Reconciling the Roles of Orbitofrontal Cortex in Reversal Learning and the Encoding of Outcome Expectancies

Abstract: Damage to orbitofrontal cortex (OFC) has long been associated with decision‐making deficits. Such deficits are epitomized by impairments in reversal learning. Historically, reversal learning deficits have been linked to a response inhibition function or to the rapid reversal of associative encoding in OFC neurons. However here we will suggest that OFC supports reversal learning not because its encoding is particularly flexible—indeed it actually is not—but rather because output from OFC is critical for flexible associative encoding downstream in basolateral amygdala (ABL). Consistent with this argument, we will show that reversal performance is actually inversely related to the flexibility of associative encoding in OFC (i.e., the better the reversal performance, the less flexible the encoding). Further, we will demonstrate that associative correlates in ABL are more flexible during reversal learning than in OFC, become less flexible after damage to OFC, and are required for the expression of the reversal deficit caused by OFC lesions. We will propose that OFC facilitates associative flexibility in downstream regions, such as ABL, for the same reason that it is critical for outcome‐guided behavior in a variety of setting—namely that processing in OFC signals the value of expected outcomes. In addition to their role in guiding behavior, these outcome expectancies permit the rapid recognition of unexpected outcomes, thereby driving new learning.

[1]  M. Roesch,et al.  Cocaine-induced decision-making deficits are mediated by miscoding in basolateral amygdala , 2007, Nature Neuroscience.

[2]  G. Schoenbaum,et al.  Basolateral Amygdala Lesions Abolish Orbitofrontal-Dependent Reversal Impairments , 2007, Neuron.

[3]  Jerald D. Kralik,et al.  Rhesus monkeys with orbital prefrontal cortex lesions can learn to inhibit prepotent responses in the reversed reward contingency task. , 2006, Cerebral cortex.

[4]  M. Roesch,et al.  Abnormal associative encoding in orbitofrontal neurons in cocaine‐experienced rats during decision‐making , 2006, The European journal of neuroscience.

[5]  J. Morton,et al.  Choosing the Lesser of Two Evils, the Better of Two Goods: Specifying the Roles of Ventromedial Prefrontal Cortex and Dorsal Anterior Cingulate in Object Choice , 2006, The Journal of Neuroscience.

[6]  M. Roesch,et al.  Encoding of Time-Discounted Rewards in Orbitofrontal Cortex Is Independent of Value Representation , 2006, Neuron.

[7]  M. Quirk,et al.  Representation of Spatial Goals in Rat Orbitofrontal Cortex , 2006, Neuron.

[8]  C. Padoa-Schioppa,et al.  Neurons in the orbitofrontal cortex encode economic value , 2006, Nature.

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

[10]  Geoffrey Schoenbaum,et al.  Encoding changes in orbitofrontal cortex in reversal-impaired aged rats. , 2006, Journal of neurophysiology.

[11]  Joseph J. Paton,et al.  The primate amygdala represents the positive and negative value of visual stimuli during learning , 2006, Nature.

[12]  M. Roesch,et al.  Orbitofrontal cortex, decision-making and drug addiction , 2006, Trends in Neurosciences.

[13]  J. O'Doherty,et al.  Human Neural Learning Depends on Reward Prediction Errors in the Blocking Paradigm , 2005, Journal of neurophysiology.

[14]  M. Roesch,et al.  Neuronal activity in primate orbitofrontal cortex reflects the value of time. , 2005, Journal of neurophysiology.

[15]  Michela Gallagher,et al.  Lesions of Orbitofrontal Cortex Impair Rats' Differential Outcome Expectancy Learning But Not Conditioned Stimulus-Potentiated Feeding , 2005, The Journal of Neuroscience.

[16]  Geoffrey Schoenbaum,et al.  Rapid Associative Encoding in Basolateral Amygdala Depends on Connections with Orbitofrontal Cortex , 2005, Neuron.

[17]  Michael E. Ragozzino,et al.  The involvement of the orbitofrontal cortex in learning under changing task contingencies , 2005, Neurobiology of Learning and Memory.

[18]  E. Murray,et al.  Bilateral Orbital Prefrontal Cortex Lesions in Rhesus Monkeys Disrupt Choices Guided by Both Reward Value and Reward Contingency , 2004, The Journal of Neuroscience.

[19]  M. Roesch,et al.  Neuronal Activity Related to Reward Value and Motivation in Primate Frontal Cortex , 2004, Science.

[20]  Masataka Watanabe,et al.  Long‐ and short‐range reward expectancy in the primate orbitofrontal cortex , 2004, The European journal of neuroscience.

[21]  S. Thorpe,et al.  The orbitofrontal cortex: Neuronal activity in the behaving monkey , 2004, Experimental Brain Research.

[22]  Geoffrey Schoenbaum,et al.  Different Roles for Orbitofrontal Cortex and Basolateral Amygdala in a Reinforcer Devaluation Task , 2003, The Journal of Neuroscience.

[23]  V. Brown,et al.  Orbital prefrontal cortex mediates reversal learning and not attentional set shifting in the rat , 2003, Behavioural Brain Research.

[24]  T. Robbins,et al.  Dissociable Contributions of the Orbitofrontal and Infralimbic Cortex to Pavlovian Autoshaping and Discrimination Reversal Learning: Further Evidence for the Functional Heterogeneity of the Rodent Frontal Cortex , 2003, The Journal of Neuroscience.

[25]  G. Schoenbaum,et al.  Encoding Predicted Outcome and Acquired Value in Orbitofrontal Cortex during Cue Sampling Depends upon Input from Basolateral Amygdala , 2003, Neuron.

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

[27]  Wolfgang Hauber,et al.  Orbital prefrontal cortex and guidance of instrumental behaviour in rats under reversal conditions , 2003, Behavioural Brain Research.

[28]  P. Holland,et al.  Double dissociation of the effects of lesions of basolateral and central amygdala on conditioned stimulus‐potentiated feeding and Pavlovian‐instrumental transfer , 2003, The European journal of neuroscience.

[29]  Geoffrey Schoenbaum,et al.  Lesions of orbitofrontal cortex and basolateral amygdala complex disrupt acquisition of odor-guided discriminations and reversals. , 2003, Learning & memory.

[30]  P. Holland,et al.  Amygdalo-Hypothalamic Circuit Allows Learned Cues to Override Satiety and Promote Eating , 2002, The Journal of Neuroscience.

[31]  E. Murray,et al.  The amygdala and reward , 2002, Nature Reviews Neuroscience.

[32]  Geoffrey Schoenbaum,et al.  Orbitofrontal lesions in rats impair reversal but not acquisition of go, no-go odor discriminations , 2002, Neuroreport.

[33]  J. O'Doherty,et al.  Neural Responses during Anticipation of a Primary Taste Reward , 2002, Neuron.

[34]  Stephen Maren,et al.  Contextual and auditory fear conditioning are mediated by the lateral, basal, and central amygdaloid nuclei in rats. , 2001, Learning & memory.

[35]  W. Schultz,et al.  Reward-related neuronal activity during go-nogo task performance in primate orbitofrontal cortex. , 2000, Journal of neurophysiology.

[36]  K. Hikosaka,et al.  Delay activity of orbital and lateral prefrontal neurons of the monkey varying with different rewards. , 2000, Cerebral cortex.

[37]  John Patrick Aggleton,et al.  The Amygdala : a functional analysis , 2000 .

[38]  Joseph E LeDoux,et al.  Different lateral amygdala outputs mediate reactions and actions elicited by a fear-arousing stimulus , 2000, Nature Neuroscience.

[39]  Rudolf N. Cardinal,et al.  Differential involvement of amygdala subsystems in appetitive conditioning and drug addiction. , 2000 .

[40]  Joseph E LeDoux,et al.  Contribution of Ventrolateral Prefrontal Cortex to the Acquisition and Extinction of Conditioned Fear in Rats , 1999, Neurobiology of Learning and Memory.

[41]  G. Schoenbaum,et al.  Orbitofrontal Cortex and Representation of Incentive Value in Associative Learning , 1999, The Journal of Neuroscience.

[42]  W. Schultz,et al.  Relative reward preference in primate orbitofrontal cortex , 1999, Nature.

[43]  G. Schoenbaum,et al.  Neural Encoding in Orbitofrontal Cortex and Basolateral Amygdala during Olfactory Discrimination Learning , 1999, The Journal of Neuroscience.

[44]  C. Frith,et al.  Orbitofrontal cortex is activated during breaches of expectation in tasks of visual attention , 1999, Nature Neuroscience.

[45]  M. Cassell,et al.  Cortical, thalamic, and amygdaloid connections of the anterior and posterior insular cortices , 1998, The Journal of comparative neurology.

[46]  G. Schoenbaum,et al.  Orbitofrontal cortex and basolateral amygdala encode expected outcomes during learning , 1998, Nature Neuroscience.

[47]  Joseph E LeDoux,et al.  Fear Conditioning Enhances Different Temporal Components of Tone-Evoked Spike Trains in Auditory Cortex and Lateral Amygdala , 1997, Neuron.

[48]  M. Mishkin,et al.  Effects of orbital frontal and anterior cingulate lesions on object and spatial memory in rhesus monkeys , 1997, Neuropsychologia.

[49]  E. Rolls,et al.  Orbitofrontal cortex neurons: role in olfactory and visual association learning. , 1996, Journal of neurophysiology.

[50]  E T Rolls,et al.  Olfactory neuronal responses in the primate orbitofrontal cortex: analysis in an olfactory discrimination task. , 1996, Journal of neurophysiology.

[51]  T. Robbins,et al.  Dissociation in prefrontal cortex of affective and attentional shifts , 1996, Nature.

[52]  Joseph E LeDoux,et al.  Fear conditioning enhances short-latency auditory responses of lateral amygdala neurons: Parallel recordings in the freely behaving rat , 1995, Neuron.

[53]  E. Rolls,et al.  Emotion-related learning in patients with social and emotional changes associated with frontal lobe damage. , 1994, Journal of neurology, neurosurgery, and psychiatry.

[54]  H. Kita,et al.  Amygdaloid projections to the frontal cortex and the striatum in the rat , 1990, The Journal of comparative neurology.

[55]  Joseph E LeDoux,et al.  The lateral amygdaloid nucleus: sensory interface of the amygdala in fear conditioning , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[56]  J. Price,et al.  Projections from the amygdaloid complex to the cerebral cortex and thalamus in the rat and cat , 1977, The Journal of comparative neurology.

[57]  M. Mishkin,et al.  Limbic lesions and the problem of stimulus--reinforcement associations. , 1972, Experimental neurology.

[58]  H. Teitelbaum.  A COMPARISON OF EFFECTS OF ORBITOFRONTAL AND HIPPOCAMPAL LESIONS UPON DISCRIMINATION LEARNING AND REVERSAL IN THE CAT. , 1964, Experimental neurology.

[59]  L. Weiskrantz,et al.  Behavioral changes associated with ablation of the amygdaloid complex in monkeys. , 1956, Journal of comparative and physiological psychology.