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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2019.00925

Methylphenidate Treatment of Cognitive Dysfunction in Adults After Mild to Moderate Traumatic Brain Injury: Rationale, Efficacy, and Neural Mechanisms

 Harvey S. Levin1, 2*,  Maya Troyanskaya1, 2,  Jo Ann Petrie3, Elizabeth A. Wilde1, 3, 4*, Tracy J. Abildskov3 and Randall S. Scheibel1, 2
  • 1Baylor College of Medicine, United States
  • 2Michael E. DeBakey VA Medical Center, United States
  • 3Department of Neurology, The University of Utah, United States
  • 4VA Salt Lake City Health Care System, United States

Abstract
Positive effects of methylphenidate (MPH) on attention and cognitive processing speed have been reported in studies of patients with moderate to severe traumatic brain injury (TBI). Studies which have acquired functional brain imaging before and while using MPH have also found alteration of brain activation while performing a cognitive task; in some studies, this alteration of activation in selective brain regions was also related to improved performance on cognitive tests administered outside of the scanning environment. Enhanced cognitive performance has been reported after single doses of MPH and after daily treatment over durations of up to and exceeding one month. Preclinical research and both positron emission tomography and single photon emission tomography of humans have shown that MPH increases extracellular dopamine and norepinephrine; the dose effects of MPH have an inverted U-shaped function where high doses may cause insomnia, nervousness, and increased heart rate among other symptoms and impair cognitive performance, whereas too low a dose fails to improve cognitive performance. In the past five years, small clinical trials and experimental pilot studies have found therapeutic effects of single and repeated low doses of MPH in patients with mild TBI who reported cognitive dysfunction. This literature also suggests that MPH may interact with concurrent cognitive interventions to enhance their effects. This focused review will critically evaluate the recent literature on MPH effects on cognitive dysfunction after mild to moderate TBI. To elucidate the neural mechanisms of MPH effects, this review will also include recent imaging research, preclinical, and experimental human studies.

Keywords: Traumatic Brain Injury, Methylphenidate, clinical trials, imaging, cognitive dysfunction

Received: 20 Feb 2019; Accepted: 09 Aug 2019.

Copyright: © 2019 Levin, Troyanskaya, Petrie, Wilde, Abildskov and Scheibel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Harvey S. Levin, Baylor College of Medicine, Houston, United States, hlevin@bcm.edu
PhD. Elizabeth A. Wilde, The University of Utah, Department of Neurology, Salt Lake City, 84112, Utah, United States, elisabeth.wilde@hsc.utah.edu