Elsevier

Behavioural Brain Research

Volume 194, Issue 2, 12 December 2008, Pages 138-145
Behavioural Brain Research

Research report
Lipopolysaccharide-induced immune activation impairs attention but has little effect on short-term working memory

https://doi.org/10.1016/j.bbr.2008.06.032Get rights and content

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.

Section snippets

Experiment 1: attention

The goal of the first experiment was to determine the extent to which attention is disrupted by LPS. LPS, saline, and chlordiazepoxide (CDP) were each administered to pigeons prior to performance of a well-learned SMTS task. Attention was measured by varying the duration of the sample stimulus, a yellow or blue light. The shorter the length of the sample stimulus, the greater was the attentional burden. If LPS impairs attention, then an interaction should be observed between LPS and sample

Experiment 2: working memory

The goal of the second experiment was to determine the extent to which working memory is disrupted by LPS. LPS, saline, and scopolamine were each administered to pigeons performing on a well-learned delayed matching to sample task. The length of the delay between the sample stimulus and the required choice constituted the short-term working memory burden. If the LPS impairs short-term working memory, it should produce delay-dependent deficits in matching accuracy, with greater disruptions at

General discussion

LPS endotoxin has been demonstrated to temporarily activate the immune system, stimulating cytokine production, and in a correlated fashion to disrupt learning in some tasks (e.g., [13], [14]). But successful learning depends upon a variety of constituent cognitive processes, any one of which might be the underlying cause for the disruption of learning. Such deficits in acquisition might be attributable to LPS disruption of the (a) ability of the subject to detect or perceive stimuli, (b) the

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    • Cited by (0)

    1

    The first two authors of this paper were the major contributors and did so equally. Experiment 1 was carried out by Julia E. Meyers-Manor while Experiment 2 was carried out by John M. Holden.

    2

    Now at Winona State University, MN.

    3

    Now at Humboldt State University, CA.

    4

    Now at University of Wisconsin, WI, USA.

    5

    Now at University of Kentucky, KY, USA.

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