Mesolimbic Functional Magnetic Resonance Imaging Activations during Reward Anticipation Correlate with Reward-Related Ventral Striatal Dopamine Release

The dopaminergic mechanisms that control reward-motivated behavior are the subject of intense study, but it is yet unclear how, in humans, neural activity in mesolimbic reward-circuitry and its functional neuroimaging correlates are related to dopamine release. To address this question, we obtained functional magnetic resonance imaging (fMRI) measures of reward-related neural activity and [11C]raclopride positron emission tomography measures of dopamine release in the same human participants, while they performed a delayed monetary incentive task. Across the cohort, a positive correlation emerged between neural activity of the substantia nigra/ventral tegmental area (SN/VTA), the main origin of dopaminergic neurotransmission, during reward anticipation and reward-related [11C]raclopride displacement as an index of dopamine release in the ventral striatum, major target of SN/VTA dopamine neurons. Neural activity in the ventral striatum/nucleus accumbens itself also correlated with ventral striatal dopamine release. Additionally, high-reward-related dopamine release was associated with increased activation of limbic structures, such as the amygdala and the hippocampus. The observed correlations of reward-related mesolimbic fMRI activation and dopamine release provide evidence that dopaminergic neurotransmission plays a quantitative role in human mesolimbic reward processing. Moreover, the combined neurochemical and hemodynamic imaging approach used here opens up new perspectives for the investigation of molecular mechanisms underlying human cognition.

[1]  Jean-Luc Anton,et al.  Region of interest analysis using an SPM toolbox , 2010 .

[2]  S. J. Shammah-Lagnado,et al.  Organization of ventral tegmental area projections to the ventral tegmental area–nigral complex in the rat , 2008, Neuroscience.

[3]  Simon Cervenka,et al.  Associations between dopamine D2-receptor binding and cognitive performance indicate functional compartmentalization of the human striatum , 2008, NeuroImage.

[4]  Samuel M. McClure,et al.  BOLD Responses Reflecting Dopaminergic Signals in the Human Ventral Tegmental Area , 2008, Science.

[5]  Michael Bauer,et al.  Reward anticipation and outcomes in adult males with attention-deficit/hyperactivity disorder , 2008, NeuroImage.

[6]  S. Ikemoto.  Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex , 2007, Brain Research Reviews.

[7]  Alexander Hammers,et al.  Volumes, spatial extents and a probabilistic atlas of the human basal ganglia and thalamus , 2007, NeuroImage.

[8]  Raymond J. Dolan,et al.  Anticipation of novelty recruits reward system and hippocampus while promoting recollection , 2007, NeuroImage.

[9]  A. Grace,et al.  The Yin and Yang of dopamine release: a new perspective , 2007, Neuropharmacology.

[10]  H. Heinze,et al.  Ageing and early-stage Parkinson's disease affect separable neural mechanisms of mesolimbic reward processing. , 2007, Brain : a journal of neurology.

[11]  Rony Paz,et al.  Gamma Oscillations Coordinate Amygdalo-Rhinal Interactions during Learning , 2007, The Journal of Neuroscience.

[12]  J. O'Doherty,et al.  Contributions of the Amygdala to Reward Expectancy and Choice Signals in Human Prefrontal Cortex , 2007, Neuron.

[13]  Frank Telang,et al.  Depressed dopamine activity in caudate and preliminary evidence of limbic involvement in adults with attention-deficit/hyperactivity disorder. , 2007, Archives of general psychiatry.

[14]  Robert A. Koeppe,et al.  Individual Differences in Reward Responding Explain Placebo-Induced Expectations and Effects , 2007, Neuron.

[15]  R. P. Maguire,et al.  Consensus Nomenclature for in vivo Imaging of Reversibly Binding Radioligands , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[16]  A. Björklund,et al.  Dopamine neuron systems in the brain: an update , 2007, Trends in Neurosciences.

[17]  A. Grace,et al.  Regulation of firing of dopaminergic neurons and control of goal-directed behaviors , 2007, Trends in Neurosciences.

[18]  Yasushi Kobayashi,et al.  Reward Prediction Error Computation in the Pedunculopontine Tegmental Nucleus Neurons , 2007, Annals of the New York Academy of Sciences.

[19]  H. Haas,et al.  Sleep Deprivation Increases A1 Adenosine Receptor Binding in the Human Brain: A Positron Emission Tomography Study , 2007, The Journal of Neuroscience.

[20]  T. Robbins,et al.  Differential Roles of Dopamine D1 and D2 Receptors in the Nucleus Accumbens in Attentional Performance on the Five-Choice Serial Reaction Time Task , 2007, Neuropsychopharmacology.

[21]  Brian Knutson,et al.  Linking nucleus accumbens dopamine and blood oxygenation , 2007, Psychopharmacology.

[22]  R. Dolan,et al.  Dopamine-dependent prediction errors underpin reward-seeking behaviour in humans , 2006, Nature.

[23]  N. Bunzeck,et al.  Absolute Coding of Stimulus Novelty in the Human Substantia Nigra/VTA , 2006, Neuron.

[24]  Brian Knutson,et al.  Reward-Motivated Learning: Mesolimbic Activation Precedes Memory Formation , 2006, Neuron.

[25]  Ji-Kyung Choi,et al.  Brain hemodynamic changes mediated by dopamine receptors: Role of the cerebral microvasculature in dopamine-mediated neurovascular coupling , 2006, NeuroImage.

[26]  K. Berman,et al.  Cerebral Cortex doi:10.1093/cercor/bhj004 Neural Coding of Distinct Statistical Properties of Reward Information in Humans , 2005 .

[27]  Ewelina Knapska,et al.  Differential involvement of the central amygdala in appetitive versus aversive learning. , 2006, Learning & memory.

[28]  Arno Villringer,et al.  Dysfunction of ventral striatal reward prediction in schizophrenia , 2006, NeuroImage.

[29]  J. O'Doherty,et al.  Predictive Neural Coding of Reward Preference Involves Dissociable Responses in Human Ventral Midbrain and Ventral Striatum , 2006, Neuron.

[30]  H. Heinze,et al.  The Dopaminergic Midbrain Participates in Human Episodic Memory Formation: Evidence from Genetic Imaging , 2006, The Journal of Neuroscience.

[31]  Jeffrey C. Cooper,et al.  Functional magnetic resonance imaging of reward prediction , 2005, Current opinion in neurology.

[32]  J. Lisman,et al.  The Hippocampal-VTA Loop: Controlling the Entry of Information into Long-Term Memory , 2005, Neuron.

[33]  T. Ono,et al.  Dopamine D1 receptors involved in locomotor activity and accumbens neural responses to prediction of reward associated with place. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[34]  H. Heinze,et al.  Reward-Related fMRI Activation of Dopaminergic Midbrain Is Associated with Enhanced Hippocampus- Dependent Long-Term Memory Formation , 2005, Neuron.

[35]  Hans-Jochen Heinze,et al.  Redefining implicit and explicit memory: the functional neuroanatomy of priming, remembering, and control of retrieval. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

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

[37]  Mathias Schreckenberger,et al.  Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and craving. , 2004, The American journal of psychiatry.

[38]  F. McGlone,et al.  Dopamine Transmission in the Human Striatum during Monetary Reward Tasks , 2004, The Journal of Neuroscience.

[39]  Nao Chuhma,et al.  Dopamine Neurons Mediate a Fast Excitatory Signal via Their Glutamatergic Synapses , 2004, The Journal of Neuroscience.

[40]  W. Schultz,et al.  Coding of Predicted Reward Omission by Dopamine Neurons in a Conditioned Inhibition Paradigm , 2003, The Journal of Neuroscience.

[41]  J. O'Doherty,et al.  Encoding Predictive Reward Value in Human Amygdala and Orbitofrontal Cortex , 2003, Science.

[42]  R. Elliott,et al.  Differential Response Patterns in the Striatum and Orbitofrontal Cortex to Financial Reward in Humans: A Parametric Functional Magnetic Resonance Imaging Study , 2003, The Journal of Neuroscience.

[43]  N. Logothetis.  The neural basis of the blood-oxygen-level-dependent functional magnetic resonance imaging signal. , 2002, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[44]  A. Syrota,et al.  In Vivo Detection of Striatal Dopamine Release during Reward: A PET Study with [11C]Raclopride and a Single Dynamic Scan Approach , 2002, NeuroImage.

[45]  Brian Knutson,et al.  Dissociation of reward anticipation and outcome with event-related fMRI , 2001, Neuroreport.

[46]  D. Mash,et al.  Dopamine D1 receptor expression in human basal ganglia and changes in Parkinson's disease , 2001 .

[47]  D. Mash,et al.  Dopamine D(1) receptor expression in human basal ganglia and changes in Parkinson's disease. , 2001, Brain research. Molecular brain research.

[48]  Y. Smith,et al.  Anatomy of the dopamine system in the basal ganglia , 2000, Trends in Neurosciences.

[49]  O Josephs,et al.  Event-related functional magnetic resonance imaging: modelling, inference and optimization. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[50]  S. Haber,et al.  Dopamine Neurons Make Glutamatergic Synapses In Vitro , 1998, The Journal of Neuroscience.

[51]  D. Brooks,et al.  Evidence for striatal dopamine release during a video game , 1998, Nature.

[52]  R. Turner,et al.  Event-Related fMRI: Characterizing Differential Responses , 1998, NeuroImage.

[53]  A. Malhotra,et al.  Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[54]  S. Haber,et al.  The primate substantia nigra and VTA: integrative circuitry and function. , 1997, Critical reviews in neurobiology.

[55]  A. Lammertsma,et al.  Simplified Reference Tissue Model for PET Receptor Studies , 1996, NeuroImage.

[56]  N. Volkow,et al.  Distribution Volume Ratios without Blood Sampling from Graphical Analysis of PET Data , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[57]  U Pietrzyk,et al.  An interactive technique for three-dimensional image registration: validation for PET, SPECT, MRI and CT brain studies. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[58]  M. Holschbach,et al.  A new and simple on-line method for the preparation of n.c.a. [11C]methyl iodide , 1993 .

[59]  W. Schultz,et al.  Responses of monkey dopamine neurons during learning of behavioral reactions. , 1992, Journal of neurophysiology.