The Essential Role of Primate Orbitofrontal Cortex in Conflict-Induced Executive Control Adjustment

Conflict in information processing evokes trial-by-trial behavioral modulations. Influential models suggest that adaptive tuning of executive control, mediated by mid-dorsal lateral prefrontal cortex (mdlPFC) and anterior cingulate cortex (ACC), underlies these modulations. However, mdlPFC and ACC are parts of distributed brain networks including orbitofrontal cortex (OFC), posterior cingulate cortex (PCC), and superior-dorsal lateral prefrontal cortex (sdlPFC). Contributions of these latter areas in adaptive tuning of executive control are unknown. We trained monkeys to perform a matching task in which they had to resolve the conflict between two behavior-guiding rules. Here, we report that bilateral lesions in OFC, but not in PCC or sdlPFC, impaired selection between these competing rules. In addition, the behavioral adaptation that is normally induced by experiencing conflict disappeared in OFC-lesioned, but remained normal in PCC-lesioned or sdlPFC-lesioned monkeys. Exploring underlying neuronal processes, we found that the activity of neurons in OFC represented the conflict between behavioral options independent from the other aspects of the task. Responses of OFC neurons to rewards also conveyed information of the conflict level that the monkey had experienced along the course to obtain the reward. Our findings indicate dissociable functions for five closely interconnected cortical areas suggesting that OFC and mdlPFC, but not PCC or sdlPFC or ACC, play indispensable roles in conflict-dependent executive control of on-going behavior. Both mdlPFC and OFC support detection of conflict and its integration with the task goal, but in contrast to mdlPFC, OFC does not retain the necessary information for conflict-induced modulation of future decisions.

[1]  Daeyeol Lee,et al.  Functional Specialization of the Primate Frontal Cortex during Decision Making , 2007, The Journal of Neuroscience.

[2]  Charles M. Butter,et al.  Perseveration in extinction and in discrimination reversal tasks following selective frontal ablations in Macaca mulatta , 1969 .

[3]  L. Fellows.  The Role of Orbitofrontal Cortex in Decision Making , 2007, Annals of the New York Academy of Sciences.

[4]  C. Carter,et al.  Anterior cingulate cortex and conflict detection: An update of theory and data , 2007, Cognitive, affective & behavioral neuroscience.

[5]  Robert W. Lundin.  Conditioning and extinction. , 1961 .

[6]  M. Walton,et al.  Re‐evaluating the role of the orbitofrontal cortex in reward and reinforcement , 2012, The European journal of neuroscience.

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

[8]  M. Petrides.  Lateral prefrontal cortex: architectonic and functional organization , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

[9]  F Mauguiere,et al.  The duality of the cingulate gyrus in monkey. Neuroanatomical study and functional hypothesis. , 1980, Brain : a journal of neurology.

[10]  J S Fowler,et al.  Addiction changes orbitofrontal gyrus function: involvement in response inhibition , 2001, Neuroreport.

[11]  Hatim A. Zariwala,et al.  Neural correlates, computation and behavioural impact of decision confidence , 2008, Nature.

[12]  John M. Pearson,et al.  Posterior cingulate cortex: adapting behavior to a changing world , 2011, Trends in Cognitive Sciences.

[13]  R. Knight,et al.  Prefrontal–cingulate interactions in action monitoring , 2000, Nature Neuroscience.

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

[15]  E. Awh,et al.  Conflict adaptation effects in the absence of executive control , 2003, Nature Neuroscience.

[16]  Timothy Edward John Behrens,et al.  Separate value comparison and learning mechanisms in macaque medial and lateral orbitofrontal cortex , 2010, Proceedings of the National Academy of Sciences.

[17]  Keiji Tanaka,et al.  Conflict-induced behavioural adjustment: a clue to the executive functions of the prefrontal cortex , 2009, Nature Reviews Neuroscience.

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

[19]  Keiji Tanaka,et al.  Mnemonic Function of the Dorsolateral Prefrontal Cortex in Conflict-Induced Behavioral Adjustment , 2007, Science.

[20]  A. Grabowska,et al.  Cognitive inhibition in patients with medial orbitofrontal damage , 2007, Experimental Brain Research.

[21]  Keiji Tanaka,et al.  Prefrontal Cell Activities Related to Monkeys' Success and Failure in Adapting to Rule Changes in a Wisconsin Card Sorting Test Analog , 2006, The Journal of Neuroscience.

[22]  E. Miller,et al.  Neuronal activity in primate dorsolateral and orbital prefrontal cortex during performance of a reward preference task , 2003, The European journal of neuroscience.

[23]  R. Mitchell,et al.  The BOLD response during Stroop task-like inhibition paradigms: Effects of task difficulty and task-relevant modality , 2005, Brain and Cognition.

[24]  J. Staddon,et al.  Adaptation to Reward , 1987 .

[25]  Adam Kepecs,et al.  Neural representation of behavioral outcomes in the orbitofrontal cortex , 2009, Current Opinion in Neurobiology.

[26]  M. Mishkin,et al.  Conditioning and extinction of a food-rewarded response after selective ablations of frontal cortex in rhesus monkeys. , 1963, Experimental neurology.

[27]  J. Wallis.  Orbitofrontal cortex and its contribution to decision-making. , 2007, Annual review of neuroscience.

[28]  C. Cavada,et al.  The anatomical connections of the macaque monkey orbitofrontal cortex. A review. , 2000, Cerebral cortex.

[29]  W. Schultz,et al.  Adaptation of Reward Sensitivity in Orbitofrontal Neurons , 2010, The Journal of Neuroscience.

[30]  J. Gläscher,et al.  Lesion mapping of cognitive control and value-based decision making in the prefrontal cortex , 2012, Proceedings of the National Academy of Sciences.

[31]  Keiji Tanaka,et al.  Behavioral evidence for working memory of sensory dimension in macaque monkeys , 2002, Behavioural Brain Research.

[32]  T. Robbins,et al.  Dissociable Forms of Inhibitory Control within Prefrontal Cortex with an Analog of the Wisconsin Card Sort Test: Restriction to Novel Situations and Independence from “On-Line” Processing , 1997, The Journal of Neuroscience.

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

[34]  M. Roesch,et al.  A new perspective on the role of the orbitofrontal cortex in adaptive behaviour , 2009, Nature Reviews Neuroscience.

[35]  C. Büchel,et al.  Neural representations of subjective reward value , 2010, Behavioural Brain Research.

[36]  Philip G. F. Browning,et al.  Dissociable Components of Rule-Guided Behavior Depend on Distinct Medial and Prefrontal Regions , 2009, Science.

[37]  C. Olson,et al.  Functional heterogeneity in cingulate cortex: the anterior executive and posterior evaluative regions. , 1992, Cerebral cortex.

[38]  Karl J. Friston,et al.  Investigations of the functional anatomy of attention using the stroop test , 1993, Neuropsychologia.

[39]  Robert C. Wilson,et al.  Orbitofrontal Cortex as a Cognitive Map of Task Space , 2014, Neuron.

[40]  R. Elliott,et al.  Dissociable functions in the medial and lateral orbitofrontal cortex: evidence from human neuroimaging studies. , 2000, Cerebral cortex.

[41]  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.

[42]  L. Fellows,et al.  Double Dissociation of Stimulus-Value and Action-Value Learning in Humans with Orbitofrontal or Anterior Cingulate Cortex Damage , 2011, The Journal of Neuroscience.

[43]  Timothy E. J. Behrens,et al.  Review Frontal Cortex and Reward-guided Learning and Decision-making Figure 1. Frontal Brain Regions in the Macaque Involved in Reward-guided Learning and Decision-making Finer Grained Anatomical Divisions with Frontal Cortical Systems for Reward-guided Behavior , 2022 .

[44]  Mortimer Mishkin,et al.  Visual recognition impairment follows ventromedial but not dorsolateral prefrontal lesions in monkeys , 1986, Behavioural Brain Research.

[45]  A. Roberts,et al.  Primate orbitofrontal cortex and adaptive behaviour , 2006, Trends in Cognitive Sciences.

[46]  E. Rolls.  The functions of the orbitofrontal cortex , 1999, Brain and Cognition.

[47]  Steven W Kennerley,et al.  Single-Neuron Mechanisms Underlying Cost-Benefit Analysis in Frontal Cortex , 2013, The Journal of Neuroscience.

[48]  Timothy Edward John Behrens,et al.  Separable Learning Systems in the Macaque Brain and the Role of Orbitofrontal Cortex in Contingent Learning , 2010, Neuron.

[49]  C. Padoa-Schioppa,et al.  The representation of economic value in the orbitofrontal cortex is invariant for changes of menu , 2008, Nature Neuroscience.

[50]  Barry J Richmond,et al.  Dynamic changes in representations of preceding and upcoming reward in monkey orbitofrontal cortex. , 2008, Cerebral cortex.

[51]  Colin Camerer,et al.  A framework for studying the neurobiology of value-based decision making , 2008, Nature Reviews Neuroscience.

[52]  A. Damasio,et al.  Emotion, decision making and the orbitofrontal cortex. , 2000, Cerebral cortex.

[53]  M. Botvinick,et al.  Conflict monitoring and cognitive control. , 2001, Psychological review.

[54]  R. Saunders,et al.  Prefrontal mechanisms of behavioral flexibility, emotion regulation and value updating , 2013, Nature Neuroscience.

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

[56]  T. Egner.  Congruency sequence effects and cognitive control , 2007, Cognitive, affective & behavioral neuroscience.

[57]  M. Platt,et al.  Risk-sensitive neurons in macaque posterior cingulate cortex , 2005, Nature Neuroscience.

[58]  Michael L. Platt,et al.  Causal Evidence of Performance Monitoring by Neurons in Posterior Cingulate Cortex during Learning , 2013, Neuron.