Acute effects of lithium on excitability of human motor cortex.
OBJECTIVE
Lithium has been widely used to treat bipolar affective disorder for over 60years. 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 (450mg, 900mg, or 1350mg) 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, 450mg of lithium carbonate increased the slope of the MEP IO-curve while 1350mg 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.


CONCLUSIONS
Findings are important for our understanding of the therapeutic and toxic effects of lithium on the human central nervous system.
Department of Neurology, Goethe-University Frankfurt, Frankfurt, Germany; Department of Neurology, University of Ulm, Ulm, Germany.
Annemarie
A
Hübers
Department of Neurology, Goethe-University Frankfurt, Frankfurt, Germany.
Hanna
H
Voytovych
Department of Neurology, Goethe-University Frankfurt, Frankfurt, Germany.
Tonio
T
Heidegger
Department of Neurology, Goethe-University Frankfurt, Frankfurt, Germany; Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research, Eberhard-Karls University Tübingen, Tübingen, Germany.
Florian
F
Müller-Dahlhaus
Department of Neurology, Goethe-University Frankfurt, Frankfurt, Germany; Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research, Eberhard-Karls University Tübingen, Tübingen, Germany. Electronic address: ulf.ziemann@uni-tuebingen.de.
Ulf
U
Ziemann
D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D019054:Evoked Potentials, Motor / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000494:pharmacology*; D008297:Male; D009044:Motor Cortex / Q000187:drug effects* / Q000502:physiology; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult
D016651:Lithium Carbonate
Hormesis; Inverted U-shaped dose–response relationship; Lithium; Motor cortex excitability; Motor evoked potential; Transcranial magnetic stimulation