The Effect of Topiramate Plasma Concentration on Linguistic Behavior, Verbal Recall and Working Memory

• Type of Material: Article
• Authors: S. E. Marino, University of Minnesota; S. V. S. Pakhomov, University of Minnesota; S. Han, University of Florida; K. L. Anderson, University of Florida; M. Ding, University of Florida; L. E. Eberly, University of Minnesota; David W Loring, Emory University; C. Hawkins-Taylor, University of Minnesota; J. O. Rarick, University of Minnesota; I. E. Leppik, University of Minnesota; J. E. Cibula, University of Florida; A. K. Birnbaum, University of Minnesota
• Language: English
• Date: 2012-05-30
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.yebeh.2012.04.120
• Title of Journal or Parent Work: Epilepsy and Behavior
• ISSN: 1525-5050
• Grant/Funding Information: This work was supported by the National Institutes of Health/National Institute for Neurological Diseases and Stroke [K 01 NS050309 to S.E.M.]; National Institute for Aging [R01 AG026490 to A.K.B.] and University of Minnesota/Academic Health Center Faculty Research Development Award [to S.E.M., S.V.S.P., A.K.B.]
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Neuroscience

Abstract

This is the first study of the effect of topiramate on linguistic behavior and verbal recall using a computational linguistics system for automated language and speech analysis to detect and quantify drug-induced changes in speech recorded during discourse-level tasks. Healthy volunteers were administered a single, 100-mg oral dose of topiramate in two double-blind, randomized, placebo-controlled, crossover studies. Subjects' topiramate plasma levels ranged from 0.23 to 2.81 μg/mL. We found a significant association between topiramate levels and impairment on measures of verbal fluency elicited during a picture description task, correct number of words recalled on a paragraph recall test, and reaction time recorded during a working memory task. Using the tools of clinical pharmacology and computational linguistics, we elucidated the relationship between the determinants of a drug's disposition as reflected in plasma concentrations and their impact on cognitive functioning as reflected in spoken language discourse.