Browsing by Author "Brown, Joshua W."

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    Neural evidence of switch processes during semantic and phonetic foraging in human memory
    (National Academy of Science, 2023) Lundin, Nancy B.; Brown, Joshua W.; Johns, Brendan T.; Jones, Michael N.; Purcell, John R.; Hetrick, William P.; O’Donnell, Brian F.; Todd, Peter M.; Psychiatry, School of Medicine
    Humans may retrieve words from memory by exploring and exploiting in "semantic space" similar to how nonhuman animals forage for resources in physical space. This has been studied using the verbal fluency test (VFT), in which participants generate words belonging to a semantic or phonetic category in a limited time. People produce bursts of related items during VFT, referred to as "clustering" and "switching." The strategic foraging model posits that cognitive search behavior is guided by a monitoring process which detects relevant declines in performance and then triggers the searcher to seek a new patch or cluster in memory after the current patch has been depleted. An alternative body of research proposes that this behavior can be explained by an undirected rather than strategic search process, such as random walks with or without random jumps to new parts of semantic space. This study contributes to this theoretical debate by testing for neural evidence of strategically timed switches during memory search. Thirty participants performed category and letter VFT during functional MRI. Responses were classified as cluster or switch events based on computational metrics of similarity and participant evaluations. Results showed greater hippocampal and posterior cerebellar activation during switching than clustering, even while controlling for interresponse times and linguistic distance. Furthermore, these regions exhibited ramping activity which increased during within-patch search leading up to switches. Findings support the strategic foraging model, clarifying how neural switch processes may guide memory search in a manner akin to foraging in patchy spatial environments.
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    Nicotine and cotinine exposure from electronic cigarettes: a population approach
    (Springer-Verlag, 2015-06) Vélez de Mendizábal, Nieves; Jones, David R.; Jahn, Andy; Bies, Robert R.; Brown, Joshua W.; Department of Medicine, IU School of Medicine
    BACKGROUND AND OBJECTIVES: Electronic cigarettes (e-cigarettes) are a recent technology that has gained rapid acceptance. Still, little is known about them in terms of safety and effectiveness. A basic question is how effectively they deliver nicotine; however, the literature is surprisingly unclear on this point. Here, a population pharmacokinetic model was developed for nicotine and its major metabolite cotinine with the aim to provide a reliable framework for the simulation of nicotine and cotinine concentrations over time, based solely on inhalation airflow recordings and individual covariates [i.e., weight and breath carbon monoxide (CO) levels]. METHODS: This study included ten adults self-identified as heavy smokers (at least one pack of cigarettes per day). Plasma nicotine and cotinine concentrations were measured at regular 10-min intervals for 90 min while human subjects inhaled nicotine vapor from a modified e-cigarette. Airflow measurements were recorded every 200 ms throughout the session. A population pharmacokinetic model for nicotine and cotinine was developed based on previously published pharmacokinetic parameters and the airflow recordings. All of the analyses were performed with the non-linear mixed-effect modeling software NONMEM(®) version 7.2. RESULTS: The results show that e-cigarettes deliver nicotine effectively, although the pharmacokinetic profiles are lower than those achieved with regular cigarettes. Our pharmacokinetic model effectively predicts plasma nicotine and cotinine concentrations from the inhalation volume, and initial breath CO. CONCLUSION: E-cigarettes are effective at delivering nicotine. This new pharmacokinetic model of e-cigarette usage might be used for pharmacodynamic analysis where the pharmacokinetic profiles are not available.