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Sample records for dopaminergic reward regions

  1. Cocaine abstinence following chronic treatment alters cerebral metabolism in dopaminergic reward regions. Bromocriptine enhances recovery

    International Nuclear Information System (INIS)

    Clow, D.W.; Hammer, R.P. Jr.

    1991-01-01

    2-[14C]deoxyglucose autoradiography was used to determine local cerebral glucose utilization (lCGU) in rats following chronic cocaine treatment and subsequent abstinence. lCGU was examined in 43 discrete brain regions in animals which had received daily injections of cocaine for 14 days (10 mg/kg) followed by 3 days of saline or bromocriptine (10 mg/kg) treatment. Cocaine abstinence following chronic treatment significantly reduced lCGU in several regions including mesocorticolimbic structures such as ventral tegmental area, medial prefrontal cortex, and nucleus accumbens (NAc). Within the NAc, however, only the rostral pole showed significant reduction. In contrast, when bromocriptine treatment accompanied abstinence, lCGU was no longer reduced in mesocorticolimbic and most other regions, implying that metabolic recovery was enhanced by bromocriptine treatment during early abstinence following chronic cocaine treatment. These data suggest that cerebral metabolism is decreased during cocaine abstinence following chronic treatment in critical brain regions, and that this alteration can be prevented by treatment with direct-acting dopamine agonists such as bromocriptine

  2. Cocaine abstinence following chronic treatment alters cerebral metabolism in dopaminergic reward regions. Bromocriptine enhances recovery

    Energy Technology Data Exchange (ETDEWEB)

    Clow, D.W.; Hammer, R.P. Jr. (Univ. of Hawaii School of Medicine, Honolulu (USA))

    1991-01-01

    2-(14C)deoxyglucose autoradiography was used to determine local cerebral glucose utilization (lCGU) in rats following chronic cocaine treatment and subsequent abstinence. lCGU was examined in 43 discrete brain regions in animals which had received daily injections of cocaine for 14 days (10 mg/kg) followed by 3 days of saline or bromocriptine (10 mg/kg) treatment. Cocaine abstinence following chronic treatment significantly reduced lCGU in several regions including mesocorticolimbic structures such as ventral tegmental area, medial prefrontal cortex, and nucleus accumbens (NAc). Within the NAc, however, only the rostral pole showed significant reduction. In contrast, when bromocriptine treatment accompanied abstinence, lCGU was no longer reduced in mesocorticolimbic and most other regions, implying that metabolic recovery was enhanced by bromocriptine treatment during early abstinence following chronic cocaine treatment. These data suggest that cerebral metabolism is decreased during cocaine abstinence following chronic treatment in critical brain regions, and that this alteration can be prevented by treatment with direct-acting dopamine agonists such as bromocriptine.

  3. Hemispheric Asymmetries in Striatal Reward Responses Relate to Approach-Avoidance Learning and Encoding of Positive-Negative Prediction Errors in Dopaminergic Midbrain Regions.

    Science.gov (United States)

    Aberg, Kristoffer Carl; Doell, Kimberly C; Schwartz, Sophie

    2015-10-28

    Some individuals are better at learning about rewarding situations, whereas others are inclined to avoid punishments (i.e., enhanced approach or avoidance learning, respectively). In reinforcement learning, action values are increased when outcomes are better than predicted (positive prediction errors [PEs]) and decreased for worse than predicted outcomes (negative PEs). Because actions with high and low values are approached and avoided, respectively, individual differences in the neural encoding of PEs may influence the balance between approach-avoidance learning. Recent correlational approaches also indicate that biases in approach-avoidance learning involve hemispheric asymmetries in dopamine function. However, the computational and neural mechanisms underpinning such learning biases remain unknown. Here we assessed hemispheric reward asymmetry in striatal activity in 34 human participants who performed a task involving rewards and punishments. We show that the relative difference in reward response between hemispheres relates to individual biases in approach-avoidance learning. Moreover, using a computational modeling approach, we demonstrate that better encoding of positive (vs negative) PEs in dopaminergic midbrain regions is associated with better approach (vs avoidance) learning, specifically in participants with larger reward responses in the left (vs right) ventral striatum. Thus, individual dispositions or traits may be determined by neural processes acting to constrain learning about specific aspects of the world. Copyright © 2015 the authors 0270-6474/15/3514491-10$15.00/0.

  4. Do Substantia Nigra Dopaminergic Neurons Differentiate Between Reward and Punishment?

    Institute of Scientific and Technical Information of China (English)

    Michael J. Frank; D. James Surmeier

    2009-01-01

    The activity of dopaminergic neurons are thought to be increased by stimuli that predict reward and decreased by stimuli that predict aversive outcomes. Recent work by Matsumoto and Hikosaka challenges this model by asserting that stimuli associated with either rewarding or aversive outcomes increase the activity of dopaminergic neurons in the substantia nigra pars compacta.

  5. Influence of dopaminergically mediated reward on somatosensory decision-making.

    Directory of Open Access Journals (Sweden)

    Burkhard Pleger

    2009-07-01

    Full Text Available Reward-related dopaminergic influences on learning and overt behaviour are well established, but any influence on sensory decision-making is largely unknown. We used functional magnetic resonance imaging (fMRI while participants judged electric somatosensory stimuli on one hand or other, before being rewarded for correct performance at trial end via a visual signal, at one of four anticipated financial levels. Prior to the procedure, participants received either placebo (saline, a dopamine agonist (levodopa, or an antagonist (haloperidol.higher anticipated reward improved tactile decisions. Visually signalled reward reactivated primary somatosensory cortex for the judged hand, more strongly for higher reward. After receiving a higher reward on one trial, somatosensory activations and decisions were enhanced on the next trial. These behavioural and neural effects were all enhanced by levodopa and attenuated by haloperidol, indicating dopaminergic dependency. Dopaminergic reward-related influences extend even to early somatosensory cortex and sensory decision-making.

  6. Sweet taste and nutrient value subdivide rewarding dopaminergic neurons in Drosophila.

    Science.gov (United States)

    Huetteroth, Wolf; Perisse, Emmanuel; Lin, Suewei; Klappenbach, Martín; Burke, Christopher; Waddell, Scott

    2015-03-16

    Dopaminergic neurons provide reward learning signals in mammals and insects [1-4]. Recent work in Drosophila has demonstrated that water-reinforcing dopaminergic neurons are different to those for nutritious sugars [5]. Here, we tested whether the sweet taste and nutrient properties of sugar reinforcement further subdivide the fly reward system. We found that dopaminergic neurons expressing the OAMB octopamine receptor [6] specifically convey the short-term reinforcing effects of sweet taste [4]. These dopaminergic neurons project to the β'2 and γ4 regions of the mushroom body lobes. In contrast, nutrient-dependent long-term memory requires different dopaminergic neurons that project to the γ5b regions, and it can be artificially reinforced by those projecting to the β lobe and adjacent α1 region. Surprisingly, whereas artificial implantation and expression of short-term memory occur in satiated flies, formation and expression of artificial long-term memory require flies to be hungry. These studies suggest that short-term and long-term sugar memories have different physiological constraints. They also demonstrate further functional heterogeneity within the rewarding dopaminergic neuron population. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Sweet Taste and Nutrient Value Subdivide Rewarding Dopaminergic Neurons in Drosophila

    OpenAIRE

    Huetteroth, Wolf; Perisse, Emmanuel; Lin, Suewei; Klappenbach, Mart?n; Burke, Christopher; Waddell, Scott

    2015-01-01

    Dopaminergic neurons provide reward learning signals in mammals and insects. Recent work in Drosophila has demonstrated that water-reinforcing dopaminergic neurons are different to those for nutritious sugars. Here, we tested whether the sweet taste and nutrient properties of sugar reinforcement further subdivide the fly reward system. We found that dopaminergic neurons expressing the OAMB octopamine receptor specifically convey the short-term reinforcing effects of sweet taste. These dopamin...

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

    Science.gov (United States)

    Martin-Soelch, Chantal; Szczepanik, Joanna; Nugent, Allison; Barhaghi, Krystle; Rallis, Denise; Herscovitch, Peter; Carson, Richard E; Drevets, Wayne C

    2011-05-01

    Electrophysiological studies have shown that mesostriatal dopamine (DA) neurons increase activity in response to unpredicted rewards. With respect to other functions of the mesostriatal dopaminergic system, dopamine's actions show prominent laterality effects. Whether changes in DA transmission elicited by rewards also are lateralized, however, has not been investigated. Using [¹¹C]raclopride-PET to assess the striatal DA response to unpredictable monetary rewards, we hypothesized that such rewards would induce an asymmetric reduction in [¹¹C]raclopride binding in the ventral striatum, reflecting lateralization of endogenous dopamine release. In 24 healthy volunteers, differences in the regional D₂/₃ receptor binding potential (ΔBP) between an unpredictable reward condition and a sensorimotor control condition were measured using the bolus-plus-constant-infusion [¹¹C]raclopride method. During the reward condition subjects randomly received monetary awards while performing a 'slot-machine' task. The ΔBP between conditions was assessed in striatal regions-of-interest and compared between left and right sides. We found a significant condition × lateralization interaction in the ventral striatum. A significant reduction in binding potential (BP(ND) ) in the reward condition vs. the control condition was found only in the right ventral striatum, and the ΔBP was greater in the right than the left ventral striatum. Unexpectedly, these laterality effects appeared to be partly accounted for by gender differences, as our data showed a significant bilateral BP(ND) reduction in women while in men the reduction reached significance only in the right ventral striatum. These data suggest that DA release in response to unpredictable reward is lateralized in the human ventral striatum, particularly in males. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

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

    NARCIS (Netherlands)

    da Silva Alves, Fabiana; Schmitz, Nicole; Figee, Martijn; Abeling, Nico; Hasler, Gregor; van der Meer, Johan; Nederveen, Aart; de Haan, Lieuwe; Linszen, Don; van Amelsvoort, Therese

    2011-01-01

    Reward related behaviour is linked to dopaminergic neurotransmission. Our aim was to gain insight into dopaminergic involvement in the human reward system. Combining functional magnetic resonance imaging with dopaminergic depletion by α-methylparatyrosine we measured dopamine-related brain activity

  10. Dopaminergic Neurogenetics of Sleep Disorders in Reward Deficiency Syndrome (RDS).

    Science.gov (United States)

    Blum, Kenneth; Oscar-Berman, Marlene; Badgaiyan, Rajendra D; Khurshid, Khurshid A; Gold, Mark S

    2014-02-18

    It is well-known that sleep has a vital function especially as it relates to prevention of substance-related disorders as discussed in the DSM-V. We are cognizant that certain dopaminergic gene polymorphisms have been associated with various sleep disorders. The importance of "normal dopamine homeostasis" is tantamount for quality of life especially for the recovering addict. Since it is now know that sleep per se has been linked with metabolic clearance of neurotoxins in the brain, it is parsonomiuos to encourage continued research in sleep science, which should ultimately result in attenuation of sleep deprivation especially associated with substance related disorders.

  11. Omission of expected reward sensitizes the brain dopaminergic system of classically conditioned Atlantic salmon

    DEFF Research Database (Denmark)

    Vindas, M.A.; Höglund, Erik; Folkedal, O.

    in fishes. Here we show that the omission of expected reward (OER) leads to increased aggression towards conspecifics in classically conditioned Atlantic salmon (Salmo salar). Furthermore, in response to an acute stressor, OER fish displayed increased dopaminergic (DA) neurotransmission compared to controls....... There was also a general downregulation of dopamine receptor D1 gene expression in the telencephalon of OER groups, which suggests a coping mechanism in response to unbalanced DA metabolism. These results indicate that animals subjected to unpredictable reward conditions develop a senzitation of the DA...

  12. Dopaminergic balance between reward maximization and policy complexity

    Directory of Open Access Journals (Sweden)

    Naama eParush

    2011-05-01

    Full Text Available Previous reinforcement-learning models of the basal ganglia network have highlighted the role of dopamine in encoding the mismatch between prediction and reality. Far less attention has been paid to the computational goals and algorithms of the main-axis (actor. Here, we construct a top-down model of the basal ganglia with emphasis on the role of dopamine as both a reinforcement learning signal and as a pseudo-temperature signal controlling the general level of basal ganglia excitability and motor vigilance of the acting agent. We argue that the basal ganglia endow the thalamic-cortical networks with the optimal dynamic tradeoff between two constraints: minimizing the policy complexity (cost and maximizing the expected future reward (gain. We show that this multi-dimensional optimization processes results in an experience-modulated version of the softmax behavioral policy. Thus, as in classical softmax behavioral policies, probability of actions are selected according to their estimated values and the pseudo-temperature, but in addition also vary according to the frequency of previous choices of these actions. We conclude that the computational goal of the basal ganglia is not to maximize cumulative (positive and negative reward. Rather, the basal ganglia aim at optimization of independent gain and cost functions. Unlike previously suggested single-variable maximization processes, this multi-dimensional optimization process leads naturally to a softmax-like behavioral policy. We suggest that beyond its role in the modulation of the efficacy of the cortico-striatal synapses, dopamine directly affects striatal excitability and thus provides a pseudo-temperature signal that modulates the trade-off between gain and cost. The resulting experience and dopamine modulated softmax policy can then serve as a theoretical framework to account for the broad range of behaviors and clinical states governed by the basal ganglia and dopamine systems.

  13. Generational Association Studies of Dopaminergic Genes in Reward Deficiency Syndrome (RDS Subjects: Selecting Appropriate Phenotypes for Reward Dependence Behaviors

    Directory of Open Access Journals (Sweden)

    Frank Fornari

    2011-11-01

    Full Text Available Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS. RDS results from a dysfunction in the “brain reward cascade,” a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic. Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]. Methodology: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms. Data related to RDS behaviors were collected on these subjects plus 13 deceased family members. Results: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015 more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32 and 47.8% of Family B subjects (11 of 23. No significant differences were found between the experimental and control positive rates for the other variants. Conclusions: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific

  14. Neurogenetic Impairments of Brain Reward Circuitry Links to Reward Deficiency Syndrome (RDS): Potential Nutrigenomic Induced Dopaminergic Activation

    Science.gov (United States)

    Blum, K; Oscar-Berman, M; Giordano, J; Downs, BW; Simpatico, T; Han, D; Femino, John

    2012-01-01

    Work from our laboratory in both in-patient and outpatient facilities utilizing the Comprehensive Analysis of Reported Drugs (CARD)™ found a significant lack of compliance to prescribed treatment medications and a lack of abstinence from drugs of abuse during active recovery. This unpublished, ongoing research provides an impetus to develop accurate genetic diagnosis and holistic approaches that will safely activate brain reward circuitry in the mesolimbic dopamine system. This editorial focuses on the neurogenetics of brain reward systems with particular reference to genes related to dopaminergic function. The terminology “Reward Deficiency Syndrome” (RDS), used to describe behaviors found to have an association with gene-based hypodopaminergic function, is a useful concept to help expand our understanding of Substance Use Disorder (SUD), process addictions, and other obsessive, compulsive and impulsive behaviors. This editorial covers the neurological basis of pleasure and the role of natural and unnatural reward in motivating and reinforcing behaviors. Additionally, it briefly describes the concept of natural dopamine D2 receptor agonist therapy coupled with genetic testing of a panel of reward genes, the Genetic Addiction Risk Score (GARS). It serves as a spring-board for this combination of novel approaches to the prevention and treatment of RDS that was developed from fundamental genomic research. We encourage further required studies. PMID:23264886

  15. Endogenous Opioid-Induced Neuroplasticity of Dopaminergic Neurons in the Ventral Tegmental Area Influences Natural and Opiate Reward

    NARCIS (Netherlands)

    Pitchers, Kyle K.; Coppens, Caroline M.; Beloate, Lauren N.; Fuller, Jonathan; Van, Sandy; Frohmader, Karla S.; Laviolette, Steven R.; Lehman, Michael N.; Coolen, Lique M.

    2014-01-01

    Natural reward and drugs of abuse converge on the mesolimbic pathway and activate common mechanism of neural plasticity in the nucleus accumbens. Chronic exposure to opiates induces plasticity in dopaminergic neurons of the ventral tegmental area (VTA), which regulates morphine reward tolerance.

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

    Science.gov (United States)

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

    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" (GARSp DX )™. Selection of 10 genes with appropriate variants, a statistically significant association between the ASI-Media Version-alcohol and drug severity scores and GARSp Dx 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

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

    Science.gov (United States)

    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

  18. Dopaminergic circuitry and risk/reward decision making: implications for schizophrenia.

    Science.gov (United States)

    Stopper, Colin M; Floresco, Stan B

    2015-01-01

    Abnormal reinforcement learning and representations of reward value are present in schizophrenia, and these impairments can manifest as deficits in risk/reward decision making. These abnormalities may be due in part to dopaminergic dysfunction within cortico-limbic-striatal circuitry. Evidence from studies with laboratory animal have revealed that normal DA activity within different nodes of these circuits is critical for mediating dissociable processes that can refine decision biases. Moreover, both phasic and tonic dopamine transmission appear to play separate yet complementary roles in these processes. Tonic dopamine release within the prefrontal cortex and nucleus accumbens, serves as a "running rate-meter" of reward and reflects contextual information such as reward uncertainty and overt choice behavior. On the other hand, manipulations of outcome-related phasic dopamine bursts and dips suggest these signals provide rapid feedback to allow for quick adjustments in choice as reward contingencies change. The lateral habenula is a key input to the DA system that phasic signals is necessary for expressing subjective decision biases; as suppression of activity within this nucleus leads to catastrophic impairments in decision making and random patterns of choice behavior. As schizophrenia is characterized by impairments in using positive and negative feedback to appropriately guide decision making, these findings suggest that these deficits in these processes may be mediated, at least in part, by abnormalities in both tonic and phasic dopamine transmission. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  19. Dopaminergic modulation of reward-guided decision making in alcohol-preferring AA rats.

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    Oinio, Ville; Bäckström, Pia; Uhari-Väänänen, Johanna; Raasmaja, Atso; Piepponen, Petteri; Kiianmaa, Kalervo

    2017-05-30

    R**esults from animal gambling models have highlighted the importance of dopaminergic neurotransmission in modulating decision making when large sucrose rewards are combined with uncertainty. The majority of these models use food restriction as a tool to motivate animals to accomplish operant behavioral tasks, in which sucrose is used as a reward. As enhanced motivation to obtain sucrose due to hunger may impact its reward-seeking effect, we wanted to examine the decision-making behavior of rats in a situation where rats were fed ad libitum. For this purpose, we chose alcohol-preferring AA (alko alcohol) rats, as these rats have been shown to have high preference for sweet agents. In the present study, AA rats were trained to self-administer sucrose pellet rewards in a two-lever choice task (one pellet vs. three pellets). Once rational choice behavior had been established, the probability of gaining three pellets was decreased over time (50%, 33%, 25% then 20%). The effect of d-amphetamine on decision making was studied at every probability level, as well as the effect of the dopamine D 1 receptor agonist SKF-81297 and D 2 agonist quinpirole at probability levels of 100% and 25%. d-Amphetamine increased unprofitable choices in a dose-dependent manner at the two lowest probability levels. Quinpirole increased the frequency of unprofitable decisions at the 25% probability level, and SKF-82197 did not affect choice behavior. These results mirror the findings of probabilistic discounting studies using food-restricted rats. Based on this, the use of AA rats provides a new approach for studies on reward-guided decision making. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Divergent circuitry underlying food reward and intake effects of ghrelin: dopaminergic VTA-accumbens projection mediates ghrelin's effect on food reward but not food intake.

    Science.gov (United States)

    Skibicka, Karolina P; Shirazi, Rozita H; Rabasa-Papio, Cristina; Alvarez-Crespo, Mayte; Neuber, Corinna; Vogel, Heike; Dickson, Suzanne L

    2013-10-01

    Obesity has reached global epidemic proportions and creating an urgent need to understand mechanisms underlying excessive and uncontrolled food intake. Ghrelin, the only known circulating orexigenic hormone, potently increases food reward behavior. The neurochemical circuitry that links ghrelin to the mesolimbic reward system and to the increased food reward behavior remains unclear. Here we examine whether VTA-NAc dopaminergic signaling is required for the effects of ghrelin on food reward and intake. In addition, we examine the possibility of endogenous ghrelin acting on the VTA-NAc dopamine neurons. A D1-like or a D2 receptor antagonist was injected into the NAc in combination with ghrelin microinjection into the VTA to investigate whether this blockade attenuates ghrelin-induced food reward behavior. VTA injections of ghrelin produced a significant increase in food motivation/reward behavior, as measured by sucrose-induced progressive ratio operant conditioning, and chow intake. Pretreatment with either a D1-like or D2 receptor antagonist into the NAc, completely blocked the reward effect of ghrelin, leaving chow intake intact. We also found that this circuit is potentially relevant for the effects of endogenously released ghrelin as both antagonists reduced fasting (a state of high circulating levels of ghrelin) elevated sucrose-motivated behavior but not chow hyperphagia. Taken together our data identify the VTA to NAc dopaminergic projections, along with D1-like and D2 receptors in the NAc, as essential elements of the ghrelin responsive circuits controlling food reward behavior. Interestingly results also suggest that food reward behavior and simple intake of chow are controlled by divergent circuitry, where NAc dopamine plays an important role in food reward but not in food intake. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Do dopaminergic gene polymorphisms affect mesolimbic reward activation of music listening response? Therapeutic impact on Reward Deficiency Syndrome (RDS).

    Science.gov (United States)

    Blum, Kenneth; Chen, Thomas J H; Chen, Amanda L H; Madigan, Margaret; Downs, B William; Waite, Roger L; Braverman, Eric R; Kerner, Mallory; Bowirrat, Abdalla; Giordano, John; Henshaw, Harry; Gold, Mark S

    2010-03-01

    Using fMRI, Menon and Levitin [9] clearly found for the first time that listening to music strongly modulates activity in a network of mesolimbic structures involved in reward processing including the nucleus accumbens (NAc) and the ventral tegmental area (VTA), as well as the hypothalamus, and insula, which are thought to be involved in regulating autonomic and physiological responses to rewarding and emotional stimuli. Importantly, responses in the NAc and VTA were strongly correlated pointing to an association between dopamine release and NAc response to music. Listing to pleasant music induced a strong response and significant activation of the VTA-mediated interaction of the NAc with the hypothalamus, insula, and orbitofrontal cortex. Blum et al. [10] provided the first evidence that the dopamine D2 receptor gene (DRD2) Taq 1 A1 allele significantly associated with severe alcoholism whereby the author's suggested that they found the first "reward gene" located in the mesolimbic system. The enhanced functional and effective 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. However, little is known about why some people have a more or less powerful mesolimbic experience when they are listening to music. It is well-known that music may induce an endorphinergic response that is blocked by naloxone, a known opioid antagonist (Goldstein [19]). Opioid transmission in the NAc is associated with dopamine release in the VTA. Moreover, dopamine release in the VTA is linked to polymorphisms of the DRD2 gene and even attention-deficit hyperactivity disorder (ADHD), whereby carriers of the DRD2 A1 allele show a reduced NAc release of dopamine (DA). Thus it is conjectured that similar mechanisms in terms of adequate dopamine release and subsequent activation of reward circuitry by listening to music might also be

  2. Central dopaminergic circuitry controlling food intake and reward: implications for the regulation of obesity.

    Science.gov (United States)

    Vucetic, Zivjena; Reyes, Teresa M

    2010-01-01

    Prevalence of obesity in the general population has increased in the past 15 years from 15% to 35%. With increasing obesity, the coincident medical and social consequences are becoming more alarming. Control over food intake is crucial for the maintenance of body weight and represents an important target for the treatment of obesity. Central nervous system mechanisms responsible for control of food intake have evolved to sense the nutrient and energy levels in the organism and to coordinate appropriate responses to adjust energy intake and expenditure. This homeostatic system is crucial for maintenance of stable body weight over long periods of time of uneven energy availability. However, not only the caloric and nutritional value of food but also hedonic and emotional aspects of feeding affect food intake. In modern society, the increased availability of highly palatable and rewarding (fat, sweet) food can significantly affect homeostatic balance, resulting in dysregulated food intake. This review will focus on the role of hypothalamic and mesolimbic/mesocortical dopaminergic (DA) circuitry in coding homeostatic and hedonic signals for the regulation of food intake and maintenance of caloric balance. The interaction of dopamine with peripheral and central indices of nutritional status (e.g., leptin, ghrelin, neuropeptide Y), and the susceptibility of the dopamine system to prenatal insults will be discussed. Additionally, the importance of alterations in dopamine signaling that occur coincidently with obesity will be addressed.

  3. Fifty Years in the Development of a Glutaminergic-Dopaminergic Optimization Complex (KB220) to Balance Brain Reward Circuitry in Reward Deficiency Syndrome: A Pictorial

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    Blum, K; Febo, M; Badgaiyan, RD

    2016-01-01

    Dopamine along with other chemical messengers like serotonin, cannabinoids, endorphins and glutamine, play significant roles in brain reward processing. There is a devastating opiate/opioid epidemicin the United States. According to the Centers for Disease Control and Prevention (CDC), at least 127 people, young and old, are dying every day due to narcotic overdose and alarmingly heroin overdose is on the rise. The Food and Drug Administration (FDA) has approved some Medication-Assisted Treatments (MATs) for alcoholism, opiate and nicotine dependence, but nothing for psychostimulant and cannabis abuse. While these pharmaceuticals are essential for the short-term induction of “psychological extinction,” in the long-term caution is necessary because their use favors blocking dopaminergic function indispensable for achieving normal satisfaction in life. The two institutions devoted to alcoholism and drug dependence (NIAAA & NIDA) realize that MATs are not optimal and continue to seek better treatment options. We review, herein, the history of the development of a glutaminergic-dopaminergic optimization complex called KB220 to provide for the possible eventual balancing of the brain reward system and the induction of “dopamine homeostasis.” This complex may provide substantial clinical benefit to the victims of Reward Deficiency Syndrome (RDS) and assist in recovery from iatrogenically induced addiction to unwanted opiates/opioids and other addictive behaviors. PMID:27840857

  4. BOLD responses in reward regions to hypothetical and imaginary monetary rewards.

    Science.gov (United States)

    Miyapuram, Krishna P; Tobler, Philippe N; Gregorios-Pippas, Lucy; Schultz, Wolfram

    2012-01-16

    Monetary rewards are uniquely human. Because money is easy to quantify and present visually, it is the reward of choice for most fMRI studies, even though it cannot be handed over to participants inside the scanner. A typical fMRI study requires hundreds of trials and thus small amounts of monetary rewards per trial (e.g. 5p) if all trials are to be treated equally. However, small payoffs can have detrimental effects on performance due to their limited buying power. Hypothetical monetary rewards can overcome the limitations of smaller monetary rewards but it is less well known whether predictors of hypothetical rewards activate reward regions. In two experiments, visual stimuli were associated with hypothetical monetary rewards. In Experiment 1, we used stimuli predicting either visually presented or imagined hypothetical monetary rewards, together with non-rewarding control pictures. Activations to reward predictive stimuli occurred in reward regions, namely the medial orbitofrontal cortex and midbrain. In Experiment 2, we parametrically varied the amount of visually presented hypothetical monetary reward keeping constant the amount of actually received reward. Graded activation in midbrain was observed to stimuli predicting increasing hypothetical rewards. The results demonstrate the efficacy of using hypothetical monetary rewards in fMRI studies. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. High vitamin A intake during pregnancy modifies dopaminergic reward system and decreases preference for sucrose in Wistar rat offspring.

    Science.gov (United States)

    Sánchez-Hernández, Diana; Poon, Abraham N; Kubant, Ruslan; Kim, Hwanki; Huot, Pedro S P; Cho, Clara E; Pannia, Emanuela; Reza-López, Sandra A; Pausova, Zdenka; Bazinet, Richard P; Anderson, G Harvey

    2016-01-01

    High multivitamin (HV) content in gestational diets has long-term metabolic effects in rat offspring. These changes are associated with in utero modifications of gene expression in hypothalamic food intake regulation. However, the role of fat-soluble vitamins in mediating these effects has not been explored. Vitamin A is a plausible candidate due to its role in gene methylation. Vitamin A intake above requirements during pregnancy affects the development of neurocircuitries involved in food intake and reward regulation. Pregnant Wistar rats were fed AIN-93G diets with the following content: recommended multivitamins (1-fold multivitamins: RV), high vitamin A (10-fold vitamin A: HA) or HV with only recommended vitamin A (10-fold multivitamins, 1-fold vitamin A: HVRA). Body weight, food intake and preference, mRNA expression and DNA methylation of hippocampal dopamine-related genes were assessed in male offspring brains at different developmental windows: birth, weaning and 14weeks postweaning. HA offspring had changes in dopamine-related gene expression at all developmental windows and DNA hypermethylation in the dopamine receptor 2 promoter region compared to RV offspring. Furthermore, HA diet lowered sucrose preference but had no effect on body weight and expression of hypothalamic genes. In contrast, HVRA offspring showed only at adulthood changes in expression of hippocampal genes and a modest effect on hypothalamic genes. High vitamin A intake alone in gestational diets has long-lasting programming effects on the dopaminergic system that are further translated into decreased sucrose preference but not food intake. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Dopaminergic control of motivation and reinforcement learning: a closed-circuit account for reward-oriented behavior.

    Science.gov (United States)

    Morita, Kenji; Morishima, Mieko; Sakai, Katsuyuki; Kawaguchi, Yasuo

    2013-05-15

    Humans and animals take actions quickly when they expect that the actions lead to reward, reflecting their motivation. Injection of dopamine receptor antagonists into the striatum has been shown to slow such reward-seeking behavior, suggesting that dopamine is involved in the control of motivational processes. Meanwhile, neurophysiological studies have revealed that phasic response of dopamine neurons appears to represent reward prediction error, indicating that dopamine plays central roles in reinforcement learning. However, previous attempts to elucidate the mechanisms of these dopaminergic controls have not fully explained how the motivational and learning aspects are related and whether they can be understood by the way the activity of dopamine neurons itself is controlled by their upstream circuitries. To address this issue, we constructed a closed-circuit model of the corticobasal ganglia system based on recent findings regarding intracortical and corticostriatal circuit architectures. Simulations show that the model could reproduce the observed distinct motivational effects of D1- and D2-type dopamine receptor antagonists. Simultaneously, our model successfully explains the dopaminergic representation of reward prediction error as observed in behaving animals during learning tasks and could also explain distinct choice biases induced by optogenetic stimulation of the D1 and D2 receptor-expressing striatal neurons. These results indicate that the suggested roles of dopamine in motivational control and reinforcement learning can be understood in a unified manner through a notion that the indirect pathway of the basal ganglia represents the value of states/actions at a previous time point, an empirically driven key assumption of our model.

  7. Dose Dependent Dopaminergic Modulation of Reward-Based Learning in Parkinson's Disease

    Science.gov (United States)

    van Wouwe, N. C.; Ridderinkhof, K. R.; Band, G. P. H.; van den Wildenberg, W. P. M.; Wylie, S. A.

    2012-01-01

    Learning to select optimal behavior in new and uncertain situations is a crucial aspect of living and requires the ability to quickly associate stimuli with actions that lead to rewarding outcomes. Mathematical models of reinforcement-based learning to select rewarding actions distinguish between (1) the formation of stimulus-action-reward…

  8. Modulation of risk/reward decision making by dopaminergic transmission within the basolateral amygdala.

    Science.gov (United States)

    Larkin, Joshua D; Jenni, Nicole L; Floresco, Stan B

    2016-01-01

    Dopamine (DA) transmission within cortico-limbic-striatal circuitry is integral in modulating decisions involving reward uncertainty. The basolateral amygdala (BLA) also plays a role in these processes, yet how DA transmission within this nucleus regulates cost/benefit decision making is unknown. We investigated the contribution of DA transmission within the BLA to risk/reward decision making assessed with a probabilistic discounting task. Rats were well-trained to choose between a small/certain reward and a large/risky reward, with the probability of obtaining the larger reward decreasing (100-12.5 %) or increasing (12.5-100 %) over a session. We examined the effects of antagonizing BLA D1 (SCH 23390, 0.1-1 μg) or D2 (eticlopride, 0.1-1 μg) receptors, as well as intra-BLA infusions of agonists for D1 (SKF 81297, 0.1-1 μg) and D2 (quinpirole, 1-10 μg) receptors. We also assessed how DA receptor stimulation may induce differential effects related to baseline levels of risky choice. BLA D1 receptor antagonism reduced risky choice by decreasing reward sensitivity, whereas D2 antagonism did not affect overall choice patterns. Stimulation of BLA D1 receptors optimized decision making in a baseline-dependent manner: in risk-averse rats, infusions of a lower dose of SKF81297 increased risky choice when reward probabilities were high (50 %), whereas in risk-prone rats, this drug reduced risky choice when probabilities were low (12.5 %). Quinpirole reduced risky choice in risk-prone rats, enhancing lose-shift behavior. These data highlight previously uncharacterized roles for BLA DA D1 and D2 receptors in biasing choice during risk/reward decision making through mediation of reward/negative feedback sensitivity.

  9. Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS: a commentary

    Directory of Open Access Journals (Sweden)

    Waite Roger L

    2008-11-01

    proliferation of D2 receptors. Proposal and conclusion The authors propose that D2 receptor stimulation can be accomplished via the use of Synapatmine™, a natural but therapeutic nutraceutical formulation that potentially induces DA release, causing the same induction of D2-directed mRNA and thus proliferation of D2 receptors in the human. This proliferation of D2 receptors in turn will induce the attenuation of craving behavior. In fact as mentioned earlier, this model has been proven in research showing DNA-directed compensatory overexpression (a form of gene therapy of the DRD2 receptors, resulting in a significant reduction in alcohol craving behavior in alcohol preferring rodents. Utilizing natural dopaminergic repletion therapy to promote long term dopaminergic activation will ultimately lead to a common, safe and effective modality to treat Reward Deficiency Syndrome (RDS behaviors including Substance Use Disorders (SUD, Attention Deficit Hyperactivity Disorder (ADHD, Obesity and other reward deficient aberrant behaviors. This concept is further supported by the more comprehensive understanding of the role of dopamine in the NAc as a "wanting" messenger in the meso-limbic DA system.

  10. Dorsolateral Prefrontal Cortex Drives Mesolimbic Dopaminergic Regions to Initiate Motivated Behavior

    OpenAIRE

    Ballard, Ian C.; Murty, Vishnu P.; Carter, R. McKell; MacInnes, Jeffrey J.; Huettel, Scott A.; Adcock, R. Alison

    2011-01-01

    How does the brain translate information signaling potential rewards into motivation to get them? Motivation to obtain reward is thought to depend on the midbrain, (particularly the ventral tegmental area, VTA), the nucleus accumbens (NAcc), and the dorsolateral prefrontal cortex (dlPFC), but it is not clear how the interactions amongst these regions relate to reward-motivated behavior. To study the influence of motivation on these reward-responsive regions and on their interactions, we used ...

  11. Striatal dopaminergic reward response relates to age of first drunkenness and feedback response in at-risk youth.

    Science.gov (United States)

    Weiland, Barbara J; Zucker, Robert A; Zubieta, Jon-Kar; Heitzeg, Mary M

    2017-03-01

    Dopamine receptor concentrations, primarily in the striatum, are hypothesized to contribute to a developmental imbalance between subcortical and prefrontal control systems in emerging adulthood potentially biasing motivation and increasing risky behaviors. Positron emission tomography studies have found significant reductions in striatal dopamine D2 receptors, and blunted amphetamine-induced dopamine release, in substance users compared with healthy controls. Extant literature is limited and inconsistent concerning vulnerability associated with having a family history of substance abuse (FH+). Some studies have reported familial liability associated with higher dopamine receptor levels, reduced dopamine response to stimulant challenges and decreased response to oral alcohol. However, other reports have failed to find group differences based on family history. We explored the interaction of familial liability and behavioral risk with multi-modal molecular and neural imaging of the dopaminergic system. Forty-four young adult male subjects performed monetary incentive delay tasks during both [ 11 C]raclopride positron emission tomography and functional magnetic resonance imaging scans. FH+ subjects were identified as low (n = 24) or high risk (n = 9) based on early initiation of drunkenness. FH+ high-risk subjects exhibited heightened striatal dopamine response to monetary reward but did not differ in neural activations compared with FH+ low risk subjects and controls with no familial loading (n = 11). Across all subjects, a negative relationship was found between dopamine release and age of first drunkenness and a positive relationship with neural response to reward receipt. These results suggest that in at-risk individuals, higher dopamine transmission associated with monetary reward may represent a particularly useful neurobiological phenotype. © 2016 Society for the Study of Addiction.

  12. Changes in reward-induced brain activation in opiate addicts

    NARCIS (Netherlands)

    Martin-Soelch, C; Chevalley, AF; Kunig, G; Missimer, J; Magyar, S; Mino, A; Schultz, W; Leenders, KL

    2001-01-01

    Many studies indicate a role of the cerebral dopaminergic reward system in addiction. Motivated by these findings, we examined in opiate addicts whether brain regions involved in the reward circuitry also react to human prototypical rewards. We measured regional cerebral blood flow (rCBF) with

  13. Rewards.

    Science.gov (United States)

    Gunderman, Richard B; Kamer, Aaron P

    2011-05-01

    For much of the 20th century, psychologists and economists operated on the assumption that work is devoid of intrinsic rewards, and the only way to get people to work harder is through the use of rewards and punishments. This so-called carrot-and-stick model of workplace motivation, when applied to medical practice, emphasizes the use of financial incentives and disincentives to manipulate behavior. More recently, however, it has become apparent that, particularly when applied to certain kinds of work, such approaches can be ineffective or even frankly counterproductive. Instead of focusing on extrinsic rewards such as compensation, organizations and their leaders need to devote more attention to the intrinsic rewards of work itself. This article reviews this new understanding of rewards and traces out its practical implications for radiology today. Copyright © 2011. Published by Elsevier Inc.

  14. Implication of Dopaminergic Modulation in Operant Reward Learning and the Induction of Compulsive-Like Feeding Behavior in "Aplysia"

    Science.gov (United States)

    Bedecarrats, Alexis; Cornet, Charles; Simmers, John; Nargeot, Romuald

    2013-01-01

    Feeding in "Aplysia" provides an amenable model system for analyzing the neuronal substrates of motivated behavior and its adaptability by associative reward learning and neuromodulation. Among such learning processes, appetitive operant conditioning that leads to a compulsive-like expression of feeding actions is known to be associated…

  15. Changes in sensitivity of reward and motor behavior to dopaminergic, glutamatergic, and cholinergic drugs in a mouse model of fragile X syndrome.

    Directory of Open Access Journals (Sweden)

    Eric W Fish

    Full Text Available Fragile X syndrome (FXS is a leading cause of intellectual disability. FXS is caused by loss of function of the FMR1 gene, and mice in which Fmr1 has been inactivated have been used extensively as a preclinical model for FXS. We investigated the behavioral pharmacology of drugs acting through dopaminergic, glutamatergic, and cholinergic systems in fragile X (Fmr1 (-/Y mice with intracranial self-stimulation (ICSS and locomotor activity measurements. We also measured brain expression of tyrosine hydroxylase (TH, the rate-limiting enzyme in dopamine biosynthesis. Fmr1 (-/Y mice were more sensitive than wild type mice to the rewarding effects of cocaine, but less sensitive to its locomotor stimulating effects. Anhedonic but not motor depressant effects of the atypical neuroleptic, aripiprazole, were reduced in Fmr1 (-/Y mice. The mGluR5-selective antagonist, 6-methyl-2-(phenylethynylpyridine (MPEP, was more rewarding and the preferential M1 antagonist, trihexyphenidyl, was less rewarding in Fmr1 (-/Y than wild type mice. Motor stimulation by MPEP was unchanged, but stimulation by trihexyphenidyl was markedly increased, in Fmr1 (-/Y mice. Numbers of midbrain TH+ neurons in the ventral tegmental area were unchanged, but were lower in the substantia nigra of Fmr1 (-/Y mice, although no changes in TH levels were found in their forebrain targets. The data are discussed in the context of known changes in the synaptic physiology and pharmacology of limbic motor systems in the Fmr1 (-/Y mouse model. Preclinical findings suggest that drugs acting through multiple neurotransmitter systems may be necessary to fully address abnormal behaviors in individuals with FXS.

  16. Changes in sensitivity of reward and motor behavior to dopaminergic, glutamatergic, and cholinergic drugs in a mouse model of fragile X syndrome.

    Science.gov (United States)

    Fish, Eric W; Krouse, Michael C; Stringfield, Sierra J; Diberto, Jeffrey F; Robinson, J Elliott; Malanga, C J

    2013-01-01

    Fragile X syndrome (FXS) is a leading cause of intellectual disability. FXS is caused by loss of function of the FMR1 gene, and mice in which Fmr1 has been inactivated have been used extensively as a preclinical model for FXS. We investigated the behavioral pharmacology of drugs acting through dopaminergic, glutamatergic, and cholinergic systems in fragile X (Fmr1 (-/Y)) mice with intracranial self-stimulation (ICSS) and locomotor activity measurements. We also measured brain expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine biosynthesis. Fmr1 (-/Y) mice were more sensitive than wild type mice to the rewarding effects of cocaine, but less sensitive to its locomotor stimulating effects. Anhedonic but not motor depressant effects of the atypical neuroleptic, aripiprazole, were reduced in Fmr1 (-/Y) mice. The mGluR5-selective antagonist, 6-methyl-2-(phenylethynyl)pyridine (MPEP), was more rewarding and the preferential M1 antagonist, trihexyphenidyl, was less rewarding in Fmr1 (-/Y) than wild type mice. Motor stimulation by MPEP was unchanged, but stimulation by trihexyphenidyl was markedly increased, in Fmr1 (-/Y) mice. Numbers of midbrain TH+ neurons in the ventral tegmental area were unchanged, but were lower in the substantia nigra of Fmr1 (-/Y) mice, although no changes in TH levels were found in their forebrain targets. The data are discussed in the context of known changes in the synaptic physiology and pharmacology of limbic motor systems in the Fmr1 (-/Y) mouse model. Preclinical findings suggest that drugs acting through multiple neurotransmitter systems may be necessary to fully address abnormal behaviors in individuals with FXS.

  17. Coping with unpredictability: Dopaminergic and neurotrophic responses to omission of expected reward in Atlantic salmon (Salmo salar L.)

    DEFF Research Database (Denmark)

    Vindas, Marco A; Sørensen, Christina; Johansen, Ida

    2014-01-01

    Comparative studies are imperative for understanding the evolution of adaptive neurobiological processes such as neural plasticity, cognition, and emotion. Previously we have reported that prolonged omission of expected rewards (OER, or 'frustrative nonreward') causes increased aggression....... Subsequently, the expected food reward was delayed for 30 minutes during two out of three meals per day in the OER treatment, while the previously established routine was maintained in control groups. After 8 days there was no effect of OER on baseline brain stem serotonin (5-HT) or dopamine (DA) activity....... Subsequent exposure to acute confinement stress led to increased plasma cortisol and elevated turnover of brain stem DA and 5-HT in all animals. The DA response was potentiated and DA receptor 1 (D1) mRNA abundance was reduced in the OER-exposed fish, indicating a sensitization of the DA system. In addition...

  18. White noise improves learning by modulating activity in dopaminergic midbrain regions and right superior temporal sulcus.

    Science.gov (United States)

    Rausch, Vanessa H; Bauch, Eva M; Bunzeck, Nico

    2014-07-01

    In neural systems, information processing can be facilitated by adding an optimal level of white noise. Although this phenomenon, the so-called stochastic resonance, has traditionally been linked with perception, recent evidence indicates that white noise may also exert positive effects on cognitive functions, such as learning and memory. The underlying neural mechanisms, however, remain unclear. Here, on the basis of recent theories, we tested the hypothesis that auditory white noise, when presented during the encoding of scene images, enhances subsequent recognition memory performance and modulates activity within the dopaminergic midbrain (i.e., substantia nigra/ventral tegmental area, SN/VTA). Indeed, in a behavioral experiment, we can show in healthy humans that auditory white noise-but not control sounds, such as a sinus tone-slightly improves recognition memory. In an fMRI experiment, white noise selectively enhances stimulus-driven phasic activity in the SN/VTA and auditory cortex. Moreover, it induces stronger connectivity between SN/VTA and right STS, which, in addition, exhibited a positive correlation with subsequent memory improvement by white noise. Our results suggest that the beneficial effects of auditory white noise on learning depend on dopaminergic neuromodulation and enhanced connectivity between midbrain regions and the STS-a key player in attention modulation. Moreover, they indicate that white noise could be particularly useful to facilitate learning in conditions where changes of the mesolimbic system are causally related to memory deficits including healthy and pathological aging.

  19. Neurochemical evidence that cocaine- and amphetamine-regulated transcript (CART) 55-102 peptide modulates the dopaminergic reward system by decreasing the dopamine release in the mouse nucleus accumbens.

    Science.gov (United States)

    Rakovska, Angelina; Baranyi, Maria; Windisch, Katalin; Petkova-Kirova, Polina; Gagov, Hristo; Kalfin, Reni

    2017-09-01

    CART (Cocaine- and Amphetamine-Regulated Transcript) peptide is a neurotransmitter naturally occurring in the CNS and found mostly in nucleus accumbens, ventrotegmental area, ventral pallidum, amygdalae and striatum, brain regions associated with drug addiction. In the nucleus accumbens, known for its significant role in motivation, pleasure, reward and reinforcement learning, CART peptide inhibits cocaine and amphetamine-induced dopamine-mediated increases in locomotor activity and behavior, suggesting a CART peptide interaction with the dopaminergic system. Thus in the present study, we examined the effect of CART (55-102) peptide on the basal, electrical field stimulation-evoked (EFS-evoked) (30V, 2Hz, 120 shocks) and returning basal dopamine (DA) release and on the release of the DA metabolites 3,4-dihydroxyphenyl acetaldehyde (DOPAL), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3,4-dihydroxyphenylethanol (DOPET), 3-methoxytyramine (3-MT) as well as on norepinephrine (NE) and dopamine-o-quinone (Daq) in isolated mouse nucleus accumbens, in a preparation, in which any CART peptide effects on the dendrites or soma of ventral tegmental projection neurons have been excluded. We further extended our study to assess the effect of CART (55-102) peptide on basal cocaine-induced release of dopamine and its metabolites DOPAL, DOPAC, HVA, DOPET and 3-MT as well as on NE and Daq. To analyze the amount of [ 3 H]dopamine, dopamine metabolites, Daq and NE in the nucleus accumbens superfusate, a high-pressure liquid chromatography (HPLC), coupled with electrochemical, UV and radiochemical detections was used. CART (55-102) peptide, 0.1μM, added alone, exerted: (i) a significant decrease in the basal and EFS-evoked levels of extracellular dopamine (ii) a significant increase in the EFS-evoked and returning basal levels of the dopamine metabolites DOPAC and HVA, major products of dopamine degradation and (iii) a significant decrease in the returning basal

  20. Coping with unpredictability: dopaminergic and neurotrophic responses to omission of expected reward in Atlantic salmon (Salmo salar L..

    Directory of Open Access Journals (Sweden)

    Marco A Vindas

    Full Text Available Comparative studies are imperative for understanding the evolution of adaptive neurobiological processes such as neural plasticity, cognition, and emotion. Previously we have reported that prolonged omission of expected rewards (OER, or 'frustrative nonreward' causes increased aggression in Atlantic salmon (Salmo salar. Here we report changes in brain monoaminergic activity and relative abundance of brain derived neurotrophic factor (BDNF and dopamine receptor mRNA transcripts in the same paradigm. Groups of fish were initially conditioned to associate a flashing light with feeding. Subsequently, the expected food reward was delayed for 30 minutes during two out of three meals per day in the OER treatment, while the previously established routine was maintained in control groups. After 8 days there was no effect of OER on baseline brain stem serotonin (5-HT or dopamine (DA activity. Subsequent exposure to acute confinement stress led to increased plasma cortisol and elevated turnover of brain stem DA and 5-HT in all animals. The DA response was potentiated and DA receptor 1 (D1 mRNA abundance was reduced in the OER-exposed fish, indicating a sensitization of the DA system. In addition OER suppressed abundance of BDNF in the telencephalon of non-stressed fish. Regardless of OER treatment, a strong positive correlation between BDNF and D1 mRNA abundance was seen in non-stressed fish. This correlation was disrupted by acute stress, and replaced by a negative correlation between BDNF abundance and plasma cortisol concentration. These observations indicate a conserved link between DA, neurotrophin regulation, and corticosteroid-signaling pathways. The results also emphasize how fish models can be important tools in the study of neural plasticity and responsiveness to environmental unpredictability.

  1. Coping with unpredictability: dopaminergic and neurotrophic responses to omission of expected reward in Atlantic salmon (Salmo salar L.).

    Science.gov (United States)

    Vindas, Marco A; Sørensen, Christina; Johansen, Ida B; Folkedal, Ole; Höglund, Erik; Khan, Uniza W; Stien, Lars H; Kristiansen, Tore S; Braastad, Bjarne O; Øverli, Øyvind

    2014-01-01

    Comparative studies are imperative for understanding the evolution of adaptive neurobiological processes such as neural plasticity, cognition, and emotion. Previously we have reported that prolonged omission of expected rewards (OER, or 'frustrative nonreward') causes increased aggression in Atlantic salmon (Salmo salar). Here we report changes in brain monoaminergic activity and relative abundance of brain derived neurotrophic factor (BDNF) and dopamine receptor mRNA transcripts in the same paradigm. Groups of fish were initially conditioned to associate a flashing light with feeding. Subsequently, the expected food reward was delayed for 30 minutes during two out of three meals per day in the OER treatment, while the previously established routine was maintained in control groups. After 8 days there was no effect of OER on baseline brain stem serotonin (5-HT) or dopamine (DA) activity. Subsequent exposure to acute confinement stress led to increased plasma cortisol and elevated turnover of brain stem DA and 5-HT in all animals. The DA response was potentiated and DA receptor 1 (D1) mRNA abundance was reduced in the OER-exposed fish, indicating a sensitization of the DA system. In addition OER suppressed abundance of BDNF in the telencephalon of non-stressed fish. Regardless of OER treatment, a strong positive correlation between BDNF and D1 mRNA abundance was seen in non-stressed fish. This correlation was disrupted by acute stress, and replaced by a negative correlation between BDNF abundance and plasma cortisol concentration. These observations indicate a conserved link between DA, neurotrophin regulation, and corticosteroid-signaling pathways. The results also emphasize how fish models can be important tools in the study of neural plasticity and responsiveness to environmental unpredictability.

  2. BOLD responses in reward regions to hypothetical and imaginary monetary rewards

    NARCIS (Netherlands)

    Miyapuram, K.P.; Tobler, P.N.; Gregorios-Pippas, L.; Schultz, W.

    2012-01-01

    Monetary rewards are uniquely human. Because money is easy to quantify and present visually, it is the reward of choice for most fMRI studies, even though it cannot be handed over to participants inside the scanner. A typical fMRI study requires hundreds of trials and thus small amounts of monetary

  3. Opioid receptors in midbrain dopaminergic regions of the rat. 1. Mu receptor autoradiography

    International Nuclear Information System (INIS)

    German, D.C.; Speciale, S.G.; Manaye, K.F.; Sadeq, M.

    1993-01-01

    Several lines of evidence indicate that an interaction exists between opioid peptides and midbrain dopaminergic neurons. The purpose of this study was to map and quantify the density of the mu opioid receptor subtype relative to the location of the dopaminergic (DA) neurons in the retrorubral field (nucleus A8), substantia nigra (nucleus A9), and ventral tegmental area and related nuclei (nucleus A10) in the rat. Sections through the rostral-caudal extent of the midbrain were stained with an antibody against tyrosine hydroxylase, as a DA cell marker, and comparable sections were processed for in vitro receptor autoradiography using the mu-selective ligand, 3 H-Tyr-D-Ala-N-MePhe-Gyl-ol enkephalin. In the nucleus A8 region, there were low levels of mu binding. In the rostral portion of nucleus A9, there was prominent mu binding both in the ventral pars compacta, which contains numerous DA neurons, and in regions that correspond to the location of the DA dendrites which project ventrally into the underlying substantia nigra pars reticulata. In the caudal portion of nucleus A9, mu binding was greatest in the substantia nigra pars reticulata, but also in the same region that contains DA neurons. In nucleus A10, mu receptor densities differed depending upon the nucleus A10 subdivision, and the rostral-caudal position in the nucleus. Low receptor densities were observed in rostral portions of the ventral tegmental area and interfascicular nucleus, and there was negligible binding in the parabrachial pigmented nucleus and paranigral nucleus at the level of the interpeduncular nucleus; all regions where there are high densities of DA somata. Mu binding was relatively high in the central linear nucleus, and in the dorsal and medial divisions of the medial terminal nucleus of the accessory optic system, which has been shown to contain DA dendrites. These data indicate that mu opioid receptors are located in certain regions occupied by all three midbrain DA nuclei, but in a

  4. BOLD responses in reward regions to hypothetical and imaginary monetary rewards.

    OpenAIRE

    Miyapuram Krishna P; Tobler Philippe N; Gregorios-Pippas Lucy; Schultz Wolfram

    2012-01-01

    Monetary rewards are uniquely human. Because money is easy to quantify and present visually, it is the reward of choice for most fMRI studies, even though it cannot be handed over to participants inside the scanner. A typical fMRI study requires hundreds of trials and thus small amounts of monetary rewards per trial (e.g. 5p) if all trials are to be treated equally. However, small payoffs can have detrimental effects on performance due to their limited buying power. Hypothetical monetary rewa...

  5. Voluntary ethanol intake predicts κ-opioid receptor supersensitivity and regionally distinct dopaminergic adaptations in macaques.

    Science.gov (United States)

    Siciliano, Cody A; Calipari, Erin S; Cuzon Carlson, Verginia C; Helms, Christa M; Lovinger, David M; Grant, Kathleen A; Jones, Sara R

    2015-04-15

    The dopaminergic projections from the ventral midbrain to the striatum have long been implicated in mediating motivated behaviors and addiction. Previously it was demonstrated that κ-opioid receptor (KOR) signaling in the striatum plays a critical role in the increased reinforcing efficacy of ethanol following ethanol vapor exposure in rodent models. Although rodents have been used extensively to determine the neurochemical consequences of chronic ethanol exposure, establishing high levels of voluntary drinking in these models has proven difficult. Conversely, nonhuman primates exhibit similar intake and pattern to humans in regard to drinking. Here we examine the effects of chronic voluntary ethanol self-administration on dopamine neurotransmission and the ability of KORs to regulate dopamine release in the dorsolateral caudate (DLC) and nucleus accumbens (NAc) core. Using voltammetry in brain slices from cynomolgus macaques after 6 months of ad libitum ethanol drinking, we found increased KOR sensitivity in both the DLC and NAc. The magnitude of ethanol intake predicted increases in KOR sensitivity in the NAc core, but not the DLC. Additionally, ethanol drinking increased dopamine release and uptake in the NAc, but decreased both of these measures in the DLC. These data suggest that chronic daily drinking may result in regionally distinct disruptions of striatal outputs. In concert with previous reports showing increased KOR regulation of drinking behaviors induced by ethanol exposure, the strong relationship between KOR activity and voluntary ethanol intake observed here gives further support to the hypothesis that KORs may provide a promising pharmacotherapeutic target in the treatment of alcoholism. Copyright © 2015 the authors 0270-6474/15/355959-10$15.00/0.

  6. Weak reward source memory in depression reflects blunted activation of VTA/SN and parahippocampus.

    Science.gov (United States)

    Dillon, Daniel G; Dobbins, Ian G; Pizzagalli, Diego A

    2014-10-01

    Reward responses in the medial temporal lobes and dopaminergic midbrain boost episodic memory formation in healthy adults, and weak memory for emotionally positive material in depression suggests this mechanism may be dysfunctional in major depressive disorder (MDD). To test this hypothesis, we performed a study in which unmedicated adults with MDD and healthy controls encoded drawings paired with reward or zero tokens during functional magnetic resonance imaging. In a recognition test, participants judged whether drawings were previously associated with the reward token ('reward source') or the zero token ('zero source'). Unlike controls, depressed participants failed to show better memory for drawings from the reward source vs the zero source. Consistent with predictions, controls also showed a stronger encoding response to reward tokens vs zero tokens in the right parahippocampus and dopaminergic midbrain, whereas the MDD group showed the opposite pattern-stronger responses to zero vs reward tokens-in these regions. Differential activation of the dopaminergic midbrain by reward vs zero tokens was positively correlated with the reward source memory advantage in controls, but not depressed participants. These data suggest that weaker memory for positive material in depression reflects blunted encoding responses in the dopaminergic midbrain and medial temporal lobes. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  7. Brain reward region responsivity of adolescents with and without parental substance use disorders.

    Science.gov (United States)

    Stice, Eric; Yokum, Sonja

    2014-09-01

    The present study tested the competing hypotheses that adolescents at risk for future substance abuse and dependence by virtue of parental substance use disorders show either weaker or stronger responsivity of brain regions implicated in reward relative to youth without parental history of substance use disorders. Adolescents (n = 52) matched on demographics with and without parental substance use disorders, as determined by diagnostic interviews, who denied substance use in the past year were compared on functional MRI (fMRI) paradigms assessing neural response to receipt and anticipated receipt of monetary and food reward. Parental-history-positive versus -negative adolescents showed greater activation in the left dorsolateral prefrontal cortex and bilateral putamen, and less activation in the fusiform gyrus and inferior temporal gyrus in response to anticipating winning money, as well as greater activation in the left midbrain and right paracentral lobule, and less activation in the right middle frontal gyrus in response to milkshake receipt. Results indicate that adolescents at risk for future onset of substance use disorders show elevated responsivity of brain regions implicated in reward, extending results from 2 smaller prior studies that found that individuals with versus without parental alcohol use disorders showed greater reward region response to anticipated monetary reward and pictures of alcohol. Collectively, results provide support for the reward surfeit model of substance use disorders, rather than the reward deficit model.

  8. Response of neural reward regions to food cues in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Cascio Carissa J

    2012-05-01

    Full Text Available Abstract Background One hypothesis for the social deficits that characterize autism spectrum disorders (ASD is diminished neural reward response to social interaction and attachment. Prior research using established monetary reward paradigms as a test of non-social reward to compare with social reward may involve confounds in the ability of individuals with ASD to utilize symbolic representation of money and the abstraction required to interpret monetary gains. Thus, a useful addition to our understanding of neural reward circuitry in ASD includes a characterization of the neural response to primary rewards. Method We asked 17 children with ASD and 18 children without ASD to abstain from eating for at least four hours before an MRI scan in which they viewed images of high-calorie foods. We assessed the neural reward network for increases in the blood oxygenation level dependent (BOLD signal in response to the food images Results We found very similar patterns of increased BOLD signal to these images in the two groups; both groups showed increased BOLD signal in the bilateral amygdala, as well as in the nucleus accumbens, orbitofrontal cortex, and insula. Direct group comparisons revealed that the ASD group showed a stronger response to food cues in bilateral insula along the anterior-posterior gradient and in the anterior cingulate cortex than the control group, whereas there were no neural reward regions that showed higher activation for controls than for ASD. Conclusion These results suggest that neural response to primary rewards is not diminished but in fact shows an aberrant enhancement in children with ASD.

  9. Changes in reward-induced brain activation in opiate addicts.

    Science.gov (United States)

    Martin-Soelch, C; Chevalley, A F; Künig, G; Missimer, J; Magyar, S; Mino, A; Schultz, W; Leenders, K L

    2001-10-01

    Many studies indicate a role of the cerebral dopaminergic reward system in addiction. Motivated by these findings, we examined in opiate addicts whether brain regions involved in the reward circuitry also react to human prototypical rewards. We measured regional cerebral blood flow (rCBF) with H(2)(15)O positron emission tomography (PET) during a visuo-spatial recognition task with delayed response in control subjects and in opiate addicts participating in a methadone program. Three conditions were defined by the types of feedback: nonsense feedback; nonmonetary reinforcement; or monetary reward, received by the subjects for a correct response. We found in the control subjects rCBF increases in regions associated with the meso-striatal and meso-corticolimbic circuits in response to both monetary reward and nonmonetary reinforcement. In opiate addicts, these regions were activated only in response to monetary reward. Furthermore, nonmonetary reinforcement elicited rCBF increases in limbic regions of the opiate addicts that were not activated in the control subjects. Because psychoactive drugs serve as rewards and directly affect regions of the dopaminergic system like the striatum, we conclude that the differences in rCBF increases between controls and addicts can be attributed to an adaptive consequence of the addiction process.

  10. "Liking" and "wanting" linked to Reward Deficiency Syndrome (RDS): hypothesizing differential responsivity in brain reward circuitry.

    Science.gov (United States)

    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.

  11. Reward modulation of hippocampal subfield activation during successful associative encoding and retrieval

    Science.gov (United States)

    Wolosin, Sasha M.; Zeithamova, Dagmar; Preston, Alison R.

    2012-01-01

    Emerging evidence suggests that motivation enhances episodic memory formation through interactions between medial temporal lobe (MTL) structures and dopaminergic midbrain. In addition, recent theories propose that motivation specifically facilitates hippocampal associative binding processes, resulting in more detailed memories that are readily reinstated from partial input. Here, we used high-resolution functional magnetic resonance imaging to determine how motivation influences associative encoding and retrieval processes within human MTL subregions and dopaminergic midbrain. Participants intentionally encoded object associations under varying conditions of reward and performed a retrieval task during which studied associations were cued from partial input. Behaviorally, cued recall performance was superior for high-value relative to low-value associations; however, participants differed in the degree to which rewards influenced memory. The magnitude of behavioral reward modulation was associated with reward-related activation changes in dentate gyrus/CA2,3 during encoding and enhanced functional connectivity between dentate gyrus/CA2,3 and dopaminergic midbrain during both the encoding and retrieval phases of the task. These findings suggests that within the hippocampus, reward-based motivation specifically enhances dentate gyrus/CA2,3 associative encoding mechanisms through interactions with dopaminergic midbrain. Furthermore, within parahippocampal cortex and dopaminergic midbrain regions, activation associated with successful memory formation was modulated by reward across the group. During the retrieval phase, we also observed enhanced activation in hippocampus and dopaminergic midbrain for high-value associations that occurred in the absence of any explicit cues to reward. Collectively, these findings shed light on fundamental mechanisms through which reward impacts associative memory formation and retrieval through facilitation of MTL and VTA/SN processing

  12. Hatching the behavioral addiction egg: Reward Deficiency Solution System (RDSS)™ as a function of dopaminergic neurogenetics and brain functional connectivity linking all addictions under a common rubric.

    Science.gov (United States)

    Blum, Kenneth; Febo, Marcelo; McLaughlin, Thomas; Cronjé, Frans J; Han, David; Gold, S Mark

    2014-09-01

    Following the first association between the dopamine D2 receptor gene polymorphism and severe alcoholism, there has been an explosion of research reports in the psychiatric and behavioral addiction literature and neurogenetics. With this increased knowledge, the field has been rife with controversy. Moreover, with the advent of Whole Genome-Wide Studies (GWAS) and Whole Exome Sequencing (WES), along with Functional Genome Convergence, the multiple-candidate gene approach still has merit and is considered by many as the most prudent approach. However, it is the combination of these two approaches that will ultimately define real, genetic allelic relationships, in terms of both risk and etiology. Since 1996, our laboratory has coined the umbrella term Reward Deficiency Syndrome (RDS) to explain the common neurochemical and genetic mechanisms involved with both substance and non-substance, addictive behaviors. This is a selective review of peer-reviewed papers primary listed in Pubmed and Medline. A review of the available evidence indicates the importance of dopaminergic pathways and resting-state, functional connectivity of brain reward circuits. Importantly, the proposal is that the real phenotype is RDS and impairments in the brain's reward cascade, either genetically or environmentally (epigenetically) induced, influence both substance and non-substance, addictive behaviors. Understanding shared common mechanisms will ultimately lead to better diagnosis, treatment and prevention of relapse. While, at this juncture, we cannot as yet state that we have "hatched the behavioral addiction egg", we are beginning to ask the correct questions and through an intense global effort will hopefully find a way of "redeeming joy" and permitting homo sapiens live a life, free of addiction and pain.

  13. Stimulatory effect of the D2 antagonist sulpiride on glucose utilization in dopaminergic regions of rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Pizzolato, G; Soncrant, T T; Larson, D M; Rapoport, S I

    1987-08-01

    Local cerebral glucose utilization (LCGU) was measured, using the quantitative autoradiographic (/sup 14/C)2-deoxy-D-glucose method, in 56 brain regions of 3-month-old, awake Fischer-344 rats, after intraperitoneal administration of sulpiride (SULP) 100 mg/kg. SULP, an atypical neuroleptic, is a selective antagonist of D2 dopamine receptors. LCGU was reduced in a few nondopaminergic regions at 1 h after drug administration. Thereafter, SULP progressively elevated LCGU in many other regions. At 3 h, LCGU was elevated in 23% of the regions examined, most of which are related to the CNS dopaminergic system (caudate-putamen, nucleus accumbens, olfactory tubercle, lateral habenula, median eminence, paraventricular hypothalamic nucleus). Increases of LCGU were observed also in the suprachiasmatic nucleus, lateral geniculate, and inferior olive. These effects of SULP on LCGU differ from the effects of the typical neuroleptic haloperidol, which produces widespread decreases in LCGU in the rat brain. Selective actions on different subpopulations of dopamine receptors may explain the different effects of the two neuroleptics on brain metabolism, which correspond to their different clinical and behavioral actions.

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

    Science.gov (United States)

    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.

  15. Neurobiological underpinnings of reward anticipation and outcome evaluation in gambling disorder

    DEFF Research Database (Denmark)

    Linnet, Jakob

    2014-01-01

    Gambling disorder is characterized by persistent and recurrent maladaptive gambling behavior, which leads to clinically significant impairment or distress. The disorder is associated with dysfunctions in the dopamine system. The dopamine system codes reward anticipation and outcome evaluation....... Reward anticipation refers to dopaminergic activation prior to reward, while outcome evaluation refers to dopaminergic activation after reward. This article reviews evidence of dopaminergic dysfunctions in reward anticipation and outcome evaluation in gambling disorder from two vantage points: a model...... in gambling disorder are suggested....

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Patricia Rosell-Negre

    Full Text Available 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.

  19. Dopaminergic dysfunction in abstinent dexamphetamine users: results from a pharmacological fMRI study using a reward anticipation task and a methylphenidate challenge.

    Science.gov (United States)

    Schouw, M L J; De Ruiter, M B; Kaag, A M; van den Brink, W; Lindauer, R J L; Reneman, L

    2013-06-01

    Dopamine (DA) is involved in systems governing motor actions, motivational processes and cognitive functions. Preclinical studies have shown that even relatively low doses of d-amphetamine (dAMPH) (equivalent to doses used in clinical Practice) can lead to DA neurotoxicity in rodents and non-human primates (Ricaurte et al., 2005). Therefore, we investigated the DAergic function in eight male recreational users of dAMPH and eight male healthy controls using functional magnetic resonance imaging (fMRI). We compared brain activation between both groups during a monetary incentive delay task (Knutson et al., 2001) with and without an oral methylphenidate (MPH) challenge. All subjects were abstinent for at least 2 weeks during the baseline scan. The second scan was performed on the same day 1.5 h after receiving an oral dose of 35 mg MPH (approximately 0.5 mg/kg) when peak MPH binding was assumed. When anticipating reward, dAMPH users showed lower striatal activation in comparison to control subjects. In addition, MPH induced a reduction in the striatal activation during reward anticipation in healthy controls, whereas no such effect was observed in dAMPH users. The combination of these findings provides further evidence for frontostriatal DAergic dysfunction in recreational dAMPH users and is consistent with preclinical data suggesting neurotoxic effects of chronic dAMPH use. The findings of this explorative study could have important implications for humans in need for treatment with dAMPH, such as patients suffering from ADHD and therefore this study needs replication in a larger sample. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. Nicotine Withdrawal Induces Neural Deficits in Reward Processing.

    Science.gov (United States)

    Oliver, Jason A; Evans, David E; Addicott, Merideth A; Potts, Geoffrey F; Brandon, Thomas H; Drobes, David J

    2017-06-01

    Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task. Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors. Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p nicotine dependence (p Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes. Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in smokers' neural activity. This may play a role in the subjective aversive experience of nicotine withdrawal and potentially contribute to smoking relapse. Interventions that address abnormal responding to both pleasant and

  1. Role of ghrelin in drug abuse and reward-relevant behaviors: a burgeoning field and gaps in the literature.

    Science.gov (United States)

    Revitsky, A R; Klein, L C

    2013-09-01

    Ghrelin is a gut-brain hormone that regulates energy balance through food consumption. While ghrelin is well known for its role in hypothalamic activation and homeostatic feeding, more recent evidence suggests that ghrelin also is involved in hedonic feeding through the dopaminergic reward pathway. This paper investigated how ghrelin administration (intraperitoneal, intracerebroventricular, or directly into dopaminergic reward-relevant brain regions) activates the dopaminergic reward pathway and associated reward-relevant behavioral responses in rodents. A total of 19 empirical publications that examined one or more of these variables were included in this review. Overall, ghrelin administration increases dopamine levels in the nucleus accumbens, as well as reward-relevant behaviors such as food (both standard chow and palatable foods) and alcohol consumption. Ghrelin administration also increases operant responding for sucrose, and conditioned place preference. Following a review of the small body of literature examining the effects of ghrelin administration on the dopamine reward pathway, we present a model of the relationship between ghrelin and dopaminergic reward activation. Specifically, ghrelin acts on ghrelin receptors (GHS-R1A) in the ventral tegmental area (VTA) and lateral dorsal tegmental nucleus (LDTg) to stimulate the mesolimbic dopamine reward pathway, which results in increased rewarding behaviors in rodents. Results from this review suggest that selective antagonism of the ghrelin system may serve as potential treatment for addictive drug use. This review highlights gaps in the literature, including a lack of examination of sex- or age-related differences in the effects of ghrelin on dopamine reward processes. In light of vulnerability to drug abuse among female and adolescent populations, future studies should target these individual difference factors.

  2. Addiction: beyond dopamine reward circuitry.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Fowler, Joanna S; Tomasi, Dardo; Telang, Frank

    2011-09-13

    Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction.

  3. Addiction: Beyond dopamine reward circuitry

    International Nuclear Information System (INIS)

    Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.; Telang, F.

    2011-01-01

    Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction.

  4. Addiction: Beyond dopamine reward circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.; Telang, F.

    2011-09-13

    Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction.

  5. Age-related functional changes in gustatory and reward processing regions: An fMRI study.

    Science.gov (United States)

    Jacobson, Aaron; Green, Erin; Murphy, Claire

    2010-11-01

    Changes in appetite in older adults may result in unhealthy weight change and negatively affect overall nutrition. Research examining gustatory processing in young adults has linked changes in patterns of the hemodynamic response of gustatory and motivation related brain regions to the physiological states of hunger and satiety. Whether the same brain regions are involved in taste processing in older adults is unknown. The current study used functional magnetic resonance imaging (fMRI) to examine age-related changes in gustatory processing during hedonic assessment. Caffeine, citric acid, sucrose, and NaCl were administered orally during two event-related fMRI sessions, one during hunger and one after a pre-load. Participants assessed the pleasantness of the solutions in each session. Increased activity of the insula was seen in both age groups during hunger. Activity of secondary and higher order taste processing and reward regions such as the orbitofrontal cortex, amygdala, hippocampus, thalamus, and caudate nucleus was also observed. Hunger and satiety differentially affected the hemodynamic response, resulting in positive global activation during hunger and negative during satiety in both age groups. While in a state of hunger, the frequency and consistency of positive activation in gustatory and reward processing regions was greater in older adults. Additional regions not commonly associated with taste processing were also activated in older adults. Investigating the neurological response of older adults to taste stimuli under conditions of hunger and satiety may aid in understanding appetite, health, and functional changes in this population. Copyright 2010 Elsevier Inc. All rights reserved.

  6. Individual Differences in Reward and Somatosensory-Motor Brain Regions Correlate with Adiposity in Adolescents.

    Science.gov (United States)

    Rapuano, Kristina M; Huckins, Jeremy F; Sargent, James D; Heatherton, Todd F; Kelley, William M

    2016-06-01

    The prevalence of adolescent obesity has increased dramatically over the past three decades, and research has documented that the number of television shows viewed during childhood is associated with greater risk for obesity. In particular, considerable evidence suggests that exposure to food marketing promotes eating habits that contribute to obesity. The present study examines neural responses to dynamic food commercials in overweight and healthy-weight adolescents using functional magnetic resonance imaging (fMRI). Compared with non-food commercials, food commercials more strongly engaged regions involved in attention and saliency detection (occipital lobe, precuneus, superior temporal gyri, and right insula) and in processing rewards [left and right nucleus accumbens (NAcc) and left orbitofrontal cortex (OFC)]. Activity in the left OFC and right insula further correlated with subjects' percent body fat at the time of the scan. Interestingly, this reward-related activity to food commercials was accompanied by the additional recruitment of mouth-specific somatosensory-motor cortices-a finding that suggests the intriguing possibility that higher-adiposity adolescents mentally simulate eating behaviors and offers a potential neural mechanism for the formation and reinforcement of unhealthy eating habits that may hamper an individual's ability lose weight later in life. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Increased Fos expression among midbrain dopaminergic cell groups during birdsong tutoring.

    Science.gov (United States)

    Nordeen, E J; Holtzman, D A; Nordeen, K W

    2009-08-01

    During avian vocal learning, birds memorize conspecific song patterns and then use auditory feedback to match their vocal output to this acquired template. Some models of song learning posit that during tutoring, conspecific visual, social and/or auditory cues activate neuromodulatory systems that encourage acquisition of the tutor's song and attach incentive value to that specific acoustic pattern. This hypothesis predicts that stimuli experienced during social tutoring activate cell populations capable of signaling reward. Using immunocytochemistry for the protein product of the immediate early gene c-Fos, we found that brief exposure of juvenile male zebra finches to a live familiar male tutor increased the density of Fos+ cells within two brain regions implicated in reward processing: the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). This activation of Fos appears to involve both dopaminergic and non-dopaminergic VTA/SNc neurons. Intriguingly, a familiar tutor was more effective than a novel tutor in stimulating Fos expression within these regions. In the periaqueductal gray, a dopamine-enriched cell population that has been implicated in emotional processing, Fos labeling also was increased after tutoring, with a familiar tutor again being more effective than a novel conspecific. As several neural regions implicated in song acquisition receive strong dopaminergic projections from these midbrain nuclei, their activation in conjunction with hearing the tutor's song could help to establish sensory representations that later guide motor sequence learning.

  8. Dysfunctional involvement of emotion and reward brain regions on social decision making in excess weight adolescents.

    Science.gov (United States)

    Verdejo-García, Antonio; Verdejo-Román, Juan; Rio-Valle, Jacqueline S; Lacomba, Juan A; Lagos, Francisco M; Soriano-Mas, Carles

    2015-01-01

    Obese adolescents suffer negative social experiences, but no studies have examined whether obesity is associated with dysfunction of the social brain or whether social brain abnormalities relate to disadvantageous traits and social decisions. We aimed at mapping functional activation differences in the brain circuitry of social decision making in adolescents with excess versus normal weight, and at examining whether these separate patterns correlate with reward/punishment sensitivity, disordered eating features, and behavioral decisions. In this fMRI study, 80 adolescents aged 12 to 18 years old were classified in two groups based on age adjusted body mass index (BMI) percentiles: normal weight (n = 44, BMI percentiles 5th-84th) and excess weight (n = 36, BMI percentile ≥ 85th). Participants were scanned while performing a social decision-making task (ultimatum game) in which they chose to "accept" or "reject" offers to split monetary stakes made by another peer. Offers varied in fairness (Fair vs. Unfair) but in all cases "accepting" meant both players win the money, whereas "rejecting" meant both lose it. We showed that adolescents with excess weight compared to controls display significantly decreased activation of anterior insula, anterior cingulate, and midbrain during decisions about Unfair versus Fair offers. Moreover, excess weight subjects show lower sensitivity to reward and more maturity fears, which correlate with insula activation. Indeed, blunted insula activation accounted for the relationship between maturity fears and acceptance of unfair offers. Excess weight adolescents have diminished activation of brain regions essential for affective tracking of social decision making, which accounts for the association between maturity fears and social decisions. © 2014 Wiley Periodicals, Inc.

  9. Dopamine modulates reward system activity during subconscious processing of sexual stimuli.

    Science.gov (United States)

    Oei, Nicole Y L; Rombouts, Serge Arb; Soeter, Roelof P; van Gerven, Joop M; Both, Stephanie

    2012-06-01

    Dopaminergic medication influences conscious processing of rewarding stimuli, and is associated with impulsive-compulsive behaviors, such as hypersexuality. Previous studies have shown that subconscious subliminal presentation of sexual stimuli activates brain areas known to be part of the 'reward system'. In this study, it was hypothesized that dopamine modulates activation in key areas of the reward system, such as the nucleus accumbens, during subconscious processing of sexual stimuli. Young healthy males (n=53) were randomly assigned to two experimental groups or a control group, and were administered a dopamine antagonist (haloperidol), a dopamine agonist (levodopa), or placebo. Brain activation was assessed during a backward-masking task with subliminally presented sexual stimuli. Results showed that levodopa significantly enhanced the activation in the nucleus accumbens and dorsal anterior cingulate when subliminal sexual stimuli were shown, whereas haloperidol decreased activations in those areas. Dopamine thus enhances activations in regions thought to regulate 'wanting' in response to potentially rewarding sexual stimuli that are not consciously perceived. This running start of the reward system might explain the pull of rewards in individuals with compulsive reward-seeking behaviors such as hypersexuality and patients who receive dopaminergic medication.

  10. The endocannabinoid system in brain reward processes.

    Science.gov (United States)

    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.

  11. Influence of reward motivation on human declarative memory.

    Science.gov (United States)

    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.

  12. Neurobiological underpinnings of reward anticipation and outcome evaluation in gambling disorder

    DEFF Research Database (Denmark)

    Linnet, Jakob

    2014-01-01

    Gambling disorder is characterized by persistent and recurrent maladaptive gambling behavior, which leads to clinically significant impairment or distress. The disorder is associated with dysfunctions in the dopamine system. The dopamine system codes reward anticipation and outcome evaluation....... Reward anticipation refers to dopaminergic activation prior to reward, while outcome evaluation refers to dopaminergic activation after reward. This article reviews evidence of dopaminergic dysfunctions in reward anticipation and outcome evaluation in gambling disorder from two vantage points: a model...... of reward prediction and reward prediction error by Wolfram Schultz et al. and a model of “wanting” and “liking” by Terry E. Robinson and Kent C. Berridge. Both models offer important insights on the study of dopaminergic dysfunctions in addiction, and implications for the study of dopaminergic dysfunctions...

  13. Context-dependent colonization dynamics: Regional reward contagion drives local compression in aquatic beetles.

    Science.gov (United States)

    Pintar, Matthew R; Resetarits, William J

    2017-09-01

    Habitat selection by colonizing organisms is an important factor in determining species abundance and community dynamics at multiple spatial scales. Many organisms select habitat patches based on intrinsic patch quality, but patches exist in complex landscapes linked by dispersal and colonization, forming metapopulations and metacommunities. Perceived patch quality can be influenced by neighbouring patches through spatial contagion, wherein perceived quality of one patch can extend beyond its borders and either increase or decrease the colonization of neighbouring patches and localities. These spatially explicit colonization dynamics can result in habitat compression, wherein more colonists occupy a patch or locality than in the absence of spatial context dependence. Previous work on contagion/compression focused primarily on the role of predators in driving colonization patterns. Our goal was to determine whether resource abundance can drive multi-scale colonization dynamics of aquatic beetles through the processes of contagion and compression in naturally colonized experimental pools. We established two levels (high/low quality) of within-patch resource abundances (leaf litter) using an experimental landscape of mesocosms, and assayed colonization by 35 species of aquatic beetles. Patches were arranged in localities (sets of two patches), which consisted of a combination of two patch-level resource levels in a 2 × 2 factorial design, allowing us to assay colonization at both locality and patch levels. We demonstrate that patterns of species abundance and richness of colonizing aquatic beetles are determined by patch quality and context-dependent processes at multiple spatial scales. Localities that consisted of at least one high-quality patch were colonized at equivalent rates that were higher than localities containing only low-quality patches, displaying regional reward contagion. In localities that consisted of one high- and one low-quality patch, reward

  14. Selection of the regions of interest (SRI) in the SPECT semi-quantitative analysis of central dopaminergic receptors

    International Nuclear Information System (INIS)

    Baulieu, J.L.; Prunier-Levilion, C.; Tranquart, F.; Ribeiro, M.J.; Chartier, J.R.; Guilloteau, D.; Autret, A.; Besnard, J.C.; Bekhechi, D.; Chossat, F.

    1997-01-01

    The aim of this work was to compare different types of SRIs used in the SPECT semi-quantitative analysis of central dopaminergic receptors. The SPECT with 123 I iodolisuride (Cis bio international) was carried out in the same center with a Helix - Elscint double head camera with 'fan beam', one hour after injection of 123 I iodolisuride (190 ± 31 MBq). In 8 patients afflicted with Parkinson's disease (group 1) and 9 patients presenting an extra-pyramidal syndrome by striatal stretching (group 2), two approaches of SRI tracing were undertaken: 1. Geometrical and standard (circles, ellipses, rectangles) SRIs; 2. Anatomical and individual SRIs based on TDM and perfusion scintigraphy. The SRIs were placed on the entire striatum, the head of cauda nucleus, putamen, thalamus, frontal, occipital cortex and cerebellum. In total, for each patient, 31 ratios were calculated of the striatal activity and the activity of a references zone. The discriminative value of the ratios was evaluated by the p value of comparison between groups 1 and 2. A correlation has been searched for between the ratios taken 2 by 2. The most discriminative ratios were: cauda/occipital, cauda/frontal, striatum/occipital based on geometrical standard SRIs (p 0.001, p = 0.002, p = 0.003, respectively). A close correlation has been found between the ratios with occipital and cerebellar references (r 2 0.71) but not between the ratios with frontal or occipital reference, or frontal and cerebellum reference. In the employed conditions, the geometrical tracing of the SRIs is preferable as against an anatomic tracing. The occipital cortex is the best reference while the frontal activity can not be retained as reference. The cauda/occipital ratios allow a very good discrimination between the Parkinson's disease and other extra pyramidal syndromes investigated by 123 I iodolisuride SPECT

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

    Science.gov (United States)

    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.

  16. Goal or gold: overlapping reward processes in soccer players upon scoring and winning money.

    Directory of Open Access Journals (Sweden)

    Alexander Niklas Häusler

    Full Text Available Social rewards are important incentives for human behavior. This is especially true in team sports such as the most popular one worldwide: soccer. We investigated reward processing upon scoring a soccer goal in a standard two-versus-one situation and in comparison to winning in a monetary incentive task. The results show a strong overlap in brain activity between the two conditions in established reward regions of the mesolimbic dopaminergic system, including the ventral striatum and ventromedial pre-frontal cortex. The three main components of reward-associated learning, i.e., reward probability (RP, reward reception (RR and reward prediction errors (RPE showed highly similar activation in both con-texts, with only the RR and RPE components displaying overlapping reward activity. Passing and shooting behavior did not correlate with individual egoism scores, but we observe a positive correlation be-tween egoism and activity in the left middle frontal gyrus upon scoring after a pass versus a direct shot. Our findings suggest that rewards in the context of soccer and monetary incentives are based on similar neural processes.

  17. Goal or Gold: Overlapping Reward Processes in Soccer Players upon Scoring and Winning Money

    Science.gov (United States)

    Häusler, Alexander Niklas; Becker, Benjamin; Bartling, Marcel; Weber, Bernd

    2015-01-01

    Social rewards are important incentives for human behavior. This is especially true in team sports such as the most popular one worldwide: soccer. We investigated reward processing upon scoring a soccer goal in a standard two-versus-one situation and in comparison to winning in a monetary incentive task. The results show a strong overlap in brain activity between the two conditions in established reward regions of the mesolimbic dopaminergic system, including the ventral striatum and ventromedial pre-frontal cortex. The three main components of reward-associated learning i.e. reward probability (RP), reward reception (RR) and reward prediction errors (RPE) showed highly similar activation in both con-texts, with only the RR and RPE components displaying overlapping reward activity. Passing and shooting behavior did not correlate with individual egoism scores, but we observe a positive correlation be-tween egoism and activity in the left middle frontal gyrus upon scoring after a pass versus a direct shot. Our findings suggest that rewards in the context of soccer and monetary incentives are based on similar neural processes. PMID:25875594

  18. Regional brain activation supporting cognitive control in the context of reward is associated with treated adolescents’ marijuana problem severity at follow-up: A preliminary study

    Directory of Open Access Journals (Sweden)

    Tammy Chung

    2015-12-01

    Full Text Available This preliminary study examined the extent to which regional brain activation during a reward cue antisaccade (AS task was associated with 6-month treatment outcome in adolescent substance users. Antisaccade performance provides a sensitive measure of executive function and cognitive control, and generally improves with reward cues. We hypothesized that when preparing to execute an AS, greater activation in regions associated with cognitive and oculomotor control supporting AS, particularly during reward cue trials, would be associated with lower substance use severity at 6-month follow-up. Adolescents (n = 14, ages 14–18 recruited from community-based outpatient treatment completed an fMRI reward cue AS task (reward and neutral conditions, and provided follow-up data. Results indicated that AS errors decreased in reward, compared to neutral, trials. AS behavioral performance, however, was not associated with treatment outcome. As hypothesized, activation in regions of interest (ROIs associated with cognitive (e.g., ventrolateral prefrontal cortex and oculomotor control (e.g., supplementary eye field during reward trials were inversely correlated with marijuana problem severity at 6-months. ROI activation during neutral trials was not associated with outcomes. Results support the role of motivational (reward cue factors to enhance cognitive control processes, and suggest a potential brain-based correlate of youth treatment outcome.

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

    Science.gov (United States)

    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

  20. Reward, dopamine and the control of food intake: implications for obesity

    Energy Technology Data Exchange (ETDEWEB)

    Volkow N. D.; Wang G.; Volkow, N.D.; Wang, G.-J.; Baler, R.D.

    2011-10-01

    The ability to resist the urge to eat requires the proper functioning of neuronal circuits involved in top-down control to oppose the conditioned responses that predict reward from eating the food and the desire to eat the food. Imaging studies show that obese subjects might have impairments in dopaminergic pathways that regulate neuronal systems associated with reward sensitivity, conditioning and control. It is known that the neuropeptides that regulate energy balance (homeostatic processes) through the hypothalamus also modulate the activity of dopamine cells and their projections into regions involved in the rewarding processes underlying food intake. It is postulated that this could also be a mechanism by which overeating and the resultant resistance to homoeostatic signals impairs the function of circuits involved in reward sensitivity, conditioning and cognitive control.

  1. Reward, dopamine and the control of food intake: implications for obesity

    International Nuclear Information System (INIS)

    Volkow, N.D.; Wang, G.J.; Baler, R.D.

    2011-01-01

    The ability to resist the urge to eat requires the proper functioning of neuronal circuits involved in top-down control to oppose the conditioned responses that predict reward from eating the food and the desire to eat the food. Imaging studies show that obese subjects might have impairments in dopaminergic pathways that regulate neuronal systems associated with reward sensitivity, conditioning and control. It is known that the neuropeptides that regulate energy balance (homeostatic processes) through the hypothalamus also modulate the activity of dopamine cells and their projections into regions involved in the rewarding processes underlying food intake. It is postulated that this could also be a mechanism by which overeating and the resultant resistance to homoeostatic signals impairs the function of circuits involved in reward sensitivity, conditioning and cognitive control.

  2. Food-Related Odors Activate Dopaminergic Brain Areas

    OpenAIRE

    Agnieszka Sorokowska; Agnieszka Sorokowska; Katherina Schoen; Cornelia Hummel; Pengfei Han; Jonathan Warr; Thomas Hummel

    2017-01-01

    Food-associated cues of different sensory categories have often been shown to be a potent elicitor of cerebral activity in brain reward circuits. Smells influence and modify the hedonic qualities of eating experience, and in contrast to smells not associated with food, perception of food-associated odors may activate dopaminergic brain areas. In this study, we aimed to verify previous findings related to the rewarding value of food-associated odors by means of an fMRI design involving careful...

  3. Consolidation power of extrinsic rewards: reward cues enhance long-term memory for irrelevant past events.

    Science.gov (United States)

    Murayama, Kou; Kitagami, Shinji

    2014-02-01

    Recent research suggests that extrinsic rewards promote memory consolidation through dopaminergic modulation processes. However, no conclusive behavioral evidence exists given that the influence of extrinsic reward on attention and motivation during encoding and consolidation processes are inherently confounded. The present study provides behavioral evidence that extrinsic rewards (i.e., monetary incentives) enhance human memory consolidation independently of attention and motivation. Participants saw neutral pictures, followed by a reward or control cue in an unrelated context. Our results (and a direct replication study) demonstrated that the reward cue predicted a retrograde enhancement of memory for the preceding neutral pictures. This retrograde effect was observed only after a delay, not immediately upon testing. An additional experiment showed that emotional arousal or unconscious resource mobilization cannot explain the retrograde enhancement effect. These results provide support for the notion that the dopaminergic memory consolidation effect can result from extrinsic reward.

  4. Future planning: default network activity couples with frontoparietal control network and reward-processing regions during process and outcome simulations.

    Science.gov (United States)

    Gerlach, Kathy D; Spreng, R Nathan; Madore, Kevin P; Schacter, Daniel L

    2014-12-01

    We spend much of our daily lives imagining how we can reach future goals and what will happen when we attain them. Despite the prevalence of such goal-directed simulations, neuroimaging studies on planning have mainly focused on executive processes in the frontal lobe. This experiment examined the neural basis of process simulations, during which participants imagined themselves going through steps toward attaining a goal, and outcome simulations, during which participants imagined events they associated with achieving a goal. In the scanner, participants engaged in these simulation tasks and an odd/even control task. We hypothesized that process simulations would recruit default and frontoparietal control network regions, and that outcome simulations, which allow us to anticipate the affective consequences of achieving goals, would recruit default and reward-processing regions. Our analysis of brain activity that covaried with process and outcome simulations confirmed these hypotheses. A functional connectivity analysis with posterior cingulate, dorsolateral prefrontal cortex and anterior inferior parietal lobule seeds showed that their activity was correlated during process simulations and associated with a distributed network of default and frontoparietal control network regions. During outcome simulations, medial prefrontal cortex and amygdala seeds covaried together and formed a functional network with default and reward-processing regions. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  5. Reward anticipation revisited- evidence from an fMRI study in euthymic bipolar I patients and healthy first-degree relatives.

    Science.gov (United States)

    Kollmann, Bianca; Scholz, Vanessa; Linke, Julia; Kirsch, Peter; Wessa, Michèle

    2017-09-01

    Symptomatic phases in bipolar disorder (BD) are hypothesized to result from a hypersensitive behavioral activation system (BAS) being sensitive to potential rewards. However, studies on the neuronal underpinnings of reward anticipation in BD are scarce with contradictory findings and possibly confounded by effects of dopaminergic medication, necessitating further research on dysfunctional motivation in BD. Moreover, its role as vulnerability marker for BD is unclear. Functional imaging was conducted in 16 euthymic BD-I patients free from dopaminergic medication and 19 healthy first-degree relatives using a monetary incentive delay task and compared to parallelized control groups. Further, reward proneness, using the BIS/BAS questionnaire, and its relationship to neural reward anticipation was investigated. BD-I patients displayed greater anterior cingulate cortex (ACC) activity during reward anticipation and higher BIS total scores compared to controls, with a positive relationship between the two measures. There were no neural or self-report group differences between relatives and controls. Due to the experimental design, the role of the ACC during receipt of reward remains unknown, sample sizes were rather small, and patients were not naïve to dopaminergic drugs, making an exclusion of medication effects on findings impossible. Our findings give new insights on reward anticipation in BD. BD-I patients rated themselves as more risk avoidant and showed larger recruitment of the ACC rather than ventral striatum compared to controls during reward anticipation, possibly to down-regulate hyperactive limbic reward regions. This activation seems to be a consequence of rather than a vulnerability marker for the disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Dopaminergic agonists for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Gluud, L L; Gluud, C

    2004-01-01

    Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy....

  7. A tribute to Charlie Chaplin: Induced positive affect improves reward-based decision-learning in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    K. Richard eRidderinkhof

    2012-06-01

    Full Text Available Reward-based decision-learning refers to the process of learning to select those actions that lead to rewards while avoiding actions that lead to punishments. This process, known to rely on dopaminergic activity in striatal brain regions, is compromised in Parkinson’s disease (PD. We hypothesized that such decision-learning deficits are alleviated by induced positive affect, which is thought to incur transient boosts in midbrain and striatal dopaminergic activity. Computational measures of probabilistic reward-based decision-learning were determined for 51 patients diagnosed with PD. Previous work has shown these measures to rely on the nucleus caudatus (outcome evaluation during the early phases of learning and the putamen (reward prediction during later phases of learning. We observed that induced positive affect facilitated learning, through its effects on reward prediction rather than outcome evaluation. Viewing a few minutes of comedy clips served to remedy dopamine-related problems in putamen-based frontostriatal circuitry and, consequently, in learning to predict which actions will yield reward.

  8. Reward anticipation modulates the effect of stress-related increases in cortisol on episodic memory.

    Science.gov (United States)

    Quent, Jörn A; McCullough, Andrew M; Sazma, Matt; Wolf, Oliver T; Yonelinas, Andrew P

    2018-01-01

    When acute stress is experienced shortly after an event is encoded into memory, this can slow the forgetting of the study event, which is thought to reflect the effect of cortisol on consolidation. In addition, when events are encoded under conditions of high reward they tend to be remembered better than those encoded under non-rewarding conditions, and these effects are thought to reflect the operation of the dopaminergic reward system. Although both modulatory systems are believed to impact the medial temporal lobe regions critical for episodic memory, the manner, and even the extent, to which these two systems interact is currently unknown. To address this question in the current study, participants encoded words under reward or non-reward conditions, then one half of the participants were stressed using the social evaluation cold pressor task and the other half completed a non-stress control task. After a two-hour delay, all participants received a free recall and recognition memory test. There were no significant effects of stress or reward on overall memory performance. However, for the non-reward items, increases in stress-related cortisol in stressed participants were related to increases in recall and increases in recollection-based recognition responses. In contrast, for the reward items, increases in stress-related cortisol were not related to increases in memory performance. The results indicate that the stress and the reward systems interact in the way they impact episodic memory. The results are consistent with tag and capture models in the sense that cortisol reactivity can only affect non-reward items because plasticity-related products are already provided by reward anticipation. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Low putamen activity associated with poor reward sensitivity in childhood chronic fatigue syndrome

    Directory of Open Access Journals (Sweden)

    Kei Mizuno, Ph.D.

    2016-01-01

    Full Text Available Motivational signals influence a wide variety of cognitive processes and components of behavioral performance. Cognitive dysfunction in patients with childhood chronic fatigue syndrome (CCFS may be closely associated with a low motivation to learn induced by impaired neural reward processing. However, the extent to which reward processing is impaired in CCFS patients is unclear. The aim of the present functional magnetic resonance imaging (fMRI study was to determine whether brain activity in regions related to reward sensitivity is impaired in CCFS patients. fMRI data were collected from 13 CCFS patients (mean age, 13.6 ± 1.0 years and 13 healthy children and adolescents (HCA (mean age, 13.7 ± 1.3 years performing a monetary reward task. Neural activity in high- and low-monetary-reward conditions was compared between CCFS and HCA groups. Severity of fatigue and the reward obtained from learning in daily life were evaluated by questionnaires. Activity of the putamen was lower in the CCFS group than in the HCA group in the low-reward condition, but not in the high-reward condition. Activity of the putamen in the low-reward condition in CCFS patients was negatively and positively correlated with severity of fatigue and the reward from learning in daily life, respectively. We previously revealed that motivation to learn was correlated with striatal activity, particularly the neural activity in the putamen. This suggests that in CCFS patients low putamen activity, associated with altered dopaminergic function, decreases reward sensitivity and lowers motivation to learn.

  10. A nap to recap or how reward regulates hippocampal-prefrontal memory networks during daytime sleep in humans.

    Science.gov (United States)

    Igloi, Kinga; Gaggioni, Giulia; Sterpenich, Virginie; Schwartz, Sophie

    2015-10-16

    Sleep plays a crucial role in the consolidation of newly acquired memories. Yet, how our brain selects the noteworthy information that will be consolidated during sleep remains largely unknown. Here we show that post-learning sleep favors the selectivity of long-term consolidation: when tested three months after initial encoding, the most important (i.e., rewarded, strongly encoded) memories are better retained, and also remembered with higher subjective confidence. Our brain imaging data reveals that the functional interplay between dopaminergic reward regions, the prefrontal cortex and the hippocampus contributes to the integration of rewarded associative memories. We further show that sleep spindles strengthen memory representations based on reward values, suggesting a privileged replay of information yielding positive outcomes. These findings demonstrate that post-learning sleep determines the neural fate of motivationally-relevant memories and promotes a value-based stratification of long-term memory stores.

  11. Deep brain stimulation of nucleus accumbens region in alcoholism affects reward processing.

    Science.gov (United States)

    Heldmann, Marcus; Berding, Georg; Voges, Jürgen; Bogerts, Bernhard; Galazky, Imke; Müller, Ulf; Baillot, Gunther; Heinze, Hans-Jochen; Münte, Thomas F

    2012-01-01

    The influence of bilateral deep brain stimulation (DBS) of the nucleus nucleus (NAcc) on the processing of reward in a gambling paradigm was investigated using H(2)[(15)O]-PET (positron emission tomography) in a 38-year-old man treated for severe alcohol addiction. Behavioral data analysis revealed a less risky, more careful choice behavior under active DBS compared to DBS switched off. PET showed win- and loss-related activations in the paracingulate cortex, temporal poles, precuneus and hippocampus under active DBS, brain areas that have been implicated in action monitoring and behavioral control. Except for the temporal pole these activations were not seen when DBS was deactivated. These findings suggest that DBS of the NAcc may act partially by improving behavioral control.

  12. Serotonergic modulation of reward and punishment: evidence from pharmacological fMRI studies.

    Science.gov (United States)

    Macoveanu, Julian

    2014-03-27

    Until recently, the bulk of research on the human reward system was focused on studying the dopaminergic and opioid neurotransmitter systems. However, extending the initial data from animal studies on reward, recent pharmacological brain imaging studies on human participants bring a new line of evidence on the key role serotonin plays in reward processing. The reviewed research has revealed how central serotonin availability and receptor specific transmission modulates the neural response to both appetitive (rewarding) and aversive (punishing) stimuli in putative reward-related brain regions. Thus, serotonin is suggested to be involved in behavioral control when there is a prospect of reward or punishment. The new findings may have implications in understanding psychiatric disorders such as major depression which is characterized by abnormal serotonergic function and reward-related processing and may also provide a neural correlated for the emotional blunting observed in the clinical treatment of psychiatric disorders with selective serotonin reuptake inhibitors. Given the unique profile of action of each serotonergic receptor subtype, future pharmacological studies may favor receptor specific investigations to complement present research mainly focused on global serotonergic manipulations. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Heterogeneity of reward mechanisms.

    Science.gov (United States)

    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.

  14. Dopamine Signaling in reward-related behaviors

    OpenAIRE

    Baik, Ja-Hyun

    2013-01-01

    Dopamine (DA) regulates emotional and motivational behavior through the mesolimbic dopaminergic pathway. Changes in DA mesolimbic neurotransmission have been found to modify behavioral responses to various environmental stimuli associated with reward behaviors. Psychostimulants, drugs of abuse, and natural reward such as food can cause substantial synaptic modifications to the mesolimbic DA system. Recent studies using optogenetics and DREADDs, together with neuron-specific or circuit-specifi...

  15. The role of the dopaminergic projections in MFB self-stimulation.

    Science.gov (United States)

    Gallistel, C R

    1986-11-01

    Psychophysical experiments indicate that the first stage of the reward pathway in medial forebrain bundle self-stimulation consists of small myelinated descending axons. Pharmacological experiments show that neuroleptics attenuate or abolish the rewarding effect. This had led to the hypothesis that the descending myelinated axons synapse on an ascending dopaminergic second stage projection. 2-Deoxy-[14C]glucose autoradiography in self-stimulating animals or animals receiving automatically administered rewarding stimulation after treatment with reward-blocking doses of pimozide reveals activation of a descending myelinated system but no stimulation-produced activation of an ascending dopaminergic projection system, even though the autoradiographic method reveals the mild elevations and depressions of activity in dopaminergic terminal fields consequent upon injections of neuroleptics and amphetamine, respectively, and the strong activation of the nigrostriatal projection produced by stimulating directly in the substantia nigra. When the effects of neuroleptics and clonidine are measured by the psychophysical method (that is, by lateral shifts in the rate-frequency function), it is found that both drugs produce only gradual and rather small attenuations of rewarding efficacy up to doses at which it is no longer possible to measure their effects. It is suggested that, for neuroleptics at least, the rewarding effect abruptly fails at these doses. It is further suggested that these drugs do not act on the rewarding pathway itself, but on the process by which the rewarding signal is converted to an enduring rewarding effect.

  16. Oxytocin selectively facilitates learning with social feedback and increases activity and functional connectivity in emotional memory and reward processing regions.

    Science.gov (United States)

    Hu, Jiehui; Qi, Song; Becker, Benjamin; Luo, Lizhu; Gao, Shan; Gong, Qiyong; Hurlemann, René; Kendrick, Keith M

    2015-06-01

    In male Caucasian subjects, learning is facilitated by receipt of social compared with non-social feedback, and the neuropeptide oxytocin (OXT) facilitates this effect. In this study, we have first shown a cultural difference in that male Chinese subjects actually perform significantly worse in the same reinforcement associated learning task with social (emotional faces) compared with non-social feedback. Nevertheless, in two independent double-blind placebo (PLC) controlled between-subject design experiments we found OXT still selectively facilitated learning with social feedback. Similar to Caucasian subjects this OXT effect was strongest with feedback using female rather than male faces. One experiment performed in conjunction with functional magnetic resonance imaging showed that during the response, but not feedback phase of the task, OXT selectively increased activity in the amygdala, hippocampus, parahippocampal gyrus and putamen during the social feedback condition, and functional connectivity between the amygdala and insula and caudate. Therefore, OXT may be increasing the salience and reward value of anticipated social feedback. In the PLC group, response times and state anxiety scores during social feedback were associated with signal changes in these same regions but not in the OXT group. OXT may therefore have also facilitated learning by reducing anxiety in the social feedback condition. Overall our results provide the first evidence for cultural differences in social facilitation of learning per se, but a similar selective enhancement of learning with social feedback under OXT. This effect of OXT may be associated with enhanced responses and functional connectivity in emotional memory and reward processing regions. © 2015 Wiley Periodicals, Inc.

  17. Learning Reward Uncertainty in the Basal Ganglia.

    Directory of Open Access Journals (Sweden)

    John G Mikhael

    2016-09-01

    Full Text Available Learning the reliability of different sources of rewards is critical for making optimal choices. However, despite the existence of detailed theory describing how the expected reward is learned in the basal ganglia, it is not known how reward uncertainty is estimated in these circuits. This paper presents a class of models that encode both the mean reward and the spread of the rewards, the former in the difference between the synaptic weights of D1 and D2 neurons, and the latter in their sum. In the models, the tendency to seek (or avoid options with variable reward can be controlled by increasing (or decreasing the tonic level of dopamine. The models are consistent with the physiology of and synaptic plasticity in the basal ganglia, they explain the effects of dopaminergic manipulations on choices involving risks, and they make multiple experimental predictions.

  18. Beyond Rewards

    Science.gov (United States)

    Hall, Philip S.

    2009-01-01

    Using rewards to impact students' behavior has long been common practice. However, using reward systems to enhance student learning conveniently masks the larger and admittedly more difficult task of finding and implementing the structure and techniques that children with special needs require to learn. More important, rewarding the child for good…

  19. Neural correlates of reward processing in adults with 22q11 deletion syndrome.

    Science.gov (United States)

    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

  20. Dissonance-Based Eating Disorder Prevention Program Reduces Reward Region Response to Thin Models; How Actions Shape Valuation.

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    Eric Stice

    Full Text Available Research supports the effectiveness of a dissonance-based eating disorder prevention program wherein high-risk young women with body dissatisfaction critique the thin ideal, which reduces pursuit of this ideal, and the theory that dissonance induction contributes to these effects. Based on evidence that dissonance produces attitudinal change by altering neural representation of valuation, we tested whether completing the Body Project would reduce response of brain regions implicated in reward valuation to thin models. Young women with body dissatisfaction were randomized to this intervention or an educational control condition, completing assessments and fMRI scans while viewing images of thin versus average-weight female models at pre and post. Whole brain analyses indicated that, compared to controls, Body Project participants showed greater reductions in caudate response to images of thin versus average-weight models, though participants in the two conditions showed pretest differences in responsivity of other brain regions that might have contributed to this effect. Greater pre-post reductions in caudate and putamen response to thin models correlated with greater reductions in body dissatisfaction. The finding that the Body Project reduces caudate response to thin models provides novel preliminary evidence that this intervention reduces valuation of media images thought to contribute to body dissatisfaction and eating disorders, providing support for the intervention theory by documenting that this intervention alters an objective biological outcome.

  1. Cognitive control of drug craving inhibits brain reward regions in cocaine abusers

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    Volkow, N.D.; Fowler, J.; Wang, G.J.; Telang, F.; Logan, J.; Jayne, M.; Ma, Y.; Pradhan, K.; Wong, C.T.; Swanson, J.M.

    2010-01-01

    Loss of control over drug taking is considered a hallmark of addiction and is critical in relapse. Dysfunction of frontal brain regions involved with inhibitory control may underlie this behavior. We evaluated whether addicted subjects when instructed to purposefully control their craving responses to drug-conditioned stimuli can inhibit limbic brain regions implicated in drug craving. We used PET and 2-deoxy-2[18F]fluoro-D-glucose to measure brain glucose metabolism (marker of brain function) in 24 cocaine abusers who watched a cocaine-cue video and compared brain activation with and without instructions to cognitively inhibit craving. A third scan was obtained at baseline (without video). Statistical parametric mapping was used for analysis and corroborated with regions of interest. The cocaine-cue video increased craving during the no-inhibition condition (pre 3 {+-} 3, post 6 {+-} 3; p < 0.001) but not when subjects were instructed to inhibit craving (pre 3 {+-} 2, post 3 {+-} 3). Comparisons with baseline showed visual activation for both cocaine-cue conditions and limbic inhibition (accumbens, orbitofrontal, insula, cingulate) when subjects purposefully inhibited craving (p < 0.001). Comparison between cocaine-cue conditions showed lower metabolism with cognitive inhibition in right orbitofrontal cortex and right accumbens (p < 0.005), which was associated with right inferior frontal activation (r = -0.62, p < 0.005). Decreases in metabolism in brain regions that process the predictive (nucleus accumbens) and motivational value (orbitofrontal cortex) of drug-conditioned stimuli were elicited by instruction to inhibit cue-induced craving. This suggests that cocaine abusers may retain some ability to inhibit craving and that strengthening fronto-accumbal regulation may be therapeutically beneficial in addiction.

  2. Cognitive control of drug craving inhibits brain reward regions in cocaine abusers

    International Nuclear Information System (INIS)

    Volkow, N.D.; Fowler, J.; Wang, G.J.; Telang, F.; Logan, J.; Jayne, M.; Ma, Y.; Pradhan, K.; Wong, C.T.; Swanson, J.M.

    2010-01-01

    Loss of control over drug taking is considered a hallmark of addiction and is critical in relapse. Dysfunction of frontal brain regions involved with inhibitory control may underlie this behavior. We evaluated whether addicted subjects when instructed to purposefully control their craving responses to drug-conditioned stimuli can inhibit limbic brain regions implicated in drug craving. We used PET and 2-deoxy-2[18F]fluoro-D-glucose to measure brain glucose metabolism (marker of brain function) in 24 cocaine abusers who watched a cocaine-cue video and compared brain activation with and without instructions to cognitively inhibit craving. A third scan was obtained at baseline (without video). Statistical parametric mapping was used for analysis and corroborated with regions of interest. The cocaine-cue video increased craving during the no-inhibition condition (pre 3 ± 3, post 6 ± 3; p < 0.001) but not when subjects were instructed to inhibit craving (pre 3 ± 2, post 3 ± 3). Comparisons with baseline showed visual activation for both cocaine-cue conditions and limbic inhibition (accumbens, orbitofrontal, insula, cingulate) when subjects purposefully inhibited craving (p < 0.001). Comparison between cocaine-cue conditions showed lower metabolism with cognitive inhibition in right orbitofrontal cortex and right accumbens (p < 0.005), which was associated with right inferior frontal activation (r = -0.62, p < 0.005). Decreases in metabolism in brain regions that process the predictive (nucleus accumbens) and motivational value (orbitofrontal cortex) of drug-conditioned stimuli were elicited by instruction to inhibit cue-induced craving. This suggests that cocaine abusers may retain some ability to inhibit craving and that strengthening fronto-accumbal regulation may be therapeutically beneficial in addiction.

  3. Familiarity to a Feed Additive Modulates Its Effects on Brain Responses in Reward and Memory Regions in the Pig Model.

    Science.gov (United States)

    Val-Laillet, David; Meurice, Paul; Clouard, Caroline

    2016-01-01

    Brain responses to feed flavors with or without a feed additive (FA) were investigated in piglets familiarized or not with this FA. Sixteen piglets were allocated to 2 dietary treatments from weaning until d 37: the naive group (NAI) received a standard control feed and the familiarized group (FAM) received the same feed added with a FA mainly made of orange extracts. Animals were subjected to a feed transition at d 16 post-weaning, and to 2-choice feeding tests at d 16 and d 23. Production traits of the piglets were assessed up to d 28 post-weaning. From d 26 onwards, animals underwent 2 brain imaging sessions (positron emission tomography of 18FDG) under anesthesia to investigate the brain activity triggered by the exposure to the flavors of the feed with (FA) or without (C) the FA. Images were analyzed with SPM8 and a region of interest (ROI)-based small volume correction (p reward, and included the prefrontal cortex, insular cortex, fusiform gyrus, limbic system and corpus striatum. The FAM animals showed a moderate preference for the novel post-transition FA feed compared to the C feed on d 16, i.e., day of the feed transition (67% of total feed intake). The presence or absence of the FA in the diet from weaning had no impact on body weight, average daily gain, and feed efficiency of the animals over the whole experimental period (p ≥ 0.10). Familiar feed flavors activated the prefrontal cortex. The amygdala, insular cortex, and prepyriform area were only activated in familiarized animals exposed to the FA feed flavor. The perception of FA feed flavor in the familiarized animals activated the dorsal striatum differently than the perception of the C feed flavor in naive animals. Our data demonstrated that the perception of FA in familiarized individuals induced different brain responses in regions involved in reward anticipation and/or perception processes than the familiar control feed flavor in naive animals. Chronic exposure to the FA might be necessary

  4. Familiarity to a Feed Additive Modulates Its Effects on Brain Responses in Reward and Memory Regions in the Pig Model.

    Directory of Open Access Journals (Sweden)

    David Val-Laillet

    Full Text Available Brain responses to feed flavors with or without a feed additive (FA were investigated in piglets familiarized or not with this FA. Sixteen piglets were allocated to 2 dietary treatments from weaning until d 37: the naive group (NAI received a standard control feed and the familiarized group (FAM received the same feed added with a FA mainly made of orange extracts. Animals were subjected to a feed transition at d 16 post-weaning, and to 2-choice feeding tests at d 16 and d 23. Production traits of the piglets were assessed up to d 28 post-weaning. From d 26 onwards, animals underwent 2 brain imaging sessions (positron emission tomography of 18FDG under anesthesia to investigate the brain activity triggered by the exposure to the flavors of the feed with (FA or without (C the FA. Images were analyzed with SPM8 and a region of interest (ROI-based small volume correction (p < 0.05, k ≥ 25 voxels per cluster. The brain ROI were selected upon their role in sensory evaluation, cognition and reward, and included the prefrontal cortex, insular cortex, fusiform gyrus, limbic system and corpus striatum. The FAM animals showed a moderate preference for the novel post-transition FA feed compared to the C feed on d 16, i.e., day of the feed transition (67% of total feed intake. The presence or absence of the FA in the diet from weaning had no impact on body weight, average daily gain, and feed efficiency of the animals over the whole experimental period (p ≥ 0.10. Familiar feed flavors activated the prefrontal cortex. The amygdala, insular cortex, and prepyriform area were only activated in familiarized animals exposed to the FA feed flavor. The perception of FA feed flavor in the familiarized animals activated the dorsal striatum differently than the perception of the C feed flavor in naive animals. Our data demonstrated that the perception of FA in familiarized individuals induced different brain responses in regions involved in reward anticipation and

  5. Rewards and Performance Incentives.

    Science.gov (United States)

    Zigon, Jack

    1994-01-01

    Discusses rewards and performance incentives for employees, including types of rewards; how rewards help in managing; dysfunctional awards; selecting the right reward; how to find rewards that fit; and delivering rewards effectively. Examples are included. (three references) (LRW)

  6. In vivo binding of tritiated dopaminergic ligands in mouse brain

    International Nuclear Information System (INIS)

    Baudry, Michel; Martres, M.-P.; Le Sellin, Michel; Schwartz, J.-C.; Guyon, Anne; Morgat, J.-L.

    1977-01-01

    The regional distribution of various dopaminergic radiolabelled ligands has been studied in the mouse brain after their intravenous injections. Among them, 3 H-pimozide and, to a lesser extent, 3 H-apomorphine are preferentially accumulated in the striatum, a region rich in dopaminergic receptors, as compared to cerebellum, a region believed not to contain dopaminergic receptors. For 3 H-pimozide, this preferential retention is due to a more rapid disappearance from the cerebellum than from the striatum. Moreover, prior administration of various neuroleptics which do not modify 3 H-pimozide levels recovered in the cerebellum, abolishes the differential retention of 3 H-pimozide in the striatum. These results indicate that the retention of 3 H-pimozide in the brain may be regarded as the sum of two components: a non-specific retention evaluated by 3 H-pimozide level in the cerebellum and the binding to dopaminergic receptors [fr

  7. Dopamine and reward: comment on Hernandez et al. (2006).

    Science.gov (United States)

    Gallistel, C R

    2006-08-01

    Many lines of evidence suggest that the dopaminergic projection from the midbrain tegmentum to the forebrain must play a critical role in mediating the behavioral effects of natural and artificial rewards, with brain stimulation reward and addictive drugs included in the latter category. However, a closer look reveals many incongruities. The work of G. Hernandez et al. (2006) resolves several puzzles. It implies that the dopaminergic projection does not carry the signal that encodes the magnitude of a brain stimulation reward. It suggests that the elevation in the tonic levels of dopamine consequent on brain stimulation reward modulates the registration of the magnitude of the reward. This reconciles the psychophysical evidence with the pharmacological, electrophysiological, and anatomical evidence. However, some serious puzzles do remain.

  8. Addictive drugs and brain stimulation reward.

    Science.gov (United States)

    Wise, R A

    1996-01-01

    Direct electrical or chemical stimulation of specific brain regions can establish response habits similar to those established by natural rewards such as food or sexual contact. Cocaine, mu and delta opiates, nicotine, phencyclidine, and cannabis each have actions that summate with rewarding electrical stimulation of the medial forebrain bundle (MFB). The reward-potentiating effects of amphetamine and opiates are associated with central sites of action where these drugs also have their direct rewarding effects, suggesting common mechanisms for drug reward per se and for drug potentiation of brain stimulation reward. The central sites at which these and perhaps other drugs of abuse potentiate brain stimulation reward and are rewarding in their own right are consistent with the hypothesis that the laboratory reward of brain stimulation and the pharmacological rewards of addictive drugs are habit forming because they act in the brain circuits that subserve more natural and biologically significant rewards.

  9. An update on the role of serotonin and its interplay with dopamine for reward

    NARCIS (Netherlands)

    Fischer, A.G.; Ullsperger, M.

    2017-01-01

    The specific role of serotonin and its interplay with dopamine in adaptive, reward guided behavior as well as drug dependence, still remains elusive. Recently, novel methods allowed cell type specific anatomical, functional, and interventional analyses of serotonergic and dopaminergic circuits,

  10. Hunger and Satiety Gauge Reward Sensitivity

    Directory of Open Access Journals (Sweden)

    Ryan Michael Cassidy

    2017-05-01

    Full Text Available Many of the neurocircuits and hormones known to underlie the sensations of hunger and satiety also substantially alter the activity of the dopaminergic reward system. Much interest lies in the ways that hunger, satiety, and reward tie together, as the epidemic of obesity seems tied to the recent development and mass availability of highly palatable foods. In this review, we will first discuss the basic neurocircuitry of the midbrain and basal forebrain reward system. We will elaborate how several important mediators of hunger—the agouti-related protein neurons of the arcuate nucleus, the lateral hypothalamic nucleus, and ghrelin—enhance the sensitivity of the dopaminergic reward system. Then, we will elaborate how mediators of satiety—the nucleus tractus solitarius, pro-opiomelanocortin neurons of the arcuate nucleus, and its peripheral hormonal influences such as leptin—reduce the reward system sensitivity. We hope to provide a template by which future research may identify the ways in which highly rewarding foods bypass this balanced system to produce excessive food consumption.

  11. Song-associated reward correlates with endocannabinoid-related gene expression in male European starlings (Sturnus vulgaris).

    Science.gov (United States)

    Hahn, Allison H; Merullo, Devin P; Spool, Jeremy A; Angyal, Caroline S; Stevenson, Sharon A; Riters, Lauren V

    2017-03-27

    Vocal communication is required for successful social interactions in numerous species. During the breeding season, songbirds produce songs that are reinforced by behavioral consequences (e.g., copulation). However, some songbirds also produce songs not obviously directed at other individuals. The consequences maintaining or reinforcing these songs are less obvious and the neural mechanisms associated with undirected communication are not well-understood. Previous studies indicate that undirected singing is intrinsically rewarding and mediated by opioid or dopaminergic systems; however, endocannabinoids are also involved in regulating reward and singing behavior. We used a conditioned place preference paradigm to examine song-associated reward in European starlings and quantitative real-time PCR to measure expression of endocannabinoid-related neural markers (CB 1 , FABP7, FABP5, FAAH, DAGLα), in brain regions involved in social behavior, reward and motivation (ventral tegmental area [VTA], periaqueductal gray [PAG], and medial preoptic nucleus [POM]), and a song control region (Area X). Our results indicate that starlings producing high rates of song developed a conditioned place preference, suggesting that undirected song is associated with a positive affective state. We found a significant positive relationship between song-associated reward and CB 1 receptors in VTA and a significant negative relationship between song-associated reward and CB 1 in PAG. There was a significant positive relationship between reward and the cannabinoid transporter FABP7 in POM and a significant negative relationship between reward and FABP7 in PAG. In Area X, FABP5 and DAGLα correlated positively with singing. These results suggest a role for endocannabinoid signaling in vocal production and reward associated with undirected communication. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Dopamine-signalled reward predictions generated by competitive excitation and inhibition in a spiking neural network model

    Directory of Open Access Journals (Sweden)

    Paul eChorley

    2011-05-01

    Full Text Available Dopaminergic neurons in the mammalian substantia nigra displaycharacteristic phasic responses to stimuli which reliably predict thereceipt of primary rewards. These responses have been suggested toencode reward prediction-errors similar to those used in reinforcementlearning. Here, we propose a model of dopaminergic activity in whichprediction error signals are generated by the joint action ofshort-latency excitation and long-latency inhibition, in a networkundergoing dopaminergic neuromodulation of both spike-timing dependentsynaptic plasticity and neuronal excitability. In contrast toprevious models, sensitivity to recent events is maintained by theselective modification of specific striatal synapses, efferent tocortical neurons exhibiting stimulus-specific, temporally extendedactivity patterns. Our model shows, in the presence of significantbackground activity, (i a shift in dopaminergic response from rewardto reward predicting stimuli, (ii preservation of a response tounexpected rewards, and (iii a precisely-timed below-baseline dip inactivity observed when expected rewards are omitted.

  13. Intersection of reward and memory in monkey rhinal cortex.

    Science.gov (United States)

    Clark, Andrew M; Bouret, Sebastien; Young, Adrienne M; Richmond, Barry J

    2012-05-16

    In humans and other animals, the vigor with which a reward is pursued depends on its desirability, that is, on the reward's predicted value. Predicted value is generally context-dependent, varying according to the value of rewards obtained in the recent and distant past. Signals related to reward prediction and valuation are believed to be encoded in a circuit centered around midbrain dopamine neurons and their targets in the prefrontal cortex and basal ganglia. Notably absent from this hypothesized reward pathway are dopaminergic targets in the medial temporal lobe. Here we show that a key part of the medial temporal lobe memory system previously reported to be important for sensory mnemonic and perceptual processing, the rhinal cortex (Rh), is required for using memories of previous reward values to predict the value of forthcoming rewards. We tested monkeys with bilateral Rh lesions on a task in which reward size varied across blocks of uncued trials. In this experiment, the only cues for predicting current reward value are the sizes of rewards delivered in previous blocks. Unexpectedly, monkeys with Rh ablations, but not intact controls, were insensitive to differences in predicted reward, responding as if they expected all rewards to be of equal magnitude. Thus, it appears that Rh is critical for using memory of previous rewards to predict the value of forthcoming rewards. These results are in agreement with accumulating evidence that Rh is critical for establishing the relationships between temporally interleaved events, which is a key element of episodic memory.

  14. The dopaminergic system in the aging brain of Drosophila

    Directory of Open Access Journals (Sweden)

    Katherine E White

    2010-12-01

    Full Text Available Drosophila models of Parkinson’s disease are characterised by two principal phenotypes: the specific loss of dopaminergic neurons in the aging brain and defects in motor behavior. However, an age-related analysis of these baseline parameters in wildtype Drosophila is lacking. Here we analysed the dopaminergic system and motor behavior in aging Drosophila. Dopaminergic neurons in the adult brain can be grouped into bilateral symmetric clusters, each comprising a stereotypical number of cells. Analysis of TH>mCD8::GFP and cell type-specific MARCM clones revealed that dopaminergic neurons show cluster-specific, stereotypical projection patterns with terminal arborization in target regions that represent distinct functional areas of the adult brain. Target areas include the mushroom bodies, involved in memory formation and motivation, and the central complex, involved in the control of motor behavior, indicating that similar to the mammalian brain, dopaminergic neurons in the fly brain are involved in the regulation of specific behaviors. Behavioral analysis revealed that Drosophila show an age-related decline in startle-induced locomotion and negative geotaxis. Motion tracking however, revealed that walking activity and exploration behavior, but not centrophobism increase at late stages of life. Analysis of TH>Dcr2, mCD8::GFP revealed a specific effect of Dcr2 expression on walking activity but not on exploratory or centrophobic behavior, indicating that the siRNA pathway may modulate distinct dopaminergic behaviors in Drosophila. Moreover, dopaminergic neurons were maintained between early- and late life, as quantified by TH>mCD8::GFP and anti-TH labelling, indicating that adult onset, age-related degeneration of dopaminergic neurons does not occur in the aging brain of Drosophila. Taken together, our data establish baseline parameters in Drosophila for the study of Parkinson’s disease as well as other disorders affecting dopaminergic neurons

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

    Directory of Open Access Journals (Sweden)

    Owen G O'Daly

    Full Text Available 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.

  16. Dopaminergic stimulation increases selfish behavior in the absence of punishment threat.

    Science.gov (United States)

    Pedroni, Andreas; Eisenegger, Christoph; Hartmann, Matthias N; Fischbacher, Urs; Knoch, Daria

    2014-01-01

    People often face decisions that pit self-interested behavior aimed at maximizing personal reward against normative behavior such as acting cooperatively, which benefits others. The threat of social sanctions for defying the fairness norm prevents people from behaving overly selfish. Thus, normative behavior is influenced by both seeking rewards and avoiding punishment. However, the neurochemical processes mediating the impact of these influences remain unknown. Several lines of evidence link the dopaminergic system to reward and punishment processing, respectively, but this evidence stems from studies in non-social contexts. The present study investigates dopaminergic drug effects on individuals' reward seeking and punishment avoidance in social interaction. Two-hundred one healthy male participants were randomly assigned to receive 300 mg of L-3,4-dihydroxyphenylalanine (L-DOPA) or a placebo before playing an economic bargaining game. This game involved two conditions, one in which unfair behavior could be punished and one in which unfair behavior could not be punished. In the absence of punishment threats, L-DOPA administration led to more selfish behavior, likely mediated through an increase in reward seeking. In contrast, L-DOPA administration had no significant effect on behavior when faced with punishment threats. The results of this study broaden the role of the dopaminergic system in reward seeking to human social interactions. We could show that even a single dose of a dopaminergic drug may bring selfish behavior to the fore, which in turn may shed new light on potential causal relationships between the dopaminergic system and norm abiding behaviors in certain clinical subpopulations.

  17. Introduction: Addiction and Brain Reward and Anti-Reward Pathways

    Science.gov (United States)

    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

  18. The anatomy of the human medial forebrain bundle: Ventral tegmental area connections to reward-associated subcortical and frontal lobe regions

    Directory of Open Access Journals (Sweden)

    Volker Arnd Coenen

    Full Text Available Introduction: Despite their importance in reward, motivation, and learning there is only sparse anatomical knowledge about the human medial forebrain bundle (MFB and the connectivity of the ventral tegmental area (VTA. A thorough anatomical and microstructural description of the reward related PFC/OFC regions and their connection to the VTA - the superolateral branch of the MFB (slMFB - is however mandatory to enable an interpretation of distinct therapeutic effects from different interventional treatment modalities in neuropsychiatric disorders (DBS, TMS etc.. This work aims at a normative description of the human MFB (and more detailed the slMFB anatomy with respect to distant prefrontal connections and microstructural features. Methods and material: Healthy subjects (n = 55; mean age ± SD, 40 ± 10 years; 32 females underwent high resolution anatomical magnetic resonance imaging including diffusion tensor imaging. Connectivity of the VTA and the resulting slMFB were investigated on the group level using a global tractography approach. The Desikan/Killiany parceling (8 segments of the prefrontal cortex was used to describe sub-segments of the MFB. A qualitative overlap with Brodmann areas was additionally described. Additionally, a pure visual analysis was performed comparing local and global tracking approaches for their ability to fully visualize the slMFB. Results: The MFB could be robustly described both in the present sample as well as in additional control analyses in data from the human connectome project. Most VTA- connections reached the superior frontal gyrus, the middel frontal gyrus and the lateral orbitofrontal region corresponding to Brodmann areas 10, 9, 8, 11, and 11m. The projections to these regions comprised 97% (right and 98% (left of the total relative fiber counts of the slMFB. Discussion: The anatomical description of the human MFB shows far reaching connectivity of VTA to reward-related subcortical and

  19. Reward Circuitry in Addiction.

    Science.gov (United States)

    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.

  20. Dopamine signaling in reward-related behaviors.

    Science.gov (United States)

    Baik, Ja-Hyun

    2013-01-01

    Dopamine (DA) regulates emotional and motivational behavior through the mesolimbic dopaminergic pathway. Changes in DA mesolimbic neurotransmission have been found to modify behavioral responses to various environmental stimuli associated with reward behaviors. Psychostimulants, drugs of abuse, and natural reward such as food can cause substantial synaptic modifications to the mesolimbic DA system. Recent studies using optogenetics and DREADDs, together with neuron-specific or circuit-specific genetic manipulations have improved our understanding of DA signaling in the reward circuit, and provided a means to identify the neural substrates of complex behaviors such as drug addiction and eating disorders. This review focuses on the role of the DA system in drug addiction and food motivation, with an overview of the role of D1 and D2 receptors in the control of reward-associated behaviors.

  1. Dopamine Signaling in reward-related behaviors

    Directory of Open Access Journals (Sweden)

    Ja-Hyun eBaik

    2013-10-01

    Full Text Available Dopamine (DA regulates emotional and motivational behavior through the mesolimbic dopaminergic pathway. Changes in DAmesolimbic neurotransmission have been found to modify behavioral responses to various environmental stimuli associated with reward behaviors. Psychostimulants, drugs of abuse, and natural rewards such as food can cause substantial synaptic modifications to the mesolimbic DA system. Recent studies using optogenetics and DREADDs, together with neuron-specific or circuit-specific genetic manipulations have improved our understanding of DA signaling in the reward circuit, and provided a means to identify the neural substrates of complex behaviors such as drug addiction and eating disorders. This review focuses on the role of the DA system in drug addiction and food motivation, with an overview of the role of D1 and D2 receptors in the control of reward-associated behaviors.

  2. Serotonergic modulation of reward and punishment

    DEFF Research Database (Denmark)

    Macoveanu, Julian

    2014-01-01

    Until recently, the bulk of research on the human reward system was focused on studying the dopaminergic and opioid neurotransmitter systems. However, extending the initial data from animal studies on reward, recent pharmacological brain imaging studies on human participants bring a new line......-related processing and may also provide a neural correlated for the emotional blunting observed in the clinical treatment of psychiatric disorders with selective serotonin reuptake inhibitors. Given the unique profile of action of each serotonergic receptor subtype, future pharmacological studies may favor receptor...

  3. Neurocircuitry of drug reward

    Science.gov (United States)

    Ikemoto, Satoshi; Bonci, Antonello

    2013-01-01

    In recent years, neuroscientists have produced profound conceptual and mechanistic advances on the neurocircuitry of reward and substance use disorders. Here, we will provide a brief review of intracranial drug self-administration and optogenetic self-stimulation studies that identified brain regions and neurotransmitter systems involved in drug- and reward-related behaviors. Also discussed is a theoretical framework that helps to understand the functional properties of the circuitry involved in these behaviors. The circuitry appears to be homeostatically regulated and mediate anticipatory processes that regulate behavioral interaction with the environment in response to salient stimuli. That is, abused drugs or, at least, some may act on basic motivation and mood processes, regulating behavior-environment interaction. Optogenetics and related technologies have begun to uncover detailed circuit mechanisms linking key brain regions in which abused drugs act for rewarding effects. PMID:23664810

  4. Molecular role of dopamine in anhedonia linked to reward deficiency syndrome (RDS) and anti- reward systems.

    Science.gov (United States)

    Gold, Mark S; Blum, Kenneth; Febo, Marcelo; Baron, David; Modestino, Edward Justin; Elman, Igor; Badgaiyan, Rajendra D

    2018-03-01

    Anhedonia is a condition that leads to the loss of feelings pleasure in response to natural reinforcers like food, sex, exercise, and social activities. This disorder occurs in addiction, and an array of related neuropsychiatric syndromes, including schizophrenia, depression, and Post Traumatic Stress Disorder (PTSD). Anhedonia may by due to derangements in mesolimbic dopaminergic pathways and their terminal fields (e.g., striatum, amygdala, and prefrontal cortex) that persist long after the traces of the causative drugs are eliminated (pharmacokinetically). Here we postulate that anhedonia is not a distinct entity but is rather an epiphenomenon of hypodopaminergic states and traits arising from the interaction of genetic traits and epigenetic neurobiological alterations in response to environmental influences. Moreover, dopaminergic activity is rather complex, and so it may give rise to differential pathophysiological processes such as incentive sensitization, aberrant learning and stress-like "anti-reward" phenomena. These processes may have additive, synergistic or antagonistic interactions with the concurrent reward deficiency states leading in some instances to more severe and long-lasting symptoms. Operant understanding of the neurogenetic antecedents to reward deficiency syndrome (RDS) and the elucidation of reward gene polymorphisms may provide a map for accessing an individual's genetic risk for developing Anhedonia. Prevention techniques that can restore homeostatic balance via physiological activation of dopaminergic receptors (D2/D3) may be instrumental for targeting not only anhedonia per se but also drug craving and relapse.

  5. Neural activity in the reward-related brain regions predicts implicit self-esteem: A novel validity test of psychological measures using neuroimaging.

    Science.gov (United States)

    Izuma, Keise; Kennedy, Kate; Fitzjohn, Alexander; Sedikides, Constantine; Shibata, Kazuhisa

    2018-03-01

    Self-esteem, arguably the most important attitudes an individual possesses, has been a premier research topic in psychology for more than a century. Following a surge of interest in implicit attitude measures in the 90s, researchers have tried to assess self-esteem implicitly to circumvent the influence of biases inherent in explicit measures. However, the validity of implicit self-esteem measures remains elusive. Critical tests are often inconclusive, as the validity of such measures is examined in the backdrop of imperfect behavioral measures. To overcome this serious limitation, we tested the neural validity of the most widely used implicit self-esteem measure, the implicit association test (IAT). Given the conceptualization of self-esteem as attitude toward the self, and neuroscience findings that the reward-related brain regions represent an individual's attitude or preference for an object when viewing its image, individual differences in implicit self-esteem should be associated with neural signals in the reward-related regions during passive-viewing of self-face (the most obvious representation of the self). Using multi-voxel pattern analysis (MVPA) on functional MRI (fMRI) data, we demonstrate that the neural signals in the reward-related regions were robustly associated with implicit (but not explicit) self-esteem, thus providing unique evidence for the neural validity of the self-esteem IAT. In addition, both implicit and explicit self-esteem were related, although differently, to neural signals in regions involved in self-processing. Our finding highlights the utility of neuroscience methods in addressing fundamental psychological questions and providing unique insights into important psychological constructs. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  6. Dopaminergic Modulation of Medial Prefrontal Cortex Deactivation in Parkinson Depression

    Directory of Open Access Journals (Sweden)

    Anders H. Andersen

    2015-01-01

    Full Text Available Parkinson’s disease (PD is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD patients. Participants included 18 ndPD patients (11 men, 7 women and 10 dPD patients (7 men, 3 women. Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after medication had been temporarily discontinued. Results indicate that dopaminergic medications have opposite effects in the prefrontal cortex depending upon depression status. DPD patients show greater deactivation in the ventromedial prefrontal cortex (VMPFC on dopaminergic medications than off, while ndPD patients show greater deactivation in this region off drugs. The VMPFC is in the default-mode network (DMN. DMN activity is negatively correlated with activity in brain systems used for external visual attention. Thus dopaminergic medications may promote increased attention to external visual stimuli among dPD patients but impede normal suppression of DMN activity during external stimulation among ndPD patients.

  7. An imperfect dopaminergic error signal can drive temporal-difference learning.

    Directory of Open Access Journals (Sweden)

    Wiebke Potjans

    2011-05-01

    Full Text Available An open problem in the field of computational neuroscience is how to link synaptic plasticity to system-level learning. A promising framework in this context is temporal-difference (TD learning. Experimental evidence that supports the hypothesis that the mammalian brain performs temporal-difference learning includes the resemblance of the phasic activity of the midbrain dopaminergic neurons to the TD error and the discovery that cortico-striatal synaptic plasticity is modulated by dopamine. However, as the phasic dopaminergic signal does not reproduce all the properties of the theoretical TD error, it is unclear whether it is capable of driving behavior adaptation in complex tasks. Here, we present a spiking temporal-difference learning model based on the actor-critic architecture. The model dynamically generates a dopaminergic signal with realistic firing rates and exploits this signal to modulate the plasticity of synapses as a third factor. The predictions of our proposed plasticity dynamics are in good agreement with experimental results with respect to dopamine, pre- and post-synaptic activity. An analytical mapping from the parameters of our proposed plasticity dynamics to those of the classical discrete-time TD algorithm reveals that the biological constraints of the dopaminergic signal entail a modified TD algorithm with self-adapting learning parameters and an adapting offset. We show that the neuronal network is able to learn a task with sparse positive rewards as fast as the corresponding classical discrete-time TD algorithm. However, the performance of the neuronal network is impaired with respect to the traditional algorithm on a task with both positive and negative rewards and breaks down entirely on a task with purely negative rewards. Our model demonstrates that the asymmetry of a realistic dopaminergic signal enables TD learning when learning is driven by positive rewards but not when driven by negative rewards.

  8. Behavioral Specifications of Reward-Associated Long-Term Memory Enhancement in Humans

    Science.gov (United States)

    Wittmann, Bianca C.; Dolan, Raymond J.; Duzel, Emrah

    2011-01-01

    Recent functional imaging studies link reward-related activation of the midbrain substantia nigra-ventral tegmental area (SN/VTA), the site of origin of ascending dopaminergic projections, with improved long-term episodic memory. Here, we investigated in two behavioral experiments how (1) the contingency between item properties and reward, (2) the…

  9. Trial-by-Trial Modulation of Associative Memory Formation by Reward Prediction Error and Reward Anticipation as Revealed by a Biologically Plausible Computational Model.

    Science.gov (United States)

    Aberg, Kristoffer C; Müller, Julia; Schwartz, Sophie

    2017-01-01

    Anticipation and delivery of rewards improves memory formation, but little effort has been made to disentangle their respective contributions to memory enhancement. Moreover, it has been suggested that the effects of reward on memory are mediated by dopaminergic influences on hippocampal plasticity. Yet, evidence linking memory improvements to actual reward computations reflected in the activity of the dopaminergic system, i.e., prediction errors and expected values, is scarce and inconclusive. For example, different previous studies reported that the magnitude of prediction errors during a reinforcement learning task was a positive, negative, or non-significant predictor of successfully encoding simultaneously presented images. Individual sensitivities to reward and punishment have been found to influence the activation of the dopaminergic reward system and could therefore help explain these seemingly discrepant results. Here, we used a novel associative memory task combined with computational modeling and showed independent effects of reward-delivery and reward-anticipation on memory. Strikingly, the computational approach revealed positive influences from both reward delivery, as mediated by prediction error magnitude, and reward anticipation, as mediated by magnitude of expected value, even in the absence of behavioral effects when analyzed using standard methods, i.e., by collapsing memory performance across trials within conditions. We additionally measured trait estimates of reward and punishment sensitivity and found that individuals with increased reward (vs. punishment) sensitivity had better memory for associations encoded during positive (vs. negative) prediction errors when tested after 20 min, but a negative trend when tested after 24 h. In conclusion, modeling trial-by-trial fluctuations in the magnitude of reward, as we did here for prediction errors and expected value computations, provides a comprehensive and biologically plausible description of

  10. Representation of spontaneous movement by dopaminergic neurons is cell-type selective and disrupted in parkinsonism

    DEFF Research Database (Denmark)

    Dodson, Paul D.; Dreyer, Jakob K.; Jennings, Katie Ann

    2016-01-01

    receptor expressed by striatal neurons. Importantly, in aged mice harboring a genetic burden relevant for human Parkinson's disease, the precise movement-related firing of SNc dopaminergic neurons and the resultant striatal dopamine signaling were lost. These data show that distinct dopaminergic cell types......Midbrain dopaminergic neurons are essential for appropriate voluntary movement, as epitomized by the cardinal motor impairments arising in Parkinson's disease. Understanding the basis of such motor control requires understanding how the firing of different types of dopaminergic neuron relates...... of these dopaminergic neurons can manifest as rapid and robust fluctuations in striatal dopamine concentration and receptor activity. The exact nature of the movement-related signaling in the striatum depended on the type of dopaminergic neuron providing inputs, the striatal region innervated, and the type of dopamine...

  11. Distinct Reward Properties are Encoded via Corticostriatal Interactions

    OpenAIRE

    David V. Smith; Anastasia E. Rigney; Mauricio R. Delgado

    2016-01-01

    The striatum serves as a critical brain region for reward processing. Yet, understanding the link between striatum and reward presents a challenge because rewards are composed of multiple properties. Notably, affective properties modulate emotion while informative properties help obtain future rewards. We approached this problem by emphasizing affective and informative reward properties within two independent guessing games. We found that both reward properties evoked activation within the nu...

  12. Adaptive scaling of reward in episodic memory:a replication study

    OpenAIRE

    Mason, Alice; Ludwig, Casimir; Farrell, Simon

    2017-01-01

    Reward is thought to enhance episodic memory formation via dopaminergic consolidation. Bunzeck, Dayan, Dolan, and Duzel [(2010). A common mechanism for adaptive scaling of reward and novelty. Human Brain Mapping, 31, 1380–1394] provided functional magnetic resonance imaging (fMRI) and behavioural evidence that reward and episodic memory systems are sensitive to the contextual value of a reward—whether it is relatively higher or lower—as opposed to absolute value or prediction error. We carrie...

  13. Adaptive scaling of reward in episodic memory: a replication study.

    Science.gov (United States)

    Mason, Alice; Ludwig, Casimir; Farrell, Simon

    2017-11-01

    Reward is thought to enhance episodic memory formation via dopaminergic consolidation. Bunzeck, Dayan, Dolan, and Duzel [(2010). A common mechanism for adaptive scaling of reward and novelty. Human Brain Mapping, 31, 1380-1394] provided functional magnetic resonance imaging (fMRI) and behavioural evidence that reward and episodic memory systems are sensitive to the contextual value of a reward-whether it is relatively higher or lower-as opposed to absolute value or prediction error. We carried out a direct replication of their behavioural study and did not replicate their finding that memory performance associated with reward follows this pattern of adaptive scaling. An effect of reward outcome was in the opposite direction to that in the original study, with lower reward outcomes leading to better memory than higher outcomes. There was a marginal effect of reward context, suggesting that expected value affected memory performance. We discuss the robustness of the reward memory relationship to variations in reward context, and whether other reward-related factors have a more reliable influence on episodic memory.

  14. It's in the eye of the beholder: selective attention to drink properties during tasting influences brain activation in gustatory and reward regions.

    Science.gov (United States)

    van Rijn, Inge; de Graaf, Cees; Smeets, Paul A M

    2018-04-01

    Statements regarding pleasantness, taste intensity or caloric content on a food label may influence the attention consumers pay to such characteristics during consumption. There is little research on the effects of selective attention on taste perception and associated brain activation in regular drinks. The aim of this study was to investigate the effect of selective attention on hedonics, intensity and caloric content on brain responses during tasting drinks. Using functional MRI brain responses of 27 women were measured while they paid attention to the intensity, pleasantness or caloric content of fruit juice, tomato juice and water. Brain activation during tasting largely overlapped between the three selective attention conditions and was found in the rolandic operculum, insula and overlying frontal operculum, striatum, amygdala, thalamus, anterior cingulate cortex and middle orbitofrontal cortex (OFC). Brain activation was higher during selective attention to taste intensity compared to calories in the right middle OFC and during selective attention to pleasantness compared to intensity in the right putamen, right ACC and bilateral middle insula. Intensity ratings correlated with brain activation during selective attention to taste intensity in the anterior insula and lateral OFC. Our data suggest that not only the anterior insula but also the middle and lateral OFC are involved in evaluating taste intensity. Furthermore, selective attention to pleasantness engaged regions associated with food reward. Overall, our results indicate that selective attention to food properties can alter the activation of gustatory and reward regions. This may underlie effects of food labels on the consumption experience of consumers.

  15. Managing Parkinson's disease with continuous dopaminergic stimulation

    NARCIS (Netherlands)

    Wolters, Erik; Lees, Andrew J.; Volkmann, Jens; van Laar, Teus; Hovestadt, Ad

    The pathophysiology of Parkinson's disease is marked by the loss of dopaminergic neurons, which leads to striatal dopaminergic deficiency. This causes resting tremor, hypokinesia, rigidity, bradykinesia, and loss of postural reflexes. Most current treatments for Parkinson's disease aim to restore

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

    Science.gov (United States)

    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, pcortisol 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

  17. Cholinergic modulation of mesolimbic dopamine function and reward.

    Science.gov (United States)

    Mark, Gregory P; Shabani, Shkelzen; Dobbs, Lauren K; Hansen, Stephen T

    2011-07-25

    The substantial health risk posed by obesity and compulsive drug use has compelled a serious research effort to identify the neurobiological substrates that underlie the development these pathological conditions. Despite substantial progress, an understanding of the neurochemical systems that mediate the motivational aspects of drug-seeking and craving remains incomplete. Important work from the laboratory of Bart Hoebel has provided key information on neurochemical systems that interact with dopamine (DA) as potentially important components in both the development of addiction and the expression of compulsive behaviors such as binge eating. One such modulatory system appears to be cholinergic pathways that interact with DA systems at all levels of the reward circuit. Cholinergic cells in the pons project to DA-rich cell body regions in the ventral tegmental area (VTA) and substantial nigra (SN) where they modulate the activity of dopaminergic neurons and reward processing. The DA terminal region of the nucleus accumbens (NAc) contains a small but particularly important group of cholinergic interneurons, which have extensive dendritic arbors that make synapses with a vast majority of NAc neurons and afferents. Together with acetylcholine (ACh) input onto DA cell bodies, cholinergic systems could serve a vital role in gating information flow concerning the motivational value of stimuli through the mesolimbic system. In this report we highlight evidence that CNS cholinergic systems play a pivotal role in behaviors that are motivated by both natural and drug rewards. We argue that the search for underlying neurochemical substrates of compulsive behaviors, as well as attempts to identify potential pharmacotherapeutic targets to combat them, must include a consideration of central cholinergic systems. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Electroacupuncture decreases excessive alcohol consumption involving reduction of FosB/ΔFosB levels in reward-related brain regions.

    Directory of Open Access Journals (Sweden)

    Jing Li

    Full Text Available New therapies are needed for alcohol abuse, a major public health problem in the U.S. and worldwide. There are only three FDA-approved drugs for treatment of alcohol abuse (naltrexone, acamprosate and disulfuram. On average these drugs yield only moderate success in reducing long-term alcohol consumption. Electroacupuncture has been shown to alleviate various drugs of abuse, including alcohol. Although previous studies have shown that electroacupuncture reduced alcohol consumption, the underlying mechanisms have not been fully elucidated. ΔFosB and FosB are members of the Fos family of transcription factors implicated in neural plasticity in drug addiction; a connection between electroacupuncture's treatment of alcohol abuse and the Fos family has not been established. In this study, we trained rats to drink large quantities of ethanol in a modified intermittent access two-bottle choice drinking procedure. When rats achieved a stable baseline of ethanol consumption, electroacupuncture (100 Hz or 2 Hz, 30 min each day was administered at Zusanli (ST36 for 6 consecutive days. The level of FosB/ΔFosB in reward-related brain regions was assessed by immunohistochemistry. We found that the intake of and preference for ethanol in rats under 100 Hz, but not 2 Hz electroacupuncture regiment were sharply reduced. The reduction was maintained for at least 72 hours after the termination of electroacupuncture treatment. Conversely, 100 Hz electroacupuncture did not alter the intake of and preference for the natural rewarding agent sucrose. Additionally, FosB/ΔFosB levels in the prefrontal cortex, striatal region and the posterior region of ventral tegmental area were increased following excessive ethanol consumption, but were reduced after six-day 100 Hz electroacupuncture. Thus, this study demonstrates that six-day 100 Hz electroacupuncture treatment effectively reduces ethanol consumption and preference in rats that chronically drink excessive amount of

  19. Imaging of dopaminergic system in movement disorders

    International Nuclear Information System (INIS)

    Kim, Yu Kyeong; Kim, Sang Eun

    2007-01-01

    Parkinson's disease is a common neurodegenerative disorder that is mainly caused by dopaminergic neuron loss in the substantia nigra. Several radiopharmaceutics have been developed to evaluated the integrity of dopaminergic neuronal system. In vivo PET and SPECT imaging of presynaptic dopamine imaging are already applied to Parkinson's disease and other parkinsonism, and can demonstrate the dopaminergic dysfunction. This review summarized the use of the presynaptic dopaminergic imaging in PD as biomarkers in evaluation of disease progression as well as in diagnosis of PD

  20. Complementary neural correlates of motivation in dopaminergic and noradrenergic neurons of monkeys.

    Directory of Open Access Journals (Sweden)

    Sebastien eBouret

    2012-07-01

    Full Text Available Rewards have many influences on learning, decision-making and performance. All seem to rely on complementary actions of two closely related catecholaminergic neuromodulators, dopamine and noradrenaline. We compared single unit activity of dopaminergic neurons of the substantia nigra pars compacta and noradrenergic neurons of the locus coeruleus in monkeys performing a reward schedule task. Their motivation, indexed using operant performance, increased as they progressed through schedules ending in reward delivery. The responses of dopaminergic and noradrenergic neurons around the time of major task events, visual cues predicting trial outcome and operant action to complete a trial, were similar, in that they occurred at the same time. They were also similar in that they both responded most strongly to the first cues in schedules, which are the most informative cues. The neuronal responses around the time of the monkeys’ actions were different, in that the response intensity profiles changed in opposite directions. Dopaminergic responses were stronger around predictably rewarded correct actions whereas noradrenergic responses were greater around predictably unrewarded correct actions. The complementary response profiles related to the monkeys operant actions suggest that dopamine neurons might relate to the value of the current action whereas the noradrenergic neurons relate to the psychological cost of that action.

  1. Regionally Selective Requirement for D[subscript 1]/D[subscript 5] Dopaminergic Neurotransmission in the Medial Prefrontal Cortex in Object-in-Place Associative Recognition Memory

    Science.gov (United States)

    Savalli, Giorgia; Bashir, Zafar I.; Warburton, E. Clea

    2015-01-01

    Object-in-place (OiP) memory is critical for remembering the location in which an object was last encountered and depends conjointly on the medial prefrontal cortex, perirhinal cortex, and hippocampus. Here we examined the role of dopamine D[subscript 1]/D[subscript 5] receptor neurotransmission within these brain regions for OiP memory. Bilateral…

  2. Food-Related Odors Activate Dopaminergic Brain Areas

    Directory of Open Access Journals (Sweden)

    Agnieszka Sorokowska

    2017-12-01

    Full Text Available Food-associated cues of different sensory categories have often been shown to be a potent elicitor of cerebral activity in brain reward circuits. Smells influence and modify the hedonic qualities of eating experience, and in contrast to smells not associated with food, perception of food-associated odors may activate dopaminergic brain areas. In this study, we aimed to verify previous findings related to the rewarding value of food-associated odors by means of an fMRI design involving carefully preselected odors of edible and non-edible substances. We compared activations generated by three food and three non-food odorants matching in terms of intensity, pleasantness and trigeminal qualities. We observed that for our mixed sample of 30 hungry and satiated participants, food odors generated significantly higher activation in the anterior cingulate cortex (right and left, insula (right, and putamen (right than non-food odors. Among hungry subjects, regardless of the odor type, we found significant activation in the ventral tegmental area in response to olfactory stimulation. As our stimuli were matched in terms of various perceptual qualities, this result suggests that edibility of an odor source indeed generates specific activation in dopaminergic brain areas.

  3. Antagonism at the NR2B subunit of NMDA receptors induces increased connectivity of the prefrontal and subcortical regions regulating reward behavior.

    Science.gov (United States)

    Gass, Natalia; Becker, Robert; Sack, Markus; Schwarz, Adam J; Reinwald, Jonathan; Cosa-Linan, Alejandro; Zheng, Lei; von Hohenberg, Christian Clemm; Inta, Dragos; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang; Gass, Peter; Sartorius, Alexander

    2018-04-01

    Evidence indicates that ketamine's rapid antidepressant efficacy likely results from its antagonism of NR2B-subunit-containing NMDA receptors (NMDAR). Since ketamine equally blocks NR2A- and NR2B-containing NMDAR, and has affinity to other receptors, NR2B-selective drugs might have improved therapeutic efficiency and side effect profile. We aimed to compare the effects of (S)-ketamine and two different types of NR2B-selective antagonists on functional brain networks in rats, in order to find common circuits, where their effects intersect, and that might explain their antidepressant action. The experimental design comprised four parallel groups of rats (N = 37), each receiving (S)-Ketamine, CP-101,606, Ro 25-6981 or saline. After compound injection, we acquired resting-state functional magnetic resonance imaging time series. We used graph theoretical approach to calculate brain network properties. Ketamine and CP-101,606 diminished the global clustering coefficient and small-worldness index. At the nodal level, all compounds induced increased connectivity of the regions mediating reward and cognitive aspects of emotional processing, such as ventromedial prefrontal cortex, septal nuclei, and nucleus accumbens. The dorsal hippocampus and regions involved in sensory processing and aversion, such as superior and inferior colliculi, exhibited an opposite effect. The effects common to ketamine and NR2B-selective compounds were localized to the same brain regions as those reported in depression, but in the opposite direction. The upregulation of the reward circuitry might partially underlie the antidepressant and anti-anhedonic effects of the antagonists and could potentially serve as a translational imaging phenotype for testing putative antidepressants, especially those targeting the NR2B receptor subtype.

  4. Cigarette smoking modulates medication-associated deficits in a monetary reward task in patients with schizophrenia.

    Science.gov (United States)

    Lernbass, Birgit; Grön, Georg; Wolf, Nadine D; Abler, Birgit

    2013-09-01

    Imaging studies of reward processing have demonstrated a mesolimbic-mesocortical dopaminergic dysfunction in schizophrenia. Such studies on reward processing in patients and also in healthy controls showed that differential activations of dopaminergic brain areas are associated with adaptive changes in response speed related to different reward values. Given this relationship, we investigated reward processing on the behavioural level in a larger sample of 49 medicated patients with a diagnosis of schizophrenia (ICD-10 F20) and 49 healthy controls. Subjects were instructed to react by button press upon two different stimuli in order to retain a 60 % chance winning a previously announced high (1$) or low (20¢) amount of money paid to participants after the experiment. Concordant with previous reports on deficits in reward processing, acceleration of reaction times in patients upon low rewards differed significantly (p non-smoking subgroup of patients (n = 24). In this subgroup, we also observed a significant (p monetary reward task might constitute a feasible behavioural proxy for dopaminergic dysfunction and its different dimensions regarding psychopathology but also medication in patients with schizophrenia. In line with clinical observations, our findings support the notion that smoking modulates medication-associated side effects on reward processing in patients with schizophrenia.

  5. Cocaine-associated odor cue re-exposure increases blood oxygenation level dependent signal in memory and reward regions of the maternal rat brain.

    Science.gov (United States)

    Caffrey, Martha K; Febo, Marcelo

    2014-01-01

    Cue triggered relapse during the postpartum period can negatively impact maternal care. Given the high reward value of pups in maternal rats, we designed an fMRI experiment to test whether offspring presence reduces the neural response to a cocaine associated olfactory cue. Cocaine conditioned place preference was carried out before pregnancy in the presence of two distinct odors that were paired with cocaine or saline (+Cue and -Cue). The BOLD response to +Cue and -Cue was measured in dams on postpartum days 2-4. Odor cues were delivered to dams in the absence and then the presence of pups. Our data indicate that several limbic and cognitive regions of the maternal rat brain show a greater BOLD signal response to a +Cue versus -Cue. These include dorsal striatum, prelimbic cortex, parietal cortex, habenula, bed nucleus of stria terminalis, lateral septum and the mediodorsal and the anterior thalamic nucleus. Of the aforementioned brain regions, only the parietal cortex of cocaine treated dams showed a significant modulatory effect of pup presence. In this area of the cortex, cocaine exposed maternal rats showed a greater BOLD activation in response to the +Cue in the presence than in the absence of pups. Specific regions of the cocaine exposed maternal rat brain are strongly reactive to drug associated cues. The regions implicated in cue reactivity have been previously reported in clinical imaging work, and previous work supports their role in various motivational and cognitive functions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. COCAINE-ASSOCIATED ODOR CUE RE-EXPOSURE INCREASES BLOOD OXYGENATION LEVEL DEPENDENT SIGNAL IN MEMORY AND REWARD REGIONS OF THE MATERNAL RAT BRAIN*

    Science.gov (United States)

    Caffrey, Martha K.; Febo, Marcelo

    2013-01-01

    BACKGROUND Cue triggered relapse during the postpartum period can negatively impact maternal care. Given the high reward value of pups in maternal rats, we designed an fMRI experiment to test whether offspring presence reduces the neural response to a cocaine associated olfactory cue. METHODS Cocaine conditioned place preference was carried out before pregnancy in the presence of two distinct odors that were paired with cocaine or saline (+Cue and −Cue). The BOLD response to +Cue and −Cue was measured in dams on postpartum days 2–4. Odor cues were delivered to dams in the absence and then the presence of pups. RESULTS Our data indicate that several limbic and cognitive regions of the maternal rat brain show a greater BOLD signal response to a +Cue versus −Cue. These include dorsal striatum, prelimbic cortex, parietal cortex, habenula, bed nucleus of stria terminalis, lateral septum and the mediodorsal and the anterior thalamic nucleus. Of the aforementioned brain regions, only the parietal cortex of cocaine treated dams showed a significant modulatory effect of pup presence. In this area of the cortex, cocaine exposed maternal rats showed a greater BOLD activation in response to the +Cue in the presence than in the absence of pups. CONCLUSIONS Specific regions of the cocaine exposed maternal rat brain are strongly reactive to drug associated cues. The regions implicated in cue reactivity have been previously reported in clinical imaging work, and previous work supports their role in various motivational and cognitive functions. PMID:24183499

  7. Motivation and reward systems

    NARCIS (Netherlands)

    van Eerde, W.; Vodosek, M.; den Hartog, D.N.; McNett, J.M.

    2014-01-01

    Reward systems are identified as one of the human resource management (HRM) practices that may impact motivation. Reward systems may consist of several components, including financial and nonfinancial rewards, in fixed and variable amounts. Reinforcement, expectancy, and equity principles are

  8. INFLUENCE OF DOPAMINERGIC SYSTEM ON INTERNET ADDICTION

    Directory of Open Access Journals (Sweden)

    Jelena Jović

    2011-03-01

    Full Text Available Internet addiction is a clinical anomaly with strong negative consequences on social, work-related, family, financial, and economic function of a person. It is regarded as a serious public health issue. The basic idea of this paper is to, based on the currently available body of research work on this topic, point out to neurobiological pathos of Internet addiction, and its connection to the dopaminergic system. Dopamine contains all physiological functions of neurotransmitters and it is a part of chatecholamine family. Five dopaminergic receptors (D1 - D5 belong to the super family of receptors related to G-protein. Through these receptors, dopamine achieves its roles: regulation of voluntary movement, regulation of center of pleasure, hormonal regulation, and regulation of hypertension. In order to recognize an Internet user as an addict, he or she needs to comply with the criteria suggested by the American Psychiatric Association (APA. Phenomenological, neurobiological, and pharmacological data indicates similarities in pathopsychology of substance addiction and pathological gambling, which are indirectly related to the similarity with the Internet addiction. Responding to stimuli from the game, addicts have shown more brain activity in the nape region, left dorsolateral, prefrontal cortex, and left parachipocampal gyrus than in the control group. After the six-week bupropion therapy, desire to play Internet and video games, the total duration of playing, and induced brain activity in dorsolateral prefrontal cortex are lowered with the addicts.

  9. Ascending Midbrain Dopaminergic Axons Require Descending GAD65 Axon Fascicles for Normal Pathfinding

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    Claudia Marcela Garcia-Peña

    2014-06-01

    Full Text Available The Nigrostriatal pathway (NSP is formed by dopaminergic axons that project from the ventral midbrain to the dorsolateral striatum as part of the medial forebrain bundle. Previous studies have implicated chemotropic proteins in the formation of the NSP during development but little is known of the role of substrate-anchored signals in this process. We observed in mouse and rat embryos that midbrain dopaminergic axons ascend in close apposition to descending GAD65-positive axon bundles throughout their trajectory to the striatum. To test whether such interaction is important for dopaminergic axon pathfinding, we analyzed transgenic mouse embryos in which the GAD65 axon bundle was reduced by the conditional expression of the diphtheria toxin. In these embryos we observed dopaminergic misprojection into the hypothalamic region and abnormal projection in the striatum. In addition, analysis of Robo1/2 and Slit1/2 knockout embryos revealed that the previously described dopaminergic misprojection in these embryos is accompanied by severe alterations in the GAD65 axon scaffold. Additional studies with cultured dopaminergic neurons and whole embryos suggest that NCAM and Robo proteins are involved in the interaction of GAD65 and dopaminergic axons. These results indicate that the fasciculation between descending GAD65 axon bundles and ascending dopaminergic axons is required for the stereotypical NSP formation during brain development and that known guidance cues may determine this projection indirectly by instructing the pathfinding of the axons that are part of the GAD65 axon scaffold.

  10. Music-related reward responses predict episodic memory performance.

    Science.gov (United States)

    Ferreri, Laura; Rodriguez-Fornells, Antoni

    2017-12-01

    Music represents a special type of reward involving the recruitment of the mesolimbic dopaminergic system. According to recent theories on episodic memory formation, as dopamine strengthens the synaptic potentiation produced by learning, stimuli triggering dopamine release could result in long-term memory improvements. Here, we behaviourally test whether music-related reward responses could modulate episodic memory performance. Thirty participants rated (in terms of arousal, familiarity, emotional valence, and reward) and encoded unfamiliar classical music excerpts. Twenty-four hours later, their episodic memory was tested (old/new recognition and remember/know paradigm). Results revealed an influence of music-related reward responses on memory: excerpts rated as more rewarding were significantly better recognized and remembered. Furthermore, inter-individual differences in the ability to experience musical reward, measured through the Barcelona Music Reward Questionnaire, positively predicted memory performance. Taken together, these findings shed new light on the relationship between music, reward and memory, showing for the first time that music-driven reward responses are directly implicated in higher cognitive functions and can account for individual differences in memory performance.

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

    Science.gov (United States)

    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.

  12. Mapping of olfactory memory circuits: region-specific c-fos activation after odor-reward associative learning or after its retrieval.

    Science.gov (United States)

    Tronel, Sophie; Sara, Susan J

    2002-01-01

    Although there is growing knowledge about intracellular mechanisms underlying neuronal plasticity and memory consolidation and reconsolidation after retrieval, information concerning the interaction among brain areas during formation and retrieval of memory is relatively sparse and fragmented. Addressing this question requires simultaneous monitoring of activity in multiple brain regions during learning, the post-acquisition consolidation period, and retrieval and subsequent reconsolidation. Immunoreaction to the immediate early gene c-fos is a powerful tool to mark neuronal activation of specific populations of neurons. Using this method, we are able to report, for the first time, post-training activation of a network of closely related brain regions, particularly in the frontal cortex and the basolateral amygdala (BLA), that is specific to the learning of an odor-reward association. On the other hand, retrieval of a well-established associative memory trace does not seem to differentially activate the same regions. The amygdala, in particular, is not engaged after retrieval, whereas the lateral habenula (LHab) shows strong activation that is restricted to animals having previously learned the association. Although intracellular mechanisms may be similar during consolidation and reconsolidation, this study indicates that different brain circuits are involved in the two processes, at least with respect to a rapidly learned olfactory task.

  13. Orexin/hypocretin role in reward: implications for opioid and other addictions.

    Science.gov (United States)

    Baimel, Corey; Bartlett, Selena E; Chiou, Lih-Chu; Lawrence, Andrew J; Muschamp, John W; Patkar, Omkar; Tung, Li-Wei; Borgland, Stephanie L

    2015-01-01

    Addiction is a devastating disorder that affects 15.3 million people worldwide. While prevalent, few effective treatments exist. Orexin receptors have been proposed as a potential target for anti-craving medications. Orexins, also known as hypocretins, are neuropeptides produced in neurons of the lateral and dorsomedial hypothalamus and perifornical area, which project widely throughout the brain. The absence of orexins in rodents and humans leads to narcolepsy. However, orexins also have an established role in reward seeking. This review will discuss some of the original studies describing the roles of the orexins in reward seeking as well as specific works that were presented at the 2013 International Narcotics Research Conference. Orexin signalling can promote drug-induced plasticity of glutamatergic synapses onto dopamine neurons of the ventral tegmental area (VTA), a brain region implicated in motivated behaviour. Additional evidence suggests that orexin signalling can also promote drug seeking by initiating an endocannabinoid-mediated synaptic depression of GABAergic inputs to the VTA, and thereby disinhibiting dopaminergic neurons. Orexin neurons co-express the inhibitory opioid peptide dynorphin. It has been proposed that orexin in the VTA may not mediate reward per se, but rather occludes the 'anti-reward' effects of dynorphin. Finally, orexin signalling in the prefrontal cortex and the central amygdala is implicated in reinstatement of reward seeking. This review will highlight recent work describing the role of orexin signalling in cellular processes underlying addiction-related behaviours and propose novel hypotheses for the mechanisms by which orexin signalling may impart drug seeking. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. © 2014 The British Pharmacological Society.

  14. Pain and suicidality: insights from reward and addiction neuroscience.

    Science.gov (United States)

    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.

  15. The genetic basis of individual differences in reward processing and the link to addictive behavior and social cognition.

    Science.gov (United States)

    Yacubian, J; Büchel, C

    2009-11-24

    Dopaminergic neurotransmission is widely recognized to be critical to the neurobiology of reward, motivation and addiction. Interestingly, social interactions and related behavior also activate the same neuronal system. Consequently, genetic variations of dopamine neurotransmission are thought influence reward processing that in turn may affect distinctive social behavior and susceptibility to addiction. This review focuses on advances made to date in an effort to link genetic individual variations and reward processing as a possible basis for addictive behaviors.

  16. Redundant dopaminergic activity may enable compensatory axonal sprouting in Parkinson disease.

    Science.gov (United States)

    Arkadir, David; Bergman, Hagai; Fahn, Stanley

    2014-03-25

    Neurodegenerative diseases become clinically apparent only after a substantial population of neurons is lost. This raises the possibility of compensatory mechanisms in the early phase of these diseases. The importance of understanding these mechanisms cannot be underestimated because it may guide future disease-modifying strategies. Because the anatomy and physiology of the nigrostriatal dopaminergic pathways have been well described, the study of Parkinson disease can offer insight into these early compensatory mechanisms. Collateral axonal sprouting of dopaminergic terminals into the denervated striatum is the most studied compensatory mechanism in animal (almost exclusively rodent) models of Parkinson disease and is correlated with behavioral recovery after partial lesions. This sprouting, however, does not respect the normal anatomy of the original nigrostriatal pathways and leads to aberrant neuronal networks. We suggest here that the unique physiologic property of the dopaminergic innervation of the striatum, namely redundancy of information encoding, is crucial to the efficacy of compensatory axonal sprouting in the presence of aberrant anatomical connections. Redundant information encoding results from the similarity of representation of salient and rewarding events by many dopaminergic neurons, from the wide axonal field of a single dopaminergic neuron in the striatum, and from the nonspecific spatial effect of dopamine on striatal neurons (volume conductance). Finally, we discuss the relevance of these findings in animal models to human patients with Parkinson disease.

  17. Neural activation to monetary reward is associated with amphetamine reward sensitivity.

    Science.gov (United States)

    Crane, Natania A; Gorka, Stephanie M; Weafer, Jessica; Langenecker, Scott A; de Wit, Harriet; Phan, K Luan

    2018-03-14

    One known risk factor for drug use and abuse is sensitivity to rewarding effects of drugs. It is not known whether this risk factor extends to sensitivity to non-drug rewards. In this study with healthy young adults, we examined the association between sensitivity to the subjective rewarding effects of amphetamine and a neural indicator of anticipation of monetary reward. We hypothesized that greater euphorigenic response to amphetamine would be associated with greater neural activation to anticipation of monetary reward (Win > Loss). Healthy participants (N = 61) completed four laboratory sessions in which they received d-amphetamine (20 mg) and placebo in alternating order, providing self-report measures of euphoria and stimulation at regular intervals. At a separate visit 1-3 weeks later, participants completed the guessing reward task (GRT) during fMRI in a drug-free state. Participants reporting greater euphoria after amphetamine also exhibited greater neural activation during monetary reward anticipation in mesolimbic reward regions, including the bilateral caudate and putamen. This is the first study to show a relationship between neural correlates of monetary reward and sensitivity to the subjective rewarding effects of amphetamine in humans. These findings support growing evidence that sensitivity to reward in general is a risk factor for drug use and abuse, and suggest that sensitivity of drug-induced euphoria may reflect a general sensitivity to rewards. This may be an index of vulnerability for drug use or abuse.

  18. Underconnectivity between voice-selective cortex and reward circuitry in children with autism.

    Science.gov (United States)

    Abrams, Daniel A; Lynch, Charles J; Cheng, Katherine M; Phillips, Jennifer; Supekar, Kaustubh; Ryali, Srikanth; Uddin, Lucina Q; Menon, Vinod

    2013-07-16

    Individuals with autism spectrum disorders (ASDs) often show insensitivity to the human voice, a deficit that is thought to play a key role in communication deficits in this population. The social motivation theory of ASD predicts that impaired function of reward and emotional systems impedes children with ASD from actively engaging with speech. Here we explore this theory by investigating distributed brain systems underlying human voice perception in children with ASD. Using resting-state functional MRI data acquired from 20 children with ASD and 19 age- and intelligence quotient-matched typically developing children, we examined intrinsic functional connectivity of voice-selective bilateral posterior superior temporal sulcus (pSTS). Children with ASD showed a striking pattern of underconnectivity between left-hemisphere pSTS and distributed nodes of the dopaminergic reward pathway, including bilateral ventral tegmental areas and nucleus accumbens, left-hemisphere insula, orbitofrontal cortex, and ventromedial prefrontal cortex. Children with ASD also showed underconnectivity between right-hemisphere pSTS, a region known for processing speech prosody, and the orbitofrontal cortex and amygdala, brain regions critical for emotion-related associative learning. The degree of underconnectivity between voice-selective cortex and reward pathways predicted symptom severity for communication deficits in children with ASD. Our results suggest that weak connectivity of voice-selective cortex and brain structures involved in reward and emotion may impair the ability of children with ASD to experience speech as a pleasurable stimulus, thereby impacting language and social skill development in this population. Our study provides support for the social motivation theory of ASD.

  19. Neural reward and punishment sensitivity in cigarette smokers.

    Science.gov (United States)

    Potts, Geoffrey F; Bloom, Erika L; Evans, David E; Drobes, David J

    2014-11-01

    Nicotine addiction remains a major public health problem but the neural substrates of addictive behavior remain unknown. One characteristic of smoking behavior is impulsive choice, selecting the immediate reward of smoking despite the potential long-term negative consequences. This suggests that drug users, including cigarette smokers, may be more sensitive to rewards and less sensitive to punishment. We used event-related potentials (ERPs) to test the hypothesis that smokers are more responsive to reward signals and less responsive to punishment, potentially predisposing them to risky behavior. We conducted two experiments, one using a reward prediction design to elicit a Medial Frontal Negativity (MFN) and one using a reward- and punishment-motivated flanker task to elicit an Error Related Negativity (ERN), ERP components thought to index activity in the cortical projection of the dopaminergic reward system. The smokers had a greater MFN response to unpredicted rewards, and non-smokers, but not smokers, had a larger ERN on punishment motivated trials indicating that smokers are more reward sensitive and less punishment sensitive than nonsmokers, overestimating the appetitive value and underestimating aversive outcomes of stimuli and actions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Dopaminergic neurons encode a distributed, asymmetric representation of temperature in Drosophila.

    Science.gov (United States)

    Tomchik, Seth M

    2013-01-30

    Dopaminergic circuits modulate a wide variety of innate and learned behaviors in animals, including olfactory associative learning, arousal, and temperature-preference behavior. It is not known whether distinct or overlapping sets of dopaminergic neurons modulate these behaviors. Here, I have functionally characterized the dopaminergic circuits innervating the Drosophila mushroom body with in vivo calcium imaging and conditional silencing of genetically defined subsets of neurons. Distinct subsets of PPL1 dopaminergic neurons innervating the vertical lobes of the mushroom body responded to decreases in temperature, but not increases, with rapidly adapting bursts of activity. PAM neurons innervating the horizontal lobes did not respond to temperature shifts. Ablation of the antennae and maxillary palps reduced, but did not eliminate, the responses. Genetic silencing of dopaminergic neurons innervating the vertical mushroom body lobes substantially reduced behavioral cold avoidance, but silencing smaller subsets of these neurons had no effect. These data demonstrate that overlapping dopaminergic circuits encode a broadly distributed, asymmetric representation of temperature that overlays regions implicated previously in learning, memory, and forgetting. Thus, diverse behaviors engage overlapping sets of dopaminergic neurons that encode multimodal stimuli and innervate a single anatomical target, the mushroom body.

  1. Neural processing of reward in adolescent rodents

    Directory of Open Access Journals (Sweden)

    Nicholas W. Simon

    2015-02-01

    Full Text Available Immaturities in adolescent reward processing are thought to contribute to poor decision making and increased susceptibility to develop addictive and psychiatric disorders. Very little is known; however, about how the adolescent brain processes reward. The current mechanistic theories of reward processing are derived from adult models. Here we review recent research focused on understanding of how the adolescent brain responds to rewards and reward-associated events. A critical aspect of this work is that age-related differences are evident in neuronal processing of reward-related events across multiple brain regions even when adolescent rats demonstrate behavior similar to adults. These include differences in reward processing between adolescent and adult rats in orbitofrontal cortex and dorsal striatum. Surprisingly, minimal age related differences are observed in ventral striatum, which has been a focal point of developmental studies. We go on to discuss the implications of these differences for behavioral traits affected in adolescence, such as impulsivity, risk-taking, and behavioral flexibility. Collectively, this work suggests that reward-evoked neural activity differs as a function of age and that regions such as the dorsal striatum that are not traditionally associated with affective processing in adults may be critical for reward processing and psychiatric vulnerability in adolescents.

  2. Weak reward source memory in depression reflects blunted activation of VTA/SN and parahippocampus

    OpenAIRE

    Dillon, Daniel G.; Dobbins, Ian G.; Pizzagalli, Diego A.

    2013-01-01

    Reward responses in the medial temporal lobes and dopaminergic midbrain boost episodic memory formation in healthy adults, and weak memory for emotionally positive material in depression suggests this mechanism may be dysfunctional in major depressive disorder (MDD). To test this hypothesis, we performed a study in which unmedicated adults with MDD and healthy controls encoded drawings paired with reward or zero tokens during functional magnetic resonance imaging. In a recognition test, parti...

  3. Monetary reward activates human prefrontal cortex

    International Nuclear Information System (INIS)

    Thut, G.; Roelcke, U.; Nienhusmeier, M.; Missimer, J.; Maguire, R.P.; Leenders, K.L.; Schultz, W.

    1997-01-01

    We present a rCBF PET activation study, in which we demonstrated that reward processing in humans activates a cortical-subcortical network including dorsolateral prefrontal, orbital frontal, thalamic and midbrain regions. It is suggested that, as found for non-human primates, the basal ganglia-thalamo-cortical system is implicated in reward processing. (author) 1 fig., 3 refs

  4. PET measurements od dopaminergic pathways in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Perlmutter, J.S. [Washington Univ., St. Louis, MO (United States). School of Medicine. Dept. of Neurology and Neurological Surgery, Anatomy and Neurobiology; Moerlein, S.M. [Washington Univ., St. Louis, MO (United States). School of Medicine. Dept. of Biochemistry and Molecular Biophysics, Mallinckrodt Institute of Radiology

    1999-06-01

    Position emission tomography (PET) measurements of dopaminergic pathways have revealed several new insights into the role of dopamine in the pathophysiology and pharmacology of brain diseases such as Parkinson's disease (PD), dystonia and schizophrenia. PET studies of regional blood flow of metabolism identifies sites of regional pathology. Drug-induced changes in flow or metabolism indicate the function of dopamine-mediated pathways. Measurements of radioligand binding 'in vivo' with PET reveals abnormalities associated with specific diseases and the actions of various drugs that effect the dopaminergic system. Finally, PET measurements of the uptake of analogues of levodopa provide clues to the function of dopamine pathways potentially important for diagnosis and treatment of disease like PD.

  5. At what stage of neural processing does cocaine act to boost pursuit of rewards?

    Directory of Open Access Journals (Sweden)

    Giovanni Hernandez

    2010-11-01

    Full Text Available Dopamine-containing neurons have been implicated in reward and decision making. One element of the supporting evidence is that cocaine, like other drugs that increase dopaminergic neurotransmission, powerfully potentiates reward seeking. We analyze this phenomenon from a novel perspective, introducing a new conceptual framework and new methodology for determining the stage(s of neural processing at which drugs, lesions and physiological manipulations act to influence reward-seeking behavior. Cocaine strongly boosts the proclivity of rats to work for rewarding electrical brain stimulation. We show that the conventional conceptual framework and methods do not distinguish between three conflicting accounts of how the drug produces this effect: increased sensitivity of brain reward circuitry, increased gain, or decreased subjective reward costs. Sensitivity determines the stimulation strength required to produce a reward of a given intensity (a measure analogous to the KM of an enzyme whereas gain determines the maximum intensity attainable (a measure analogous to the vmax of an enzyme-catalyzed reaction. To distinguish sensitivity changes from the other determinants, we measured and modeled reward seeking as a function of both stimulation strength and opportunity cost. The principal effect of cocaine was a two-fourfold increase in willingness to pay for the electrical reward, an effect consistent with increased gain or decreased subjective cost. This finding challenges the long-standing view that cocaine increases the sensitivity of brain reward circuitry. We discuss the implications of the results and the analytic approach for theories of how dopaminergic neurons and other diffuse modulatory brain systems contribute to reward pursuit, and we explore the implications of the conceptual framework for the study of natural rewards, drug reward, and mood.

  6. Reinforcement learning signals in the human striatum distinguish learners from nonlearners during reward-based decision making.

    Science.gov (United States)

    Schönberg, Tom; Daw, Nathaniel D; Joel, Daphna; O'Doherty, John P

    2007-11-21

    The computational framework of reinforcement learning has been used to forward our understanding of the neural mechanisms underlying reward learning and decision-making behavior. It is known that humans vary widely in their performance in decision-making tasks. Here, we used a simple four-armed bandit task in which subjects are almost evenly split into two groups on the basis of their performance: those who do learn to favor choice of the optimal action and those who do not. Using models of reinforcement learning we sought to determine the neural basis of these intrinsic differences in performance by scanning both groups with functional magnetic resonance imaging. We scanned 29 subjects while they performed the reward-based decision-making task. Our results suggest that these two groups differ markedly in the degree to which reinforcement learning signals in the striatum are engaged during task performance. While the learners showed robust prediction error signals in both the ventral and dorsal striatum during learning, the nonlearner group showed a marked absence of such signals. Moreover, the magnitude of prediction error signals in a region of dorsal striatum correlated significantly with a measure of behavioral performance across all subjects. These findings support a crucial role of prediction error signals, likely originating from dopaminergic midbrain neurons, in enabling learning of action selection preferences on the basis of obtained rewards. Thus, spontaneously observed individual differences in decision making performance demonstrate the suggested dependence of this type of learning on the functional integrity of the dopaminergic striatal system in humans.

  7. Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding

    International Nuclear Information System (INIS)

    Du, Huiyun; Deng, Wei; Aimone, James B.; Ge, Minyan; Parylak, Sarah

    2016-01-01

    Rewarding experiences are often well remembered, and such memory formation is known to be dependent on dopamine modulation of the neural substrates engaged in learning and memory; however, it is unknown how and where in the brain dopamine signals bias episodic memory toward preceding rather than subsequent events. Here we found that photostimulation of channelrhodopsin-2–expressing dopaminergic fibers in the dentate gyrus induced a long-term depression of cortical inputs, diminished theta oscillations, and impaired subsequent contextual learning. Computational modeling based on this dopamine modulation indicated an asymmetric association of events occurring before and after reward in memory tasks. In subsequent behavioral experiments, preexposure to a natural reward suppressed hippocampus-dependent memory formation, with an effective time window consistent with the duration of dopamine-induced changes of dentate activity. Altogether, our results suggest a mechanism by which dopamine enables the hippocampus to encode memory with reduced interference from subsequent experience.

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

    Science.gov (United States)

    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 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.

  9. Convergent dysregulation of frontal cortical cognitive and reward systems in eating disorders.

    Science.gov (United States)

    Stefano, George B; Ptáček, Radek; Kuželová, Hana; Mantione, Kirk J; Raboch, Jiří; Papezova, Hana; Kream, Richard M

    2013-05-10

    A substantive literature has drawn a compelling case for the functional involvement of mesolimbic/prefrontal cortical neural reward systems in normative control of eating and in the etiology and persistence of severe eating disorders that affect diverse human populations. Presently, we provide a short review that develops an equally compelling case for the importance of dysregulated frontal cortical cognitive neural networks acting in concert with regional reward systems in the regulation of complex eating behaviors and in the presentation of complex pathophysiological symptoms associated with major eating disorders. Our goal is to highlight working models of major eating disorders that incorporate complementary approaches to elucidate functionally interactive neural circuits defined by their regulatory neurochemical phenotypes. Importantly, we also review evidence-based linkages between widely studied psychiatric and neurodegenerative syndromes (e.g., autism spectrum disorders and Parkinson's disease) and co-morbid eating disorders to elucidate basic mechanisms involving dopaminergic transmission and its regulation by endogenously expressed morphine in these same cortical regions.

  10. Dopaminergic variants in siblings at high risk for autism: Associations with initiating joint attention.

    Science.gov (United States)

    Gangi, Devon N; Messinger, Daniel S; Martin, Eden R; Cuccaro, Michael L

    2016-11-01

    Younger siblings of children with autism spectrum disorder (ASD; high-risk siblings) exhibit lower levels of initiating joint attention (IJA; sharing an object or experience with a social partner through gaze and/or gesture) than low-risk siblings of children without ASD. However, high-risk siblings also exhibit substantial variability in this domain. The neurotransmitter dopamine is linked to brain areas associated with reward, motivation, and attention, and common dopaminergic variants have been associated with attention difficulties. We examined whether these common dopaminergic variants, DRD4 and DRD2, explain variability in IJA in high-risk (n = 55) and low-risk (n = 38) siblings. IJA was assessed in the first year during a semi-structured interaction with an examiner. DRD4 and DRD2 genotypes were coded according to associated dopaminergic functioning to create a gene score, with higher scores indicating more genotypes associated with less efficient dopaminergic functioning. Higher dopamine gene scores (indicative of less efficient dopaminergic functioning) were associated with lower levels of IJA in the first year for high-risk siblings, while the opposite pattern emerged in low-risk siblings. Findings suggest differential susceptibility-IJA was differentially associated with dopaminergic functioning depending on familial ASD risk. Understanding genes linked to ASD-relevant behaviors in high-risk siblings will aid in early identification of children at greatest risk for difficulties in these behavioral domains, facilitating targeted prevention and intervention. Autism Res 2016, 9: 1142-1150. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

  11. The globus pallidus sends reward-related signals to the lateral habenula.

    Science.gov (United States)

    Hong, Simon; Hikosaka, Okihide

    2008-11-26

    As a major output station of the basal ganglia, the globus pallidus internal segment (GPi) projects to the thalamus and brainstem nuclei thereby controlling motor behavior. A less well known fact is that the GPi also projects to the lateral habenula (LHb) which is often associated with the limbic system. Using the monkey performing a saccade task with positionally biased reward outcomes, we found that antidromically identified LHb-projecting neurons were distributed mainly in the dorsal and ventral borders of the GPi and that their activity was strongly modulated by expected reward outcomes. A majority of them were excited by the no-reward-predicting target and inhibited by the reward-predicting target. These reward-dependent modulations were similar to those in LHb neurons but started earlier than those in LHb neurons. These results suggest that GPi may initiate reward-related signals through its effects on the LHb, which then influences the dopaminergic and serotonergic systems.

  12. Reward-seeking behavior and addiction: cause or cog?

    Science.gov (United States)

    Arias-Carrión, Oscar; Salama, Mohamed

    2012-09-01

    Although dopaminergic system represents the cornerstone in rewarding, other neurotransmitters can modulate both the reward system and the psychomotor effects of addictive drugs. Many hypotheses have been proposed for a better understanding of the reward system and its role in drug addiction. However, after many years of investigation, no single theory can completely explain the neural basis of drug addiction. Recent reports introduce novel neurotransmitters into the game e.g. dynorphins, orexins, histamine, gheralin and galanin. The interacting functions of these neurotransmitters have shown that the reward system and its role in drug dependence, is far more complicated than was thought before. Individual variations exist regarding response to drug exposure, vulnerability for addiction and the effects of different cues on reward systems. Consequently, genetic variations of neurotransmission are thought to influence reward processing that in turn may affect distinctive social behavior and susceptibility to addiction. However, the individual variations can not be based mainly on genetics; environmental factors seem to play a role too. Here we discuss the current knowledge about the orquestic regulation of different neurotransmitters on reward-seeking behavior and their potential effect on drug addiction.

  13. Distinct Reward Properties are Encoded via Corticostriatal Interactions.

    Science.gov (United States)

    Smith, David V; Rigney, Anastasia E; Delgado, Mauricio R

    2016-02-02

    The striatum serves as a critical brain region for reward processing. Yet, understanding the link between striatum and reward presents a challenge because rewards are composed of multiple properties. Notably, affective properties modulate emotion while informative properties help obtain future rewards. We approached this problem by emphasizing affective and informative reward properties within two independent guessing games. We found that both reward properties evoked activation within the nucleus accumbens, a subregion of the striatum. Striatal responses to informative, but not affective, reward properties predicted subsequent utilization of information for obtaining monetary reward. We hypothesized that activation of the striatum may be necessary but not sufficient to encode distinct reward properties. To investigate this possibility, we examined whether affective and informative reward properties were differentially encoded in corticostriatal interactions. Strikingly, we found that the striatum exhibited dissociable connectivity patterns with the ventrolateral prefrontal cortex, with increasing connectivity for affective reward properties and decreasing connectivity for informative reward properties. Our results demonstrate that affective and informative reward properties are encoded via corticostriatal interactions. These findings highlight how corticostriatal systems contribute to reward processing, potentially advancing models linking striatal activation to behavior.

  14. Identification of a dopamine receptor-mediated opiate reward memory switch in the basolateral amygdala-nucleus accumbens circuit.

    Science.gov (United States)

    Lintas, Alessandra; Chi, Ning; Lauzon, Nicole M; Bishop, Stephanie F; Gholizadeh, Shervin; Sun, Ninglei; Tan, Huibing; Laviolette, Steven R

    2011-08-03

    The basolateral amygdala (BLA), ventral tegmental area (VTA), and nucleus accumbens (NAc) play central roles in the processing of opiate-related associative reward learning and memory. The BLA receives innervation from dopaminergic fibers originating in the VTA, and both dopamine (DA) D1 and D2 receptors are expressed in this region. Using a combination of in vivo single-unit extracellular recording in the NAc combined with behavioral pharmacology studies, we have identified a double dissociation in the functional roles of DA D1 versus D2 receptor transmission in the BLA, which depends on opiate exposure state; thus, in previously opiate-naive rats, blockade of intra-BLA D1, but not D2, receptor transmission blocked the acquisition of associative opiate reward memory, measured in an unbiased conditioned place preference procedure. In direct contrast, in rats made opiate dependent and conditioned in a state of withdrawal, intra-BLA D2, but not D1, receptor blockade blocked opiate reward encoding. This functional switch was dependent on cAMP signaling as comodulation of intra-BLA cAMP levels reversed or replicated the functional effects of intra-BLA D1 or D2 transmission during opiate reward processing. Single-unit in vivo extracellular recordings performed in neurons of the NAc confirmed an opiate-state-dependent role for BLA D1/D2 transmission in NAc neuronal response patterns to morphine. Our results characterize and identify a novel opiate addiction switching mechanism directly in the BLA that can control the processing of opiate reward information as a direct function of opiate exposure state via D1 or D2 receptor signaling substrates.

  15. The role of the central ghrelin system in reward from food and chemical drugs.

    Science.gov (United States)

    Dickson, Suzanne L; Egecioglu, Emil; Landgren, Sara; Skibicka, Karolina P; Engel, Jörgen A; Jerlhag, Elisabet

    2011-06-20

    Here we review recent advances that identify a role for the central ghrelin signalling system in reward from both natural rewards (such as food) and artificial rewards (that include alcohol and drugs of abuse). Whereas ghrelin emerged as a stomach-derived hormone involved in energy balance, hunger and meal initiation via hypothalamic circuits, it now seems clear that it also has a role in motivated reward-driven behaviours via activation of the so-called "cholinergic-dopaminergic reward link". This reward link comprises a dopamine projection from the ventral tegmental area (VTA) to the nucleus accumbens together with a cholinergic input, arising primarily from the laterodorsal tegmental area. Ghrelin administration into the VTA or LDTg activates the "cholinergic-dopaminergic" reward link, suggesting that ghrelin may increase the incentive value of motivated behaviours such as reward-seeking behaviour ("wanting" or "incentive motivation"). Further, direct injection of ghrelin into the brain ventricles or into the VTA increases the consumption of rewarding foods as well as alcohol in mice and rats. Studies in rodents show beneficial effects of ghrelin receptor (GHS-R1A) antagonists to suppress the intake of palatable food, to reduce preference for caloric foods, to suppress food reward and motivated behaviour for food. They have also been shown to reduce alcohol consumption, suppress reward induced by alcohol, cocaine and amphetamine. Furthermore, variations in the GHS-R1A and pro-ghrelin genes have been associated with high alcohol consumption, smoking and increased weight gain in alcohol dependent individuals as well as with bulimia nervosa and obesity. Thus, the central ghrelin signalling system interfaces neurobiological circuits involved in reward from food as well as chemical drugs; agents that directly or indirectly suppress this system emerge as potential candidate drugs for suppressing problematic over-eating that leads to obesity as well as for the

  16. Integration of reward signalling and appetite regulating peptide systems in the control of food-cue responses.

    Science.gov (United States)

    Reichelt, A C; Westbrook, R F; Morris, M J

    2015-11-01

    Understanding the neurobiological substrates that encode learning about food-associated cues and how those signals are modulated is of great clinical importance especially in light of the worldwide obesity problem. Inappropriate or maladaptive responses to food-associated cues can promote over-consumption, leading to excessive energy intake and weight gain. Chronic exposure to foods rich in fat and sugar alters the reinforcing value of foods and weakens inhibitory neural control, triggering learned, but maladaptive, associations between environmental cues and food rewards. Thus, responses to food-associated cues can promote cravings and food-seeking by activating mesocorticolimbic dopamine neurocircuitry, and exert physiological effects including salivation. These responses may be analogous to the cravings experienced by abstaining drug addicts that can trigger relapse into drug self-administration. Preventing cue-triggered eating may therefore reduce the over-consumption seen in obesity and binge-eating disorder. In this review we discuss recent research examining how cues associated with palatable foods can promote reward-based feeding behaviours and the potential involvement of appetite-regulating peptides including leptin, ghrelin, orexin and melanin concentrating hormone. These peptide signals interface with mesolimbic dopaminergic regions including the ventral tegmental area to modulate reactivity to cues associated with palatable foods. Thus, a novel target for anti-obesity therapeutics is to reduce non-homeostatic, reward driven eating behaviour, which can be triggered by environmental cues associated with highly palatable, fat and sugar rich foods. © 2015 The British Pharmacological Society.

  17. Preserved dopaminergic homeostasis and dopamine-related behaviour in hemizygous TH-Cre mice.

    Science.gov (United States)

    Runegaard, Annika H; Jensen, Kathrine L; Fitzpatrick, Ciarán M; Dencker, Ditte; Weikop, Pia; Gether, Ulrik; Rickhag, Mattias

    2017-01-01

    Cre-driver mouse lines have been extensively used as genetic tools to target and manipulate genetically defined neuronal populations by expression of Cre recombinase under selected gene promoters. This approach has greatly advanced neuroscience but interpretations are hampered by the fact that most Cre-driver lines have not been thoroughly characterized. Thus, a phenotypic characterization is of major importance to reveal potential aberrant phenotypes prior to implementation and usage to selectively inactivate or induce transgene expression. Here, we present a biochemical and behavioural assessment of the dopaminergic system in hemizygous tyrosine hydroxylase (TH)-Cre mice in comparison to wild-type (WT) controls. Our data show that TH-Cre mice display preserved dopaminergic homeostasis with unaltered levels of TH and dopamine as well as unaffected dopamine turnover in striatum. TH-Cre mice also show preserved dopamine transporter expression and function supporting sustained dopaminergic transmission. In addition, TH-Cre mice demonstrate normal responses in basic behavioural paradigms related to dopaminergic signalling including locomotor activity, reward preference and anxiolytic behaviour. Our results suggest that TH-Cre mice represent a valid tool to study the dopamine system, though careful characterization must always be performed to prevent false interpretations following Cre-dependent transgene expression and manipulation of selected neuronal pathways. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  18. Addiction and brain reward and antireward pathways.

    Science.gov (United States)

    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

  19. Ventromedial Prefrontal Cortex Activation Is Associated with Memory Formation for Predictable Rewards

    Science.gov (United States)

    Bialleck, Katharina A.; Schaal, Hans-Peter; Kranz, Thorsten A.; Fell, Juergen; Elger, Christian E.; Axmacher, Nikolai

    2011-01-01

    During reinforcement learning, dopamine release shifts from the moment of reward consumption to the time point when the reward can be predicted. Previous studies provide consistent evidence that reward-predicting cues enhance long-term memory (LTM) formation of these items via dopaminergic projections to the ventral striatum. However, it is less clear whether memory for items that do not precede a reward but are directly associated with reward consumption is also facilitated. Here, we investigated this question in an fMRI paradigm in which LTM for reward-predicting and neutral cues was compared to LTM for items presented during consumption of reliably predictable as compared to less predictable rewards. We observed activation of the ventral striatum and enhanced memory formation during reward anticipation. During processing of less predictable as compared to reliably predictable rewards, the ventral striatum was activated as well, but items associated with less predictable outcomes were remembered worse than items associated with reliably predictable outcomes. Processing of reliably predictable rewards activated the ventromedial prefrontal cortex (vmPFC), and vmPFC BOLD responses were associated with successful memory formation of these items. Taken together, these findings show that consumption of reliably predictable rewards facilitates LTM formation and is associated with activation of the vmPFC. PMID:21326612

  20. Reward speeds up and increases consistency of visual selective attention: a lifespan comparison.

    Science.gov (United States)

    Störmer, Viola; Eppinger, Ben; Li, Shu-Chen

    2014-06-01

    Children and older adults often show less favorable reward-based learning and decision making, relative to younger adults. It is unknown, however, whether reward-based processes that influence relatively early perceptual and attentional processes show similar lifespan differences. In this study, we investigated whether stimulus-reward associations affect selective visual attention differently across the human lifespan. Children, adolescents, younger adults, and older adults performed a visual search task in which the target colors were associated with either high or low monetary rewards. We discovered that high reward value speeded up response times across all four age groups, indicating that reward modulates attentional selection across the lifespan. This speed-up in response time was largest in younger adults, relative to the other three age groups. Furthermore, only younger adults benefited from high reward value in increasing response consistency (i.e., reduction of trial-by-trial reaction time variability). Our findings suggest that reward-based modulations of relatively early and implicit perceptual and attentional processes are operative across the lifespan, and the effects appear to be greater in adulthood. The age-specific effect of reward on reducing intraindividual response variability in younger adults likely reflects mechanisms underlying the development and aging of reward processing, such as lifespan age differences in the efficacy of dopaminergic modulation. Overall, the present results indicate that reward shapes visual perception across different age groups by biasing attention to motivationally salient events.

  1. Adaptive neural reward processing during anticipation and receipt of monetary rewards in mindfulness meditators.

    Science.gov (United States)

    Kirk, Ulrich; Brown, Kirk Warren; Downar, Jonathan

    2015-05-01

    Reward seeking is ubiquitous and adaptive in humans. But excessive reward seeking behavior, such as chasing monetary rewards, may lead to diminished subjective well-being. This study examined whether individuals trained in mindfulness meditation show neural evidence of lower susceptibility to monetary rewards. Seventy-eight participants (34 meditators, 44 matched controls) completed the monetary incentive delay task while undergoing functional magnetic resonance imaging. The groups performed equally on the task, but meditators showed lower neural activations in the caudate nucleus during reward anticipation, and elevated bilateral posterior insula activation during reward anticipation. Meditators also evidenced reduced activations in the ventromedial prefrontal cortex during reward receipt compared with controls. Connectivity parameters between the right caudate and bilateral anterior insula were attenuated in meditators during incentive anticipation. In summary, brain regions involved in reward processing-both during reward anticipation and receipt of reward-responded differently in mindfulness meditators than in nonmeditators, indicating that the former are less susceptible to monetary incentives. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  2. Reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors.

    Science.gov (United States)

    Blum, K; Braverman, E R; Holder, J M; Lubar, J F; Monastra, V J; Miller, D; Lubar, J O; Chen, T J; Comings, D E

    2000-11-01

    The dopaminergic system, and in particular the dopamine D2 receptor, has been implicated in reward mechanisms. The net effect of neurotransmitter interaction at the mesolimbic brain region induces "reward" when dopamine (DA) is released from the neuron at the nucleus accumbens and interacts with a dopamine D2 receptor. "The reward cascade" involves the release of serotonin, which in turn at the hypothalmus stimulates enkephalin, which in turn inhibits GABA at the substania nigra, which in turn fine tunes the amount of DA released at the nucleus accumbens or "reward site." It is well known that under normal conditions in the reward site DA works to maintain our normal drives. In fact, DA has become to be known as the "pleasure molecule" and/or the "antistress molecule." When DA is released into the synapse, it stimulates a number a DA receptors (D1-D5) which results in increased feelings of well-being and stress reduction. A consensus of the literature suggests that when there is a dysfunction in the brain reward cascade, which could be caused by certain genetic variants (polygenic), especially in the DA system causing a hypodopaminergic trait, the brain of that person requires a DA fix to feel good. This trait leads to multiple drug-seeking behavior. This is so because alcohol, cocaine, heroin, marijuana, nicotine, and glucose all cause activation and neuronal release of brain DA, which could heal the abnormal cravings. Certainly after ten years of study we could say with confidence that carriers of the DAD2 receptor A1 allele have compromised D2 receptors. Therefore lack of D2 receptors causes individuals to have a high risk for multiple addictive, impulsive and compulsive behavioral propensities, such as severe alcoholism, cocaine, heroin, marijuana and nicotine use, glucose bingeing, pathological gambling, sex addiction, ADHD, Tourette's Syndrome, autism, chronic violence, posttraumatic stress disorder, schizoid/avoidant cluster, conduct disorder and antisocial

  3. Active reward processing during human sleep: insights from sleep-related eating disorder

    Directory of Open Access Journals (Sweden)

    Lampros ePerogamvros

    2012-11-01

    Full Text Available In this paper, we present two carefully documented cases of patients with sleep-related eating disorder (SRED, a parasomnia which is characterized by involuntary compulsive eating during the night and whose pathophysiology is not known. Using video-polysomnography and psychometric examination, we found that both patients present elevated novelty seeking and increased reward sensitivity on reward-related questionnaires. In light of new evidence on the mesolimbic dopaminergic implication in compulsive eating disorders, our findings suggest a role of an active reward system during sleep in the manifestation of SRED.

  4. Dopamine reward prediction errors reflect hidden state inference across time

    Science.gov (United States)

    Starkweather, Clara Kwon; Babayan, Benedicte M.; Uchida, Naoshige; Gershman, Samuel J.

    2017-01-01

    Midbrain dopamine neurons signal reward prediction error (RPE), or actual minus expected reward. The temporal difference (TD) learning model has been a cornerstone in understanding how dopamine RPEs could drive associative learning. Classically, TD learning imparts value to features that serially track elapsed time relative to observable stimuli. In the real world, however, sensory stimuli provide ambiguous information about the hidden state of the environment, leading to the proposal that TD learning might instead compute a value signal based on an inferred distribution of hidden states (a ‘belief state’). In this work, we asked whether dopaminergic signaling supports a TD learning framework that operates over hidden states. We found that dopamine signaling exhibited a striking difference between two tasks that differed only with respect to whether reward was delivered deterministically. Our results favor an associative learning rule that combines cached values with hidden state inference. PMID:28263301

  5. Sexual dimorphism in striatal dopaminergic responses promotes monogamy in social songbirds.

    Science.gov (United States)

    Tokarev, Kirill; Hyland Bruno, Julia; Ljubičić, Iva; Kothari, Paresh J; Helekar, Santosh A; Tchernichovski, Ofer; Voss, Henning U

    2017-08-11

    In many songbird species, males sing to attract females and repel rivals. How can gregarious, non-territorial songbirds such as zebra finches, where females have access to numerous males, sustain monogamy? We found that the dopaminergic reward circuitry of zebra finches can simultaneously promote social cohesion and breeding boundaries. Surprisingly, in unmated males but not in females, striatal dopamine neurotransmission was elevated after hearing songs. Behaviorally too, unmated males but not females persistently exchanged mild punishments in return for songs. Song reinforcement diminished when dopamine receptors were blocked. In females, we observed song reinforcement exclusively to the mate's song, although their striatal dopamine neurotransmission was only slightly elevated. These findings suggest that song-triggered dopaminergic activation serves a dual function in social songbirds: as low-threshold social reinforcement in males and as ultra-selective sexual reinforcement in females. Co-evolution of sexually dimorphic reinforcement systems can explain the coexistence of gregariousness and monogamy.

  6. Segregated encoding of reward-identity and stimulus-reward associations in human orbitofrontal cortex.

    Science.gov (United States)

    Klein-Flügge, Miriam Cornelia; Barron, Helen Catharine; Brodersen, Kay Henning; Dolan, Raymond J; Behrens, Timothy Edward John

    2013-02-13

    A dominant focus in studies of learning and decision-making is the neural coding of scalar reward value. This emphasis ignores the fact that choices are strongly shaped by a rich representation of potential rewards. Here, using fMRI adaptation, we demonstrate that responses in the human orbitofrontal cortex (OFC) encode a representation of the specific type of food reward predicted by a visual cue. By controlling for value across rewards and by linking each reward with two distinct stimuli, we could test for representations of reward-identity that were independent of associative information. Our results show reward-identity representations in a medial-caudal region of OFC, independent of the associated predictive stimulus. This contrasts with a more rostro-lateral OFC region encoding reward-identity representations tied to the predicate stimulus. This demonstration of adaptation in OFC to reward specific representations opens an avenue for investigation of more complex decision mechanisms that are not immediately accessible in standard analyses, which focus on correlates of average activity.

  7. Individual differences in sensitivity to reward and punishment and neural activity during reward and avoidance learning.

    Science.gov (United States)

    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.

  8. Hypothesizing Music Intervention Enhances Brain Functional Connectivity Involving Dopaminergic Recruitment: Common Neuro-correlates to Abusable Drugs.

    Science.gov (United States)

    Blum, Kenneth; Simpatico, Thomas; Febo, Marcelo; Rodriquez, Chris; Dushaj, Kristina; Li, Mona; Braverman, Eric R; Demetrovics, Zsolt; Oscar-Berman, Marlene; Badgaiyan, Rajendra D

    2017-07-01

    The goal of this review is to explore the clinical significance of music listening on neuroplasticity and dopaminergic activation by understanding the role of music therapy in addictive behavior treatment. fMRI data has shown that music listening intensely modifies mesolimbic structural changes responsible for reward processing (e.g., nucleus accumbens [NAc]) and may control the emotional stimuli's effect on autonomic and physiological responses (e.g., hypothalamus). Music listening has been proven to induce the endorphinergic response blocked by naloxone, a common opioid antagonist. NAc opioid transmission is linked to the ventral tegmental area (VTA) dopamine release. There are remarkable commonalities between listening to music and the effect of drugs on mesolimbic dopaminergic activation. It has been found that musical training before the age of 7 results in changes in white-matter connectivity, protecting carriers with low dopaminergic function (DRD2A1 allele, etc.) from poor decision-making, reward dependence, and impulsivity. In this article, we briefly review a few studies on the neurochemical effects of music and propose that these findings are relevant to the positive clinical findings observed in the literature. We hypothesize that music intervention enhances brain white matter plasticity through dopaminergic recruitment and that more research is needed to explore the efficacy of these therapies.

  9. Topography and collateralization of dopaminergic projections to primary motor cortex in rats.

    Science.gov (United States)

    Hosp, Jonas A; Nolan, Helen E; Luft, Andreas R

    2015-05-01

    Dopaminergic signaling within the primary motor cortex (M1) is necessary for successful motor skill learning. Dopaminergic neurons projecting to M1 are located in the ventral tegmental area (VTA, nucleus A10) of the midbrain. It is unknown which behavioral correlates are encoded by these neurons. The objective here is to investigate whether VTA-M1 fibers are collaterals of projections to prefrontal cortex (PFC) or nucleus accumbens (NAc) or if they form a distinct pathway. In rats, multiple-site retrograde fluorescent tracers were injected into M1, PFC and the core region of the NAc and VTA sections investigated for concomitant labeling of different tracers. Dopaminergic neurons projecting to M1, PFC and NAc were found in nucleus A10 and to a lesser degree in the medial nucleus A9. Neurons show high target specificity, minimal collateral branching to other than their target area and hardly cross the midline. Whereas PFC- and NAc-projecting neurons are indistinguishably intermingled within the ventral portion of dopaminergic nuclei in middle and caudal midbrain, M1-projecting neurons are only located within the dorsal part of the rostral midbrain. Within M1, the forelimb representation receives sevenfold more dopaminergic projections than the hindlimb representation. This strong rostro-caudal gradient as well as the topographical preference to dorsal structures suggest that projections to M1 emerged late in the development of the dopaminergic systems in and form a functionally distinct system.

  10. Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory.

    Science.gov (United States)

    Ikemoto, Satoshi

    2010-11-01

    Reductionist attempts to dissect complex mechanisms into simpler elements are necessary, but not sufficient for understanding how biological properties like reward emerge out of neuronal activity. Recent studies on intracranial self-administration of neurochemicals (drugs) found that rats learn to self-administer various drugs into the mesolimbic dopamine structures-the posterior ventral tegmental area, medial shell nucleus accumbens and medial olfactory tubercle. In addition, studies found roles of non-dopaminergic mechanisms of the supramammillary, rostromedial tegmental and midbrain raphe nuclei in reward. To explain intracranial self-administration and related effects of various drug manipulations, I outlined a neurobiological theory claiming that there is an intrinsic central process that coordinates various selective functions (including perceptual, visceral, and reinforcement processes) into a global function of approach. Further, this coordinating process for approach arises from interactions between brain structures including those structures mentioned above and their closely linked regions: the medial prefrontal cortex, septal area, ventral pallidum, bed nucleus of stria terminalis, preoptic area, lateral hypothalamic areas, lateral habenula, periaqueductal gray, laterodorsal tegmental nucleus and parabrachical area. Published by Elsevier Ltd.

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

    Science.gov (United States)

    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.

  12. Reward sensitivity is associated with brain activity during erotic stimulus processing.

    Science.gov (United States)

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

    2013-01-01

    The behavioral approach system (BAS) from Gray's reinforcement sensitivity theory is a neurobehavioral system involved in the processing of rewarding stimuli that has been related to dopaminergic brain areas. Gray's theory hypothesizes that the functioning of reward brain areas is modulated by BAS-related traits. To test this hypothesis, we performed an fMRI study where participants viewed erotic and neutral pictures, and cues that predicted their appearance. Forty-five heterosexual men completed the Sensitivity to Reward scale (from the Sensitivity to Punishment and Sensitivity to Reward Questionnaire) to measure BAS-related traits. Results showed that Sensitivity to Reward scores correlated positively with brain activity during reactivity to erotic pictures in the left orbitofrontal cortex, left insula, and right ventral striatum. These results demonstrated a relationship between the BAS and reward sensitivity during the processing of erotic stimuli, filling the gap of previous reports that identified the dopaminergic system as a neural substrate for the BAS during the processing of other rewarding stimuli such as money and food.

  13. Reward sensitivity is associated with brain activity during erotic stimulus processing.

    Directory of Open Access Journals (Sweden)

    Victor Costumero

    Full Text Available The behavioral approach system (BAS from Gray's reinforcement sensitivity theory is a neurobehavioral system involved in the processing of rewarding stimuli that has been related to dopaminergic brain areas. Gray's theory hypothesizes that the functioning of reward brain areas is modulated by BAS-related traits. To test this hypothesis, we performed an fMRI study where participants viewed erotic and neutral pictures, and cues that predicted their appearance. Forty-five heterosexual men completed the Sensitivity to Reward scale (from the Sensitivity to Punishment and Sensitivity to Reward Questionnaire to measure BAS-related traits. Results showed that Sensitivity to Reward scores correlated positively with brain activity during reactivity to erotic pictures in the left orbitofrontal cortex, left insula, and right ventral striatum. These results demonstrated a relationship between the BAS and reward sensitivity during the processing of erotic stimuli, filling the gap of previous reports that identified the dopaminergic system as a neural substrate for the BAS during the processing of other rewarding stimuli such as money and food.

  14. Dopamine reward prediction error coding

    OpenAIRE

    Schultz, Wolfram

    2016-01-01

    Reward prediction errors consist of the differences between received and predicted rewards. They are crucial for basic forms of learning about rewards and make us strive for more rewards?an evolutionary beneficial trait. Most dopamine neurons in the midbrain of humans, monkeys, and rodents signal a reward prediction error; they are activated by more reward than predicted (positive prediction error), remain at baseline activity for fully predicted rewards, and show depressed activity with less...

  15. Reward processing in the value-driven attention network: reward signals tracking cue identity and location.

    Science.gov (United States)

    Anderson, Brian A

    2017-03-01

    Through associative reward learning, arbitrary cues acquire the ability to automatically capture visual attention. Previous studies have examined the neural correlates of value-driven attentional orienting, revealing elevated activity within a network of brain regions encompassing the visual corticostriatal loop [caudate tail, lateral occipital complex (LOC) and early visual cortex] and intraparietal sulcus (IPS). Such attentional priority signals raise a broader question concerning how visual signals are combined with reward signals during learning to create a representation that is sensitive to the confluence of the two. This study examines reward signals during the cued reward training phase commonly used to generate value-driven attentional biases. High, compared with low, reward feedback preferentially activated the value-driven attention network, in addition to regions typically implicated in reward processing. Further examination of these reward signals within the visual system revealed information about the identity of the preceding cue in the caudate tail and LOC, and information about the location of the preceding cue in IPS, while early visual cortex represented both location and identity. The results reveal teaching signals within the value-driven attention network during associative reward learning, and further suggest functional specialization within different regions of this network during the acquisition of an integrated representation of stimulus value. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  16. Nigrostriatal and Mesolimbic D2/3 Receptor Expression in Parkinson's Disease Patients with Compulsive Reward-Driven Behaviors.

    Science.gov (United States)

    Stark, Adam J; Smith, Christopher T; Lin, Ya-Chen; Petersen, Kalen J; Trujillo, Paula; van Wouwe, Nelleke C; Kang, Hakmook; Donahue, Manus J; Kessler, Robert M; Zald, David H; Claassen, Daniel O

    2018-03-28

    The nigrostriatal and mesocorticolimbic dopamine networks regulate reward-driven behavior. Regional alterations to mesolimbic dopamine D 2/3 receptor expression are described in drug-seeking and addiction disorders. Parkinson's disease (PD) patients are frequently prescribed D 2 -like dopamine agonist (DAgonist) therapy for motor symptoms, yet a proportion develop clinically significant behavioral addictions characterized by impulsive and compulsive behaviors (ICBs). Until now, changes in D 2/3 receptor binding in both striatal and extrastriatal regions have not been concurrently quantified in this population. We identified 35 human PD patients (both male and female) receiving DAgonist therapy, with ( n = 17) and without ( n = 18) ICBs, matched for age, disease duration, disease severity, and dose of dopamine therapy. In the off-dopamine state, all completed PET imaging with [ 18 F]fallypride, a high affinity D 2 -like receptor ligand that can measure striatal and extrastriatal D 2/3 nondisplaceable binding potential (BP ND ). Striatal differences between ICB+/ICB- patients localized to the ventral striatum and putamen, where ICB+ subjects had reduced BP ND In this group, self-reported severity of ICB symptoms positively correlated with midbrain D 2/3 receptor BP ND Group differences in regional D 2/3 BP ND relationships were also notable: ICB+ (but not ICB-) patients expressed positive correlations between midbrain and caudate, putamen, globus pallidus, and amygdala BP ND s. These findings support the hypothesis that compulsive behaviors in PD are associated with reduced ventral and dorsal striatal D 2/3 expression, similar to changes in comparable behavioral disorders. The data also suggest that relatively preserved ventral midbrain dopaminergic projections throughout nigrostriatal and mesolimbic networks are characteristic of ICB+ patients, and may account for differential DAgonist therapeutic response. SIGNIFICANCE STATEMENT The biologic determinants of

  17. Expected reward modulates encoding-related theta activity before an event.

    Science.gov (United States)

    Gruber, Matthias J; Watrous, Andrew J; Ekstrom, Arne D; Ranganath, Charan; Otten, Leun J

    2013-01-01

    Oscillatory brain activity in the theta frequency range (4-8 Hz) before the onset of an event has been shown to affect the likelihood of successfully encoding the event into memory. Recent work has also indicated that frontal theta activity might be modulated by reward, but it is not clear how reward expectancy, anticipatory theta activity, and memory formation might be related. Here, we used scalp electroencephalography (EEG) to assess the relationship between these factors. EEG was recorded from healthy adults while they memorized a series of words. Each word was preceded by a cue that indicated whether a high or low monetary reward would be earned if the word was successfully remembered in a later recognition test. Frontal theta power between the presentation of the reward cue and the onset of a word was predictive of later memory for the word, but only in the high reward condition. No theta differences were observed before word onset following low reward cues. The magnitude of prestimulus encoding-related theta activity in the high reward condition was correlated with the number of high reward words that were later confidently recognized. These findings provide strong evidence for a link between reward expectancy, theta activity, and memory encoding. Theta activity before event onset seems to be especially important for the encoding of motivationally significant stimuli. One possibility is that dopaminergic activity during reward anticipation mediates frontal theta activity related to memory. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Dopaminergic Therapy Increases Go Timeouts in the Go/No-Go Task in Patients with Parkinson’s Disease

    Science.gov (United States)

    Yang, Xue Q.; Lauzon, Brian; Seergobin, Ken N.; MacDonald, Penny A.

    2018-01-01

    Parkinson’s disease (PD) is characterized by resting tremor, rigidity and bradykinesia. Dopaminergic medications such as L-dopa treat these motor symptoms, but can have complex effects on cognition. Impulse control is an essential cognitive function. Impulsivity is multifaceted in nature. Motor impulsivity involves the inability to withhold pre-potent, automatic, erroneous responses. In contrast, cognitive impulsivity refers to improper risk-reward assessment guiding behavior. Informed by our previous research, we anticipated that dopaminergic therapy would decrease motor impulsivity though it is well known to enhance cognitive impulsivity. We employed the Go/No-go paradigm to assess motor impulsivity in PD. Patients with PD were tested using a Go/No-go task on and off their normal dopaminergic medication. Participants completed cognitive, mood, and physiological measures. PD patients on medication had a significantly higher proportion of Go trial Timeouts (i.e., trials in which Go responses were not completed prior to a deadline of 750 ms) compared to off medication (p = 0.01). No significant ON-OFF differences were found for Go trial or No-go trial response times (RTs), or for number of No-go errors. We interpret that dopaminergic therapy induces a more conservative response set, reflected in Go trial Timeouts in PD patients. In this way, dopaminergic therapy decreased motor impulsivity in PD patients. This is in contrast to the widely recognized effects of dopaminergic therapy on cognitive impulsivity leading in some patients to impulse control disorders. Understanding the nuanced effects of dopaminergic treatment in PD on cognitive functions such as impulse control will clarify therapeutic decisions. PMID:29354045

  19. Dopaminergic Dysregulation, Artistic Expressiveness, and Parkinson's Disease

    Science.gov (United States)

    López-Pousa, S.; Lombardía-Fernández, C.; Olmo, J. Garre; Monserrat-Vila, S.; Vilalta-Franch, J.; Calvó-Perxas, L.

    2012-01-01

    Background The most frequent behavioral manifestations in Parkinson's disease (PD) are attributed to the dopaminergic dysregulation syndrome (DDS), which is considered to be secondary to the iatrogenic effects of the drugs that replace dopamine. Over the past few years some cases of patients improving their creative abilities after starting treatment with dopaminergic pharmaceuticals have been reported. These effects have not been clearly associated to DDS, but a relationship has been pointed out. Methods Case study of a patient with PD. The evolution of her paintings along medication changes and disease advance has been analyzed. Results The patient showed a compulsive increase of pictorial production after the diagnosis of PD was made. She made her best paintings when treated with cabergolide, and while painting, she reported a feeling of well-being, with loss of awareness of the disease and reduction of physical limitations. Conclusions Dopaminergic antagonists (DA) trigger a dopaminergic dysfunction that alters artistic creativity in patients having a predisposition for it. The development of these skills might be due to the dopaminergic overstimulation due to the therapy with DA, which causes a neurophysiological alteration that globally determines DDS. PMID:23185168

  20. Working Memory Load Strengthens Reward Prediction Errors.

    Science.gov (United States)

    Collins, Anne G E; Ciullo, Brittany; Frank, Michael J; Badre, David

    2017-04-19

    Reinforcement learning (RL) in simple instrumental tasks is usually modeled as a monolithic process in which reward prediction errors (RPEs) are used to update expected values of choice options. This modeling ignores the different contributions of different memory and decision-making systems thought to contribute even to simple learning. In an fMRI experiment, we investigated how working memory (WM) and incremental RL processes interact to guide human learning. WM load was manipulated by varying the number of stimuli to be learned across blocks. Behavioral results and computational modeling confirmed that learning was best explained as a mixture of two mechanisms: a fast, capacity-limited, and delay-sensitive WM process together with slower RL. Model-based analysis of fMRI data showed that striatum and lateral prefrontal cortex were sensitive to RPE, as shown previously, but, critically, these signals were reduced when the learning problem was within capacity of WM. The degree of this neural interaction related to individual differences in the use of WM to guide behavioral learning. These results indicate that the two systems do not process information independently, but rather interact during learning. SIGNIFICANCE STATEMENT Reinforcement learning (RL) theory has been remarkably productive at improving our understanding of instrumental learning as well as dopaminergic and striatal network function across many mammalian species. However, this neural network is only one contributor to human learning and other mechanisms such as prefrontal cortex working memory also play a key role. Our results also show that these other players interact with the dopaminergic RL system, interfering with its key computation of reward prediction errors. Copyright © 2017 the authors 0270-6474/17/374332-11$15.00/0.

  1. rsfMRI effects of KB220Z™ on Neural Pathways in Reward Circuitry of Abstinent Genotyped Heroin Addicts

    Science.gov (United States)

    Blum, Kenneth; Liu, Yijun; Wang, Wei; Wang, Yarong; Zhang, Yi; Oscar-Berman, Marlene; Smolen, Andrew; Febo, Marcelo; Han, David; Simpatico, Thomas; Cronjé, Frans J; Demetrovics, Zsolt; Gold, Mark S.

    2016-01-01

    Recently Willuhn et al. reported that cocaine use and even non-substance related addictive behavior, increases, as dopaminergic function is reduced. Chronic cocaine exposure has been associated with decreases in D2/D3 receptors, also associated with lower activation to cues in occipital cortex and cerebellum in a recent PET study from Volkow’s group. Therefore, treatment strategies, like dopamine agonist therapy, that might conserve dopamine function may be an interesting approach to relapse prevention in psychoactive drug and behavioral addictions. To this aim, we evaluated the effect of KB220Z™ on reward circuitry of ten heroin addicts undergoing protracted abstinence, an average 16.9 months. In a randomized placebo-controlled crossover study of KB220Z™ five subjects completed a triple blinded–experiment in which the subject, the person administering the treatment and the person evaluating the response to treatment were blinded as to which treatment any particular subject was receiving. In addition, nine subjects total were genotyped utilizing the GARSRX™ test. We preliminarily report that KB220Z ™ induced an increase in BOLD activation in caudate-accumbens-dopaminergic pathways compared to placebo following one-hour acute administration. Furthermore, KB220Z™ also reduced resting state activity in the putamen of abstinent heroin addicts. In the second phase of this pilot study of all ten abstinent heroin-dependent subjects, three brain regions of interest (ROIs) we observed to be significantly activated from resting state by KB220Z compared to placebo (P addiction by direct or indirect dopaminergic interaction. Due to small sample size, we caution definitive interpretation of these preliminary results and confirmation with additional research and ongoing rodent and human studies of KB220Z, is required. PMID:25526228

  2. The role of reward and reward uncertainty in episodic memory

    OpenAIRE

    Mason, Alice; Farrell, Simon; Howard-Jones, Paul; Ludwig, Casimir

    2017-01-01

    Declarative memory has been found to be sensitive to reward-related changes in the environment. The reward signal can be broken down into information regarding the expected value of the reward, reward uncertainty and the prediction error. Research has established that high as opposed to low reward values enhance declarative memory. Research in neuroscience suggests that high uncertainty activates the reward system, which could lead to enhanced learning and memory. Here we present the results ...

  3. Reward Systems in the Brain and Nutrition.

    Science.gov (United States)

    Rolls, Edmund T

    2016-07-17

    The taste cortex in the anterior insula provides separate and combined representations of the taste, temperature, and texture of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex, these sensory inputs are combined by associative learning with olfactory and visual inputs for some neurons, and these neurons encode food reward value in that they respond to food only when hunger is present and in that activations correlate linearly with subjective pleasantness. Cognitive factors, including word-level descriptions and selective attention to affective value, modulate the representation of the reward value of taste, olfactory, and flavor stimuli in the orbitofrontal cortex and a region to which it projects, the anterior cingulate cortex. These food reward representations are important in the control of appetite and food intake. Individual differences in reward representations may contribute to obesity, and there are age-related differences in these reward representations. Implications of how reward systems in the brain operate for understanding, preventing, and treating obesity are described.

  4. Reward Merit with Praise.

    Science.gov (United States)

    Andrews, Hans A.

    1987-01-01

    Describes the efforts of two educational institutions to reward teaching excellence using positive feedback rather than merit pay incentives. An Arizona district, drawing on Herzberg's motivation theories, offers highly individualized rewards ranging from computers to conference money, while an Illinois community college bestows engraved plaques…

  5. Dopamine reward prediction error coding.

    Science.gov (United States)

    Schultz, Wolfram

    2016-03-01

    Reward prediction errors consist of the differences between received and predicted rewards. They are crucial for basic forms of learning about rewards and make us strive for more rewards-an evolutionary beneficial trait. Most dopamine neurons in the midbrain of humans, monkeys, and rodents signal a reward prediction error; they are activated by more reward than predicted (positive prediction error), remain at baseline activity for fully predicted rewards, and show depressed activity with less reward than predicted (negative prediction error). The dopamine signal increases nonlinearly with reward value and codes formal economic utility. Drugs of addiction generate, hijack, and amplify the dopamine reward signal and induce exaggerated, uncontrolled dopamine effects on neuronal plasticity. The striatum, amygdala, and frontal cortex also show reward prediction error coding, but only in subpopulations of neurons. Thus, the important concept of reward prediction errors is implemented in neuronal hardware.

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

    Science.gov (United States)

    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.

  7. Mesocortical dopaminergic function and human cognition

    International Nuclear Information System (INIS)

    Weinberger, D.R.; Berman, K.F.; Chase, T.N.

    1988-01-01

    In summary, we have reviewed rCBF data in humans that suggest that mesoprefrontal dopaminergic activity is involved in human cognition. In patients with Parkinson's disease and possibly in patients with schizophrenia, prefrontal physiological activation during a cognitive task that appears to depend on prefrontal neural systems correlates positively with cognitive performance on the task and with clinical signs of dopaminergic function. It may be possible in the future to examine prefrontal dopamine metabolism directly during prefrontal cognition using positron emission tomography and tracers such as F-18 DOPA. 21 references

  8. Evidence of dopaminergic processing of executive inhibition.

    Directory of Open Access Journals (Sweden)

    Rajendra D Badgaiyan

    Full Text Available Inhibition of unwanted response is an important function of the executive system. Since the inhibitory system is impaired in patients with dysregulated dopamine system, we examined dopamine neurotransmission in the human brain during processing of a task of executive inhibition. The experiment used a recently developed dynamic molecular imaging technique to detect and map dopamine released during performance of a modified Eriksen's flanker task. In this study, young healthy volunteers received an intravenous injection of a dopamine receptor ligand ((11C-raclopride after they were positioned in the PET camera. After the injection, volunteers performed the flanker task under Congruent and Incongruent conditions in a single scan session. They were required to inhibit competing options to select an appropriate response in the Incongruent but not in the Congruent condition. The PET data were dynamically acquired during the experiment and analyzed using two variants of the simplified reference region model. The analysis included estimation of a number of receptor kinetic parameters before and after initiation of the Incongruent condition. We found increase in the rate of ligand displacement (from receptor sites and decrease in the ligand binding potential in the Incongruent condition, suggesting dopamine release during task performance. These changes were observed in small areas of the putamen and caudate bilaterally but were most significant on the dorsal aspect of the body of left caudate. The results provide evidence of dopaminergic processing of executive inhibition and demonstrate that neurochemical changes associated with cognitive processing can be detected and mapped in a single scan session using dynamic molecular imaging.

  9. Enriched encoding: reward motivation organizes cortical networks for hippocampal detection of unexpected events.

    Science.gov (United States)

    Murty, Vishnu P; Adcock, R Alison

    2014-08-01

    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. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Lighting up the brain's reward circuitry.

    Science.gov (United States)

    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.

  11. Neural Correlates of Impaired Reward-Effort Integration in Remitted Bulimia Nervosa.

    Science.gov (United States)

    Mueller, Stefanie Verena; Morishima, Yosuke; Schwab, Simon; Wiest, Roland; Federspiel, Andrea; Hasler, Gregor

    2018-03-01

    The integration of reward magnitudes and effort costs is required for an effective behavioral guidance. This reward-effort integration was reported to be dependent on dopaminergic neurotransmission. As bulimia nervosa has been associated with a dysregulated dopamine system and catecholamine depletion led to reward-processing deficits in remitted bulimia nervosa, the purpose of this study was to identify the role of catecholamine dysfunction and its relation to behavioral and neural reward-effort integration in bulimia nervosa. To investigate the interaction between catecholamine functioning and behavioral, and neural responses directly, 17 remitted bulimic (rBN) and 21 healthy individuals (HC) received alpha-methyl-paratyrosine (AMPT) over 24 h to achieve catecholamine depletion in a randomized, crossover study design. We used functional magnetic resonance imaging (fMRI) and the monetary incentive delay (MID) task to assess reward-effort integration in relation to catecholaminergic neurotransmission at the behavioral and neural level. AMPT reduced the ability to integrate rewards and efforts effectively in HC participants. In contrast, in rBN participants, the reduced reward-effort integration was associated with illness duration in the sham condition and unrelated to catecholamine depletion. Regarding neural activation, AMPT decreased the reward anticipation-related neural activation in the anteroventral striatum. This decrease was associated with the AMPT-induced reduction of monetary earning in HC in contrast to rBN participants. Our findings contributed to the theory of a desensitized dopaminergic system in bulimia nervosa. A disrupted processing of reward magnitudes and effort costs might increase the probability of maintenance of bulimic symptoms.

  12. Model Checking Markov Reward Models with Impulse Rewards

    NARCIS (Netherlands)

    Cloth, Lucia; Katoen, Joost-Pieter; Khattri, Maneesh; Pulungan, Reza; Bondavalli, Andrea; Haverkort, Boudewijn; Tang, Dong

    This paper considers model checking of Markov reward models (MRMs), continuous-time Markov chains with state rewards as well as impulse rewards. The reward extension of the logic CSL (Continuous Stochastic Logic) is interpreted over such MRMs, and two numerical algorithms are provided to check the

  13. Dopaminergic Polymorphisms, Academic Achievement, and Violent Delinquency.

    Science.gov (United States)

    Yun, Ilhong; Lee, Julak; Kim, Seung-Gon

    2015-12-01

    Recent research in the field of educational psychology points to the salience of self-control in accounting for the variance in students' report card grades. At the same time, a novel empirical study from molecular genetics drawing on the National Longitudinal Study of Adolescent Health (Add Health) data has revealed that polymorphisms in three dopaminergic genes (dopamine transporter [DAT1], dopamine D2 receptor [DRD2], and dopamine D4 receptor [DRD4]) are also linked to adolescents' grade point averages (GPAs). Juxtaposing these two lines of research, the current study reanalyzed the Add Health genetic subsample to assess the relative effects of these dopaminergic genes and self-control on GPAs. The results showed that the effects of the latter were far stronger than those of the former. The interaction effects between the dopaminergic genes and a set of environmental factors on academic performance were also examined, producing findings that are aligned with the "social push hypothesis" in behavioral genetics. Finally, based on the criminological literature on the link between academic performance and delinquency, we tested whether dopaminergic effects on violent delinquency were mediated by GPAs. The results demonstrated that academic performance fully mediated the linkage between these genes and violent delinquency. © The Author(s) 2014.

  14. Ketogenic diet alters dopaminergic activity in the mouse cortex.

    Science.gov (United States)

    Church, William H; Adams, Ryan E; Wyss, Livia S

    2014-06-13

    The present study was conducted to determine if the ketogenic diet altered basal levels of monoamine neurotransmitters in mice. The catecholamines dopamine (DA) and norephinephrine (NE) and the indolamine serotonin (5HT) were quantified postmortem in six different brain regions of adult mice fed a ketogenic diet for 3 weeks. The dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the serotonin metabolite 5-hydroxyindole acetic acid (5HIAA) were also measured. Tissue punches were collected bilaterally from the motor cortex, somatosensory cortex, nucleus accumbens, anterior caudate-putamen, posterior caudate-putamen and the midbrain. Dopaminergic activity, as measured by the dopamine metabolites to dopamine content ratio - ([DOPAC]+[HVA])/[DA] - was significantly increased in the motor and somatosensory cortex regions of mice fed the ketogenic diet when compared to those same areas in brains of mice fed a normal diet. These results indicate that the ketogenic diet alters the activity of the meso-cortical dopaminergic system, which may contribute to the diet's therapeutic effect in reducing epileptic seizure activity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Reward-modulated motor information in identified striatum neurons.

    Science.gov (United States)

    Isomura, Yoshikazu; Takekawa, Takashi; Harukuni, Rie; Handa, Takashi; Aizawa, Hidenori; Takada, Masahiko; Fukai, Tomoki

    2013-06-19

    It is widely accepted that dorsal striatum neurons participate in either the direct pathway (expressing dopamine D1 receptors) or the indirect pathway (expressing D2 receptors), controlling voluntary movements in an antagonistically balancing manner. The D1- and D2-expressing neurons are activated and inactivated, respectively, by dopamine released from substantia nigra neurons encoding reward expectation. However, little is known about the functional representation of motor information and its reward modulation in individual striatal neurons constituting the two pathways. In this study, we juxtacellularly recorded the spike activity of single neurons in the dorsolateral striatum of rats performing voluntary forelimb movement in a reward-predictable condition. Some of these neurons were identified morphologically by a combination of juxtacellular visualization and in situ hybridization for D1 mRNA. We found that the striatal neurons exhibited distinct functional activations before and during the forelimb movement, regardless of the expression of D1 mRNA. They were often positively, but rarely negatively, modulated by expecting a reward for the correct motor response. The positive reward modulation was independent of behavioral differences in motor performance. In contrast, regular-spiking and fast-spiking neurons in any layers of the motor cortex displayed only minor and unbiased reward modulation of their functional activation in relation to the execution of forelimb movement. Our results suggest that the direct and indirect pathway neurons cooperatively rather than antagonistically contribute to spatiotemporal control of voluntary movements, and that motor information is subcortically integrated with reward information through dopaminergic and other signals in the skeletomotor loop of the basal ganglia.

  16. Reward and punishment.

    Science.gov (United States)

    Sigmund, K; Hauert, C; Nowak, M A

    2001-09-11

    Minigames capturing the essence of Public Goods experiments show that even in the absence of rationality assumptions, both punishment and reward will fail to bring about prosocial behavior. This result holds in particular for the well-known Ultimatum Game, which emerges as a special case. But reputation can induce fairness and cooperation in populations adapting through learning or imitation. Indeed, the inclusion of reputation effects in the corresponding dynamical models leads to the evolution of economically productive behavior, with agents contributing to the public good and either punishing those who do not or rewarding those who do. Reward and punishment correspond to two types of bifurcation with intriguing complementarity. The analysis suggests that reputation is essential for fostering social behavior among selfish agents, and that it is considerably more effective with punishment than with reward.

  17. A Markov reward model checker

    NARCIS (Netherlands)

    Katoen, Joost P.; Maneesh Khattri, M.; Zapreev, I.S.; Zapreev, I.S.

    2005-01-01

    This short tool paper introduces MRMC, a model checker for discrete-time and continuous-time Markov reward models. It supports reward extensions of PCTL and CSL, and allows for the automated verification of properties concerning long-run and instantaneous rewards as well as cumulative rewards. In

  18. Reward, Context, and Human Behaviour

    Directory of Open Access Journals (Sweden)

    Clare L. Blaukopf

    2007-01-01

    Full Text Available Animal models of reward processing have revealed an extensive network of brain areas that process different aspects of reward, from expectation and prediction to calculation of relative value. These results have been confirmed and extended in human neuroimaging to encompass secondary rewards more unique to humans, such as money. The majority of the extant literature covers the brain areas associated with rewards whilst neglecting analysis of the actual behaviours that these rewards generate. This review strives to redress this imbalance by illustrating the importance of looking at the behavioural outcome of rewards and the context in which they are produced. Following a brief review of the literature of reward-related activity in the brain, we examine the effect of reward context on actions. These studies reveal how the presence of reward vs. reward and punishment, or being conscious vs. unconscious of reward-related actions, differentially influence behaviour. The latter finding is of particular importance given the extent to which animal models are used in understanding the reward systems of the human mind. It is clear that further studies are needed to learn about the human reaction to reward in its entirety, including any distinctions between conscious and unconscious behaviours. We propose that studies of reward entail a measure of the animal's (human or nonhuman knowledge of the reward and knowledge of its own behavioural outcome to achieve that reward.

  19. Functional Relevance of Different Basal Ganglia Pathways Investigated in a Spiking Model with Reward Dependent Plasticity

    Directory of Open Access Journals (Sweden)

    Pierre Berthet

    2016-07-01

    Full Text Available The brain enables animals to behaviourally adapt in order to survive in a complex and dynamic environment, but how reward-oriented behaviours are achieved and computed by its underlying neural circuitry is an open question. To address this concern, we have developed a spiking model of the basal ganglia (BG that learns to dis-inhibit the action leading to a reward despite ongoing changes in the reward schedule. The architecture of the network features the two pathways commonly described in BG, the direct (denoted D1 and the indirect (denoted D2 pathway, as well as a loop involving striatum and the dopaminergic system. The activity of these dopaminergic neurons conveys the reward prediction error (RPE, which determines the magnitude of synaptic plasticity within the different pathways. All plastic connections implement a versatile four-factor learning rule derived from Bayesian inference that depends upon pre- and postsynaptic activity, receptor type and dopamine level. Synaptic weight updates occur in the D1 or D2 pathways depending on the sign of the RPE, and an efference copy informs upstream nuclei about the action selected. We demonstrate successful performance of the system in a multiple-choice learning task with a transiently changing reward schedule. We simulate lesioning of the various pathways and show that a condition without the D2 pathway fares worse than one without D1. Additionally, we simulate the degeneration observed in Parkinson’s disease (PD by decreasing the number of dopaminergic neurons during learning. The results suggest that the D1 pathway impairment in PD might have been overlooked. Furthermore, an analysis of the alterations in the synaptic weights shows that using the absolute reward value instead of the RPE leads to a larger change in D1.

  20. The endocannabinoid system and nondrug rewarding behaviours.

    Science.gov (United States)

    Fattore, Liana; Melis, Miriam; Fadda, Paola; Pistis, Marco; Fratta, Walter

    2010-07-01

    Rewarding behaviours such as sexual activity, eating, nursing, parenting, social interactions, and play activity are conserved strongly in evolution, and they are essential for development and survival. All of these behaviours are enjoyable and represent pleasant experiences with a high reward value. Remarkably, rewarding behaviours activate the same brain circuits that mediate the positive reinforcing effects of drugs of abuse and of other forms of addiction, such as gambling and food addiction. Given the involvement of the endocannabinoid system in a variety of physiological functions of the nervous system, it is not surprising that it takes part in the complex machinery that regulates gratification and perception of pleasure. In this review, we focus first on the role of the endocannabinoid system in the modulation of neural activity and synaptic functions in brain regions that are involved in natural and nonnatural rewards (namely, the ventral tegmental area, striatum, amygdala, and prefrontal cortex). Then, we examine the role of the endocannabinoid system in modulating behaviours that directly or indirectly activate these brain reward pathways. More specifically, current knowledge of the effects of the pharmacological manipulation of the endocannabinoid system on natural (eating, sexual behaviour, parenting, and social play) and pathological (gambling) rewarding behaviours is summarised and discussed. Copyright 2010 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  2. Effects of exogenous testosterone on the ventral striatal BOLD response during reward anticipation in healthy women.

    Science.gov (United States)

    Hermans, Erno J; Bos, Peter A; Ossewaarde, Lindsey; Ramsey, Nick F; Fernández, Guillén; van Honk, Jack

    2010-08-01

    Correlational evidence in humans shows that levels of the androgen hormone testosterone are positively related to reinforcement sensitivity and competitive drive. Structurally similar anabolic-androgenic steroids (AAS) are moreover widely abused, and animal studies show that rodents self-administer testosterone. These observations suggest that testosterone exerts activational effects on mesolimbic dopaminergic pathways involved in incentive processing and reinforcement regulation. However, there are no data on humans supporting this hypothesis. We used functional magnetic resonance imaging (fMRI) to investigate the effects of testosterone administration on neural activity in terminal regions of the mesolimbic pathway. In a placebo-controlled double-blind crossover design, 12 healthy women received a single sublingual administration of .5 mg of testosterone. During MRI scanning, participants performed a monetary incentive delay task, which is known to elicit robust activation of the ventral striatum during reward anticipation. Results show a positive main effect of testosterone on the differential response in the ventral striatum to cues signaling potential reward versus nonreward. Notably, this effect interacted with levels self-reported intrinsic appetitive motivation: individuals with low intrinsic appetitive motivation exhibited larger testosterone-induced increases but had smaller differential responses after placebo. Thus, the present study lends support to the hypothesis that testosterone affects activity in terminal regions of the mesolimbic dopamine system but suggests that such effects may be specific to individuals with low intrinsic appetitive motivation. By showing a potential mechanism underlying central reinforcement of androgen use, the present findings may moreover have implications for our understanding of the pathophysiology of AAS dependency. Copyright 2010 Elsevier Inc. All rights reserved.

  3. Dopamine agonist increases risk taking but blunts reward-related brain activity.

    Directory of Open Access Journals (Sweden)

    Jordi Riba

    Full Text Available The use of D2/D3 dopaminergic agonists in Parkinson's disease (PD may lead to pathological gambling. In a placebo-controlled double-blind study in healthy volunteers, we observed riskier choices in a lottery task after administration of the D3 receptor-preferring agonist pramipexole thus mimicking risk-taking behavior in PD. Moreover, we demonstrate decreased activation in the rostral basal ganglia and midbrain, key structures of the reward system, following unexpected high gains and therefore propose that pathological gambling in PD results from the need to seek higher rewards to overcome the blunted response in this system.

  4. Rewarding and aversive effects of nicotine are segregated within the nucleus accumbens.

    Science.gov (United States)

    Sellings, Laurie H L; Baharnouri, Golriz; McQuade, Lindsey E; Clarke, Paul B S

    2008-07-01

    Forebrain dopamine plays a critical role in motivated behavior. According to the classic view, mesolimbic dopamine selectively guides behavior motivated by positive reinforcers. However, this has been challenged in favor of a wider role encompassing aversively motivated behavior. This controversy is particularly striking in the case of nicotine, with opposing claims that either the rewarding or the aversive effect of nicotine is critically dependent on mesolimbic dopamine transmission. In the present study, the effects of 6-hydroxydopamine lesions of nucleus accumbens core vs. medial shell on intravenous nicotine conditioned place preference and conditioned taste aversion were examined in male adult rats. Dopaminergic denervation in accumbens medial shell was associated with decreased nicotine conditioned place preference. Conversely, denervation in accumbens core was associated with an increase in conditioned place preference. In addition, dopaminergic denervation of accumbens core but not medial shell abolished conditioned taste aversion for nicotine. We conclude that nucleus accumbens core and medial shell dopaminergic innervation exert segregated effects on rewarding and aversive effects of nicotine. More generally, our findings indicate that dopaminergic transmission may mediate or enable opposing motivational processes within functionally distinct domains of the accumbens.

  5. Advances in non-dopaminergic pharmacological treatments of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Sandy eStayte

    2014-05-01

    Full Text Available Since the 1960’s treatments for Parkinson's disease (PD have traditionally been directed to effectively restore or replace dopamine, with L-Dopa the gold standard. However, chronic L-Dopa use is associated with debilitating dyskinesias, limiting its effectiveness. This has created a need to develop new therapies that work in ways other than restoring or replacing dopamine. We provide a comprehensive overview of the emerging non-dopaminergic pharmacological treatments including drugs targeting adenosine, glutamate, adrenergic, and serotonin receptors, as well as GLP-1 agonists, calcium channel blockers, iron chelators, anti-inflammatories, neurotrophic factors and gene therapy, with a detailed overview of their success in animal models and their translation to human clinical trials. We suggest that further developments in the identification of novel therapeutics, particularly those offering disease-modifying effects, will consistently be met with challenges until improvements in clinical trial design and advances in understanding the basic science of PD are made. We consider how developments in genetics, the possibility that PD may consist of multiple disease states, and potential etiology in non-dopaminergic regions will influence drug development. We conclude that despite the challenges ahead patients have much cause for optimism that novel therapeutics that offer better disease management and/or which slow disease progression are inevitable.

  6. Rasgrf2 controls dopaminergic adaptations to alcohol in mice.

    Science.gov (United States)

    Easton, Alanna C; Rotter, Andrea; Lourdusamy, Anbarasu; Desrivières, Sylvane; Fernández-Medarde, Alberto; Biermann, Teresa; Fernandes, Cathy; Santos, Eugenio; Kornhuber, Johannes; Schumann, Gunter; Müller, Christian P

    2014-10-01

    Alcohol abuse leads to serious health problems with no effective treatment available. Recent evidence suggests a role for ras-specific guanine-nucleotide releasing factor 2 (RASGRF2) in alcoholism. Rasgrf2 is a calcium sensor and MAPK/ERK activating protein, which has been linked to neurotransmitter release and monoaminergic receptor adaptations. Rasgrf2 knock out (KO) mice do not develop a dopamine response in the nucleus accumbens after an alcohol challenge and show a reduced consumption of alcohol. The present study aims to further characterise the role of Rasgrf2 in dopaminergic activation beyond the nucleus accumbens following alcohol treatment. Using in vivo microdialysis we found that alcohol induces alterations in dopamine levels in the dorsal striatum between wildtype (WT) and Rasgrf2 KO mice. There was no difference in the expression of dopamine transporter (DAT), dopamine receptor regulating factor (DRRF), or dopamine D2 receptor (DRD2) mRNA in the brain between Rasgrf2 KO and WT mice. After sub-chronic alcohol treatment, DAT and DRRF, but not DRD2 mRNA expression differed between WT and Rasgrf2 KO mice. Brain adaptations were positively correlated with splenic expression levels. These data suggest that Rasgrf2 controls dopaminergic signalling and adaptations to alcohol also in other brain regions, beyond the nucleus accumbens. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Natural Rewards, Neuroplasticity, and Non-Drug Addictions

    Science.gov (United States)

    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

  8. Serotonergic neurons signal reward and punishment on multiple timescales

    Science.gov (United States)

    Cohen, Jeremiah Y; Amoroso, Mackenzie W; Uchida, Naoshige

    2015-01-01

    Serotonin's function in the brain is unclear. One challenge in testing the numerous hypotheses about serotonin's function has been observing the activity of identified serotonergic neurons in animals engaged in behavioral tasks. We recorded the activity of dorsal raphe neurons while mice experienced a task in which rewards and punishments varied across blocks of trials. We ‘tagged’ serotonergic neurons with the light-sensitive protein channelrhodopsin-2 and identified them based on their responses to light. We found three main features of serotonergic neuron activity: (1) a large fraction of serotonergic neurons modulated their tonic firing rates over the course of minutes during reward vs punishment blocks; (2) most were phasically excited by punishments; and (3) a subset was phasically excited by reward-predicting cues. By contrast, dopaminergic neurons did not show firing rate changes across blocks of trials. These results suggest that serotonergic neurons signal information about reward and punishment on multiple timescales. DOI: http://dx.doi.org/10.7554/eLife.06346.001 PMID:25714923

  9. Competitive Pressure on China : Factor Rewards Migration

    NARCIS (Netherlands)

    Ten Raa, T.; Pan, H.

    2001-01-01

    Our objective is to assess personal income under perfect competition, when factors are rewarded according to their productivities, and to contrast the ensuing distribution with the status quo.Competition will yield winners and losers, both in terms of factor claims and in terms of regions or

  10. Reward deficiency and anti-reward in pain chronification

    OpenAIRE

    Borsook, D.; Linnman, C.; Faria, Vanda; Strassman, A. M.; Becerra, L.; Elman, I.

    2016-01-01

    Converging lines of evidence suggest that the pathophysiology of pain is mediated to a substantial degree via allostatic neuroadaptations in reward- and stress-related brain circuits. Thus, reward deficiency (RD) represents a within-system neuroadaptation to pain-induced protracted activation of the reward circuits that leads to depletion-like hypodopaminergia, clinically manifested anhedonia, and diminished motivation for natural reinforcers. Anti-reward (AR) conversely pertains to a between...

  11. Differential encoding of factors influencing predicted reward value in monkey rostral anterior cingulate cortex.

    Science.gov (United States)

    Toda, Koji; Sugase-Miyamoto, Yasuko; Mizuhiki, Takashi; Inaba, Kiyonori; Richmond, Barry J; Shidara, Munetaka

    2012-01-01

    The value of a predicted reward can be estimated based on the conjunction of both the intrinsic reward value and the length of time to obtain it. The question we addressed is how the two aspects, reward size and proximity to reward, influence the responses of neurons in rostral anterior cingulate cortex (rACC), a brain region thought to play an important role in reward processing. We recorded from single neurons while two monkeys performed a multi-trial reward schedule task. The monkeys performed 1-4 sequential color discrimination trials to obtain a reward of 1-3 liquid drops. There were two task conditions, a valid cue condition, where the number of trials and reward amount were associated with visual cues, and a random cue condition, where the cue was picked from the cue set at random. In the valid cue condition, the neuronal firing is strongly modulated by the predicted reward proximity during the trials. Information about the predicted reward amount is almost absent at those times. In substantial subpopulations, the neuronal responses decreased or increased gradually through schedule progress to the predicted outcome. These two gradually modulating signals could be used to calculate the effect of time on the perception of reward value. In the random cue condition, little information about the reward proximity or reward amount is encoded during the course of the trial before reward delivery, but when the reward is actually delivered the responses reflect both the reward proximity and reward amount. Our results suggest that the rACC neurons encode information about reward proximity and amount in a manner that is dependent on utility of reward information. The manner in which the information is represented could be used in the moment-to-moment calculation of the effect of time and amount on predicted outcome value.

  12. Adaptive increase in D3 dopamine receptors in the brain reward circuits of human cocaine fatalities.

    Science.gov (United States)

    Staley, J K; Mash, D C

    1996-10-01

    The mesolimbic dopaminergic system plays a primary role in mediating the euphoric and rewarding effects of most abused drugs. Chronic cocaine use is associated with an increase in dopamine neurotransmission resulting from the blockade of dopamine uptake and is mediated by the activation of dopamine receptors. Recent studies have suggested that the D3 receptor subtype plays a pivotal role in the reinforcing effects of cocaine. The D3 receptor-preferring agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) is a reinforcer in rhesus monkeys trained to self-administer cocaine, but not in cocainenaive monkeys. In vitro autoradiographic localization of [3H]-(+)-7-OH-DPAT binding in the human brain demonstrated that D3 receptors were prevalent and highly localized over the ventromedial sectors of the striatum. Pharmacological characterization of [3H]-(+)-7-OH-DPAT binding to the human nucleus accumbens demonstrated a rank order of potency similar to that observed for binding to the cloned D3 receptor expressed in transfected cell lines. Region-of-interest analysis of [3H]-(+)-7-OH-DPAT binding to the D3 receptor demonstrated a one- to threefold elevation in the number of binding sites over particular sectors of the striatum and substantia nigra in cocaine overdose victims as compared with age-matched and drug-free control subjects. The elevated number of [3H]-(+)-7-OH-DPAT binding sites demonstrates that adaptive changes in the D3 receptor in the reward circuitry of the brain are associated with chronic cocaine abuse. These results suggest that the D3 receptor may be a useful target for drug development of anticocaine medications.

  13. Interaction of Synuclein and Inflammation in Dopaminergic Neurodegeneration

    Science.gov (United States)

    2014-06-01

    induces degeneration of dopaminergic neurons: implications for progression of Parkinson’s disease. Neurotox Res. 19: 63-72, (2011). Kalia, L. V., S...1998). Zhang J, Niu N, Wang M, McNutt MA, Zhang D, Zhang B, Lu S, Liu Y, Liu Z. Neuron-derived IgG protects dopaminergic neurons from insult by 6...AD_________________ Award Number: W81XWH-08-1-0465 TITLE: Interaction of Synuclein and Inflammation in Dopaminergic

  14. Role of Inflammation in MPTP-Induced Dopaminergic Neuronal Death

    Science.gov (United States)

    2008-12-01

    of MPTP to MPP+ and MPP+ entry into dopaminergic neurons are key to the neurotoxic effects of MPTP and interference in any of these processes...presented at the Society for Neuroscience Meetings in 2006 Figure 1. Tempol Structure 29 Figure 2. Tempol protects dopaminergic neurons...in PD. Dopaminergic neurons in the SNpc were protected to a significant degree against the damaging effects of MPTP by M40401 whereas its isoforms

  15. Human neuromelanin: an endogenous microglial activator for dopaminergic neuron death

    OpenAIRE

    Zhang, Wei; Zecca, Luigi; Wilson, Belinda; Ren, RW; Wang, Yong-jun; Wang, Xiao-min; Hong, Jau-Shyong

    2013-01-01

    Substantial evidence indicates that neuroinflammation caused by over-activation of microglial in the substantia nigra is critical in the pathogenesis of dopaminergic neurodegeneration in Parkinson’s disease (PD). Increasing data demonstrates that environmental factors such as rotenone, paraquat play pivotal roles in the death of dopaminergic neurons. Here, potential role and mechanism of neuromelanin (NM), a major endogenous component in dopaminergic neurons of the substantia nigra, on microg...

  16. Pervasive competition between threat and reward in the brain.

    Science.gov (United States)

    Choi, Jong Moon; Padmala, Srikanth; Spechler, Philip; Pessoa, Luiz

    2014-06-01

    In the current functional MRI study, we investigated interactions between reward and threat processing. Visual cues at the start of each trial informed participants about the chance of winning monetary reward and/or receiving a mild aversive shock. We tested two competing hypothesis: according to the 'salience hypothesis', in the condition involving both reward and threat, enhanced activation would be observed because of increased salience; according to the 'competition hypothesis', the processing of reward and threat would trade-off against each other, leading to reduced activation. Analysis of skin conductance data during a delay phase revealed an interaction between reward and threat processing, such that the effect of reward was reduced during threat and the effect of threat was reduced during reward. Analysis of imaging data during the same task phase revealed interactions between reward and threat processing in several regions, including the midbrain/ventral tegmental area, caudate, putamen, bed nucleus of the stria terminalis, anterior insula, middle frontal gyrus and dorsal anterior cingulate cortex. Taken together, our findings reveal conditions during which reward and threat trade-off against each other across multiple sites. Such interactions are suggestive of competitive processes and may reflect the organization of opponent systems in the brain. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

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

    Science.gov (United States)

    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

  18. Neuropharmacological mechanisms of drug reward: beyond dopamine in the nucleus accumbens.

    Science.gov (United States)

    Bardo, M T

    1998-01-01

    Multiple lines of research have implicated the mesolimbic dopamine system in drug reward measured by either the drug self-administration or conditioned place preference paradigm. The present review summarizes recent work that examines the neuropharmacological mechanisms by which drugs impinge on this dopaminergic neural circuitry, as well as other systems that provide input and output circuits to the mesolimbic dopamine system. Studies examining the effect of selective agonist and antagonist drugs administered systemically have indicated that multiple neurotransmitters are involved, including dopamine, serotonin, acetylcholine, glutamate, GABA, and various peptides. Direct microinjection studies have also provided crucial evidence indicating that, in addition to the mesolimbic dopamine system, other structures play a role in drug reward, including the ventral pallidum, amygdala, hippocampus, hypothalamus, and pedunculopontine tegmental nucleus. GABAergic circuitry descending from the nucleus accumbens to the pedunculopontine tegmental nucleus via the ventral pallidum appears to be especially important in directing the behavioral sequelae associated with reward produced by various drugs of abuse. However, activation of the reward circuitry is achieved differently for various drugs of abuse. With amphetamine and cocaine, initiation of reward is controlled within the nucleus accumbens and prefrontal cortex, respectively. With opiates, initiation of reward involves the ventral tegmental area, nucleus accumbens, hippocampus, and hypothalamus. It is not clear presently if these multiple anatomical structures mediate opiate reward by converging on a single output system or multiple output systems.

  19. Episodic Memory Encoding Interferes with Reward Learning and Decreases Striatal Prediction Errors

    Science.gov (United States)

    Braun, Erin Kendall; Daw, Nathaniel D.

    2014-01-01

    Learning is essential for adaptive decision making. The striatum and its dopaminergic inputs are known to support incremental reward-based learning, while the hippocampus is known to support encoding of single events (episodic memory). Although traditionally studied separately, in even simple experiences, these two types of learning are likely to co-occur and may interact. Here we sought to understand the nature of this interaction by examining how incremental reward learning is related to concurrent episodic memory encoding. During the experiment, human participants made choices between two options (colored squares), each associated with a drifting probability of reward, with the goal of earning as much money as possible. Incidental, trial-unique object pictures, unrelated to the choice, were overlaid on each option. The next day, participants were given a surprise memory test for these pictures. We found that better episodic memory was related to a decreased influence of recent reward experience on choice, both within and across participants. fMRI analyses further revealed that during learning the canonical striatal reward prediction error signal was significantly weaker when episodic memory was stronger. This decrease in reward prediction error signals in the striatum was associated with enhanced functional connectivity between the hippocampus and striatum at the time of choice. Our results suggest a mechanism by which memory encoding may compete for striatal processing and provide insight into how interactions between different forms of learning guide reward-based decision making. PMID:25378157

  20. Episodic memory encoding interferes with reward learning and decreases striatal prediction errors.

    Science.gov (United States)

    Wimmer, G Elliott; Braun, Erin Kendall; Daw, Nathaniel D; Shohamy, Daphna

    2014-11-05

    Learning is essential for adaptive decision making. The striatum and its dopaminergic inputs are known to support incremental reward-based learning, while the hippocampus is known to support encoding of single events (episodic memory). Although traditionally studied separately, in even simple experiences, these two types of learning are likely to co-occur and may interact. Here we sought to understand the nature of this interaction by examining how incremental reward learning is related to concurrent episodic memory encoding. During the experiment, human participants made choices between two options (colored squares), each associated with a drifting probability of reward, with the goal of earning as much money as possible. Incidental, trial-unique object pictures, unrelated to the choice, were overlaid on each option. The next day, participants were given a surprise memory test for these pictures. We found that better episodic memory was related to a decreased influence of recent reward experience on choice, both within and across participants. fMRI analyses further revealed that during learning the canonical striatal reward prediction error signal was significantly weaker when episodic memory was stronger. This decrease in reward prediction error signals in the striatum was associated with enhanced functional connectivity between the hippocampus and striatum at the time of choice. Our results suggest a mechanism by which memory encoding may compete for striatal processing and provide insight into how interactions between different forms of learning guide reward-based decision making. Copyright © 2014 the authors 0270-6474/14/3414901-12$15.00/0.

  1. Anticipatory and foraging behaviors in response to palatable food reward in chickens: Effects of dopamine D2 receptor blockade and domestication

    NARCIS (Netherlands)

    Moe, R.O.; Nordgreen, J.; Janczak, A.M.; Bakken, M.; Spruijt, Berry; Jensen, P.

    2014-01-01

    Behaviors associated with anticipation and search for palatable food may provide information about dopaminergic reward processes and positive motivational affect in animals. The overall aim was to investigate the involvement of dopamine signaling in the regulation of cue-induced anticipation and

  2. Stress and reward

    DEFF Research Database (Denmark)

    Chumbley, J R; Hulme, O; Köchli, H

    2014-01-01

    Healthy individuals tend to consume available rewards like food and sex. This tendency is attenuated or amplified in most stress-related psychiatric conditions, so we asked if it depends on endogenous levels of the 'canonical stress hormone' cortisol. We unobtrusively quantified how hard healthy...

  3. Bribes or Rewards.

    Science.gov (United States)

    Megyeri, Kathy A.

    Small tangible rewards for student progress, such as candy bars, pens, or ribbons, add potency to the verbal and written praise offered by the teacher, thus increasing student motivation. Giving students small prizes enhances the cooperative atmosphere of learning, especially for those who do not normally do well. Research indicates that low…

  4. Midbrain dopamine neurons associated with reward processing innervate the neurogenic subventricular zone.

    Science.gov (United States)

    Lennington, Jessica B; Pope, Sara; Goodheart, Anna E; Drozdowicz, Linda; Daniels, Stephen B; Salamone, John D; Conover, Joanne C

    2011-09-14

    Coordinated regulation of the adult neurogenic subventricular zone (SVZ) is accomplished by a myriad of intrinsic and extrinsic factors. The neurotransmitter dopamine is one regulatory molecule implicated in SVZ function. Nigrostriatal and ventral tegmental area (VTA) midbrain dopamine neurons innervate regions adjacent to the SVZ, and dopamine synapses are found on SVZ cells. Cell division within the SVZ is decreased in humans with Parkinson's disease and in animal models of Parkinson's disease following exposure to toxins that selectively remove nigrostriatal neurons, suggesting that dopamine is critical for SVZ function and nigrostriatal neurons are the main suppliers of SVZ dopamine. However, when we examined the aphakia mouse, which is deficient in nigrostriatal neurons, we found no detrimental effect to SVZ proliferation or organization. Instead, dopamine innervation of the SVZ tracked to neurons at the ventrolateral boundary of the VTA. This same dopaminergic neuron population also innervated the SVZ of control mice. Characterization of these neurons revealed expression of proteins indicative of VTA neurons. Furthermore, exposure to the neurotoxin MPTP depleted neurons in the ventrolateral VTA and resulted in decreased SVZ proliferation. Together, these results reveal that dopamine signaling in the SVZ originates from a population of midbrain neurons more typically associated with motivational and reward processing.

  5. A Tyrosine-Hydroxylase Characterization of Dopaminergic Neurons in the Honey Bee Brain

    Directory of Open Access Journals (Sweden)

    Stevanus R. Tedjakumala

    2017-07-01

    Full Text Available Dopamine (DA plays a fundamental role in insect behavior as it acts both as a general modulator of behavior and as a value system in associative learning where it mediates the reinforcing properties of unconditioned stimuli (US. Here we aimed at characterizing the dopaminergic neurons in the central nervous system of the honey bee, an insect that serves as an established model for the study of learning and memory. We used tyrosine hydroxylase (TH immunoreactivity (ir to ensure that the neurons detected synthesize DA endogenously. We found three main dopaminergic clusters, C1–C3, which had been previously described; the C1 cluster is located in a small region adjacent to the esophagus (ES and the antennal lobe (AL; the C2 cluster is situated above the C1 cluster, between the AL and the vertical lobe (VL of the mushroom body (MB; the C3 cluster is located below the calyces (CA of the MB. In addition, we found a novel dopaminergic cluster, C4, located above the dorsomedial border of the lobula, which innervates the visual neuropils of the bee brain. Additional smaller processes and clusters were found and are described. The profuse dopaminergic innervation of the entire bee brain and the specific connectivity of DA neurons, with visual, olfactory and gustatory circuits, provide a foundation for a deeper understanding of how these sensory modules are modulated by DA, and the DA-dependent value-based associations that occur during associative learning.

  6. Resting-State Brain and the FTO Obesity Risk Allele: Default Mode, Sensorimotor, and Salience Network Connectivity Underlying Different Somatosensory Integration and Reward Processing between Genotypes.

    Science.gov (United States)

    Olivo, Gaia; Wiemerslage, Lyle; Nilsson, Emil K; Solstrand Dahlberg, Linda; Larsen, Anna L; Olaya Búcaro, Marcela; Gustafsson, Veronica P; Titova, Olga E; Bandstein, Marcus; Larsson, Elna-Marie; Benedict, Christian; Brooks, Samantha J; Schiöth, Helgi B

    2016-01-01

    Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN), sensorimotor (SMN), and salience network (SN) in 30 male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS) and Behavioral Activation System (BAS) questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr) accounting for features of both scores. A prominence of BIS over BAS (higher BBr) resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention.

  7. Reward positivity: Reward prediction error or salience prediction error?

    Science.gov (United States)

    Heydari, Sepideh; Holroyd, Clay B

    2016-08-01

    The reward positivity is a component of the human ERP elicited by feedback stimuli in trial-and-error learning and guessing tasks. A prominent theory holds that the reward positivity reflects a reward prediction error signal that is sensitive to outcome valence, being larger for unexpected positive events relative to unexpected negative events (Holroyd & Coles, 2002). Although the theory has found substantial empirical support, most of these studies have utilized either monetary or performance feedback to test the hypothesis. However, in apparent contradiction to the theory, a recent study found that unexpected physical punishments also elicit the reward positivity (Talmi, Atkinson, & El-Deredy, 2013). The authors of this report argued that the reward positivity reflects a salience prediction error rather than a reward prediction error. To investigate this finding further, in the present study participants navigated a virtual T maze and received feedback on each trial under two conditions. In a reward condition, the feedback indicated that they would either receive a monetary reward or not and in a punishment condition the feedback indicated that they would receive a small shock or not. We found that the feedback stimuli elicited a typical reward positivity in the reward condition and an apparently delayed reward positivity in the punishment condition. Importantly, this signal was more positive to the stimuli that predicted the omission of a possible punishment relative to stimuli that predicted a forthcoming punishment, which is inconsistent with the salience hypothesis. © 2016 Society for Psychophysiological Research.

  8. An Update on the Role of Serotonin and its Interplay with Dopamine for Reward.

    Science.gov (United States)

    Fischer, Adrian G; Ullsperger, Markus

    2017-01-01

    The specific role of serotonin and its interplay with dopamine (DA) in adaptive, reward guided behavior as well as drug dependance, still remains elusive. Recently, novel methods allowed cell type specific anatomical, functional and interventional analyses of serotonergic and dopaminergic circuits, promising significant advancement in understanding their functional roles. Furthermore, it is increasingly recognized that co-release of neurotransmitters is functionally relevant, understanding of which is required in order to interpret results of pharmacological studies and their relationship to neural recordings. Here, we review recent animal studies employing such techniques with the aim to connect their results to effects observed in human pharmacological studies and subjective effects of drugs. It appears that the additive effect of serotonin and DA conveys significant reward related information and is subjectively highly euphorizing. Neither DA nor serotonin alone have such an effect. This coincides with optogenetically targeted recordings in mice, where the dopaminergic system codes reward prediction errors (PE), and the serotonergic system mainly unsigned PE. Overall, this pattern of results indicates that joint activity between both systems carries essential reward information and invites parallel investigation of both neurotransmitter systems.

  9. An Update on the Role of Serotonin and its Interplay with Dopamine for Reward

    Directory of Open Access Journals (Sweden)

    Adrian G. Fischer

    2017-10-01

    Full Text Available The specific role of serotonin and its interplay with dopamine (DA in adaptive, reward guided behavior as well as drug dependance, still remains elusive. Recently, novel methods allowed cell type specific anatomical, functional and interventional analyses of serotonergic and dopaminergic circuits, promising significant advancement in understanding their functional roles. Furthermore, it is increasingly recognized that co-release of neurotransmitters is functionally relevant, understanding of which is required in order to interpret results of pharmacological studies and their relationship to neural recordings. Here, we review recent animal studies employing such techniques with the aim to connect their results to effects observed in human pharmacological studies and subjective effects of drugs. It appears that the additive effect of serotonin and DA conveys significant reward related information and is subjectively highly euphorizing. Neither DA nor serotonin alone have such an effect. This coincides with optogenetically targeted recordings in mice, where the dopaminergic system codes reward prediction errors (PE, and the serotonergic system mainly unsigned PE. Overall, this pattern of results indicates that joint activity between both systems carries essential reward information and invites parallel investigation of both neurotransmitter systems.

  10. A neurogenetic dissociation between punishment-, reward- and relief-learning in Drosophila

    Directory of Open Access Journals (Sweden)

    ayse Yarali

    2010-12-01

    Full Text Available What is particularly worth remembering about a traumatic experience is what brought it about, and what made it cease. For example, fruit flies avoid an odour which during training had preceded electric shock punishment; on the other hand, if the odour had followed shock during training, it is later on approached as a signal for the relieving end of shock. We provide a neurogenetic analysis of such relief learning. Blocking, using UAS-shibirets1, the output from a particular set of dopaminergic neurons defined by the TH-Gal4 driver partially impaired punishment learning, but left relief learning intact. Thus, with respect to these particular neurons, relief learning differs from punishment learning. Targeting another set of dopaminergic/ serotonergic neurons defined by the DDC-Gal4 driver on the other hand affected neither punishment nor relief learning. As for the octopaminergic system, the tbhM18 mutation, compromising octopamine biosynthesis, partially impaired sugar-reward learning, but not relief learning. Thus, with respect to this particular mutation, relief learning and reward learning are dissociated. Finally, blocking output from the set of octopaminergic/ tyraminergic neurons defined by the TDC2-Gal4 driver affected neither reward, nor relief learning. We conclude that regarding the used genetic tools, relief learning is neurogenetically dissociated from both punishment and reward learning.

  11. Commitment to Self-Rewards

    OpenAIRE

    Koch, Alexander K.; Nafziger, Julia

    2009-01-01

    Self-administered rewards are ubiquitous. They serve as incentives for personal accomplish¬ments and are widely recommended as tools for overcoming self-control problems. However, it seems puzzling why self-rewards can work: the prospect of a reward has a motivating force only if the threat of self-denial of the reward after low performance is credible. We explain how a rational forward-looking individual may achieve commitment to self-rewards, by applying Köszegi and Rabin's (2006) model of ...

  12. HIV-1 TAT protein enhances sensitization to methamphetamine by affecting dopaminergic function.

    Science.gov (United States)

    Kesby, James P; Najera, Julia A; Romoli, Benedetto; Fang, Yiding; Basova, Liana; Birmingham, Amanda; Marcondes, Maria Cecilia G; Dulcis, Davide; Semenova, Svetlana

    2017-10-01

    Methamphetamine abuse is common among humans with immunodeficiency virus (HIV). The HIV-1 regulatory protein TAT induces dysfunction of mesolimbic dopaminergic systems which may result in impaired reward processes and contribute to methamphetamine abuse. These studies investigated the impact of TAT expression on methamphetamine-induced locomotor sensitization, underlying changes in dopamine function and adenosine receptors in mesolimbic brain areas and neuroinflammation (microgliosis). Transgenic mice with doxycycline-induced TAT protein expression in the brain were tested for locomotor activity in response to repeated methamphetamine injections and methamphetamine challenge after a 7-day abstinence period. Dopamine function in the nucleus accumbens (Acb) was determined using high performance liquid chromatography. Expression of dopamine and/or adenosine A receptors (ADORA) in the Acb and caudate putamen (CPu) was assessed using RT-PCR and immunohistochemistry analyses. Microarrays with pathway analyses assessed dopamine and adenosine signaling in the CPu. Activity-dependent neurotransmitter switching of a reserve pool of non-dopaminergic neurons to a dopaminergic phenotype in the ventral tegmental area (VTA) was determined by immunohistochemistry and quantified with stereology. TAT expression enhanced methamphetamine-induced sensitization. TAT expression alone decreased striatal dopamine (D1, D2, D4, D5) and ADORA1A receptor expression, while increasing ADORA2A receptors expression. Moreover, TAT expression combined with methamphetamine exposure was associated with increased adenosine A receptors (ADORA1A) expression and increased recruitment of dopamine neurons in the VTA. TAT expression and methamphetamine exposure induced microglia activation with the largest effect after combined exposure. Our findings suggest that dopamine-adenosine receptor interactions and reserve pool neuronal recruitment may represent potential targets to develop new treatments for

  13. Dopaminergic Modulation of Risky Decision-Making

    Science.gov (United States)

    Simon, Nicholas W.; Montgomery, Karienn S.; Beas, Blanca S.; Mitchell, Marci R.; LaSarge, Candi L.; Mendez, Ian A.; Bañuelos, Cristina; Vokes, Colin M.; Taylor, Aaron B.; Haberman, Rebecca P.; Bizon, Jennifer L.; Setlow, Barry

    2012-01-01

    Many psychiatric disorders are characterized by abnormal risky decision-making and dysregulated dopamine receptor expression. The current study was designed to determine how different dopamine receptor subtypes modulate risk-taking in young adult rats, using a “Risky Decision-making Task” that involves choices between small “safe” rewards and large “risky” rewards accompanied by adverse consequences. Rats showed considerable, stable individual differences in risk preference in the task, which were not related to multiple measures of reward motivation, anxiety, or pain sensitivity. Systemic activation of D2-like receptors robustly attenuated risk-taking, whereas drugs acting on D1-like receptors had no effect. Systemic amphetamine also reduced risk-taking, an effect which was attenuated by D2-like (but not D1-like) receptor blockade. Dopamine receptor mRNA expression was evaluated in a separate cohort of drug-naive rats characterized in the task. D1 mRNA expression in both nucleus accumbens shell and insular cortex was positively associated with risk-taking, while D2 mRNA expression in orbitofrontal and medial prefrontal cortex predicted risk preference in opposing nonlinear patterns. Additionally, lower levels of D2 mRNA in dorsal striatum were associated with greater risk-taking. These data strongly implicate dopamine signaling in prefrontal corticalstriatal circuitry in modulating decision-making processes involving integration of reward information with risks of adverse consequences. PMID:22131407

  14. The amygdala, reward and emotion.

    Science.gov (United States)

    Murray, Elisabeth A

    2007-11-01

    Recent research provides new insights into amygdala contributions to positive emotion and reward. Studies of neuronal activity in the monkey amygdala and of autonomic responses mediated by the monkey amygdala show that, contrary to a widely held view, the amygdala is just as important for processing positive reward and reinforcement as it is for negative. In addition, neuropsychological studies reveal that the amygdala is essential for only a fraction of what might be considered 'stimulus-reward processing', and that the neural substrates for emotion and reward are partially nonoverlapping. Finally, evidence suggests that two systems within the amygdala, operating in parallel, enable reward-predicting cues to influence behavior; one mediates a general, arousing effect of reward and the other links the sensory properties of reward to emotion.

  15. The dopaminergic system in autoimmune diseases

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    Rodrigo ePacheco

    2014-03-01

    Full Text Available Bidirectional interactions between the immune and the nervous systems are of considerable interest both for deciphering their functioning and for designing novel therapeutic strategies. The past decade has brought a burst of insights into the molecular mechanisms involved in neuro-immune communications mediated by dopamine. Studies of dendritic cells (DCs revealed that they express the whole machinery to synthesize and store dopamine, which may act in an autocrine manner to stimulate dopamine receptors (DARs. Depending on specific DARs stimulated on DCs and T cells, dopamine may differentially favor CD4+ T cell differentiation into Th1 or Th17 inflammatory cells. Regulatory T cells can also release high amounts of dopamine that acts in an autocrine DAR-mediated manner to inhibit their suppressive activity. These dopaminergic regulations could represent a driving force during autoimmunity. Indeed, dopamine levels are altered in the brain of mouse models of multiple sclerosis (MS and lupus, and in inflamed tissues of patients with inflammatory bowel diseases or rheumatoid arthritis. The distorted expression of DARs in peripheral lymphocytes of lupus and MS patients also supports the importance of dopaminergic regulations in autoimmunity. Moreover, dopamine analogs had beneficial therapeutic effects in animal models, and in patients with lupus or rheumatoid arthritis. We propose models that may underlie key roles of dopamine and its receptors in autoimmune diseases.

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

    Science.gov (United States)

    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.

  17. Cognitive judgment bias interacts with risk based decision making and sensitivity to dopaminergic challenge in rats

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    Robert Drozd

    2016-08-01

    Full Text Available Although cognitive theory has implicated judgement bias in various psychopathologies, its role in decision making under risk remains relatively unexplored. In the present study we assessed the effects of cognitive judgment bias on risky choices in rats. First, we trained and tested the animals on the rat version of the probability-discounting task. During discrete trials, the rats chose between two levers; a press on the ‘small/certain’ lever always resulted in the delivery of one reward pellet, whereas a press on the ‘large/risky’ lever resulted in the delivery of four pellets. However, the probability of receiving a reward from the ‘large/risky’ lever gradually decreased over the four trial blocks. Subsequently, the rats were re-trained and evaluated on a series of ambiguous-cue interpretation tests, which permitted their classification according to the display of ‘optimistic’ or ‘pessimistic’ traits. Because dopamine has been implicated in both: risky choices and optimism, in the last experiment, we compared the reactivity of the dopaminergic system in the ‘optimistic’ and ‘pessimistic’ animals using the apomorphine (2mg/kg s.c. sensitivity test. We demonstrated that as risk increased, the proportion of risky lever choices decreased significantly slower in ‘optimists’ compared with ‘pessimists’ and that these differences between the two groups of rats were associated with different levels of dopaminergic system reactivity. Our findings suggest that cognitive judgement bias, risky decision-making and dopamine are linked, and they provide a foundation for further investigation of the behavioural traits and cognitive processes that influence risky choices in animal models.

  18. Reward and punishment

    OpenAIRE

    Sigmund, Karl; Hauert, Christoph; Nowak, Martin A.

    2001-01-01

    Minigames capturing the essence of Public Goods experiments show that even in the absence of rationality assumptions, both punishment and reward will fail to bring about prosocial behavior. This result holds in particular for the well-known Ultimatum Game, which emerges as a special case. But reputation can induce fairness and cooperation in populations adapting through learning or imitation. Indeed, the inclusion of reputation effects in the corresponding dynamical models leads to the evolut...

  19. Elevated Striatal Reactivity Across Monetary and Social Rewards in Bipolar I Disorder

    Science.gov (United States)

    Dutra, Sunny J.; Cunningham, William A.; Kober, Hedy; Gruber, June

    2016-01-01

    Bipolar disorder (BD) is associated with increased reactivity to rewards and heightened positive affectivity. It is less clear to what extent this heightened reward sensitivity is evident across contexts and what the associated neural mechanisms might be. The present investigation employed both a monetary and social incentive delay task among adults with remitted BD type I (N=24) and a healthy non-psychiatric control group (HC; N=25) using fMRI. Both whole-brain and region-of-interest analyses revealed elevated ventral and dorsal striatal reactivity across monetary and social reward receipt, but not anticipation, in the BD group. Post-hoc analyses further suggested that greater striatal reactivity to reward receipt across monetary and social reward tasks predicted decreased self-reported positive affect when anticipating subsequent rewards in the HC, but not BD, group. Results point toward elevated striatal reactivity to reward receipt as a potential neural mechanism of reward reactivity. PMID:26390194

  20. Frontal glutamate and reward processing in adolescence and adulthood.

    Science.gov (United States)

    Gleich, Tobias; Lorenz, Robert C; Pöhland, Lydia; Raufelder, Diana; Deserno, Lorenz; Beck, Anne; Heinz, Andreas; Kühn, Simone; Gallinat, Jürgen

    2015-11-01

    The fronto-limbic network interaction, driven by glutamatergic and dopaminergic neurotransmission, represents a core mechanism of motivated behavior and personality traits. Reward seeking behavior undergoes tremendous changes in adolescence paralleled by neurobiological changes of this network including the prefrontal cortex, striatum and amygdala. Since fronto-limbic dysfunctions also underlie major psychiatric diseases beginning in adolescence, this investigation focuses on network characteristics separating adolescents from adults. To investigate differences in network interactions, the brain reward system activity (slot machine task) together with frontal glutamate concentration (anterior cingulate cortex, ACC) was measured in 28 adolescents and 26 adults employing functional magnetic resonance imaging and magnetic resonance spectroscopy, respectively. An inverse coupling of glutamate concentrations in the ACC and activation of the ventral striatum was observed in adolescents. Further, amygdala response in adolescents was negatively correlated with the personality trait impulsivity. For adults, no significant associations of network components or correlations with impulsivity were found. The inverse association between frontal glutamate concentration and striatal activation in adolescents is in line with the triadic model of motivated behavior stressing the important role of frontal top-down inhibition on limbic structures. Our data identified glutamate as the mediating neurotransmitter of this inhibitory process and demonstrates the relevance of glutamate on the reward system and related behavioral traits like impulsivity. This fronto-limbic coupling may represent a vulnerability factor for psychiatric disorders starting in adolescence but not in adulthood.

  1. Reward association facilitates distractor suppression in human visual search.

    Science.gov (United States)

    Gong, Mengyuan; Yang, Feitong; Li, Sheng

    2016-04-01

    Although valuable objects are attractive in nature, people often encounter situations where they would prefer to avoid such distraction while focusing on the task goal. Contrary to the typical effect of attentional capture by a reward-associated item, we provide evidence for a facilitation effect derived from the active suppression of a high reward-associated stimulus when cuing its identity as distractor before the display of search arrays. Selection of the target is shown to be significantly faster when the distractors were in high reward-associated colour than those in low reward-associated or non-rewarded colours. This behavioural reward effect was associated with two neural signatures before the onset of the search display: the increased frontal theta oscillation and the strengthened top-down modulation from frontal to anterior temporal regions. The former suggests an enhanced working memory representation for the reward-associated stimulus and the increased need for cognitive control to override Pavlovian bias, whereas the latter indicates that the boost of inhibitory control is realized through a frontal top-down mechanism. These results suggest a mechanism in which the enhanced working memory representation of a reward-associated feature is integrated with task demands to modify attentional priority during active distractor suppression and benefit behavioural performance. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  2. Acute Stress Influences Neural Circuits of Reward Processing

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    Anthony John Porcelli

    2012-11-01

    Full Text Available People often make decisions under aversive conditions such as acute stress. Yet, less is known about the process in which acute stress can influence decision-making. A growing body of research has established that reward-related information associated with the outcomes of decisions exerts a powerful influence over the choices people make and that an extensive network of brain regions, prominently featuring the striatum, is involved in the processing of this reward-related information. Thus, an important step in research on the nature of acute stress’ influence over decision-making is to examine how it may modulate responses to rewards and punishments within reward-processing neural circuitry. In the current experiment, we employed a simple reward processing paradigm – where participants received monetary rewards and punishments – known to evoke robust striatal responses. Immediately prior to performing each of two task runs, participants were exposed to acute stress (i.e., cold pressor or a no stress control procedure in a between-subjects fashion. No stress group participants exhibited a pattern of activity within the dorsal striatum and orbitofrontal cortex consistent with past research on outcome processing – specifically, differential responses for monetary rewards over punishments. In contrast, acute stress group participants’ dorsal striatum and orbitofrontal cortex demonstrated decreased sensitivity to monetary outcomes and a lack of differential activity. These findings provide insight into how neural circuits may process rewards and punishments associated with simple decisions under acutely stressful conditions.

  3. Nicotine, alcohol and cocaine coupling to reward processes via endogenous morphine signaling: the dopamine-morphine hypothesis.

    Science.gov (United States)

    Stefano, George B; Bianchi, Enrica; Guarna, Massimo; Fricchione, Gregory L; Zhu, Wei; Cadet, Patrick; Mantione, Kirk J; Casares, Federico M; Kream, Richard M; Esch, Tobias

    2007-06-01

    Pleasure is described as a state or feeling of happiness and satisfaction resulting from an experience that one enjoys. We examine the neurobiological factors underlying reward processes and pleasure phenomena. With regard to possible negative effects of pleasure, we focus on addiction and motivational toxicity. Pleasure can serve cognition, productivity and health, but simultaneously promotes addiction and other negative behaviors. It is a complex neurobiological phenomenon, relying on reward circuitry or limbic activity. These processes involve dopaminergic signaling. Moreover, nicotine, cocaine and alcohol appear to exert their pleasure providing action via endogenous morphinergic mechanisms. Natural rewarding activities are necessary for survival and appetitive motivation, usually governing beneficial biological behaviors like eating, sex and reproduction. Social contacts can further facilitate the positive effects exerted by pleasurable experiences. However, artificial stimulants can be detrimental, since flexibility and normal control of behavior are deteriorated. Additionally, addictive drugs are capable of directly acting on reward pathways, now, in part, via endogenous morphine processes.

  4. Can the dopaminergic-related effects of general anesthetics be linked to mechanisms involved in drug abuse and addiction?

    Science.gov (United States)

    Melo, A; Tavares, I; Sousa, N; Pêgo, J M

    2015-08-01

    General anesthetics (GA) are well known for the ability to induce a state of reversible loss of consciousness and unresponsiveness to painful stimuli. However, evidence from animal models and clinical studies show that GA exposure may induce behavioral changes beyond acute effects. Most research and concerns are focused on changes in cognition and memory. We will look at effects of GA on behavior that is mediated by the dopaminergic system. Pharmacological resemblance of GA with drugs of abuse, and the complexity and importance of dopaminergic systems in both reward seeking and addictive illnesses make us believe that it deserves an overview about what is already known and what matters to us as healthcare workers and specifically as anesthesiologists. A review of available evidence strongly suggests that there may be a link between the effects of GA on the brain and substance abuse, partly explained by their influence on the dopaminergic system. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  5. Intermittent Theta Burst Stimulation Increases Reward Responsiveness in Individuals with Higher Hedonic Capacity.

    Science.gov (United States)

    Duprat, Romain; De Raedt, Rudi; Wu, Guo-Rong; Baeken, Chris

    2016-01-01

    Repetitive transcranial magnetic stimulation over the left dorsolateral prefrontal cortex (DLPFC) has been documented to influence striatal and orbitofrontal dopaminergic activity implicated in reward processing. However, the exact neuropsychological mechanisms of how DLPFC stimulation may affect the reward system and how trait hedonic capacity may interact with the effects remains to be elucidated. In this sham-controlled study in healthy individuals, we investigated the effects of a single session of neuronavigated intermittent theta burst stimulation (iTBS) on reward responsiveness, as well as the influence of trait hedonic capacity. We used a randomized crossover single session iTBS design with an interval of 1 week. We assessed reward responsiveness using a rewarded probabilistic learning task and measured individual trait hedonic capacity (the ability to experience pleasure) with the temporal experience of pleasure scale questionnaire. As expected, the participants developed a response bias toward the most rewarded stimulus (rich stimulus). Reaction time and accuracy for the rich stimulus were respectively shorter and higher as compared to the less rewarded stimulus (lean stimulus). Active or sham stimulation did not seem to influence the outcome. However, when taking into account individual trait hedonic capacity, we found an early significant increase in the response bias only after active iTBS. The higher the individual's trait hedonic capacity, the more the response bias toward the rich stimulus increased after the active stimulation. When taking into account trait hedonic capacity, one active iTBS session over the left DLPFC improved reward responsiveness in healthy male participants with higher hedonic capacity. This suggests that individual differences in hedonic capacity may influence the effects of iTBS on the reward system.

  6. Silicon surface biofunctionalization with dopaminergic tetrahydroisoquinoline derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Lucena-Serrano, A.; Lucena-Serrano, C.; Contreras-Cáceres, R.; Díaz, A.; Valpuesta, M. [Dep. Química Orgánica, Facultad de Ciencias, Universidad de Málaga, 29071 Málaga (Spain); Cai, C. [Dep. Chemistry, University of Houston, Houston, TX 77204-5003 (United States); López-Romero, J.M., E-mail: jmromero@uma.es [Dep. Química Orgánica, Facultad de Ciencias, Universidad de Málaga, 29071 Málaga (Spain)

    2016-01-01

    Graphical abstract: - Highlights: • Two dopaminergic tetrahydroisoquinolines (THI) were synthesized. • Vinyl-terminated THI incorporated onto the H−Si(1 1 1) substrates via a hydrosilylation. • The highest yield in coverage was obtained in DMSO, at 4 h of irradiation and 0.1 mbar of vacuum. • Alkynyl-terminated Si surface was produced for incorporation of azide-THI by click reaction. • Best yields on grafted molecule were obtained by click reaction in absence of ascorbic acid. - Abstract: In this work we grafted vinyl- and azido-terminated tetrahydroisoquinolines (compounds 1 and 2, respectively) onto H−Si(1 1 1) silicon wafers obtaining highly stable modified surfaces. A double bond was incorporated into the tetrahydroisoquinoline structure of 1 to be immobilized by a light induced hydrosilylation reaction on hydrogen-terminated Si(1 1 1). The best results were obtained employing a polar solvent (DMSO), rather than a non-polar solvent (toluene). The azide derivative 2 was grafted onto alkenyl-terminated silicon substrates with copper-catalyzed azide-alkyne cycloaddition (CuAAC). Atomic force microscopy (AFM), contact angle goniometry (CA) and X-ray photoemission spectroscopy (XPS) were used to demonstrate the incorporation of 1 and 2 into the surfaces, study the morphology of the modified surfaces and to calculate the yield of grafting and surface coverage. CA measurements showed the increase in the surface hydrophobicity when 1 or 2 were incorporated into the surface. Moreover, compounds 1 and 2 were prepared starting from 1-(p-nitrophenyl)tetrahydroisoquinoline 3 under smooth conditions and in good yields. The structures of 1 and 2 were designed with a reduced A-ring, two substituents at positions C-6 and C-7, an N-methyl group and a phenyl moiety at C-1 in order to provide a high affinity against dopaminergic receptors. Moreover, O-demethylation of 1 was carried out once it was adsorbed onto the surface by treatment with BBr{sub 3}. The method

  7. Cocaine Effects on Dopaminergic Transmission Depend on a Balance between Sigma-1 and Sigma-2 Receptor Expression.

    Science.gov (United States)

    Aguinaga, David; Medrano, Mireia; Vega-Quiroga, Ignacio; Gysling, Katia; Canela, Enric I; Navarro, Gemma; Franco, Rafael

    2018-01-01

    Sigma σ 1 and σ 2 receptors are targets of cocaine. Despite sharing a similar name, the two receptors are structurally unrelated and their physiological role is unknown. Cocaine increases the level of dopamine, a key neurotransmitter in CNS motor control and reward areas. While the drug also affects dopaminergic signaling by allosteric modulations exerted by σ 1 R interacting with dopamine D 1 and D 2 receptors, the potential regulation of dopaminergic transmission by σ 2 R is also unknown. We here demonstrate that σ 2 R may form heteroreceptor complexes with D 1 but not with D 2 receptors. Remarkably σ 1 , σ 2 , and D 1 receptors may form heterotrimers with particular signaling properties. Determination of cAMP levels, MAP kinase activation and label-free assays demonstrate allosteric interactions within the trimer. Importantly, the presence of σ 2 R induces bias in signal transduction as σ 2 R ligands increase cAMP signaling whereas reduce MAP kinase activation. These effects, which are opposite to those exerted via σ 1 R, suggest that the D 1 receptor-mediated signaling depends on the degree of trimer formation and the differential balance of sigma receptor and heteroreceptor expression in acute versus chronic cocaine consumption. Although the physiological role is unknown, the heteroreceptor complex formed by σ 1 , σ 2 , and D 1 receptors arise as relevant to convey the cocaine actions on motor control and reward circuits and as a key factor in acquisition of the addictive habit.

  8. Cocaine Effects on Dopaminergic Transmission Depend on a Balance between Sigma-1 and Sigma-2 Receptor Expression

    Directory of Open Access Journals (Sweden)

    David Aguinaga

    2018-02-01

    Full Text Available Sigma σ1 and σ2 receptors are targets of cocaine. Despite sharing a similar name, the two receptors are structurally unrelated and their physiological role is unknown. Cocaine increases the level of dopamine, a key neurotransmitter in CNS motor control and reward areas. While the drug also affects dopaminergic signaling by allosteric modulations exerted by σ1R interacting with dopamine D1 and D2 receptors, the potential regulation of dopaminergic transmission by σ2R is also unknown. We here demonstrate that σ2R may form heteroreceptor complexes with D1 but not with D2 receptors. Remarkably σ1, σ2, and D1 receptors may form heterotrimers with particular signaling properties. Determination of cAMP levels, MAP kinase activation and label-free assays demonstrate allosteric interactions within the trimer. Importantly, the presence of σ2R induces bias in signal transduction as σ2R ligands increase cAMP signaling whereas reduce MAP kinase activation. These effects, which are opposite to those exerted via σ1R, suggest that the D1 receptor-mediated signaling depends on the degree of trimer formation and the differential balance of sigma receptor and heteroreceptor expression in acute versus chronic cocaine consumption. Although the physiological role is unknown, the heteroreceptor complex formed by σ1, σ2, and D1 receptors arise as relevant to convey the cocaine actions on motor control and reward circuits and as a key factor in acquisition of the addictive habit.

  9. Social reward shapes attentional biases.

    Science.gov (United States)

    Anderson, Brian A

    2016-01-01

    Paying attention to stimuli that predict a reward outcome is important for an organism to survive and thrive. When visual stimuli are associated with tangible, extrinsic rewards such as money or food, these stimuli acquire high attentional priority and come to automatically capture attention. In humans and other primates, however, many behaviors are not motivated directly by such extrinsic rewards, but rather by the social feedback that results from performing those behaviors. In the present study, I examine whether positive social feedback can similarly influence attentional bias. The results show that stimuli previously associated with a high probability of positive social feedback elicit value-driven attentional capture, much like stimuli associated with extrinsic rewards. Unlike with extrinsic rewards, however, such stimuli also influence task-specific motivation. My findings offer a potential mechanism by which social reward shapes the information that we prioritize when perceiving the world around us.

  10. Monetary rewards modulate inhibitory control

    Directory of Open Access Journals (Sweden)

    Paula Marcela Herrera

    2014-05-01

    Full Text Available The ability to override a dominant response, often referred to as behavioural inhibiton, is considered a key element of executive cognition. Poor behavioural inhibition is a defining characteristic of several neurological and psychiatric populations. Recently, there has been increasing interest in the motivational dimension of behavioural inhibition, with some experiments incorporating emotional contingencies in classical inhibitory paradigms such as the Go/Nogo and Stop Signal Tasks. Several studies have reported a positive modulatory effect of reward on the performance of such tasks in pathological conditions such as substance abuse, pathological gambling, and ADHD. However, experiments that directly investigate the modulatory effects of reward magnitudes on the performance of inhibitory paradigms are rare and consequently, little is known about the finer grained relationship between motivation and self-control. Here, we probed the effect of reward and reward magnitude on behavioural inhibition using two modified version of the widely used Stop Signal Task. The first task compared no reward with reward, whilst the other compared two different reward magnitudes. The reward magnitude effect was confirmed by the second study, whereas it was less compelling in the first study, possibly due to the effect of having no reward in some conditions. In addition, our results showed a kick start effect over global performance measures. More specifically, there was a long lasting improvement in performance throughout the task, when participants received the highest reward magnitudes at the beginning of the protocol. These results demonstrate that individuals’ behavioural inhibition capacities are dynamic not static because they are modulated by the reward magnitude and initial reward history of the task at hand.

  11. Impaired reward responsiveness in schizophrenia.

    Science.gov (United States)

    Taylor, Nicholas; Hollis, Jeffrey P; Corcoran, Sarah; Gross, Robin; Cuthbert, Bruce; Swails, Lisette W; Duncan, Erica

    2018-03-08

    Anhedonia is a core negative symptom of schizophrenia. Schizophrenia patients report largely intact pleasure in consuming rewards, but have impairments in generating motivated behavior to pursue rewards, and show reduced fMRI activation of the reward pathway during presentation of rewarded stimuli. A computer based task measuring the development of a response bias in favor of rewarded stimuli permits assessment of reward-induced motivation. We hypothesized that subjects with schizophrenia would be impaired on this task. 58 schizophrenia subjects (SCZ) and 52 healthy controls (CON) were studied with a signal detection task to assess reward responsiveness. In multiple trials over three blocks subjects were asked to correctly identify two stimuli that were paired with unequal chance of monetary reward. The critical outcome variable was response bias, the development of a greater percent correct identification of the stimulus that was rewarded more often. An ANOVA on response bias with Block as a repeated-measures factor and Diagnosis as a between-group factor indicated that SCZ subjects achieved a lower bias to rewarded stimuli than CON subjects (F(1,105)=8.82, p=0.004, η 2 =0.078). Post hoc tests indicated that SCZ subjects had significantly impaired bias in Block 1 (p=0.002) and Block 2 (p=0.05), indicating that SCZ were slower to achieve normal levels of bias during the session. SCZ subjects were slower to develop response bias to rewarded stimuli than CON subjects. This finding is consonant with the hypothesis that people with schizophrenia have a blunted capacity to modify behavior in response to reward. Copyright © 2018. Published by Elsevier B.V.

  12. Motivational orientation modulates the neural response to reward.

    Science.gov (United States)

    Linke, Julia; Kirsch, Peter; King, Andrea V; Gass, Achim; Hennerici, Michael G; Bongers, André; Wessa, Michèle

    2010-02-01

    Motivational orientation defines the source of motivation for an individual to perform a particular action and can either originate from internal desires (e.g., interest) or external compensation (e.g., money). To this end, motivational orientation should influence the way positive or negative feedback is processed during learning situations and this might in turn have an impact on the learning process. In the present study, we thus investigated whether motivational orientation, i.e., extrinsic and intrinsic motivation modulates the neural response to reward and punishment as well as learning from reward and punishment in 33 healthy individuals. To assess neural responses to reward, punishment and learning of reward contingencies we employed a probabilistic reversal learning task during functional magnetic resonance imaging. Extrinsic and intrinsic motivation were assessed with a self-report questionnaire. Rewarding trials fostered activation in the medial orbitofrontal cortex and anterior cingulate gyrus (ACC) as well as the amygdala and nucleus accumbens, whereas for punishment an increased neural response was observed in the medial and inferior prefrontal cortex, the superior parietal cortex and the insula. High extrinsic motivation was positively correlated to increased neural responses to reward in the ACC, amygdala and putamen, whereas a negative relationship between intrinsic motivation and brain activation in these brain regions was observed. These findings show that motivational orientation indeed modulates the responsiveness to reward delivery in major components of the human reward system and therefore extends previous results showing a significant influence of individual differences in reward-related personality traits on the neural processing of reward. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  13. Commitment to self-rewards

    DEFF Research Database (Denmark)

    Koch, Alexander; Nafziger, Julia

    People often overcome self-control problems by promising to reward themselves for accomplishing a task. Such strategies based on self-administered rewards however require the person to believe that she would indeed deny herself the reward if she should fail to achieve the desired outcome. Drawing...... on Koszegi and Rabin's (2006) model of endogenous reference point formation, we show how a rational forward-looking individual can achieve such internal commitment. But our results also demonstrate the limitations of self regulation based on self-rewards....

  14. Control of sleep by dopaminergic inputs to the Drosophila mushroom body

    Directory of Open Access Journals (Sweden)

    Divya eSitaraman

    2015-11-01

    Full Text Available The Drosophila mushroom body (MB is an associative learning network that is important for the control of sleep. We have recently identified particular intrinsic MB Kenyon cell (KC classes that regulate sleep through synaptic activation of particular MB output neurons (MBONs whose axons convey sleep control signals out of the MB to downstream target regions. Specifically, we found that sleep-promoting KCs increase sleep by preferentially activating cholinergic sleep-promoting MBONs, while wake-promoting KCs decrease sleep by preferentially activating glutamatergic wake-promoting MBONs. Here we use a combination of genetic and physiological approaches to identify wake-promoting dopaminergic neurons (DANs that innervate the MB, and show that they activate wake-promoting MBONs. These studies reveal a dopaminergic sleep control mechanism that likely operates by modulation of KC-MBON microcircuits.

  15. Brain metabolic correlates of dopaminergic degeneration in de novo idiopathic Parkinson's disease

    International Nuclear Information System (INIS)

    Berti, Valentina; Polito, Cristina; Vanzi, Eleonora; Cristofaro, Maria Teresa de; Pellicano, Giannantonio; Mungai, Francesco; Formiconi, Andreas Robert; Pupi, Alberto; Ramat, Silvia; Marini, Paolo; Sorbi, Sandro

    2010-01-01

    The aim of the present study was to evaluate the reciprocal relationships between motor impairment, dopaminergic dysfunction, and cerebral metabolism (rCMRglc) in de novo Parkinson's disease (PD) patients. Twenty-six de novo untreated PD patients were scanned with 123 I-FP-CIT SPECT and 18 F-FDG PET. The dopaminergic impairment was measured with putaminal 123 I-FP-CIT binding potential (BP), estimated with two different techniques: an iterative reconstruction algorithm (BP OSEM ) and the least-squares (LS) method (BP LS ). Statistical parametric mapping (SPM) multiple regression analyses were performed to determine the specific brain regions in which UPDRS III scores and putaminal BP values correlated with rCMRglc. The SPM results showed a negative correlation between UPDRS III and rCMRglc in premotor cortex, and a positive correlation between BP OSEM and rCMRglc in premotor and dorsolateral prefrontal cortex, not surviving at multiple comparison correction. Instead, there was a positive significant correlation between putaminal BP LS and rCMRglc in premotor, dorsolateral prefrontal, anterior prefrontal, and orbitofrontal cortex (p LS is an efficient parameter for exploring the correlations between PD severity and rCMRglc cortical changes. The correlation between dopaminergic degeneration and rCMRglc in several prefrontal regions likely represents the cortical functional correlate of the dysfunction in the motor basal ganglia-cortical circuit in PD. This finding suggests focusing on the metabolic course of these areas to follow PD progression and to analyze treatment effects. (orig.)

  16. Investigations into potential extrasynaptic communication between the dopaminergic and nitrergic systems

    Directory of Open Access Journals (Sweden)

    Miso eMitkovski

    2012-09-01

    Full Text Available Nitric oxide is unconstrained by cell membranes and can therefore act along a broad distance as a volume transmitter. Spillover of nitric oxide between neurons may have a major impact on central nervous system diseases and particularly on neurodegeneration. There is evidence whereby communication between nitrergic and dopaminergic systems plays an essential role in the control of the nigrostriatal pathway. However, there is sparse information for either the coexistence or overlap of nitric oxide and dopaminergic structures. The present study used double-labeling immunofluorescent microscopy to investigate the degree of cellular co-localization between nitric oxide synthase and tyrosine hydroxylase, enzymes responsible for the synthesis of nitric oxide and dopamine, respectively, was examined in neurons of the nigrostriatal pathway regions in the rat brain. After perfusional fixation, the brains were cut and double immunostained. A proximity analysis of tyrosine hydroxylase and nitric oxide synthase structures was made using confocal laser scanning microscopy, in nigrostriatal regions of the rat brain. We used image acquired at the optical limit and generated binary masks at 2µm-wide margin from the respective maximum projections. Co-localization between the two antigens was infrequent (<10% in most areas examined. However, tyrosine hydroxylase labeling was particularly concentrated close to nitric oxide synthase dendrites/axons and the cell bodies. These results further substantiate an extrasynaptic substrate for interaction between nitrergic and dopaminergic systems, thereby modulating sensitivity to neural inputs and its gene expression.

  17. Imbalance in the sensitivity to different types of rewards in pathological gambling.

    Science.gov (United States)

    Sescousse, Guillaume; Barbalat, Guillaume; Domenech, Philippe; Dreher, Jean-Claude

    2013-08-01

    Pathological gambling is an addictive disorder characterized by a persistent and compulsive desire to engage in gambling activities. This maladaptive behaviour has been suggested to result from a decreased sensitivity to experienced rewards, regardless of reward type. Alternatively, pathological gambling might reflect an imbalance in the sensitivity to monetary versus non-monetary incentives. To directly test these two hypotheses, we examined how the brain reward circuit of pathological gamblers responds to different types of rewards. Using functional magnetic resonance imaging, we compared the brain responses of 18 pathological gamblers and 20 healthy control subjects while they engaged in a simple incentive task manipulating both monetary and visual erotic rewards. During reward anticipation, the ventral striatum of pathological gamblers showed a differential response to monetary versus erotic cues, essentially driven by a blunted reactivity to cues predicting erotic stimuli. This differential response correlated with the severity of gambling symptoms and was paralleled by a reduced behavioural motivation for erotic rewards. During reward outcome, a posterior orbitofrontal cortex region, responding to erotic rewards in both groups, was further recruited by monetary gains in pathological gamblers but not in control subjects. Moreover, while ventral striatal activity correlated with subjective ratings assigned to monetary and erotic rewards in control subjects, it only correlated with erotic ratings in gamblers. Our results point to a differential sensitivity to monetary versus non-monetary rewards in pathological gambling, both at the motivational and hedonic levels. Such an imbalance might create a bias towards monetary rewards, potentially promoting addictive gambling behaviour.

  18. COMT Val158Met genotype is associated with reward learning: A replication study and meta-analysis

    Science.gov (United States)

    Corral-Frías, Nadia S.; Pizzagalli, Diego A.; Carré, Justin; Michalski, Lindsay J; Nikolova, Yuliya S.; Perlis, Roy H.; Fagerness, Jesen; Lee, Mary R.; Conley, Emily Drabant; Lancaster, Thomas M.; Haddad, Stephen; Wolf, Aaron; Smoller, Jordan W.; Hariri, Ahmad R.; Bogdan, Ryan

    2016-01-01

    Identifying mechanisms through which individual differences in reward learning emerge offers an opportunity to understand both a fundamental form of adaptive responding as well as etiological pathways through which aberrant reward learning may contribute to maladaptive behaviors and psychopathology. One candidate mechanism through which individual differences in reward learning may emerge is variability in dopaminergic reinforcement signaling. A common functional polymorphism within the catechol-O-methyl transferase gene (COMT; rs4680, Val158Met) has been linked to reward learning where homozygosity for the Met allele (associated with heightened prefrontal dopamine function and decreased dopamine synthesis in the midbrain) has been associated with relatively increased reward learning. Here, we used a probabilistic reward learning task to asses response bias, a behavioral form of reward learning, across 3 separate samples that were combined for analyses (age: 21.80 ± 3.95; n=392; 268 female; European-American, n=208). We replicate prior reports that COMT rs4680 Met allele homozygosity is associated with increased reward learning in European-American participants (β=0.20, t= 2.75, p< 0.01; ΔR2= 0.04). Moreover, a meta-analysis of 4 studies, including the current one, confirmed the association between COMT rs4680 genotype and reward learning (95% CI −0.11 to −0.03; z=3.2; p<0.01). These results suggest that variability in dopamine signaling associated with COMT rs4680 influences individual differences in reward which may potentially contribute to psychopathology characterized by reward dysfunction. PMID:27138112

  19. Marijuana and cannabinoid regulation of brain reward circuits

    OpenAIRE

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

    2004-01-01

    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, Δ9-THC, interacting primarily with CB1 cannabinoid receptors in a large number of brain areas. However, it is the activation o...

  20. Dopamine in the Brain: Hypothesizing Surfeit or Deficit Links to Reward and Addiction.

    Science.gov (United States)

    Blum, Kenneth; Thanos, Peter K; Oscar-Berman, Marlene; Febo, Marcelo; Baron, David; Badgaiyan, Rajendra D; Gardner, Eliot; Demetrovics, Zsolt; Fahlke, Claudia; Haberstick, Brett C; Dushaj, Kristina; Gold, Mark S

    Recently there has been debate concerning the role of brain dopamine in reward and addiction. David Nutt and associates eloquently proposed that dopamine (DA) may be central to psycho stimulant dependence and some what important for alcohol, but not important for opiates, nicotine or even cannabis. Others have also argued that surfeit theories can explain for example cocaine seeking behavior as well as non-substance-related addictive behaviors. It seems prudent to distinguish between what constitutes "surfeit" compared to" deficit" in terms of short-term (acute) and long-term (chronic) brain reward circuitry responsivity. In an attempt to resolve controversy regarding the contributions of mesolimbic DA systems to reward, we review the three main competing explanatory categories: "liking", "learning", and "wanting". They are (a) the hedonic impact -liking reward, (b) the ability to predict rewarding effects-learning and (c) the incentive salience of reward-related stimuli -wanting. In terms of acute effects, most of the evidence seems to favor the "surfeit theory". Due to preferential dopamine release at mesolimbic-VTA-caudate-accumbens loci most drugs of abuse and Reward Deficiency Syndrome (RDS) behaviors have been linked to heightened feelings of well-being and hyperdopaminergic states.The "dopamine hypotheses" originally thought to be simple, is now believed to be quite complex and involves encoding the set point of hedonic tone, encoding attention, reward expectancy, and incentive motivation. Importantly, Willuhn et al. shows that in a self-administration paradigm, (chronic) excessive use of cocaine is caused by decreased phasic dopamine signaling in the striatum. In terms of chronic addictions, others have shown a blunted responsivity at brain reward sites with food, nicotine, and even gambling behavior. Finally, we are cognizant of the differences in dopaminergic function as addiction progresses and argue that relapse may be tied to dopamine deficiency

  1. Monetary rewards influence retrieval orientations.

    Science.gov (United States)

    Halsband, Teresa M; Ferdinand, Nicola K; Bridger, Emma K; Mecklinger, Axel

    2012-09-01

    Reward anticipation during learning is known to support memory formation, but its role in retrieval processes is so far unclear. Retrieval orientations, as a reflection of controlled retrieval processing, are one aspect of retrieval that might be modulated by reward. These processes can be measured using the event-related potentials (ERPs) elicited by retrieval cues from tasks with different retrieval requirements, such as via changes in the class of targeted memory information. To determine whether retrieval orientations of this kind are modulated by reward during learning, we investigated the effects of high and low reward expectancy on the ERP correlates of retrieval orientation in two separate experiments. The reward manipulation at study in Experiment 1 was associated with later memory performance, whereas in Experiment 2, reward was directly linked to accuracy in the study task. In both studies, the participants encoded mixed lists of pictures and words preceded by high- or low-reward cues. After 24 h, they performed a recognition memory exclusion task, with words as the test items. In addition to a previously reported material-specific effect of retrieval orientation, a frontally distributed, reward-associated retrieval orientation effect was found in both experiments. These findings suggest that reward motivation during learning leads to the adoption of a reward-associated retrieval orientation to support the retrieval of highly motivational information. Thus, ERP retrieval orientation effects not only reflect retrieval processes related to the sought-for materials, but also relate to the reward conditions with which items were combined during encoding.

  2. Floral reward in Ranunculaceae species

    Directory of Open Access Journals (Sweden)

    Bożena Denisow

    2016-04-01

    Full Text Available Floral reward is important in ecological and evolutionary perspectives and essential in pollination biology. For example, floral traits, nectar and pollen features are essential for understanding the functional ecology, the dynamics of pollen transport, competition for pollinator services, and patterns of specialization and generalization in plant–pollinator interactions. We believe to present a synthetic description in the field of floral reward in Ranunculaceae family important in pollination biology and indicating connections between ecological and evolutionary approaches. The links between insect visitors’ behaviour and floral reward type and characteristics exist. Ranunculaceae is a family of aboot 1700 species (aboot 60 genera, distributed worldwide, however the most abundant representatives are in temperate and cool regions of the northern and southern hemispheres. The flowers are usually radially symmetric (zygomorphic and bisexual, but in Aconitum, Aquilegia are bilaterally symmetric (zygomorphic. Most Ranunculaceae flowers offer no nectar, only pollen (e.g., Ranunculus, Adonis vernalis, Thalictrum, but numerous species create trophic niches for different wild pollinators (e.g. Osmia, Megachile, Bombus, Andrena (Denisow et al. 2008. Pollen is a source of protein, vitamins, mineral salts, organic acids and hormones, but the nutritional value varies greatly between different plant species. The pollen production can differ significantly between Ranunculacea species. The mass of pollen produced in anthers differ due to variations in the number of developed anthers. For example, interspecies differences are considerable, 49 anthers are noted in Aquilegia vulgaris, 70 anthers in Ranunculus lanuginosus, 120 in Adonis vernalis. A significant intra-species differences’ in the number of anthers are also noted (e.g. 41 to 61 in Aquilegia vulgaris, 23-45 in Ranunculus cassubicus. Pollen production can be up to 62 kg per ha for Ranunculus acer

  3. Gender dimorphism of brain reward system volumes in alcoholism.

    Science.gov (United States)

    Sawyer, Kayle S; Oscar-Berman, Marlene; Barthelemy, Olivier J; Papadimitriou, George M; Harris, Gordon J; Makris, Nikos

    2017-05-30

    The brain's reward network has been reported to be smaller in alcoholic men compared to nonalcoholic men, but little is known about the volumes of reward regions in alcoholic women. Morphometric analyses were performed on magnetic resonance brain scans of 60 long-term chronic alcoholics (ALC; 30 men) and 60 nonalcoholic controls (NC; 29 men). We derived volumes of total brain, and cortical and subcortical reward-related structures including the dorsolateral prefrontal (DLPFC), orbitofrontal, and cingulate cortices, and the temporal pole, insula, amygdala, hippocampus, nucleus accumbens septi (NAc), and ventral diencephalon (VDC). We examined the relationships of the volumetric findings to drinking history. Analyses revealed a significant gender interaction for the association between alcoholism and total reward network volumes, with ALC men having smaller reward volumes than NC men and ALC women having larger reward volumes than NC women. Analyses of a priori subregions revealed a similar pattern of reward volume differences with significant gender interactions for DLPFC and VDC. Overall, the volume of the cerebral ventricles in ALC participants was negatively associated with duration of abstinence, suggesting decline in atrophy with greater length of sobriety. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  4. Model Checking Multivariate State Rewards

    DEFF Research Database (Denmark)

    Nielsen, Bo Friis; Nielson, Flemming; Nielson, Hanne Riis

    2010-01-01

    We consider continuous stochastic logics with state rewards that are interpreted over continuous time Markov chains. We show how results from multivariate phase type distributions can be used to obtain higher-order moments for multivariate state rewards (including covariance). We also generalise...

  5. Social and physical environment alter cocaine conditioned place preference and dopaminergic markers in adolescent male rats.

    Science.gov (United States)

    Zakharova, E; Miller, J; Unterwald, E; Wade, D; Izenwasser, S

    2009-10-20

    This study was done to determine whether social and environmental factors alter cocaine reward and proteins implicated in mediating drug reward in rats during early adolescence. On postnatal day (PND) 23, rats were housed under conditions where both social (number of rats per cage) and environmental (availability of toys) factors were manipulated. Socially isolated rats were housed alone impoverished with no toys (II) or enriched with toys (IE). Social rats were housed two rats/cage with no toys (SI2) or with toys (SE2), or three/cage with (SE3) or without (SI3) toys. On PND 43, cocaine conditioned place preference (CPP) sessions began with the post-test done on PND 47. Cocaine CPP was established in response to 5 or 10 mg/kg cocaine in II rats, and CPP was decreased with the addition of cage mates or toys. No CPP was seen to any dose in SI3 or SE3 rats. Enriched housing (SE3) increased dopamine transporter (DAT) protein in the nucleus accumbens compared to II. There also were differential effects of cocaine on tyrosine hydroxylase and DAT depending on housing, with both increased by cocaine in II but not SE3 rats. DARPP-32 was unchanged by housing or cocaine, while phospho-Thr(34)-DARPP-32 was increased by cocaine treatment across conditions. Thus, both social and environmental enrichment decrease cocaine CPP during adolescence and different housing alters proteins that regulate dopaminergic neurotransmission in a manner that may account for the observed differences in cocaine-induced reward.

  6. Risk and reward

    International Nuclear Information System (INIS)

    Kellas, G.K.; Hodgshon, S.G.

    1992-01-01

    This paper looks at the problems facing the international oil explorationist and host Governments in 1992, under a cloud of low oil prices and falling company profits, yet with more quality acreage available worldwide than for many years, especially with the emergence of the CIS states as prospective hunting grounds for the western oil company. Given the extent of the spread of opportunities available to companies and recognition of the increasing need to justify, on economic grounds, progress with any licence application this paper suggests two approaches that companies can adopt to rank the opportunities available, and maximize the value, on an after risk basis, of their (limited) international exploration budget : subjective rating by factor or the Risk/Reward balance. Both of these approaches include measures of prospectivity and measures of local cost and fiscal effects in providing an overall exploration rating which can be used by companies to rank the available opportunities

  7. ATLAS rewards industry

    CERN Multimedia

    2006-01-01

    Showing excellence in mechanics, electronics and cryogenics, three industries are honoured for their contributions to the ATLAS experiment. Representatives of the three award-wining companies after the ceremony. For contributing vital pieces to the ATLAS puzzle, three industries were recognized on Friday 5 May during a supplier awards ceremony. After a welcome and overview of the ATLAS experiment by spokesperson Peter Jenni, CERN Secretary-General Maximilian Metzger stressed the importance of industry to CERN's scientific goals. Close interaction with CERN was a key factor in the selection of each rewarded company, in addition to the high-quality products they delivered to the experiment. Alu Menziken Industrie AG, of Switzerland, was honoured for the production of 380,000 aluminium tubes for the Monitored Drift Tube Chambers (MDT). As Giora Mikenberg, the Muon System Project Leader stressed, the aluminium tubes were delivered on time with an extraordinary quality and precision. Between October 2000 and Jan...

  8. Functional connectivity in cortico-subcortical brain networks underlying reward processing in attention-deficit/hyperactivity disorder

    NARCIS (Netherlands)

    Oldehinkel, Marianne; Beckmann, Christian F.; Franke, Barbara; Hartman, Catharina A.; Hoekstra, Pieter J.; Oosterlaan, Jaap; Heslenfeld, Dirk; Buitelaar, Jan K.; Mennes, Maarten

    2016-01-01

    Background: Many patients with attention-deficit/hyperactivity disorder (ADHD) display aberrant reward-related behavior. Task-based fMRI studies have related atypical reward processing in ADHD to altered BOLD activity in regions underlying reward processing such as ventral striatum and orbitofrontal

  9. Reward deficiency and anti-reward in pain chronification.

    Science.gov (United States)

    Borsook, D; Linnman, C; Faria, V; Strassman, A M; Becerra, L; Elman, I

    2016-09-01

    Converging lines of evidence suggest that the pathophysiology of pain is mediated to a substantial degree via allostatic neuroadaptations in reward- and stress-related brain circuits. Thus, reward deficiency (RD) represents a within-system neuroadaptation to pain-induced protracted activation of the reward circuits that leads to depletion-like hypodopaminergia, clinically manifested anhedonia, and diminished motivation for natural reinforcers. Anti-reward (AR) conversely pertains to a between-systems neuroadaptation involving over-recruitment of key limbic structures (e.g., the central and basolateral amygdala nuclei, the bed nucleus of the stria terminalis, the lateral tegmental noradrenergic nuclei of the brain stem, the hippocampus and the habenula) responsible for massive outpouring of stressogenic neurochemicals (e.g., norepinephrine, corticotropin releasing factor, vasopressin, hypocretin, and substance P) giving rise to such negative affective states as anxiety, fear and depression. We propose here the Combined Reward deficiency and Anti-reward Model (CReAM), in which biopsychosocial variables modulating brain reward, motivation and stress functions can interact in a 'downward spiral' fashion to exacerbate the intensity, chronicity and comorbidities of chronic pain syndromes (i.e., pain chronification). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Drosophila divalent metal ion transporter Malvolio is required in dopaminergic neurons for feeding decisions.

    Science.gov (United States)

    Søvik, E; LaMora, A; Seehra, G; Barron, A B; Duncan, J G; Ben-Shahar, Y

    2017-06-01

    Members of the natural resistance-associated macrophage protein (NRAMP) family are evolutionarily conserved metal ion transporters that play an essential role in regulating intracellular divalent cation homeostasis in both prokaryotes and eukaryotes. Malvolio (Mvl), the sole NRAMP family member in insects, plays a role in food choice behaviors in Drosophila and other species. However, the specific physiological and cellular processes that require the action of Mvl for appropriate feeding decisions remain elusive. Here, we show that normal food choice requires Mvl function specifically in the dopaminergic system, and can be rescued by supplementing food with manganese. Collectively, our data indicate that the action of the Mvl transporter affects food choice behavior via the regulation of dopaminergic innervation of the mushroom bodies, a principle brain region associated with decision-making in insects. Our studies suggest that the homeostatic regulation of the intraneuronal levels of divalent cations plays an important role in the development and function of the dopaminergic system and associated behaviors. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  11. Clinical Investigation of the Dopaminergic System with PET and FLUORINE-18-FLUORO-L-DOPA.

    Science.gov (United States)

    Oakes, Terrence Rayford

    1995-01-01

    Positron Emission Tomography (PET) is a tool that provides quantitative physiological information. It is valuable both in a clinical environment, where information is sought for an individual, and in a research environment, to answer more fundamental questions about physiology and disease states. PET is particularly attractive compared to other nuclear medicine imaging techniques in cases where the anatomical regions of interest are small or when true metabolic rate constants are required. One example with both of these requirements is the investigation of Parkinson's Disease, which is characterized as a presynaptic motor function deficit affecting the striatum. As dopaminergic neurons die, the ability of the striatum to affect motor function decreases. The extent of functional neuronal damage in the small sub-structures may be ascertained by measuring the ability of the caudate and putamen to trap and store dopamine, a neurotransmitter. PET is able to utilize a tracer of dopamine activity, ^ {18}F- scL-DOPA, to quantitate the viability of the striatum. This thesis work deals with implementing and optimizing the many different elements that compose a PET study of the dopaminergic system, including: radioisotope production; conversion of aqueous ^{18}F ^-into [^ {18}F]-F2; synthesis of ^{18}F- scL -DOPA; details of the PET scan itself; measurements to estimate the radiation dosimetry; accurate measurement of a plasma input function; and the quantitation of dopaminergic activity in normal human subjects as well as in Parkinson's Disease patients.

  12. Reward deficiency syndrome: genetic aspects of behavioral disorders.

    Science.gov (United States)

    Comings, D E; Blum, K

    2000-01-01

    The dopaminergic and opioidergic reward pathways of the brain are critical for survival since they provide the pleasure drives for eating, love and reproduction; these are called 'natural rewards' and involve the release of dopamine in the nucleus accumbens and frontal lobes. However, the same release of dopamine and production of sensations of pleasure can be produced by 'unnatural rewards' such as alcohol, cocaine, methamphetamine, heroin, nicotine, marijuana, and other drugs, and by compulsive activities such as gambling, eating, and sex, and by risk taking behaviors. Since only a minority of individuals become addicted to these compounds or behaviors, it is reasonable to ask what factors distinguish those who do become addicted from those who do not. It has usually been assumed that these behaviors are entirely voluntary and that environmental factors play the major role; however, since all of these behaviors have a significant genetic component, the presence of one or more variant genes presumably act as risk factors for these behaviors. Since the primary neurotransmitter of the reward pathway is dopamine, genes for dopamine synthesis, degradation, receptors, and transporters are reasonable candidates. However, serotonin, norepinephrine, GABA, opioid, and cannabinoid neurons all modify dopamine metabolism and dopamine neurons. We have proposed that defects in various combinations of the genes for these neurotransmitters result in a Reward Deficiency Syndrome (RDS) and that such individuals are at risk for abuse of the unnatural rewards. Because of its importance, the gene for the [figure: see text] dopamine D2 receptor was a major candidate gene. Studies in the past decade have shown that in various subject groups the Taq I A1 allele of the DRD2 gene is associated with alcoholism, drug abuse, smoking, obesity, compulsive gambling, and several personality traits. A range of other dopamine, opioid, cannabinoid, norepinephrine, and related genes have since been

  13. Effects of motivation on reward and attentional networks: an fMRI study.

    Science.gov (United States)

    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

  14. Contribution of dopamine to mitochondrial complex I inhibition and dopaminergic deficits caused by methylenedioxymethamphetamine in mice.

    Science.gov (United States)

    Barros-Miñones, L; Goñi-Allo, B; Suquia, V; Beitia, G; Aguirre, N; Puerta, E

    2015-06-01

    Methylenedioxymethamphetamine (MDMA) causes a persistent loss of dopaminergic cell bodies in the substantia nigra of mice. Current evidence indicates that MDMA-induced neurotoxicity is mediated by oxidative stress probably due to the inhibition of mitochondrial complex I activity. In this study we investigated the contribution of dopamine (DA) to such effects. For this, we modulated the dopaminergic system of mice at the synthesis, uptake or metabolism levels. Striatal mitochondrial complex I activity was decreased 1 h after MDMA; an effect not observed in the striatum of DA depleted mice or in the hippocampus, a dopamine spare region. The DA precursor, L-dopa, caused a significant reduction of mitochondrial complex I activity by itself and exacerbated the dopaminergic deficits when combined with systemic MDMA. By contrast, no damage was observed when L-dopa was combined with intrastriatal injections of MDMA. On the other hand, dopamine uptake blockade using GBR 12909, inhibited both, the acute inhibition of complex I activity and the long-term dopaminergic toxicity caused by MDMA. Moreover, the inhibition of DA metabolism with the monoamine oxidase (MAO) inhibitor, pargyline, afforded a significant protection against MDMA-induced complex I inhibition and neurotoxicity. Taken together, these findings point to the formation of hydrogen peroxide subsequent to DA metabolism by MAO, rather than a direct DA-mediated mitochondrial complex I inhibition, and the contribution of a peripheral metabolite of MDMA, as the key steps in the chain of biochemical events leading to DA neurotoxicity caused by MDMA in mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Dopamine mediates testosterone-induced social reward in male Syrian hamsters.

    Science.gov (United States)

    Bell, Margaret R; Sisk, Cheryl L

    2013-03-01

    Adolescent maturation of responses to social stimuli is essential for adult-typical sociosexual behavior. Naturally occurring developmental changes in male Syrian hamster responses to a salient social cue, female hamster vaginal secretions (VS), provide a good model system for investigating neuroendocrine mechanisms of adolescent change in social reward. Sexually naïve adult, but not juvenile, males show a conditioned place preference (CPP) to VS, indicating that VS is not rewarding before puberty. In this series of experiments, the authors examined the roles of testosterone and dopamine receptor activation in mediating the adolescent gain in positive valence of VS. Experiment 1 showed that testosterone replacement is necessary for gonadectomized adult hamsters to form a CPP to VS. Experiment 2 showed that testosterone treatment is sufficient for juvenile hamsters to form a CPP to VS, and that the dopamine receptor antagonist haloperidol blocks formation of a CPP to VS in these animals. Experiments 3 and 4 demonstrated that the disruption of VS CPP with low doses of haloperidol is the result of a reduction in the attractive properties of VS and not attributable to aversive properties of haloperidol. Together, these studies demonstrate that the unconditioned rewarding properties of a social cue necessary for successful adult sociosexual interactions come about as the result of the pubertal increase in circulating testosterone in male hamsters. Furthermore, this social reward can be prevented by dopamine receptor antagonism, indicating that hypothalamic and/or mesocorticolimbic dopaminergic circuits are targets for hormonal activation of social reward.

  16. The role of BDNF, leptin, and catecholamines in reward learning in bulimia nervosa.

    Science.gov (United States)

    Homan, Philipp; Grob, Simona; Milos, Gabriella; Schnyder, Ulrich; Eckert, Anne; Lang, Undine; Hasler, Gregor

    2014-12-07

    A relationship between bulimia nervosa and reward-related behavior is supported by several lines of evidence. The dopaminergic dysfunctions in the processing of reward-related stimuli have been shown to be modulated by the neurotrophin brain derived neurotrophic factor (BDNF) and the hormone leptin. Using a randomized, double-blind, placebo-controlled, crossover design, a reward learning task was applied to study the behavior of 20 female subjects with remitted bulimia nervosa and 27 female healthy controls under placebo and catecholamine depletion with alpha-methyl-para-tyrosine (AMPT). The plasma levels of BDNF and leptin were measured twice during the placebo and the AMPT condition, immediately before and 1 hour after a standardized breakfast. AMPT-induced differences in plasma BDNF levels were positively correlated with the AMPT-induced differences in reward learning in the whole sample (P=.05). Across conditions, plasma brain derived neurotrophic factor levels were higher in remitted bulimia nervosa subjects compared with controls (diagnosis effect; P=.001). Plasma BDNF and leptin levels were higher in the morning before compared with after a standardized breakfast across groups and conditions (time effect; Pbulimia nervosa and controls. A role of leptin in reward learning is not supported by this study. However, leptin levels were sensitive to a depletion of catecholamine stores in both remitted bulimia nervosa and controls. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  17. Serotonergic and dopaminergic modulation of attentional processes.

    Science.gov (United States)

    Boulougouris, Vasileios; Tsaltas, Eleftheria

    2008-01-01

    Disturbances in attentional processes are a common feature of several psychiatric disorders such as schizophrenia, attention deficit/hyperactivity disorder and Huntington's disease. The use of animal models has been useful in defining various candidate neural systems thus enabling us to translate basic laboratory science to the clinic and vice-versa. In this chapter, a comparative and integrated account is provided on the neuroanatomical and neurochemical modulation of basic behavioural operations such as selective attention, vigilance, set-shifting and executive control focusing on the comparative functions of the serotonin and dopamine systems in the cognitive control exerted by the prefrontal cortex. Specifically, we have reviewed evidence emerging from several behavioural paradigms in experimental animals and humans each of which centres on a different aspect of the attentional function. These paradigms offering both human and animal variants include the five-choice serial reaction time task (5CSRTT), attentional set-shifting and stop-signal reaction time task. In each case, the types of operation that are measured by the given paradigm and their neural correlates are defined. Then, the role of the ascending dopaminergic and serotonergic systems in the neurochemical modulation of its behavioural output are examined, and reference is made to clinical implications for neurological and neuropsychiatric disorders which exhibit deficits in these cognitive tests.

  18. Hemispheric differences in the mesostriatal dopaminergic system

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    Ilana eMolochnikov

    2014-06-01

    Full Text Available The mesostriatal dopaminergic system, which comprises the mesolimbic and the nigrostriatal pathways, plays a major role in neural processing underlying motor and limbic functions. Multiple reports suggest that these processes are influenced by hemispheric differences in striatal dopamine (DA levels, DA turnover and its receptor activity. Here, we review studies which measured the concentration of DA and its metabolites to examine the relationship between DA imbalance and animal behavior under different conditions. Specifically, we assess evidence in support of endogenous, inter-hemispheric DA imbalance; determine whether the known anatomy provides a suitable substrate for this imbalance; examine the relationship between DA imbalance and animal behavior; and characterize the symmetry of the observed inter-hemispheric laterality in the nigrostriatal and the mesolimbic DA systems. We conclude that many studies provide supporting evidence for the occurrence of experience-dependent endogenous DA imbalance which is controlled by a dedicated regulatory/compensatory mechanism. Additionally, it seems that the link between DA imbalance and animal behavior is better characterized in the nigrostriatal than in the mesolimbic system. Nonetheless, a variety of brain and behavioral manipulations demonstrate that the nigrostriatal system displays symmetrical laterality whereas the mesolimbic system displays asymmetrical laterality which supports hemispheric specialization in rodents. The reciprocity of the relationship between DA imbalance and animal behavior (i.e. the capacity of animal training to alter DA imbalance for prolonged time periods remains controversial, however, if confirmed, may provide a valuable noninvasive therapeutic means for treating abnormal DA imbalance.

  19. Brain dopaminergic systems : imaging with positron tomography

    Energy Technology Data Exchange (ETDEWEB)

    Baron, J C [University of Caen/INSERM U, Caen (France). CYCERON; Comar, D [E.E.C. Concerted Action on P.E.T. Investigations of Cellular Regeneration and Degeneration, Orsay (France) CEA, 91 - Orsay (France). Service Hospitalier Frederic Joliot; Farde, L [Karolinska Sjukhuset, Stockholm (Sweden); Martinot, J L; Mazoyer, B [CEA, 91 - Orsay (France). Service Hospitalier Frederic Joliot Paris-

    1991-01-01

    Imaging of the dopaminergic system in the human brain with the in vivo use of Positron Emission Tomography emerged in the late 1980s as a tool of major importance in clinical neurosciences and pharmacology. The last few years have witnessed rapid development of new radiotracers specific to receptors, reuptake sites and enzymes of the dopamine system; the application of these radiotracers has led to major break-troughs in the pathophysiology and therapy of movement disorders and schizophrenic-like psychoses. This book is the first to collect, in a single volume, state-of-the-art contributions to the various aspects of this research. Its contents address methodological issues related to the design, labelling, quantitative imaging and compartmental modeli-sation of radioligands of the post-synaptic, pre-synaptic and enzyme sites of the dopamine system and to their use in clinical research in the fields of Parkinson's disease as well as other movement disorders, psychoses and neuroleptic receptor occupancy. The chapters were written by leading European scientists in the field of PET, gathered together in Caen (France, November 1990) under the aegis of the EEC Concerted Action on PET Investigations of Cellular Regeneration and Degeneration. This book provides a current and comprehensive overview on PET studies of the brain dopamine system which should aid and interest neurologists , psychiatrists, pharmacologists and medical imaging scientists. (author). refs.; figs.; tabs.

  20. A discrete dopaminergic projection from the incertohypothalamic A13 cell group to the dorsolateral periaqueductal gray in rat

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    Fany eMessanvi

    2013-12-01

    Full Text Available Several findings have indicated an involvement of dopamine in panic and defensive behaviors. The dorsolateral column of the periaqueductal gray (dlPAG is crucially involved in the expression of panic attacks in humans and defensive behaviors, also referred to as panic-like behaviors, in animals. Although the dlPAG is known to receive a specific innervation of dopaminergic fibers and abundantly expresses dopamine receptors, the origin of this dopaminergic input is largely unknown. This study aimed at mapping the dopaminergic projections to the dlPAG in order to provide further insight into the panic-like related behavior circuitry of the dlPAG. For this purpose, the retrograde tracer cholera toxin subunit b (CTb was injected into the dlPAG of male Wistar rats and double immunofluorescence for CTb and tyrosine hydroxylase (TH, the rate-limiting enzyme in the synthesis of dopamine, was performed. Neurons labeled for both CTb and TH were counted in different dopaminergic cell groups. The findings indicate that the dopaminergic nerve terminals present in the dlPAG originate from multiple dopamine-containing cell groups in the hypothalamus and mesencephalon. Interestingly, the A13 cell group is the main source of dopaminergic afferents to the dlPAG and contains at least 45% of the total number of CTb/TH-positive neurons. Anterograde tracing with biotinylated dextran amine (BDA combined with double immunofluorescence for BDA and TH confirmed the projections from the A13 cell group to the dlPAG. The remainder of the dopamine-positive terminals present in the dlPAG was found to originate from the extended A10 cell group and the A11 group. The A13 cell group is known to send dopaminergic efferents to several other brain regions implicated in defensive behavior, including the central amygdala and ventromedial hypothalamus. Therefore, although direct behavioral evidence is lacking, our finding that the A13 cell group is also the main source of dopaminergic

  1. Improvement of Brain Reward Abnormalities by Antipsychotic Monotherapy in Schizophrenia

    DEFF Research Database (Denmark)

    Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne

    2012-01-01

    CONTEXT Schizophrenic symptoms are linked to a dysfunction of dopamine neurotransmission and the brain reward system. However, it remains unclear whether antipsychotic treatment, which blocks dopamine transmission, improves, alters, or even worsens the reward-related abnormalities. OBJECTIVE....... Antipsychotic treatment tends to normalize the response of the reward system; this was especially seen in the patients with the most pronounced treatment effect on the positive symptoms. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01154829....... To investigate changes in reward-related brain activations in schizophrenia before and after antipsychotic monotherapy with a dopamine D2/D3 antagonist. DESIGN Longitudinal cohort study. SETTING Psychiatric inpatients and outpatients in the Capital Region of Denmark. PARTICIPANTS Twenty-three antipsychotic...

  2. Individual differences in anticipatory activity to food rewards predict cue-induced appetitive 50-kHz calls in rats.

    Science.gov (United States)

    Brenes, Juan C; Schwarting, Rainer K W

    2015-10-01

    Reward-related stimuli come to acquire incentive salience through Pavlovian learning and become capable of controlling reward-oriented behaviors. Here, we examined individual differences in anticipatory activity elicited by reward-related cues as indicative of how animals attribute incentive salience to otherwise neutral stimuli. Since adult rats can signal incentive motivation states through ultrasonic vocalizations (USVs) at around 50-kHz, such calls were recorded in food-deprived rats trained to associate cues with food rewards, which were subsequently devalued by satiation.We found that the extent to which animals developed conditioned anticipatory activity to food cues while food deprived determined the level of cue-induced appetitive USVs while sated. Re-exposure to reward cues after a free-testing period reinstated USVs, invigorated reward seeking and consumption, and again, increases in calling occurred only in animals with high levels of cue-induced anticipatory activity. Reward-experienced rats systemically challenged with the catecholamine agonist amphetamine or with the dopamine receptor antagonist flupenthixol showed attenuated responses to these drugs, especially for USVs and in subjects with high levels of cue-induced anticipatory activity. Our results suggest that individuals prone to attribute incentive salience to reward cues showed heightened reward-induced USVs which were reliably expressed over time and persisted despite physiological needs being fulfilled. Also, prone subjects seemed to undergo particular adaptations in their dopaminergic system related with incentive learning. Our findings may have translational relevance in preclinical research modeling compulsive disorders, which may be due to excessive attribution of incentive salience to reward cues, such as overeating, pathological gambling, and drug addiction.

  3. Monetary reward magnitude effects on behavior and brain function during goal-directed behavior.

    Science.gov (United States)

    Rosell-Negre, P; Bustamante, J C; Fuentes-Claramonte, P; Costumero, V; Benabarre, S; Barrós-Loscertales, A

    2017-08-01

    Reward may modulate the cognitive processes required for goal achievement, while individual differences in personality may affect reward modulation. Our aim was to test how different monetary reward magnitudes modulate brain activation and performance during goal-directed behavior, and whether individual differences in reward sensitivity affect this modulation. For this purpose, we scanned 37 subjects with a parametric design in which we varied the magnitude of monetary rewards (€0, €0.01, €0.5, €1 or €1.5) in a blocked fashion while participants performed an interference counting-Stroop condition. The results showed that the brain activity of left dorsolateral prefrontal cortex (DLPFC) and the striatum were modulated by increasing and decreasing reward magnitudes, respectively. Behavioral performance improved as the magnitude of monetary reward increased while comparing the non reward (€0) condition to any other reward condition, or the lower €0.01 to any other reward condition, and this improvement was related with individual differences in reward sensitivity. In conclusion, the locus of influence of monetary incentives overlaps the activity of the regions commonly involved in cognitive control.

  4. Employee Reward Systems in Organizations

    Directory of Open Access Journals (Sweden)

    Došenović Dragana

    2016-06-01

    Full Text Available Employee rewarding is one of the activities of human resource management concerning the management of money, goods and services that employees receive from their employer in exchange for their work. Given that a properly designed reward system is one of the conditions for a stable business, successful performance of work activities and the achievement of set objectives in each organization, the basic theme of this paper is the employee reward system, with a special focus on different elements of it. The purpose of this paper is to describe the role and significance of the observed system and to draw attention to its role in employee’s motivation.

  5. A common neural code for social and monetary rewards in the human striatum.

    Science.gov (United States)

    Wake, Stephanie J; Izuma, Keise

    2017-10-01

    Although managing social information and decision making on the basis of reward is critical for survival, it remains uncertain whether differing reward type is processed in a uniform manner. Previously, we demonstrated that monetary reward and the social reward of good reputation activated the same striatal regions including the caudate nucleus and putamen. However, it remains unclear whether overlapping activations reflect activities of identical neuronal populations or two overlapping but functionally independent neuronal populations. Here, we re-analyzed the original data and addressed this question using multivariate-pattern-analysis and found evidence that in the left caudate nucleus and bilateral nucleus accumbens, social vs monetary reward were represented similarly. The findings suggest that social and monetary rewards are processed by the same population of neurons within these regions of the striatum. Additional findings demonstrated similar neural patterns when participants experience high social reward compared to viewing others receiving low social reward (potentially inducing schadenfreude). This is possibly an early indication that the same population of neurons may be responsible for processing two different types of social reward (good reputation and schadenfreude). These findings provide a supplementary perspective to previous research, helping to further elucidate the mechanisms behind social vs non-social reward processing. © The Author (2017). Published by Oxford University Press.

  6. Physiological characterisation of human iPS-derived dopaminergic neurons.

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    Elizabeth M Hartfield

    Full Text Available Human induced pluripotent stem cells (hiPSCs offer the potential to study otherwise inaccessible cell types. Critical to this is the directed differentiation of hiPSCs into functional cell lineages. This is of particular relevance to research into neurological disease, such as Parkinson's disease (PD, in which midbrain dopaminergic neurons degenerate during disease progression but are unobtainable until post-mortem. Here we report a detailed study into the physiological maturation over time of human dopaminergic neurons in vitro. We first generated and differentiated hiPSC lines into midbrain dopaminergic neurons and performed a comprehensive characterisation to confirm dopaminergic functionality by demonstrating dopamine synthesis, release, and re-uptake. The neuronal cultures include cells positive for both tyrosine hydroxylase (TH and G protein-activated inward rectifier potassium channel 2 (Kir3.2, henceforth referred to as GIRK2, representative of the A9 population of substantia nigra pars compacta (SNc neurons vulnerable in PD. We observed for the first time the maturation of the slow autonomous pace-making (<10 Hz and spontaneous synaptic activity typical of mature SNc dopaminergic neurons using a combination of calcium imaging and electrophysiology. hiPSC-derived neurons exhibited inositol tri-phosphate (IP3 receptor-dependent release of intracellular calcium from the endoplasmic reticulum in neuronal processes as calcium waves propagating from apical and distal dendrites, and in the soma. Finally, neurons were susceptible to the dopamine neuron-specific toxin 1-methyl-4-phenylpyridinium (MPP+ which reduced mitochondrial membrane potential and altered mitochondrial morphology. Mature hiPSC-derived dopaminergic neurons provide a neurophysiologically-defined model of previously inaccessible vulnerable SNc dopaminergic neurons to bridge the gap between clinical PD and animal models.

  7. Flavor vs Energy Sensing in Brain Reward Circuits

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    Ivan E De Araujo

    2014-07-01

    much lesser role in inflexible behavioral actions, [5]. Thus, our findings suggest that sugar metabolism is a critical signal involved in the formation of behavioral habits linked to sugar overconsumption. The observations above bring about the problem of which physiological signaling pathways may link peripheral glucose sensors to dopaminergic neurons. Our more recent experiments indicate that glucose infusions into the portal vein are sufficient to induce robust dopamine release into dorsal striatum. This suggests that hepatoportal glucose sensors, known to regulate a number of physiological functions including enhancement of glucose utilization [6], may directly influence dopaminergic activity via the modulation of glucose utilization rates. It is also of note that neither glucose-induced flavor preferences [7] nor portal glucose-induced Fos activity in forebrain [8] seem to depend on vagal afferents; this brings to light a potentially critical role for spinal afferents innervating the hepatoportal system in linking peripheral glucose sensing to brain reward circuits [8]. These findings obviously do not rule out a potential role for brain glucosensing in linking glucose ingestion to dopaminergic activity: Early studies show that hindbrain catecholamine neurons detect glucose deficits [9] and may influence dopamine cells directly. Potentially important may be the activity of KATP ion channels expressed on neurons sending afferents to midbrain dopamine cells [10], not to mention the possibility that Substantia nigra compacta cells may sense glucose directly [11]. Finally, it is intriguing that sugar metabolism seems to control nutrient reinforcement in invertebrate species including Drosophila, since tasteless mutant flies were shown to develop preferences for metabolizable sugars but not for their non-metabolizable analogues (Burke & Waddell 2011; Dus et al. 2011. It thus appears that the metabolic control of sugar reward is a highly conserved mechanism whose

  8. The neurobiology of pleasure, reward processes, addiction and their health implications.

    Science.gov (United States)

    Esch, Tobias; Stefano, George B

    2004-08-01

    Modern science begins to understand pleasure as a potential component of salutogenesis. Thereby, pleasure is described as a state or feeling of happiness and satisfaction resulting from an experience that one enjoys. We examine the neurobiological factors underlying reward processes and pleasure phenomena. Further, health implications related to pleasurable activities are analyzed. With regard to possible negative effects of pleasure, we focus on addiction and motivational toxicity. Pleasure can serve cognition, productivity and health, but simultaneously promotes addiction and other negative behaviors, i.e., motivational toxicity. It is a complex neurobiological phenomenon, relying on reward circuitry or limbic activity. These processes involve dopaminergic signaling. Moreover, endorphin and endogenous morphinergic mechanisms may play a role. Natural rewarding activities are necessary for survival and appetitive motivation, usually governing beneficial biological behaviors like eating, sex and reproduction. Social contacts can further facilitate the positive effects exerted by pleasurable experiences. However, artificial stimulants can be detrimental, since flexibility and normal control of behavior are deteriorated. Additionally, addictive drugs are capable of directly acting on reward pathways. Thus, the concrete outcome of pleasant experiences may be a question of dose. Moderate pleasurable experiences are able to enhance biological flexibility and health. Hence, pleasure can be a resistance resource or may serve salutogenesis. Natural rewards are mediated by sensory organ stimulation, thereby exhibiting a potential association with complementary medical approaches. Trust and belief can be part of a self-healing potential connected with rewarding stimuli. Further, the placebo response physiologically resembles pleasure phenomena, since both involve brain's reward circuitry stimulation and subjective feelings of well-being. Pleasurable activities can stimulate

  9. Random reward priming is task-contingent

    DEFF Research Database (Denmark)

    Ásgeirsson, Árni Gunnar; Kristjánsson, Árni

    2014-01-01

    Consistent financial reward of particular features influences the allocation of visual attention in many ways. More surprising are 1-trial reward priming effects on attention where reward schedules are random and reward on one trial influences attentional allocation on the next. Those findings...

  10. A Neural Correlate of Predicted and Actual Reward-Value Information in Monkey Pedunculopontine Tegmental and Dorsal Raphe Nucleus during Saccade Tasks

    Science.gov (United States)

    Okada, Ken-ichi; Nakamura, Kae; Kobayashi, Yasushi

    2011-01-01

    Dopamine, acetylcholine, and serotonin, the main modulators of the central nervous system, have been proposed to play important roles in the execution of movement, control of several forms of attentional behavior, and reinforcement learning. While the response pattern of midbrain dopaminergic neurons and its specific role in reinforcement learning have been revealed, the role of the other neuromodulators remains rather elusive. Here, we review our recent studies using extracellular recording from neurons in the pedunculopontine tegmental nucleus, where many cholinergic neurons exist, and the dorsal raphe nucleus, where many serotonergic neurons exist, while monkeys performed eye movement tasks to obtain different reward values. The firing patterns of these neurons are often tonic throughout the task period, while dopaminergic neurons exhibited a phasic activity pattern to the task event. The different modulation patterns, together with the activity of dopaminergic neurons, reveal dynamic information processing between these different neuromodulator systems. PMID:22013541

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

    Science.gov (United States)

    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

  12. Premotor and Motor Cortices Encode Reward.

    Directory of Open Access Journals (Sweden)

    Pavan Ramkumar

    Full Text Available Rewards associated with actions are critical for motivation and learning about the consequences of one's actions on the world. The motor cortices are involved in planning and executing movements, but it is unclear whether they encode reward over and above limb kinematics and dynamics. Here, we report a categorical reward signal in dorsal premotor (PMd and primary motor (M1 neurons that corresponds to an increase in firing rates when a trial was not rewarded regardless of whether or not a reward was expected. We show that this signal is unrelated to error magnitude, reward prediction error, or other task confounds such as reward consumption, return reach plan, or kinematic differences across rewarded and unrewarded trials. The availability of reward information in motor cortex is crucial for theories of reward-based learning and motivational influences on actions.

  13. CRF1 receptor-deficiency increases cocaine reward.

    Science.gov (United States)

    Contarino, Angelo; Kitchener, Pierre; Vallée, Monique; Papaleo, Francesco; Piazza, Pier-Vincenzo

    2017-05-01

    Stimulant drugs produce reward but also activate stress-responsive systems. The corticotropin-releasing factor (CRF) and the related hypothalamus-pituitary-adrenal (HPA) axis stress-responsive systems are activated by stimulant drugs. However, their role in stimulant drug-induced reward remains poorly understood. Herein, we report that CRF 1 receptor-deficient (CRF 1 -/-), but not wild-type, mice show conditioned place preference (CPP) responses to a relatively low cocaine dose (5 mg/kg, i.p.). Conversely, wild-type, but not CRF 1 -/-, mice display CPP responses to a relatively high cocaine dose (20 mg/kg, i.p.), indicating that CRF 1 receptor-deficiency alters the rewarding effects of cocaine. Acute pharmacological antagonism of the CRF 1 receptor by antalarmin also eliminates cocaine reward. Nevertheless, CRF 1 -/- mice display higher stereotypy responses to cocaine than wild-type mice. Despite the very low plasma corticosterone concentration, CRF 1 -/- mice show higher nuclear glucocorticoid receptor (GR) levels in the brain region of the hippocampus than wild-type mice. Full rescue of wild-type-like corticosterone and GR circadian rhythm and level in CRF 1 -/- mice by exogenous corticosterone does not affect CRF 1 receptor-dependent cocaine reward but induces stereotypy responses to cocaine. These results indicate a critical role for the CRF 1 receptor in cocaine reward, independently of the closely related HPA axis activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Marijuana and cannabinoid regulation of brain reward circuits.

    Science.gov (United States)

    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.

  15. Why the carrot is more effective than the stick: different dynamics of punishment memory and reward memory and its possible biological basis.

    Science.gov (United States)

    Nakatani, Yoshihiro; Matsumoto, Yukihisa; Mori, Yasuhiro; Hirashima, Daisuke; Nishino, Hiroshi; Arikawa, Kentaro; Mizunami, Makoto

    2009-10-01

    One of the most extensively debated topics in educational psychology is whether punishment or reward is more effective for producing short-term and long-term behavioral changes, and it has been proposed that the effect of punishment is less durable than the effect of reward. However, no conclusive evidence to support this proposal has been obtained in any animals. We recently found that punishment memory decayed much faster than reward memory in olfactory learning and visual pattern learning in crickets. We also found that neurotransmitters conveying punishment and reward signals differ in crickets: dopaminergic and octopaminergic neurons play critical roles in conveying punishment and reward signals, respectively. In this study, we investigated whether these features are general features of cricket learning or are specific to olfactory and visual pattern learning. We found that crickets have the capability of color learning and that their color learning has the same features. Based on our findings in crickets and those reported in other species of insects, we conclude that these two features are conserved in many forms of insect learning. In mammals, aminergic neurons are known to convey reward and punishment signals in learning of a variety of sensory stimuli. We propose that the faster decay of punishment memory than reward memory observed in insects and humans reflects different cellular and biochemical processes after activation of receptors for amines conveying punishment and reward signals. The possible adaptive significance of relatively limited durability of punishment memory is proposed.

  16. Sensitivity and bias in decision-making under risk: evaluating the perception of reward, its probability and value.

    Directory of Open Access Journals (Sweden)

    Madeleine E Sharp

    Full Text Available BACKGROUND: There are few clinical tools that assess decision-making under risk. Tests that characterize sensitivity and bias in decisions between prospects varying in magnitude and probability of gain may provide insights in conditions with anomalous reward-related behaviour. OBJECTIVE: We designed a simple test of how subjects integrate information about the magnitude and the probability of reward, which can determine discriminative thresholds and choice bias in decisions under risk. DESIGN/METHODS: Twenty subjects were required to choose between two explicitly described prospects, one with higher probability but lower magnitude of reward than the other, with the difference in expected value between the two prospects varying from 3 to 23%. RESULTS: Subjects showed a mean threshold sensitivity of 43% difference in expected value. Regarding choice bias, there was a 'risk premium' of 38%, indicating a tendency to choose higher probability over higher reward. An analysis using prospect theory showed that this risk premium is the predicted outcome of hypothesized non-linearities in the subjective perception of reward value and probability. CONCLUSIONS: This simple test provides a robust measure of discriminative value thresholds and biases in decisions under risk. Prospect theory can also make predictions about decisions when subjective perception of reward or probability is anomalous, as may occur in populations with dopaminergic or striatal dysfunction, such as Parkinson's disease and schizophrenia.

  17. Sensitivity and Bias in Decision-Making under Risk: Evaluating the Perception of Reward, Its Probability and Value

    Science.gov (United States)

    Sharp, Madeleine E.; Viswanathan, Jayalakshmi; Lanyon, Linda J.; Barton, Jason J. S.

    2012-01-01

    Background There are few clinical tools that assess decision-making under risk. Tests that characterize sensitivity and bias in decisions between prospects varying in magnitude and probability of gain may provide insights in conditions with anomalous reward-related behaviour. Objective We designed a simple test of how subjects integrate information about the magnitude and the probability of reward, which can determine discriminative thresholds and choice bias in decisions under risk. Design/Methods Twenty subjects were required to choose between two explicitly described prospects, one with higher probability but lower magnitude of reward than the other, with the difference in expected value between the two prospects varying from 3 to 23%. Results Subjects showed a mean threshold sensitivity of 43% difference in expected value. Regarding choice bias, there was a ‘risk premium’ of 38%, indicating a tendency to choose higher probability over higher reward. An analysis using prospect theory showed that this risk premium is the predicted outcome of hypothesized non-linearities in the subjective perception of reward value and probability. Conclusions This simple test provides a robust measure of discriminative value thresholds and biases in decisions under risk. Prospect theory can also make predictions about decisions when subjective perception of reward or probability is anomalous, as may occur in populations with dopaminergic or striatal dysfunction, such as Parkinson's disease and schizophrenia. PMID:22493669

  18. The influence of motherhood on neural systems for reward processing in low income, minority, young women.

    Science.gov (United States)

    Moses-Kolko, Eydie L; Forbes, Erika E; Stepp, Stephanie; Fraser, David; Keenan, Kate E; Guyer, Amanda E; Chase, Henry W; Phillips, Mary L; Zevallos, Carlos R; Guo, Chaohui; Hipwell, Alison E

    2016-04-01

    Given the association between maternal caregiving behavior and heightened neural reward activity in experimental animal studies, the present study examined whether motherhood in humans positively modulates reward-processing neural circuits, even among mothers exposed to various life stressors and depression. Subjects were 77 first-time mothers and 126 nulliparous young women from the Pittsburgh Girls Study, a longitudinal study beginning in childhood. Subjects underwent a monetary reward task during functional magnetic resonance imaging in addition to assessment of current depressive symptoms. Life stress was measured by averaging data collected between ages 8-15 years. Using a region-of-interest approach, we conducted hierarchical regression to examine the relationship of psychosocial factors (life stress and current depression) and motherhood with extracted ventral striatal (VST) response to reward anticipation. Whole-brain regression analyses were performed post-hoc to explore non-striatal regions associated with reward anticipation in mothers vs nulliparous women. Anticipation of monetary reward was associated with increased neural activity in expected regions including caudate, orbitofrontal, occipital, superior and middle frontal cortices. There was no main effect of motherhood nor motherhood-by-psychosocial factor interaction effect on VST response during reward anticipation. Depressive symptoms were associated with increased VST activity across the entire sample. In exploratory whole brain analysis, motherhood was associated with increased somatosensory cortex activity to reward (FWE cluster forming threshold preward anticipation-related VST activity nor does motherhood modulate the impact of depression or life stress on VST activity. Future studies are needed to evaluate whether earlier postpartum assessment of reward function, inclusion of mothers with more severe depressive symptoms, and use of reward tasks specific for social reward might reveal an

  19. 3-aminopyridazine derivatives with atypical antidepressant, serotonergic, and dopaminergic activities.

    Science.gov (United States)

    Wermuth, C G; Schlewer, G; Bourguignon, J J; Maghioros, G; Bouchet, M J; Moire, C; Kan, J P; Worms, P; Biziere, K

    1989-03-01

    Minaprine [3-[(beta-morpholinoethyl)amino]-4-methyl-6-phenylpyridazine dihydrochloride] is active in most animal models of depression and exhibits in vivo a dual dopaminomimetic and serotoninomimetic activity profile. In an attempt to dissociate these two effects and to characterize the responsible structural requirements, a series of 47 diversely substituted analogues of minaprine were synthesized and tested for their potential antidepressant, serotonergic, and dopaminergic activities. The structure-activity relationships show that dopaminergic and serotonergic activities can be dissociated. Serotonergic activity appears to be correlated mainly with the substituent in the 4-position of the pyridazine ring whereas the dopaminergic activity appears to be dependent on the presence, or in the formation, of a para-hydroxylated aryl ring in the 6-position of the pyridazine ring.

  20. Increased dopaminergic signaling impairs aversive olfactory memory retention in Drosophila.

    Science.gov (United States)

    Zhang, Shixing; Yin, Yan; Lu, Huimin; Guo, Aike

    2008-05-23

    Dopamine is necessary for the aversive olfactory associative memory formation in Drosophila, but its effect on other stages of memory is not known. Herein, we studied the effect of enhanced dopaminergic signaling on aversive olfactory memory retention in flies. We used l-3,4-dihydroxyphenylalanine (l-DOPA) to elevate dopamine levels: l-DOPA-treated flies exhibited a normal learning performance, but a decrease in 1-h memory. Dopamine transporter (DAT) mutant flies or flies treated with the DAT inhibitor desipramine exhibited poor memory retention. Flies subjected to heat stress after training exhibited a decrease in memory. Memory was restored by blocking dopaminergic neuronal output during heat stress, suggesting that dopamine is involved in heat stress-induced memory impairment in flies. Taken together, our findings suggest that increased dopaminergic signaling impairs aversive olfactory memory retention in flies.

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

    Science.gov (United States)

    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.

  2. Frontal theta and beta synchronizations for monetary reward increase visual working memory capacity.

    Science.gov (United States)

    Kawasaki, Masahiro; Yamaguchi, Yoko

    2013-06-01

    Visual working memory (VWM) capacity is affected by motivational influences; however, little is known about how reward-related brain activities facilitate the VWM systems. To investigate the dynamic relationship between VWM- and reward-related brain activities, we conducted time-frequency analyses using electroencephalograph (EEG) data obtained during a monetary-incentive delayed-response task that required participants to memorize the position of colored disks. In case of a correct answer, participants received a monetary reward (0, 10 or 50 Japanese yen) announced at the beginning of each trial. Behavioral results showed that VWM capacity under high-reward condition significantly increased compared with that under low- or no-reward condition. EEG results showed that frontal theta (6 Hz) amplitudes enhanced during delay periods and positively correlated with VWM capacity, indicating involvement of theta local synchronizations in VWM. Moreover, frontal beta activities (24 Hz) were identified as reward-related activities, because delay-period amplitudes correlated with increases in VWM capacity between high-reward and no-reward conditions. Interestingly, cross-frequency couplings between frontal theta and beta phases were observed only under high-reward conditions. These findings suggest that the functional dynamic linking between VWM-related theta and reward-related beta activities on the frontal regions plays an integral role in facilitating increases in VWM capacity.

  3. Assessment of Dopaminergic Homeostasis in Mice by Use of High-performance Liquid Chromatography Analysis and Synaptosomal Dopamine Uptake

    DEFF Research Database (Denmark)

    Jensen, Kathrine L; Runegaard, Annika H; Weikop, Pia

    2017-01-01

    Dopamine (DA) is a modulatory neurotransmitter controlling motor activity, reward processes and cognitive function. Impairment of dopaminergic (DAergic) neurotransmission is strongly associated with several central nervous system-associated diseases such as Parkinson's disease, attention...... therapeutic targets for these diseases. Here, we present two useful experimental protocols that when combined provide a functional read-out of the DAergic system in mice. Biochemical and functional parameters on DA homeostasis are obtained through assessment of DA levels and dopamine transporter (DAT......) functionality(5). When investigating the DA system, the ability to reliably measure endogenous levels of DA from adult brain is essential. Therefore, we present how to perform high-performance liquid chromatography (HPLC) on brain tissue from mice to determine levels of DA. We perform the experiment on tissue...

  4. Ghrelin receptor antagonism of morphine-induced conditioned place preference and behavioral and accumbens dopaminergic sensitization in rats.

    Science.gov (United States)

    Jerabek, Pavel; Havlickova, Tereza; Puskina, Nina; Charalambous, Chrysostomos; Lapka, Marek; Kacer, Petr; Sustkova-Fiserova, Magdalena

    2017-11-01

    An increasing number of studies over the past few years have demonstrated ghrelin's role in alcohol, cocaine and nicotine abuse. However, the role of ghrelin in opioid effects has rarely been examined. Recently we substantiated in rats that ghrelin growth hormone secretagogue receptors (GHS-R1A) appear to be involved in acute opioid-induced changes in the mesolimbic dopaminergic system associated with the reward processing. The aim of the present study was to ascertain whether a ghrelin antagonist (JMV2959) was able to inhibit morphine-induced biased conditioned place preference and challenge-morphine-induced accumbens dopaminergic sensitization and behavioral sensitization in adult male rats. In the place preference model, the rats were conditioned for 8 days with morphine (10 mg/kg s.c.). On the experimental day, JMV2959 (3 and 6 mg/kg i.p.) or saline were administered before testing. We used in vivo microdialysis to determine changes of dopamine and its metabolites in the nucleus accumbens in rats following challenge-morphine dose (5 mg/kg s.c.) with or without JMV2959 (3 and 6 mg/kg i.p.) pretreatment, administered on the 12th day of spontaneous abstinence from morphine repeated treatment (5 days, 10-40 mg/kg). Induced behavioral changes were simultaneously monitored. Pretreatment with JMV2959 significantly and dose dependently reduced the morphine-induced conditioned place preference and significantly and dose dependently reduced the challenge-morphine-induced dopaminergic sensitization and affected concentration of by-products associated with dopamine metabolism in the nucleus accumbens. JMV2959 pretreatment also significantly reduced challenge-morphine-induced behavioral sensitization. Our present data suggest that GHS-R1A antagonists deserve to be further investigated as a novel treatment strategy for opioid addiction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. The anorexic agents, sibutramine and fenfluramine, depress GABAB-induced inhibitory postsynaptic potentials in rat mesencephalic dopaminergic cells

    Science.gov (United States)

    Ledonne, Ada; Sebastianelli, Luca; Federici, Mauro; Bernardi, Giorgio; Mercuri, Nicola Biagio

    2009-01-01

    Background and purpose Nutrition is the result of a complex interaction among environmental, homeostatic and reward-related processes. Accumulating evidence supports key roles for the dopaminergic neurons of the ventral midbrain in regulating feeding behaviour. For this reason, in the present study, we have investigated the electrophysiological effects of two centrally acting anorexic agents, fenfluramine and sibutramine, on these cells. Experimental approach Rat midbrain slices were used to make intracellular recordings from dopaminergic neurons of the substantia nigra and the ventral tegmental area. Gamma-aminobutyric acid (GABA)-mediated synaptic transmission was assessed from the inhibitory postsynaptic potentials (IPSPs) mediated by GABAA and GABAB receptors. Key results Fenfluramine and sibutramine reduced, concentration-dependently, the GABAB IPSPs, without affecting the GABAA-mediated potentials. This effect is presynaptic, as postsynaptic membrane responses induced by application of a GABAB receptor agonist, baclofen, were not affected by the two drugs. Furthermore, the selective 5-hydroxytriptamine 1B (5-HT1B) receptor antagonist, SB216641, blocked the reduction of GABAB IPSPs caused by fenfluramine and sibutramine, indicating that the receptor mediating this effect is 5-HT1B. Conclusions and implications Two anorexic agents, fenfluramine and sibutramine, induced the activation of 5-HT1B receptors located on presynaptic GABAergic terminals, thus reducing the release of GABA. This action can alter the strength of synaptic afferents that modify the activity of dopaminergic neurons, inducing neuronal excitation. Our results reveal an additional mechanism of action for fenfluramine and sibutramine that might contribute to reducing food intake, by influencing the pleasurable and motor aspects of feeding behaviour. PMID:19298257

  6. Renin angiotensin system and gender differences in dopaminergic degeneration

    Directory of Open Access Journals (Sweden)

    Rodriguez-Perez Ana I

    2011-08-01

    Full Text Available Abstract Background There are sex differences in dopaminergic degeneration. Men are approximately two times as likely as premenopausal women of the same age to develop Parkinson's disease (PD. It has been shown that the local renin angiotensin system (RAS plays a prominent role in sex differences in the development of chronic renal and cardiovascular diseases, and there is a local RAS in the substantia nigra and dopaminergic cell loss is enhanced by angiotensin via type 1 (AT1 receptors. Results In the present study, we observed that intrastriatal injection of 6-hydroxydopamine induced a marked loss of dopaminergic neurons in the substantia nigra of male rats, which was significantly higher than the loss induced in ovariectomized female rats given estrogen implants (i.e. rats with estrogen. However, the loss of dopaminergic neurons was significantly lower in male rats treated with the AT1 antagonist candesartan, and similar to that observed in female rats with estrogen. The involvement of the RAS in gender differences in dopaminergic degeneration was confirmed with AT1a-null mice lesioned with the dopaminergic neurotoxin MPTP. Significantly higher expression of AT1 receptors, angiotensin converting enzyme activity, and NADPH-oxidase complex activity, and much lower levels of AT2 receptors were observed in male rats than in female rats with estrogen. Conclusions The results suggest that brain RAS plays a major role in the increased risk of developing PD in men, and that manipulation of brain RAS may be an efficient approach for neuroprotective treatment of PD in men, without the feminizing effects of estrogen.

  7. Dopaminergic profile of new heterocyclic N-phenylpiperazine derivatives

    Directory of Open Access Journals (Sweden)

    Neves G.

    2003-01-01

    Full Text Available Dopamine constitutes about 80% of the content of central catecholamines and has a crucial role in the etiology of several neuropsychiatric disorders, including Parkinson's disease, depression and schizophrenia. Several dopaminergic drugs are used to treat these pathologies, but many problems are attributed to these therapies. Within this context, the search for new more efficient dopaminergic agents with less adverse effects represents a vast research field. The aim of the present study was to report the structural design of two N-phenylpiperazine derivatives, compound 4: 1-[1-(4-chlorophenyl-1H-4-pyrazolylmethyl]-4-phenylhexahydropyrazine and compound 5: 1-[1-(4-chlorophenyl-1H-1,2,3-triazol-4-ylmethyl]-4-phenylhexahydropyrazine, planned to be dopamine ligands, and their dopaminergic action profile. The two compounds were assayed (dose range of 15-40 mg/kg in three experimental models: 1 blockade of amphetamine (30 mg/kg, ip-induced stereotypy in rats; 2 the catalepsy test in mice, and 3 apomorphine (1 mg/kg, ip-induced hypothermia in mice. Both derivatives induced cataleptic behavior (40 mg/kg, ip and a hypothermic response (30 mg/kg, ip which was not prevented by haloperidol (0.5 mg/kg, ip. Compound 5 (30 mg/kg, ip also presented a synergistic hypothermic effect with apomorphine (1 mg/kg, ip. Only compound 4 (30 mg/kg, ip significantly blocked the amphetamine-induced stereotypy in rats. The N-phenylpiperazine derivatives 4 and 5 seem to have a peculiar profile of action on dopaminergic functions. On the basis of the results of catalepsy and amphetamine-induced stereotypy, the compounds demonstrated an inhibitory effect on dopaminergic behaviors. However, their hypothermic effect is compatible with the stimulation of dopaminergic function which seems not to be mediated by D2/D3 receptors.

  8. Remembering with Gains and Losses: Effects of Monetary Reward and Punishment on Successful Encoding Activation of Source Memories

    Science.gov (United States)

    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

  9. Remembering with gains and losses: effects of monetary reward and punishment on successful encoding activation of source memories.

    Science.gov (United States)

    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.

  10. Lesions of the dopaminergic innervation of the nucleus accumbens medial shell delay the generation of preference for sucrose, but not of sexual pheromones.

    Science.gov (United States)

    Martínez-Hernández, José; Lanuza, Enrique; Martínez-García, Fernando

    2012-01-15

    Male sexual pheromones are rewarding stimuli for female mice, able to induce conditioned place preference. To test whether processing these natural reinforcing stimuli depends on the dopaminergic innervation of the nucleus accumbens, as for other natural rewards, we compare the effects of specific lesions of the dopaminergic innervation of the medial shell of the nucleus accumbens on two different appetitive behaviours, 'pheromone seeking' and sucrose preferential intake. Female mice, with no previous experience with either adult male chemical stimuli or with sucrose, received injections of 6-hydroxydopamine (or vehicle) in the medial shell of the accumbens. Then, we analyzed their preference for male soiled-bedding and their preferential intake of a sucrose solution, with particular emphasis on the dynamics of acquisition of both natural rewards. The results indicate that both lesioned and sham animals showed similar preference for male sexual pheromones, which was constant along the test (linear dynamics). In contrast, lesioned animals differed from sham operated mice in the dynamics of sucrose consumption in their first test of sucrose preference. Sham animals showed an initial sucrose preference followed by preference for water, which can be interpreted as sucrose neophobia. Lesioned animals showed no preference at the beginning of the test, and a delayed sucrose preference appeared followed by a delayed neophobia. The next day, during a second sucrose-preference test, both groups displayed comparable and sustained preferential sucrose intake. Therefore, dopamine in the medial shell of the nucleus accumbens has a different role on the reward of sexual pheromones and sucrose. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Effects of dopaminergic and subthalamic stimulation on musical performance.

    Science.gov (United States)

    van Vugt, Floris T; Schüpbach, Michael; Altenmüller, Eckart; Bardinet, Eric; Yelnik, Jérôme; Hälbig, Thomas D

    2013-05-01

    Although subthalamic-deep brain stimulation (STN-DBS) is an efficient treatment for Parkinson's disease (PD), its effects on fine motor functions are not clear. We present the case of a professional violinist with PD treated with STN-DBS. DBS improved musical articulation, intonation and emotional expression and worsened timing relative to a timekeeper (metronome). The same effects were found for dopaminergic treatment. These results suggest that STN-DBS, mimicking the effects of dopaminergic stimulation, improves fine-tuned motor behaviour whilst impairing timing precision.

  12. Brain metabolic correlates of dopaminergic degeneration in de novo idiopathic Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Berti, Valentina; Polito, Cristina; Vanzi, Eleonora; Cristofaro, Maria Teresa de; Pellicano, Giannantonio; Mungai, Francesco; Formiconi, Andreas Robert; Pupi, Alberto [University of Florence, Department of Clinical Pathophysiology, Florence (Italy); Ramat, Silvia; Marini, Paolo; Sorbi, Sandro [University of Florence, Department of Psychiatric and Neurological Sciences, Florence (Italy)

    2010-03-15

    The aim of the present study was to evaluate the reciprocal relationships between motor impairment, dopaminergic dysfunction, and cerebral metabolism (rCMRglc) in de novo Parkinson's disease (PD) patients. Twenty-six de novo untreated PD patients were scanned with {sup 123}I-FP-CIT SPECT and {sup 18}F-FDG PET. The dopaminergic impairment was measured with putaminal {sup 123}I-FP-CIT binding potential (BP), estimated with two different techniques: an iterative reconstruction algorithm (BP{sub OSEM}) and the least-squares (LS) method (BP{sub LS}). Statistical parametric mapping (SPM) multiple regression analyses were performed to determine the specific brain regions in which UPDRS III scores and putaminal BP values correlated with rCMRglc. The SPM results showed a negative correlation between UPDRS III and rCMRglc in premotor cortex, and a positive correlation between BP{sub OSEM} and rCMRglc in premotor and dorsolateral prefrontal cortex, not surviving at multiple comparison correction. Instead, there was a positive significant correlation between putaminal BP{sub LS} and rCMRglc in premotor, dorsolateral prefrontal, anterior prefrontal, and orbitofrontal cortex (p < 0.05, corrected for multiple comparison). Putaminal BP{sub LS} is an efficient parameter for exploring the correlations between PD severity and rCMRglc cortical changes. The correlation between dopaminergic degeneration and rCMRglc in several prefrontal regions likely represents the cortical functional correlate of the dysfunction in the motor basal ganglia-cortical circuit in PD. This finding suggests focusing on the metabolic course of these areas to follow PD progression and to analyze treatment effects. (orig.)

  13. Evolutionary advantages of adaptive rewarding

    International Nuclear Information System (INIS)

    Szolnoki, Attila; Perc, Matjaž

    2012-01-01

    Our well-being depends on both our personal success and the success of our society. The realization of this fact makes cooperation an essential trait. Experiments have shown that rewards can elevate our readiness to cooperate, but since giving a reward inevitably entails paying a cost for it, the emergence and stability of such behavior remains elusive. Here we show that allowing for the act of rewarding to self-organize in dependence on the success of cooperation creates several evolutionary advantages that instill new ways through which collaborative efforts are promoted. Ranging from indirect territorial battle to the spontaneous emergence and destruction of coexistence, phase diagrams and the underlying spatial patterns reveal fascinatingly rich social dynamics that explain why this costly behavior has evolved and persevered. Comparisons with adaptive punishment, however, uncover an Achilles heel of adaptive rewarding, coming from over-aggression, which in turn hinders optimal utilization of network reciprocity. This may explain why, despite its success, rewarding is not as firmly embedded into our societal organization as punishment. (paper)

  14. A novel dopamine transporter transgenic mouse line for identification and purification of midbrain dopaminergic neurons reveals midbrain heterogeneity

    DEFF Research Database (Denmark)

    Christiansen, Mia Apuschkin; Stilling, Sara; Rahbek-Clemmensen, Troels

    2015-01-01

    Midbrain dopaminergic (DAergic) neurons are a heterogeneous cell group, composed of functionally distinct cell populations projecting to the basal ganglia, prefrontal cortex and limbic system. Despite their functional significance, the midbrain population of DAergic neurons is sparse, constituting...... of the dopamine transporter (DAT) promoter was characterized. Confocal microscopy analysis of brain sections showed strong eGFP signal reporter in midbrain regions and striatal terminals that co-localized with the DAergic markers DAT and tyrosine hydroxylase (TH). Thorough quantification of co...

  15. Neural correlates of reward processing in adults with 22q11 deletion syndrome

    NARCIS (Netherlands)

    van Duin, Esther D. A.; Goossens, Liesbet; Hernaus, Dennis; da Silva Alves, Fabiana; Schmitz, Nicole; Schruers, Koen; van Amelsvoort, Therese

    2016-01-01

    Background: 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

  16. The Social Rewards of Engagement

    DEFF Research Database (Denmark)

    Robison, Joshua

    2017-01-01

    Political interest is a crucial precursor to political engagement, but little is known about how to stimulate greater interest. The article explores the role social motives have in generating interest. A laboratory experiment is used in which it is possible to manipulate beliefs about the social...... rewards of political engagement as well as external efficacy beliefs. Across two types of measures for political interest (self-reports and revealed preferences), connecting political engagement with social rewards led to substantial increases in political interest. Moreover, these effects were...... particularly strong among individuals with low levels of external efficacy. Ultimately, the data provide clear evidence that political interest can be positively stimulated with social rewards mobilisation techniques and that it is rooted in beliefs about the potential motives pursuable through politics...

  17. Dopaminergic expression of the Parkinsonian gene LRRK2-G2019S leads to non-autonomous visual neurodegeneration, accelerated by increased neural demands for energy

    Science.gov (United States)

    Hindle, Samantha; Afsari, Farinaz; Stark, Meg; Middleton, C. Adam; Evans, Gareth J.O.; Sweeney, Sean T.; Elliott, Christopher J.H.

    2013-01-01

    Parkinson's disease (PD) is associated with loss of dopaminergic signalling, and affects not just movement, but also vision. As both mammalian and fly visual systems contain dopaminergic neurons, we investigated the effect of LRRK2 mutations (the most common cause of inherited PD) on Drosophila electroretinograms (ERGs). We reveal progressive loss of photoreceptor function in flies expressing LRRK2-G2019S in dopaminergic neurons. The photoreceptors showed elevated autophagy, apoptosis and mitochondrial disorganization. Head sections confirmed extensive neurodegeneration throughout the visual system, including regions not directly innervated by dopaminergic neurons. Other PD-related mutations did not affect photoreceptor function, and no loss of vision was seen with kinase-dead transgenics. Manipulations of the level of Drosophila dLRRK suggest G2019S is acting as a gain-of-function, rather than dominant negative mutation. Increasing activity of the visual system, or of just the dopaminergic neurons, accelerated the G2019S-induced deterioration of vision. The fly visual system provides an excellent, tractable model of a non-autonomous deficit reminiscent of that seen in PD, and suggests that increased energy demand may contribute to the mechanism by which LRRK2-G2019S causes neurodegeneration. PMID:23396536

  18. Crosstalk between insulin-like growth factor-1 and angiotensin-II in dopaminergic neurons and glial cells: role in neuroinflammation and aging

    Science.gov (United States)

    Rodriguez-Perez, Ana I.; Borrajo, Ana; Diaz-Ruiz, Carmen; Garrido-Gil, Pablo; Labandeira-Garcia, Jose L.

    2016-01-01

    The local renin-angiotensin system (RAS) and insulin-like growth factor 1 (IGF-1) have been involved in longevity, neurodegeneration and aging-related dopaminergic degeneration. However, it is not known whether IGF-1 and angiotensin-II (AII) activate each other. In the present study, AII, via type 1 (AT1) receptors, exacerbated neuroinflammation and dopaminergic cell death. AII, via AT1 receptors, also increased the levels of IGF-1 and IGF-1 receptors in microglial cells. IGF-1 inhibited RAS activity in dopaminergic neurons and glial cells, and also inhibited the AII-induced increase in markers of the M1 microglial phenotype. Consistent with this, IGF-1 decreased dopaminergic neuron death induced by the neurotoxin MPP+ both in the presence and in the absence of glia. Intraventricular administration of AII to young rats induced a significant increase in IGF-1 expression in the nigral region. However, aged rats showed decreased levels of IGF-1 relative to young controls, even though RAS activity is known to be enhanced in aged animals. The study findings show that IGF-1 and the local RAS interact to inhibit or activate neuroinflammation (i.e. transition from the M1 to the M2 phenotype), oxidative stress and dopaminergic degeneration. The findings also show that this mechanism is impaired in aged animals. PMID:27167199

  19. Adrenal androgen secretion and dopaminergic activity in anorexia nervosa.

    Science.gov (United States)

    Devesa, J; Pérez-Fernández, R; Bokser, L; Gaudiero, G J; Lima, L; Casanueva, F F

    1988-01-01

    The aim of the present study was to investigate if the postulated deficient adrenal androgen secretion in Anorexia Nervosa (AN), could be associated with a status of sustained dopaminergic hyperactivity. The adrenal responses to ACTH and PRL response to dopaminergic receptor blockade were studied in seven patients with Anorexia Nervosa and seven regularly menstruating women. AN patients showed lower baseline DHEA-sulphate (DHEA-S), androstenedione (Adione) and prolactin (PRL) levels than controls. The response to ACTH revealed evidences of significantly decreased 17-20 desmolase activity in AN, with apparent predominance of glucocorticoid over androgenic pathways relative to controls. Because dopaminergic receptor blockade with Domperidone (DOM) showed intense dopaminergic hyperactivity in AN, we postulate that the adrenal regression seen in the disease is the consequence of a reduced zona reticularis as a consequence of the lack of trophic support by PRL and/or intermediate lobe proopiomelanocortin (IL-POMC). This is consistent with our previous results in pre-adrenarchal dogs and rabbits.

  20. Dopaminergic and clinical correlates of pathological gambling in Parkinson's disease

    DEFF Research Database (Denmark)

    Callesen, Mette Buhl; Hansen, K V; Gjedde, A

    2013-01-01

    Dopaminergic medication for motor symptoms in Parkinson's disease (PD) recently has been linked with impulse control disorders, including pathological gambling (PG), which affects up to 8% of patients. PG often is considered a behavioral addiction associated with disinhibition, risky decision-mak...... decision-making. Overall, the findings are consistent with the hypothesis of medication-related PG in PD and underscore the importance of taking clinical variables, such as age and personality, into account when patients with PD are medicated, to reduce the risk of PG.......Dopaminergic medication for motor symptoms in Parkinson's disease (PD) recently has been linked with impulse control disorders, including pathological gambling (PG), which affects up to 8% of patients. PG often is considered a behavioral addiction associated with disinhibition, risky decision-making......, and altered striatal dopaminergic neurotransmission. Using [(11)C]raclopride with positron emission tomography, we assessed dopaminergic neurotransmission during Iowa Gambling Task performance. Here we present data from a single patient with PD and concomitant PG. We noted a marked decrease in [(11)C...

  1. The dopaminergic system and aggression in laying hens

    Science.gov (United States)

    The dopaminergic system regulates aggression in humans and other mammals. To investigate if birds with genetic propensity for high and low aggressiveness may exhibit distinctly different aggressive mediation via dopamine (DA) D1 and D2 receptor pathways, two high aggressive (DXL and LGPS) and one lo...

  2. Pharmacological imaging as a tool to visualise dopaminergic neurotoxicity.

    Science.gov (United States)

    Schrantee, A; Reneman, L

    2014-09-01

    Dopamine abnormalities underlie a wide variety of psychopathologies, including ADHD and schizophrenia. A new imaging technique, pharmacological magnetic resonance imaging (phMRI), is a promising non-invasive technique to visualize the dopaminergic system in the brain. In this review we explore the clinical potential of phMRI in detecting dopamine dysfunction or neurotoxicity, assess its strengths and weaknesses and identify directions for future research. Preclinically, phMRI is able to detect severe dopaminergic abnormalities quite similar to conventional techniques such as PET and SPECT. phMRI benefits from its high spatial resolution and the possibility to visualize both local and downstream effects of dopaminergic neurotransmission. In addition, it allows for repeated measurements and assessments in vulnerable populations. The major challenge is the complex interpretation of phMRI results. Future studies in patients with dopaminergic abnormalities need to confirm the currently reviewed preclinical findings to validate the technique in a clinical setting. Eventually, based on the current review we expect that phMRI can be of use in a clinical setting involving vulnerable populations (such as children and adolescents) for diagnosis and monitoring treatment efficacy. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Dopaminergic medication affects choice bias in Parkinson's disease

    NARCIS (Netherlands)

    Nuland, A.J.M. van; Helmich, R.C.G.; Dirkx, M.F.M.; Zach, H.; Bloem, B.R.; Toni, I.; Cools, R.; Ouden, H.E.M. den

    2016-01-01

    Objective: Assess dopaminergic effects on choice bias in Parkinson's disease (PD). Background: Bradykinesia, rigidity and resting tremor are the core symptoms of PD, but many patients also suffer from cognitive dysfunction. For instance, PD patients have an increased tendency to learn from aversive

  4. Zic-Proteins Are Repressors of Dopaminergic Forebrain Fate in Mice and C. elegans.

    Science.gov (United States)

    Tiveron, Marie-Catherine; Beclin, Christophe; Murgan, Sabrina; Wild, Stefan; Angelova, Alexandra; Marc, Julie; Coré, Nathalie; de Chevigny, Antoine; Herrera, Eloisa; Bosio, Andreas; Bertrand, Vincent; Cremer, Harold

    2017-11-01

    In the postnatal forebrain regionalized neural stem cells along the ventricular walls produce olfactory bulb (OB) interneurons with varying neurotransmitter phenotypes and positions. To understand the molecular basis of this region-specific variability we analyzed gene expression in the postnatal dorsal and lateral lineages in mice of both sexes from stem cells to neurons. We show that both lineages maintain transcription factor signatures of their embryonic site of origin, the pallium and subpallium. However, additional factors, including Zic1 and Zic2, are postnatally expressed in the dorsal stem cell compartment and maintained in the lineage that generates calretinin-positive GABAergic neurons for the OB. Functionally, we show that Zic1 and Zic2 induce the generation of calretinin-positive neurons while suppressing dopaminergic fate in the postnatal dorsal lineage. We investigated the evolutionary conservation of the dopaminergic repressor function of Zic proteins and show that it is already present in C. elegans SIGNIFICANCE STATEMENT The vertebrate brain generates thousands of different neuron types. In this work we investigate the molecular mechanisms underlying this variability. Using a genomics approach we identify the transcription factor signatures of defined neural stem cells and neuron populations. Based thereon we show that two related transcription factors, Zic1 and Zic2, are essential to control the balance between two defined neuron types in the postnatal brain. We show that this mechanism is conserved in evolutionary very distant species. Copyright © 2017 the authors 0270-6474/17/3710611-13$15.00/0.

  5. Dopaminergic Neurons Controlling Anterior Pituitary Functions: Anatomy and Ontogenesis in Zebrafish.

    Science.gov (United States)

    Fontaine, Romain; Affaticati, Pierre; Bureau, Charlotte; Colin, Ingrid; Demarque, Michaël; Dufour, Sylvie; Vernier, Philippe; Yamamoto, Kei; Pasqualini, Catherine

    2015-08-01

    Dopaminergic (DA) neurons located in the preoptico-hypothalamic region of the brain exert a major neuroendocrine control on reproduction, growth, and homeostasis by regulating the secretion of anterior pituitary (or adenohypophysis) hormones. Here, using a retrograde tract tracing experiment, we identified the neurons playing this role in the zebrafish. The DA cells projecting directly to the anterior pituitary are localized in the most anteroventral part of the preoptic area, and we named them preoptico-hypophyseal DA (POHDA) neurons. During development, these neurons do not appear before 72 hours postfertilization (hpf) and are the last dopaminergic cell group to differentiate. We found that the number of neurons in this cell population continues to increase throughout life proportionally to the growth of the fish. 5-Bromo-2'-deoxyuridine incorporation analysis suggested that this increase is due to continuous neurogenesis and not due to a phenotypic change in already-existing neurons. Finally, expression profiles of several genes (foxg1a, dlx2a, and nr4a2a/b) were different in the POHDA compared with the adjacent suprachiasmatic DA neurons, suggesting that POHDA neurons develop as a distinct DA cell population in the preoptic area. This study offers some insights into the regional identity of the preoptic area and provides the first bases for future functional genetic studies on the development of DA neurons controlling anterior pituitary functions.

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

    Science.gov (United States)

    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

  7. The rise and fall of mesodiencephalic dopaminergic neurons : Molecular programming by transcription factors Engrailed 1, Pitx3, and Nkx2.9 during the development of mesodiencephalic neurons

    NARCIS (Netherlands)

    Kouwenhoven, W.M.

    2016-01-01

    The mid- and hindbrain harbor two essential monoaminergic neuronal populations: the mesodiencephalic dopaminergic (mdDA) neurons in the midbrain and the serotonergic (5HT) neurons in the hindbrain. Both systems innervate multiple regions in the forebrain and are involved in the guidance of our mood,

  8. Tp53 gene mediates distinct dopaminergic neuronal damage in different dopaminergic neurotoxicant models

    Directory of Open Access Journals (Sweden)

    Tao Lu

    2017-01-01

    Full Text Available Tp53, a stress response gene, is involved in diverse cell death pathways and its activation is implicated in the pathogenesis of Parkinson's disease. However, whether the neuronal Tp53 protein plays a direct role in regulating dopaminergic (DA neuronal cell death or neuronal terminal damage in different neurotoxicant models is unknown. In our recent studies, in contrast to the global inhibition of Tp53 function by pharmacological inhibitors and in traditional Tp53 knock-out mice, we examined the effects of DA-specific Tp53 gene deletion after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and methamphetamine exposure. Our data suggests that the Tp53 gene might be involved in both neuronal apoptosis and neuronal terminal damage caused by different neurotoxicants. Additional results from other studies also suggest that as a master regulator of many pathways that regulate apoptosis and synaptic terminal damage, it is possible that Tp53 may function as a signaling hub to integrate different signaling pathways to mediate distinctive target pathways. Tp53 protein as a signaling hub might be able to evaluate the microenvironment of neurons, assess the forms and severities of injury incurred, and determine whether apoptotic cell death or neuronal terminal degeneration occurs. Identification of the precise mechanisms activated in distinct neuronal damage caused by different forms and severities of injuries might allow for development of specific Tp53 inhibitors or ways to modulate distinct downstream target pathways involved.

  9. Mindfulness meditation modulates reward prediction errors in the striatum in a passive conditioning task

    Directory of Open Access Journals (Sweden)

    Ulrich eKirk

    2015-02-01

    Full Text Available Reinforcement learning models have demonstrated that phasic activity of dopamine neurons during reward expectation encodes information about the predictability of rewards and cues that predict reward. Evidence indicates that mindfulness-based approaches reduce reward anticipation signal in the striatum to negative and positive incentives suggesting the hypothesis that such training influence basic reward processing. Using a passive conditioning task and fMRI in a group of experienced mindfulness meditators and age-matched controls, we tested the hypothesis that mindfulness meditation influence reward and reward prediction error signals. We found diminished positive and negative prediction error-related blood-oxygen level-dependent (BOLD responses in the putamen in meditators compared with controls. In the meditators, this decrease in striatal BOLD responses to reward prediction was paralleled by increased activity in posterior insula, a primary interoceptive region. Critically, responses in the putamen during early trials of the conditioning procedure (run 1 were elevated in both meditators and controls. These results provide evidence that experienced mindfulness meditators show attenuated reward prediction signals to valenced stimuli, which may be related to interoceptive processes encoded in the posterior insula.

  10. Neural correlates of RDoC reward constructs in adolescents with diverse psychiatric symptoms: A Reward Flanker Task pilot study.

    Science.gov (United States)

    Bradley, Kailyn A L; Case, Julia A C; Freed, Rachel D; Stern, Emily R; Gabbay, Vilma

    2017-07-01

    There has been growing interest under the Research Domain Criteria initiative to investigate behavioral constructs and their underlying neural circuitry. Abnormalities in reward processes are salient across psychiatric conditions and may precede future psychopathology in youth. However, the neural circuitry underlying such deficits has not been well defined. Therefore, in this pilot, we studied youth with diverse psychiatric symptoms and examined the neural underpinnings of reward anticipation, attainment, and positive prediction error (PPE, unexpected reward gain). Clinically, we focused on anhedonia, known to reflect deficits in reward function. Twenty-two psychotropic medication-free youth, 16 with psychiatric symptoms, exhibiting a full range of anhedonia, were scanned during the Reward Flanker Task. Anhedonia severity was quantified using the Snaith-Hamilton Pleasure Scale. Functional magnetic resonance imaging analyses were false discovery rate corrected for multiple comparisons. Anticipation activated a broad network, including the medial frontal cortex and ventral striatum, while attainment activated memory and emotion-related regions such as the hippocampus and parahippocampal gyrus, but not the ventral striatum. PPE activated a right-dominant fronto-temporo-parietal network. Anhedonia was only correlated with activation of the right angular gyrus during anticipation and the left precuneus during PPE at an uncorrected threshold. Findings are preliminary due to the small sample size. This pilot characterized the neural circuitry underlying different aspects of reward processing in youth with diverse psychiatric symptoms. These results highlight the complexity of the neural circuitry underlying reward anticipation, attainment, and PPE. Furthermore, this study underscores the importance of RDoC research in youth. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Belief reward shaping in reinforcement learning

    CSIR Research Space (South Africa)

    Marom, O

    2018-02-01

    Full Text Available A key challenge in many reinforcement learning problems is delayed rewards, which can significantly slow down learning. Although reward shaping has previously been introduced to accelerate learning by bootstrapping an agent with additional...

  12. Dopamine D2/3- and μ-opioid receptor antagonists reduce cue-induced responding and reward impulsivity in humans.

    Science.gov (United States)

    Weber, S C; Beck-Schimmer, B; Kajdi, M-E; Müller, D; Tobler, P N; Quednow, B B

    2016-07-05

    Increased responding to drug-associated stimuli (cue reactivity) and an inability to tolerate delayed gratification (reward impulsivity) have been implicated in the development and maintenance of drug addiction. Whereas data from animal studies suggest that both the dopamine and opioid system are involved in these two reward-related processes, their role in humans is less clear. Moreover, dopaminergic and opioidergic drugs have not been directly compared with regard to these functions, even though a deeper understanding of the underlying mechanisms might inform the development of specific treatments for elevated cue reactivity and reward impulsivity. In a randomized, double-blind, between-subject design we administered the selective dopamine D2/D3 receptor antagonist amisulpride (400 mg, n=41), the unspecific opioid receptor antagonist naltrexone (50 mg, n=40) or placebo (n=40) to healthy humans and measured cue-induced responding with a Pavlovian-instrumental transfer task and reward impulsivity with a delay discounting task. Mood was assessed using a visual analogue scale. Compared with placebo, amisulpride significantly suppressed cue-induced responding and reward impulsivity. The effects of naltrexone were similar, although less pronounced. Both amisulpride and naltrexone decreased average mood ratings compared with placebo. Our results demonstrate that a selective blockade of dopamine D2/D3 receptors reduces cue-induced responding and reward impulsivity in healthy humans. Antagonizing μ-opioid receptors has similar effects for cue-induced responding and to a lesser extent for reward impulsivity.

  13. Distributed hippocampal patterns that discriminate reward context are associated with enhanced associative binding.

    Science.gov (United States)

    Wolosin, Sasha M; Zeithamova, Dagmar; Preston, Alison R

    2013-11-01

    Recent research indicates that reward-based motivation impacts medial temporal lobe (MTL) encoding processes, leading to enhanced memory for rewarded events. In particular, previous functional magnetic resonance imaging (fMRI) studies of motivated learning have shown that MTL activation is greater for highly rewarded events, with the degree of reward-related activation enhancement tracking the corresponding behavioral memory advantage. These studies, however, do not directly address leading theoretical perspectives that propose such reward-based enhancements in MTL encoding activation reflect enhanced discrimination of the motivational context of specific events. In this study, a high-value or low-value monetary cue preceded a pair of objects, indicating the future reward for successfully remembering the pair. Using representational similarity analysis and high-resolution fMRI, we show that MTL activation patterns are more similar for encoding trials preceded by the same versus different reward cues, indicating a distributed code in this region that distinguishes between motivational contexts. Moreover, we show that activation patterns in hippocampus and parahippocampal cortex (PHc) that differentiate reward conditions during anticipatory cues and object pairs relate to successful associative memory. Additionally, the degree to which patterns differentiate reward contexts in dentate gyrus/CA2,3 and PHc is related to individual differences in reward modulation of memory. Collectively, these findings suggest that distributed activation patterns in the human hippocampus and PHc reflect the rewards associated with individual events. Furthermore, we show that these activation patterns-which discriminate between reward conditions--may influence memory through the incorporation of information about motivational contexts into stored memory representations. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  14. The role of the dorsal raphé nucleus in reward-seeking behavior

    Directory of Open Access Journals (Sweden)

    Kae eNakamura

    2013-08-01

    Full Text Available Pharmacological experiments have shown that the modulation of brain serotonin levels has a strong impact on value-based decision making. Anatomical and physiological evidence also revealed that the dorsal raphé nucleus (DRN, a major source of serotonin, and the dopamine system receive common inputs from brain regions associated with appetitive and aversive information processing. The serotonin and dopamine systems also have reciprocal functional influences on each other. However, the specific mechanism by which serotonin affects value-based decision making is not clear.To understand the information carried by the DRN for reward-seeking behavior, we measured single neuron activity in the primate DRN during the performance of saccade tasks to obtain different amounts of a reward. We found that DRN neuronal activity was characterized by tonic modulation that was altered by the expected and received reward value. Consistent reward-dependent modulation across different task periods suggested that DRN activity kept track of the reward value throughout a trial. The DRN was also characterized by modulation of its activity in the opposite direction by different neuronal subgroups, one firing strongly for the prediction and receipt of large rewards, with the other firing strongly for small rewards. Conversely, putative dopamine neurons showed positive phasic responses to reward-indicating cues and the receipt of an unexpected reward amount, which supports the reward prediction error signal hypothesis of dopamine.I suggest that the tonic reward monitoring signal of the DRN, possibly together with its interaction with the dopamine system, reports a continuous level of motivation throughout the performance of a task. Such a signal may provide reward context information to the targets of DRN projections, where it may be integrated further with incoming motivationally salient information.

  15. Favorite brands as cultural objects modulate reward circuit.

    Science.gov (United States)

    Schaefer, Michael; Rotte, Michael

    2007-01-22

    On the basis of the hypothesis that brands may function as reward stimuli, we investigated brain responses to favorite brands. Participants viewed brand logos while we measured cortical activity with functional magnetic resonance imaging. Results revealed activity in the striatum for favorite brands that positively correlated with sports and luxury characteristics, but negatively with attributions to a brand of rational choice. Reduced activation of a single region in the dorsolateral prefrontal cortex was demonstrated when viewing the most beloved brand, possibly suggesting reduced strategic reasoning on the basis of affect. The results propose that brands that have been associated with appetitive stimuli owing to marketing efforts engage brain networks similar to those engaged by artificially associated reward stimuli. Moreover, social stimuli may function as secondary inducers of reward mechanisms.

  16. Glutamatergic transmission in drug reward: implications for drug addiction.

    Science.gov (United States)

    D'Souza, Manoranjan S

    2015-01-01

    Individuals addicted to drugs of abuse such as alcohol, nicotine, cocaine, and heroin are a significant burden on healthcare systems all over the world. The positive reinforcing (rewarding) effects of the above mentioned drugs play a major role in the initiation and maintenance of the drug-taking habit. Thus, understanding the neurochemical mechanisms underlying the reinforcing effects of drugs of abuse is critical to reducing the burden of drug addiction in society. Over the last two decades, there has been an increasing focus on the role of the excitatory neurotransmitter glutamate in drug addiction. In this review, pharmacological and genetic evidence supporting the role of glutamate in mediating the rewarding effects of the above described drugs of abuse will be discussed. Further, the review will discuss the role of glutamate transmission in two complex heterogeneous brain regions, namely the nucleus accumbens (NAcc) and the ventral tegmental area (VTA), which mediate the rewarding effects of drugs of abuse. In addition, several medications approved by the Food and Drug Administration that act by blocking glutamate transmission will be discussed in the context of drug reward. Finally, this review will discuss future studies needed to address currently unanswered gaps in knowledge, which will further elucidate the role of glutamate in the rewarding effects of drugs of abuse.

  17. Glutamatergic transmission in drug reward: Implications for drug addiction

    Directory of Open Access Journals (Sweden)

    Manoranjan S Dsouza

    2015-11-01

    Full Text Available Individuals addicted to drugs of abuse such as alcohol, nicotine, cocaine, and heroin are a significant burden on healthcare systems all over the world. The positive reinforcing (rewarding effects of the above mentioned drugs play a major role in the initiation and maintenance of the drug-taking habit. Thus, understanding the neurochemical mechanisms underlying the reinforcing effects of drugs of abuse is critical to reducing the burden of drug addiction in society. Over the last two decades, there has been an increasing focus on the role of the excitatory neurotransmitter glutamate in drug addiction. In this review, pharmacological and genetic evidence supporting the role of glutamate in mediating the rewarding effects of the above described drugs of abuse will be discussed. Further, the review will discuss the role of glutamate transmission in two complex heterogeneous brain regions, namely the nucleus accumbens (NAcc and the ventral tegmental area (VTA, which mediate the rewarding effects of drugs of abuse. In addition, several medications approved by the Food and Drug Administration that act by blocking glutamate transmission will be discussed in the context of drug reward. Finally, this review will discuss future studies needed to address currently unanswered gaps in knowledge, which will further elucidate the role of glutamate in the rewarding effects of drugs of abuse.

  18. The anticipation and outcome phases of reward and loss processing: A neuroimaging meta-analysis of the monetary incentive delay task.

    Science.gov (United States)

    Oldham, Stuart; Murawski, Carsten; Fornito, Alex; Youssef, George; Yücel, Murat; Lorenzetti, Valentina

    2018-04-25

    The processing of rewards and losses are crucial to everyday functioning. Considerable interest has been attached to investigating the anticipation and outcome phases of reward and loss processing, but results to date have been inconsistent. It is unclear if anticipation and outcome of a reward or loss recruit similar or distinct brain regions. In particular, while the striatum has widely been found to be active when anticipating a reward, whether it activates in response to the anticipation of losses as well remains ambiguous. Furthermore, concerning the orbitofrontal/ventromedial prefrontal regions, activation is often observed during reward receipt. However, it is unclear if this area is active during reward anticipation as well. We ran an Activation Likelihood Estimation meta-analysis of 50 fMRI studies, which used the Monetary Incentive Delay Task (MIDT), to identify which brain regions are implicated in the anticipation of rewards, anticipation of losses, and the receipt of reward. Anticipating rewards and losses recruits overlapping areas including the striatum, insula, amygdala and thalamus, suggesting that a generalised neural system initiates motivational processes independent of valence. The orbitofrontal/ventromedial prefrontal regions were recruited only during the reward outcome, likely representing the value of the reward received. Our findings help to clarify the neural substrates of the different phases of reward and loss processing, and advance neurobiological models of these processes. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  19. The Hidden Costs of Rewards.

    Science.gov (United States)

    Deci, Edward L.

    1976-01-01

    This paper discusses ways managers can motivate their employees to work and at the same time to increase their performance. Two theories of motivation--Vroom's theory and Atkinson's theory--focus on the use of extrinsic and intrinsic rewards respectively. A managerial strategy that combines the best of both intrinsic and extrinsic approaches to…

  20. Virtual Rewards for Driving Green

    Science.gov (United States)

    Pritchard, Josh

    2010-01-01

    Carbon dioxide from automobiles is a major contributor to global climate change. In "Virtual Rewards for Driving Green," Josh Pritchard proposes a computer application that will enable fuel-efficient drivers to earn "green" dollars with which to buy digital merchandise on the Web. Can getting items that exist only in cyberspace actually change a…

  1. Video game training and the reward system

    OpenAIRE

    Lorenz, R.; Gleich, T.; Gallinat, J.; Kühn, S.

    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 ...

  2. TGF-β Signaling in Dopaminergic Neurons Regulates Dendritic Growth, Excitatory-Inhibitory Synaptic Balance, and Reversal Learning

    Directory of Open Access Journals (Sweden)

    Sarah X. Luo

    2016-12-01

    Full Text Available Neural circuits involving midbrain dopaminergic (DA neurons regulate reward and goal-directed behaviors. Although local GABAergic input is known to modulate DA circuits, the mechanism that controls excitatory/inhibitory synaptic balance in DA neurons remains unclear. Here, we show that DA neurons use autocrine transforming growth factor β (TGF-β signaling to promote the growth of axons and dendrites. Surprisingly, removing TGF-β type II receptor in DA neurons also disrupts the balance in TGF-β1 expression in DA neurons and neighboring GABAergic neurons, which increases inhibitory input, reduces excitatory synaptic input, and alters phasic firing patterns in DA neurons. Mice lacking TGF-β signaling in DA neurons are hyperactive and exhibit inflexibility in relinquishing learned behaviors and re-establishing new stimulus-reward associations. These results support a role for TGF-β in regulating the delicate balance of excitatory/inhibitory synaptic input in local microcircuits involving DA and GABAergic neurons and its potential contributions to neuropsychiatric disorders.

  3. A correction term for the covariance of renewal-reward processes with multivariate rewards

    NARCIS (Netherlands)

    Patch, B.; Nazarathy, Y.; Taimre, T.

    We consider a renewal-reward process with multivariate rewards. Such a process is constructed from an i.i.d. sequence of time periods, to each of which there is associated a multivariate reward vector. The rewards in each time period may depend on each other and on the period length, but not on the

  4. Neural Processing of Calories in Brain Reward Areas Can be Modulated by Reward Sensitivity

    NARCIS (Netherlands)

    van Rijn, Inge; Griffioen-Roose, Sanne; de Graaf, Cees; Smeets, Paul A M

    A food's reward value is dependent on its caloric content. Furthermore, a food's acute reward value also depends on hunger state. The drive to obtain rewards (reward sensitivity), however, differs between individuals. Here, we assessed the association between brain responses to calories in the mouth

  5. Compensatory weight gain due to dopaminergic hypofunction: new evidence and own incidental observations

    Directory of Open Access Journals (Sweden)

    Bohr Iwo

    2008-12-01

    Full Text Available Abstract There is increasing evidence for a role of dopamine in the development of obesity. More specifically, dopaminergic hypofunction might lead to (overcompensatory food intake. Overeating and resulting weight gain may be induced by genetic predisposition for lower dopaminergic activity, but might also be a behavioral mechanism of compensating for decreased dopamine signaling after dopaminergic overstimulation, for example after smoking cessation or overconsumption of high palatable food. This hypothesis is in line with our incidental finding of increased weight gain after discontinuation of pharmaceutical dopaminergic overstimulation in rats. These findings support the crucial role of dopaminergic signaling for eating behaviors and offer an explanation for weight-gain after cessation of activities associated with high dopaminergic signaling. They further support the possibility that dopaminergic medication could be used to moderate food intake.

  6. Discrete-time rewards model-checked

    NARCIS (Netherlands)

    Larsen, K.G.; Andova, S.; Niebert, Peter; Hermanns, H.; Katoen, Joost P.

    2003-01-01

    This paper presents a model-checking approach for analyzing discrete-time Markov reward models. For this purpose, the temporal logic probabilistic CTL is extended with reward constraints. This allows to formulate complex measures – involving expected as well as accumulated rewards – in a precise and

  7. Renewal processes with costs and rewards

    NARCIS (Netherlands)

    Vlasiou, M.; Cochran, J.J.; Cox, L.A.; Keskinocak, P.; Kharoufeh, J.P.; Smith, J.C.

    2011-01-01

    We review the theory of renewal reward processes, which describes renewal processes that have some cost or reward associated with each cycle. We present a new simplified proof of the renewal reward theorem that mimics the proof of the Elementary Renewal Theorem and avoids the technicalities in the

  8. Reward, Distraction, and the Overjustification Effect

    Science.gov (United States)

    Smith, Timothy W.; Pittman, Thane S.

    1978-01-01

    This study tests two differing hypotheses: the competing response hypothesis, which states that both reward and non-reward distractions produce decreases in interest which weaken over repeated trials, and the attribution/overjustification hypothesis, which maintains that rewards produce a decrease in interest that does not weaken over trials.…

  9. Incentive theory: IV. Magnitude of reward

    OpenAIRE

    Killeen, Peter R.

    1985-01-01

    Incentive theory is successfully applied to data from experiments in which the amount of food reward is varied. This is accomplished by assuming that incentive value is a negatively accelerated function of reward duration. The interaction of the magnitude of a reward with its delay is confirmed, and the causes and implications of this interaction are discussed.

  10. Spatiotemporal neural characterization of prediction error valence and surprise during reward learning in humans.

    Science.gov (United States)

    Fouragnan, Elsa; Queirazza, Filippo; Retzler, Chris; Mullinger, Karen J; Philiastides, Marios G

    2017-07-06

    Reward learning depends on accurate reward associations with potential choices. These associations can be attained with reinforcement learning mechanisms using a reward prediction error (RPE) signal (the difference between actual and expected rewards) for updating future reward expectations. Despite an extensive body of literature on the influence of RPE on learning, little has been done to investigate the potentially separate contributions of RPE valence (positive or negative) and surprise (absolute degree of deviation from expectations). Here, we coupled single-trial electroencephalography with simultaneously acquired fMRI, during a probabilistic reversal-learning task, to offer evidence of temporally overlapping but largely distinct spatial representations of RPE valence and surprise. Electrophysiological variability in RPE valence correlated with activity in regions of the human reward network promoting approach or avoidance learning. Electrophysiological variability in RPE surprise correlated primarily with activity in regions of the human attentional network controlling the speed of learning. Crucially, despite the largely separate spatial extend of these representations our EEG-informed fMRI approach uniquely revealed a linear superposition of the two RPE components in a smaller network encompassing visuo-mnemonic and reward areas. Activity in this network was further predictive of stimulus value updating indicating a comparable contribution of both signals to reward learning.

  11. Frontal-striatum dysfunction during reward processing: Relationships to amotivation in schizophrenia.

    Science.gov (United States)

    Chung, Yu Sun; Barch, Deanna M

    2016-04-01

    Schizophrenia is characterized by deficits of context processing, thought to be related to dorsolateral prefrontal cortex (DLPFC) impairment. Despite emerging evidence suggesting a crucial role of the DLPFC in integrating reward and goal information, we do not know whether individuals with schizophrenia can represent and integrate reward-related context information to modulate cognitive control. To address this question, 36 individuals with schizophrenia (n = 29) or schizoaffective disorder (n = 7) and 27 healthy controls performed a variant of a response conflict task (Padmala & Pessoa, 2011) during fMRI scanning, in both baseline and reward conditions, with monetary incentives on some reward trials. We used a mixed state-item design that allowed us to examine both sustained and transient reward effects on cognitive control. Different from predictions about impaired DLPFC function in schizophrenia, we found an intact pattern of increased sustained DLPFC activity during reward versus baseline blocks in individuals with schizophrenia at a group level but blunted sustained activations in the putamen. Contrary to our predictions, individuals with schizophrenia showed blunted cue-related activations in several regions of the basal ganglia responding to reward-predicting cues. Importantly, as predicted, individual differences in anhedonia/amotivation symptoms severity were significantly associated with reduced sustained DLPFC activation in the same region that showed overall increased activity as a function of reward. These results suggest that individual differences in motivational impairments in schizophrenia may be related to dysfunction of the DLPFC and striatum in motivationally salient situations. (c) 2016 APA, all rights reserved).

  12. Prediction-error in the context of real social relationships modulates reward system activity.

    Science.gov (United States)

    Poore, Joshua C; Pfeifer, Jennifer H; Berkman, Elliot T; Inagaki, Tristen K; Welborn, Benjamin L; Lieberman, Matthew D

    2012-01-01

    The human reward system is sensitive to both social (e.g., validation) and non-social rewards (e.g., money) and is likely integral for relationship development and reputation building. However, data is sparse on the question of whether implicit social reward processing meaningfully contributes to explicit social representations such as trust and attachment security in pre-existing relationships. This event-related fMRI experiment examined reward system prediction-error activity in response to a potent social reward-social validation-and this activity's relation to both attachment security and trust in the context of real romantic relationships. During the experiment, participants' expectations for their romantic partners' positive regard of them were confirmed (validated) or violated, in either positive or negative directions. Primary analyses were conducted using predefined regions of interest, the locations of which were taken from previously published research. Results indicate that activity for mid-brain and striatal reward system regions of interest was modulated by social reward expectation violation in ways consistent with prior research on reward prediction-error. Additionally, activity in the striatum during viewing of disconfirmatory information was associated with both increases in post-scan reports of attachment anxiety and decreases in post-scan trust, a finding that follows directly from representational models of attachment and trust.

  13. Ventromedial Frontal Cortex Is Critical for Guiding Attention to Reward-Predictive Visual Features in Humans.

    Science.gov (United States)

    Vaidya, Avinash R; Fellows, Lesley K

    2015-09-16

    Adaptively interacting with our environment requires extracting information that will allow us to successfully predict reward. This can be a challenge, particularly when there are many candidate cues, and when rewards are probabilistic. Recent work has demonstrated that visual attention is allocated to stimulus features that have been associated with reward on previous trials. The ventromedial frontal lobe (VMF) has been implicated in learning in dynamic environments of this kind, but the mechanism by which this region influences this process is not clear. Here, we hypothesized that the VMF plays a critical role in guiding attention to reward-predictive stimulus features based on feedback. We tested the effects of VMF damage in human subjects on a visual search task in which subjects were primed to attend to task-irrelevant colors associated with different levels of reward, incidental to the search task. Consistent with previous work, we found that distractors had a greater influence on reaction time when they appeared in colors associated with high reward in the previous trial compared with colors associated with low reward in healthy control subjects and patients with prefrontal damage sparing the VMF. However, this reward modulation of attentional priming was absent in patients with VMF damage. Thus, an intact VMF is necessary for directing attention based on experience with cue-reward associations. We suggest that this region plays a role in selecting reward-predictive cues to facilitate future learning. There has been a swell of interest recently in the ventromedial frontal cortex (VMF), a brain region critical to associative learning. However, the underlying mechanism by which this region guides learning is not well understood. Here, we tested the effects of damage to this region in humans on a task in which rewards were linked incidentally to visual features, resulting in trial-by-trial attentional priming. Controls and subjects with prefrontal damage

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

    Directory of Open Access Journals (Sweden)

    Jinhee Kim

    2017-10-01

    Full Text Available 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

  15. A Selective Role for Dopamine in Learning to Maximize Reward But Not to Minimize Effort: Evidence from Patients with Parkinson's Disease.

    Science.gov (United States)

    Skvortsova, Vasilisa; Degos, Bertrand; Welter, Marie-Laure; Vidailhet, Marie; Pessiglione, Mathias

    2017-06-21

    Instrumental learning is a fundamental process through which agents optimize their choices, taking into account various dimensions of available options such as the possible reward or punishment outcomes and the costs associated with potential actions. Although the implication of dopamine in learning from choice outcomes is well established, less is known about its role in learning the action costs such as effort. Here, we tested the ability of patients with Parkinson's disease (PD) to maximize monetary rewards and minimize physical efforts in a probabilistic instrumental learning task. The implication of dopamine was assessed by comparing performance ON and OFF prodopaminergic medication. In a first sample of PD patients ( n = 15), we observed that reward learning, but not effort learning, was selectively impaired in the absence of treatment, with a significant interaction between learning condition (reward vs effort) and medication status (OFF vs ON). These results were replicated in a second, independent sample of PD patients ( n = 20) using a simplified version of the task. According to Bayesian model selection, the best account for medication effects in both studies was a specific amplification of reward magnitude in a Q-learning algorithm. These results suggest that learning to avoid physical effort is independent from dopaminergic circuits and strengthen the general idea that dopaminergic signaling amplifies the effects of reward expectation or obtainment on instrumental behavior. SIGNIFICANCE STATEMENT Theoretically, maximizing reward and minimizing effort could involve the same computations and therefore rely on the same brain circuits. Here, we tested whether dopamine, a key component of reward-related circuitry, is also implicated in effort learning. We found that patients suffering from dopamine depletion due to Parkinson's disease were selectively impaired in reward learning, but not effort learning. Moreover, anti-parkinsonian medication restored the

  16. Positron emission tomography (PET) studies of dopaminergic/cholinergic interactions in the baboon brain

    International Nuclear Information System (INIS)

    Dewey, S.L.; Brodie, J.D.; Fowler, J.S.; MacGregor, R.R.; Schlyer, D.J.; King, P.T.; Alexoff, D.L.; Volkow, N.D.; Shiue, C.Y.; Wolf, A.P.

    1990-01-01

    Interactions between the dopaminergic D2 receptor system and the muscarinic cholinergic system in the corpus striatum of adult female baboons (Papio anubis) were examined using positron emission tomography (PET) combined with [18F]N-methylspiroperidol [( 18F]NMSP) (to probe D2 receptor availability) and [N-11C-methyl]benztropine (to probe muscarinic cholinergic receptor availability). Pretreatment with benztropine, a long-lasting anticholinergic drug, bilaterally reduced the incorporation of radioactivity in the corpus striatum but did not alter that observed in the cerebellum or the rate of metabolism of [18F]NMSP in plasma. Pretreatment with unlabelled NMSP, a potent dopaminergic antagonist, reduced the incorporation of [N-11C-methyl]benztropine in all brain regions, with the greatest effect being in the corpus striatum greater than cortex greater than thalamus greater than cerebellum, but did not alter the rate of metabolism of the labelled benztropine in the plasma. These reductions in the incorporation of either [18F]NMSP or [N-11C-methyl]benztropine exceeded the normal variation in tracer incorporation in repeated studies in the same animal. This study demonstrates that PET can be used as a tool for investigating interactions between neurochemically different yet functionally linked neurotransmitters systems in vivo and provides insight into the consequences of multiple pharmacologic administration

  17. Effects of dopaminergic drug treatments on in vivo radioligand binding to brain vesicular monoamine transporters

    Energy Technology Data Exchange (ETDEWEB)

    Kilbourn, Michael R; Frey, Kirk A; Vander Borght, Thierry; Sherman, Phillip S

    1996-05-01

    The effects of various dopaminergic drug treatments on the in vivo regional brain distribution of high-affinity radioligands ([{sup 11}C]dihydrotetrabenazine and [{sup 11}C]methoxytetrabenazine) for the rat brain vesicular monoamine transporter (VMAT2) were determined. Acute treatments with reserpine (2 mg/kg i.p.), tetrabenazine (10 mg/kg i.v.) or related benzoisoquinolines significantly reduced radiotracer binding in vivo. In contrast, radiotracer distributions remained unchanged after treatments with other dopaminergic drugs, whether given by single injection (haloperidol, 1 mg/kg i.p., pargyline 80 mg/kg), repeatedly (pargyline, 80 mg/kg s.c., 14 days), or by continuous infusion (deprenyl, 10 mg/kg/day, 5 days; L-DOPA methyl ester 100 mg/kg/day, 5 days). Repeated injections of tetrabenazine (5 mg/kg i.p., twice daily, 3 days) did not alter in vivo radioligand binding measured after allowing drug washout from the brain. These studies support the proposal that in vivo PET imaging of VMAT2 radioligands in patients with extrapyramidal movement disorders will not be affected by concurrent use of L-DOPA or deprenyl.

  18. Oxidative stress induces nuclear translocation of C-terminus of α-synuclein in dopaminergic cells

    International Nuclear Information System (INIS)

    Xu Shengli; Zhou Ming; Yu Shun; Cai Yanning; Zhang Alex; Ueda, Kenji; Chan Piu

    2006-01-01

    Growing evidence suggests that oxidative stress is involved in the neuronal degeneration and can promote the aggregation of α-synuclein. However, the role of α-synuclein under physiological and pathological conditions remains poorly understood. In the present study, we examined the possible interaction between the α-synuclein and oxidative stress. In a dopaminergic cell line MES23.5, we have found that the 200 μM H 2 O 2 treatment induced the translocation of α-synuclein from cytoplasm to nuclei at 30 min post-treatment. The immunoactivity of α-synuclein became highly intensive in the nuclei after 2 h treatment. The protein translocated to nucleus was a 10 kDa fragment of C-terminus region of α-synuclein, while full-length α-synuclein remained in cytoplasm. Thioflavine-S staining suggested that the C-terminal fragment in the nuclei has no β-sheet structures. Our present results indicated that 200 μM H 2 O 2 treatment induces the intranuclear accumulation of the C-terminal fragment of α-synuclein in dopaminergic neurons, whose role remains to be investigated

  19. Taking two to tango: a role for ghrelin receptor heterodimerization in stress and reward.

    Science.gov (United States)

    Schellekens, Harriët; Dinan, Timothy G; Cryan, John F

    2013-08-30

    The gut hormone, ghrelin, is the only known peripherally derived orexigenic signal. It activates its centrally expressed receptor, the growth hormone secretagogue receptor (GHS-R1a), to stimulate food intake. The ghrelin signaling system has recently been suggested to play a key role at the interface of homeostatic control of appetite and the hedonic aspects of food intake, as a critical role for ghrelin in dopaminergic mesolimbic circuits involved in reward signaling has emerged. Moreover, enhanced plasma ghrelin levels are associated with conditions of physiological stress, which may underline the drive to eat calorie-dense "comfort-foods" and signifies a role for ghrelin in stress-induced food reward behaviors. These complex and diverse functionalities of the ghrelinergic system are not yet fully elucidated and likely involve crosstalk with additional signaling systems. Interestingly, accumulating data over the last few years has shown the GHS-R1a receptor to dimerize with several additional G-protein coupled receptors (GPCRs) involved in appetite signaling and reward, including the GHS-R1b receptor, the melanocortin 3 receptor (MC3), dopamine receptors (D1 and D2), and more recently, the serotonin 2C receptor (5-HT2C). GHS-R1a dimerization was shown to affect downstream signaling and receptor trafficking suggesting a potential novel mechanism for fine-tuning GHS-R1a receptor mediated activity. This review summarizes ghrelin's role in food reward and stress and outlines the GHS-R1a dimer pairs identified to date. In addition, the downstream signaling and potential functional consequences of dimerization of the GHS-R1a receptor in appetite and stress-induced food reward behavior are discussed. The existence of multiple GHS-R1a heterodimers has important consequences for future pharmacotherapies as it significantly increases the pharmacological diversity of the GHS-R1a receptor and has the potential to enhance specificity of novel ghrelin-targeted drugs.

  20. Putting Desire on a Budget: Dopamine and Energy Expenditure, Reconciling Reward and Resources

    Directory of Open Access Journals (Sweden)

    Jeff A Beeler

    2012-07-01

    Full Text Available Accumulating evidence indicates integration of dopamine function with metabolic signals, highlighting a potential role for dopamine in energy balance, frequently construed as modulating reward in response to homeostatic state. Though its precise role remains controversial, the reward perspective of dopamine has dominated investigation of motivational disorders, including obesity. In the hypothesis outlined here, we suggest instead that the primary role of dopamine in behavior is to modulate activity to adapt behavioral energy expenditure to the prevailing environmental energy conditions, with the role of dopamine in reward and motivated behaviors derived from its primary role in energy balance. Dopamine has long been known to modulate activity, exemplified by psychostimulants that act via dopamine. More recently, there has been nascent investigation into the role of dopamine in modulating voluntary activity, with some investigators suggesting that dopamine may serve as a final common pathway that couples energy sensing to regulated voluntary energy expenditure. We suggest that interposed between input from both the internal and external world, dopamine modulates behavioral energy expenditure along two axes: a conserve-expend axis that regulates generalized activity and an explore-exploit axes that regulates the degree to which reward value biases the distribution of activity. In this view, increased dopamine does not promote consumption of tasty food. Instead increased dopamine promotes energy expenditure and exploration while decreased dopamine favors energy conservation and exploitation. This hypothesis provides a mechanistic interpretation to an apparent paradox: the well-established role of dopamine in food seeking and the findings that low dopaminergic functions are associated with obesity. Our hypothesis provides an alternative perspective on the role of dopamine in obesity and reinterprets the ‘reward deficiency hypothesis’ as a

  1. Diet-induced obesity causes ghrelin resistance in reward processing tasks.

    Science.gov (United States)

    Lockie, Sarah H; Dinan, Tara; Lawrence, Andrew J; Spencer, Sarah J; Andrews, Zane B

    2015-12-01

    Diet-induced obesity (DIO) causes ghrelin resistance in hypothalamic Agouti-related peptide (AgRP) neurons. However, ghrelin promotes feeding through actions at both the hypothalamus and mesolimbic dopamine reward pathways. Therefore, we hypothesized that DIO would also establish ghrelin resistance in the ventral tegmental area (VTA), a major site of dopaminergic cell bodies important in reward processing. We observed reduced sucrose and saccharin consumption in Ghrelin KO vs Ghrelin WT mice. Moreover, DIO reduced saccharin consumption relative to chow-fed controls. These data suggest that the deletion of ghrelin and high fat diet both cause anhedonia. To assess if these are causally related, we tested whether DIO caused ghrelin resistance in a classic model of drug reward, conditioned place preference (CPP). Chow or high fat diet (HFD) mice were conditioned with ghrelin (1mg/kg in 10ml/kg ip) in the presence or absence of food in the conditioning chamber. We observed a CPP to ghrelin in chow-fed mice but not in HFD-fed mice. HFD-fed mice still showed a CPP for cocaine (20mg/kg), indicating that they maintained the ability to develop conditioned behaviour. The absence of food availability during ghrelin conditioning sessions induced a conditioned place aversion, an effect that was still present in both chow and HFD mice. Bilateral intra-VTA ghrelin injection (0.33μg/μl in 0.5μl) robustly increased feeding in both chow-fed and high fat diet (HFD)-fed mice; however, this was correlated with body weight only in the chow-fed mice. Our results suggest that DIO causes ghrelin resistance albeit not directly in the VTA. We suggest there is impaired ghrelin sensitivity in upstream pathways regulating reward pathways, highlighting a functional role for ghrelin linking appropriate metabolic sensing with reward processing. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Cocaine enhances the conditioned rewarding effects of MDMA in adolescent mice.

    Science.gov (United States)

    Aguilar, M A; Roger-Sánchez, C; Rodríguez-Arias, M; Miñarro, J

    2015-04-01

    Although the consumption of cocaine is frequent in young users of MDMA (3,4-methylenedioxymethamphetamine), the influence of exposure to cocaine on the rewarding effects of MDMA in adolescents has not been studied. The purpose of the present work was to evaluate the effect of co-administration of cocaine (1 and 10 mg/kg) and a sub-threshold dose of MDMA (1.25 mg/kg) on the acquisition of conditioned place preference (CPP) (experiment 1). In addition, the effect of pre-treatment with cocaine on MDMA-induced CPP was evaluated (experiment 2). Levels of monoamines in striatum, hippocampus and cortex were measured in both experiments. Our hypotheses were that cocaine co-administration or pre-treatment would increase the rewarding effects of MDMA, and that these effects would be related with changes in brain monoamine levels. Our results showed that cocaine potentiated the rewarding effects of MDMA, since a sub-threshold dose of MDMA, which did not induce CPP by itself, induced a significant CPP in adolescent mice when administered along with cocaine during conditioning (experiment 1). Moreover, pre-treatment with cocaine several days before conditioning also increased the rewarding effects of MDMA (experiment 2). No significant changes in the levels of biogenic amines, which correlated with these behavioural effects, were observed. Our results confirm the involvement of the dopaminergic system in MDMA-induced CPP in adolescent mice and suggest that combined consumption with or pre-exposure to cocaine increases the conditioned rewarding effects of MDMA, which may enhance the capacity of MDMA to induce dependence. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Multivariate analysis of dopaminergic gene variants as risk factors of heroin dependence.

    Directory of Open Access Journals (Sweden)

    Andrea Vereczkei

    Full Text Available BACKGROUND: Heroin dependence is a debilitating psychiatric disorder with complex inheritance. Since the dopaminergic system has a key role in rewarding mechanism of the brain, which is directly or indirectly targeted by most drugs of abuse, we focus on the effects and interactions among dopaminergic gene variants. OBJECTIVE: To study the potential association between allelic variants of dopamine D2 receptor (DRD2, ANKK1 (ankyrin repeat and kinase domain containing 1, dopamine D4 receptor (DRD4, catechol-O-methyl transferase (COMT and dopamine transporter (SLC6A3 genes and heroin dependence in Hungarian patients. METHODS: 303 heroin dependent subjects and 555 healthy controls were genotyped for 7 single nucleotide polymorphisms (SNPs rs4680 of the COMT gene; rs1079597 and rs1800498 of the DRD2 gene; rs1800497 of the ANKK1 gene; rs1800955, rs936462 and rs747302 of the DRD4 gene. Four variable number of tandem repeats (VNTRs were also genotyped: 120 bp duplication and 48 bp VNTR in exon 3 of DRD4 and 40 bp VNTR and intron 8 VNTR of SLC6A3. We also perform a multivariate analysis of associations using Bayesian networks in Bayesian multilevel analysis (BN-BMLA. FINDINGS AND CONCLUSIONS: In single marker analysis the TaqIA (rs1800497 and TaqIB (rs1079597 variants were associated with heroin dependence. Moreover, -521 C/T SNP (rs1800955 of the DRD4 gene showed nominal association with a possible protective effect of the C allele. After applying the Bonferroni correction TaqIB was still significant suggesting that the minor (A allele of the TaqIB SNP is a risk component in the genetic background of heroin dependence. The findings of the additional multiple marker analysis are consistent with the results of the single marker analysis, but this method was able to reveal an indirect effect of a promoter polymorphism (rs936462 of the DRD4 gene and this effect is mediated through the -521 C/T (rs1800955 polymorphism in the promoter.

  4. Brief debrisoquin administration to assess central dopaminergic function in children.

    Science.gov (United States)

    Riddle, M A; Shaywitz, B A; Leckman, J F; Anderson, G M; Shaywitz, S E; Hardin, M T; Ort, S I; Cohen, D J

    1986-03-17

    Central dopaminergic (DA) function in children was assessed by monitoring plasma-free homovanillic acid (pHVA) levels after brief (18 hour) administration with debrisoquin sulfate, a peripherally active antihypertensive agent that blocks peripheral, but not central, HVA production. Brief debrisoquin administration resulted in marked reductions in pHVA in each of six patients studied. In five of the six patients, post-debrisoquin pHVA levels remained relatively stable over the six-hour period of observation. No significant cardiovascular or behavioral side effects of debrisoquin were observed. The brief debrisoquin administration method appears to be a safe, simple, and potentially valid peripheral technique for evaluating aspects of central dopaminergic function in children with neuropsychiatric disorders. Additional work is needed to further establish this method's validity and reliability.

  5. Incremental effects of reward on creativity.

    Science.gov (United States)

    Eisenberger, R; Rhoades, L

    2001-10-01

    The authors examined 2 ways reward might increase creativity. First, reward contingent on creativity might increase extrinsic motivation. Studies 1 and 2 found that repeatedly giving preadolescent students reward for creative performance in 1 task increased their creativity in subsequent tasks. Study 3 reported that reward promised for creativity increased college students' creative task performance. Second, expected reward for high performance might increase creativity by enhancing perceived self-determination and, therefore, intrinsic task interest. Study 4 found that employees' intrinsic job interest mediated a positive relationship between expected reward for high performance and creative suggestions offered at work. Study 5 found that employees' perceived self-determination mediated a positive relationship between expected reward for high performance and the creativity of anonymous suggestions for helping the organization.

  6. Brain Circuits Encoding Reward from Pain Relief.

    Science.gov (United States)

    Navratilova, Edita; Atcherley, Christopher W; Porreca, Frank

    2015-11-01

    Relief from pain in humans is rewarding and pleasurable. Primary rewards, or reward-predictive cues, are encoded in brain reward/motivational circuits. While considerable advances have been made in our understanding of reward circuits underlying positive reinforcement, less is known about the circuits underlying the hedonic and reinforcing actions of pain relief. We review findings from electrophysiological, neuroimaging, and behavioral studies supporting the concept that the rewarding effect of pain relief requires opioid signaling in the anterior cingulate cortex (ACC), activation of midbrain dopamine neurons, and the release of dopamine in the nucleus accumbens (NAc). Understanding of circuits that govern the reward of pain relief may allow the discovery of more effective and satisfying therapies for patients with acute or chronic pain.

  7. Ventral pallidum roles in reward and motivation.

    Science.gov (United States)

    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.

  8. Diagnosis and Healing In Veterans Suspected of Suffering from Post-Traumatic Stress Disorder (PTSD) Using Reward Gene Testing and Reward Circuitry Natural Dopaminergic Activation

    OpenAIRE

    Blum, Kenneth; Giordano, John; Oscar-Berman, Marlene; Bowirrat, Abdalla; Simpatico, Thomas; Barh, Debmalya

    2012-01-01

    There is a need for understanding and treating post-traumatic stress disorder (PTSD), in soldiers returning to the United States of America after combat. Likewise, it would be beneficial to finding a way to reduce violence committed by soldiers, here and abroad, who are suspected of having post-traumatic stress disorder (PTSD). We hypothesize that even before combat, soldiers with a childhood background of violence (or with a familial susceptibility risk) would benefit from being genotyped fo...

  9. Reward Motivation Enhances Task Coding in Frontoparietal Cortex.

    Science.gov (United States)

    Etzel, Joset A; Cole, Michael W; Zacks, Jeffrey M; Kay, Kendrick N; Braver, Todd S

    2016-04-01

    Reward motivation often enhances task performance, but the neural mechanisms underlying such cognitive enhancement remain unclear. Here, we used a multivariate pattern analysis (MVPA) approach to test the hypothesis that motivation-related enhancement of cognitive control results from improved encoding and representation of task set information. Participants underwent two fMRI sessions of cued task switching, the first under baseline conditions, and the second with randomly intermixed reward incentive and no-incentive trials. Information about the upcoming task could be successfully decoded from cue-related activation patterns in a set of frontoparietal regions typically associated with task control. More critically, MVPA classifiers trained on the baseline session had significantly higher decoding accuracy on incentive than non-incentive trials, with decoding improvement mediating reward-related enhancement of behavioral performance. These results strongly support the hypothesis that reward motivation enhances cognitive control, by improving the discriminability of task-relevant information coded and maintained in frontoparietal brain regions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Learned reward association improves visual working memory.

    Science.gov (United States)

    Gong, Mengyuan; Li, Sheng

    2014-04-01

    Statistical regularities in the natural environment play a central role in adaptive behavior. Among other regularities, reward association is potentially the most prominent factor that influences our daily life. Recent studies have suggested that pre-established reward association yields strong influence on the spatial allocation of attention. Here we show that reward association can also improve visual working memory (VWM) performance when the reward-associated feature is task-irrelevant. We established the reward association during a visual search training session, and investigated the representation of reward-associated features in VWM by the application of a change detection task before and after the training. The results showed that the improvement in VWM was significantly greater for items in the color associated with high reward than for those in low reward-associated or nonrewarded colors. In particular, the results from control experiments demonstrate that the observed reward effect in VWM could not be sufficiently accounted for by attentional capture toward the high reward-associated item. This was further confirmed when the effect of attentional capture was minimized by presenting the items in the sample and test displays of the change detection task with the same color. The results showed significantly larger improvement in VWM performance when the items in a display were in the high reward-associated color than those in the low reward-associated or nonrewarded colors. Our findings suggest that, apart from inducing space-based attentional capture, the learned reward association could also facilitate the perceptual representation of high reward-associated items through feature-based attentional modulation.

  11. Hunger does not motivate reward in women remitted from anorexia nervosa.

    Science.gov (United States)

    Wierenga, Christina E; Bischoff-Grethe, Amanda; Melrose, A James; Irvine, Zoe; Torres, Laura; Bailer, Ursula F; Simmons, Alan; Fudge, Julie L; McClure, Samuel M; Ely, Alice; Kaye, Walter H

    2015-04-01

    Hunger enhances sensitivity to reward, yet individuals with anorexia nervosa (AN) are not motivated to eat when starved. This study investigated brain response to rewards during hunger and satiated states to examine whether diminished response to reward could underlie food restriction in AN. Using a delay discounting monetary decision task known to discriminate brain regions contributing to processing of immediate rewards and cognitive control important for decision making regarding future rewards, we compared 23 women remitted from AN (RAN group; to reduce the confounding effects of starvation) with 17 healthy comparison women (CW group). Monetary rewards were used because the rewarding value of food may be confounded by anxiety in AN. Interactions of Group (RAN, CW) × Visit (hunger, satiety) revealed that, for the CW group, hunger significantly increased activation in reward salience circuitry (ventral striatum, dorsal caudate, anterior cingulate cortex) during processing of immediate reward, whereas satiety increased activation in cognitive control circuitry (ventrolateral prefrontal cortex, insula) during decision making. In contrast, brain response in reward and cognitive neurocircuitry did not differ during hunger and satiety in the RAN group. A main effect of group revealed elevated response in the middle frontal gyrus for the RAN group compared with the CW group. Women remitted from AN failed to increase activation of reward valuation circuitry when hungry and showed elevated response in cognitive control circuitry independent of metabolic state. Decreased sensitivity to the motivational drive of hunger may explain the ability of individuals with AN to restrict food when emaciated. Difficulties in valuating emotional salience may contribute to inabilities to appreciate the risks inherent in this disorder. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Ventral striatum activation to prosocial rewards predicts longitudinal declines in adolescent risk taking.

    Science.gov (United States)

    Telzer, Eva H; Fuligni, Andrew J; Lieberman, Matthew D; Galván, Adriana

    2013-01-01

    Adolescence is a period of intensified emotions and an increase in motivated behaviors and passions. Evidence from developmental neuroscience suggests that this heightened emotionality occurs, in part, due to a peak in functional reactivity to rewarding stimuli, which renders adolescents more oriented toward reward-seeking behaviors. Most prior work has focused on how reward sensitivity may create vulnerabilities, leading to increases in risk taking. Here, we test whether heightened reward sensitivity may potentially be an asset for adolescents when engaged in prosocial activities. Thirty-two adolescents were followed over a one-year period to examine whether ventral striatum activation to prosocial rewards predicts decreases in risk taking over a year. Results show that heightened ventral striatum activation to prosocial stimuli relates to longitudinal declines in risk taking. Therefore, the very same neural region that has conferred vulnerability for adolescent risk taking may also be protective against risk taking. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Reward and Punishment in Minigames

    OpenAIRE

    Sigmund, K.; Hauert, C.; Nowak, M.A.

    2001-01-01

    Minigames capturing the essence of Public Goods experiments show that even in the absence of rationality assumptions, both punishment and reward will fail to bring about prosocial behavior. This result holds in particular for the well-known Ultimatum Game, which emerges as a special case. But reputation can induce fairness and cooperation in populations adapting through learning or imitation. Indeed, the inclusion of reputation effects in the corresponding dynamical models leads to the evolut...

  14. (76Br) Bromolisuride: a new radiopharmaceutical for in vivo study of the physiopathology of D2 dopaminergic receptors

    International Nuclear Information System (INIS)

    Maziere, B.; Loc'h, C.; Stulzaft, O.; Hantraye, P.; Ottaviani, M.; Comar, D.; Maziere, M.

    1986-01-01

    The in vivo binding of bromine-76 labelled bromolisurine was studied in rat brain using positron emission tomography. The regional distribution of the radioligand paralleled the morphologic distribution of dopamine receptors which are known to be dense in striatum and les sabundant in other brain regions. Striatum binding was saturable and displaceable. The striatal concentration reached its maximum 3.5 hours after injection of the radioligand. The rational for the development of 76 Br-bromolisuride as a radiopharmaceutical for use in imaging cerebral dopaminergic receptor areas was presented [fr

  15. Epigallocatechin gallate protects dopaminergic neurons against 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity by inhibiting microglial cell activation.

    Science.gov (United States)

    Li, Rui; Peng, Ning; Du, Fang; Li, Xu-ping; Le, Wei-dong

    2006-04-01

    To observe whether the dopaminergic neuroprotective effect of (-)-epigallocatechin gallate (EGCG) is associated with its inhibition of microglial cell activation in vivo. The effects of EGCG at different doses on dopaminergic neuronal survival were tested in a methyl-4-phenyl-pyridinium (MPP+)-induced dopaminergic neuronal injury model in the primary mesencephalic cell cultures. With unbiased stereological method, tyrosine hydroxylase-immunoreactive (TH-ir) cells were counted in the A8, A9 and A10 regions of the substantia nigra (SN) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57BL/6 mice. The effect of EGCG on microglial activation in the SN was also investigated. Pretreatment with EGCG (1 to 100 micromol/L) significantly attenuated MPP+-induced TH-ir cell loss by 22.2% to 80.5% in the mesencephalic cell cultures. In MPTP-treated C57BL/6 mice, EGCG at a low concentration (1 mg/kg) provided significant protection against MPTP-induced TH-ir cell loss by 50.9% in the whole nigral area and by 71.7% in the A9 region. EGCG at 5 mg/kg showed more prominent protective effect than at 1 or 10 mg/kg. EGCG pretreatment significantly inhibited microglial activation and CD11b expression induced by MPTP. EGCG exerts potent dopaminergic neuroprotective activity by means of microglial inhibition, which shed light on the potential use of EGCG in treatment of Parkinson's disease.

  16. Motivated Memories: Effects of Reward and Recollection in the Core Recollection Network and Beyond

    Science.gov (United States)

    Elward, Rachael L.; Vilberg, Kaia L.; Rugg, Michael D.

    2015-01-01

    fMRI was employed to assess whether the neural correlates of accurate source memory are modulated by the reward value of recollected information. Study items comprised pictures of objects, each paired with a depiction of 1 of 2 coins. The reward value of the coins ($2.00 vs. $0.02) was disclosed after study. At test, a source memory procedure was employed in which subjects discriminated between studied and unstudied objects and, for objects judged studied, indicated the identity of the coin paired with the object at study. Correct judgments earned a reward corresponding to the value of the coin, whereas incorrect judgments were penalized. No regions were identified where the magnitude of recollection effects was modulated by reward. Exclusive effects of source accuracy were evident in the hippocampus. Different striatal sub-regions demonstrated exclusive recollection effects, exclusive reward effects, and overlap between the 2 effects. The left angular gyrus and medial prefrontal cortex were additively responsive to source accuracy and the reward. The findings suggest that reward value and recollection success are conjointly but independently represented in at least 2 cortical regions and that striatal retrieval success effects cannot be accounted for in terms of a single construct, such as goal satisfaction. PMID:24872520

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

    Science.gov (United States)

    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.

  18. Endocannabinoid Signaling in Motivation, Reward, and Addiction: Influences on Mesocorticolimbic Dopamine Function.

    Science.gov (United States)

    Sagheddu, Claudia; Muntoni, Anna Lisa; Pistis, Marco; Melis, Miriam

    2015-01-01

    Evidence suggests that the endocannabinoid system has been conserved in the animal kingdom for 500 million years, and this system influences many critical behavioral processes including associative learning, reward signaling, goal-directed behavior, motor skill learning, and action-habit transformation. Additionally, the neurotransmitter dopamine has long been recognized to play a critical role in the processing of natural rewards, as well as of motivation that regulates approach and avoidance behavior. This motivational role of dopamine neurons is also based upon the evidence provided by several studies investigating disorders of dopamine pathways such as drug addiction and Parkinson's disease. From an evolutionary point of view, individuals engage in behaviors aimed at maximizing and minimizing positive and aversive consequences, respectively. Accordingly, those with the greatest fitness have a better potential to survival. Hence, deviations from fitness can be viewed as a part of the evolutionary process by means of natural selection. Given the long evolutionary history of both the endocannabinoid and dopaminergic systems, it is plausible that they must serve as fundamental and basic modulators of physiological functions and needs. Notably, endocannabinoids regulate dopamine neuronal activity and its influence on behavioral output. The goal of this chapter is to examine the endocannabinoid influence on dopamine signaling specifically related to (i) those behavioral processes that allow us to successfully adapt to ever-changing environments (i.e., reward signaling and motivational processes) and (ii) derangements from behavioral flexibility that underpin drug addiction. © 2015 Elsevier Inc. All rights reserved.

  19. Distinct representations for shifts of spatial attention and changes of reward contingencies in the human brain.

    Science.gov (United States)

    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.

  20. Excessive body fat linked to blunted somatosensory cortex response to general reward in adolescents.

    Science.gov (United States)

    Navas, J F; Barrós-Loscertales, A; Costumero-Ramos, V; Verdejo-Román, J; Vilar-López, R; Verdejo-García, A

    2018-01-01

    The brain reward system is key to understanding adolescent obesity in the current obesogenic environment, rich in highly appetising stimuli, to which adolescents are particularly sensitive. We aimed to examine the association between body fat levels and brain reward system responsivity to general (monetary) rewards in male and female adolescents. Sixty-eight adolescents (34 females; mean age (s.d.)= 16.56 (1.35)) were measured for body fat levels with bioelectric impedance, and underwent a functional magnetic resonance imaging (fMRI) scan during the Monetary Incentive Delay (MID) task. The MID task reliably elicits brain activations associated with two fundamental aspects of reward processing: anticipation and feedback. We conducted regression analyses to examine the association between body fat and brain reward system responsivity during reward anticipation and feedback, while controlling for sex, age and socioeconomic status. We also analysed the moderating impact of sex on the relationship between fat levels and brain responsivity measures. Brain imaging analyses were corrected for multiple comparisons, with a cluster-defining threshold of Preward feedback after controlling for key sociodemographic variables. Although we did not find significant associations between body fat and brain activations during reward anticipation, S1/supramarginal gyrus activation during feedback was linked to increased negative prediction error, that is, less reward than expected, in illustrative post hoc analyses. Sex did not significantly moderate the association between body fat and brain activation in the MID task. In adolescents, higher adiposity is linked to hypo-responsivity of somatosensory regions during general (monetary) reward feedback. Findings suggest that adolescents with excess weight have blunted activation in somatosensory regions involved in reward feedback learning.

  1. Waiting to win: elevated striatal and orbitofrontal cortical activity during reward anticipation in euthymic bipolar disorder adults

    Science.gov (United States)

    Nusslock, Robin; Almeida, Jorge RC; Forbes, Erika E; Versace, Amelia; Frank, Ellen; LaBarbara, Edmund J; Klein, Crystal R; Phillips, Mary L

    2012-01-01

    Objective Bipolar disorder may be characterized by a hypersensitivity to reward-relevant stimuli, potentially underlying the emotional lability and dysregulation that characterizes the illness. In parallel, research highlights the predominant role of striatal and orbitofrontal cortical (OFC) regions in reward-processing and approach-related affect. We aimed to examine whether bipolar disorder, relative to healthy, participants displayed elevated activity in these regions during reward processing. Methods Twenty-one euthymic bipolar I disorder and 20 healthy control participants with no lifetime history of psychiatric disorder underwent functional magnetic resonance imaging (fMRI) scanning during a card-guessing paradigm designed to examine reward-related brain function to anticipation and receipt of monetary reward and loss. Data were collected using a 3T Siemens Trio scanner. Results Region-of-interest analyses revealed that bipolar disorder participants displayed greater ventral striatal and right-sided orbitofrontal [Brodmann area (BA) 11] activity during anticipation, but not outcome, of monetary reward, relative to healthy controls (p anticipation (p anticipation may represent a neural mechanism for predisposition to expansive mood and hypo/mania in response to reward-relevant cues that characterizes bipolar disorder. Our findings contrast with research reporting blunted activity in the ventral striatum during reward processing in unipolar depressed individuals, relative to healthy controls. Examination of reward-related neural activity in bipolar disorder is a promising research focus to facilitate identification of biological markers of the illness. PMID:22548898

  2. Distinct medial temporal networks encode surprise during motivation by reward versus punishment

    Science.gov (United States)

    Murty, Vishnu P.; LaBar, Kevin S.; Adcock, R. Alison

    2016-01-01

    Adaptive motivated behavior requires predictive internal representations of the environment, and surprising events are indications for encoding new representations of the environment. The medial temporal lobe memory system, including the hippocampus and surrounding cortex, encodes surprising events and is influenced by motivational state. Because behavior reflects the goals of an individual, we investigated whether motivational valence (i.e., pursuing rewards versus avoiding punishments) also impacts neural and mnemonic encoding of surprising events. During functional magnetic resonance imaging (fMRI), participants encountered perceptually unexpected events either during the pursuit of rewards or avoidance of punishments. Despite similar levels of motivation across groups, reward and punishment facilitated the processing of surprising events in different medial temporal lobe regions. Whereas during reward motivation, perceptual surprises enhanced activation in the hippocampus, during punishment motivation surprises instead enhanced activation in parahippocampal cortex. Further, we found that reward motivation facilitated hippocampal coupling with ventromedial PFC, whereas punishment motivation facilitated parahippocampal cortical coupling with orbitofrontal cortex. Behaviorally, post-scan testing revealed that reward, but not punishment, motivation resulted in greater memory selectivity for surprising events encountered during goal pursuit. Together these findings demonstrate that neuromodulatory systems engaged by anticipation of reward and punishment target separate components of the medial temporal lobe, modulating medial temporal lobe sensitivity and connectivity. Thus, reward and punishment motivation yield distinct neural contexts for learning, with distinct consequences for how surprises are incorporated into predictive mnemonic models of the environment. PMID:26854903

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

    Directory of Open Access Journals (Sweden)

    Esther Via

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  5. Distinct medial temporal networks encode surprise during motivation by reward versus punishment.

    Science.gov (United States)

    Murty, Vishnu P; LaBar, Kevin S; Adcock, R Alison

    2016-10-01

    Adaptive motivated behavior requires predictive internal representations of the environment, and surprising events are indications for encoding new representations of the environment. The medial temporal lobe memory system, including the hippocampus and surrounding cortex, encodes surprising events and is influenced by motivational state. Because behavior reflects the goals of an individual, we investigated whether motivational valence (i.e., pursuing rewards versus avoiding punishments) also impacts neural and mnemonic encoding of surprising events. During functional magnetic resonance imaging (fMRI), participants encountered perceptually unexpected events either during the pursuit of rewards or avoidance of punishments. Despite similar levels of motivation across groups, reward and punishment facilitated the processing of surprising events in different medial temporal lobe regions. Whereas during reward motivation, perceptual surprises enhanced activation in the hippocampus, during punishment motivation surprises instead enhanced activation in parahippocampal cortex. Further, we found that reward motivation facilitated hippocampal coupling with ventromedial PFC, whereas punishment motivation facilitated parahippocampal cortical coupling with orbitofrontal cortex. Behaviorally, post-scan testing revealed that reward, but not punishment, motivation resulted in greater memory selectivity for surprising events encountered during goal pursuit. Together these findings demonstrate that neuromodulatory systems engaged by anticipation of reward and punishment target separate components of the medial temporal lobe, modulating medial temporal lobe sensitivity and connectivity. Thus, reward and punishment motivation yield distinct neural contexts for learning, with distinct consequences for how surprises are incorporated into predictive mnemonic models of the environment. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Disrupted reward circuits is associated with cognitive deficits and depression severity in major depressive disorder.

    Science.gov (United States)

    Gong, Liang; Yin, Yingying; He, Cancan; Ye, Qing; Bai, Feng; Yuan, Yonggui; Zhang, Haisan; Lv, Luxian; Zhang, Hongxing; Xie, Chunming; Zhang, Zhijun

    2017-01-01

    Neuroimaging studies have demonstrated that major depressive disorder (MDD) patients show blunted activity responses to reward-related tasks. However, whether abnormal reward circuits affect cognition and depression in MDD patients remains unclear. Seventy-five drug-naive MDD patients and 42 cognitively normal (CN) subjects underwent a resting-state functional magnetic resonance imaging scan. The bilateral nucleus accumbens (NAc) were selected as seeds to construct reward circuits across all subjects. A multivariate linear regression analysis was employed to investigate the neural substrates of cognitive function and depression severity on the reward circuits in MDD patients. The common pathway underlying cognitive deficits and depression was identified with conjunction analysis. Compared with CN subjects, MDD patients showed decreased reward network connectivity that was primarily located in the prefrontal-striatal regions. Importantly, distinct and common neural pathways underlying cognition and depression were identified, implying the independent and synergistic effects of cognitive deficits and depression severity on reward circuits. This study demonstrated that disrupted topological organization within reward circuits was significantly associated with cognitive deficits and depression severity in MDD patients. These findings suggest that in addition to antidepressant treatment, normalized reward circuits should be a focus and a target for improving depression and cognitive deficits in MDD patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Esther eHanssen

    2015-09-01

    Full Text Available 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

  8. Short post-weaning social isolation induces long-term changes in the dopaminergic system and increases susceptibility to psychostimulants in female rats.

    Science.gov (United States)

    Lampert, Carine; Arcego, Danusa Mar; de Sá Couto-Pereira, Natividade; Dos Santos Vieira, Aline; Toniazzo, Ana Paula; Krolow, Rachel; Garcia, Emily; Vendite, Deusa Aparecida; Calcagnotto, Maria Elisa; Dalmaz, Carla

    2017-10-01

    Childhood and adolescence are sensitive periods of development, marked by high brain maturation and plasticity. Exposure to early life stress, such as social isolation, is able to prompt changes in sensitive brain circuitries, essentially in the mesolimbic dopaminergic system and increase the risk for addictive behaviors later in life. Post-weaning social isolation can stimulate the consumption of rewarding substances, like drugs of abuse and palatable foods. However, most studies analyze long periods of social isolation and very little is known about the effects of a brief social isolation in a sensitive period of development and its association with palatable food on the reward system sensitization. Furthermore, females are more susceptible to the reinforcing effect of drugs than males. Therefore, the aim of this study was to analyze the effects of a short post-weaning social isolation combined with a free access to a chronic high sugar diet (HSD) on the dopaminergic system, oxidative status and behavioral response to an amphetamine-like drug in adulthood. We used female Wistar rats that were socially isolated from post-natal days (PD) 21 to 35 and received free access to a HSD until PD 60. On PD 65, animals were submitted to a challenge with diethylpropion (DEP), an amphetamine-like drug and different responses were analyzed: locomotor activity, immmunocontent of dopamine related proteins, and the oxidative status in the striatum, before and after the DEP challenge. We showed that a short post-weaning social isolation (SI) increased the locomotor response to DEP, when compared with previous saline administration. Social isolation also increased dopamine transporter, tyrosine hydroxylase, and decreased dopamine D2 receptor immunocontent. Additionally, SI increased the overall oxidative status parameters after the challenge with DEP. Interestingly, the exposure to a HSD prevented the SI effects on locomotor response, but did not interfere in the dopaminergic

  9. Monetary reward speeds up voluntary saccades.

    Science.gov (United States)

    Chen, Lewis L; Chen, Y Mark; Zhou, Wu; Mustain, William D

    2014-01-01

    Past studies have shown that reward contingency is critical for sensorimotor learning, and reward expectation speeds up saccades in animals. Whether monetary reward speeds up saccades in human remains unknown. Here we addressed this issue by employing a conditional saccade task, in which human subjects performed a series of non-reflexive, visually-guided horizontal saccades. The subjects were (or were not) financially compensated for making a saccade in response to a centrally-displayed visual congruent (or incongruent) stimulus. Reward modulation of saccadic velocities was quantified independently of the amplitude-velocity coupling. We found that reward expectation significantly sped up voluntary saccades up to 30°/s, and the reward modulation was consistent across tests. These findings suggest that monetary reward speeds up saccades in human in a fashion analogous to how juice reward sped up saccades in monkeys. We further noticed that the idiosyncratic nasal-temporal velocity asymmetry was highly consistent regardless of test order, and its magnitude was not correlated with the magnitude of reward modulation. This suggests that reward modulation and the intrinsic velocity asymmetry may be governed by separate mechanisms that regulate saccade generation.

  10. Reward system dysfunction in autism spectrum disorders

    Science.gov (United States)

    Schulte-Rüther, Martin; Nehrkorn, Barbara; Müller, Kristin; Fink, Gereon R.; Kamp-Becker, Inge; Herpertz-Dahlmann, Beate; Schultz, Robert T.; Konrad, Kerstin

    2013-01-01

    Although it has been suggested that social deficits of autism spectrum disorders (ASDs) are related to reward circuitry dysfunction, very little is known about the neural reward mechanisms in ASD. In the current functional magnetic resonance imaging study, we investigated brain activations in response to both social and monetary reward in a group of children with ASD, relative to matched controls. Participants with ASD showed the expected hypoactivation in the mesocorticolimbic circuitry in response to both reward types. In particular, diminished activation in the nucleus accumbens was observed when money, but not when social reward, was at stake, whereas the amygdala and anterior cingulate cortex were hypoactivated within the ASD group in response to both rewards. These data indicate that the reward circuitry is compromised in ASD in social as well as in non-social, i.e. monetary conditions, which likely contributes to atypical motivated behaviour. Taken together, with incentives used in this study sample, there is evidence for a general reward dysfunction in ASD. However, more ecologically valid social reward paradigms are needed to fully understand, whether there is any domain specificity to the reward deficit that appears evident in ASD, which would be most consistent with the ASD social phenotype. PMID:22419119

  11. Memory Consolidation and Neural Substrate of Reward

    Directory of Open Access Journals (Sweden)

    Redolar-Ripoll, Diego

    2012-08-01

    Full Text Available The aim of this report is to analyze the relationships between reward and learning and memory processes. Different studies have described how information about rewards influences behavior and how the brain uses this reward information to control learning and memory processes. Reward nature seems to be processed in different ways by neurons in different brain structures, ranging from the detection and perception of rewards to the use of information about predicted rewards for the control of goal-directed behavior. The neural substrate underling this processing of reward information is a reliable way of improving learning and memory processes. Evidence from several studies indicates that this neural system can facilitate memory consolidation in a wide variety of learning tasks. From a molecular perspective, certain cardinal features of reward have been described as forms of memory. Studies of human addicts and studies in animal models of addiction show that chronic drug exposure produces stable changes in the brain at the cellular and molecular levels that underlie the long-lasting behavioral plasticity associated with addiction. These molecular and cellular adaptations involved in addiction are also implicated in learning and memory processes. Dopamine seems to be a critical common signal to activate different genetic mechanisms that ultimately remodel synapses and circuits. Despite memory is an active and complex process mediated by different brain areas, the neural substrate of reward is able to improve memory consolidation in a several paradigms. We believe that there are many equivalent traits between reward and learning and memory processes.

  12. Just watching the game ain't enough: striatal fMRI reward responses to successes and failures in a video game during active and vicarious playing.

    Science.gov (United States)

    Kätsyri, Jari; Hari, Riitta; Ravaja, Niklas; Nummenmaa, Lauri

    2013-01-01

    Although the multimodal stimulation provided by modern audiovisual video games is pleasing by itself, the rewarding nature of video game playing depends critically also on the players' active engagement in the gameplay. The extent to which active engagement influences dopaminergic brain reward circuit responses remains unsettled. Here we show that striatal reward circuit responses elicited by successes (wins) and failures (losses) in a video game are stronger during active than vicarious gameplay. Eleven healthy males both played a competitive first-person tank shooter game (active playing) and watched a pre-recorded gameplay video (vicarious playing) while their hemodynamic brain activation was measured with 3-tesla functional magnetic resonance imaging (fMRI). Wins and losses were paired with symmetrical monetary rewards and punishments during active and vicarious playing so that the external reward context remained identical during both conditions. Brain activation was stronger in the orbitomedial prefrontal cortex (omPFC) during winning than losing, both during active and vicarious playing. In contrast, both wins and losses suppressed activations in the midbrain and striatum during active playing; however, the striatal suppression, particularly in the anterior putamen, was more pronounced during loss than win events. Sensorimotor confounds related to joystick movements did not account for the results. Self-ratings indicated losing to be more unpleasant during active than vicarious playing. Our findings demonstrate striatum to be selectively sensitive to self-acquired rewards, in contrast to frontal components of the reward circuit that process both self-acquired and passively received rewards. We propose that the striatal responses to repeated acquisition of rewards that are contingent on game related successes contribute to the motivational pull of video-game playing.

  13. Just watching the game ain’t enough: Striatal fMRI reward responses to successes and failures in a video game during active and vicarious playing

    Directory of Open Access Journals (Sweden)

    Jari eKätsyri

    2013-06-01

    Full Text Available Although the multimodal stimulation provided by modern audiovisual video games is pleasing by itself, the rewarding nature of video game playing depends critically also on the players’ active engagement in the gameplay. The extent to which active engagement influences dopaminergic brain reward circuit responses remains unsettled. Here we show that striatal reward circuit responses elicited by successes (wins and failures (losses in a video game are stronger during active than vicarious gameplay. Eleven healthy males both played a competitive first-person tank shooter game (active playing and watched a pre-recorded gameplay video (vicarious playing while their hemodynamic brain activation was measured with 3-tesla functional magnetic resonance imaging (fMRI. Wins and losses were paired with symmetrical monetary rewards and punishments during active and vicarious playing so that the external reward context remained identical during both conditions. Brain activation was stronger in the orbitomedial prefrontal cortex (omPFC during winning than losing, both during active and vicarious playing conditions. In contrast, both wins and losses suppressed activations in the midbrain and striatum during active playing; however, the striatal suppression, particularly in the anterior putamen, was more pronounced during loss than win events. Sensorimotor confounds related to joystick movements did not account for the results. Self-ratings indicated losing to be more unpleasant during active than vicarious playing. Our findings demonstrate striatum to be selectively sensitive to self-acquired rewards, in contrast to frontal components of the reward circuit that process both self-acquired and passively received rewards. We propose that the striatal responses to repeated acquisition of rewards that are contingent on game related successes contribute to the motivational pull of video-game playing.

  14. Maladaptive Reward-Learning and Impulse Control Disorders in Patients with Parkinson’s Disease: A Clinical Overview and Pathophysiology Update

    Directory of Open Access Journals (Sweden)

    Jee-Young Lee

    2014-10-01

    Full Text Available Impulse control disorders (ICD in Parkinson’s disease (PD are a disabling non-motor symptom with frequencies of 13–35% among patients receiving dopamine replacement therapy. ICD in PD is strongly associated with dopaminergic drug use, especially non-ergot dopamine agonists (DA. However, individual susceptibility and disease-related neural changes are also important contributors to the development of ICD. Discrepancies between nigrostriatal and mesolimbic dopaminergic degeneration and non-physiological administration of dopaminergic drugs may induce abnormal ’hyperstimulation’ of the mesolimbic system, which alters reward-learning behaviors in PD patients. In addition, DA can make patients more impulsive during decision-making and seek risk-taking behaviors. DA intake is also related to the biased representation of rewards. Ultimately, loss of negative feedback control due to dysfunctional frontostriatal connections is necessary for the establishment of ICD in PD. The subsequent behavioral and neural changes are affected by PD treatment and disease progression; thus, proper treatment guidelines for physicians are needed to prevent the development of ICD. Future studies aimed at producing novel therapeutics to control the risk factors for ICD or treat ICD behaviors in PD are warranted. This review summarizes recent advances from epidemiological and pathophysiological studies on ICD in PD. Management principles and limitations of current therapeutics are briefly discussed.

  15. Endorphinic neurons are contacting the tuberoinfundibular dopaminergic neurons in the rat brain

    International Nuclear Information System (INIS)

    Morel, G.; Pelletier, G.

    1986-01-01

    The anatomical relationships between endorphinic neurons and dopaminergic neurons were evaluated in the rat hypothalamus using a combination of immunocytochemistry and autoradiography. In the arcuate nucleus, endorphinic endings were seen making contacts with dopaminergic cell bodies and dendrites. No synapsis could be observed at the sites of contacts. These results strongly suggest that the endorphinic neurons are directly acting on dopaminergic neurons to modify the release of dopamine into the pituitary portal system

  16. Neural signal during immediate reward anticipation in schizophrenia: Relationship to real-world motivation and function

    Science.gov (United States)

    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

  17. Neural signal during immediate reward anticipation in schizophrenia: Relationship to real-world motivation and function

    Directory of Open Access Journals (Sweden)

    Karuna Subramaniam

    2015-01-01

    Full Text Available 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.

  18. Prediction-error in the context of real social relationships modulates reward system activity

    Directory of Open Access Journals (Sweden)

    Joshua ePoore

    2012-08-01

    Full Text Available The human reward system is sensitive to both social (e.g., validation and non-social rewards (e.g., money and is likely integral for relationship development and reputation building. However, data is sparse on the question of whether implicit social reward processing meaningfully contributes to explicit social representations such as trust and attachment security in pre-existing relationships. This event-related fMRI experiment examined reward system prediction-error activity in response to a potent social reward—social validation—and this activity’s relation to both attachment security and trust in the context of real romantic relationships. During the experiment, participants’ expectations for their romantic partners’ positive regard of them were confirmed (validated or violated, in either positive or negative directions. Primary analyses were conducted using predefined regions of interest, the locations of which were taken from previously published research. Results indicate that activity for mid-brain and striatal reward system regions of interest was modulated by social reward expectation violation in ways consistent with prior research on reward prediction-error. Additionally, activity in the striatum during viewing of disconfirmatory information was associated with both increases in post-scan reports of attachment anxiety and decreases in post-scan trust, a finding that follows directly from representational models of attachment and trust.

  19. Withdrawal from Buprenorphine/Naloxone and Maintenance with a Natural Dopaminergic Agonist: A Cautionary Note.

    Science.gov (United States)

    Blum, Kenneth; Oscar-Berman, Marlene; Femino, John; Waite, Roger L; Benya, Lisa; Giordano, John; Borsten, Joan; Downs, William B; Braverman, Eric R; Loehmann, Raquel; Dushaj, Kristina; Han, David; Simpatico, Thomas; Hauser, Mary; Barh, Debmalya; McLaughlin, Thomas

    2013-04-23

    While numerous studies support the efficacy of methadone and buprenorphine for the stabilization and maintenance of opioid dependence, clinically significant opioid withdrawal symptoms occur upon tapering and cessation of dosage. We present a case study of a 35 year old Caucasian female (Krissie) who was prescribed increasing dosages of prescription opioids after carpel tunnel surgery secondary to chronic pain from reflex sympathetic dystrophy and fibromyalgia. Over the next 5 years, daily dosage requirements increased to over 80 mg of Methadone and 300 ug/hr Fentanyl transdermal patches, along with combinations of 12-14 1600 mcg Actig lollipop and oral 100 mg Morphine and 30 mg oxycodone 1-2 tabs q4-6hr PRN for breakthrough pain. Total monthly prescription costs including supplemental benzodiazepines, hypnotics and stimulants exceeded $50,000. The patient was subsequently transferred to Suboxone® in 2008, and the dosage was gradually tapered until her admission for inpatient detoxification with KB220Z a natural dopaminergic agonist. We carefully documented her withdrawal symptoms when she precipitously stopped taking buprenorphine/naloxone and during follow-up while taking KB220Z daily. We also genotyped the patient using a reward gene panel including (9 genes 18 alleles): DRD 2,3,4; MOA-A; COMT; DAT1; 5HTTLLR; OPRM1; and GABRA3. At 432 days post Suboxone® withdrawal the patient is being maintained on KB220Z, has been urine tested and is opioid free. Genotyping data revealed a moderate genetic risk for addiction showing a hypodopaminergic trait. This preliminary case data suggest that the daily use of KB220Z could provide a cost effective alternative substitution adjunctive modality for Suboxone®. We encourage double-blind randomized -placebo controlled studies to test the proposition that KB220Z may act as a putative natural opioid substitution maintenance adjunct.

  20. Dopaminergic tone does not influence pain levels during placebo interventions in patients with chronic neuropathic pain.

    Science.gov (United States)

    Skyt, Ina; Moslemi, Kurosh; Baastrup, Cathrine; Grosen, Kasper; Benedetti, Fabrizio; Petersen, Gitte L; Price, Donald D; Hall, Kathryn T; Kaptchuk, Ted J; Svensson, Peter; Jensen, Troels S; Vase, Lene

    2017-10-23

    Placebo effects have been reported in patients with chronic neuropathic pain. Expected pain levels and positive emotions are involved in the observed pain relief, but the underlying neurobiology is largely unknown. Patients with neuropathic pain are highly motivated for pain relief, and as motivational factors such as expectations of reward, as well as pain processing in itself, are related to the dopaminergic system, it can be speculated that dopamine release contributes to placebo effects in neuropathic pain. Nineteen patients with neuropathic pain after thoracic surgery were tested during a placebo intervention consisting of open and hidden applications of the pain-relieving agent lidocaine (2 mL) and no treatment. The dopamine antagonist haloperidol (2 mg) and the agonist levodopa/carbidopa (100/25 mg) were administered to test the involvement of dopamine. Expected pain levels, desire for pain relief, and ongoing and evoked pain were assessed on mechanical visual analog scales (0-10). Significant placebo effects on ongoing (P ≤ 0.003) and evoked (P ≤ 0.002) pain were observed. Expectancy and desire accounted for up to 41.2% and 71.5% of the variance in ongoing and evoked pain, respectively, after the open application of lidocaine. We found no evidence for an effect of haloperidol and levodopa/carbidopa on neuropathic pain levels (P = 0.071-0.963). Dopamine seemed to influence the levels of expectancy and desire, yet there was no evidence for indirect or interaction effects on the placebo effect. This is the first study to suggest that dopamine does not contribute to placebo effects in chronic neuropathic pain.

  1. Development of clinical study and application on dopaminergic neurotransmitters and neuroreceptor imaging

    International Nuclear Information System (INIS)

    Wang Rongfu

    2000-01-01

    In recent years, the neurotransmitter mapping has been rapidly developed from a lot of fundamental researches to the studies of clinical applications. At present, the dopaminergic neurotransmitter and receptor imaging in the central neurotransmitter mapping study are the most active area including dopaminergic receptor, dopaminergic neurotransmitter and dopaminergic transporter imaging, etc,. The nuclear medicine functional imaging technique with positron emission tomography and single photon emission computed tomography possesses potential advantages in the diagnosis and distinguished diagnosis of neuropsychiatric disorders and movement disorders, and in the study of recognition function

  2. Value-based modulation of memory encoding involves strategic engagement of fronto-temporal semantic processing regions.

    Science.gov (United States)

    Cohen, Michael S; Rissman, Jesse; Suthana, Nanthia A; Castel, Alan D; Knowlton, Barbara J

    2014-06-01

    A number of prior fMRI studies have focused on the ways in which the midbrain dopaminergic reward system coactivates with hippocampus to potentiate memory for valuable items. However, another means by which people could selectively remember more valuable to-be-remembered items is to be selective in their use of effective but effortful encoding strategies. To broadly examine the neural mechanisms of value on subsequent memory, we used fMRI to assess how differences in brain activity at encoding as a function of value relate to subsequent free recall for words. Each word was preceded by an arbitrarily assigned point value, and participants went through multiple study-test cycles with feedback on their point total at the end of each list, allowing for sculpting of cognitive strategies. We examined the correlation between value-related modulation of brain activity and participants' selectivity index, which measures how close participants were to their optimal point total, given the number of items recalled. Greater selectivity scores were associated with greater differences in the activation of semantic processing regions, including left inferior frontal gyrus and left posterior lateral temporal cortex, during the encoding of high-value words relative to low-value words. Although we also observed value-related modulation within midbrain and ventral striatal reward regions, our fronto-temporal findings suggest that strategic engagement of deep semantic processing may be an important mechanism for selectively encoding valuable items.

  3. Value-based modulation of memory encoding involves strategic engagement of fronto-temporal semantic processing regions

    Science.gov (United States)

    Cohen, Michael S.; Rissman, Jesse; Suthana, Nanthia A.; Castel, Alan D.; Knowlton, Barbara J.

    2014-01-01

    A number of prior fMRI studies have focused on the ways in which the midbrain dopaminergic reward system co-activates with hippocampus to potentiate memory for valuable items. However, another means by which people could selectively remember more valuable to-be-remembered items is to be selective in their use of effective but effortful encoding strategies. To broadly examine the neural mechanisms of value on subsequent memory, we used fMRI to examine how differences in brain activity at encoding as a function of value relate to subsequent free recall for words. Each word was preceded by an arbitrarily assigned point value, and participants went through multiple study-test cycles with feedback on their point total at the end of each list, allowing for sculpting of cognitive strategies. We examined the correlation between value-related modulation of brain activity and participants’ selectivity index, a measure of how close participants were to their optimal point total given the number of items recalled. Greater selectivity scores were associated with greater differences in activation of semantic processing regions, including left inferior frontal gyrus and left posterior lateral temporal cortex, during encoding of high-value words relative to low-value words. Although we also observed value-related modulation within midbrain and ventral striatal reward regions, our fronto-temporal findings suggest that strategic engagement of deep semantic processing may be an important mechanism for selectively encoding valuable items. PMID:24683066

  4. Reward disrupts reactivated human skill memory

    OpenAIRE

    Dayan, Eran; Laor-Maayany, Rony; Censor, Nitzan

    2016-01-01

    Accumulating evidence across species and memory domains shows that when an existing memory is reactivated, it becomes susceptible to modifications. However, the potential role of reward signals in these mechanisms underlying human memory dynamics is unknown. Leaning on a wealth of findings on the role of reward in reinforcing memory, we tested the impact of reinforcing a skill memory trace with monetary reward following memory reactivation, on strengthening of the memory trace. Reinforcing re...

  5. An expert system for reward systems design.

    OpenAIRE

    Erturk, Alper

    2000-01-01

    Approved for public release; distribution is unlimited Today's business environment is a highly competitive marketplace. In this competition, organizations distribute numerous rewards to motivate, attract and retain employees, such as pay, fringe benefits and promotions. However, not all managers have the necessary knowledge and expertise to effectively decide and structure reward systems. This thesis presents an expert system to assist managers with designing the most appropriate reward s...

  6. An in vivo study of the dopaminergic receptors in the brain of man using 11C-pimozide and positron emission tomography

    International Nuclear Information System (INIS)

    Baron, J.C.; Comar, D.; Crouzel, C.; Mestelan, G.; Zarifian, E.; Loo, H.; Agid, Y.

    1982-09-01

    Positron emission tomography was used to establish the regional cerebral pharmacokinetics of a carbon 11-labelled neuroleptic, pimozide, in an attempt to observe its specific bonding to dopaminergic receptors in vivo. The 11 C-pimozide kinetics were compared in two brain structures at the two ends of the dopaminergic receptor density scale: the striatum and cerebellum, very rich in and devoid of these receptors respectively. In 8 patients a significant radioactivity uptake was observed in the striatum as compared with the cerebellum, in agreement with in vivo studies on animals using tritiated pimozide. In 5 patients pre-treated by a therapeutic dose of a cold neuroleptic (haloperidol) this difference in kinetics no longer existed. Moreover no kinetic difference is observed, either before or after haloperidol administration, between the frontal cortex (relatively low in dopaminergic receptors) and cerebellum. These results strongly suggest that pharmacokinetic phenomena directly related to the specific bonding of 11 C-pimozide on the striatal dopaminergic receptors are observable on man in vivo. This specific bonding however remains quantitatively weak as compared with the strong non-specific bonding

  7. Lesion of the locus coeruleus aggravates dopaminergic neuron degeneration by modulating microglial function in mouse models of Parkinson׳s disease.

    Science.gov (United States)

    Yao, Ning; Wu, Yanhong; Zhou, Yan; Ju, Lili; Liu, Yujun; Ju, Rongkai; Duan, Deyi; Xu, Qunyuan

    2015-11-02

    The degeneration of noradrenergic neurons in the locus coeruleus (LC) commonly occurs in patients with Parkinson's disease (PD), which is characterized by a selective injury of dopaminergic neurons in the substantia nigra (SN). The pathological impact of the LC on the SN in the disease is unknown. In the present study, we used a noradrenergic toxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), to deplete noradrenaline (NA) derived from the LC to explore its influence on degeneration or injury of dopaminergic neurons in the SN in mouse model produced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or lipopolysaccharide (LPS). Our results demonstrated that lesion of the LC could change microglial function in the brain, which led to enhanced or prolonged expression of pro-inflammatory cytokines, diminished neurotrophic factors, and weakened ability of anti-oxidation in the SN. The in vitro experiments further confirmed that NA could reduce the inflammatory reaction of microglia. The selective injury of dopaminergic neurons by inflammation, however, was due to the inflammation in different brain regions rather than the depletion of NA. Our results indicate that the lesion in the LC is an important factor in promoting dopaminergic neuron degeneration by impacting the function of microglia in the midbrain. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Self-stimulating rats combine subjective reward magnitude and subjective reward rate multiplicatively.

    Science.gov (United States)

    Leon, M I; Gallistel, C R

    1998-07-01

    For rats that bar pressed for intracranial electrical stimulation in a 2-lever matching paradigm with concurrent variable interval schedules of reward, the authors found that the time allocation ratio is based on a multiplicative combination of the ratio of subjective reward magnitudes and the ratio of the rates of reward. Multiplicative combining was observed in a range covering approximately 2 orders of magnitude in the ratio of the rates of reward from about 1:10 to 10:1) and an order of magnitude change in the size of rewards. After determining the relation between the pulse frequency of stimulation and subjective reward magnitude, the authors were able to predict from knowledge of the subjective magnitudes of the rewards and the obtained relative rates of reward the subject's time allocation ratio over a range in which it varied by more than 3 orders of magnitude.

  9. Extrastriatal dopaminergic changes in Parkinson's disease patients with impulse control disorders.

    Science.gov (United States)

    Lee, Jee-Young; Seo, Seong Ho; Kim, Yu Kyeong; Yoo, Hye Bin; Kim, Young Eun; Song, In Chan; Lee, Jae Sung; Jeon, Beom S

    2014-01-01

    To investigate the extrastriatal dopaminergic neural changes in relation to the medication-related impulse control disorders (ICD) in Parkinson's disease (PD). A total of 31 subjects (11 and 11 drug-treated PD patients with and without medication-related ICDs and 9 healthy controls) having no other co-morbid psychiatric disorders participated in this study. Each subject underwent dynamic N-(3-[(18)F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography scans. Binding potentials (BP) at nucleus accumbens, amygdala, orbitofrontal and ventromedial prefrontal cortex (VMPFC), putamen and caudate nucleus were estimated, and whole brain parametric maps of [(18)F]-FP-CIT binding were analysed by original and putaminal normalised manners. Compared with the healthy controls, BPs at both VMPFCs were significantly high and the extrastriatal to putaminal BP ratios at all regions were approximately three times higher in both PD groups. The PD ICD patients showed significantly higher BPs at the right VMPFC and tendency to lower BPs at the left nucleus accumbens compared with those free of ICD. The ICD subjects also showed reduced uptakes at both ventral striatal regions in the original parametric analysis and higher uptakes at the left insular and right posterior cingulate cortex and lower uptakes at both ventral pallidums in the putaminal normalised parametric analysis compared with the non-ICD subjects. A great gap in extrastriatal versus striatal dopaminergic fibre degenerations is an intrinsic condition predisposing to ICD in PD. Distinct pattern of extrastriatal changes between the ICD and non-ICD patients could provide a further insight into a mechanism of ICD in PD.

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

    Science.gov (United States)

    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.

  11. Effects of cannabinoid CB₁ receptor antagonist rimonabant on acquisition and reinstatement of psychostimulant reward memory in mice.

    Science.gov (United States)

    Yu, Lu-Lu; Zhou, Shuang-Jiang; Wang, Xue-Yi; Liu, Jian-Feng; Xue, Yan-Xue; Jiang, Wengao; Lu, Lin

    2011-02-02

    Drug addiction processes are considered to be mainly controlled by the mesocorticolimbic dopamine system. Cannabinoids, a class of psychoactive drugs of abuse, elicit their rewarding and pharmacological effects through the endocannabinoid system. Previous research has indicated that dopaminergic neurons in the mesocorticolimbic system are also under the control of the endocannabinoid system. Recently, evidence has suggested that the endocannabinoid system may also participate in the modulation of the common reward system. The present study examined whether rimonabant, a cannabinoid CB₁ receptor antagonist, disrupts the acquisition and reinstatement of psychostimulant reward memory measured by conditioned place preference (CPP). Mice were trained to acquire methamphetamine or cocaine-induced CPP. A priming injection of methamphetamine (0.5 mg/kg, i.p.) or cocaine (5 mg/kg, i.p.) was respectively given to reinstate methamphetamine or cocaine-induced CPP after extinction. Vehicle or rimonabant (1 or 3 mg/kg, i.p.) was administered at different time-points: 30 min before each CPP training session (acquisition) or 30 min before the priming injection (reinstatement). Rimonabant at doses of 1 and 3 mg/kg significantly inhibited the acquisition of methamphetamine- and cocaine-induced CPP. At the high dose (3 mg/kg), rimonabant disrupted the reinstatement of extinguished methamphetamine- or cocaine-induced CPP. These findings indicate that cannabinoid CB₁ receptors play a major role in psychostimulant reward memory, and rimonabant may be a potential pharmacotherapy for psychostimulant addiction. Copyright © 2010. Published by Elsevier B.V.

  12. Neural alterations of fronto-striatal circuitry during reward anticipation in euthymic bipolar disorder.

    Science.gov (United States)

    Schreiter, S; Spengler, S; Willert, A; Mohnke, S; Herold, D; Erk, S; Romanczuk-Seiferth, N; Quinlivan, E; Hindi-Attar, C; Banzhaf, C; Wackerhagen, C; Romund, L; Garbusow, M; Stamm, T; Heinz, A; Walter, H; Bermpohl, F

    2016-11-01

    Bipolar disorder (BD), with the hallmark symptoms of elevated and depressed mood, is thought to be characterized by underlying alterations in reward-processing networks. However, to date the neural circuitry underlying abnormal responses during reward processing in BD remains largely unexplored. The aim of this study was to investigate whether euthymic BD is characterized by aberrant ventral striatal (VS) activation patterns and altered connectivity with the prefrontal cortex in response to monetary gains and losses. During functional magnetic resonance imaging 20 euthymic BD patients and 20 age-, gender- and intelligence quotient-matched healthy controls completed a monetary incentive delay paradigm, to examine neural processing of reward and loss anticipation. A priori defined regions of interest (ROIs) included the VS and the anterior prefrontal cortex (aPFC). Psychophysiological interactions (PPIs) between these ROIs were estimated and tested for group differences for reward and loss anticipation separately. BD participants, relative to healthy controls, displayed decreased activation selectively in the left and right VS during anticipation of reward, but not during loss anticipation. PPI analyses showed decreased functional connectivity between the left VS and aPFC in BD patients compared with healthy controls during reward anticipation. This is the first study showing decreased VS activity and aberrant connectivity in the reward-processing circuitry in euthymic, medicated BD patients during reward anticipation. Our findings contrast with research supporting a reward hypersensitivity model of BD, and add to the body of literature suggesting that blunted activation of reward processing circuits may be a vulnerability factor for mood disorders.

  13. Association of Elevated Reward Prediction Error Response With Weight Gain in Adolescent Anorexia Nervosa.

    Science.gov (United States)

    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.

  14. Value and probability coding in a feedback-based learning task utilizing food rewards.

    Science.gov (United States)

    Tricomi, Elizabeth; Lempert, Karolina M

    2015-01-01

    For the consequences of our actions to guide behavior, the brain must represent different types of outcome-related information. For example, an outcome can be construed as negative because an expected reward was not delivered or because an outcome of low value was delivered. Thus behavioral consequences can differ in terms of the information they provide about outcome probability and value. We investigated the role of the striatum in processing probability-based and value-based negative feedback by training participants to associate cues with food rewards and then employing a selective satiety procedure to devalue one food outcome. Using functional magnetic resonance imaging, we examined brain activity related to receipt of expected rewards, receipt of devalued outcomes, omission of expected rewards, omission of devalued outcomes, and expected omissions of an outcome. Nucleus accumbens activation was greater for rewarding outcomes than devalued outcomes, but activity in this region did not correlate with the probability of reward receipt. Activation of the right caudate and putamen, however, was largest in response to rewarding outcomes relative to expected omissions of reward. The dorsal striatum (caudate and putamen) at the time of feedback also showed a parametric increase correlating with the trialwise probability of reward receipt. Our results suggest that the ventral striatum is sensitive to the motivational relevance, or subjective value, of the outcome, while the dorsal striatum codes for a more complex signal that incorporates reward probability. Value and probability information may be integrated in the dorsal striatum, to facilitate action planning and allocation of effort. Copyright © 2015 the American Physiological Society.

  15. An Expert System for Reward Systems Design

    National Research Council Canada - National Science Library

    Erturk, Alper

    2000-01-01

    Today's business environment is a highly competitive marketplace. In this competition, organizations distribute numerous rewards to motivate, attract and retain employees, such as pay, fringe benefits and promotions...

  16. Noradrenaline and dopamine neurons in the reward/effort trade-off: a direct electrophysiological comparison in behaving monkeys.

    Science.gov (United States)

    Varazzani, Chiara; San-Galli, Aurore; Gilardeau, Sophie; Bouret, Sebastien

    2015-05-20

    Motivation determines multiple aspects of behavior, including action selection and energization of behavior. Several components of the underlying neural systems have been examined closely, but the specific role of the different neuromodulatory systems in motivation remains unclear. Here, we compare directly the activity of dopaminergic neurons from the substantia nigra pars compacta and noradrenergic neurons from the locus coeruleus in monkeys performing a task manipulating the reward/effort trade-off. Consistent with previous reports, dopaminergic neurons encoded the expected reward, but we found that they also anticipated the upcoming effort cost in connection with its negative influence on action selection. Conversely, the firing of noradrenergic neurons increased with both pupil dilation and effort production in relation to the energization of behavior. Therefore, this work underlines the contribution of dopamine to effort-based decision making and uncovers a specific role of noradrenaline in energizing behavior to face challenges. Copyright © 2015 the authors 0270-6474/15/357866-12$15.00/0.

  17. Embedding reward signals into perception and cognition

    Directory of Open Access Journals (Sweden)

    Luiz Pessoa

    2010-09-01

    Full Text Available Despite considerable interest in the neural basis of valuation, how valuation affects cognitive processing has received relatively less attention. Here, we review evidence from recent behavioral and neuroimaging studies supporting the notion that motivation can enhance perceptual and executive control processes to achieve more efficient goal-directed behavior. Specifically, in the context of cognitive tasks offering monetary gains, improved behavioral performance has been repeatedly observed in conjunction with elevated neural activations in task-relevant perceptual, cognitive, and reward-related regions. We address the neural basis of motivation-cognition interactions by suggesting various modes of communication between relevant neural networks: (1 global hub regions may integrate information from multiple inputs providing a communicative link between specialized networks, (2 point-to-point interactions allow for more specific cross-network communication, and (3 diffuse neuromodulatory systems can relay motivational signals to cortex and enhance signal processing. Together, these modes of communication allow information regarding motivational significance to reach relevant brain regions and shape behavior.

  18. Protection of dopaminergic neurons by 5-lipoxygenase inhibitor.

    Science.gov (United States)

    Kang, Kai-Hsiang; Liou, Horng-Hui; Hour, Mann-Jen; Liou, Houng-Chi; Fu, Wen-Mei

    2013-10-01

    Neuroinflammation and oxidative stress are important factors that induce neurodegeneration in age-related neurological disorders. 5-Lipoxygenase (5-LOX) is the enzyme responsible for catalysing the synthesis of leukotriene or 5-HETE from arachidonic acid. 5-LOX is expressed in the central nervous system and may cause neurodegenerative disease. In this study, we investigated the effect of the pharmacological inhibition of 5-lipoxygenase on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/MPP(+)-induced dopaminergic neuronal death in midbrain neuron-glia co-cultures and in mice. It was found that 5-LOX was over-expressed in astrocytes after the injection of MPTP into C57BL6 mice. MK-886, a specific inhibitor of 5-LOX activating protein (FLAP), significantly increased [(3)H]-dopamine uptake, a functional indicator of the integrity of dopaminergic neurons, in midbrain cultures or the SH-SY5Y human dopaminergic cell line following MPP(+) treatment. In addition, LTB₄, one of 5-LOX's downstream products, was increased in the striatum and substantia nigra following MPTP injection in mice. LTB₄ but not LTD₄ and 5-HETE enhanced MPP(+)-induced neurotoxicity in primary midbrain cultures. MK-886 administration increased the number of tyrosine hydroxylase-positive neurons in the substantia nigra and the dopamine content in the striatum in MPTP-induced parkinsonian mice. Furthermore, the MPTP-induced upregulation of LTB₄ in the striatum and substantia nigra was antagonised by MK-886. These results suggest that 5-LOX inhibitors may be developed as novel neuroprotective agents and LTB₄ may play an important pathological role in Parkinson's disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Selective Activation of Cholinergic Interneurons Enhances Accumbal Phasic Dopamine Release: Setting the Tone for Reward Processing

    Directory of Open Access Journals (Sweden)

    Roger Cachope

    2012-07-01

    Full Text Available Dopamine plays a critical role in motor control, addiction, and reward-seeking behaviors, and its release dynamics have traditionally been linked to changes in midbrain dopamine neuron activity. Here, we report that selective endogenous cholinergic activation achieved via in vitro optogenetic stimulation of nucleus accumbens, a terminal field of dopaminergic neurons, elicits real-time dopamine release. This mechanism occurs via direct actions on dopamine terminals, does not require changes in neuron firing within the midbrain, and is dependent on glutamatergic receptor activity. More importantly, we demonstrate that in vivo selective activation of cholinergic interneurons is sufficient to elicit dopamine release in the nucleus accumbens. Therefore, the control of accumbal extracellular dopamine levels by endogenous cholinergic activity results from a complex convergence of neurotransmitter/neuromodulator systems that may ultimately synergize to drive motivated behavior.

  20. Social Influences on Creativity: Interactive Effects of Reward and Choice.

    Science.gov (United States)

    Amabile, Teresa M.

    In a test of intrinsic motivation hypothesis of creativity, 60 undergraduate women did an artistic creativity task with either the expectation of receiving a reward or no expectation of reward. Reward was crossed with choice in task engagement, such that half of the reward Ss contracted to do the task in order to receive reward, and half simply…

  1. Major depressive disorder is characterized by greater reward network activation to monetary than pleasant image rewards.

    Science.gov (United States)

    Smoski, Moria J; Rittenberg, Alison; Dichter, Gabriel S

    2011-12-30

    Anhedonia, the loss of interest or pleasure in normally rewarding activities, is a hallmark feature of unipolar Major Depressive Disorder (MDD). A growing body of literature has identified frontostriatal dysfunction during reward anticipation and outcomes in MDD. However, no study to date has directly compared responses to different types of rewards such as pleasant images and monetary rewards in MDD. To investigate the neural responses to monetary and pleasant image rewards in MDD, a modified Monetary Incentive Delay task was used during functional magnetic resonance imaging to assess neural responses during anticipation and receipt of monetary and pleasant image rewards. Participants included nine adults with MDD and 13 affectively healthy controls. The MDD group showed lower activation than controls when anticipating monetary rewards in right orbitofrontal cortex and subcallosal cortex, and when anticipating pleasant image rewards in paracingulate and supplementary motor cortex. The MDD group had relatively greater activation in right putamen when anticipating monetary versus pleasant image rewards, relative to the control group. Results suggest reduced reward network activation in MDD when anticipating rewards, as well as relatively greater hypoactivation to pleasant image than monetary rewards. 2011 Elsevier Ireland Ltd. All rights reserved.

  2. Random reward priming is task-contingent: The robustness of the 1-trial reward priming effect

    Directory of Open Access Journals (Sweden)

    Árni Gunnar Ásgeirsson

    2014-04-01

    Full Text Available Consistent financial reward of particular features influences the allocation of visual attention in many ways. More surprising are 1-trial reward priming effects on attention where reward schedules are random and reward on one trial influences attentional allocation on the next. Those findings are thought to reflect that rewarded features become more salient than unrewarded ones on the subsequent trial. Here we attempt to conceptually replicate this effect, testing its generalizability. In three versions of an analogous paradigm to the additional singleton paradigm involving singleton search for a Gabor patch of odd spatial frequency we found no evidence of reward priming, while we only partially replicate the reward priming in the exact original paradigm tested by Hickey and colleagues. The results cast doubt on the proposal that random reward enhances salience, suggested in the original papers, and highlight the need for a more nuanced account. In many other paradigms reward effects have been found to progress gradually, becoming stronger as they build up, and we argue that for robust reward priming, reward schedules need to be more consistent than in the original 1-trial reward priming paradigm.

  3. The Role of Mesolimbic Reward Neurocircuitry in Prevention and Rescue of the Activity-Based Anorexia (ABA) Phenotype in Rats.

    Science.gov (United States)

    Foldi, Claire J; Milton, Laura K; Oldfield, Brian J

    2017-11-01

    Patients suffering from anorexia nervosa (AN) become anhedonic; unable or unwilling to derive normal pleasures and avoid rewarding outcomes, most profoundly in food intake. The activity-based anorexia (ABA) model recapitulates many of the characteristics of the human condition, including anhedonia, and allows investigation of the underlying neurobiology of AN. The potential for increased neuronal activity in reward/hedonic circuits to prevent and rescue weight loss is investigated in this model. The mesolimbic pathway extending from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) was activated using a dual viral strategy, involving retrograde transport of Cre (CAV-2-Cre) to the VTA and coincident injection of DREADD receptors (AAV-hSyn-DIO-hM3D(Gq)-mCherry). Systemic clozapine-n-oxide (CNO; 0.3 mg/kg) successfully recruited a large proportion of the VTA-NAc dopaminergic projections, with activity evidenced by colocalization with elevated levels of Fos protein. The effects of reward circuit activation on energy balance and predicted survival was investigated in female Sprague-Dawley rats, where free access to running wheels was paired with time-limited (90 min) access to food, a paradigm (ABA) which will cause anorexia and death if unchecked. Excitation of the reward pathway substantially increased food intake and food anticipatory activity (FAA) to prevent ABA-associated weight loss, while overall locomotor activity was unchanged. Similar activation of reward circuitry, delayed until establishment of the ABA phenotype, rescued rats from their precipitous weight loss. Although these data are consistent with shifts primarily in food intake, the contribution of mechanisms including energy expenditure to survival remains to be determined. These results will inform the neurobiological underpinnings of AN, and provide insight into the mechanisms of reward circuitry relevant to feeding and weight loss.

  4. Reward guides vision when it's your thing: trait reward-seeking in reward-mediated visual priming.

    Directory of Open Access Journals (Sweden)

    Clayton Hickey

    Full Text Available Reward-related mesolimbic dopamine is thought to play an important role in guiding animal behaviour, biasing approach towards potentially beneficial environmental stimuli and away from objects unlikely to garner positive outcome. This is considered to result in part from an impact on perceptual and attentional processes: dopamine initiates a series of cognitive events that result in the priming of reward-associated perceptual features. We have provided behavioural and electrophysiological evidence that this mechanism guides human vision in search, an effect we refer to as reward priming. We have also demonstrated that there is substantial individual variability in this effect. Here we show that behavioural differences in reward priming are predicted remarkably well by a personality index that captures the degree to which a person's behaviour is driven by reward outcome. Participants with reward-seeking personalities are found to be those who allocate visual resources to objects characterized by reward-associated visual features. These results add to a rapidly developing literature demonstrating the crucial role reward plays in attentional control. They additionally illustrate the striking impact personality traits can have on low-level cognitive processes like perception and selective attention.

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

    OpenAIRE

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

    2014-01-01

    Summary 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 PETstudies indicate that the stress hormone cortisol may be crucial in the interaction between st...

  6. The habenula governs the attribution of incentive salience to reward predictive cues

    OpenAIRE

    Danna, Carey L.; Shepard, Paul D.; Elmer, Greg I.

    2013-01-01

    The attribution of incentive salience to reward associated cues is critical for motivation and the pursuit of rewards. Disruptions in the integrity of the neural systems controlling these processes can lead to avolition and anhedonia, symptoms that cross the diagnostic boundaries of many neuropsychiatric illnesses. Here, we consider whether the habenula (Hb), a region recently demonstrated to encode negatively valenced events, also modulates the attribution of incentive salience to a neutral...

  7. Dopamine selectively remediates 'model-based' reward learning: a computational approach.

    Science.gov (United States)

    Sharp, Madeleine E; Foerde, Karin; Daw, Nathaniel D; Shohamy, Daphna

    2016-02-01

    Patients with loss of dopamine due to Parkinson's disease are impaired at learning from reward. However, it remains unknown precisely which aspect of learning is impaired. In particular, learning from reward, or reinforcement learning, can be driven by two distinct computational processes. One involves habitual stamping-in of stimulus-response associations, hypothesized to arise computationally from 'model-free' learning. The other, 'model-based' learning, involves learning a model of the world that is believed to support goal-directed behaviour. Much work has pointed to a role for dopamine in model-free learning. But recent work suggests model-based learning may also involve dopamine modulation, raising the possibility that model-based learning may contribute to the learning impairment in Parkinson's disease. To directly test this, we used a two-step reward-learning task which dissociates model-free versus model-based learning. We evaluated learning in patients with Parkinson's disease tested ON versus OFF their dopamine replacement medication and in healthy controls. Surprisingly, we found no effect of disease or medication on model-free learning. Instead, we found that patients tested OFF medication showed a marked impairment in model-based learning, and that this impairment was remediated by dopaminergic medication. Moreover, model-based learning was positively correlated with a separate measure of working memory performance, raising the possibility of common neural substrates. Our results suggest that some learning deficits in Parkinson's disease may be related to an inability to pursue reward based on complete representations of the environment. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

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    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

  9. Interaction between the dopaminergic and opioidergic systems in dorsal hippocampus in modulation of formalin-induced orofacial pain in rats.

    Science.gov (United States)

    Reisi, Zahra; Haghparast, Amir; Pahlevani, Pouyan; Shamsizadeh, Ali; Haghparast, Abbas

    2014-09-01

    The hippocampus is a region of the brain that serves several functions. The dopaminergic system acts through D1- and D2-like receptors to interfere in pain modulation and the opioid receptors play major roles in analgesic processes and there are obvious overlaps between these two systems. The present study investigated the interaction between the opioidergic and dopaminergic systems in the dorsal hippocampus (CA1) region for formalin-induced orofacial pain. Two guide cannulae were stereotaxically implanted in the CA1 region and morphine (0.5, 1, 2 and 4 μg/0.5 μl saline) and naloxone (0.3, 1 and 3 μg/0.5 μl saline) were used as the opioid receptor agonist and antagonist, respectively. SKF-38393 (1 μg/0.5 μl saline) was used as a D1-like receptor agonist, quinpirole (2 μg/0.5 μl saline) as a D2-like receptor agonist, SCH-23390 (0.5 μg/0.5 μl saline) as a D1-like receptor antagonist and sulpiride (3 μg/0.5 μl DMSO) as a D2-like receptor antagonist. To induce orofacial pain, 50 μl of 1% formalin was subcutaneously injected into the left side of the upper lip. Our results showed that different doses of morphine significantly reduced orofacial pain in both phases induced by formalin. Naloxone (1 and 3 μg) reversed morphine induced analgesia in CA1. SKF-38393 and quinpirole with naloxone (1 μg) significantly decreased formalin-induced orofacial pain in both phases. SCH-23390 had no effect on the antinociceptive response of morphine in both phases of orofacial pain. Sulpiride reversed the antinociceptive effects of morphine only in the first phase, but this result was not significant. Our findings suggest that there is cross-talk between the opioidergic and dopaminergic systems. Opioidergic neurons also exerted antinociceptive effects by modulation of the dopaminergic system in the CA1 region of the brain. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Differences between Dorsal and Ventral Striatum in the Sensitivity of Tonically Active Neurons to Rewarding Events

    Directory of Open Access Journals (Sweden)

    Kevin Marche

    2017-07-01

    Full Text Available Within the striatum, cholinergic interneurons, electrophysiologically identified as tonically active neurons (TANs, represent a relatively homogeneous group in terms of their functional properties. They display typical pause in tonic firing in response to rewarding events which are of crucial importance for reinforcement learning. These responses are uniformly distributed throughout the dorsal striatum (i.e., motor and associative striatum, but it is unknown, at least in monkeys, whether differences in the modulation of TAN activity exist in the ventral striatum (i.e., limbic striatum, a region specialized for processing of motivational information. To address this issue, we examined the activity of dorsal and ventral TANs in two monkeys trained on a Pavlovian conditioning task in which a visual stimulus preceded the delivery of liquid reward by a fixed time interval. We found that the proportion of TANs responding to the stimulus predictive of reward did not vary significantly across regions (58%–80%, whereas the fraction of TANs responding to reward was higher in the limbic striatum (100% compared to the motor (65% and associative striatum (52%. By examining TAN modulation at the level of both the population and the individual neurons, we showed that the duration of pause responses to the stimulus and reward was longer in the ventral than in the dorsal striatal regions. Also, the magnitude of the pause was greater in ventral than dorsal striatum for the stimulus predictive of reward but not for the reward itself. We found similar region-specific differences in pause response duration to the stimulus when the timing of reward was less predictable (fixed replaced by variable time interval. Regional variations in the duration and magnitude of the pause response were transferred from the stimulus to reward when reward was delivered in the absence of any predictive stimulus. It therefore appears that ventral TANs exhibit stronger responses to

  11. Ventral tegmental area disruption selectively affects CA1/CA2 but not CA3 place fields during a differential reward working memory task.

    Science.gov (United States)

    Martig, Adria K; Mizumori, Sheri J Y

    2011-02-01

    Hippocampus (HPC) receives dopaminergic (DA) projections from the ventral tegmental area (VTA) and substantia nigra. These inputs appear to provide a modulatory signal that influences HPC dependent behaviors and place fields. We examined how efferent projections from VTA to HPC influence spatial working memory and place fields when the reward context changes. CA1 and CA3 process environmental context changes differently and VTA preferentially innervates CA1. Given these anatomical data and electrophysiological evidence that implicate DA in reward processing, we predicted that CA1 place fields would respond more strongly to both VTA disruption and changes in the reward context than CA3 place fields. Rats (N = 9) were implanted with infusion cannula targeting VTA and recording tetrodes aimed at HPC. Then they were tested on a differential reward, win-shift working memory task. One recording session consisted of 5 baseline and 5 manipulation trials during which place cells in CA1/CA2 (N = 167) and CA3 (N = 94) were recorded. Prior to manipulation trials rats were infused with either baclofen or saline and then subjected to control or reward conditions during which the learned locations of large and small reward quantities were reversed. VTA disruption resulted in an increase in errors, and in CA1/CA2 place field reorganization. There were no changes in any measures of CA3 place field stability during VTA disruption. Reward manipulations did not affect performance or place field stability in CA1/CA2 or CA3; however, changes in the reward locations "rescued" performance and place field stability in CA1/CA2 when VTA activity was compromised, perhaps by trigging compensatory mechanisms. These data support the hypothesis that VTA contributes to spatial working memory performance perhaps by maintaining place field stability selectively in CA1/CA2. Copyright © 2009 Wiley-Liss, Inc.

  12. Effects of emotion and reward motivation on neural correlates of episodic memory encoding: a PET study.

    Science.gov (United States)

    Shigemune, Yayoi; Abe, Nobuhito; Suzuki, Maki; Ueno, Aya; Mori, Etsuro; Tashiro, Manabu; Itoh, Masatoshi; Fujii, Toshikatsu

    2010-05-01

    It is known that emotion and reward motivation promote long-term memory formation. It remains unclear, however, how and where emotion and reward are integrated during episodic memory encoding. In the present study, subjects were engaged in intentional encoding of photographs under four different condition