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The Journal of Neuroscience, August 13, 2008, 28(33):8285-8293; doi:10.1523/JNEUROSCI.1963-08.2008

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Development/Plasticity/Repair
Cortisol Inhibits Neuroplasticity Induction in Human Motor Cortex

Martin V. Sale, Michael C. Ridding, and Michael A. Nordstrom

Discipline of Physiology and Research Centre for Human Movement Control, School of Molecular and Biomedical Science, The University of Adelaide, Adelaide SA 5005, Australia

Correspondence should be addressed to Assoc. Prof. Michael A. Nordstrom, Discipline of Physiology and Research Centre for Human Movement Control, School of Molecular and Biomedical Science, The University of Adelaide, Adelaide SA 5005, Australia. Email: michael.nordstrom{at}adelaide.edu.au

We investigated whether plasticity of human motor cortex (M1) is influenced by time of day, and whether changes in circulating levels of cortisol contribute to this effect. Neuroplasticity was induced using paired associative stimulation (PAS), involving electrical stimulation of left median nerve, paired with transcranial magnetic stimulation over the right M1 25 ms later (90 pairs at 0.05 Hz). Surface EMG was recorded from the left abductor pollicis brevis (APB) and first dorsal interosseous muscle. Cortisol levels were assessed from saliva. Time-of-day modulation of PAS effectiveness was assessed in 25 subjects who were tested twice, at 8:00 A.M. and 8:00 P.M. on separate days. In a second double-blind study, 17 subjects were tested with PAS at 8:00 P.M. on two occasions after administration of oral hydrocortisone (24 mg) or placebo. The motor-evoked potential (MEP) in resting APB increased significantly after PAS in the evening (when endogenous cortisol levels were low), but not in the morning. Oral hydrocortisone prevented facilitation of the APB MEP after PAS, and in the drug study, mean salivary cortisol levels were negatively associated with PAS effectiveness. The GABA_B-mediated cortical silent period for APB was longer in the morning than in the evening, and was lengthened by PAS and oral hydrocortisone. We conclude that neuroplasticity in human M1 and GABA_B-dependent intracortical inhibitory systems are influenced by time of day and modified by circulating levels of cortisol.

Key words: transcranial magnetic stimulation; cortisol; paired associative stimulation; circadian; plasticity; cortical inhibition

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Received Jan. 16, 2008; accepted June 20, 2008.

Correspondence should be addressed to Assoc. Prof. Michael A. Nordstrom, Discipline of Physiology and Research Centre for Human Movement Control, School of Molecular and Biomedical Science, The University of Adelaide, Adelaide SA 5005, Australia. Email: michael.nordstrom{at}adelaide.edu.au

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