Approximately 7% of the adult population has OSA, defined as abnormal repetitive cessation of breathing during sleep. Apneic moments occur as the airway is obstructed, leading to hypercapnia (increased carbon dioxide), hypoxia (decreased oxygen) and resulting sleep fragmentation as the airway is reestablished. In both animal models and humans, neuronal circuitry abnormalities due to apnea have been shown, as well as physiological consequences including cognitive and motor impairment, hypersomnia and metabolic and cardiovascular complications (Dempsey et al., 2010; Wang et al., 2010; Brown et al., 2012; Lal et al., 2012). In this paper, the authors investigated the

well-established link between apnea and fine motor skill deficits (Beebe et al., 2003). Baseline motor cortex excitability was first evaluated. Motor MDV3100 concentration evoked potential thresholds were ABT-199 manufacturer elevated,

compared to a non-apneic control group, reflecting abnormal corticospinal excitability. The authors then used a specific rTMS protocol to produce LTD in the motor cortex. Previous work in healthy subjects (Huang et al., 2005) showed that short bursts of stimuli (three pulses at 50 Hz intraburst frequency) repeated at theta frequency, i.e. at 5 Hz, induced long-term potentiation when applied in an intermittent pattern or LTD when applied continuously for 40 s, termed continuous theta-burst stimulation (cTBS). Opie et al. (2013) thus applied cTBS to a particular subregion of the motor cortex, shown previously to innervate hand muscles, and in which motor evoked potentials were suppressed in healthy

subjects, therefore demonstrating cTBS-induced LTD. Apneic patients, though, showed an abnormal response to cTBS, for motor evoked potentials were not attenuated. The authors ruled out PJ34 HCl the possibility that intracortical inhibition played a role in the observed impairment, and concluded that the impaired baseline threshold level for evoked motor potentials, as well as the observed LTD impairment, reflected impaired neuroplasticity in the motor cortex. This exciting and novel investigation by Opie et al. (2013) is the first to use TMS to evaluate cortical neuroplasticity in OSA patients. Although more investigations are needed to describe the mechanism by which cortical neuroplastic changes are induced by cTBS protocols, the results of this study may facilitate OSA treatment. At present, few treatments are available to improve the attentional, mnemonic and/or motor deficits seen in apnea, beyond continuous positive airway pressure (CPAP) treatment. Cortical plasticity in the motor cortex could be evaluated following pharmacological, surgical and/or CPAP treatment, to gauge efficacy of treatment. In future studies, other TMS stimulation protocols may also be applied, such as those that induce long-term potentiation, and alternative cortical regions may also be explored.