Department of Morphology, Medical School, Autonomous University of Madrid, Spain and , 1 Institute of Physiology, University of Fribourg, Switzerland
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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.