The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology

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Abstract

The human orbitofrontal cortex is an important brain region for the processing of rewards and punishments, which is a prerequisite for the complex and flexible emotional and social behaviour which contributes to the evolutionary success of humans. Yet much remains to be discovered about the functions of this key brain region, and new evidence from functional neuroimaging and clinical neuropsychology is affording new insights into the different functions of the human orbitofrontal cortex. We review the neuroanatomical and neuropsychological literature on the human orbitofrontal cortex, and propose two distinct trends of neural activity based on a meta-analysis of neuroimaging studies. One is a mediolateral distinction, whereby medial orbitofrontal cortex activity is related to monitoring the reward value of many different reinforcers, whereas lateral orbitofrontal cortex activity is related to the evaluation of punishers which may lead to a change in ongoing behaviour. The second is a posterior–anterior distinction with more complex or abstract reinforcers (such as monetary gain and loss) represented more anteriorly in the orbitofrontal cortex than simpler reinforcers such as taste or pain. Finally, we propose new neuroimaging methods for obtaining further evidence on the localisation of function in the human orbitofrontal cortex.

Introduction

Over the last hundred years we have learned more about the localisation of function in the human brain than in the rest of recorded history. The early, poorly founded efforts of phrenology as practiced by Gall and his followers have been replaced by a corpus of solid neuroscientific evidence from experiments in other animals. Even so, with the advent of human neuroimaging over the last 15–20 years, there have been some who use this technique with its pretty pictures of coloured blobs on brain slices almost as a modern-day phrenology. It is crucial that we remember that these pretty pictures can easily mislead us, and that their interpretation needs to take into account the wealth of scientific evidence obtained with different methods from both humans and other animals.

The orbitofrontal cortex provides in many ways a good example of how functional neuroimaging can advance our understanding of the functional role of a human brain region but also how it needs to take into account other neuroscientific research. Some of the functions of the primate orbitofrontal cortex have been previously elucidated in a variety of experiments in non-human primates (for reviews, see Rolls, 2000a, Rolls, 2002, Rolls, 2004). Some of the conclusions of this research are that the orbitofrontal cortex represents the changing and relative reward value of many different primary (unlearned) reinforcers such as taste and somatosensory stimuli; of many different secondary (learned) reinforcers including olfactory and visual stimuli; and learns and rapidly reverses associations between secondary and primary reinforcers, that is it implements stimulus-reinforcement association learning, which is the type of learning that is involved in emotion (Rolls, 1999a, Rolls, 2002).

This review demonstrates how recent neuroimaging (and neuropsychological) experiments have confirmed the important functional role of the human orbitofrontal cortex in emotion. Neuroimaging experiments have, however, more to offer than mere confirmation of the phylogenetic continuity of brain function in primates. One of the main premises of this review is that neuroimaging offers important new spatial information on neural activity in the human orbitofrontal cortex, which can serve to further elucidate the functional role of the subareas within this brain region. We should remember though that functional neuroimaging has limitations in that there are many sometimes quite small populations of neurons with different responses to different types of stimulus or event in the orbitofrontal cortex and other brain regions which may not all be revealed by neuroimaging, which reflects the average metabolic demands of a brain region (Deco et al., in preparation, Rolls, 1999a). Further, brain imaging does not address the issue of the information that is represented by virtue of the different tuning of individual neurons (which are the computing elements of the brain), and so does not provide the evidence on which computational models of brain function must be based (Rolls and Deco, 2002). It is thus very important to consider the results of human functional neuroimaging in the light of what is known from complementary studies using for example neurophysiology in primates, and the effects of brain damage.

The focus of this review is on elucidating the functional neuroanatomy of the human orbitofrontal cortex. We first review the neuroanatomical data on the cytoarchitecture and connections of the orbitofrontal cortex, which is based on relevant information from other primates and humans. We then review a number of relevant studies from the human neuropsychological literature. We then proceed to perform a meta-analysis of existing neuroimaging studies in the literature to determine to what extent it is possible to localise different functions in separate parts of the orbitofrontal cortex.

Section snippets

Neuroanatomy of the orbitofrontal cortex

The primate orbitofrontal cortex occupies the ventral surface of the frontal part of the brain (see Fig. 1) and can be defined as the part of the prefrontal cortex that receives projections from the magnocellular, medial, nucleus of the mediodorsal thalamus (Fuster, 1997). This is in contrast to other parts of the prefrontal cortex which receive projections from other parts of the mediodorsal thalamus, such the dorsolateral prefrontal cortex which receives projections from the parvocellular,

The functional role of the orbitofrontal cortex

Converging evidence from lesions of the orbitofrontal cortex in both non-human primates and humans as well as neurophysiological recordings in non-human primates has led to a number of theories on the functional role of this brain region. Foremost this evidence has linked the orbitofrontal cortex to the study of emotion. In this section, first the orbitofrontal cortex is placed within the context of the current state of emotional research. Then follows a review of the evidence from lesions to

Meta-analysis of neuroimaging data

The aim of this section is to elucidate the functions of the human orbitofrontal cortex and its subareas by presenting a meta-analysis of the findings from a large portion of the published neuroimaging studies in which activations in the orbitofrontal cortex have been investigated.

Conclusions

Based on evidence from neuroimaging experiments and complemented by evidence from primate neuroanatomy and neurophysiology, and human neuropsychology, this review has tried to synthesise the functions of the human orbitofrontal cortex in terms of the spatial distribution of the observed activations in the neuroimaging literature. Two general trends of neural activity have emerged, with a mediolateral distinction between activity related to monitoring the reward value of reinforcers versus their

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