Ketamine Disrupts Frontal and Hippocampal Contribution to Encoding and Retrieval of Episodic Memory: An fMRI Study
G. Honey, R. Honey, C. O'Loughlin, S. Sharar, D. Kumaran, J. Suckling, D. K. Menon, C. Sleator, E. Bullmore, P. Fletcher
Cerebral Cortex November 10, 2004 DOI: 10.1093/cercor/bhh176 via Semantic Scholar
Summary
Ketamine, a drug that blocks NMDA receptors, impairs episodic memory. Using fMRI, brain activity was measured in healthy volunteers during memory encoding and retrieval under two intravenous doses of ketamine in a double-blind, placebo-controlled, randomized, within-subjects design. Encoding and retrieval were separated across two study-test cycles to isolate drug effects on each process. Results suggest that ketamine increases left frontal activation when elaborative semantic processing is needed during encoding, and successful encoding on the drug relies on additional incidental non-verbal processing. At retrieval, ketamine appears to impair access to contextual features of studied items. Even when behavior appears normal, ketamine alters recruitment of key brain regions for episodic memory.
Study at a glance
| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Population | Healthy volunteers |
| Keywords | Medicine Psychology |
| Citations | 116 |
| Key finding | Ketamine augments left frontal activation during elaborative semantic encoding and impairs access to contextual features during retrieval, altering brain region recruitment even when behavior is unimpaired. |
Abstract
The N-methyl-d-aspartate (NMDA) receptor antagonist ketamine produces episodic memory deficits. We used functional magnetic resonance imaging to characterize the effects of ketamine on frontal and hippocampal responses to memory encoding and retrieval in healthy volunteers using a double-blind, placebo-controlled, randomized, within-subjects comparison of two doses of intravenous ketamine. Dissociation of the effects of ketamine on encoding and retrieval processes was achieved using two study-test cycles: in the first, items were encoded prior to drug infusion and retrieval tested, during scanning, on drug; in the second, encoding was scanned on drug, and retrieval tested once ketamine plasma levels had declined. We additionally determined the interaction of ketamine with the depth of processing that occurred at encoding. A number of effects upon task-dependent activations were seen. Overall, our results suggest that left frontal activation is augmented by ketamine when elaborative semantic processing is required at encoding. In addition, successful encoding on ketamine is supplemented by additional non-verbal processing that is incidental to task demands. The effects of ketamine at retrieval are consistent with impaired access to accompanying contextual features of studied items. Our findings show that, even when overt behaviour is unimpaired, ketamine has an impact upon the recruitment of key regions in episodic memory task performance.