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Extent of single-neuron activity modulation by hippocampal interictal discharges predicts declarative memory disruption in humans

Reed, Chrystal M. and Mosher, Clayton P. and Chandravadia, Nand and Chung, Jeffrey M. and Mamelak, Adam N. and Rutishauser, Ueli (2020) Extent of single-neuron activity modulation by hippocampal interictal discharges predicts declarative memory disruption in humans. Journal of Neuroscience, 40 (3). pp. 682-693. ISSN 0270-6474. PMCID PMC6961998. doi:10.1523/jneurosci.1380-19.2019.

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Memory deficits are common in epilepsy patients. In these patients, the interictal EEG commonly shows interictal epileptiform discharges (IEDs). While IEDs are associated with transient cognitive impairments, it remains poorly understood why this is. We investigated the effects of human (male and female) hippocampal IEDs on single-neuron activity during a memory task in patients with medically refractory epilepsy undergoing depth electrode monitoring. We quantified the effects of hippocampal IEDs on single-neuron activity and the impact of this modulation on subjectively declared memory strength. Across all recorded neurons, the activity of 50 of 728 neurons were significantly modulated by IEDs, with the strongest modulation in the medial temporal lobe (33 of 416) and in particular the right hippocampus (12 of 58). Putative inhibitory neurons, as identified by their extracellular signature, were more likely to be modulated by IEDs than putative excitatory neurons (19 of 157 vs 31 of 571). Behaviorally, the occurrence of hippocampal IEDs was accompanied by a disruption of recognition of familiar images only if they occurred up to 2 s before stimulus onset. In contrast, IEDs did not impair encoding or recognition of novel images, indicating high temporal and task specificity of the effects of IEDs. The degree of modulation of individual neurons by an IED correlated with the declared confidence of a retrieval trial, with higher firing rates indicative of reduced confidence. Together, these data link the transient modulation of individual neurons by IEDs to specific declarative memory deficits in specific cell types, thereby revealing a mechanism by which IEDs disrupt medial temporal lobe-dependent declarative memory retrieval processes.

Item Type:Article
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URLURL TypeDescription CentralArticle
Reed, Chrystal M.0000-0002-7157-3645
Mamelak, Adam N.0000-0002-4245-6431
Rutishauser, Ueli0000-0002-9207-7069
Alternate Title:Disruption of human declarative memory by IEDs
Additional Information:© 2019 Reed et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. Received: 13 June 2019; Revised: 17 October 2019; Accepted: 17 November 2019. This work was supported by National Institutes of Health R01MH110831 and U01NS103792 to U.R. We thank all patients for generous participation; and Cody Holland and the EEG technicians for support. The authors declare no competing financial interests.
Funding AgencyGrant Number
Subject Keywords:declarative memory; episodic memory; hippocampus; human-single neuron; interictal epileptic discharges; intracranial
Issue or Number:3
PubMed Central ID:PMC6961998
Record Number:CaltechAUTHORS:20191125-091014565
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Official Citation:Extent of Single-Neuron Activity Modulation by Hippocampal Interictal Discharges Predicts Declarative Memory Disruption in Humans. Chrystal M. Reed, Clayton P. Mosher, Nand Chandravadia, Jeffrey M. Chung, Adam N. Mamelak, Ueli Rutishauser. Journal of Neuroscience 15 January 2020, 40 (3) 682-693; DOI: 10.1523/JNEUROSCI.1380-19.2019
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:100021
Deposited By: Tony Diaz
Deposited On:25 Nov 2019 17:19
Last Modified:16 Nov 2021 17:51

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