Caffeine has no effect on measures of cortical excitability M. Orth a,b, * , B. Amann b , N. Ratnaraj c , P.N. Patsalos c , J.C. Rothwell a a Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Royal Free and University College Medical School, Box 77, Queen Square, London WC1N 3BG, UK b Department of Neuropsychiatry, Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Royal Free and University College Medical School, Queen Square, London WC1N 3BG, UK c Pharmacology and Therapeutics Unit, Department of Clinical and Experimental Epilepsy, Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Royal Free and University College Medical School, Queen Square, London WC1N 3BG, UK Accepted 27 August 2004 Available online 1 October 2004 Abstract Objective: To assess the effect of caffeine on motor thresholds, short interval intra-cortical inhibition (SICI), intra-cortical facilitation (ICF) and cortical silent periods in a placebo controlled double-blinded trial. Methods: In eleven healthy non-smoking subjects the following parameters were measured using transcranial magnetic stimulation (TMS): motor thresholds (rest, RMT and active, AMT), SICI and ICF at different conditioning stimulus intensities (60, 70, 80, 90% AMT), cortical silent periods at 130, 150 and 175% AMT, and size of motor evoked potential at rest at 110, 125 and 150% RMT. Measurements were repeated after one cup of decaffeinated coffee. On another day, measurements were obtained before and after one cup of decaffeinated coffee that contained caffeine (3 mg/kg bodyweight). Caffeine concentrations were measured in serum before and after experiments. Experiments were conducted and data were evaluated blinded to the experimental condition. Results: The results of repeated measurements of all parameters were similar comparing experiments on each day, or when comparing the caffeine arm of the study with the placebo arm. Conclusions: Caffeine in a concentration similar to that in a strong cup of coffee does not have a major effect on TMS measures of motor cortex excitability. Significance: In healthy controls, the design of TMS experiments that investigate the parameters assessed in this TMS study does not need to control for caffeine. q 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. Keywords: Transcranial magnetic stimulation; Caffeine; Motor–motor inhibition; Cortical silent period; Paired-pulse 1. Introduction Coffee presumably originated in the highlands of Ethiopia, and from there spread into the Arabic world. It was brought to Venice in the early 17th century and became known in Europe during that century, at first as a medicine, and then as a social drink in the Arab tradition. Coffee has ever since been valued as stimulating the mind and sharpening the senses; the coffee houses founded in England were soon known as ‘penny universities’. Caffeine, the psycho-active substance responsible for these effects, may be the most consumed psycho-active drug in the world (Fredholm et al., 1999). Almost all caffeine originates from dietary sources with coffee and tea being the most popular. The widely appreciated effects of caffeine on alertness and performance have been reproduced in a number of behavioural studies in humans (Botella et al., 2001; Brice and Smith, 2001), and in rats caffeine was shown to increase motor activity (Kaplan et al., 1992). However, it is not known whether these behavioural effects reflect changes in the electrophysiology of the brain. In humans, the effect Clinical Neurophysiology 116 (2005) 308–314 www.elsevier.com/locate/clinph 1388-2457/$30.00 q 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2004.08.012 * Corresponding author. Address: Sobell Department of Motor Neuro- science and Movement Disorders, Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Royal Free and University College Medical School, Box 77, Queen Square, London WC1N 3BG, UK. Tel.: C44 207 8373611x3947; fax: C44 207 2788772. E-mail address: m.orth@ion.ucl.ac.uk (M. Orth).