Neurogenetics and Pharmacology of Learning, Motivation, and Cognition

Many of the individual differences in cognition, motivation, and learning—and the disruption of these processes in neurological conditions—are influenced by genetic factors. We provide an integrative synthesis across human and animal studies, focusing on a recent spate of evidence implicating a role for genes controlling dopaminergic function in frontostriatal circuitry, including COMT, DARPP-32, DAT1, DRD2, and DRD4. These genetic effects are interpreted within theoretical frameworks developed in the context of the broader cognitive and computational neuroscience literature, constrained by data from pharmacological, neuroimaging, electrophysiological, and patient studies. In this framework, genes modulate the efficacy of particular neural computations, and effects of genetic variation are revealed by assays designed to be maximally sensitive to these computations. We discuss the merits and caveats of this approach and outline a number of novel candidate genes of interest for future study.

[1]  M. Brownstein Studies of the distribution of biologically active peptides in the brain. , 1977, Advances in experimental medicine and biology.

[2]  H. Y. Yang,et al.  On the locaticn of methicnine enkephalin neurons in rat striatum , 1977, Neuropharmacology.

[3]  J. C. Stoof,et al.  Opposing roles for D-1 and D-2 dopamine receptors in efflux of cyclic AMP from rat neostriatum , 1981, Nature.

[4]  P. Greengard,et al.  DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. III. Immunocytochemical localization , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  C. Gerfen The neostriatal mosaic: compartmentalization of corticostriatal input and striatonigral output systems , 1984, Nature.

[6]  J. Lewis,et al.  Enhancing effects of methylphenidate on normal young adults' cognitive processes. , 1984, Psychopharmacology bulletin.

[7]  Werner G. Kuhr,et al.  The effect of l-DOPA on in vivo dopamine release from nigrostriatal bundle neurons , 1988, Brain Research.

[8]  R. M. Wightman,et al.  Real-time characterization of dopamine overflow and uptake in the rat striatum , 1988, Neuroscience.

[9]  J. Palacios,et al.  Dopamine receptors in human brain: Autoradiographic distribution of D1 sites , 1989, Neuroscience.

[10]  P. Goldman-Rakic,et al.  D1 dopamine receptors in prefrontal cortex: involvement in working memory , 1991, Science.

[11]  S. Scarr,et al.  Developmental theories for the 1990s: development and individual differences. , 1992, Child development.

[12]  Joel L. Davis,et al.  A Model of How the Basal Ganglia Generate and Use Neural Signals That Predict Reinforcement , 1994 .

[13]  Ming Xu,et al.  Dopamine D1 receptor mutant mice are deficient in striatal expression of dynorphin and in dopamine-mediated behavioral responses , 1994, Cell.

[14]  J. M. Daly,et al.  Dopamine Receptors in the Human Brain , 1994 .

[15]  A C Roberts,et al.  6-Hydroxydopamine lesions of the prefrontal cortex in monkeys enhance performance on an analog of the Wisconsin Card Sort Test: possible interactions with subcortical dopamine , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[16]  A. Grace,et al.  Activation of dopamine cell firing by repeated L-DOPA administration to dopamine-depleted rats: its potential role in mediating the therapeutic response to L-DOPA treatment , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[17]  Joel L. Davis,et al.  Adaptive Critics and the Basal Ganglia , 1995 .

[18]  M. Matsumoto,et al.  Low Levels of mRNA for Dopamine D4 Receptor in Human Cerebral Cortex and Striatum , 1996, Journal of neurochemistry.

[19]  Peter Dayan,et al.  A Neural Substrate of Prediction and Reward , 1997, Science.

[20]  M. Farah,et al.  Effects of bromocriptine on human subjects depend on working memory capacity , 1997, Neuroreport.

[21]  R. Elliott,et al.  Effects of methylphenidate on spatial working memory and planning in healthy young adults , 1997, Psychopharmacology.

[22]  D. Pfaff,et al.  Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Allan I. Levey,et al.  Dopamine Axon Varicosities in the Prelimbic Division of the Rat Prefrontal Cortex Exhibit Sparse Immunoreactivity for the Dopamine Transporter , 1998, The Journal of Neuroscience.

[24]  Alexandre Pouget,et al.  Probabilistic Interpretation of Population Codes , 1996, Neural Computation.

[25]  Paul Greengard,et al.  DARPP-32: Regulator of the Efficacy of Dopaminergic Neurotransmission , 1998 .

[26]  D. Surmeier,et al.  Coordinated expression of dopamine receptors in neostriatal medium spiny neurons. , 1998, Advances in pharmacology.

[27]  J O Rinne,et al.  The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers , 1998, Molecular Psychiatry.

[28]  Joshua W. Brown,et al.  How the Basal Ganglia Use Parallel Excitatory and Inhibitory Learning Pathways to Selectively Respond to Unexpected Rewarding Cues , 1999, The Journal of Neuroscience.

[29]  R. Quirion,et al.  Expression of dopamine receptors in the subthalamic nucleus of the rat: characterization using reverse transcriptase–polymerase chain reaction and autoradiography , 1999, Neuroscience.

[30]  T. Robbins,et al.  Systemic sulpiride in young adult volunteers simulates the profile of cognitive deficits in Parkinson’s disease , 1999, Psychopharmacology.

[31]  M. J. Emerson,et al.  The Unity and Diversity of Executive Functions and Their Contributions to Complex “Frontal Lobe” Tasks: A Latent Variable Analysis , 2000, Cognitive Psychology.

[32]  H. Kita,et al.  Excitatory Cortical Inputs to Pallidal Neurons Via the Subthalamic Nucleus in the Monkey , 2000 .

[33]  T. Sejnowski,et al.  Dopamine-mediated stabilization of delay-period activity in a network model of prefrontal cortex. , 2000, Journal of neurophysiology.

[34]  J. Callicott,et al.  The Relationship between Dorsolateral Prefrontal Neuronal N-Acetylaspartate and Evoked Release of Striatal Dopamine in Schizophrenia , 2000, Neuropsychopharmacology.

[35]  H. V. Van Tol,et al.  The dopamine D(4) receptor: one decade of research. , 2000, European journal of pharmacology.

[36]  P. Greengard,et al.  Dopamine and cAMP-Regulated Phosphoprotein 32 kDa Controls Both Striatal Long-Term Depression and Long-Term Potentiation, Opposing Forms of Synaptic Plasticity , 2000, The Journal of Neuroscience.

[37]  Michael J. Frank,et al.  Interactions between frontal cortex and basal ganglia in working memory: A computational model , 2001, Cognitive, affective & behavioral neuroscience.

[38]  J. Girault,et al.  Gαolf is necessary for coupling D1 and A2a receptors to adenylyl cyclase in the striatum , 2001, Journal of neurochemistry.

[39]  N. Perrimon,et al.  Dual role of the fringe connection gene in both heparan sulphate and fringe-dependent signalling events , 2001, Nature Cell Biology.

[40]  J. Wickens,et al.  Dopamine D-1/D-5 receptor activation is required for long-term potentiation in the rat neostriatum in vitro. , 2001, Journal of neurophysiology.

[41]  R. Straub,et al.  Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[42]  M. Jackson,et al.  Stimulation of prefrontal cortex at physiologically relevant frequencies inhibits dopamine release in the nucleus accumbens , 2001, Journal of neurochemistry.

[43]  J. Wickens,et al.  A cellular mechanism of reward-related learning , 2001, Nature.

[44]  T. Robbins,et al.  Mechanisms of cognitive set flexibility in Parkinson's disease. , 2001, Brain : a journal of neurology.

[45]  M. Low,et al.  The role of the D2 dopamine receptor (D2R) in A2A adenosine receptor (A2AR)-mediated behavioral and cellular responses as revealed by A2A and D2 receptor knockout mice , 2001 .

[46]  S. Goto,et al.  UDP–sugar transporter implicated in glycosylation and processing of Notch , 2001, Nature Cell Biology.

[47]  Jonathan D. Cohen,et al.  Computational perspectives on dopamine function in prefrontal cortex , 2002, Current Opinion in Neurobiology.

[48]  M. Posner,et al.  Assessing the molecular genetics of attention networks , 2002, BMC Neuroscience.

[49]  J. Salamone,et al.  Motivational views of reinforcement: implications for understanding the behavioral functions of nucleus accumbens dopamine , 2002, Behavioural Brain Research.

[50]  I. Craig,et al.  Expression of the dopamine transporter gene is regulated by the 3' UTR VNTR: Evidence from brain and lymphocytes using quantitative RT-PCR. , 2002, American journal of medical genetics.

[51]  M. Posner,et al.  Mapping the genetic variation of executive attention onto brain activity , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[52]  J. Wickens,et al.  Neural mechanisms of reward-related motor learning , 2003, Current Opinion in Neurobiology.

[53]  P. Calabresi,et al.  Distinct Roles of D1 and D5 Dopamine Receptors in Motor Activity and Striatal Synaptic Plasticity , 2003, The Journal of Neuroscience.

[54]  W. Schmidt,et al.  Catalepsy intensifies context-dependently irrespective of whether it is induced by intermittent or chronic dopamine deficiency , 2003, Behavioural pharmacology.

[55]  R. Coppola,et al.  Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. , 2003, Archives of general psychiatry.

[56]  Tatsuo K Sato,et al.  Correlated Coding of Motivation and Outcome of Decision by Dopamine Neurons , 2003, The Journal of Neuroscience.

[57]  B. Lipska,et al.  Catechol O-methyltransferase mRNA expression in human and rat brain: evidence for a role in cortical neuronal function , 2003, Neuroscience.

[58]  J. Seamans,et al.  The principal features and mechanisms of dopamine modulation in the prefrontal cortex , 2004, Progress in Neurobiology.

[59]  Jonathan D. Cohen,et al.  Computational roles for dopamine in behavioural control , 2004, Nature.

[60]  Paul J. Harrison,et al.  Catechol-O-Methyltransferase Inhibition Improves Set-Shifting Performance and Elevates Stimulated Dopamine Release in the Rat Prefrontal Cortex , 2004, The Journal of Neuroscience.

[61]  Mitul A Mehta,et al.  Methylphenidate improves working memory and set-shifting in AD/HD: relationships to baseline memory capacity. , 2004, Journal of child psychology and psychiatry, and allied disciplines.

[62]  M. Weisbrod,et al.  Differential dopaminergic modulation of executive control in healthy subjects , 2005, Psychopharmacology.

[63]  Michael J. Frank,et al.  By Carrot or by Stick: Cognitive Reinforcement Learning in Parkinsonism , 2004, Science.

[64]  D. Sibley,et al.  Phenotypic analysis of dopamine receptor knockout mice; recent insights into the functional specificity of dopamine receptor subtypes , 2004, Neuropharmacology.

[65]  A. Grace,et al.  The Catechol-O-Methyltransferase Polymorphism: Relations to the Tonic–Phasic Dopamine Hypothesis and Neuropsychiatric Phenotypes , 2004, Neuropsychopharmacology.

[66]  Giovanni Montana,et al.  Statistical tests for admixture mapping with case-control and cases-only data. , 2004, American journal of human genetics.

[67]  K. Någren,et al.  C957T polymorphism of the dopamine D2 receptor (DRD2) gene affects striatal DRD2 availability in vivo , 2004, Molecular Psychiatry.

[68]  M. Egan,et al.  Effect of Catechol-O-Methyltransferase val158met Genotype on Attentional Control , 2005, The Journal of Neuroscience.

[69]  Angus C Nairn,et al.  Regulation of a protein phosphatase cascade allows convergent dopamine and glutamate signals to activate ERK in the striatum. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[70]  B. Madras,et al.  The Dopamine Transporter and Attention-Deficit/Hyperactivity Disorder , 2005, Biological Psychiatry.

[71]  Clinton D Kilts,et al.  The variable number of tandem repeats element in DAT1 regulates in vitro dopamine transporter density , 2005, BMC Genetics.

[72]  R. Nussbaum,et al.  Midbrain dopamine and prefrontal function in humans: interaction and modulation by COMT genotype , 2005, Nature Neuroscience.

[73]  T. Robbins,et al.  Neural systems of reinforcement for drug addiction: from actions to habits to compulsion , 2005, Nature Neuroscience.

[74]  M. Munafo,et al.  Does measurement instrument moderate the association between the serotonin transporter gene and anxiety-related personality traits? A meta-analysis , 2005, Molecular Psychiatry.

[75]  Michael J. Frank,et al.  Dynamic Dopamine Modulation in the Basal Ganglia: A Neurocomputational Account of Cognitive Deficits in Medicated and Nonmedicated Parkinsonism , 2005, Journal of Cognitive Neuroscience.

[76]  N C Andreasen,et al.  Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow , 2005 .

[77]  E. Rolls,et al.  Synaptic and spiking dynamics underlying reward reversal in the orbitofrontal cortex. , 2004, Cerebral cortex.

[78]  J. Waddington,et al.  Phenotypic studies on dopamine receptor subtype and associated signal transduction mutants: insights and challenges from 10 years at the psychopharmacology–molecular biology interface , 2005, Psychopharmacology.

[79]  Trevor W. Robbins,et al.  Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[80]  P. Glimcher,et al.  Midbrain Dopamine Neurons Encode a Quantitative Reward Prediction Error Signal , 2005, Neuron.

[81]  N C Andreasen,et al.  Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow , 2005, Molecular Psychiatry.

[82]  K. Shokat,et al.  Human Catechol-O-Methyltransferase Haplotypes Modulate Protein Expression by Altering mRNA Secondary Structure , 2006, Science.

[83]  Dagoberto Tapia,et al.  Control of the subthalamic innervation of the rat globus pallidus by D2/3 and D4 dopamine receptors. , 2006, Journal of neurophysiology.

[84]  P. Greengard,et al.  Regulation of phosphorylation of the GluR1 AMPA receptor by dopamine D2 receptors , 2006, Journal of neurochemistry.

[85]  K. Berridge The debate over dopamine’s role in reward: the case for incentive salience , 2007, Psychopharmacology.

[86]  Jeanette Kotaleski,et al.  Transient Calcium and Dopamine Increase PKA Activity and DARPP-32 Phosphorylation , 2006, PLoS Comput. Biol..

[87]  Thomas E. Nichols,et al.  Impact of complex genetic variation in COMT on human brain function , 2006, Molecular Psychiatry.

[88]  P. Dayan,et al.  Cortical substrates for exploratory decisions in humans , 2006, Nature.

[89]  Michael J. Frank,et al.  A mechanistic account of striatal dopamine function in human cognition: psychopharmacological studies with cabergoline and haloperidol. , 2006, Behavioral neuroscience.

[90]  Kae Nakamura,et al.  Role of Dopamine in the Primate Caudate Nucleus in Reward Modulation of Saccades , 2006, The Journal of Neuroscience.

[91]  Michael J. Frank,et al.  Hold your horses: A dynamic computational role for the subthalamic nucleus in decision making , 2006, Neural Networks.

[92]  A. Meyer-Lindenberg,et al.  Prefrontal-Hippocampal Coupling During Memory Processing Is Modulated by COMT Val158Met Genotype , 2006, Biological Psychiatry.

[93]  M. D’Esposito,et al.  Reversal learning in Parkinson's disease depends on medication status and outcome valence , 2006, Neuropsychologia.

[94]  M. Frank,et al.  Anatomy of a decision: striato-orbitofrontal interactions in reinforcement learning, decision making, and reversal. , 2006, Psychological review.

[95]  C. Ledent,et al.  Attenuation of nicotine-induced rewarding effects in A2A knockout mice , 2006, Neuropharmacology.

[96]  T. Robbins,et al.  A role for mesencephalic dopamine in activation: commentary on Berridge (2006) , 2007, Psychopharmacology.

[97]  David G Standaert,et al.  Dopamine D1 Activation Potentiates Striatal NMDA Receptors by Tyrosine Phosphorylation-Dependent Subunit Trafficking , 2006, The Journal of Neuroscience.

[98]  Andreas Meyer-Lindenberg,et al.  Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition. , 2007, The Journal of clinical investigation.

[99]  S. Dudek,et al.  Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice , 2007, Nature.

[100]  Leonardo Fazio,et al.  Polymorphisms in human dopamine D2 receptor gene affect gene expression, splicing, and neuronal activity during working memory , 2007, Proceedings of the National Academy of Sciences.

[101]  M. Reuter,et al.  Genetically Determined Differences in Learning from Errors , 2007, Science.

[102]  Michael J. Frank,et al.  Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning , 2007, Proceedings of the National Academy of Sciences.

[103]  Josep Marco-Pallarés,et al.  The Impact of Catechol-O-Methyltransferase and Dopamine D4 Receptor Genotypes on Neurophysiological Markers of Performance Monitoring , 2007, The Journal of Neuroscience.

[104]  Mary Kay Lobo,et al.  Genetic control of instrumental conditioning by striatopallidal neuron–specific S1P receptor Gpr6 , 2007, Nature Neuroscience.

[105]  J. Callicott,et al.  Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis of schizophrenia. , 2007, Cerebral cortex.

[106]  M. Roesch,et al.  Dopamine neurons encode the better option in rats deciding between differently delayed or sized rewards , 2007, Nature Neuroscience.

[107]  Timothy Edward John Behrens,et al.  Triangulating a Cognitive Control Network Using Diffusion-Weighted Magnetic Resonance Imaging (MRI) and Functional MRI , 2007, The Journal of Neuroscience.

[108]  E. Costa,et al.  Epigenetic mechanisms expressed in basal ganglia GABAergic neurons differentiate schizophrenia from bipolar disorder , 2007, Schizophrenia Research.

[109]  M. Nicolelis,et al.  Dopamine levels modulate the updating of tastant values , 2007, Genes, brain, and behavior.

[110]  Michael X. Cohen,et al.  Dopamine gene predicts the brain's response to dopaminergic drug , 2007, The European journal of neuroscience.

[111]  L. Excoffier,et al.  Statistical evaluation of alternative models of human evolution , 2007, Proceedings of the National Academy of Sciences.

[112]  Masataka Watanabe,et al.  Integration of cognitive and motivational context information in the primate prefrontal cortex. , 2007, Cerebral cortex.

[113]  M. D’Esposito,et al.  Impulsive Personality Predicts Dopamine-Dependent Changes in Frontostriatal Activity during Component Processes of Working Memory , 2007, The Journal of Neuroscience.

[114]  A. Meyer-Lindenberg,et al.  Catechol-O-Methyltransferase Val158Met Modulation of Prefrontal–Parietal–Striatal Brain Systems during Arithmetic and Temporal Transformations in Working Memory , 2007, The Journal of Neuroscience.

[115]  Michael J. Frank,et al.  Hold Your Horses: Impulsivity, Deep Brain Stimulation, and Medication in Parkinsonism , 2007, Science.

[116]  Jonathan D. Cohen,et al.  On the Control of Control: The Role of Dopamine in Regulating Prefrontal Function and Working Memory , 2007 .

[117]  J. Gläscher,et al.  Gene–gene interaction associated with neural reward sensitivity , 2007, Proceedings of the National Academy of Sciences.

[118]  Benjamin M. Robinson,et al.  Selective Reinforcement Learning Deficits in Schizophrenia Support Predictions from Computational Models of Striatal-Cortical Dysfunction , 2007, Biological Psychiatry.

[119]  Tim Curran,et al.  Cross-task individual differences in error processing: Neural, electrophysiological, and genetic components , 2007, Cognitive, affective & behavioral neuroscience.

[120]  Young T. Hong,et al.  Nucleus Accumbens D2/3 Receptors Predict Trait Impulsivity and Cocaine Reinforcement , 2007, Science.

[121]  Joshua L Plotkin,et al.  Differential Excitability and Modulation of Striatal Medium Spiny Neuron Dendrites , 2008, The Journal of Neuroscience.

[122]  Lars Nyberg,et al.  Plasticity of executive functioning in young and older adults: immediate training gains, transfer, and long-term maintenance. , 2008, Psychology and aging.

[123]  B. Kolachana,et al.  COMT genotype predicts cortical-limbic D1 receptor availability measured with [11C]NNC112 and PET , 2008, Molecular Psychiatry.

[124]  Hannah S. Locke,et al.  Motivational influences on cognitive control: Behavior, brain activation, and individual differences , 2008, Cognitive, affective & behavioral neuroscience.

[125]  Edward T. Bullmore,et al.  The role of the orbitofrontal cortex in human discrimination learning , 2008, Neuropsychologia.

[126]  M. Gluck,et al.  Risk and protective haplotypes of the alpha‐synuclein gene associated with Parkinson’s disease differentially affect cognitive sequence learning , 2007, Genes, brain, and behavior.

[127]  Z. Xi,et al.  Attenuation of basal and cocaine-enhanced locomotion and nucleus accumbens dopamine in cannabinoid CB1-receptor-knockout mice , 2009, Psychopharmacology.

[128]  E. Kandel,et al.  Transient and selective overexpression of D2 receptors in the striatum causes persistent deficits in conditional associative learning , 2008, Proceedings of the National Academy of Sciences.

[129]  Michael X. Cohen,et al.  A Role for Dopamine in Temporal Decision Making and Reward Maximization in Parkinsonism , 2008, The Journal of Neuroscience.

[130]  D. Durstewitz,et al.  The Dual-State Theory of Prefrontal Cortex Dopamine Function with Relevance to Catechol-O-Methyltransferase Genotypes and Schizophrenia , 2008, Biological Psychiatry.

[131]  Adam E. Green,et al.  Using genetic data in cognitive neuroscience: from growing pains to genuine insights , 2008, Nature Reviews Neuroscience.

[132]  E. Nestler,et al.  ΔFosB Mediates Epigenetic Desensitization of the c-fos Gene After Chronic Amphetamine Exposure , 2008, The Journal of Neuroscience.

[133]  M. D’Esposito,et al.  Working Memory Capacity Predicts Dopamine Synthesis Capacity in the Human Striatum , 2008, The Journal of Neuroscience.

[134]  Marcus R. Munafò,et al.  Meta-Analysis of the Cognitive Effects of the Catechol-O-Methyltransferase Gene Val158/108Met Polymorphism , 2008, Biological Psychiatry.

[135]  B. Kolachana,et al.  Epistasis between Dopamine Regulating Genes Identifies a Nonlinear Response of the Human Hippocampus During Memory Tasks , 2008, Biological Psychiatry.

[136]  Terry E. Goldberg,et al.  Genetic Variation in Catechol-O-Methyltransferase: Effects on Working Memory in Schizophrenic Patients, Their Siblings, and Healthy Controls , 2008, Biological Psychiatry.

[137]  E. Vaadia,et al.  Midbrain Dopaminergic Neurons and Striatal Cholinergic Interneurons Encode the Difference between Reward and Aversive Events at Different Epochs of Probabilistic Classical Conditioning Trials , 2008, The Journal of Neuroscience.

[138]  P. Greengard,et al.  A Translational Profiling Approach for the Molecular Characterization of CNS Cell Types , 2008, Cell.

[139]  Paul Greengard,et al.  A phosphatase cascade by which rewarding stimuli control nucleosomal response , 2008, Nature.

[140]  W. Pan,et al.  Tripartite Mechanism of Extinction Suggested by Dopamine Neuron Activity and Temporal Difference Model , 2008, The Journal of Neuroscience.

[141]  Michael J. Frank,et al.  A dopaminergic basis for working memory, learning and attentional shifting in Parkinsonism , 2008, Neuropsychologia.

[142]  Lars Bäckman,et al.  Transfer of Learning After Updating Training Mediated by the Striatum , 2008, Science.

[143]  E. Rolls,et al.  Computational models of schizophrenia and dopamine modulation in the prefrontal cortex , 2008, Nature Reviews Neuroscience.

[144]  Russell G. Port,et al.  Nucleus Accumbens Adenosine A2A Receptors Regulate Exertion of Effort by Acting on the Ventral Striatopallidal Pathway , 2008, The Journal of Neuroscience.

[145]  Trevor W. Robbins,et al.  High Impulsivity Predicts the Switch to Compulsive Cocaine-Taking , 2008, Science.

[146]  Roshan Cools,et al.  Role of Dopamine in the Motivational and Cognitive Control of Behavior , 2008, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[147]  A. Miyake,et al.  Individual differences in executive functions are almost entirely genetic in origin. , 2008, Journal of experimental psychology. General.

[148]  P. Greengard,et al.  Dichotomous Dopaminergic Control of Striatal Synaptic Plasticity , 2008, Science.

[149]  J. Girault,et al.  Opposing Patterns of Signaling Activation in Dopamine D1 and D2 Receptor-Expressing Striatal Neurons in Response to Cocaine and Haloperidol , 2008, The Journal of Neuroscience.

[150]  Thomas V. Wiecki,et al.  A neurocomputational account of catalepsy sensitization induced by D2 receptor blockade in rats: context dependency, extinction, and renewal , 2009, Psychopharmacology.

[151]  M. Lobo Molecular profiling of striatonigral and striatopallidal medium spiny neurons past, present, and future. , 2009, International review of neurobiology.

[152]  I. Waldman,et al.  Candidate gene studies of ADHD: a meta-analytic review , 2009, Human Genetics.

[153]  H. Yin,et al.  Genetic Deletion of A2A Adenosine Receptors in the Striatum Selectively Impairs Habit Formation , 2009, The Journal of Neuroscience.

[154]  Timothy Edward John Behrens,et al.  How Green Is the Grass on the Other Side? Frontopolar Cortex and the Evidence in Favor of Alternative Courses of Action , 2009, Neuron.

[155]  M. Frank,et al.  Instructional control of reinforcement learning: A behavioral and neurocomputational investigation , 2009, Brain Research.

[156]  B. Kolachana,et al.  Variation in dopamine genes influences responsivity of the human reward system , 2009, Proceedings of the National Academy of Sciences.

[157]  Jianxin Shi,et al.  Common variants on chromosome 6p22.1 are associated with schizophrenia , 2009, Nature.

[158]  David Goldman,et al.  The Role of COMT Val158Met in Cognition , 2009, Biological Psychiatry.

[159]  R. Palmiter,et al.  Disruption of NMDAR-dependent burst firing by dopamine neurons provides selective assessment of phasic dopamine-dependent behavior , 2009, Proceedings of the National Academy of Sciences.

[160]  C. Y. Chen,et al.  Caffeine and a selective adenosine A2A receptor antagonist induce reward and sensitization behavior associated with increased phospho-Thr75-DARPP-32 in mice , 2009, Psychopharmacology.

[161]  P. Visscher,et al.  Common polygenic variation contributes to risk of schizophrenia and bipolar disorder , 2009, Nature.

[162]  Young T. Hong,et al.  Dopamine Release in Dissociable Striatal Subregions Predicts the Different Effects of Oral Methylphenidate on Reversal Learning and Spatial Working Memory , 2009, The Journal of Neuroscience.

[163]  M. Pessiglione,et al.  Pharmacological modulation of subliminal learning in Parkinson's and Tourette's syndromes , 2009, Proceedings of the National Academy of Sciences.

[164]  Peter N. C. Mohr,et al.  Genetic variation in dopaminergic neuromodulation influences the ability to rapidly and flexibly adapt decisions , 2009, Proceedings of the National Academy of Sciences.

[165]  Alan C. Evans,et al.  Differences in genetic and environmental influences on the human cerebral cortex associated with development during childhood and adolescence , 2009, Human brain mapping.

[166]  X. Zhuang,et al.  Adenylyl Cyclase Type 5 Contributes to Corticostriatal Plasticity and Striatum-Dependent Learning , 2009, The Journal of Neuroscience.

[167]  Michael X. Cohen,et al.  Neurocomputational models of basal ganglia function in learning, memory and choice , 2009, Behavioural Brain Research.

[168]  Pall I. Olason,et al.  Common variants conferring risk of schizophrenia , 2009, Nature.

[169]  M. Frank,et al.  Striatal Dopamine Predicts Outcome-Specific Reversal Learning and Its Sensitivity to Dopaminergic Drug Administration , 2009, The Journal of Neuroscience.

[170]  M. Frank,et al.  Genetic contributions to avoidance-based decisions: striatal D2 receptor polymorphisms , 2009, Neuroscience.

[171]  M. Vreugdenhil,et al.  Modulation of gamma oscillations by endogenous adenosine through A1 and A2A receptors in the mouse hippocampus , 2009, Neuropharmacology.

[172]  V. Willour,et al.  Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study , 2009, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[173]  A. Hariri,et al.  Genetic variation in components of dopamine neurotransmission impacts ventral striatal reactivity associated with impulsivity , 2009, Molecular Psychiatry.

[174]  M. Kahana,et al.  Human Substantia Nigra Neurons Encode Unexpected Financial Rewards , 2009, Science.

[175]  Bradley B. Doll,et al.  The basal ganglia in reward and decision making: computational models and empirical studies , 2009 .

[176]  J. Stockman,et al.  Dopamine Transporter Genotype Conveys Familial Risk of Attention-Deficit/Hyperactivity Disorder Through Striatal Activation , 2009 .

[177]  K. Deisseroth,et al.  Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning , 2009, Science.

[178]  J. Salamone,et al.  Dopamine, Behavioral Economics, and Effort , 2009, Front. Behav. Neurosci..

[179]  M. Gluck,et al.  Reward-learning and the novelty-seeking personality: a between- and within-subjects study of the effects of dopamine agonists on young Parkinson's patients. , 2009, Brain : a journal of neurology.

[180]  M. Frank,et al.  Prefrontal and striatal dopaminergic genes predict individual differences in exploration and exploitation. , 2009, Nature neuroscience.

[181]  M. Reuter,et al.  Dopamine DRD2 polymorphism alters reversal learning and associated neural activity , 2009, NeuroImage.

[182]  Samuel M. McClure,et al.  Patients with schizophrenia have a reduced neural response to both unpredictable and predictable primary reinforcers , 2008, Neuropsychopharmacology.

[183]  M. Hallett,et al.  Mechanisms Underlying Dopamine-Mediated Reward Bias in Compulsive Behaviors , 2010, Neuron.

[184]  A Theory of the Basal Ganglia and Their Disorders, R. Miller, Publishers CRC Press, Taylor & Francis Group (2008), Price: $164.95, ISBN: 1-4200-5897-5 , 2010 .

[185]  A. Meyer-Lindenberg,et al.  Neural substrates of pleiotropic action of genetic variation in COMT: a meta-analysis , 2010, Molecular Psychiatry.

[186]  C. Escera,et al.  The role of the dopamine transporter DAT1 genotype on the neural correlates of cognitive flexibility , 2010, The European journal of neuroscience.

[187]  Stephen M Fleming,et al.  Overcoming status quo bias in the human brain , 2010, Proceedings of the National Academy of Sciences.

[188]  S. Nakanishi,et al.  Distinct Roles of Synaptic Transmission in Direct and Indirect Striatal Pathways to Reward and Aversive Behavior , 2010, Neuron.

[189]  A. Kanthasamy,et al.  Environmental Neurotoxic Pesticide Increases Histone Acetylation to Promote Apoptosis in Dopaminergic Neuronal Cells: Relevance to Epigenetic Mechanisms of Neurodegeneration , 2010, Molecular Pharmacology.

[190]  Randy L. Gollub,et al.  The COMT Val108/158Met polymorphism and medial temporal lobe volumetry in patients with schizophrenia and healthy adults , 2009, NeuroImage.

[191]  Chandan J. Vaidya,et al.  Neural response to working memory load varies by dopamine transporter genotype in children , 2010, NeuroImage.

[192]  David B. Goldstein,et al.  Rare Variants Create Synthetic Genome-Wide Associations , 2010, PLoS biology.

[193]  M. Ullsperger Genetic association studies of performance monitoring and learning from feedback: The role of dopamine and serotonin , 2010, Neuroscience & Biobehavioral Reviews.

[194]  N. Martin,et al.  The heritability of general cognitive ability increases linearly from childhood to young adulthood , 2010, Molecular Psychiatry.

[195]  James F. Cavanagh,et al.  Frontal theta links prediction errors to behavioral adaptation in reinforcement learning , 2010, NeuroImage.

[196]  Peter Kirsch,et al.  Motivational orientation modulates the neural response to reward , 2010, NeuroImage.

[197]  T. Kosten,et al.  Immediate and enduring effects of neonatal isolation on maternal behavior in rats , 2010, International Journal of Developmental Neuroscience.

[198]  Thomas E. Hazy,et al.  Neural mechanisms of acquired phasic dopamine responses in learning , 2010, Neuroscience & Biobehavioral Reviews.

[199]  Russell G. Port,et al.  Nucleus accumbens and effort-related functions: behavioral and neural markers of the interactions between adenosine A2A and dopamine D2 receptors , 2010, Neuroscience.