An association between resting state EEG parameters and the severity of topiramate-related cognitive impairment

Christopher M Barkley; Zhenhong Hu; Ann M Fieberg; Lynn E Eberly; Angela K Birnbaum; Ilo E Leppik; Susan E Marino

doi:10.1016/j.yebeh.2020.107598

An association between resting state EEG parameters and the severity of topiramate-related cognitive impairment

Epilepsy Behav. 2021 Jan;114(Pt A):107598. doi: 10.1016/j.yebeh.2020.107598. Epub 2020 Nov 29.

Authors

Christopher M Barkley¹, Zhenhong Hu², Ann M Fieberg³, Lynn E Eberly⁴, Angela K Birnbaum⁵, Ilo E Leppik⁶, Susan E Marino⁷

Affiliations

¹ Center for Clinical and Cognitive Neuropharmacology, Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 308 Harvard Street, Minneapolis, MN 55455, United States. Electronic address: barkl025@umn.edu.
² Department of Biomedical Engineering, University of Florida, 1275 Center Drive, Gainesville, FL 32611, United States.
³ Division of Biostatistics, University of Minnesota, 429 Delaware Street SE, Minneapolis, MN 55455, United States. Electronic address: afieberg@umn.edu.
⁴ Division of Biostatistics, University of Minnesota, 429 Delaware Street SE, Minneapolis, MN 55455, United States. Electronic address: leberly@umn.edu.
⁵ Center for Clinical and Cognitive Neuropharmacology, Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 308 Harvard Street, Minneapolis, MN 55455, United States. Electronic address: birnb002@umn.edu.
⁶ Center for Clinical and Cognitive Neuropharmacology, Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 308 Harvard Street, Minneapolis, MN 55455, United States. Electronic address: leppi001@umn.edu.
⁷ Center for Clinical and Cognitive Neuropharmacology, Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 308 Harvard Street, Minneapolis, MN 55455, United States. Electronic address: marin007@umn.edu.

PMID: 33268020
DOI: 10.1016/j.yebeh.2020.107598

Abstract

Introduction: Many commonly prescribed drugs cause cognitive deficits. We investigated whether parameters of the resting-state electroencephalogram (rsEEG) are related to the severity of cognitive impairments associated with administration of the antiseizure drug topiramate (TPM) and the benzodiazepine lorazepam (LZP).

Methods: We conducted a double-blind, randomized, placebo-controlled crossover study. After a baseline visit, subjects completed three sessions at which they received either a single dose of TPM, LZP, or placebo. Four-hours after drug administration and at baseline, subjects completed a working memory (WM) task after their rsEEG was recorded. After quantifying drug-related behavioral (WM accuracy (ACC)/reaction time (RT)) and electrophysiological (alpha, theta, beta (1,2), gamma power) change for each subject, we constructed drug-specific mixed effects models of change for each WM and EEG measure. Regression models were constructed to characterize the relationship between baseline rsEEG measures and drug-related performance changes.

Results: Linear mixed effects models showed theta power increases in response to TPM administration. The results of the regression models revealed a number of robust relationships between baseline rsEEG parameters and TPM-related, but not LZP-related, WM impairment.

Conclusions: We showed for the first time that parameters of the rsEEG are associated with the severity of TPM-related WM deficits; this suggests that rsEEG measures may have novel clinical applications in the future.

Keywords: Drug-related cognitive impairment; Resting-state EEG.

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural

MeSH terms

Cognitive Dysfunction* / chemically induced
Cross-Over Studies
Electroencephalography*
Humans
Reaction Time
Topiramate

Substances

Topiramate

Grants and funding

R01 NS076665/NS/NINDS NIH HHS/United States