ORBITOFRONTAL FUNCTION, OBJECT ALTERNATION AND PERSEVERATION

Object alternation (OA) is a well-established measure of perseveration and orbitofrontal function in non-human primates. Although several st udies have used OA to examine orbitofrontal system dysfunction in huma ns with neurological and psychiatric disease, this task itself has not been validated as a bona fide measure of frontal dysfunction in human s. To address this issue, six patients with bilateral frontal lobe les ions documented by computerized tomography (CT) or magnetic resonance imaging (MRI) and 15 healthy controls were given OA, as well as other measures of frontal system dysfunction, delayed alternation (DA), dela yed response (DR), and the Wisconsin Card Sorting Test (WCST). The CT and MRI scans were interpreted blindly. The patients with bilateral fr ontal lesions were significantly impaired on OA, DA, DR and the WCST. Analyses of the CT/MRI lesions suggest that the neuroanatomical region s involved in the deficits on OA include Brodmann areas 10, 24, 32 and 47, as well as possibly 11, and that OA is a sensitive measure of ven trolateral-orbitofrontal and medial frontal dysfunction in humans. Our findings lend further support for the use of experimental paradigms a dopted from animal models to study the functional neuroanatomy and neu ropsychological mechanisms underlying cognitive functions in humans wi th neurological and psychiatric disease.