Cortisol Inhibits Neuroplasticity Induction in Human Motor Cortex

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 GABAB-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 GABAB-dependent intracortical inhibitory systems are influenced by time of day and modified by circulating levels of cortisol.

[1]  P. Ashby,et al.  Mechanism of the silent period following transcranial magnetic stimulation Evidence from epidural recordings , 1999, Experimental Brain Research.

[2]  Carl W. Cotman,et al.  Exercise Enhances and Protects Brain Function , 2002, Exercise and sport sciences reviews.

[3]  Michael C. Ridding,et al.  Influence of Combined Afferent Stimulation and Task-Specific Training Following Stroke: A Pilot Randomized Controlled Trial , 2007, Neurorehabilitation and neural repair.

[4]  Paolo Maria Rossini,et al.  Modulation of corticospinal excitability by paired associative stimulation: Reproducibility of effects and intraindividual reliability , 2006, Clinical Neurophysiology.

[5]  S. Paul,et al.  Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. , 1986, Science.

[6]  M. Ridding,et al.  Prolonged peripheral nerve stimulation induces persistent changes in excitability of human motor cortex , 2003, Journal of the Neurological Sciences.

[7]  M. Ridding,et al.  Does induction of plastic change in motor cortex improve leg function after stroke? , 2003, Neurology.

[8]  A Berardelli,et al.  Silent period evoked by transcranial stimulation of the human cortex and cervicomedullary junction. , 1993, The Journal of physiology.

[9]  Melatonin blocks the induction of long-term potentiation in an N-methyl-d-aspartate independent manner , 1997, Brain Research.

[10]  J. Rothwell,et al.  Magnetic transcranial stimulation at intensities below active motor threshold activates intracortical inhibitory circuits , 1998, Experimental Brain Research.

[11]  Ulf Ziemann,et al.  Homeostatic plasticity in human motor cortex demonstrated by two consecutive sessions of paired associative stimulation , 2007, The European journal of neuroscience.

[12]  M. Hallett,et al.  Repetitive Transcranial Magnetic Stimulation–Induced Corticomotor Excitability and Associated Motor Skill Acquisition in Chronic Stroke , 2006, Stroke.

[13]  Michael C. Ridding,et al.  Factors influencing the magnitude and reproducibility of corticomotor excitability changes induced by paired associative stimulation , 2007, Experimental Brain Research.

[14]  K. R. Mills,et al.  Covariation between human intrinsic hand muscles of the silent periods and compound muscle action potentials evoked by magnetic brain stimulation: evidence for common inhibitory connections , 1998, Experimental Brain Research.

[15]  T. Sinkjaer,et al.  Associative plasticity in human motor cortex during voluntary muscle contraction. , 2006, Journal of neurophysiology.

[16]  K J Werhahn,et al.  Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans , 1999, The Journal of physiology.

[17]  Ulf Ziemann,et al.  Pharmacology of TMS. , 2003, Supplements to Clinical neurophysiology.

[18]  P M Rossini,et al.  Non-invasive evaluation of central motor tract excitability changes following peripheral nerve stimulation in healthy humans. , 1991, Electroencephalography and clinical neurophysiology.

[19]  B. Greenberg,et al.  Menstrual cycle effects on cortical excitability , 1999, Neurology.

[20]  S. Pullman,et al.  Physiological basis of voluntary activity inhibition induced by transcranial cortical stimulation. , 1993, Electroencephalography and clinical neurophysiology.

[21]  K. Sakai,et al.  Paired‐pulse magnetic stimulation of the human motor cortex: differences among I waves , 1998, The Journal of physiology.

[22]  Ulf Ziemann,et al.  Suppression of LTP-like plasticity in human motor cortex by the GABAB receptor agonist baclofen , 2007, Experimental Brain Research.

[23]  T. Raghunathan,et al.  Modeling cortisol rhythms in a population-based study , 2005, Psychoneuroendocrinology.

[24]  C. Allen,et al.  GABAergic synapses of the suprachiasmatic nucleus exhibit a diurnal rhythm of short‐term synaptic plasticity , 2004, The European journal of neuroscience.

[25]  L. Cohen,et al.  A temporally asymmetric Hebbian rule governing plasticity in the human motor cortex. , 2003, Journal of neurophysiology.

[26]  L. Cohen,et al.  Mechanisms of enhancement of human motor cortex excitability induced by interventional paired associative stimulation , 2002, The Journal of physiology.

[27]  S. Wise,et al.  Mechanisms of use-dependent plasticity in the human motor cortex. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[28]  F. Hucklebridge,et al.  Exploration of the awakening cortisol response in relation to diurnal cortisol secretory activity. , 2001, Life sciences.

[29]  Ulf Ziemann,et al.  Chapter 23 Pharmacology of TMS , 2003 .

[30]  Diane Ruge,et al.  Short‐interval paired‐pulse inhibition and facilitation of human motor cortex: the dimension of stimulus intensity , 2002, The Journal of physiology.

[31]  S. Riek,et al.  Reliability of the input–output properties of the cortico-spinal pathway obtained from transcranial magnetic and electrical stimulation , 2001, Journal of Neuroscience Methods.

[32]  F. Tecchio,et al.  Age dependence of primary motor cortex plasticity induced by paired associative stimulation , 2008, Clinical Neurophysiology.

[33]  Brian L. Day,et al.  Different sites of action of electrical and magnetic stimulation of the human brain , 1987, Neuroscience Letters.

[34]  G. Tononi,et al.  Molecular and electrophysiological evidence for net synaptic potentiation in wake and depression in sleep , 2008, Nature Neuroscience.

[35]  F. Hsu,et al.  Effects of a single dose of cortisol on the neural correlates of episodic memory and error processing in healthy volunteers , 2003, Psychopharmacology.

[36]  J. Newcomer,et al.  Decreased memory performance in healthy humans induced by stress-level cortisol treatment. , 1999, Archives of general psychiatry.

[37]  K. Nakashima,et al.  Changes in somatosensory-evoked potentials and high-frequency oscillations after paired-associative stimulation , 2007, Experimental Brain Research.

[38]  E. Wassermann,et al.  A safety screening questionnaire for transcranial magnetic stimulation , 2001, Clinical Neurophysiology.

[39]  M. Hallett,et al.  Spinal motor neuron excitability during the silent period after cortical stimulation. , 1991, Electroencephalography and clinical neurophysiology.

[40]  M. Ridding,et al.  Induction of plasticity in the dominant and non-dominant motor cortices of humans , 2006, Experimental Brain Research.

[41]  B. Roozendaal,et al.  Acute cortisone administration impairs retrieval of long-term declarative memory in humans , 2000, Nature Neuroscience.

[42]  M. V. Hogan,et al.  Melatonin regulates neuronal plasticity in the hippocampus , 2003, Journal of neuroscience research.

[43]  Timothy S Miles,et al.  Changes in corticomotor representations induced by prolonged peripheral nerve stimulation in humans , 2001, Clinical Neurophysiology.

[44]  C. Marsden,et al.  Corticocortical inhibition in human motor cortex. , 1993, The Journal of physiology.

[45]  K. Inokuchi,et al.  Dopaminergic modulation of LTP induction in the dentate gyrus of intact brain , 1997, Neuroreport.

[46]  Francesca Morgante,et al.  Motor cortex plasticity in Parkinson's disease and levodopa-induced dyskinesias. , 2006, Brain : a journal of neurology.

[47]  M. Hallett,et al.  Changes in spinal excitability after PAS. , 2007, Journal of neurophysiology.

[48]  Jonathan R. Whitlock,et al.  Learning Induces Long-Term Potentiation in the Hippocampus , 2006, Science.

[49]  J. Donoghue,et al.  Learning-induced LTP in neocortex. , 2000, Science.

[50]  G. Tononi,et al.  Sleep function and synaptic homeostasis. , 2006, Sleep medicine reviews.

[51]  F. Mora,et al.  Circadian rhythms of dopamine, glutamate and GABA in the striatum and nucleus accumbens of the awake rat: modulation by light , 2004, Journal of pineal research.

[52]  C. Fuller,et al.  Diurnal modulation of long-term potentiation in the hamster hippocampal slice , 1999, Brain Research.

[53]  M. Hallett,et al.  Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. , 1994, Brain : a journal of neurology.

[54]  J. L. Taylor,et al.  Mechanisms of motor‐evoked potential facilitation following prolonged dual peripheral and central stimulation in humans , 2001, The Journal of physiology.

[55]  K. Stefan,et al.  Modulation of associative human motor cortical plasticity by attention. , 2004, Journal of neurophysiology.

[56]  Joseph Classen,et al.  Temporary occlusion of associative motor cortical plasticity by prior dynamic motor training. , 2006, Cerebral cortex.

[57]  S. Berent,et al.  Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing's syndrome , 1992, Biological Psychiatry.

[58]  D. Ruge,et al.  Learning Modifies Subsequent Induction of Long-Term Potentiation-Like and Long-Term Depression-Like Plasticity in Human Motor Cortex , 2004, The Journal of Neuroscience.

[59]  B. Dubrovsky,et al.  Effects of corticosterone and 5α‐dihydrocorticosterone on brain excitability in the rat , 1985 .

[60]  H. Siebner,et al.  Abnormal associative plasticity of the human motor cortex in writer's cramp. , 2003, Brain : a journal of neurology.

[61]  J. Donoghue,et al.  Long-term potentiation of horizontal connections provides a mechanism to reorganize cortical motor maps. , 1994, Journal of neurophysiology.

[62]  J. Rothwell,et al.  Facilitation of muscle evoked responses after repetitive cortical stimulation in man , 1998, Experimental Brain Research.

[63]  L. Cohen,et al.  Induction of plasticity in the human motor cortex by paired associative stimulation. , 2000, Brain : a journal of neurology.

[64]  H. Tsuji,et al.  Intracortical facilitation and inhibition after transcranial magnetic stimulation in conscious humans. , 1997, The Journal of physiology.

[65]  Christopher S. Colwell,et al.  Circadian Regulation of Hippocampal Long-Term Potentiation , 2005, Journal of biological rhythms.