Abstract

Cytokine-induced CNS inflammation has been theorized to contribute to cognitive dysfunction in sickness and neurodegenerative disease. We investigated the effects of systemic endotoxin-induced acute immune activation and inflammation on working memory and attention functions in pigeons assessed through two variations of an operant symbolic matching-to-sample (SMTS) task, employing doses of lipopolysaccharide (LPS) sufficient to induce fever. LPS produced moderate impairments in comparison to saline on the SMTS task designed to measure visual vigilance and attention, but the impairments were not as marked as those produced by chlordiazepoxide (CDP) which is known to disrupt attention. In contrast, LPS had no significant effect on short-term working memory performance compared to saline, while scopolamine, a cholinergic antagonist known to disrupt working memory, did impair performance. The results have implications for the cognitive impairments seen in illnesses characterized by chronic cytokine activation (e.g., Alzheimer's disease) as well as illnesses treated with cytokines (e.g., multiple sclerosis) suggesting that some cognitive failures attributed to working memory impairments per se may better be attributed to prior attention impairments.