Acute effects of lithium on excitability of human motor cortex

Objective: Lithium has been widely used to treat bipolar affective disorder for over 60 years. Still, its acute effects in human cerebral cortex are poorly understood. This study aimed at investigating the acute effects of lithium on motor cortex excitability as measured by transcranial magnetic stimulation (TMS). Methods: Ten healthy young adults participated in a double-blind placebo-controlled randomized crossover study with four sessions, where a single oral dose of lithium carbonate (450 mg, 900 mg, or 1350 mg) or placebo was tested. Focal TMS of the hand area of left motor cortex was used to test resting and active motor thresholds, motor evoked potential input-output curve (MEP IO-curve), slope of the MEP IO-curve and paired-pulse measures of intracortical inhibition and facilitation before, and two and four hours after drug administration. Results: Two hours post drug administration, 450 mg of lithium carbonate increased the slope of the MEP IO-curve while 1350 mg tended to decrease it. Lithium had no effect on motor thresholds, or intracortical inhibition or facilitation. Conclusions: The acute effects of lithium on MEP IO-curve, a marker of corticospinal excitability, are consistent with an inverted U-shaped dose-response relationship. Significance: Findings are important for our understanding of the therapeutic and toxic effects of lithium on the human central nervous system. (C) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.