Primate orbitofrontal cortex and adaptive behaviour A.C. Roberts Department of Anatomy, University of Cambridge, Cambridge, CB2 3DY, and MRC Centre for Behavioural and Clinical Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK Orbitofrontal cortex contributes to behavioural adap- tation in response to changes in the contingent relationship and incentive value of positive affective stimuli in the environment. This article integrates early descriptions of the effects of orbitofrontal ablation in monkeys, on object discrimination reversal and extinc- tion, with contemporary theories of animal learning. Studies of incentive devaluation, conditioned reinforce- ment and changes in reward contingency are reviewed, highlighting the role of the orbitofrontal cortex in processing the affective and non-affective properties of rewarding stimuli, in reward expectation, and in goal selection. It is argued that future studies should focus on the interaction of the orbitofrontal cortex with periph- eral arousal systems and the ascending monoamine systems in order to understand fully the role of the orbitofrontal cortex in behavioural adaptation. Introduction Profoundly disturbed emotional and social behaviour and poor decision making are associated with damage to the orbitofrontal cortex (OFC), the brain region that lies above the orbits in the ventral region of the frontal lobe. In humans, such behavioural disturbance can result from brain tumors, surgical interventions for intractable epilepsy, or trauma that induce gross damage within the OFC. It is also present in drug addiction and in a variety of neuropsychiatric disorders including schizophrenia, obsessive–compulsive disorder, autism, depression and sociopathies as well as neurodegenerative disorders including the frontal variant of Pick’s disease. In all these disorders there is no gross damage to the OFC but dysregulation of its functioning. In human and non-human primates the OFC comprises several regions that are differentiable according to their cyto- and neurochemical architecture [1] (see Box 1), their connections both within and outside the frontal lobes [2] and to some extent, the behavioural deficits that have been shown to arise as a result of their damage [3,4]. The most medial region of the OFC is intimately connected with the adjacent, ventral region of the medial prefrontal cortex (PFC); the medial PFC being that area of cortex lying within the cingulate gyrus anterior to the genu of the corpus callosum. In humans, damage to much of the OFC together with the ventral aspects of the medial PFC is associated with disturbed emotional and social behaviour [5,6]. Although similar changes in social and emotional behaviour have also been observed in monkeys with orbitofrontal damage (for review see [7]), the most well described behavioural characteristic of such monkeys had been, until recently, their inflexible responding across a variety of different contexts [7,8]. Recent progress in our understanding of the role of the OFC in emotional and social behaviour has been stimulated by (i) a greater understanding of the interaction between Pavlovian and instrumental learning processes that have been proposed to underlie much of behaviour and (ii) a renewed emphasis on comparing the role of the OFC with related structures including the neighbouring medial PFC and the amyg- dala. This review will consider the unique contribution of the OFC to specific associative learning mechanisms in the context of positive affective behaviour, and how such mechanisms might provide the flexibility necessary for complex emotional and social interactions within sophis- ticated human and non-human primate societies. Although the focus will be on non-human primates, relevant evidence from human neuroimaging and rodent experimental studies will also be discussed. Early studies on discrimination learning in monkeys The importance of the primate OFC in adaptive behaviour has been recognized since the publication of a series of influential experiments in the 1960s and early 1970s. Based on ablation studies in old world monkeys using a range of discrimination tests including ‘go, no-go’, one- trial object discrimination, object discrimination reversal as well as instrumental extinction it was hypothesized that the medial sector of the OFC (mOFC: including areas 13, orbital 14, much of area 11 and the tip of orbital 10) was involved in processing affective information, consist- ent with its dense reciprocal connections with the amygdala [4], whereas the inferior prefrontal convexity (area 12/47 and parts of area 45), which included the lateral sector of OFC, was involved in the suppression of inappropriate cognitive sets [8]. More recent findings in New World monkeys have shown that the failure to suppress inappropriate cognitive sets can be fractionated; the ability to shift attentional sets and to reverse stimulus–reward associations being differentially depend- ent upon distinct regions of PFC [9]. Moreover, ablations of the posteromedial sector of OFC but to a much lesser Corresponding author: Roberts, A.C. (acr4@cam.ac.uk). Available online 27 December 2005 Review TRENDS in Cognitive Sciences Vol.10 No.2 February 2006 www.sciencedirect.com 1364-6613/$ - see front matter Q 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tics.2005.12.002