The estimated values of choices, and therefore decision-making based on those values, are influenced by both the chance that the chosen items or goods can be obtained (availability) and their current worth (desirability) as well as by the ability to link the estimated values to choices (a process sometimes called credit assignment). In primates, the prefrontal cortex (PFC) has been thought to contribute to each of these processes; however, causal relationships between particular subdivisions of the PFC and specific functions have been difficult to establish. Recent lesion-based research studies have defined the roles of two different parts of the primate PFC — the orbitofrontal cortex (OFC) and the ventral lateral frontal cortex (VLFC) — and their subdivisions in evaluating each of these factors and in mediating credit assignment during reward-based decision-making.
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Gaffan, D. Against memory systems. Philos. Trans. R. Soc. Lond. B Biol Sci. 357, 1111–1121 (2002).
Wilson, C. R., Gaffan, D., Browning, P. G. & Baxter, M. G. Functional localization within the prefrontal cortex: missing the forest for the trees? Trends Neurosci. 33, 533–540 (2010).
Kolling, N. et al. Value, search, persistence and model updating in anterior cingulate cortex. Nat. Neurosci. 19, 1280–1285 (2016).
Shenhav, A., Cohen, J. D. & Botvinick, M. M. Dorsal anterior cingulate cortex and the value of control. Nat. Neurosci. 19, 1286–1291 (2016).
Meyer, H. C. & Bucci, D. J. Imbalanced activity in the orbitofrontal cortex and nucleus accumbens impairs behavioral inhibition. Curr. Biol. 26, 2834–2839 (2016).
Jones, B. & Mishkin, M. Limbic lesions and the problem of stimulus-reinforcement associations. Exp. Neurol. 36, 362–377 (1972).
Padoa-Schioppa, C. Neurobiology of economic choice: a good-based model. Annu. Rev. Neurosci. 34, 333–359 (2011).
Rolls, E. T. The Brain and Emotion. (Oxford Univ. Press, Oxford, 1999).
Walton, M. E., Behrens, T. E., Buckley, M. J., Rudebeck, P. H. & Rushworth, M. F. Separable learning systems in the macaque brain and the role of orbitofrontal cortex in contingent learning. Neuron 65, 927–939 (2010). This article presents a landmark study of the role of the macaque OFC in stimulus–reward association learning. Macaques with aspiration lesions of the OFC were unable to form contingent associations between choices and the rewards that immediately follow them.
Wilson, R. C., Takahashi, Y. K., Schoenbaum, G. & Niv, Y. Orbitofrontal cortex as a cognitive map of task space. Neuron 81, 267–279 (2014).
Wallis, J. D. Cross-species studies of orbitofrontal cortex and value-based decision-making. Nat. Neurosci. 15, 13–19 (2011).
Stalnaker, T. A., Cooch, N. K. & Schoenbaum, G. What the orbitofrontal cortex does not do. Nat. Neurosci. 18, 620–627 (2015).
Rudebeck, P. H. & Murray, E. A. The orbitofrontal oracle: cortical mechanisms for the prediction and evaluation of specific behavioral outcomes. Neuron 84, 1143–1156 (2014).
Murray, E. A. & Rudebeck, P. H. The drive to strive: goal generation based on current needs. Front. Neurosci. 7, 112 (2013).
Menzel, C. R. Cognitive aspects of foraging in Japanese monkeys. Anim. Behav. 41, 397–402 (1991).
Rudebeck, P. H., Saunders, R. C., Lundgren, D. A. & Murray, E. A. Specialized representations of value in the orbital and ventrolateral prefrontal cortex: desirability versus availability of outcomes. Neuron 95, 1208–1220 (2017). This paper presents a compelling demonstration of the independent contributions of the macaque OFC and VLFC to different kinds of value updating. Whereas the OFC represents the desirability of potential outcomes, the VLFC represents their availability.
Thorpe, S. J., Rolls, E. T. & Maddison, S. The orbitofrontal cortex: neuronal activity in the behaving monkey. Exp. Brain Res. 49, 93–115 (1983).
Tremblay, L. & Schultz, W. Relative reward preference in primate orbitofrontal cortex. Nature 398, 704–708 (1999).
Wallis, J. D. & Miller, E. K. Neuronal activity in primate dorsolateral and orbital prefrontal cortex during performance of a reward preference task. Eur. J. Neurosci. 18, 2069–2081 (2003).
Kennerley, S. W. & Wallis, J. D. Evaluating choices by single neurons in the frontal lobe: outcome value encoded across multiple decision variables. Eur. J. Neurosci. 29, 2061–2073 (2009).
Padoa-Schioppa, C. & Assad, J. A. The representation of economic value in the orbitofrontal cortex is invariant for changes of menu. Nat. Neurosci. 11, 95–102 (2008). This article provides an elegant demonstration that OFC neurons in macaques respect transitivity in encoding the expected reward value of different juices, showing that this part of PFC encodes subjective value rather than relative preferences.
Rich, E. L. & Wallis, J. D. Decoding subjective decisions from orbitofrontal cortex. Nat. Neurosci. 19, 973–980 (2016). This study shows that, during decision-making, ensembles of neurons in the OFC represent the individual options as monkeys’ locus of attention shifts from one option to the next.
McGinty, V. B., Rangel, A. & Newsome, W. T. Orbitofrontal cortex value signals depend on fixation location during free viewing. Neuron 90, 1299–1311 (2016).
Rich, E. L. & Wallis, J. D. Medial-lateral organization of the orbitofrontal cortex. J. Cogn. Neurosci. 26, 1347–1362 (2014).
Kobayashi, S., Pinto de, C. O. & Schultz, W. Adaptation of reward sensitivity in orbitofrontal neurons. J. Neurosci. 30, 534–544 (2010).
Katz, L. N., Yates, J. L., Pillow, J. W. & Huk, A. C. Dissociated functional significance of decision-related activity in the primate dorsal stream. Nature 535, 285–288 (2016).
Preuss, T. M. in Primate Origins: Adaptations and Evolution (eds Ravosa, M. J. & Dagasto, M.) 625–675 (Springer, 2007).
Wise, S. P. Forward frontal fields: phylogeny and fundamental function. Trends Neurosci. 31, 599–608 (2008).
Walker, A. E. A cytoarchitectural study of the prefrontal area of the macaque monkey. J. Comp. Neurol. 73, 59–86 (1940).
Carmichael, S. T. & Price, J. L. Architectonic subdivision of the orbital and medial prefrontal cortex in the macaque monkey. J. Comp. Neurol. 346, 366–402 (1994).
Neubert, F. X., Mars, R. B., Thomas, A. G., Sallet, J. & Rushworth, M. F. Comparison of human ventral frontal cortex areas for cognitive control and language with areas in monkey frontal cortex. Neuron 81, 700–713 (2014).
Neubert, F. X., Mars, R. B., Sallet, J. & Rushworth, M. F. Connectivity reveals relationship of brain areas for reward-guided learning and decision making in human and monkey frontal cortex. Proc. Natl Acad. Sci. USA 112, E2695–E2704 (2015).
Porrino, L. J., Crane, A. M. & Goldman-Rakic, P. S. Direct and indirect pathways from the amygdala to the frontal lobe in rhesus monkeys. J. Comp. Neurol. 198, 121–136 (1981).
Ghashghaei, H. T., Hilgetag, C. C. & Barbas, H. Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala. Neuroimage 34, 905–923 (2007).
Saleem, K. S., Kondo, H. & Price, J. L. Complementary circuits connecting the orbital and medial prefrontal networks with the temporal, insular, and opercular cortex in the macaque monkey. J. Comp. Neurol. 506, 659–693 (2008).
Saleem, K. S., Miller, B. & Price, J. L. Subdivisions and connectional networks of the lateral prefrontal cortex in the macaque monkey. J. Comp. Neurol. 522, 1641–1690 (2014).
Gerbella, M., Baccarini, M., Borra, E., Rozzi, S. & Luppino, G. Amygdalar connections of the macaque areas 45A and 45B. Brain Struct. Funct. 219, 831–842 (2014).
Ferry, A. T., Ongur, D., An, X. & Price, J. L. Prefrontal cortical projections to the striatum in macaque monkeys: evidence for an organization related to prefrontal networks. J. Comp. Neurol. 425, 447–470 (2000).
Haber, S. N., Kunishio, K., Mizobuchi, M. & Lynd-Balta, E. The orbital and medial prefrontal circuit through the primate basal ganglia. J. Neurosci. 15, 4851–4867 (1995).
Haber, S. N., Kim, K. S., Mailly, P. & Calzavara, R. Reward-related cortical inputs define a large striatal region in primates that interface with associative cortical connections, providing a substrate for incentive-based learning. J. Neurosci. 26, 8368–8376 (2006).
Giguere, M. & Goldman-Rakic, P. S. Mediodorsal nucleus: areal, laminar, and tangential distribution of afferents and efferents in the frontal lobe of rhesus monkeys. J. Comp. Neurol. 277, 195–213 (1988).
Ray, J. P. & Price, J. L. The organization of projections from the mediodorsal nucleus of the thalamus to orbital and medial prefrontal cortex in macaque monkeys. J. Comp. Neurol. 337, 1–31 (1993).
Russchen, F. T., Amaral, D. G. & Price, J. L. The afferent input to the magnocellular division of the mediodorsal thalamic nucleus in the monkey. Macaca fascicularis. J. Comp. Neurol. 256, 175–210 (1987).
Preuss, T. M. & Goldman-Rakic, P. S. Crossed corticothalamic and thalamocortical connections of macaque prefrontal cortex. J. Comp. Neurol. 257, 269–281 (1987).
Timbie, C. & Barbas, H. Specialized pathways from the primate amygdala to posterior orbitofrontal cortex. J. Neurosci. 34, 8106–8118 (2014).
Price, J. L. Definition of the orbital cortex in relation to specific connections with limbic and visceral structures and other cortical regions. Ann. NY Acad. Sci. 1121, 54–71 (2007).
von Bonin, G. & Bailey, P. The Neocortex of Macaca mulatta (Univ. Illinois Press, 1947).
Carmichael, S. T. & Price, J. L. Sensory and premotor connections of the orbital and medial prefrontal cortex of macaque monkeys. J. Comp. Neurol. 363, 642–664 (1995).
Petrides, M. & Pandya, D. N. Comparative cytoarchitectonic analysis of the human and the macaque ventrolateral prefrontal cortex and corticocortical connection patterns in the monkey. Eur. J. Neurosci. 16, 291–310 (2002).
Webster, M. J., Bachevalier, J. & Ungerleider, L. G. Connections of inferior temporal areas TEO and TE with parietal and frontal cortex in macaque monkeys. Cereb. Cortex 4, 470–483 (1994).
Gerbella, M., Belmalih, A., Borra, E., Rozzi, S. & Luppino, G. Cortical connections of the macaque caudal ventrolateral prefrontal areas 45A and 45B. Cereb. Cortex 20, 141–168 (2010).
Passingham, R. E., Stephan, K. E. & Kotter, R. The anatomical basis of functional localization in the cortex. Nat. Rev. Neurosci. 3, 606–616 (2002).
Kondo, H., Saleem, K. S. & Price, J. L. Differential connections of the perirhinal and parahippocampal cortex with the orbital and medial prefrontal networks in macaque monkeys. J. Comp. Neurol. 493, 479–509 (2005).
Carmichael, S. T. & Price, J. L. Connectional networks within the orbital and medial prefrontal cortex of macaque monkeys. J. Comp. Neurol. 371, 179–207 (1996).
Romanski, L. M., Bates, J. F. & Goldman-Rakic, P. S. Auditory belt and parabelt projections to the prefrontal cortex in the rhesus monkey. J. Comp. Neurol. 403, 141–157 (1999).
Critchley, H. D. & Rolls, E. T. Hunger and satiety modify the responses of olfactory and visual neurons in the primate orbitofrontal cortex. J. Neurophysiol. 75, 1673–1686 (1996).
Pritchard, T. C. et al. Satiety-responsive neurons in the medial orbitofrontal cortex of the macaque. Behav. Neurosci. 122, 174–182 (2008).
Cai, X. & Padoa-Schioppa, C. Contributions of orbitofrontal and lateral prefrontal cortices to economic choice and the good-to-action transformation. Neuron 81, 1140–1151 (2014).
Tsujimoto, S., Genovesio, A. & Wise, S. P. Neuronal activity during a cued strategy task: comparison of dorsolateral, orbital, and polar prefrontal cortex. J. Neurosci. 32, 11017–11031 (2012).
Asaad, W. F., Lauro, P. M., Perge, J. A. & Eskandar, E. N. Prefrontal neurons encode a solution to the credit-assignment problem. J. Neurosci. 37, 6995–7007 (2017).
Izquierdo, A., Suda, R. K. & Murray, E. A. Bilateral orbital prefrontal cortex lesions in rhesus monkeys disrupt choices guided by both reward value and reward contingency. J. Neurosci. 24, 7540–7548 (2004).
Machado, C. J. & Bachevalier, J. The effects of selective amygdala, orbital frontal cortex or hippocampal formation lesions on reward assessment in nonhuman primates. Eur. J. Neurosci. 25, 2885–2904 (2007).
Noonan, M. P. et al. Separate value comparison and learning mechanisms in macaque medial and lateral orbitofrontal cortex. Proc. Natl Acad. Sci. USA 107, 20547–20552 (2010).
Iversen, S. D. & Mishkin, M. Perseverative interference in monkeys following selective lesions of the inferior prefrontal convexity. Exp. Brain Res. 11, 376–386 (1970).
Rygula, R., Walker, S. C., Clarke, H. F., Robbins, T. W. & Roberts, A. C. Differential contributions of the primate ventrolateral prefrontal and orbitofrontal cortex to serial reversal learning. J. Neurosci. 30, 14552–14559 (2010).
Groman, S. M. et al. Monoamine levels within the orbitofrontal cortex and putamen interact to predict reversal learning performance. Biol. Psychiatry 73, 756–762 (2013).
Jocham, G. et al. Reward-guided learning with and without causal attribution. Neuron 90, 177–190 (2016).
Butter, C. M., McDonald, J. A. & Snyder, D. R. Orality, preference behavior, and reinforcement value of nonfood object in monkeys with orbital frontal lesions. Science 164, 1306–1307 (1969).
McEnaney, K. W. & Butter, C. M. Perseveration of responding and nonresponding in monkeys with orbital frontal ablations. J. Comp. Physiol. Psychol. 68, 558–561 (1969).
Mishkin, M. in The Frontal Granular Cortex and Behavior (eds Warren, J. M. & Akert, K.) 219–241 (McGraw-Hill, 1964).
Butter, C. M. Perseveration in extinction and in discrimination reversal tasks following selective frontal ablations in Macaca mulatta. Physiol. Behav. 4, 163–171 (1969).
Butter, C. M., Snyder, D. R. & McDonald, J. A. Effects of orbital frontal lesions on aversive and aggressive behaviors in rhesus monkeys. J. Comp. Physiol. Psychol. 72, 132–144 (1970).
Deng, W. et al. Separate neural systems for behavioral change and for emotional responses to failure during behavioral inhibition. Hum. Brain Mapp. 38, 3527–3537 (2017).
Kazama, A. & Bachevalier, J. Selective aspiration or neurotoxic lesions of orbital frontal areas 11 and 13 spared monkeys’ performance on the object discrimination reversal task. J. Neurosci. 29, 2794–2804 (2009).
Rudebeck, P. H. & Murray, E. A. Dissociable effects of subtotal lesions within the macaque orbital prefrontal cortex on reward-guided behavior. J. Neurosci. 31, 10569–10578 (2011).
Lehman, J. F., Greenberg, B. D., McIntyre, C. C., Rasmussen, S. A. & Haber, S. N. Rules ventral prefrontal cortical axons use to reach their targets: implications for diffusion tensor imaging tractography and deep brain stimulation for psychiatric illness. J. Neurosci. 31, 10392–10402 (2011).
Rudebeck, P. H., Saunders, R. C., Prescott, A. T., Chau, L. S. & Murray, E. A. Prefrontal mechanisms of behavioral flexibility, emotion regulation and value updating. Nat. Neurosci. 16, 1140–1145 (2013).
Izquierdo, A., Suda, R. K. & Murray, E. A. Comparison of the effects of bilateral orbital prefrontal cortex lesions and amygdala lesions on emotional responses in rhesus monkeys. J. Neurosci. 25, 8534–8542 (2005).
Kalin, N. H., Shelton, S. E. & Davidson, R. J. Role of the primate orbitofrontal cortex in mediating anxious temperament. Biol. Psychiatry 62, 1134–1139 (2007).
Rudebeck, P. H. et al. Frontal cortex subregions play distinct roles in choices between actions and stimuli. J. Neurosci. 28, 13775–13785 (2008).
Croxson, P. L. et al. Quantitative investigation of connections of the prefrontal cortex in the human and macaque using probabilistic diffusion tractography. J. Neurosci. 25, 8854–8866 (2005).
Schmahmann, J. D. et al. Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography. Brain 130, 630–653 (2007).
Jbabdi, S., Lehman, J. F., Haber, S. N. & Behrens, T. E. Human and monkey ventral prefrontal fibers use the same organizational principles to reach their targets: tracing versus tractography. J. Neurosci. 33, 3190–3201 (2013).
Camille, N., Tsuchida, A. & Fellows, L. K. Double dissociation of stimulus-value and action-value learning in humans with orbitofrontal or anterior cingulate cortex damage. J. Neurosci. 31, 15048–15052 (2011).
Hornak, J. et al. Reward-related reversal learning after surgical excisions in orbito-frontal or dorsolateral prefrontal cortex in humans. J. Cogn. Neurosci. 16, 463–478 (2004).
O’Doherty, J., Kringelbach, M. L., Rolls, E. T., Hornak, J. & Andrews, C. Abstract reward and punishment representations in the human orbitofrontal cortex. Nat. Neurosci. 4, 95–102 (2001).
O’Doherty, J., Critchley, H., Deichmann, R. & Dolan, R. J. Dissociating valence of outcome from behavioral control in human orbital and ventral prefrontal cortices. J. Neurosci. 23, 7931–7939 (2003).
Cools, R., Clark, L., Owen, A. M. & Robbins, T. W. Defining the neural mechanisms of probabilistic reversal learning using event-related functional magnetic resonance imaging. J. Neurosci. 22, 4563–4567 (2002).
Ghahremani, D. G., Monterosso, J., Jentsch, J. D., Bilder, R. M. & Poldrack, R. A. Neural components underlying behavioral flexibility in human reversal learning. Cereb. Cortex 20, 1843–1852 (2010).
Baxter, M. G., Gaffan, D., Kyriazis, D. A. & Mitchell, A. S. Ventrolateral prefrontal cortex is required for performance of a strategy implementation task but not reinforcer devaluation effects in rhesus monkeys. Eur. J. Neurosci. 29, 2049–2059 (2009).
Reber, J. et al. Selective impairment of goal-directed decision-making following lesions to the human ventromedial prefrontal cortex. Brain 140, 1743–1756 (2017).
Noonan, M. P., Chau, B. K. H., Rushworth, M. F. S. & Fellows, L. K. Contrasting effects of medial and lateral orbitofrontal cortex lesions on credit assignment and decision-making in humans. J. Neurosci. 37, 7023–7035 (2017).
Fellows, L. K. & Farah, M. J. The role of ventromedial prefrontal cortex in decision making: judgment under uncertainty or judgment per se? Cereb. Cortex 17, 2669–2674 (2007).
Baylis, L. L. & Gaffan, D. Amygdalectomy and ventromedial prefrontal ablation produce similar deficits in food choice and in simple object discrimination learning for an unseen reward. Exp. Brain Res. 86, 617–622 (1991).
Buckley, M. J. et al. Dissociable components of rule-guided behavior depend on distinct medial and prefrontal regions. Science 325, 52–58 (2009).
Dias, R., Robbins, T. W. & Roberts, A. C. Dissociation in prefrontal cortex of affective and attentional shifts. Nature 380, 69–72 (1996).
Rossi, A. F., Bichot, N. P., Desimone, R. & Ungerleider, L. G. Top down attentional deficits in macaques with lesions of lateral prefrontal cortex. J. Neurosci. 27, 11306–11314 (2007).
Rushworth, M. F. et al. Attentional selection and action selection in the ventral and orbital prefrontal cortex. J. Neurosci. 25, 11628–11636 (2005).
Bichot, N. P., Heard, M. T., DeGennaro, E. M. & Desimone, R. A. Source for feature-based attention in the prefrontal cortex. Neuron 88, 832–844 (2015).
Vaidya, A. R. & Fellows, L. K. Necessary contributions of human frontal lobe subregions to reward learning in a dynamic, multidimensional environment. J. Neurosci. 36, 9843–9858 (2016).
Bussey, T. J., Wise, S. P. & Murray, E. A. The role of ventral and orbital prefrontal cortex in conditional visuomotor learning and strategy use in rhesus monkeys (Macaca mulatta). Behav. Neurosci. 115, 971–982 (2001).
Rushworth, M. F., Nixon, P. D., Eacott, M. J. & Passingham, R. E. Ventral prefrontal cortex is not essential for working memory. J. Neurosci. 17, 4829–4838 (1997).
Cadoret, G. & Petrides, M. Ventrolateral prefrontal neuronal activity related to active controlled memory retrieval in nonhuman primates. Cereb. Cortex 17 (Suppl. 1), i27–i40 (2007).
Tomita, H., Ohbayashi, M., Nakahara, K., Hasegawa, I. & Miyashita, Y. Top-down signal from prefrontal cortex in executive control of memory retrieval. Nature 401, 699–703 (1999).
Fyall, A. M., El-Shamayleh, Y., Choi, H., Shea-Brown, E. & Pasupathy, A. Dynamic representation of partially occluded objects in primate prefrontal and visual cortex. eLife 6, e25784 (2017).
Chau, B. K., Kolling, N., Hunt, L. T., Walton, M. E. & Rushworth, M. F. A neural mechanism underlying failure of optimal choice with multiple alternatives. Nat. Neurosci. 17, 463–470 (2014).
FitzGerald, T. H., Seymour, B. & Dolan, R. J. The role of human orbitofrontal cortex in value comparison for incommensurable objects. J. Neurosci. 29, 8388–8395 (2009).
Rolls, E. T., Grabenhorst, F. & Parris, B. A. Neural systems underlying decisions about affective odors. J. Cogn. Neurosci. 22, 1069–1082 (2010).
Kable, J. W. & Glimcher, P. W. The neural correlates of subjective value during intertemporal choice. Nat. Neurosci. 10, 1625–1633 (2007).
Howard, J. D. & Kahnt, T. Identity-specific reward representations in orbitofrontal cortex are modulated by selective devaluation. J. Neurosci. 37, 2627–2638 (2017).
Suzuki, S., Cross, L. & O’Doherty, J. P. Elucidating the underlying components of food valuation in the human orbitofrontal cortex. Nat. Neurosci. 20, 1780–1786 (2017).
Price, J. L. Prefrontal cortical networks related to visceral function and mood. Ann. NY Acad. Sci. 877, 383–396 (1999).
Rudebeck, P. H. & Murray, E. A. Balkanizing the primate orbitofrontal cortex: distinct subregions for comparing and contrasting values. Ann. NY Acad. Sci. 1239, 1–13 (2011).
Lim, S. L., O’Doherty, J. P. & Rangel, A. The decision value computations in the vmPFC and striatum use a relative value code that is guided by visual attention. J. Neurosci. 31, 13214–13223 (2011).
Raghuraman, A. P. & Padoa-Schioppa, C. Integration of multiple determinants in the neuronal computation of economic values. J. Neurosci. 34, 11583–11603 (2014).
O’Neill, M. & Schultz, W. Coding of reward risk by orbitofrontal neurons is mostly distinct from coding of reward value. Neuron 68, 789–800 (2010).
Murray, E. A., Moylan, E. J., Saleem, K. S., Basile, B. M. & Turchi, J. Specialized areas for value updating and goal selection in the primate orbitofrontal cortex. eLife 4, e11695 (2015).
Wellman, L. L., Gale, K. & Malkova, L. GABAA-mediated inhibition of basolateral amygdala blocks reward devaluation in macaques. J. Neurosci. 25, 4577–4586 (2005).
Klein-Flugge, M. C., Barron, H. C., Brodersen, K. H., Dolan, R. J. & Behrens, T. E. Segregated encoding of reward-identity and stimulus-reward associations in human orbitofrontal cortex. J. Neurosci. 33, 3202–3211 (2013).
Teuber, H. L. Unity and diversity of frontal lobe functions. Acta Neurobiol. Exp. 32, 615–656 (1972).
Duncan, J., Emslie, H., Williams, P., Johnson, R. & Freer, C. Intelligence and the frontal lobe: the organization of goal-directed behavior. Cogn. Psychol. 30, 257–303 (1996).
McDannald, M. A., Jones, J. L., Takahashi, Y. K. & Schoenbaum, G. Learning theory: a driving force in understanding orbitofrontal function. Neurobiol. Learn. Mem. 108, 22–27 (2014).
Price, J. L. & Drevets, W. C. Neurocircuitry of mood disorders. Neuropsychopharmacology 35, 192–216 (2010).
Borra, E., Gerbella, M., Rozzi, S. & Luppino, G. Anatomical evidence for the involvement of the macaque ventrolateral prefrontal area 12r in controlling goal-directed actions. J. Neurosci. 31, 12351–12363 (2011).
Borra, E., Gerbella, M., Rozzi, S. & Luppino, G. The macaque lateral grasping network: A neural substrate for generating purposeful hand actions. Neurosci. Biobehav. Rev. 75, 65–90 (2017).
Takahara, D. et al. Multisynaptic projections from the ventrolateral prefrontal cortex to the dorsal premotor cortex in macaques - anatomical substrate for conditional visuomotor behavior. Eur. J. Neurosci. 36, 3365–3375 (2012). This study makes use of both traditional anterograde and retrograde tracers as well as a viral retrograde transneuronal tracer to identify multisynaptic routes from the VLFC to the dorsal premotor cortex in macaques. These routes are potential pathways for the OFC and VLFC to implement goal selection.
Morecraft, R. J. et al. Amygdala interconnections with the cingulate motor cortex in the rhesus monkey. J. Comp. Neurol. 500, 134–165 (2007).
Morecraft, R. J. & Van Hoesen, G. W. Convergence of limbic input to the cingulate motor cortex in the rhesus monkey. Brain Res. Bull. 45, 209–232 (1998).
Baxter, M. G., Parker, A., Lindner, C. C., Izquierdo, A. D. & Murray, E. A. Control of response selection by reinforcer value requires interaction of amygdala and orbital prefrontal cortex. J. Neurosci. 20, 4311–4319 (2000).
Fiuzat, E. C., Rhodes, S. E. & Murray, E. A. The role of orbitofrontal-amygdala interactions in updating action-outcome valuations in macaques. J. Neurosci. 37, 2463–2470 (2017).
Rhodes, S. E. & Murray, E. A. Differential effects of amygdala, orbital prefrontal cortex, and prelimbic cortex lesions on goal-directed behavior in rhesus macaques. J. Neurosci. 33, 3380–3389 (2013).
Izquierdo, A. & Murray, E. A. Functional interaction of medial mediodorsal thalamic nucleus but not nucleus accumbens with amygdala and orbital prefrontal cortex is essential for adaptive response selection after reinforcer devaluation. J. Neurosci. 30, 661–669 (2010).
Izquierdo, A. Functional heterogeneity within rat orbitofrontal cortex in reward learning and decision making. J. Neurosci. 37, 10529–10540 (2017).
Lichtenberg, N. T. et al. Basolateral amygdala to orbitofrontal cortex projections enable cue-triggered reward expectations. J. Neurosci. 37, 8374–8384 (2017). This study uses designer receptor methodology to selectively inactivate information flow in each direction between the basolateral amygdala and the OFC. Only the activity in the projection from the basolateral amygdala to the OFC was necessary to allow the expectation of specific rewards to influence reward-seeking and decision-making.
Costa, V. D., Dal Monte, O., Lucas, D. R., Murray, E. A. & Averbeck, B. B. Amygdala and ventral striatum make distinct contributions to reinforcement learning. Neuron 92, 505–517 (2016).
Padoa-Schioppa, C. & Assad, J. A. Neurons in the orbitofrontal cortex encode economic value. Nature 441, 223–226 (2006).
Pritchard, T. C. et al. Gustatory neural responses in the medial orbitofrontal cortex of the old world monkey. J. Neurosci. 25, 6047–6056 (2005).
Rudebeck, P. H., Mitz, A. R., Chacko, R. V. & Murray, E. A. Effects of amygdala lesions on reward-value coding in orbital and medial prefrontal cortex. Neuron 80, 1519–1531 (2013).
Rudebeck, P. H., Ripple, J. A., Mitz, A. R., Averbeck, B. B. & Murray, E. A. Amygdala Contributions to stimulus-reward encoding in the macaque medial and orbital frontal cortex during learning. J. Neurosci. 37, 2186–2202 (2017).
Kringelbach, M. L. & Rolls, E. T. The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology. Prog. Neurobiol. 72, 341–372 (2004).
Chudasama, Y., Kralik, J. D. & Murray, E. A. Rhesus monkeys with orbital prefrontal cortex lesions can learn to inhibit prepotent responses in the reversed reward contingency task. Cereb. Cortex 17, 1154–1159 (2007).
Passingham, R. E. & Wise, S. P. The Neurobiology of the Prefrontal Cortex. (Oxford Univ. Press, Oxford, 2012).
Strait, C. E., Blanchard, T. C. & Hayden, B. Y. Reward value comparison via mutual inhibition in ventromedial prefrontal cortex. Neuron 82, 1357–1366 (2014).
Chib, V. S., Rangel, A., Shimojo, S. & O’Doherty, J. P. Evidence for a common representation of decision values for dissimilar goods in human ventromedial prefrontal cortex. J. Neurosci. 29, 12315–12320 (2009).
McNamee, D., Rangel, A. & O’Doherty, J. P. Category-dependent and category-independent goal-value codes in human ventromedial prefrontal cortex. Nat. Neurosci. 16, 479–485 (2013).
Schuck, N. W., Cai, M. B., Wilson, R. C. & Niv, Y. Human orbitofrontal cortex represents a cognitive map of state space. Neuron 91, 1402–1412 (2016).
Preuss, T. M. & Goldman-Rakic, P. S. Myelo- and cytoarchitecture of the granular frontal cortex and surrounding regions in the strepsirhine primate Galago and the anthropoid primate Macaca. J. Comp. Neurol. 310, 429–474 (1991).
Murray, E. A., Wise, S. P. & Graham, K. S. The Evolution of Memory Systems: Ancestors, Anatomy, and Adaptations. (Oxford Univ. Press, Oxford, 2017).
Schneider, B. & Koenigs, M. Human lesion studies of ventromedial prefrontal cortex. Neuropsychologia 107, 84–93 (2017).
Fellows, L. K. Orbitofrontal contributions to value-based decision making: evidence from humans with frontal lobe damage. Ann. NY Acad. Sci. 1239, 51–58 (2011).
Wallis, C. U., Cardinal, R. N., Alexander, L., Roberts, A. C. & Clarke, H. F. Opposing roles of primate areas 25 and 32 and their putative rodent homologs in the regulation of negative emotion. Proc. Natl Acad. Sci. USA 114, E4075–E4084 (2017).
Rudebeck, P. H. et al. A role for primate subgenual cingulate cortex in sustaining autonomic arousal. Proc. Natl Acad. Sci. USA 111, 5391–5396 (2014).
Apps, M. A., Rushworth, M. F. & Chang, S. W. The anterior cingulate gyrus and social cognition: tracking the motivation of others. Neuron 90, 692–707 (2016).
Murray, E. A. & Rhodes, S. E. V. in Living Without an Amygdala. (eds Amaral, D. G. & Adolphs, R.) 252–275 (Guilford Press, 2016).
The authors thank P.-Y. Chen for help with the preparation of figures and S. P. Wise for comments on an earlier version of this manuscript. This work was supported by the Intramural Research Program of the US National Institute of Mental Health (NIMH; ZIAMH002887 (E.A.M.)), an NIMH BRAINS award (R01 MH110822 (P.H.R.)) and a NARSAD Young Investigator Award (NARSAD grant 23638 (P.H.R.)).
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
- Reward-guided learning
A general term that refers to any kind of learning facilitated by reward, including stimulus–outcome learning, action–outcome learning and stimulus–response learning.
- Inhibitory control
The ability to inhibit choices or responses that have previously been rewarded. The concept of behavioural inhibition includes the ability to suppress default, habitual and prepotent behaviours.
- Flexible stimulus–reward learning
The ability to quickly make and break associative links between objects (or other cues) and rewards.
- Value-based decision-making
The ability to make facultative choices that optimize subjective value.
- Credit assignment
The ability to learn that a particular outcome (in experiments, this is typically food or fluid) was produced by a particular choice.
- Cognitive map
A neural representation of stimuli, actions and other sensory features that occur in association with outcomes in a multidimensional array. The cognitive map has been theorized to guide value-based decision-making.
- Value updating
The process of registering a change in the neural representation of the desirability or availability of foods.
- Cortical coupling
A pattern of correlated activity between different brain areas discerned from resting-state fMRI. Cortical coupling has been used to identify brain areas in macaques and humans that have similar connectivity profiles and perhaps comparable functions.
- Aspiration lesion
A technique for removing grey matter (that is, neurons) that is based on subpial aspiration of tissue. Lesions are typically carried out with the aid of an operating microscope.
- Reversal learning
A task in which, after subjects learn to choose a rewarded item over an unrewarded item, the stimulus–outcome contingencies switch without warning. Thus, the subject must now learn to choose the object that was initially unrewarded. The only feedback to guide choices is the occurrence of reward or nonreward.
- Excitotoxic lesions
Lesions created using a technique for selectively removing grey matter (that is, neurons) and sparing white matter (that is, axons) that is based on the injection of neurotoxins. Injections are often carried out via a stereotaxic approach based on coordinates obtained from magnetic resonance images of the brain.
- Attentional selection
Concentration of visual or other (for example, somatosensory or auditory) sensory processing resources towards behaviourally important spatial locations or visual features. This process enhances sensory perception so that responses can be faster and more accurate.
About this article
Cite this article
Murray, E.A., Rudebeck, P.H. Specializations for reward-guided decision-making in the primate ventral prefrontal cortex. Nat Rev Neurosci 19, 404–417 (2018). https://doi.org/10.1038/s41583-018-0013-4
Molecular Psychiatry (2021)
Scientific Reports (2021)
Nature Reviews Neuroscience (2021)