Reward magnitude tracking by neural populations in ventral striatum

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

[1]  J. Tepper,et al.  Stimulus-evoked changes in neostriatal dopamine levels in awake and anesthetized rats as measured by microdialysis , 1991, Brain Research.

[2]  C. Gallistel,et al.  Measuring the subjective magnitude of brain stimulation reward by titration with rate of reward. , 1991, Behavioral neuroscience.

[3]  Aline Seuwen,et al.  Specificity of stimulus-evoked fMRI responses in the mouse: The influence of systemic physiological changes associated with innocuous stimulation under four different anesthetics , 2014, NeuroImage.

[4]  M. Roitman,et al.  Nucleus Accumbens Neurons Are Innately Tuned for Rewarding and Aversive Taste Stimuli, Encode Their Predictors, and Are Linked to Motor Output , 2005, Neuron.

[5]  Satoshi Ikemoto,et al.  Mapping of chemical trigger zones for reward , 2004, Neuropharmacology.

[6]  T. Duong,et al.  Imaging oxygen consumption in forepaw somatosensory stimulation in rats under isoflurane anesthesia , 2004, Magnetic resonance in medicine.

[7]  Kyle S. Smith,et al.  Disentangling pleasure from incentive salience and learning signals in brain reward circuitry , 2011, Proceedings of the National Academy of Sciences.

[8]  James L Olds,et al.  Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. , 1954, Journal of comparative and physiological psychology.

[9]  Samuel M. McClure,et al.  Time Discounting for Primary Rewards , 2007, The Journal of Neuroscience.

[10]  Adrian T. Lee,et al.  Discrimination of Large Venous Vessels in Time‐Course Spiral Blood‐Oxygen‐Level‐Dependent Magnetic‐Resonance Functional Neuroimaging , 1995, Magnetic resonance in medicine.

[11]  G. Paxinos The Rat nervous system , 1985 .

[12]  Karl J. Friston,et al.  Temporal Difference Models and Reward-Related Learning in the Human Brain , 2003, Neuron.

[13]  K. Berridge,et al.  Towards a functional neuroanatomy of pleasure and happiness , 2009, Trends in Cognitive Sciences.

[14]  A G Barto,et al.  Toward a modern theory of adaptive networks: expectation and prediction. , 1981, Psychological review.

[15]  P. Garris,et al.  Dissociation of dopamine release in the nucleus accumbens from intracranial self-stimulation , 1999, Nature.

[16]  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.

[17]  W. Schultz Multiple reward signals in the brain , 2000, Nature Reviews Neuroscience.

[18]  M. Viergever,et al.  Temporal scaling properties and spatial synchronization of spontaneous blood oxygenation level‐dependent (BOLD) signal fluctuations in rat sensorimotor network at different levels of isoflurane anesthesia , 2011, NMR in biomedicine.

[19]  David G. Norris,et al.  Spin-echo fMRI: The poor relation? , 2012, NeuroImage.

[20]  C. Gallistel,et al.  Saturation of subjective reward magnitude as a function of current and pulse frequency. , 1994, Behavioral neuroscience.

[21]  S. Nicola,et al.  Firing of nucleus accumbens neurons during the consummatory phase of a discriminative stimulus task depends on previous reward predictive cues. , 2004, Journal of neurophysiology.

[22]  P. Shizgal,et al.  The neural substrates for the rewarding and dopamine-releasing effects of medial forebrain bundle stimulation have partially discrepant frequency responses , 2016, Behavioural Brain Research SreeTestContent1.

[23]  W. Schultz Neuronal Reward and Decision Signals: From Theories to Data. , 2015, Physiological reviews.

[24]  L. Swanson The Rat Brain in Stereotaxic Coordinates, George Paxinos, Charles Watson (Eds.). Academic Press, San Diego, CA (1982), vii + 153, $35.00, ISBN: 0 125 47620 5 , 1984 .

[25]  N. Logothetis,et al.  Neurophysiological investigation of the basis of the fMRI signal , 2001, Nature.

[26]  C. Fiorillo,et al.  Optogenetic Mimicry of the Transient Activation of Dopamine Neurons by Natural Reward Is Sufficient for Operant Reinforcement , 2012, PloS one.

[27]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[28]  R. Wightman,et al.  Differential Dopamine Release Dynamics in the Nucleus Accumbens Core and Shell Reveal Complementary Signals for Error Prediction and Incentive Motivation , 2015, The Journal of Neuroscience.

[29]  M. B. Rooney,et al.  Extracellular dopamine dynamics in rat caudate–putamen during experimenter-delivered and intracranial self-stimulation , 2000, Neuroscience.

[30]  C R Gallistel,et al.  Self-stimulation in the rat: quantitative characteristics of the reward pathway. , 1978, Journal of comparative and physiological psychology.

[31]  Jeff H. Duyn,et al.  Low-frequency fluctuations in the cardiac rate as a source of variance in the resting-state fMRI BOLD signal , 2007, NeuroImage.

[32]  Ilana B. Witten,et al.  Recombinase-Driver Rat Lines: Tools, Techniques, and Optogenetic Application to Dopamine-Mediated Reinforcement , 2011, Neuron.

[33]  Z. Brodnik,et al.  Dopamine uptake dynamics are preserved under isoflurane anesthesia , 2015, Neuroscience Letters.

[34]  Edward H. Nieh,et al.  Optogenetic dissection of neural circuits underlying emotional valence and motivated behaviors , 2012, Brain Research.

[35]  P. Shizgal,et al.  Growth of brain stimulation reward as a function of duration and stimulation strength. , 2003, Behavioral neuroscience.

[36]  M. Kringelbach The human orbitofrontal cortex: linking reward to hedonic experience , 2005, Nature Reviews Neuroscience.

[37]  Hoon-Ki Min,et al.  Synchronized electrical stimulation of the rat medial forebrain bundle and perforant pathway generates an additive BOLD response in the nucleus accumbens and prefrontal cortex , 2013, NeuroImage.

[38]  Sidney I. Wiener,et al.  Lesions of the medial shell of the nucleus accumbens impair rats in finding larger rewards, but spare reward-seeking behavior , 2000, Behavioural Brain Research.

[39]  Catie Chang,et al.  Influence of heart rate on the BOLD signal: The cardiac response function , 2009, NeuroImage.

[40]  R. Wise,et al.  Synaptic and Behavioral Profile of Multiple Glutamatergic Inputs to the Nucleus Accumbens , 2012, Neuron.

[41]  K. Miyazaki,et al.  Nucleus accumbens , 2018, Radiopaedia.org.

[42]  Nikos K. Logothetis,et al.  The effect of a serotonin-induced dissociation between spiking and perisynaptic activity on BOLD functional MRI , 2008, Proceedings of the National Academy of Sciences.

[43]  J. O'Doherty,et al.  What We Know and Do Not Know about the Functions of the Orbitofrontal Cortex after 20 Years of Cross-Species Studies , 2007, The Journal of Neuroscience.

[44]  A. Hariri,et al.  Preference for Immediate over Delayed Rewards Is Associated with Magnitude of Ventral Striatal Activity , 2006, The Journal of Neuroscience.

[45]  K. Doya Modulators of decision making , 2008, Nature Neuroscience.

[46]  A portrait of the substrate for self-stimulation. , 1981 .

[47]  C. Iadecola,et al.  Glial regulation of the cerebral microvasculature , 2007, Nature Neuroscience.

[48]  G. Schoenbaum,et al.  Neural Encoding in Ventral Striatum during Olfactory Discrimination Learning , 2003, Neuron.

[49]  Samuel M. McClure,et al.  Separate Neural Systems Value Immediate and Delayed Monetary Rewards , 2004, Science.

[50]  Aviad Hai,et al.  Molecular-Level Functional Magnetic Resonance Imaging of Dopaminergic Signaling , 2014, Science.

[51]  P. Shizgal,et al.  Competition and summation between rewarding effects of sucrose and lateral hypothalamic stimulation in the rat. , 1994, Behavioral neuroscience.

[52]  Samuel M. McClure,et al.  Temporal Prediction Errors in a Passive Learning Task Activate Human Striatum , 2003, Neuron.

[53]  S. Nicola,et al.  Roles of Nucleus Accumbens Core and Shell in Incentive-Cue Responding and Behavioral Inhibition , 2011, The Journal of Neuroscience.

[54]  L. Green,et al.  Economic substitutability of electrical brain stimulation, food, and water. , 1991, Journal of the experimental analysis of behavior.

[55]  T. A. Mark,et al.  Subjective reward magnitude of medial forebrain stimulation as a function of train duration and pulse frequency. , 1993, Behavioral neuroscience.

[56]  Mark J. Thomas,et al.  Biological substrates of reward and aversion: A nucleus accumbens activity hypothesis , 2009, Neuropharmacology.

[57]  M. Buonocore,et al.  Ghost artifact reduction for echo planar imaging using image phase correction , 1997, Magnetic resonance in medicine.

[58]  Howard L Fields,et al.  Encoding of Palatability and Appetitive Behaviors by Distinct Neuronal Populations in the Nucleus Accumbens , 2005, The Journal of Neuroscience.

[59]  P. Shizgal,et al.  Psychophysical inference of frequency-following fidelity in the neural substrate for brain stimulation reward , 2015, Behavioural Brain Research.

[60]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.

[61]  N. Logothetis,et al.  The effects of electrical microstimulation on cortical signal propagation , 2010, Nature Neuroscience.

[62]  Z. Merali,et al.  Re-evaluation of the role of dopamine in intracranial self-stimulation using in vivo microdialysis , 1991, Behavioural Brain Research.

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

[64]  N. Logothetis,et al.  Neural basis of the blood-oxygen-level-dependent functional magnetic resonance imaging , 2004 .

[65]  R. Herrnstein On the law of effect. , 1970, Journal of the experimental analysis of behavior.