Prefrontal cortical contribution to risk-based decision making.

Damage to various regions of the prefrontal cortex (PFC) impairs decision making involving evaluations about risks and rewards. However, the specific contributions that different PFC subregions make to risk-based decision making are unclear. We investigated the effects of reversible inactivation of 4 subregions of the rat PFC (prelimbic medial PFC, orbitofrontal cortex [OFC], anterior cingulate, and insular cortex) on probabilistic (or risk) discounting. Rats were well trained to choose between either a "Small/Certain" lever that always delivered 1 food pellet, or another, "Large/Risky" lever, which delivered 4 pellets, but the probability of receiving reward decreased across 4 trial blocks (100%, 50%, 25%, and 12.5%). Infusions of gama-aminobutyric acid agonists muscimol/baclofen into the medial PFC increased risky choice. However, similar medial PFC inactivations decreased risky choice when the Large/Risky reward probability increased over a session. OFC inactivation increased response latencies in the latter trial blocks without affecting choice. Anterior cingulate or insular inactivations were without effect. The effects of prelimbic inactivations were not attributable to disruptions in response flexibility or judgments about the relative value of probabilistic rewards. Thus, the prelimbic, but not other PFC regions, plays a critical role in risk discounting, integrating information about changing reward probabilities to update value representations that facilitate efficient decision making.

[1]  W. Nauta,et al.  Efferent connections of the substantia nigra and ventral tegmental area in the rat , 1979, Brain Research.

[2]  Bruce W. Smith,et al.  Neural Substrates of Reward Magnitude, Probability, and Risk during a Wheel of Fortune Decision-making Task Nih Public Access Cingulate Cortex in Decision-making , 2022 .

[3]  S. Floresco,et al.  Inactivation of the medial prefrontal cortex of the rat impairs strategy set-shifting, but not reversal learning, using a novel, automated procedure , 2008, Behavioural Brain Research.

[4]  R. Cardinal,et al.  Nucleus accumbens core lesions retard instrumental learning and performance with delayed reinforcement in the rat , 2005, BMC Neuroscience.

[5]  W. N. Schoenfeld.  The Theory of reinforcement schedules , 1970 .

[6]  Donald T. Stuss,et al.  Executive functions and the frontal lobes: a conceptual view , 2000, Psychological research.

[7]  S. Floresco,et al.  Cerebral Cortex doi:10.1093/cercor/bhl073 Thalamic--Prefrontal Cortical--Ventral Striatal Circuitry Mediates Dissociable Components of Strategy Set Shifting , 2006 .

[8]  Bernd Weber,et al.  Amygdala tractography predicts functional connectivity and learning during feedback-guided decision-making , 2008, NeuroImage.

[9]  Fernando Zelaya,et al.  Distinct roles of prefrontal cortical subregions in the Iowa Gambling Task. , 2009, Cerebral cortex.

[10]  Lutz W. Kracht,et al.  Organic and psychogenic factors leading to executive dysfunctions in a patient suffering from surgery of a colloid cyst of the Foramen of Monro , 2004, Neurocase.

[11]  R. Kesner,et al.  Involvement of the Prelimbic–Infralimbic Areas of the Rodent Prefrontal Cortex in Behavioral Flexibility for Place and Response Learning , 1999, The Journal of Neuroscience.

[12]  H. Groenewegen,et al.  The medial prefrontal cortex in the rat: evidence for a dorso-ventral distinction based upon functional and anatomical characteristics , 2003, Neuroscience & Biobehavioral Reviews.

[13]  D. S. Zahm,et al.  The patterns of afferent innervation of the core and shell in the “Accumbens” part of the rat ventral striatum: Immunohistochemical detection of retrogradely transported fluoro‐gold , 1993, The Journal of comparative neurology.

[14]  Wolfgang Hauber,et al.  Involvement of the rat anterior cingulate cortex in control of instrumental responses guided by reward expectancy. , 2005, Learning & memory.

[15]  B. Balleine,et al.  Goal-directed instrumental action: contingency and incentive learning and their cortical substrates , 1998, Neuropharmacology.

[16]  M. Ragozzino.  The Contribution of the Medial Prefrontal Cortex, Orbitofrontal Cortex, and Dorsomedial Striatum to Behavioral Flexibility , 2007, Annals of the New York Academy of Sciences.

[17]  T. Robbins,et al.  Choosing between Small, Likely Rewards and Large, Unlikely Rewards Activates Inferior and Orbital Prefrontal Cortex , 1999, The Journal of Neuroscience.

[18]  Trevor W Robbins,et al.  Interactions between Serotonin and Dopamine in the Control of Impulsive Choice in Rats: Therapeutic Implications for Impulse Control Disorders , 2005, Neuropsychopharmacology.

[19]  Stan B. Floresco,et al.  Cortico-limbic-striatal circuits subserving different forms of cost-benefit decision making , 2008, Cognitive, affective & behavioral neuroscience.

[20]  Matthew F S Rushworth,et al.  Functional Specialization within Medial Frontal Cortex of the Anterior Cingulate for Evaluating Effort-Related Decisions , 2003, The Journal of Neuroscience.

[21]  A. Dale,et al.  Dorsal anterior cingulate cortex: A role in reward-based decision making , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[22]  W. Corrigall,et al.  GABA mechanisms in the pedunculopontine tegmental nucleus influence particular aspects of nicotine self-administration selectively in the rat , 2001, Psychopharmacology.

[23]  A. Damasio,et al.  Insensitivity to future consequences following damage to human prefrontal cortex , 1994, Cognition.

[24]  T. Robbins,et al.  Dissociable Deficits in the Decision-Making Cognition of Chronic Amphetamine Abusers, Opiate Abusers, Patients with Focal Damage to Prefrontal Cortex, and Tryptophan-Depleted Normal Volunteers: Evidence for Monoaminergic Mechanisms , 1999, Neuropsychopharmacology.

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

[26]  H. Uylings,et al.  Qualitative and quantitative comparison of the prefrontal cortex in rat and in primates, including humans. , 1990, Progress in brain research.

[27]  G. Fricchione.  Descartes’ Error: Emotion, Reason and the Human Brain , 1995 .

[28]  V. Galhardo,et al.  Orbitofrontal cortex lesions disrupt risk assessment in a novel serial decision-making task for rats , 2007, Neuroscience.

[29]  S. Quartz,et al.  Human Insula Activation Reflects Risk Prediction Errors As Well As Risk , 2008, The Journal of Neuroscience.

[30]  E. Audinat,et al.  Afferent connections of the medial frontal cortex of the rat. II. Cortical and subcortical afferents , 1995, The Journal of comparative neurology.

[31]  A. Damasio.  Descartes' error: emotion, reason, and the human brain. avon books , 1994 .

[32]  N. Ramnani,et al.  Distinct portions of anterior cingulate cortex and medial prefrontal cortex are activated by reward processing in separable phases of decision-making cognition , 2004, Biological Psychiatry.

[33]  S. Floresco,et al.  Dopaminergic Modulation of Risk-Based Decision Making , 2009, Neuropsychopharmacology.

[34]  T. Robbins,et al.  Contrasting Roles of Basolateral Amygdala and Orbitofrontal Cortex in Impulsive Choice , 2004, The Journal of Neuroscience.

[35]  T. Robbins,et al.  Decision-making processes following damage to the prefrontal cortex. , 2002, Brain : a journal of neurology.

[36]  Jobu Watanabe,et al.  Context-dependent cortical activation in response to financial reward and penalty: an event-related fMRI study , 2003, NeuroImage.

[37]  S. Floresco,et al.  Dopaminergic and Glutamatergic Regulation of Effort- and Delay-Based Decision Making , 2008, Neuropsychopharmacology.

[38]  M. Walton,et al.  Separate neural pathways process different decision costs , 2006, Nature Neuroscience.

[39]  Joaquín M. Fuster,et al.  Executive frontal functions , 2000, Experimental Brain Research.

[40]  S. Killcross,et al.  Coordination of actions and habits in the medial prefrontal cortex of rats. , 2003, Cerebral cortex.

[41]  J D Allen,et al.  Functional dissociation of the prefrontal cortex and the hippocampus in timing behavior. , 1998, Behavioral neuroscience.

[42]  J. O'Doherty,et al.  Dissociating Valence of Outcome from Behavioral Control in Human Orbital and Ventral Prefrontal Cortices , 2003, The Journal of Neuroscience.

[43]  Christopher S. Monk,et al.  Choice selection and reward anticipation: an fMRI study , 2004, Neuropsychologia.

[44]  Stan B. Floresco,et al.  Thalamic–Cortical–Striatal Circuitry Subserves Working Memory during Delayed Responding on a Radial Arm Maze , 1999, The Journal of Neuroscience.

[45]  M. Farah,et al.  Different underlying impairments in decision-making following ventromedial and dorsolateral frontal lobe damage in humans. , 2004, Cerebral cortex.

[46]  V. Brown,et al.  Rodent models of prefrontal cortical function , 2002, Trends in Neurosciences.

[47]  B. Kolb,et al.  Do rats have a prefrontal cortex? , 2003, Behavioural Brain Research.

[48]  M. Ragozzino,et al.  The effect of rat anterior cingulate inactivation on cognitive flexibility. , 2007, Behavioral neuroscience.

[49]  Luke Clark,et al.  The contributions of lesion laterality and lesion volume to decision-making impairment following frontal lobe damage , 2003, Neuropsychologia.

[50]  Sabrina M. Tom,et al.  The Neural Basis of Loss Aversion in Decision-Making Under Risk , 2007, Science.

[51]  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.

[52]  A. McDonald,et al.  Organization of amygdaloid projections to the prefrontal cortex and associated striatum in the rat , 1991, Neuroscience.

[53]  Rudolf N Cardinal,et al.  Effects of lesions of the nucleus accumbens core on choice between small certain rewards and large uncertain rewards in rats , 2005, BMC Neuroscience.

[54]  S. Floresco,et al.  Fundamental Contribution by the Basolateral Amygdala to Different Forms of Decision Making , 2009, The Journal of Neuroscience.

[55]  Daniel Tranel,et al.  Exploring the neurological substrate of emotional and social intelligence. , 2003, Brain : a journal of neurology.

[56]  J. Deakin,et al.  Effects of lesions of the orbitofrontal cortex on sensitivity to delayed and probabilistic reinforcement , 2002, Psychopharmacology.

[57]  Friedrich G. Woermann,et al.  Neural correlates of decision making with explicit information about probabilities and incentives in elderly healthy subjects , 2008, Experimental Brain Research.

[58]  S. Floresco,et al.  Alterations in time–place learning induced by lesions to the rat medial prefrontal cortex , 2002, Behavioural Processes.

[59]  R. Roth,et al.  Topographical organization of the efferent projections of the medial prefrontal cortex in the rat: An anterograde tract‐tracing study with Phaseolus vulgaris leucoagglutinin , 1989, The Journal of comparative neurology.

[60]  R. James R. Blair,et al.  Response options and expectations of reward in decision-making: The differential roles of dorsal and rostral anterior cingulate cortex , 2007, NeuroImage.

[61]  Takashi Hanakawa,et al.  Functional activity related to risk anticipation during performance of the Iowa gambling task , 2005, NeuroImage.

[62]  Gregory P. Lee,et al.  Different Contributions of the Human Amygdala and Ventromedial Prefrontal Cortex to Decision-Making , 1999, The Journal of Neuroscience.

[63]  T. Bussey,et al.  Dissociable effects of cingulate and medial frontal cortex lesions on stimulus-reward learning using a novel Pavlovian autoshaping procedure for the rat: implications for the neurobiology of emotion. , 1997, Behavioral neuroscience.

[64]  S. Floresco,et al.  Amygdala-prefrontal cortical circuitry regulates effort-based decision making. , 2006, Cerebral cortex.

[65]  M. Roesch,et al.  The Orbitofrontal Cortex and Ventral Tegmental Area Are Necessary for Learning from Unexpected Outcomes , 2009, Neuron.

[66]  Jeremy K. Seamans,et al.  Functional differences between the prelimbic and anterior cingulate regions of the rat prefrontal cortex. , 1995, Behavioral neuroscience.

[67]  Françoise Condé,et al.  Afferent connections of the medial frontal cortex of the rat. A study using retrograde transport of fluorescent dyes. I. Thalamic afferents , 1990, Brain Research Bulletin.

[68]  T. Robbins,et al.  Impulsive Choice Induced in Rats by Lesions of the Nucleus Accumbens Core , 2001, Science.

[69]  T. Robbins,et al.  The neuropsychology of ventral prefrontal cortex: Decision-making and reversal learning , 2004, Brain and Cognition.

[70]  T. Robbins,et al.  Differential effects of insular and ventromedial prefrontal cortex lesions on risky decision-making , 2008, Brain : a journal of neurology.

[71]  H. Damasio,et al.  Dissociation Of Working Memory from Decision Making within the Human Prefrontal Cortex , 1998, The Journal of Neuroscience.

[72]  Monique Ernst,et al.  Decision-making in a Risk-taking Task: A PET Study , 2002, Neuropsychopharmacology.

[73]  V. Brown,et al.  Medial Frontal Cortex Mediates Perceptual Attentional Set Shifting in the Rat , 2000, The Journal of Neuroscience.

[74]  T. Robbins,et al.  Planning and spatial working memory following frontal lobe lesions in man , 1990, Neuropsychologia.