Cortisol Inhibits Neuroplasticity Induction in Human Motor Cortex

Abstract

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.

Non-invasive induction of plasticity in the human cortex: Uses and limitations

“…Interestingly, we were also able to show that a component of the reduced plasticity was associated with changes in cortisol levels. This is interesting, as we have previously demonstrated that cortisol can modulate cortical plasticity (Sale, Ridding, & Nordstrom, 2008), and it is well known that preterm birth is associated with alterations in the HPA axis (Sullivan, Hawes, Winchester, & Miller, 2008). This study, again, provides evidence that NIBS techniques are useful tools for probing the pathophysiology of conditions associated with functional and behavioural deficits.…”

Imaging human brain networks to improve the clinical efficacy of non-invasive brain stimulation

“…Inconsistent treatment outcomes appear to be influenced by variability in individuals' responses to NIBS. Several factors have been shown to influence the reliability and effectiveness of NIBS (Ridding and Ziemann, 2010), including genetic factors (Cheeran et al, 2008, Antal et al, 2010, hormone and drug interactions (Sale et al, 2008), age (Rogasch et al, 2009;Todd et al, 2010;Bashir et al, 2014) and levels of physical activity ). Other important factors that appear critical in determining the brain's response to NIBS, and which will be discussed in detail in this review, are the site of stimulation (Fox et al, 2014) and the activity of the underlying networks during stimulation (Nitsche et al, 2003;Fregni et al, 2005;Hummel et al, 2005;Antal et al, 2007;Kujirai et al, 2006;Andrews et al, 2011).…”

“…Controlling or minimizing some of the factors that contribute to this variability have been shown to improve the effectiveness and reliability of the induced effects (Sale et al, 2008;Kamke et al, 2014). However, the variability of the brain's response to rTMS remains a significant impediment to the application of such approaches in the clinical domain.…”

Selective enhancement of motor cortical plasticity by observed mirror-matched actions

“…For PAS, 90 paired peripheral and cortical stimuli were delivered at a frequency of 0.1 Hz (duration 15 mins). All experiments were performed at approximately the same time of day (~ 2pm) to minimise response variability due to circadian factors (Sale et al, 2007(Sale et al, , 2008.…”