The mysterious orbitofrontal cortex. foreword

primate cerebral cortex is the orbitofrontal cortex, a part of the frontal lobe that lies on the roof of the orbit. Classic clinical evidence suggests that the orbitofrontal cortex is involved in critical human functions, such as social adjustment and the control of mood, drive and responsibility, traits that are crucial in defining the ‘personality’ of an individual. Phineas Gage is a paradigmatic patient, who, after suffering major destruction of the orbital and medial prefrontal cortices in both hemispheres, was portrayed as no longer being himself. In recent years, diverse functional studies have identified activations in the orbitofrontal cortex, suggesting that this prefrontal field is a component of brain systems critically engaged in memory, reward and decision-making mechanisms. These functions may well be considered as basic components of higher emotional and social behavior presumably involving this part of the cortex. The mounting evidence that the orbitofrontal cortex holds many clues to the ways in which complex behaviors are regulated prompted one of us (W.S.) to organize, during the June 1998 Forum of European Neuroscience held in Berlin, a symposium entitled ‘The Mysterious Orbitofrontal Cortex’. The high interest shown in the symposium argued the opportunity of collecting the most recent research devoted to unravelling the structure, function and dysfunction of the orbitofrontal cortex, in both humans and non-human primates. This special issue presents a multidisciplinary account of research efforts focusing on the primate orbitofrontal cortex. The comparative study by D. Öngür and J.L. Price places the orbital and medial prefrontal fields in the perspective of mammalian evolution on the basis of their connections in rodents and primates. In the human brain, Öngür and Price highlight recent imaging and neuropathological observations supporting the involvement of medial and orbital prefrontal regions in mood disorders. Orbitofrontal cortex affectation in Alzheimer’s disease is treated by G.W. Van Hoesen and his colleagues, who describe neurofibrillary tangles populating it with specific areal and laminar distributions. They suggest that this pathology can contribute to several behavioral abnormalities that accompany the disease. Still on structural grounds, C. Cavada and her colleagues provide a comprehensive account of the connections of the orbitofrontal cortex in the macaque monkey. A common underlying notion in these reports is the parcellation of the orbitofrontal cortex into distinct territories, which exhibit specific architecture, connections and neuropathology. This parcellation may well correspond to functional differences in situations in which decisions are made by estimating the values of different outcomes from incomplete information, as revealed in the human imaging studies of R. Elliott and colleagues. Four articles explore orbitofrontal functions in non-human primates: A.C. Roberts and J.D. Wallis describe deficits in inhibitory control functions during multidimensional discrimination following orbitofrontal lesions, while the reports by K. Hikosaka and M. Watanabe, by W. Schultz and his colleagues, and by E.T. Rolls tackle different aspects of the processing of reward information by orbitofrontal neurons in behaving monkeys. Taken together, these studies elucidate the involvement of the primate orbitofrontal cortex in emotional control and reward mechanisms, functions that are further assessed by A. Bechara and colleagues in humans suffering from brain lesions. These authors conceive the orbitofrontal cortex as part of a large-scale system that mediates decision-making in a process that also requires the participation of emotion and cognition. The last three reports focus on the involvement of the orbitofrontal cortex in addiction. N.D. Volkow and J.S. Fowler describe how the human orbitofrontal cortex may be involved in compulsive aspects of drug addiction lying beyond the simple reward mechanisms usually invoked for this behavior. The issues involved in animal models of drug addiction are presented in the paper by L.J. Porrino and D. Lyons. E.D. London and colleagues emphasize the relationship between orbitofrontal activations in humans and personality disturbances associated with substance abuse, drug expectancy, craving and decision-making. In summary, the work compiled in this special issue shows the orbitofrontal cortex to be a multifaceted cortical territory that has links to widespread brain structures and is critically involved in both complex primate behavior as well as human mental and neurological disease. The data and the paths for future research outlined here lead us to conclude that the orbitofrontal cortex should no longer be considered a genuine ‘mystery’ because it can and should be further scrutinized using the tools available to modern neuroscience. The Mysterious Orbitofrontal Cortex. Foreword Carmen Cavada and Wolfram Schultz1