BASAL FOREBRAIN LESIONS IN MONKEYS DISRUPT ATTENTION BUT NOT LEARNINGAND MEMORY

Cognitive impairments in humans and animals have been linked to dysfun ction of neurons in the basal forebrain cholinergic system (BFCS). Deg eneration of these cells may be, in part, responsible for some of the cognitive deficits observed in Alzheimer's disease (AD). Although memo ry deficits are associated with lesions of the BFCS in rats, impairmen ts in memory have been more subtle following similar lesions in monkey s. To evaluate the effects of BFCS lesions on cognitive processes in m onkeys, we have systematically investigated the behavioral effects of ibotenic acid injections in the medial septum, nucleus of the diagonal band of Broca, and nucleus basalis of Meynert in cynomolgus monkeys, using a large series of cognitive tasks that examined different mnemon ic and attentional abilities. These lesions did not impair accuracy in delayed nonmatching-to-sample, delayed response, simple or concurrent visual discriminations, spatial discriminations, or discrimination re versals. However, these lesions disrupted attentional focusing. Simila r impairments in attention have been noted in patients with AD. BFCS l esions increased sensitivity to injections of the cholinergic antagoni st scopolamine in a delayed nonmatching-to-sample task, indicating tha t the central cholinergic system was compromised in these monkeys. In concert, the results of this study suggest that the primate basal fore brain may be more involved in attentional than mnemonic processes, and that degeneration of neurons in the BFCS in cases of AD may contribut e to the attention deficits observed in these individuals.