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Single-neuron correlate of epilepsy-related cognitive deficits in visual recognition memory in right mesial temporal lobe

Lee, Seung J. and Beam, Danielle E. and Schjetnan, Andrea G. P. and Paul, Lynn K. and Chandravadia, Nand and Reed, Chrystal M. and Chung, Jeffrey M. and Ross, Ian B. and Valiante, Taufik A. and Mamelak, Adam N. and Rutishauser, Ueli (2021) Single-neuron correlate of epilepsy-related cognitive deficits in visual recognition memory in right mesial temporal lobe. Epilepsia, 62 (9). pp. 2082-2093. ISSN 0013-9580. PMCID PMC8403636. doi:10.1111/epi.17010.

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Objective: Impaired memory is a common comorbidity of refractory temporal lobe epilepsy (TLE) and often perceived by patients as more problematic than the seizures themselves. The objective of this study is to understand what the relationship of these behavioral impairments is to the underlying pathophysiology, as there are currently no treatments for these deficits, and it remains unknown what circuits are affected. Methods: We recorded single neurons in the medial temporal lobes (MTLs) of 62 patients (37 with refractory TLE) who performed a visual recognition memory task to characterize the relationship between behavior, tuning, and anatomical location of memory selective and visually selective neurons. Results: Subjects with a seizure onset zone (SOZ) in the right but not left MTL demonstrated impaired ability to recollect as indicated by the degree of asymmetry of the receiver operating characteristic curve. Of the 1973 recorded neurons, 159 were memory selective (MS) and 366 were visually selective (VS) category cells. The responses of MS neurons located within right but not left MTL SOZs were impaired during high-confidence retrieval trials, mirroring the behavioral deficit seen both in our task and in standardized neuropsychological tests. In contrast, responses of VS neurons were unimpaired in both left and right MTL SOZs. Our findings show that neuronal dysfunction within SOZs in the MTL was specific to a functional cell type and behavior, whereas other cell types respond normally even within the SOZ. We show behavioral metrics that detect right MTL SOZ-related deficits and identify a neuronal correlate of this impairment. Significance: Together, these findings show that single-cell responses can be used to assess the causal effects of local circuit disruption by an SOZ in the MTL, and establish a neural correlate of cognitive impairment due to epilepsy that can be used as a biomarker to assess the efficacy of novel treatments.

Item Type:Article
Related URLs:
URLURL TypeDescription
Lee, Seung J.0000-0001-7793-6518
Beam, Danielle E.0000-0001-5761-6621
Schjetnan, Andrea G. P.0000-0002-4319-7689
Paul, Lynn K.0000-0002-3128-8313
Reed, Chrystal M.0000-0002-7157-3645
Valiante, Taufik A.0000-0002-3443-3790
Mamelak, Adam N.0000-0002-4245-6431
Rutishauser, Ueli0000-0002-9207-7069
Additional Information:© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Issue Online: 27 August 2021; Version of Record online: 21 July 2021; Manuscript accepted: 06 July 2021; Manuscript revised: 06 July 2021; Manuscript received: 28 March 2021. We thank our patients for their time and willingness to participate in this study; members of Rutishauser Lab for discussion; the physicians and staff of the epilepsy monitoring units at Cedars-Sinai Medical Center, Huntington Memorial Hospital, and Toronto Western Hospital for their support; Minh-Tu Lee and Linda Philpott for neuropsychological testing; Bernard Gomes for help with data organization; Victoria Barkeley, Chaim Katz, and Kramay Patel for data organization and help with recordings; and Christie Clason, Jeffrey Wertheimer, David Sabsevitz, and Michael Rugg for advice on analysis of neuropsychological data. This study was supported by the National Institute of Mental Health (R01MH110831 to U.R.) and the National Institute of Neurological Disorders and Stroke, USA (U01NS103792, U01NS098961 to U.R.). Author Contributions: Conceptualization: Ueli Rutishauser; Software: Nand Chandravadia and Ueli Rutishauser; Data Curation: Seung J. Lee, Danielle E. Beam, Nand Chandravadia; Investigation: Seung J. Lee, Danielle E. Beam, Andrea G. P. Schjetnan, Lynn K. Paul, Nand Chandravadia, Ueli Rutishauser; Resources: Chrystal M. Reed, Jeffrey M. Chung, Ian B. Ross, Taufik A. Valiante, Adam N. Mamelak; Writing–Original Draft: Seung J. Lee, Danielle E. Beam, Lynn K. Paul, Adam N. Mamelak, Ueli Rutishauser; Writing–Review & Editing: Andrea G. P. Schjetnan, Chrystal M. Reed; Funding Acquisition: Ueli Rutishauser; Supervision: Ueli Rutishauser, Adam N. Mamelak, Taufik A. Valiante. Conflict of Interest: The authors report no competing interests. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Data Availability Statement: This dataset is available on the Open Science Framework in the standardized Neurodata Without Borders format (
Funding AgencyGrant Number
Subject Keywords:cognitive deficits; memory; single neuron; temporal lobe epilepsy
Issue or Number:9
PubMed Central ID:PMC8403636
Record Number:CaltechAUTHORS:20210817-151553962
Persistent URL:
Official Citation:Lee, SJ, Beam, DE, Schjetnan, AGP, Paul, LK, Chandravadia, N, Reed, CM, et al. Single-neuron correlate of epilepsy-related cognitive deficits in visual recognition memory in right mesial temporal lobe. Epilepsia. 2021; 62: 2082–2093.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:110286
Deposited By: Tony Diaz
Deposited On:18 Aug 2021 21:44
Last Modified:31 Aug 2021 19:58

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