability to learn stimulus-food associations is that the risk of overeating in response to food cues is maintained through to old age.

Stress and reward processing in bipolar disorder: a functional magnetic resonance imaging study.

PubMed

Berghorst, Lisa H; Kumar, Poornima; Greve, Doug N; Deckersbach, Thilo; Ongur, Dost; Dutra, Sunny J; Pizzagalli, Diego A

2016-11-01

A link between negative life stress and the onset of mood episodes in bipolar disorder (BD) has been established, but processes underlying such a link remain unclear. Growing evidence suggests that stress can negatively affect reward processing and related neurobiological substrates, indicating that a dysregulated reward system may provide a partial explanation. The aim of this study was to test the impact of stress on reward-related neural functioning in BD. Thirteen euthymic or mildly depressed individuals with BD and 15 controls performed a Monetary Incentive Delay (MID) task while undergoing functional magnetic resonance imaging during no-stress and stress (negative psychosocial stressor involving poor performance feedback and threat of monetary deductions) conditions. In hypothesis-driven region-of-interest analyses, a significant group-by-condition interaction emerged in the amygdala during reward anticipation. Relative to controls, while anticipating a potential reward, subjects with BD were characterized by amygdalar hyperactivation in the no-stress condition but hypoactivation during stress. Moreover, relative to controls, subjects with BD had significantly larger amygdala volumes. After controlling for structural differences, the effects of stress on amygdalar function remained, whereas groups no longer differed during the no-stress condition. During reward consumption, a group-by-condition interaction emerged in the putamen due to increased putamen activation in response to rewards in participants with BD during stress, but an opposite pattern in controls. Overall, findings highlight possible impairments in using reward-predicting cues to adaptively engage in goal-directed actions in BD, combined with stress-induced hypersensitivity to reward consumption. Potential clinical implications are discussed. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Common Dimensional Reward Deficits Across Mood and Psychotic Disorders: A Connectome-Wide Association Study.

PubMed

Sharma, Anup; Wolf, Daniel H; Ciric, Rastko; Kable, Joseph W; Moore, Tyler M; Vandekar, Simon N; Katchmar, Natalie; Daldal, Aylin; Ruparel, Kosha; Davatzikos, Christos; Elliott, Mark A; Calkins, Monica E; Shinohara, Russell T; Bassett, Danielle S; Satterthwaite, Theodore D

2017-07-01

Anhedonia is central to multiple psychiatric disorders and causes substantial disability. A dimensional conceptualization posits that anhedonia severity is related to a transdiagnostic continuum of reward deficits in specific neural networks. Previous functional connectivity studies related to anhedonia have focused on case-control comparisons in specific disorders, using region-specific seed-based analyses. Here, the authors explore the entire functional connectome in relation to reward responsivity across a population of adults with heterogeneous psychopathology. In a sample of 225 adults from five diagnostic groups (major depressive disorder, N=32; bipolar disorder, N=50; schizophrenia, N=51; psychosis risk, N=39; and healthy control subjects, N=53), the authors conducted a connectome-wide analysis examining the relationship between a dimensional measure of reward responsivity (the reward sensitivity subscale of the Behavioral Activation Scale) and resting-state functional connectivity using multivariate distance-based matrix regression. The authors identified foci of dysconnectivity associated with reward responsivity in the nucleus accumbens, the default mode network, and the cingulo-opercular network. Follow-up analyses revealed dysconnectivity among specific large-scale functional networks and their connectivity with the nucleus accumbens. Reward deficits were associated with decreased connectivity between the nucleus accumbens and the default mode network and increased connectivity between the nucleus accumbens and the cingulo-opercular network. In addition, impaired reward responsivity was associated with default mode network hyperconnectivity and diminished connectivity between the default mode network and the cingulo-opercular network. These results emphasize the centrality of the nucleus accumbens in the pathophysiology of reward deficits and suggest that dissociable patterns of connectivity among large-scale networks are critical to the neurobiology of reward dysfunction across clinical diagnostic categories.

A SOMATIC-MARKER THEORY OF ADDICTION

PubMed Central

Verdejo-García, Antonio; Bechara, Antoine

2009-01-01

Similar to patients with ventromedial prefrontal cortex (VMPC) lesions, substance abusers show altered decision-making, characterized by a tendency to choose the immediate reward, at the expense of negative future consequences. The somatic-marker model proposes that decision-making depends on neural substrates that regulate homeostasis, emotion and feeling. According to this model, there should be a link between alterations in processing emotions in substance abusers, and their impairments in decision-making. A growing evidence from neuroscientific studies indicate that core aspects of addiction may be explained in terms of abnormal emotional/homeostatic guidance of decision-making. Behavioural studies have revealed emotional processing and decision-making deficits in substance abusers. Neuroimaging studies have shown that altered decision-making in addiction is associated with abnormal functioning of a distributed neural network critical for the processing of emotional information, and the experience of “craving”, including the VMPC, the amygdala, the striatum, the anterior cingulate cortex, and the insular/somato-sensory cortices, as well as non-specific neurotransmitter systems that modulate activities of neural processes involved in decision-making. The aim of this paper is to review this growing evidence, and to examine the extent of which these studies support a somatic-marker theory of addiction. We conclude that there are at least two underlying types of dysfunctions where emotional signals (somatic-markers) turns in favor of immediate outcomes in addiction: (1) a hyperactivity in the amygdala or impulsive system, which exaggerates the rewarding impact of available incentives, and (2) hypoactivity in the prefrontal cortex or reflective system, which forecasts the long-term consequences of a given action. PMID:18722390

Interaction matters: A perceived social partner alters the neural processing of human speech.

PubMed

Rice, Katherine; Redcay, Elizabeth

2016-04-01

Mounting evidence suggests that social interaction changes how communicative behaviors (e.g., spoken language, gaze) are processed, but the precise neural bases by which social-interactive context may alter communication remain unknown. Various perspectives suggest that live interactions are more rewarding, more attention-grabbing, or require increased mentalizing-thinking about the thoughts of others. Dissociating between these possibilities is difficult because most extant neuroimaging paradigms examining social interaction have not directly compared live paradigms to conventional "offline" (or recorded) paradigms. We developed a novel fMRI paradigm to assess whether and how an interactive context changes the processing of speech matched in content and vocal characteristics. Participants listened to short vignettes--which contained no reference to people or mental states--believing that some vignettes were prerecorded and that others were presented over a real-time audio-feed by a live social partner. In actuality, all speech was prerecorded. Simply believing that speech was live increased activation in each participant's own mentalizing regions, defined using a functional localizer. Contrasting live to recorded speech did not reveal significant differences in attention or reward regions. Further, higher levels of autistic-like traits were associated with altered neural specialization for live interaction. These results suggest that humans engage in ongoing mentalizing about social partners, even when such mentalizing is not explicitly required, illustrating how social context shapes social cognition. Understanding communication in social context has important implications for typical and atypical social processing, especially for disorders like autism where social difficulties are more acute in live interaction. Copyright © 2015 Elsevier Inc. All rights reserved.

Menthol Alone Upregulates Midbrain nAChRs, Alters nAChR Subtype Stoichiometry, Alters Dopamine Neuron Firing Frequency, and Prevents Nicotine Reward.

PubMed

Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; Nichols, Weston A; Moaddel, Ruin; Xiao, Cheng; Lester, Henry A

2016-03-09

Upregulation of β2 subunit-containing (β2*) nicotinic acetylcholine receptors (nAChRs) is implicated in several aspects of nicotine addiction, and menthol cigarette smokers tend to upregulate β2* nAChRs more than nonmenthol cigarette smokers. We investigated the effect of long-term menthol alone on midbrain neurons containing nAChRs. In midbrain dopaminergic (DA) neurons from mice containing fluorescent nAChR subunits, menthol alone increased the number of α4 and α6 nAChR subunits, but this upregulation did not occur in midbrain GABAergic neurons. Thus, chronic menthol produces a cell-type-selective upregulation of α4* nAChRs, complementing that of chronic nicotine alone, which upregulates α4 subunit-containing (α4*) nAChRs in GABAergic but not DA neurons. In mouse brain slices and cultured midbrain neurons, menthol reduced DA neuron firing frequency and altered DA neuron excitability following nAChR activation. Furthermore, menthol exposure before nicotine abolished nicotine reward-related behavior in mice. In neuroblastoma cells transfected with fluorescent nAChR subunits, exposure to 500 nm menthol alone also increased nAChR number and favored the formation of (α4)3(β2)2 nAChRs; this contrasts with the action of nicotine itself, which favors (α4)2(β2)3 nAChRs. Menthol alone also increases the number of α6β2 receptors that exclude the β3 subunit. Thus, menthol stabilizes lower-sensitivity α4* and α6 subunit-containing nAChRs, possibly by acting as a chemical chaperone. The abolition of nicotine reward-related behavior may be mediated through menthol's ability to stabilize lower-sensitivity nAChRs and alter DA neuron excitability. We conclude that menthol is more than a tobacco flavorant: administered alone chronically, it alters midbrain DA neurons of the nicotine reward-related pathway. Copyright © 2016 the authors 0270-6474/16/362957-18$15.00/0.

Interactions between the nucleus accumbens and auditory cortices predict music reward value.

PubMed

Salimpoor, Valorie N; van den Bosch, Iris; Kovacevic, Natasa; McIntosh, Anthony Randal; Dagher, Alain; Zatorre, Robert J

2013-04-12

We used functional magnetic resonance imaging to investigate neural processes when music gains reward value the first time it is heard. The degree of activity in the mesolimbic striatal regions, especially the nucleus accumbens, during music listening was the best predictor of the amount listeners were willing to spend on previously unheard music in an auction paradigm. Importantly, the auditory cortices, amygdala, and ventromedial prefrontal regions showed increased activity during listening conditions requiring valuation, but did not predict reward value, which was instead predicted by increasing functional connectivity of these regions with the nucleus accumbens as the reward value increased. Thus, aesthetic rewards arise from the interaction between mesolimbic reward circuitry and cortical networks involved in perceptual analysis and valuation.

Workload-Based Automated Interface Mode Selection

DTIC Science & Technology

2012-03-22

Process . . . . . . . . . . . . . . . . . . . . . 31 3.5.10 Agent Reward Function . . . . . . . . . . . . . . . . 31 3.5.11 Accelerated Learning... Strategies . . . . . . . . . . . . 31 4. Experimental Methodology . . . . . . . . . . . . . . . . . . . . . . . . 33 4.1 System Engineering Methodology...26 5. Agent state function. . . . . . . . . . . . . . . . . . . . . . . . . . . 28 6. Agent reward function

Cellular, Molecular, and Genetic Substrates Underlying the Impact of Nicotine on Learning

PubMed Central

Gould, Thomas J.; Leach, Prescott T.

2013-01-01

Addiction is a chronic disorder marked by long-lasting maladaptive changes in behavior and in reward system function. However, the factors that contribute to the behavioral and biological changes that occur with addiction are complex and go beyond reward. Addiction involves changes in cognitive control and the development of disruptive drug-stimuli associations that can drive behavior. A reason for the strong influence drugs of abuse can exert on cognition may be the striking overlap between the neurobiological substrates of addiction and of learning and memory, especially areas involved in declarative memory. Declarative memories are critically involved in the formation of autobiographical memories, and the ability of drugs of abuse to alter these memories could be particularly detrimental. A key structure in this memory system is the hippocampus, which is critically involved in binding multimodal stimuli together to form complex long-term memories. While all drugs of abuse can alter hippocampal function, this review focuses on nicotine. Addiction to tobacco products is insidious, with the majority of smokers wanting to quit; yet the majority of those that attempt to quit fail. Nicotine addiction is associated with the presence of drug-context and drug-cue associations that trigger drug seeking behavior and altered cognition during periods of abstinence, which contributes to relapse. This suggests that understanding the effects of nicotine on learning and memory will advance understanding and potentially facilitate treating nicotine addiction. The following sections examine: 1) how the effects of nicotine on hippocampus-dependent learning change as nicotine administration transitions from acute to chronic and then to withdrawal from chronic treatment and the potential impact of these changes on addiction, 2) how nicotine usurps the cellular mechanisms of synaptic plasticity, 3) the physiological changes in the hippocampus that may contribute to nicotine withdrawal deficits in learning, and 4) the role of genetics and developmental stage (i.e., adolescence) in these effects. PMID:23973448

Remembering with gains and losses: effects of monetary reward and punishment on successful encoding activation of source memories.

PubMed

Shigemune, Yayoi; Tsukiura, Takashi; Kambara, Toshimune; Kawashima, Ryuta

2014-05-01

The motivation of getting rewards or avoiding punishments reinforces learning behaviors. Although the neural mechanisms underlying the effect of rewards on episodic memory have been demonstrated, there is little evidence of the effect of punishments on this memory. Our functional magnetic resonance imaging (fMRI) study investigated the effects of monetary rewards and punishments on activation during the encoding of source memories. During encoding, participants memorized words (item) and locations of presented words (source) under 3 conditions (Reward, Punishment, and Control). During retrieval, participants retrieved item and source memories of the words and were rewarded or penalized according to their performance. Source memories encoded with rewards or punishments were remembered better than those without such encoding. fMRI data demonstrated that the ventral tegmental area and substantia nigra and nucleus accumbens activations reflected both the processes of reward and punishment, whereas insular activation increased as a linear function of punishment. Activation in the hippocampus and parahippocampal cortex predicted subsequent retrieval success of source memories. Additionally, correlations between these reward/punishment-related regions and the hippocampus were significant. The successful encoding of source memories could be enhanced by punishments and rewards, and interactions between reward/punishment-related regions and memory-related regions could contribute to memory enhancement by reward and/or punishment.

Diminished social reward anticipation in the broad autism phenotype as revealed by event-related brain potentials

PubMed Central

Cox, Anthony; Kohls, Gregor; Naples, Adam J.; Mukerji, Cora E.; Coffman, Marika C.; Rutherford, Helena J. V.; Mayes, Linda C.

2015-01-01

Diminished responsivity to reward incentives is a key contributor to the social-communication problems seen in autism spectrum disorders (ASDs). Social motivation theories suggest that individuals with ASD do not experience social interactions as rewarding, leading to negative consequences for the development of brain circuitry subserving social information. In this study, we examined neural responses to social and non-social reward anticipation in 35 typically developing young adults, examining modulation of reward sensitivity by level of autistic traits. Using an Event-related potential incentive-delay task incorporating novel, more ecologically valid forms of reward, higher expression of autistic traits was associated with an attenuated P3 response to the anticipation of social (simulated real-time video feedback from an observer), but not non-social (candy), rewards. Exploratory analyses revealed that this was unrelated to mentalizing ability. The P3 component reflects motivated attention to reward signals, suggesting attenuated motivation allocation specific to social incentives. The study extends prior findings of atypical reward anticipation in ASD, demonstrating that attenuated social reward responsiveness extends to autistic traits in the range of typical functioning. Results support the development of innovative paradigms for investigating social and non-social reward responsiveness. Insight into vulnerabilities in reward processing is critical for understanding social function in ASD. PMID:25752905

Remembering with Gains and Losses: Effects of Monetary Reward and Punishment on Successful Encoding Activation of Source Memories

PubMed Central

Shigemune, Yayoi; Tsukiura, Takashi; Kambara, Toshimune; Kawashima, Ryuta

2014-01-01

The motivation of getting rewards or avoiding punishments reinforces learning behaviors. Although the neural mechanisms underlying the effect of rewards on episodic memory have been demonstrated, there is little evidence of the effect of punishments on this memory. Our functional magnetic resonance imaging (fMRI) study investigated the effects of monetary rewards and punishments on activation during the encoding of source memories. During encoding, participants memorized words (item) and locations of presented words (source) under 3 conditions (Reward, Punishment, and Control). During retrieval, participants retrieved item and source memories of the words and were rewarded or penalized according to their performance. Source memories encoded with rewards or punishments were remembered better than those without such encoding. fMRI data demonstrated that the ventral tegmental area and substantia nigra and nucleus accumbens activations reflected both the processes of reward and punishment, whereas insular activation increased as a linear function of punishment. Activation in the hippocampus and parahippocampal cortex predicted subsequent retrieval success of source memories. Additionally, correlations between these reward/punishment-related regions and the hippocampus were significant. The successful encoding of source memories could be enhanced by punishments and rewards, and interactions between reward/punishment-related regions and memory-related regions could contribute to memory enhancement by reward and/or punishment. PMID:23314939

Cortisol alters reward processing in the human brain.

PubMed

Kinner, Valerie L; Wolf, Oliver T; Merz, Christian J

2016-08-01

Dysfunctional reward processing is known to play a central role for the development of psychiatric disorders. Glucocorticoids that are secreted in response to stress have been shown to attenuate reward sensitivity and thereby might promote the onset of psychopathology. However, the underlying neurobiological mechanisms mediating stress hormone effects on reward processing as well as potential sex differences remain elusive. In this neuroimaging study, we administered 30mg cortisol or a placebo to 30 men and 30 women and subsequently tested them in the Monetary Incentive Delay Task. Cortisol attenuated anticipatory neural responses to a verbal and a monetary reward in the left pallidum and the right anterior parahippocampal gyrus. Furthermore, in men, activation in the amygdala, the precuneus, the anterior cingulate, and in hippocampal regions was reduced under cortisol, whereas in cortisol-treated women a signal increase was observed in these regions. Behavioral performance also indicated that reward learning in men is impaired under high cortisol concentrations, while it is augmented in women. These findings illustrate that the stress hormone cortisol substantially diminishes reward anticipation and provide first evidence that cortisol effects on the neural reward system are sensitive to sex differences, which might translate into different vulnerabilities for psychiatric disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Healthy adolescents' neural response to reward: associations with puberty, positive affect, and depressive symptoms.

PubMed

Forbes, Erika E; Ryan, Neal D; Phillips, Mary L; Manuck, Stephen B; Worthman, Carol M; Moyles, Donna L; Tarr, Jill A; Sciarrillo, Samantha R; Dahl, Ronald E

2010-02-01

Changes in reward-related behavior are an important component of normal adolescent affective development. Understanding the neural underpinnings of these normative changes creates a foundation for investigating adolescence as a period of vulnerability to affective disorders, substance use disorders, and health problems. Studies of reward-related brain function have revealed conflicting findings regarding developmental change in the reactivity of the striatum and medial prefrontal cortex (mPFC) and have not considered puberty. The current study focused on puberty-specific changes in brain function and their association with mood. A sample of 77 healthy adolescents (26 pre-/early pubertal, 51 mid-/late pubertal) recruited in a narrow age range (mean = 11.94 years, SD = 0.75) were assessed for sexual maturation and circulating testosterone, completed a functional magnetic resonance imaging (fMRI) guessing task with monetary reward, and underwent experience sampling of mood in natural environments. For comparison, 19 healthy adults completed the fMRI assessment. Adolescents with more advanced pubertal maturation exhibited less striatal and more mPFC reactivity during reward outcome than similarly aged adolescents with less advanced maturation. Testosterone was positively correlated with striatal reactivity in boys during reward anticipation and negatively correlated with striatal reactivity in girls and boys during reward outcome. Striatal reactivity was positively correlated with real-world subjective positive affect and negatively correlated with depressive symptoms. mPFC reactivity was positively correlated with depressive symptoms. Reward-related brain function changes with puberty and is associated with adolescents' positive affect and depressive symptoms. Increased reward-seeking behavior at this developmental point could serve to compensate for these changes.

Reward-related brain function and sleep in pre/early pubertal and mid/late pubertal adolescents.

PubMed

Holm, Stephanie M; Forbes, Erika E; Ryan, Neal D; Phillips, Mary L; Tarr, Jill A; Dahl, Ronald E

2009-10-01

The onset of adolescence is a time of dramatic changes, including changes in sleep, and a time of new health concerns related to increases in risk-taking, sensation seeking, depression, substance use, and accidents. As part of a larger study examining puberty-specific changes in adolescents' reward-related brain function, the current article focuses on the relationship between functional neuroimaging measures of reward and measures of sleep. A total of 58 healthy participants 11-13 years of age completed a functional magnetic resonance imaging scan using a guessing task with monetary rewards and 4 days of at-home actigraphy and self-reported sleep ratings. Sleep variables included actigraph measures of mean weekend minutes asleep, sleep onset time, and sleep offset time, as well as self-reported sleep quality. During reward anticipation, less activation in the caudate (part of the ventral striatum) was associated with fewer minutes asleep, later sleep onset time, and lower sleep quality. During reward outcome, less caudate activation was associated with later sleep onset time, earlier sleep offset time, and lower sleep quality. It has been hypothesized that adolescents' low reactivity in reward-related brain areas could lead to compensatory increases in reward-driven behavior. This study's findings suggest that sleep could contribute to such behavior. Because decreased sleep has been associated with risky behavior and negative mood, these findings raise concerns about a negative spiral whereby the effects of puberty and sleep deprivation may have synergistic effects on reward processing, contributing to adolescent behavioral and emotional health problems.

Reward-Based Spatial Learning in Teens With Bulimia Nervosa

PubMed Central

Cyr, Marilyn; Wang, Zhishun; Tau, Gregory Z.; Zhao, Guihu; Friedl, Eve; Stefan, Mihaela; Terranova, Kate; Marsh, Rachel

2016-01-01

Objective To assess the functioning of mesolimbic and fronto-striatal areas involved in reward-based spatial learning in teenaged girls with bulimia nervosa (BN) that might be involved in the development and maintenance of maladaptive behaviors characteristic of the disorder. Method We compared functional magnetic resonance imaging blood oxygen level dependent response in 27 adolescent girls with BN to that of 27 healthy, age-matched control participants during a reward-based learning task that required learning to use extra-maze cues to navigate a virtual 8-arm radial maze to find hidden rewards. We compared groups in their patterns of brain activation associated with reward-based spatial learning versus a control condition in which rewards were unexpected because they were allotted pseudo-randomly to experimentally prevent learning. Results Both groups learned to navigate the maze to find hidden rewards, but group differences in brain activity associated with maze navigation and reward processing were detected in fronto-striatal regions and right anterior hippocampus. Unlike healthy adolescents, those with BN did not engage right inferior frontal gyrus during maze navigation, activated right anterior hippocampus during the receipt of unexpected rewards (control condition), and deactivated left superior frontal gyrus and right anterior hippocampus during expected reward receipt (learning condition). These patterns of hippocampal activation in the control condition were significantly associated with the frequency of binge-eating episodes. Conclusion Adolescents with BN displayed abnormal functioning of anterior hippocampus and fronto-striatal regions during reward-based spatial learning. These findings suggest that an imbalance in control and reward circuits may arise early in the course of BN. Clinical trial registration information An fMRI Study of Self-regulation in Adolescents With Bulimia Nervosa; https://clinicaltrials.gov/ct2/show/NCT00345943; NCT00345943. PMID:27806864

Activation of the GLP-1 receptors in the nucleus of the solitary tract reduces food reward behavior and targets the mesolimbic system.

PubMed

Richard, Jennifer E; Anderberg, Rozita H; Göteson, Andreas; Gribble, Fiona M; Reimann, Frank; Skibicka, Karolina P

2015-01-01

The gut/brain peptide, glucagon like peptide 1 (GLP-1), suppresses food intake by acting on receptors located in key energy balance regulating CNS areas, the hypothalamus or the hindbrain. Moreover, GLP-1 can reduce reward derived from food and motivation to obtain food by acting on its mesolimbic receptors. Together these data suggest a neuroanatomical segregation between homeostatic and reward effects of GLP-1. Here we aim to challenge this view and hypothesize that GLP-1 can regulate food reward behavior by acting directly on the hindbrain, the nucleus of the solitary tract (NTS), GLP-1 receptors (GLP-1R). Using two models of food reward, sucrose progressive ratio operant conditioning and conditioned place preference for food in rats, we show that intra-NTS microinjections of GLP-1 or Exendin-4, a stable analogue of GLP-1, inhibit food reward behavior. When the rats were given a choice between palatable food and chow, intra-NTS Exendin-4 treatment preferentially reduced intake of palatable food but not chow. However, chow intake and body weight were reduced by the NTS GLP-1R activation if chow was offered alone. The NTS GLP-1 activation did not alter general locomotor activity and did not induce nausea, measured by PICA. We further show that GLP-1 fibers are in close apposition to the NTS noradrenergic neurons, which were previously shown to provide a monosynaptic connection between the NTS and the mesolimbic system. Central GLP-1R activation also increased NTS expression of dopamine-β-hydroxylase, a key enzyme in noradrenaline synthesis, indicating a biological link between these two systems. Moreover, NTS GLP-1R activation altered the expression of dopamine-related genes in the ventral tegmental area. These data reveal a food reward-suppressing role of the NTS GLP-1R and indicate that the neurobiological targets underlying food reward control are not limited to the mesolimbic system, instead they are distributed throughout the CNS.

Motivation and timing: clues for modeling the reward system.

PubMed

Galtress, Tiffany; Marshall, Andrew T; Kirkpatrick, Kimberly

2012-05-01

There is growing evidence that a change in reward magnitude or value alters interval timing, indicating that motivation and timing are not independent processes as was previously believed. The present paper reviews several recent studies, as well as presenting some new evidence with further manipulations of reward value during training vs. testing on a peak procedure. The combined results cannot be accounted for by any of the current psychological timing theories. However, in examining the neural circuitry of the reward system, it is not surprising that motivation has an impact on timing because the motivation/valuation system directly interfaces with the timing system. A new approach is proposed for the development of the next generation of timing models, which utilizes knowledge of the neuroanatomy and neurophysiology of the reward system to guide the development of a neurocomputational model of the reward system. The initial foundation along with heuristics for proceeding with developing such a model is unveiled in an attempt to stimulate new theoretical approaches in the field. Copyright © 2012 Elsevier B.V. All rights reserved.

Altered subjective reward valuation among drug-deprived heavy marijuana users: Aversion to uncertainty

PubMed Central

Hefner, Kathryn R.; Starr, Mark. J.; Curtin, John. J.

2015-01-01

Marijuana is the most commonly used illicit drug in the United States and its use is rising. Nonetheless, scientific efforts to clarify the risk for addiction and other harm associated with marijuana use have been lacking. Maladaptive decision-making is a cardinal feature of addiction that is likely to emerge in heavy users. In particular, distorted subjective reward valuation related to homeostatic or allostatic processes has been implicated for many drugs of abuse. Selective changes in responses to uncertainty have been observed in response to intoxication and deprivation from various drugs of abuse. To assess for these potential neuroadaptive changes in reward valuation associated with marijuana deprivation, we examined the subjective value of uncertain and certain rewards among deprived and non-deprived heavy marijuana users in a behavioral economics decision-making task. Deprived users displayed reduced valuation of uncertain rewards, particularly when these rewards were more objectively valuable. This uncertainty aversion increased with increasing quantity of marijuana use. These results suggest comparable decision-making vulnerability from marijuana use as other drugs of abuse, and highlights targets for intervention. PMID:26595464

Comparing the effects of food restriction and overeating on brain reward systems

PubMed Central

Avena, Nicole M.; Murray, Susan; Gold, Mark S.

2014-01-01

Both caloric restriction and overeating have been shown to affect neural processes associated with reinforcement. Both preclinical and some clinical studies have provided evidence that food restriction may increase reward sensitivity, and while there are mixed findings regarding the effects of overeating on reward sensitivity, there is strong evidence linking this behavior with changes in reward-related brain regions. Evidence of these changes comes in part from findings that show that such eating patterns are associated with increased drug use. The data discussed here regarding the differential effects of various eating patterns on reward systems may be particularly relevant to the aging population, as this population has been shown to exhibit altered reward sensitivity and decreased caloric consumption. Moreover, members of this population appear to be increasingly affected by the current obesity epidemic. Food, like alcohol or drugs, can stimulate its own consumption and produce similar neurochemical changes in the brain. Age-related loss of appetite, decreased eating, and caloric restriction are hypothesized to be associated with changes in the prevalence of substance misuse, abuse, and dependence seen in this cohort. PMID:23535488

Hyperresponsivity and impaired prefrontal control of the mesolimbic reward system in schizophrenia.

PubMed

Richter, Anja; Petrovic, Aleksandra; Diekhof, Esther K; Trost, Sarah; Wolter, Sarah; Gruber, Oliver

2015-12-01

Schizophrenia is characterized by substantial dysfunctions of reward processing, leading to detrimental consequences for decision-making. The neurotransmitter dopamine is responsible for the transmission of reward signals and also known to be involved in the mechanism of psychosis. Using functional magnetic resonance imaging (fMRI), sixteen medicated patients with schizophrenia and sixteen healthy controls performed the 'desire-reason dilemma' (DRD) paradigm. This paradigm allowed us to directly investigate reward-related brain activations depending on the interaction of bottom-up and top-down mechanisms, when a previously conditioned reward stimulus had to be rejected to achieve a superordinate long-term goal. Both patients and controls showed significant activations in the mesolimbic reward system. In patients with schizophrenia, however, we found a significant hyperactivation of the left ventral striatum (vStr) when they were allowed to accept the conditioned reward stimuli, and a reduced top-down regulation of activation in the ventral striatum (vStr) and ventral tegmental area (VTA) while having to reject the immediate reward to pursue the superordinate task-goal. Moreover, while healthy subjects exhibited a negative functional coupling of the vStr with both the anteroventral prefrontal cortex (avPFC) and the ventromedial prefrontal cortex (VMPFC) in the dilemma situation, this functional coupling was significantly impaired in the patient group. These findings provide evidence for an increased ventral striatal activation to reward stimuli and an impaired top-down control of reward signals by prefrontal brain regions in schizophrenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human ventromedial prefrontal lesions alter incentivisation by reward.

PubMed

Manohar, Sanjay G; Husain, Masud

2016-03-01

Although medial frontal brain regions are implicated in valuation of rewards, evidence from focal lesions to these areas is scant, with many conflicting results regarding motivation and affect, and no human studies specifically examining incentivisation by reward. Here, 19 patients with isolated, focal damage in ventral and medial prefrontal cortex were selected from a database of 453 individuals with subarachnoid haemorrhage. Using a speeded saccadic task based on the oculomotor capture paradigm, we manipulated the maximum reward available on each trial using an auditory incentive cue. Modulation of behaviour by motivation permitted quantification of reward sensitivity. At the group level, medial frontal damage was overall associated with significantly reduced effects of reward on invigorating saccadic velocity and autonomic (pupil) responses compared to age-matched, healthy controls. Crucially, however, some individuals instead showed abnormally strong incentivisation effects for vigour. Increased sensitivity to rewards within the lesion group correlated with damage in subgenual ventromedial prefrontal cortex (vmPFC) areas, which have recently become the target for deep brain stimulation (DBS) in depression. Lesion correlations with clinical apathy suggested that the apathy associated with prefrontal damage is in fact reduced by damage at those coordinates. Reduced reward sensitivity showed a trend to correlate with damage near nucleus accumbens. Lesions did not, on the other hand, influence reward sensitivity of cognitive control, as measured by distractibility. Thus, although medial frontal lesions may generally reduce reward sensitivity, damage to key subregions paradoxically protect from this effect. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Human ventromedial prefrontal lesions alter incentivisation by reward

PubMed Central

Manohar, Sanjay G.; Husain, Masud

2016-01-01

Although medial frontal brain regions are implicated in valuation of rewards, evidence from focal lesions to these areas is scant, with many conflicting results regarding motivation and affect, and no human studies specifically examining incentivisation by reward. Here, 19 patients with isolated, focal damage in ventral and medial prefrontal cortex were selected from a database of 453 individuals with subarachnoid haemorrhage. Using a speeded saccadic task based on the oculomotor capture paradigm, we manipulated the maximum reward available on each trial using an auditory incentive cue. Modulation of behaviour by motivation permitted quantification of reward sensitivity. At the group level, medial frontal damage was overall associated with significantly reduced effects of reward on invigorating saccadic velocity and autonomic (pupil) responses compared to age-matched, healthy controls. Crucially, however, some individuals instead showed abnormally strong incentivisation effects for vigour. Increased sensitivity to rewards within the lesion group correlated with damage in subgenual ventromedial prefrontal cortex (vmPFC) areas, which have recently become the target for deep brain stimulation (DBS) in depression. Lesion correlations with clinical apathy suggested that the apathy associated with prefrontal damage is in fact reduced by damage at those coordinates. Reduced reward sensitivity showed a trend to correlate with damage near nucleus accumbens. Lesions did not, on the other hand, influence reward sensitivity of cognitive control, as measured by distractibility. Thus, although medial frontal lesions may generally reduce reward sensitivity, damage to key subregions paradoxically protect from this effect. PMID:26874940

Abnormal Reward System Activation in Mania

PubMed Central

Abler, Birgit; Greenhouse, Ian; Ongur, Dost; Walter, Henrik; Heckers, Stephan

2008-01-01

Transmission of reward signals is a function of dopamine, a neurotransmitter known to be involved in the mechanism of psychosis. Using functional magnetic resonance imaging (fMRI), we investigated how expectation and receipt of monetary rewards modulate brain activation in patients with bipolar mania and schizophrenia. We studied 12 acutely manic patients with a history of bipolar disorder, 12 patients with a current episode of schizoaffective disorder or schizophrenia and 12 healthy subjects. All patients were treated with dopamine antagonists at the time of the study. Subjects performed a delayed incentive paradigm with monetary reward in the scanner that allowed for investigating effects of expectation, receipt, and omission of rewards. Patients with schizophrenia and healthy control subjects showed the expected activation of dopaminergic brain areas, that is, ventral tegmentum activation upon expectation of monetary rewards and nucleus accumbens activation during receipt vs omission of rewards. In manic patients, however, we did not find a similar pattern of brain activation and the differential signal in the nucleus accumbens upon receipt vs omission of rewards was significantly lower compared to the healthy control subjects. Our findings provide evidence for abnormal function of the dopamine system during receipt or omission of expected rewards in bipolar disorder. These deficits in prediction error processing in acute mania may help to explain symptoms of disinhibition and abnormal goal pursuit regulation. PMID:17987058

Reward salience and risk aversion underlie differential ACC activity in substance dependence

PubMed Central

Alexander, William H.; Fukunaga, Rena; Finn, Peter; Brown, Joshua W.

2015-01-01

The medial prefrontal cortex, especially the dorsal anterior cingulate cortex (ACC), has long been implicated in cognitive control and error processing. Although the association between ACC and behavior has been established, it is less clear how ACC contributes to dysfunctional behavior such as substance dependence. Evidence from neuroimaging studies investigating ACC function in substance users is mixed, with some studies showing disengagement of ACC in substance dependent individuals (SDs), while others show increased ACC activity related to substance use. In this study, we investigate ACC function in SDs and healthy individuals performing a change signal task for monetary rewards. Using a priori predictions derived from a recent computational model of ACC, we find that ACC activity differs between SDs and controls in factors related to reward salience and risk aversion between SDs and healthy individuals. Quantitative fits of a computational model to fMRI data reveal significant differences in best fit parameters for reward salience and risk preferences. Specifically, the ACC in SDs shows greater risk aversion, defined as concavity in the utility function, and greater attention to rewards relative to reward omission. Furthermore, across participants risk aversion and reward salience are positively correlated. The results clarify the role that ACC plays in both the reduced sensitivity to omitted rewards and greater reward valuation in SDs. Clinical implications of applying computational modeling in psychiatry are also discussed. PMID:26106528

Reward salience and risk aversion underlie differential ACC activity in substance dependence.

PubMed

Alexander, William H; Fukunaga, Rena; Finn, Peter; Brown, Joshua W

2015-01-01

The medial prefrontal cortex, especially the dorsal anterior cingulate cortex (ACC), has long been implicated in cognitive control and error processing. Although the association between ACC and behavior has been established, it is less clear how ACC contributes to dysfunctional behavior such as substance dependence. Evidence from neuroimaging studies investigating ACC function in substance users is mixed, with some studies showing disengagement of ACC in substance dependent individuals (SDs), while others show increased ACC activity related to substance use. In this study, we investigate ACC function in SDs and healthy individuals performing a change signal task for monetary rewards. Using a priori predictions derived from a recent computational model of ACC, we find that ACC activity differs between SDs and controls in factors related to reward salience and risk aversion between SDs and healthy individuals. Quantitative fits of a computational model to fMRI data reveal significant differences in best fit parameters for reward salience and risk preferences. Specifically, the ACC in SDs shows greater risk aversion, defined as concavity in the utility function, and greater attention to rewards relative to reward omission. Furthermore, across participants risk aversion and reward salience are positively correlated. The results clarify the role that ACC plays in both the reduced sensitivity to omitted rewards and greater reward valuation in SDs. Clinical implications of applying computational modeling in psychiatry are also discussed.

Differentiating between bipolar and unipolar depression in functional and structural MRI studies.

PubMed

Han, Kyu-Man; De Berardis, Domenico; Fornaro, Michele; Kim, Yong-Ku

2018-03-28

Distinguishing depression in bipolar disorder (BD) from unipolar depression (UD) solely based on clinical clues is difficult, which has led to the exploration of promising neural markers in neuroimaging measures for discriminating between BD depression and UD. In this article, we review structural and functional magnetic resonance imaging (MRI) studies that directly compare UD and BD depression based on neuroimaging modalities including functional MRI studies on regional brain activation or functional connectivity, structural MRI on gray or white matter morphology, and pattern classification analyses using a machine learning approach. Numerous studies have reported distinct functional and structural alterations in emotion- or reward-processing neural circuits between BD depression and UD. Different activation patterns in neural networks including the amygdala, anterior cingulate cortex (ACC), prefrontal cortex (PFC), and striatum during emotion-, reward-, or cognition-related tasks have been reported between BD and UD. A stronger functional connectivity pattern in BD was pronounced in default mode and in frontoparietal networks and brain regions including the PFC, ACC, parietal and temporal regions, and thalamus compared to UD. Gray matter volume differences in the ACC, hippocampus, amygdala, and dorsolateral prefrontal cortex (DLPFC) have been reported between BD and UD, along with a thinner DLPFC in BD compared to UD. BD showed reduced integrity in the anterior part of the corpus callosum and posterior cingulum compared to UD. Several studies performed pattern classification analysis using structural and functional MRI data to distinguish between UD and BD depression using a supervised machine learning approach, which yielded a moderate level of accuracy in classification. Copyright © 2018 Elsevier Inc. All rights reserved.

Discounting of Delayed Food Rewards in Pigeons and Rats: Is There a Magnitude Effect

ERIC Educational Resources Information Center

Green, Leonard; Myerson, Joel; Holt, Daniel D.; Slavin, John R.; Estle, Sara J.

2004-01-01

Temporal discounting refers to the decrease in the present, subjective value of a reward as the time to its receipt increases. Results from humans have shown that a hyperbola-like function describes the form of the discounting function when choices involve hypothetical monetary rewards. In addition, magnitude effects have been reported in which…

Distinct representations for shifts of spatial attention and changes of reward contingencies in the human brain

PubMed Central

Tosoni, Annalisa; Shulman, Gordon L.; Pope, Anna L. W.; McAvoy, Mark P.; Corbetta, Maurizio

2012-01-01

Success in a dynamically changing world requires both rapid shifts of attention to the location of important objects and the detection of changes in motivational contingencies that may alter future behavior. Here we addressed the relationship between these two processes by measuring the blood-oxygenation-level-dependent (BOLD) signal during a visual search task in which the location and the color of a salient cue respectively indicated where a rewarded target would appear and the monetary gain (large or small) associated with its detection. While cues that either shifted or maintained attention were presented every 4 to 8 seconds, the reward magnitude indicated by the cue changed roughly every 30 seconds, allowing us to distinguish a change in expected reward magnitude from a maintained state of expected reward magnitude. Posterior cingulate cortex was modulated by cues signaling an increase in expected reward magnitude, but not by cues for shifting versus maintaining spatial attention. Dorsal fronto-parietal regions in precuneus and FEF also showed increased BOLD activity for changes in expected reward magnitude from low to high, but in addition showed large independent modulations for shifting versus maintaining attention. In particular, the differential activation for shifting versus maintaining attention was not affected by expected reward magnitude. These results indicate that BOLD activations for shifts of attention and increases in expected reward magnitude are largely separate. Finally, visual cortex showed sustained spatially selective signals that were significantly enhanced when greater reward magnitude was expected, but this reward-related modulation was not observed in spatially selective regions of dorsal fronto-parietal cortex. PMID:22578709

Long term voluntary wheel running is rewarding and produces plasticity in the mesolimbic reward pathway

PubMed Central

Greenwood, Benjamin N.; Foley, Teresa E.; Le, Tony V.; Strong, Paul V.; Loughridge, Alice B.; Day, Heidi E.W.; Fleshner, Monika

2011-01-01

The mesolimbic reward pathway is implicated in stress-related psychiatric disorders and is a potential target of plasticity underlying the stress resistance produced by repeated voluntary exercise. It is unknown, however, whether rats find long-term access to running wheels rewarding, or if repeated voluntary exercise reward produces plastic changes in mesolimbic reward neurocircuitry. In the current studies, young adult, male Fischer 344 rats allowed voluntary access to running wheels for 6 weeks, but not 2 weeks, found wheel running rewarding, as measured by conditioned place preference (CPP). Consistent with prior reports and the behavioral data, 6 weeks of wheel running increased ΔFosB/FosB immunoreactivity in the nucleus accumbens (Acb). In addition, semi quantitative in situ hybridization revealed that 6 weeks of wheel running, compared to sedentary housing, increased tyrosine hydroxylase (TH) mRNA levels in the ventral tegmental area (VTA), increased delta opioid receptor (DOR) mRNA levels in the Acb shell, and reduced levels of dopamine receptor (DR)-D2 mRNA in the Acb core. Results indicate that repeated voluntary exercise is rewarding and alters gene transcription in mesolimbic reward neurocircuitry. The duration-dependent effects of wheel running on CPP suggest that as the weeks of wheel running progress, the rewarding effects of a night of voluntary wheel running might linger longer into the inactive cycle thus providing stronger support for CPP. The observed plasticity could contribute to the mechanisms by which exercise reduces the incidence and severity of substance abuse disorders, changes the rewarding properties of drugs of abuse, and facilitates successful coping with stress. PMID:21070820

Reduced posterior mesofrontal cortex activation by risky rewards in substance-dependent patients.

PubMed

Bjork, James M; Momenan, Reza; Smith, Ashley R; Hommer, Daniel W

2008-05-01

Substance-dependent individuals show disadvantageous decision-making, as well as alterated frontocortical recruitment when performing experimental tasks. We investigated whether substance-dependent patients (SDP) would show blunted recruitment of posterior mesofrontal cortex (PMC) by a conflict between concurrently increasing reward and risk of penalty in a monetary game of "chicken." SDP and controls performed: motor control (no reward) trials, guaranteed reward trials in which reward was not at risk, and risky trials where subjects were required to terminate their reward accrual before a secret varying time limit or else "bust" and forfeit that trial's winnings (low penalty) or the current trial's winnings plus an equal amount of previous winnings (high penalty). Reward accrual duration at risk of "busting" correlated negatively with trait neuroticism. The contrast between winning guaranteed reward versus non-reward activated the caudate head bilaterally in SDP but not controls. Accumulation of money at risk of low- or high-penalty (contrasted with accumulating guaranteed money) activated the PMC in both groups, but with a greater magnitude and more anterior extent in controls. Pre-decision signal increase in a PMC volume of interest negatively correlated with risk-taking in low-penalty trials, and was blunted in SDP relative to controls under both penalty conditions after controlling for individual differences in actual risk-taking and the higher neuroticism of SDP. These data suggest that SDP are characterized by a combination of: (a) striatal hypersensitivity to reward, and (b) under-recruitment of the specialized conflict-monitoring circuitry of the PMC when reward entails potential penalties.

Reward Pays the Cost of Noise Reduction in Motor and Cognitive Control.

PubMed

Manohar, Sanjay G; Chong, Trevor T-J; Apps, Matthew A J; Batla, Amit; Stamelou, Maria; Jarman, Paul R; Bhatia, Kailash P; Husain, Masud

2015-06-29

Speed-accuracy trade-off is an intensively studied law governing almost all behavioral tasks across species. Here we show that motivation by reward breaks this law, by simultaneously invigorating movement and improving response precision. We devised a model to explain this paradoxical effect of reward by considering a new factor: the cost of control. Exerting control to improve response precision might itself come at a cost--a cost to attenuate a proportion of intrinsic neural noise. Applying a noise-reduction cost to optimal motor control predicted that reward can increase both velocity and accuracy. Similarly, application to decision-making predicted that reward reduces reaction times and errors in cognitive control. We used a novel saccadic distraction task to quantify the speed and accuracy of both movements and decisions under varying reward. Both faster speeds and smaller errors were observed with higher incentives, with the results best fitted by a model including a precision cost. Recent theories consider dopamine to be a key neuromodulator in mediating motivational effects of reward. We therefore examined how Parkinson's disease (PD), a condition associated with dopamine depletion, alters the effects of reward. Individuals with PD showed reduced reward sensitivity in their speed and accuracy, consistent in our model with higher noise-control costs. Including a cost of control over noise explains how reward may allow apparent performance limits to be surpassed. On this view, the pattern of reduced reward sensitivity in PD patients can specifically be accounted for by a higher cost for controlling noise. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Structural and Functional Plasticity within the Nucleus Accumbens and Prefrontal Cortex Associated with Time-Dependent Increases in Food Cue-Seeking Behavior.

PubMed

Dingess, Paige M; Darling, Rebecca A; Derman, Rifka C; Wulff, Shaun S; Hunter, Melissa L; Ferrario, Carrie R; Brown, Travis E

2017-11-01

Urges to consume food can be driven by stimuli in the environment that are associated with previous food experience. Identifying adaptations within brain reward circuits that facilitate cue-induced food seeking is critical for understanding and preventing the overconsumption of food and subsequent weight gain. Utilizing electrophysiological, biochemical, and DiI labeling, we examined functional and structural changes in the nucleus accumbens (NAc) and prefrontal cortex (PFC) associated with time-dependent increases in food craving ('incubation of craving'). Rats self-administered 60% high fat or chow 45 mg pellets and were then tested for incubation of craving either 1 or 30 days after training. High fat was chosen for comparison to determine whether palatability differentially affected incubation and/or plasticity. Rats showed robust incubation of craving for both food rewards, although responding for cues previously associated with high fat was greater than chow at both 1 and 30 days. In addition, previous experience with high-fat consumption reduced dendritic spine density in the PFC at both time points. In contrast, incubation was associated with an increase in NAc spine density and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated transmission at 30 days in both groups. Finally, incubation of craving for chow and high fat was accompanied by an increase in calcium-permeable and calcium-impermeable AMPARs, respectively. Our results suggest that incubation of food craving alters brain reward circuitry and macronutrient composition specifically induces cortical changes in a way that may facilitate maladaptive food-seeking behaviors.

Idiosyncratic representation of peripersonal space depends on the success of one's own motor actions, but also the successful actions of others!

PubMed Central

Quesque, François; Gigliotti, Maria-Francesca; Ott, Laurent; Bruyelle, Jean-Luc

2018-01-01

Peripersonal space is a multisensory representation of the environment around the body in relation to the motor system, underlying the interactions with the physical and social world. Although changing body properties and social context have been shown to alter the functional processing of space, little is known about how changing the value of objects influences the representation of peripersonal space. In two experiments, we tested the effect of modifying the spatial distribution of reward-yielding targets on manual reaching actions and peripersonal space representation. Before and after performing a target-selection task consisting of manually selecting a set of targets on a touch-screen table, participants performed a two-alternative forced-choice reachability-judgment task. In the target-selection task, half of the targets were associated with a reward (change of colour from grey to green, providing 1 point), the other half being associated with no reward (change of colour from grey to red, providing no point). In Experiment 1, the target-selection task was performed individually with the aim of maximizing the point count, and the distribution of the reward-yielding targets was either 50%, 25% or 75% in the proximal and distal spaces. In Experiment 2, the target-selection task was performed in a social context involving cooperation between two participants to maximize the point count, and the distribution of the reward-yielding targets was 50% in the proximal and distal spaces. Results showed that changing the distribution of the reward-yielding targets or introducing the social context modified concurrently the amplitude of self-generated manual reaching actions and the representation of peripersonal space. Moreover, a decrease of the amplitude of manual reaching actions caused a reduction of peripersonal space when resulting from the distribution of reward-yielding targets, while this effect was not observed in a social interaction context. In that case, the decreased amplitude of manual reaching actions was accompanied by an increase of peripersonal space representation, which was not due to the mere presence of a confederate (control experiment). We conclude that reward-dependent modulation of objects values in the environment modifies the representation of peripersonal space, when resulting from either self-generated motor actions or observation of motor actions performed by a confederate. PMID:29771982

Idiosyncratic representation of peripersonal space depends on the success of one's own motor actions, but also the successful actions of others!

PubMed

Coello, Yann; Quesque, François; Gigliotti, Maria-Francesca; Ott, Laurent; Bruyelle, Jean-Luc

2018-01-01

Peripersonal space is a multisensory representation of the environment around the body in relation to the motor system, underlying the interactions with the physical and social world. Although changing body properties and social context have been shown to alter the functional processing of space, little is known about how changing the value of objects influences the representation of peripersonal space. In two experiments, we tested the effect of modifying the spatial distribution of reward-yielding targets on manual reaching actions and peripersonal space representation. Before and after performing a target-selection task consisting of manually selecting a set of targets on a touch-screen table, participants performed a two-alternative forced-choice reachability-judgment task. In the target-selection task, half of the targets were associated with a reward (change of colour from grey to green, providing 1 point), the other half being associated with no reward (change of colour from grey to red, providing no point). In Experiment 1, the target-selection task was performed individually with the aim of maximizing the point count, and the distribution of the reward-yielding targets was either 50%, 25% or 75% in the proximal and distal spaces. In Experiment 2, the target-selection task was performed in a social context involving cooperation between two participants to maximize the point count, and the distribution of the reward-yielding targets was 50% in the proximal and distal spaces. Results showed that changing the distribution of the reward-yielding targets or introducing the social context modified concurrently the amplitude of self-generated manual reaching actions and the representation of peripersonal space. Moreover, a decrease of the amplitude of manual reaching actions caused a reduction of peripersonal space when resulting from the distribution of reward-yielding targets, while this effect was not observed in a social interaction context. In that case, the decreased amplitude of manual reaching actions was accompanied by an increase of peripersonal space representation, which was not due to the mere presence of a confederate (control experiment). We conclude that reward-dependent modulation of objects values in the environment modifies the representation of peripersonal space, when resulting from either self-generated motor actions or observation of motor actions performed by a confederate.

Incentive effect on inhibitory control in adolescents with early-life stress: an antisaccade study.

PubMed

Mueller, Sven C; Hardin, Michael G; Korelitz, Katherine; Daniele, Teresa; Bemis, Jessica; Dozier, Mary; Peloso, Elizabeth; Maheu, Francoise S; Pine, Daniel S; Ernst, Monique

2012-03-01

Early-life stress (ES) such as adoption, change of caregiver, or experience of emotional neglect may influence the way in which affected individuals respond to emotional stimuli of positive or negative valence. These modified responses may stem from a direct alteration of how emotional stimuli are coded, and/or the cognitive function implicated in emotion modulation, such as self-regulation or inhibition. These ES effects have been probed on tasks either targeting reward and inhibitory function. Findings revealed deficits in both reward processing and inhibitory control in ES youths. However, no work has yet examined whether incentives can improve automatic response or inhibitory control in ES youths. To determine whether incentives would only improve self-regulated voluntary actions or generalize to automated motoric responses, participants were tested on a mixed eye movement task that included reflex-like prosaccades and voluntary controlled antisaccade eye movements. Seventeen adopted children (10 females, mean age 11.3 years) with a documented history of neglect and 29 typical healthy youths (16 females, mean age 11.9 years) performed the mixed prosaccade/antisaccade task during monetary incentive conditions or during no-incentive conditions. Across both saccade types, ES adolescents responded more slowly than controls. As expected, control participants committed fewer errors on antisaccades during the monetary incentive condition relative to the no-incentive condition. By contrast, ES youths failed to show this incentive-related improvement on inhibitory control. No significant incentive effects were found with prepotent prosaccades trials in either group. Finally, co-morbid psychopathology did not modulate the findings. These data suggest that youths with experience of early stress exhibit deficient modulation of inhibitory control by reward processes, in tandem with a reward-independent deficit in preparation for both automatic and controlled responses. These data may be relevant to interventions in ES youths. Published by Elsevier Ltd.

Individual differences in sensitivity to reward and punishment and neural activity during reward and avoidance learning

PubMed Central

Yoon, HeungSik; Kim, Hackjin; Hamann, Stephan

2015-01-01

In this functional neuroimaging study, we investigated neural activations during the process of learning to gain monetary rewards and to avoid monetary loss, and how these activations are modulated by individual differences in reward and punishment sensitivity. Healthy young volunteers performed a reinforcement learning task where they chose one of two fractal stimuli associated with monetary gain (reward trials) or avoidance of monetary loss (avoidance trials). Trait sensitivity to reward and punishment was assessed using the behavioral inhibition/activation scales (BIS/BAS). Functional neuroimaging results showed activation of the striatum during the anticipation and reception periods of reward trials. During avoidance trials, activation of the dorsal striatum and prefrontal regions was found. As expected, individual differences in reward sensitivity were positively associated with activation in the left and right ventral striatum during reward reception. Individual differences in sensitivity to punishment were negatively associated with activation in the left dorsal striatum during avoidance anticipation and also with activation in the right lateral orbitofrontal cortex during receiving monetary loss. These results suggest that learning to attain reward and learning to avoid loss are dependent on separable sets of neural regions whose activity is modulated by trait sensitivity to reward or punishment. PMID:25680989

Drug-Induced Alterations of Endocannabinoid-Mediated Plasticity in Brain Reward Regions.

PubMed

Zlebnik, Natalie E; Cheer, Joseph F

2016-10-05

The endocannabinoid (eCB) system has emerged as one of the most important mediators of physiological and pathological reward-related synaptic plasticity. eCBs are retrograde messengers that provide feedback inhibition, resulting in the suppression of neurotransmitter release at both excitatory and inhibitory synapses, and they serve a critical role in the spatiotemporal regulation of both short- and long-term synaptic plasticity that supports adaptive learning of reward-motivated behaviors. However, mechanisms of eCB-mediated synaptic plasticity in reward areas of the brain are impaired following exposure to drugs of abuse. Because of this, it is theorized that maladaptive eCB signaling may contribute to the development and maintenance of addiction-related behavior. Here we review various forms of eCB-mediated synaptic plasticity present in regions of the brain involved in reward and reinforcement and explore the potential physiological relevance of maladaptive eCB signaling to addiction vulnerability. Copyright © 2016 the authors 0270-6474/16/3610230-09$15.00/0.

Do Effort and Reward at Work Predict Changes in Cognitive Function? First Longitudinal Results from the Representative German Socio-Economic Panel.

PubMed

Riedel, Natalie; Siegrist, Johannes; Wege, Natalia; Loerbroks, Adrian; Angerer, Peter; Li, Jian

2017-11-15

It has been suggested that work characteristics, such as mental demands, job control, and occupational complexity, are prospectively related to cognitive function. However, current evidence on links between psychosocial working conditions and cognitive change over time is inconsistent. In this study, we applied the effort-reward imbalance model that allows to build on previous research on mental demands and to introduce reward-based learning as a principle with beneficial effect on cognitive function. We aimed to investigate whether high effort, high reward, and low over-commitment in 2006 were associated with positive changes in cognitive function in terms of perceptual speed and word fluency (2006-2012), and whether the co-manifestation of high effort and high reward would yield the strongest association. To this end, we used data on 1031 employees who participated in a large and representative study. Multivariate linear regression analyses supported our main hypotheses (separate and combined effects of effort and reward), particularly on changes in perceptual speed, whereas the effects of over-commitment did not reach the level of statistical significance. Our findings extend available knowledge by examining the course of cognitive function over time. If corroborated by further evidence, organization-based measures in the workplace can enrich efforts towards preventing cognitive decline in ageing workforces.

Practice expenses in the MFS (Medicare fee schedule): the service-class approach.

PubMed

Latimer, E A; Kane, N M

1995-01-01

The practice expense component of the Medicare fee schedule (MFS), which is currently based on historical charges and rewards physician procedures at the expense of cognitive services, is due to be changed by January 1, 1998. The Physician Payment Review Commission (PPRC) and others have proposed microcosting direct costs and allocating all indirect costs on a common basis, such as physician time or work plus direct costs. Without altering the treatment of direct costs, the service-class approach disaggregates indirect costs into six practice function costs. The practice function costs are then allocated to classes of services using cost-accounting and statistical methods. This approach would make the practice expense component more resource-based than other proposed alternatives.

Diminished social reward anticipation in the broad autism phenotype as revealed by event-related brain potentials.

PubMed

Cox, Anthony; Kohls, Gregor; Naples, Adam J; Mukerji, Cora E; Coffman, Marika C; Rutherford, Helena J V; Mayes, Linda C; McPartland, James C

2015-10-01

Diminished responsivity to reward incentives is a key contributor to the social-communication problems seen in autism spectrum disorders (ASDs). Social motivation theories suggest that individuals with ASD do not experience social interactions as rewarding, leading to negative consequences for the development of brain circuitry subserving social information. In this study, we examined neural responses to social and non-social reward anticipation in 35 typically developing young adults, examining modulation of reward sensitivity by level of autistic traits. Using an Event-related potential incentive-delay task incorporating novel, more ecologically valid forms of reward, higher expression of autistic traits was associated with an attenuated P3 response to the anticipation of social (simulated real-time video feedback from an observer), but not non-social (candy), rewards. Exploratory analyses revealed that this was unrelated to mentalizing ability. The P3 component reflects motivated attention to reward signals, suggesting attenuated motivation allocation specific to social incentives. The study extends prior findings of atypical reward anticipation in ASD, demonstrating that attenuated social reward responsiveness extends to autistic traits in the range of typical functioning. Results support the development of innovative paradigms for investigating social and non-social reward responsiveness. Insight into vulnerabilities in reward processing is critical for understanding social function in ASD. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Decreased prefrontal cortical sensitivity to monetary reward is associated with impaired motivation and self-control in cocaine addiction

PubMed Central

Goldstein, Rita Z.; Alia-Klein, Nelly; Tomasi, Dardo; Zhang, Lei; Cottone, Lisa A.; Maloney, Thomas; Telang, Frank; Caparelli, Elisabeth C.; Chang, Linda; Ernst, Thomas; Samaras, Dimitris; Squires, Nancy K.; Volkow, Nora D.

2008-01-01

Objective To examine the brain’s sensitivity to monetary rewards of different magnitudes in cocaine abusers and to study its association with motivation and self-control. Method Sixteen cocaine abusers and 13 matched healthy comparison subjects performed a forced-choice task under three monetary value conditions while brain activation was measured with functional magnetic resonance imaging. Objective measures of state motivation were assessed by reaction time and accuracy, and subjective measures were assessed by self-reports of task engagement. Measures of trait motivation and self-control were assessed with the Multidimensional Personality Questionnaire. Results The cocaine abusers demonstrated an overall reduced regional brain responsivity to differences between the monetary value conditions. Also, in comparison subjects but not in cocaine abusers reward-induced improvements in performance were associated with self-reports of task engagement, and money-induced activations in the lateral prefrontal cortex were associated with activations in the orbitofrontal cortex. For cocaine subjects, prefrontal cortex sensitivity to money was instead associated with motivation and self-control. Conclusions These findings suggest that in cocaine addiction (1) activation of the corticolimbic reward circuit to gradations of money is altered; (2) lack of a correlation between objective and subjective measures of state motivation may be indicative of disrupted perception of motivational drive, which could contribute to impairments in self-control; and (3) the lateral prefrontal cortex modulates trait motivation and deficits in self-control, and a possible underlying mechanism may encompass a breakdown in prefrontal-orbitofrontal cortical communication. PMID:17202543

Modeling the Effect of Reward Amount on Probability Discounting

ERIC Educational Resources Information Center

Myerson, Joel; Green, Leonard; Morris, Joshua

2011-01-01

The present study with college students examined the effect of amount on the discounting of probabilistic monetary rewards. A hyperboloid function accurately described the discounting of hypothetical rewards ranging in amount from $20 to $10,000,000. The degree of discounting increased continuously with amount of probabilistic reward. This effect…

Reward Circuitry Function in Autism during Face Anticipation and Outcomes

ERIC Educational Resources Information Center

Dichter, Gabriel S.; Richey, J. Anthony; Rittenberg, Alison M.; Sabatino, Antoinette; Bodfish, James W.

2012-01-01

The aim of this study was to investigate reward circuitry responses in autism during reward anticipation and outcomes for monetary and social rewards. During monetary anticipation, participants with autism spectrum disorders (ASDs) showed hypoactivation in right nucleus accumbens and hyperactivation in right hippocampus, whereas during monetary…

Toward isolating the role of dopamine in the acquisition of incentive salience attribution.

PubMed

Chow, Jonathan J; Nickell, Justin R; Darna, Mahesh; Beckmann, Joshua S

2016-10-01

Stimulus-reward learning has been heavily linked to the reward-prediction error learning hypothesis and dopaminergic function. However, some evidence suggests dopaminergic function may not strictly underlie reward-prediction error learning, but may be specific to incentive salience attribution. Utilizing a Pavlovian conditioned approach procedure consisting of two stimuli that were equally reward-predictive (both undergoing reward-prediction error learning) but functionally distinct in regard to incentive salience (levers that elicited sign-tracking and tones that elicited goal-tracking), we tested the differential role of D1 and D2 dopamine receptors and nucleus accumbens dopamine in the acquisition of sign- and goal-tracking behavior and their associated conditioned reinforcing value within individuals. Overall, the results revealed that both D1 and D2 inhibition disrupted performance of sign- and goal-tracking. However, D1 inhibition specifically prevented the acquisition of sign-tracking to a lever, instead promoting goal-tracking and decreasing its conditioned reinforcing value, while neither D1 nor D2 signaling was required for goal-tracking in response to a tone. Likewise, nucleus accumbens dopaminergic lesions disrupted acquisition of sign-tracking to a lever, while leaving goal-tracking in response to a tone unaffected. Collectively, these results are the first evidence of an intraindividual dissociation of dopaminergic function in incentive salience attribution from reward-prediction error learning, indicating that incentive salience, reward-prediction error, and their associated dopaminergic signaling exist within individuals and are stimulus-specific. Thus, individual differences in incentive salience attribution may be reflective of a differential balance in dopaminergic function that may bias toward the attribution of incentive salience, relative to reward-prediction error learning only. Copyright © 2016 Elsevier Ltd. All rights reserved.

Explorative Function in Williams Syndrome Analyzed through a Large-Scale Task with Multiple Rewards

ERIC Educational Resources Information Center

Foti, F.; Petrosini, L.; Cutuli, D.; Menghini, D.; Chiarotti, F.; Vicari, S.; Mandolesi, L.

2011-01-01

This study aimed to evaluate spatial function in subjects with Williams syndrome (WS) by using a large-scale task with multiple rewards and comparing the spatial abilities of WS subjects with those of mental age-matched control children. In the present spatial task, WS participants had to explore an open space to search nine rewards placed in…

Association of Elevated Reward Prediction Error Response With Weight Gain in Adolescent Anorexia Nervosa.

PubMed

DeGuzman, Marisa; Shott, Megan E; Yang, Tony T; Riederer, Justin; Frank, Guido K W

2017-06-01

Anorexia nervosa is a psychiatric disorder of unknown etiology. Understanding associations between behavior and neurobiology is important in treatment development. Using a novel monetary reward task during functional magnetic resonance brain imaging, the authors tested how brain reward learning in adolescent anorexia nervosa changes with weight restoration. Female adolescents with anorexia nervosa (N=21; mean age, 16.4 years [SD=1.9]) underwent functional MRI (fMRI) before and after treatment; similarly, healthy female control adolescents (N=21; mean age, 15.2 years [SD=2.4]) underwent fMRI on two occasions. Brain function was tested using the reward prediction error construct, a computational model for reward receipt and omission related to motivation and neural dopamine responsiveness. Compared with the control group, the anorexia nervosa group exhibited greater brain response 1) for prediction error regression within the caudate, ventral caudate/nucleus accumbens, and anterior and posterior insula, 2) to unexpected reward receipt in the anterior and posterior insula, and 3) to unexpected reward omission in the caudate body. Prediction error and unexpected reward omission response tended to normalize with treatment, while unexpected reward receipt response remained significantly elevated. Greater caudate prediction error response when underweight was associated with lower weight gain during treatment. Punishment sensitivity correlated positively with ventral caudate prediction error response. Reward system responsiveness is elevated in adolescent anorexia nervosa when underweight and after weight restoration. Heightened prediction error activity in brain reward regions may represent a phenotype of adolescent anorexia nervosa that does not respond well to treatment. Prediction error response could be a neurobiological marker of illness severity that can indicate individual treatment needs.

Association of Elevated Reward Prediction Error Response With Weight Gain in Adolescent Anorexia Nervosa

PubMed Central

DeGuzman, Marisa; Shott, Megan E.; Yang, Tony T.; Riederer, Justin; Frank, Guido K.W.

2017-01-01

Objective Anorexia nervosa is a psychiatric disorder of unknown etiology. Understanding associations between behavior and neurobiology is important in treatment development. Using a novel monetary reward task during functional magnetic resonance brain imaging, the authors tested how brain reward learning in adolescent anorexia nervosa changes with weight restoration. Method Female adolescents with anorexia nervosa (N=21; mean age, 15.2 years [SD=2.4]) underwent functional MRI (fMRI) before and after treatment; similarly, healthy female control adolescents (N=21; mean age, 16.4 years [SD=1.9]) underwent fMRI on two occasions. Brain function was tested using the reward prediction error construct, a computational model for reward receipt and omission related to motivation and neural dopamine responsiveness. Results Compared with the control group, the anorexia nervosa group exhibited greater brain response 1) for prediction error regression within the caudate, ventral caudate/nucleus accumbens, and anterior and posterior insula, 2) to unexpected reward receipt in the anterior and posterior insula, and 3) to unexpected reward omission in the caudate body. Prediction error and unexpected reward omission response tended to normalize with treatment, while unexpected reward receipt response remained significantly elevated. Greater caudate prediction error response when underweight was associated with lower weight gain during treatment. Punishment sensitivity correlated positively with ventral caudate prediction error response. Conclusions Reward system responsiveness is elevated in adolescent anorexia nervosa when underweight and after weight restoration. Heightened prediction error activity in brain reward regions may represent a phenotype of adolescent anorexia nervosa that does not respond well to treatment. Prediction error response could be a neurobiological marker of illness severity that can indicate individual treatment needs. PMID:28231717

Music and the nucleus accumbens.

PubMed

Mavridis, Ioannis N

2015-03-01

Music is a universal feature of human societies over time, mainly because it allows expression and regulation of strong emotions, thus influencing moods and evoking pleasure. The nucleus accumbens (NA), the most important pleasure center of the human brain (dominates the reward system), is the 'king of neurosciences' and dopamine (DA) can be rightfully considered as its 'crown' due to the fundamental role that this neurotransmitter plays in the brain's reward system. Purpose of this article was to review the existing literature regarding the relation between music and the NA. Studies have shown that reward value for music can be coded by activity levels in the NA, whose functional connectivity with auditory and frontal areas increases as a function of increasing musical reward. Listening to music strongly modulates activity in a network of mesolimbic structures involved in reward processing including the NA. The functional connectivity between brain regions mediating reward, autonomic and cognitive processing provides insight into understanding why listening to music is one of the most rewarding and pleasurable human experiences. Musical stimuli can significantly increase extracellular DA levels in the NA. NA DA and serotonin were found significantly higher in animals exposed to music. Finally, passive listening to unfamiliar although liked music showed activations in the NA.

Neuropsychology of reward learning and negative symptoms in schizophrenia.

PubMed

Nestor, Paul G; Choate, Victoria; Niznikiewicz, Margaret; Levitt, James J; Shenton, Martha E; McCarley, Robert W

2014-11-01

We used the Iowa Gambling Test (IGT) to examine the relationship of reward learning to both neuropsychological functioning and symptom formation in 65 individuals with schizophrenia. Results indicated that compared to controls, participants with schizophrenia showed significantly reduced reward learning, which in turn correlated with reduced intelligence, memory and executive function, and negative symptoms. The current findings suggested that a disease-related disturbance in reward learning may underlie both cognitive and motivation deficits, as expressed by neuropsychological impairment and negative symptoms in schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

General functioning predicts reward and punishment learning in schizophrenia.

PubMed

Somlai, Zsuzsanna; Moustafa, Ahmed A; Kéri, Szabolcs; Myers, Catherine E; Gluck, Mark A

2011-04-01

Previous studies investigating feedback-driven reinforcement learning in patients with schizophrenia have provided mixed results. In this study, we explored the clinical predictors of reward and punishment learning using a probabilistic classification learning task. Patients with schizophrenia (n=40) performed similarly to healthy controls (n=30) on the classification learning task. However, more severe negative and general symptoms were associated with lower reward-learning performance, whereas poorer general psychosocial functioning was correlated with both lower reward- and punishment-learning performances. Multiple linear regression analyses indicated that general psychosocial functioning was the only significant predictor of reinforcement learning performance when education, antipsychotic dose, and positive, negative and general symptoms were included in the analysis. These results suggest a close relationship between reinforcement learning and general psychosocial functioning in schizophrenia. Published by Elsevier B.V.

Stress and reward processing in bipolar disorder: an fMRI study

PubMed Central

Berghorst, Lisa H; Kumar, Poornima; Greve, Doug N; Deckersbach, Thilo; Ongur, Dost; Dutra, Sunny; Pizzagalli, Diego A

2016-01-01

Objectives A link between negative life stress and the onset of mood episodes in bipolar disorder (BD) has been established, but processes underlying such a link remain unclear. Growing evidence suggests that stress can negatively affect reward processing and related neurobiological substrates, indicating that a dysregulated reward system may provide a partial explanation. The aim of this study was to test the impact of stress on reward-related neural functioning in BD. Methods Thirteen euthymic or mildly depressed individuals with BD and 15 controls performed a Monetary Incentive Delay task while undergoing functional magnetic resonance imaging during no-stress and stress (negative psychosocial stressor involving poor performance feedback and threat of monetary deductions) conditions. Results In hypothesis-driven region-of- interest-based analyses, a significant group by condition interaction emerged in the amygdala during reward anticipation. Relative to controls, while anticipating a potential reward, subjects with BD were characterized by amygdalar hyperactivation in the no-stress condition but hypoactivation during stress. Moreover, relative to controls, subjects with BD had significantly larger amygdala volumes. After controlling for structural differences, the effects of stress on amygdalar function remained, whereas groups no longer differed during the no-stress condition. During reward consumption, a group by condition interaction emerged in the putamen due to increased putamen activation to rewards in participants with BD during stress, but an opposite pattern in controls. Conclusions Overall, findings highlight possible impairments in using reward-predicting cues to adaptively engage in goal-directed actions in BD, combined with stress-induced hypersensitivity to reward consumption. Potential clinical implications are discussed. PMID:27870507

Compromised Dopaminergic Encoding of Reward Accompanying Suppressed Willingness to Overcome High Effort Costs Is a Prominent Prodromal Characteristic of the Q175 Mouse Model of Huntington's Disease.

PubMed

Covey, Dan P; Dantrassy, Hannah M; Zlebnik, Natalie E; Gildish, Iness; Cheer, Joseph F

2016-05-04

Huntington's disease (HD) is a heritable neurodegenerative disorder caused by expansion of CAG (glutamine) repeats in the HTT gene. A prodromal stage characterized by psychiatric disturbances normally precedes primary motor symptoms and suppressed motivation represents one of the earliest and most common psychiatric symptoms. Although dopamine in the nucleus accumbens (NAc) critically regulates motivation and altered dopamine signaling is implicated in HD, the nature of dopaminergic deficits and contribution to symptoms in HD is poorly understood. We therefore tested whether altered NAc dopamine release accompanies motivational deficits in the Q175 knock-in HD mouse model. Q175 mice express a CAG expansion of the human mutant huntingtin allele in the native mouse genome and gradually manifest symptoms late in life, closely mimicking the genotypic context and disease progression in human HD. Sub-second extracellular dopamine release dynamics were monitored using fast-scan cyclic voltammetry, whereas motivation was assessed using a progressive ratio reinforcement schedule. As the response ratio (lever presses per reward) escalated, Q175 mice exerted less effort to earn fewer rewards versus wild-type (WT). Moreover, dopamine released at reward delivery dynamically encoded increasing reward cost in WT but not Q175 mice. Deficits were specific to situations of high effortful demand as no difference was observed in locomotion, free feeding, hedonic processing, or reward seeking when the response requirement was low. This compromised dopaminergic encoding of reward delivery coincident with suppressed motivation to work for reward in Q175 mice provides novel, neurobiological insight into an established and clinically relevant endophenotype of prodromal HD. Psychiatric impairments in Huntington's disease (HD) typically manifest early in disease progression, before motor deficits. However, the neurobiological factors contributing to psychiatric symptoms are poorly understood. We used a mouse HD model and assessed whether impaired dopamine release in the nucleus accumbens (NAc), a brain region critical to goal-directed behaviors, accompanies motivational deficits, one of the most common early HD symptoms. HD mice exhibited blunted motivation to work for food reward coincident with diminished dopamine release to reward receipt. Motivational and NAc dopaminergic deficits were not associated with gross motor deficits or impaired food seeking when effortful demands were low. This work identifies a specific prodromal HD phenotype associated with a prominent and previously unidentified neurobiological impairment. Copyright © 2016 the authors 0270-6474/16/364993-10$15.00/0.

Prenatal exposure to methylphenidate affects the dopamine system and the reactivity to natural reward in adulthood in rats.

PubMed

Lepelletier, François-Xavier; Tauber, Clovis; Nicolas, Céline; Solinas, Marcello; Castelnau, Pierre; Belzung, Catherine; Emond, Patrick; Cortese, Samuele; Faraone, Stephen V; Chalon, Sylvie; Galineau, Laurent

2014-10-31

Methylphenidate (MPH) is a commonly-used medication for the treatment of children with Attention-Deficit/Hyperactivity Disorders (ADHD). However, its prescription to adults with ADHD and narcolepsy raises the question of how the brain is impacted by MPH exposure during pregnancy. The goal of this study was to elucidate the long-term neurobiological consequences of prenatal exposure to MPH using a rat model. We focused on the effects of such treatment on the adult dopamine (DA) system and on the reactivity of animals to natural rewards. This study shows that adult male rats prenatally exposed to MPH display elevated expression of presynaptic DA markers in the DA cell bodies and the striatum. Our results also suggest that MPH-treated animals could exhibit increased tonic DA activity in the mesolimbic pathway, altered signal-to-noise ratio after a pharmacological stimulation, and decreased reactivity to the locomotor effects of cocaine. Finally, we demonstrated that MPH rats display a decreased preference and motivation for sucrose. This is the first preclinical study reporting long-lasting neurobiological alterations of DA networks as well as alterations in motivational behaviors for natural rewards after a prenatal exposure to MPH. These results raise concerns about the possible neurobiological consequences of MPH treatment during pregnancy. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Announced reward counteracts the effects of chronic social stress on anticipatory behavior and hippocampal synaptic plasticity in rats.

PubMed

Kamal, Amer; Van der Harst, Johanneke E; Kapteijn, Chantal M; Baars, Annemarie J M; Spruijt, Berry M; Ramakers, Geert M J

2010-04-01

Chronic stress causes insensitivity to rewards (anhedonia) in rats, reflected by the absence of anticipatory behavior for a sucrose-reward, which can be reversed by antidepressant treatment or repeated announced transfer to an enriched cage. It was, however, not clear whether the highly rewarding properties of the enriched cage alone caused this reversal or whether the anticipation of this reward as such had an additional effect. Therefore, the present study compared the consequences of the announcement of a reward to the mere effect of a reward alone with respect to their efficacy to counteract the consequences of chronic stress. Two forms of synaptic plasticity, long-term potentiation and long-term depression were investigated in area CA1 of the hippocampus. This was done in socially stressed rats (induced by defeat and subsequent long-term individual housing), socially stressed rats that received a reward (short-term enriched housing) and socially stressed rats to which this reward was announced by means of a stimulus that was repeatedly paired to the reward. The results were compared to corresponding control rats. We show that announcement of enriched housing appeared to have had an additional effect compared to the enriched housing per se as indicated by a significant higher amount of LTP. In conclusion, announced short-term enriched housing has a high and long-lasting counteracting efficacy on stress-induced alterations of hippocampal synaptic plasticity. This information is important for counteracting the consequences of chronic stress in both human and captive rats.

Interaction between COMT Val(158)Met polymorphism and childhood adversity affects reward processing in adulthood.

PubMed

Boecker-Schlier, Regina; Holz, Nathalie E; Buchmann, Arlette F; Blomeyer, Dorothea; Plichta, Michael M; Jennen-Steinmetz, Christine; Wolf, Isabella; Baumeister, Sarah; Treutlein, Jens; Rietschel, Marcella; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

2016-05-15

Accumulating evidence suggests that altered dopamine transmission may increase the risk of mental disorders such as ADHD, schizophrenia or depression, possibly mediated by reward system dysfunction. This study aimed to clarify the impact of the COMT Val(158)Met polymorphism in interaction with environmental variation (G×E) on neuronal activity during reward processing. 168 healthy young adults from a prospective study conducted over 25years participated in a monetary incentive delay task measured with simultaneous EEG-fMRI. DNA was genotyped for COMT, and childhood family adversity (CFA) up to age 11 was assessed by a standardized parent interview. At reward delivery, a G×E revealed that fMRI activation for win vs. no-win trials in reward-related regions increased with the level of CFA in Met homozygotes as compared to Val/Met heterozygotes and Val homozygotes, who showed no significant effect. During the anticipation of monetary vs. verbal rewards, activation decreased with the level of CFA, which was also observed for EEG, in which the CNV declined with the level of CFA. These results identify convergent genetic and environmental effects on reward processing in a prospective study. Moreover, G×E effects during reward delivery suggest that stress during childhood is associated with higher reward sensitivity and reduced efficiency in processing rewarding stimuli in genetically at-risk individuals. Together with previous evidence, these results begin to define a specific system mediating interacting effects of early environmental and genetic risk factors, which may be targeted by early intervention and prevention. Copyright © 2016 Elsevier Inc. All rights reserved.

Mapping anhedonia onto reinforcement learning: a behavioural meta-analysis

PubMed Central

2013-01-01

Background Depression is characterised partly by blunted reactions to reward. However, tasks probing this deficiency have not distinguished insensitivity to reward from insensitivity to the prediction errors for reward that determine learning and are putatively reported by the phasic activity of dopamine neurons. We attempted to disentangle these factors with respect to anhedonia in the context of stress, Major Depressive Disorder (MDD), Bipolar Disorder (BPD) and a dopaminergic challenge. Methods Six behavioural datasets involving 392 experimental sessions were subjected to a model-based, Bayesian meta-analysis. Participants across all six studies performed a probabilistic reward task that used an asymmetric reinforcement schedule to assess reward learning. Healthy controls were tested under baseline conditions, stress or after receiving the dopamine D2 agonist pramipexole. In addition, participants with current or past MDD or BPD were evaluated. Reinforcement learning models isolated the contributions of variation in reward sensitivity and learning rate. Results MDD and anhedonia reduced reward sensitivity more than they affected the learning rate, while a low dose of the dopamine D2 agonist pramipexole showed the opposite pattern. Stress led to a pattern consistent with a mixed effect on reward sensitivity and learning rate. Conclusion Reward-related learning reflected at least two partially separable contributions. The first related to phasic prediction error signalling, and was preferentially modulated by a low dose of the dopamine agonist pramipexole. The second related directly to reward sensitivity, and was preferentially reduced in MDD and anhedonia. Stress altered both components. Collectively, these findings highlight the contribution of model-based reinforcement learning meta-analysis for dissecting anhedonic behavior. PMID:23782813

A transient dopamine signal encodes subjective value and causally influences demand in an economic context

PubMed Central

Schelp, Scott A.; Pultorak, Katherine J.; Rakowski, Dylan R.; Gomez, Devan M.; Krzystyniak, Gregory; Das, Raibatak; Oleson, Erik B.

2017-01-01

The mesolimbic dopamine system is strongly implicated in motivational processes. Currently accepted theories suggest that transient mesolimbic dopamine release events energize reward seeking and encode reward value. During the pursuit of reward, critical associations are formed between the reward and cues that predict its availability. Conditioned by these experiences, dopamine neurons begin to fire upon the earliest presentation of a cue, and again at the receipt of reward. The resulting dopamine concentration scales proportionally to the value of the reward. In this study, we used a behavioral economics approach to quantify how transient dopamine release events scale with price and causally alter price sensitivity. We presented sucrose to rats across a range of prices and modeled the resulting demand curves to estimate price sensitivity. Using fast-scan cyclic voltammetry, we determined that the concentration of accumbal dopamine time-locked to cue presentation decreased with price. These data confirm and extend the notion that dopamine release events originating in the ventral tegmental area encode subjective value. Using optogenetics to augment dopamine concentration, we found that enhancing dopamine release at cue made demand more sensitive to price and decreased dopamine concentration at reward delivery. From these observations, we infer that value is decreased because of a negative reward prediction error (i.e., the animal receives less than expected). Conversely, enhancing dopamine at reward made demand less sensitive to price. We attribute this finding to a positive reward prediction error, whereby the animal perceives they received a better value than anticipated. PMID:29109253

Improving control over the impulse for reward: sensitivity of harmful alcohol drinkers to delayed reward but not immediate punishment.

PubMed

Rossiter, Sarah; Thompson, Julian; Hester, Robert

2012-09-01

Cognitive control dysfunction has been identified in dependent alcohol users and implicated in the transition from abuse to dependence, although evidence of dyscontrol in chronic but non-dependent 'harmful' alcohol abusers is mixed. The current study examined harmful alcohol users response inhibition over rewarding stimuli in the presence of monetary reward and punishment, to determine whether changes in sensitivity to these factors, noted in imaging studies of dependent users, influences impulse control. Harmful (n=30) and non-hazardous (n=55) alcohol users were administered a Monetary Incentive Go/No-go task that required participants to inhibit a prepotent motor response associated with reward. Harmful alcohol users showed a significantly poorer ability to withhold their impulse for a rewarding stimulus in the presence of immediate monetary punishment for failure, while retaining equivalent response inhibition performance under neutral conditions (associated with neither monetary loss or gain), and significantly better performance under delayed reward conditions. The results of the present study suggest that non-dependent alcohol abusers have altered sensitivity to reward and punishment that influences their impulse control for reward, in the absence of gross dyscontrol that is consistent with past findings in which such performance contingencies were not used. The ability of delayed monetary reward, but not punishment, to increase sustained impulse control in this sample has implications for the mechanism that might underlie the transition from alcohol abuse to dependence, as well as intervention strategies aimed at preventing this transition. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Repeated intermittent administration of psychomotor stimulant drugs alters the acquisition of Pavlovian approach behavior in rats: differential effects of cocaine, d-amphetamine and 3,4- methylenedioxymethamphetamine ("Ecstasy").

PubMed

Taylor, J R; Jentsch, J D

2001-07-15

Psychomotor stimulant drugs can produce long-lasting changes in neurochemistry and behavior after multiple doses. In particular, neuroadaptations within corticolimbic brain structures that mediate incentive learning and motivated behavior have been demonstrated after chronic exposure to cocaine, d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). As stimulus-reward learning is likely relevant to addictive behavior (i.e., augmented conditioned reward and stimulus control of behavior), we have investigated whether prior repeated administration of psychomotor stimulant drugs (of abuse, including cocaine, d-amphetamine, or MDMA, would affect the acquisition of Pavlovian approach behavior. Water-deprived rats were tested for the acquisition of Pavlovian approach behavior after 5 days treatment with cocaine (15-20 mg/kg once or twice daily), d-amphetamine (2.5 mg/kg once or twice daily), or MDMA (2.5 mg/kg twice daily) followed by a 7-day, drug-free period. Prior repeated treatment with cocaine or d-amphetamine produced a significant enhancement of acquisition of Pavlovian approach behavior, indicating accelerated stimulus-reward learning, whereas MDMA administration produced increased inappropriate responding, indicating impulsivity. Abnormal drug-induced approach behavior was found to persist throughout the testing period. These studies demonstrate that psychomotor stimulant-induced sensitization can produce long-term alterations in stimulus-reward learning and impulse control that may contribute to the compulsive drug taking that typifies addiction.

Reward prediction error signal enhanced by striatum-amygdala interaction explains the acceleration of probabilistic reward learning by emotion.

PubMed

Watanabe, Noriya; Sakagami, Masamichi; Haruno, Masahiko

2013-03-06

Learning does not only depend on rationality, because real-life learning cannot be isolated from emotion or social factors. Therefore, it is intriguing to determine how emotion changes learning, and to identify which neural substrates underlie this interaction. Here, we show that the task-independent presentation of an emotional face before a reward-predicting cue increases the speed of cue-reward association learning in human subjects compared with trials in which a neutral face is presented. This phenomenon was attributable to an increase in the learning rate, which regulates reward prediction errors. Parallel to these behavioral findings, functional magnetic resonance imaging demonstrated that presentation of an emotional face enhanced reward prediction error (RPE) signal in the ventral striatum. In addition, we also found a functional link between this enhanced RPE signal and increased activity in the amygdala following presentation of an emotional face. Thus, this study revealed an acceleration of cue-reward association learning by emotion, and underscored a role of striatum-amygdala interactions in the modulation of the reward prediction errors by emotion.

Reward and Aversion.

PubMed

Hu, Hailan

2016-07-08

To benefit from opportunities and cope with challenges in the environment, animals must adapt their behavior to acquire rewards and to avoid punishments. Maladaptive changes in the neuromodulatory systems and neural circuits for reward and aversion can lead to manifestation of several prominent psychiatric disorders including addiction and depression. Recent progress is pushing the boundaries of knowledge on two major fronts in research on reward and aversion: First, new layers of complexity have been reported on the functions of dopamine (DA) and serotonin (5-HT) neuromodulatory systems in reward and aversion. Second, specific circuit components in the neural pathways that encode reward and aversion have begun to be identified. This review aims to outline historic perspectives and new insights into the functions of DA and 5-HT systems in coding the distinct components of rewards. It also highlights recent advances in neural circuit studies enabled by new technologies, such as cell-type-specific electrophysiology and tracing, and optogenetics-based behavioral manipulation. This knowledge may provide guidance for developing novel treatment strategies for neuropsychiatric diseases related to the malfunction of the reward system.

Reward circuitry in resilience to severe trauma: An fMRI investigation of resilient special forces soldiers

PubMed Central

Vythilingam, Meena; Nelson, Eric E.; Scaramozza, Matthew; Waldeck, Tracy; Hazlett, Gary; Southwick, Steven M.; Pine, Daniel S.; Drevets, Wayne; Charney, Dennis S.; Ernst, Monique

2008-01-01

Enhanced brain reward function could contribute to resilience to trauma. Reward circuitry in active duty, resilient special forces (SF) soldiers was evaluated using fMRI during a monetary incentive delay task. Findings in this group of resilient individuals revealed unique patterns of activation during expectation of reward in the subgenual prefrontal cortex and nucleus accumbens area; regions pivotal to reward processes. PMID:19243926

Obese adults have visual attention bias for food cue images: evidence for altered reward system function.

PubMed

Castellanos, E H; Charboneau, E; Dietrich, M S; Park, S; Bradley, B P; Mogg, K; Cowan, R L

2009-09-01

The major aim of this study was to investigate whether the motivational salience of food cues (as reflected by their attention-grabbing properties) differs between obese and normal-weight subjects in a manner consistent with altered reward system function in obesity. A total of 18 obese and 18 normal-weight, otherwise healthy, adult women between the ages of 18 and 35 participated in an eye-tracking paradigm in combination with a visual probe task. Eye movements and reaction time to food and non-food images were recorded during both fasted and fed conditions in a counterbalanced design. Eating behavior and hunger level were assessed by self-report measures. Obese individuals had higher scores than normal-weight individuals on self-report measures of responsiveness to external food cues and vulnerability to disruptions in control of eating behavior. Both obese and normal-weight individuals demonstrated increased gaze duration for food compared to non-food images in the fasted condition. In the fed condition, however, despite reduced hunger in both groups, obese individuals maintained the increased attention to food images, whereas normal-weight individuals had similar gaze duration for food and non-food images. Additionally, obese individuals had preferential orienting toward food images at the onset of each image. Obese and normal-weight individuals did not differ in reaction time measures in the fasted or fed condition. Food cue incentive salience is elevated equally in normal-weight and obese individuals during fasting. Obese individuals retain incentive salience for food cues despite feeding and decreased self-report of hunger. Sensitization to food cues in the environment and their dysregulation in obese individuals may play a role in the development and/or maintenance of obesity.

Neural connectivity during reward expectation dissociates psychopathic criminals from non-criminal individuals with high impulsive/antisocial psychopathic traits

PubMed Central

von Borries, Katinka; Volman, Inge; Bulten, Berend Hendrik; Cools, Roshan; Verkes, Robbert-Jan

2016-01-01

Criminal behaviour poses a big challenge for society. A thorough understanding of the neurobiological mechanisms underlying criminality could optimize its prevention and management. Specifically,elucidating the neural mechanisms underpinning reward expectation might be pivotal to understanding criminal behaviour. So far no study has assessed reward expectation and its mechanisms in a criminal sample. To fill this gap, we assessed reward expectation in incarcerated, psychopathic criminals. We compared this group to two groups of non-criminal individuals: one with high levels and another with low levels of impulsive/antisocial traits. Functional magnetic resonance imaging was used to quantify neural responses to reward expectancy. Psychophysiological interaction analyses were performed to examine differences in functional connectivity patterns of reward-related regions. The data suggest that overt criminality is characterized, not by abnormal reward expectation per se, but rather by enhanced communication between reward-related striatal regions and frontal brain regions. We establish that incarcerated psychopathic criminals can be dissociated from non-criminal individuals with comparable impulsive/antisocial personality tendencies based on the degree to which reward-related brain regions interact with brain regions that control behaviour. The present results help us understand why some people act according to their impulsive/antisocial personality while others are able to behave adaptively despite reward-related urges. PMID:27217111

Enriched Encoding: Reward Motivation Organizes Cortical Networks for Hippocampal Detection of Unexpected Events

PubMed Central

Murty, Vishnu P.; Adcock, R. Alison

2014-01-01

Learning how to obtain rewards requires learning about their contexts and likely causes. How do long-term memory mechanisms balance the need to represent potential determinants of reward outcomes with the computational burden of an over-inclusive memory? One solution would be to enhance memory for salient events that occur during reward anticipation, because all such events are potential determinants of reward. We tested whether reward motivation enhances encoding of salient events like expectancy violations. During functional magnetic resonance imaging, participants performed a reaction-time task in which goal-irrelevant expectancy violations were encountered during states of high- or low-reward motivation. Motivation amplified hippocampal activation to and declarative memory for expectancy violations. Connectivity of the ventral tegmental area (VTA) with medial prefrontal, ventrolateral prefrontal, and visual cortices preceded and predicted this increase in hippocampal sensitivity. These findings elucidate a novel mechanism whereby reward motivation can enhance hippocampus-dependent memory: anticipatory VTA-cortical–hippocampal interactions. Further, the findings integrate literatures on dopaminergic neuromodulation of prefrontal function and hippocampus-dependent memory. We conclude that during reward motivation, VTA modulation induces distributed neural changes that amplify hippocampal signals and records of expectancy violations to improve predictions—a potentially unique contribution of the hippocampus to reward learning. PMID:23529005

Distinct representations for shifts of spatial attention and changes of reward contingencies in the human brain.

PubMed

Tosoni, Annalisa; Shulman, Gordon L; Pope, Anna L W; McAvoy, Mark P; Corbetta, Maurizio

2013-06-01

Success in a dynamically changing world requires both rapid shifts of attention to the location of important objects and the detection of changes in motivational contingencies that may alter future behavior. Here we addressed the relationship between these two processes by measuring the blood-oxygenation-level-dependent (BOLD) signal during a visual search task in which the location and the color of a salient cue respectively indicated where a rewarded target would appear and the monetary gain (large or small) associated with its detection. While cues that either shifted or maintained attention were presented every 4 to 8 sec, the reward magnitude indicated by the cue changed roughly every 30 sec, allowing us to distinguish a change in expected reward magnitude from a maintained state of expected reward magnitude. Posterior cingulate cortex was modulated by cues signaling an increase in expected reward magnitude, but not by cues for shifting versus maintaining spatial attention. Dorsal fronto-parietal regions in precuneus and frontal eye field (FEF) also showed increased BOLD activity for changes in expected reward magnitude from low to high, but in addition showed large independent modulations for shifting versus maintaining attention. In particular, the differential activation for shifting versus maintaining attention was not affected by expected reward magnitude. These results indicate that BOLD activations for shifts of attention and increases in expected reward magnitude are largely separate. Finally, visual cortex showed sustained spatially selective signals that were significantly enhanced when greater reward magnitude was expected, but this reward-related modulation was not observed in spatially selective regions of dorsal fronto-parietal cortex. Copyright © 2012 Elsevier Ltd. All rights reserved.

Long-term voluntary wheel running is rewarding and produces plasticity in the mesolimbic reward pathway.

PubMed

Greenwood, Benjamin N; Foley, Teresa E; Le, Tony V; Strong, Paul V; Loughridge, Alice B; Day, Heidi E W; Fleshner, Monika

2011-03-01

The mesolimbic reward pathway is implicated in stress-related psychiatric disorders and is a potential target of plasticity underlying the stress resistance produced by repeated voluntary exercise. It is unknown, however, whether rats find long-term access to running wheels rewarding, or if repeated voluntary exercise reward produces plastic changes in mesolimbic reward neurocircuitry. In the current studies, young adult, male Fischer 344 rats allowed voluntary access to running wheels for 6 weeks, but not 2 weeks, found wheel running rewarding, as measured by conditioned place preference (CPP). Consistent with prior reports and the behavioral data, 6 weeks of wheel running increased ΔFosB/FosB immunoreactivity in the nucleus accumbens (Acb). In addition, semi quantitative in situ hybridization revealed that 6 weeks of wheel running, compared to sedentary housing, increased tyrosine hydroxylase (TH) mRNA levels in the ventral tegmental area (VTA), increased delta opioid receptor (DOR) mRNA levels in the Acb shell, and reduced levels of dopamine receptor (DR)-D2 mRNA in the Acb core. Results indicate that repeated voluntary exercise is rewarding and alters gene transcription in mesolimbic reward neurocircuitry. The duration-dependent effects of wheel running on CPP suggest that as the weeks of wheel running progress, the rewarding effects of a night of voluntary wheel running might linger longer into the inactive cycle thus providing stronger support for CPP. The observed plasticity could contribute to the mechanisms by which exercise reduces the incidence and severity of substance abuse disorders, changes the rewarding properties of drugs of abuse, and facilitates successful coping with stress. Copyright © 2010 Elsevier B.V. All rights reserved.

Individual differences in sensitivity to reward and punishment and neural activity during reward and avoidance learning.

PubMed

Kim, Sang Hee; Yoon, HeungSik; Kim, Hackjin; Hamann, Stephan

2015-09-01

In this functional neuroimaging study, we investigated neural activations during the process of learning to gain monetary rewards and to avoid monetary loss, and how these activations are modulated by individual differences in reward and punishment sensitivity. Healthy young volunteers performed a reinforcement learning task where they chose one of two fractal stimuli associated with monetary gain (reward trials) or avoidance of monetary loss (avoidance trials). Trait sensitivity to reward and punishment was assessed using the behavioral inhibition/activation scales (BIS/BAS). Functional neuroimaging results showed activation of the striatum during the anticipation and reception periods of reward trials. During avoidance trials, activation of the dorsal striatum and prefrontal regions was found. As expected, individual differences in reward sensitivity were positively associated with activation in the left and right ventral striatum during reward reception. Individual differences in sensitivity to punishment were negatively associated with activation in the left dorsal striatum during avoidance anticipation and also with activation in the right lateral orbitofrontal cortex during receiving monetary loss. These results suggest that learning to attain reward and learning to avoid loss are dependent on separable sets of neural regions whose activity is modulated by trait sensitivity to reward or punishment. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Encoding of reward expectation by monkey anterior insular neurons

PubMed Central

Mizuhiki, Takashi; Richmond, Barry J.

2012-01-01

The insula, a cortical brain region that is known to encode information about autonomic, visceral, and olfactory functions, has recently been shown to encode information during reward-seeking tasks in both single neuronal recording and functional magnetic resonance imaging studies. To examine the reward-related activation, we recorded from 170 single neurons in anterior insula of 2 monkeys during a multitrial reward schedule task, where the monkeys had to complete a schedule of 1, 2, 3, or 4 trials to earn a reward. In one block of trials a visual cue indicated whether a reward would or would not be delivered in the current trial after the monkey successfully detected that a red spot turned green, and in other blocks the visual cue was random with respect to reward delivery. Over one-quarter of 131 responsive neurons were activated when the current trial would (certain or uncertain) be rewarded if performed correctly. These same neurons failed to respond in trials that were certain, as indicated by the cue, to be unrewarded. Another group of neurons responded when the reward was delivered, similar to results reported previously. The dynamics of population activity in anterior insula also showed strong signals related to knowing when a reward is coming. The most parsimonious explanation is that this activity codes for a type of expected outcome, where the expectation encompasses both certain and uncertain rewards. PMID:22402653

Association Between Reward Reactivity and Drug Use Severity is Substance Dependent: Preliminary Evidence From the Human Connectome Project.

PubMed

Peechatka, Alyssa L; Janes, Amy C

2017-06-01

Blunted nucleus accumbens (NAc) reactivity to reward is common across drug users. One theory is that individuals abuse substances due to this reward deficit. However, whether there is a relationship between the amount an individual uses and the severity of NAc dysfunction is unclear. It also is possible that such a relationship is substance specific, as nicotine transiently increases reward system sensitivity while alcohol, another commonly used substance, does not. As smokers may use nicotine to bolster NAc reward function, we hypothesize that NAc reactivity to reward will be related to volume of cigarette use, but not volume of alcohol use. A functional magnetic resonance imaging incentive-processing task collected by the Human Connectome Project was assessed in a cohort of tobacco smokers who reported smoking between 5-20 cigarettes/day and a cohort of alcohol users who reported drinking 7-25 drinks/wk. Number of cigarettes/day and drinks/wk were correlated with right and left NAc reactivity to the receipt of a monetary reward relative to baseline. Individuals who smoke greater numbers of cigarettes/day showed lower right NAc reactivity to reward (r = 0.853, p ≤ .001). Left NAc reactivity was not correlated with cigarettes/day. No association was found with drinks/wk. A negative association was found between NAc reactivity to reward and cigarettes/day, but not alcohol drinks/wk. Given nicotine's unique ability to increase sensitivity to rewards, these findings suggest that individuals who smoke more cigarettes/day may be compensating for more dysfunctional NAc reward reactivity. The present study demonstrates that a relationship between NAc reactivity to nondrug reward and volume of substance use is present in nicotine but not alcohol use. While prior work has implicated dysfunctional reward processing in addictions, these findings clarify a substance-specific role that blunted reward function has in determining patterns of use among chronic users. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Reward-Based Spatial Learning in Teens With Bulimia Nervosa.

PubMed

Cyr, Marilyn; Wang, Zhishun; Tau, Gregory Z; Zhao, Guihu; Friedl, Eve; Stefan, Mihaela; Terranova, Kate; Marsh, Rachel

2016-11-01

To assess the functioning of mesolimbic and fronto-striatal areas involved in reward-based spatial learning in teenaged girls with bulimia nervosa (BN) that might be involved in the development and maintenance of maladaptive behaviors characteristic of the disorder. We compared functional magnetic resonance imaging blood oxygen level-dependent response in 27 adolescent girls with BN to that of 27 healthy, age-matched control participants during a reward-based learning task that required learning to use extra-maze cues to navigate a virtual 8-arm radial maze to find hidden rewards. We compared groups in their patterns of brain activation associated with reward-based spatial learning versus a control condition in which rewards were unexpected because they were allotted pseudo-randomly to experimentally prevent learning. Both groups learned to navigate the maze to find hidden rewards, but group differences in brain activity associated with maze navigation and reward processing were detected in the fronto-striatal regions and right anterior hippocampus. Unlike healthy adolescents, those with BN did not engage the right inferior frontal gyrus during maze navigation, activated the right anterior hippocampus during the receipt of unexpected rewards (control condition), and deactivated the left superior frontal gyrus and right anterior hippocampus during expected reward receipt (learning condition). These patterns of hippocampal activation in the control condition were significantly associated with the frequency of binge-eating episodes. Adolescents with BN displayed abnormal functioning of the anterior hippocampus and fronto-striatal regions during reward-based spatial learning. These findings suggest that an imbalance in control and reward circuits may arise early in the course of BN. Clinical trial registration information-An fMRI Study of Self-Regulation in Adolescents With Bulimia Nervosa; https://clinicaltrials.gov/; NCT00345943. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Neural correlates of reward-based spatial learning in persons with cocaine dependence.

PubMed

Tau, Gregory Z; Marsh, Rachel; Wang, Zhishun; Torres-Sanchez, Tania; Graniello, Barbara; Hao, Xuejun; Xu, Dongrong; Packard, Mark G; Duan, Yunsuo; Kangarlu, Alayar; Martinez, Diana; Peterson, Bradley S

2014-02-01

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.

Cholinergic Mesopontine Signals Govern Locomotion and Reward Through Dissociable Midbrain Pathways

PubMed Central

Xiao, Cheng; Cho, Jounhong Ryan; Zhou, Chunyi; Treweek, Jennifer B.; Chan, Ken; McKinney, Sheri L.; Yang, Bin; Gradinaru, Viviana

2016-01-01

The mesopontine tegmentum, including the pedunculopontine and laterodorsal tegmental nuclei (PPN and LDT), provides major cholinergic inputs to midbrain and regulates locomotion and reward. To delineate the underlying projection-specific circuit mechanisms we employed optogenetics to control mesopontine cholinergic neurons at somata and at divergent projections within distinct midbrain areas. Bidirectional manipulation of PPN cholinergic cell bodies exerted opposing effects on locomotor behavior and reinforcement learning. These motor and reward effects were separable via limiting photostimulation to PPN cholinergic terminals in the ventral substantia nigra pars compacta (vSNc) or to the ventral tegmental area (VTA), respectively. LDT cholinergic neurons also form connections with vSNc and VTA neurons, however although photo-excitation of LDT cholinergic terminals in the VTA caused positive reinforcement, LDT-to-vSNc modulation did not alter locomotion or reward. Therefore, the selective targeting of projection-specific mesopontine cholinergic pathways may offer increased benefit in treating movement and addiction disorders. PMID:27100197

Do Effort and Reward at Work Predict Changes in Cognitive Function? First Longitudinal Results from the Representative German Socio-Economic Panel

PubMed Central

Riedel, Natalie; Siegrist, Johannes; Wege, Natalia; Loerbroks, Adrian; Angerer, Peter; Li, Jian

2017-01-01

It has been suggested that work characteristics, such as mental demands, job control, and occupational complexity, are prospectively related to cognitive function. However, current evidence on links between psychosocial working conditions and cognitive change over time is inconsistent. In this study, we applied the effort–reward imbalance model that allows to build on previous research on mental demands and to introduce reward-based learning as a principle with beneficial effect on cognitive function. We aimed to investigate whether high effort, high reward, and low over-commitment in 2006 were associated with positive changes in cognitive function in terms of perceptual speed and word fluency (2006–2012), and whether the co-manifestation of high effort and high reward would yield the strongest association. To this end, we used data on 1031 employees who participated in a large and representative study. Multivariate linear regression analyses supported our main hypotheses (separate and combined effects of effort and reward), particularly on changes in perceptual speed, whereas the effects of over-commitment did not reach the level of statistical significance. Our findings extend available knowledge by examining the course of cognitive function over time. If corroborated by further evidence, organization-based measures in the workplace can enrich efforts towards preventing cognitive decline in ageing workforces. PMID:29140258

The joint effect of tangible and non-tangible rewards on healthy food choices in children.

PubMed

Grubliauskiene, Aiste; Verhoeven, Maxime; Dewitte, Siegfried

2012-10-01

This study investigated how a combination of tangible and non-tangible rewards can alter health-related decisions made by children. Children chose between an unhealthy food option (a bowl of potato crisps) and a healthy food option (a bowl of grapes) on two occasions. In the first round, we manipulated the expected tangible reward and praise. The tangible reward was manipulated by means of a game that the child received upon choosing the healthy product, and the praise was manipulated by means of the teacher's applause and smiles if the child selected the healthy option. The second trial occurred three days after the first trial using the same food item options. Neither tangible rewards nor praise influenced the children's choices by themselves, but combining the two substantially increased the children's likelihood of selecting the healthy food choice. The data were consistent with a reattribution process akin to social labelling. Although initially externally motivated to select the healthy option, the children who received praise appeared to interpret their choice as internally motivated and therefore continued to select the healthy option even in the absence of reward. Copyright © 2012 Elsevier Ltd. All rights reserved.

Comparing the effects of food restriction and overeating on brain reward systems.

PubMed

Avena, Nicole M; Murray, Susan; Gold, Mark S

2013-10-01

Both caloric restriction and overeating have been shown to affect neural processes associated with reinforcement. Both preclinical and some clinical studies have provided evidence that food restriction may increase reward sensitivity, and while there are mixed findings regarding the effects of overeating on reward sensitivity, there is strong evidence linking this behavior with changes in reward-related brain regions. Evidence of these changes comes in part from findings that show that such eating patterns are associated with increased drug use. The data discussed here regarding the differential effects of various eating patterns on reward systems may be particularly relevant to the aging population, as this population has been shown to exhibit altered reward sensitivity and decreased caloric consumption. Moreover, members of this population appear to be increasingly affected by the current obesity epidemic. Food, like alcohol or drugs, can stimulate its own consumption and produce similar neurochemical changes in the brain. Age-related loss of appetite, decreased eating, and caloric restriction are hypothesized to be associated with changes in the prevalence of substance misuse, abuse, and dependence seen in this cohort. Copyright © 2013 Elsevier Inc. All rights reserved.

Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer's disease.

PubMed

Muñoz-Moreno, Emma; Tudela, Raúl; López-Gil, Xavier; Soria, Guadalupe

2018-02-07

Animal models of Alzheimer's disease (AD) are essential to understanding the disease progression and to development of early biomarkers. Because AD has been described as a disconnection syndrome, magnetic resonance imaging (MRI)-based connectomics provides a highly translational approach to characterizing the disruption in connectivity associated with the disease. In this study, a transgenic rat model of AD (TgF344-AD) was analyzed to describe both cognitive performance and brain connectivity at an early stage (5 months of age) before a significant concentration of β-amyloid plaques is present. Cognitive abilities were assessed by a delayed nonmatch-to-sample (DNMS) task preceded by a training phase where the animals learned the task. The number of training sessions required to achieve a learning criterion was recorded and evaluated. After DNMS, MRI acquisition was performed, including diffusion-weighted MRI and resting-state functional MRI, which were processed to obtain the structural and functional connectomes, respectively. Global and regional graph metrics were computed to evaluate network organization in both transgenic and control rats. The results pointed to a delay in learning the working memory-related task in the AD rats, which also completed a lower number of trials in the DNMS task. Regarding connectivity properties, less efficient organization of the structural brain networks of the transgenic rats with respect to controls was observed. Specific regional differences in connectivity were identified in both structural and functional networks. In addition, a strong correlation was observed between cognitive performance and brain networks, including whole-brain structural connectivity as well as functional and structural network metrics of regions related to memory and reward processes. In this study, connectivity and neurocognitive impairments were identified in TgF344-AD rats at a very early stage of the disease when most of the pathological hallmarks have not yet been detected. Structural and functional network metrics of regions related to reward, memory, and sensory performance were strongly correlated with the cognitive outcome. The use of animal models is essential for the early identification of these alterations and can contribute to the development of early biomarkers of the disease based on MRI connectomics.