Top–down‐directed synchrony from medial frontal cortex to nucleus accumbens during reward anticipation

The nucleus accumbens and medial frontal cortex (MFC) are part of a loop involved in modulating behavior according to anticipated rewards. However, the precise temporal landscape of their electrophysiological interactions in humans remains unknown because it is not possible to record neural activity from the nucleus accumbens using noninvasive techniques. We recorded electrophysiological activity simultaneously from the nucleus accumbens and cortex (via surface EEG) in humans who had electrodes implanted as part of deep‐brain‐stimulation treatment for obsessive–compulsive disorder. Patients performed a simple reward motivation task previously shown to activate the ventral striatum. Spectral Granger causality analyses were applied to dissociate “top–down” (cortex → nucleus accumbens)‐ from “bottom–up” (nucleus accumbens → cortex)‐directed synchronization (functional connectivity). “Top–down”‐directed synchrony from cortex to nucleus accumbens was maximal over medial frontal sites and was significantly stronger when rewards were anticipated. These findings provide direct electrophysiological evidence for a role of the MFC in modulating nucleus accumbens reward‐related processing and may be relevant to understanding the mechanisms of deep‐brain stimulation and its beneficial effects on psychiatric conditions. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.

[1]  Alan C. Evans,et al.  Changes in brain activity related to eating chocolate: from pleasure to aversion. , 2001, Brain : a journal of neurology.

[2]  S. Haber,et al.  Reward-Related Cortical Inputs Define a Large Striatal Region in Primates That Interface with Associative Cortical Connections, Providing a Substrate for Incentive-Based Learning , 2006, The Journal of Neuroscience.

[3]  R. Wise,et al.  Addictive drugs and brain stimulation reward. , 1996, Annual review of neuroscience.

[4]  Nikolai Axmacher,et al.  Good Vibrations: Cross-frequency Coupling in the Human Nucleus Accumbens during Reward Processing , 2009, Journal of Cognitive Neuroscience.

[5]  H. Westenberg,et al.  P.1.b.014 Deep brain stimulation of the nucleus accumbens for therapy-refractory obsessive-compulsive disorder , 2010, European Neuropsychopharmacology.

[6]  S. Haber,et al.  The Reward Circuit: Linking Primate Anatomy and Human Imaging , 2010, Neuropsychopharmacology.

[7]  Hans-Jochen Heinze,et al.  Nucleus Accumbens is Involved in Human Action Monitoring: Evidence from Invasive Electrophysiological Recordings , 2007, Frontiers in human neuroscience.

[8]  H. Uylings,et al.  Reduced orbitofrontal-striatal activity on a reversal learning task in obsessive-compulsive disorder. , 2006, Archives of general psychiatry.

[9]  A. Heinz,et al.  Dopamine and the diseased brain. , 2006, CNS & neurological disorders drug targets.

[10]  H. Groenewegen,et al.  The nucleus accumbens: gateway for limbic structures to reach the motor system? , 1996, Progress in brain research.

[11]  Ning Ma,et al.  Addiction related alteration in resting-state brain connectivity , 2010, NeuroImage.

[12]  A. Grace,et al.  Nucleus Accumbens Deep Brain Stimulation Produces Region-Specific Alterations in Local Field Potential Oscillations and Evoked Responses In Vivo , 2009, The Journal of Neuroscience.

[13]  Wolfram Schultz,et al.  Relative reward processing in primate striatum , 2005, Experimental Brain Research.

[14]  Nikolaus R. McFarland,et al.  Striatonigrostriatal Pathways in Primates Form an Ascending Spiral from the Shell to the Dorsolateral Striatum , 2000, The Journal of Neuroscience.

[15]  Timothy Edward John Behrens,et al.  A Tractography Analysis of Two Deep Brain Stimulation White Matter Targets for Depression , 2009, Biological Psychiatry.

[16]  Arnaud Delorme,et al.  EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis , 2004, Journal of Neuroscience Methods.

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

[18]  Michael X. Cohen,et al.  Functional connectivity with anterior cingulate and orbitofrontal cortices during decision-making. , 2005, Brain research. Cognitive brain research.

[19]  Karl J. Friston,et al.  Dissociable Roles of Ventral and Dorsal Striatum in Instrumental Conditioning , 2004, Science.

[20]  S. Sesack,et al.  Projections from the Rat Prefrontal Cortex to the Ventral Tegmental Area: Target Specificity in the Synaptic Associations with Mesoaccumbens and Mesocortical Neurons , 2000, The Journal of Neuroscience.

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

[22]  Michael X. Cohen,et al.  Deep Brain Stimulation to Reward Circuitry Alleviates Anhedonia in Refractory Major Depression , 2008, Neuropsychopharmacology.

[23]  Brian Knutson,et al.  Anticipation of Increasing Monetary Reward Selectively Recruits Nucleus Accumbens , 2001, The Journal of Neuroscience.

[24]  H. Critchley,et al.  Inflammation Causes Mood Changes Through Alterations in Subgenual Cingulate Activity and Mesolimbic Connectivity , 2009, Biological Psychiatry.

[25]  S. Haber,et al.  The cortico-basal ganglia integrative network: The role of the thalamus , 2009, Brain Research Bulletin.

[26]  Michael X. Cohen,et al.  Nuclei Accumbens Phase Synchrony Predicts Decision-Making Reversals Following Negative Feedback , 2009, The Journal of Neuroscience.

[27]  A. Lozano,et al.  Deep Brain Stimulation for Treatment-Resistant Depression , 2005, Neuron.

[28]  E. Lynd-Balta,et al.  The orbital and medial prefrontal circuit through the primate basal ganglia , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  P. O’Donnell,et al.  Dopaminergic Modulation of Prefrontal Cortical Input to Nucleus Accumbens Neurons In Vivo , 2004, The Journal of Neuroscience.