, 2002, 2005), which is thought to involve sleep-related changes in cortical connectivity and plasticity (Maquet et al., 2003). However, it is not clear whether the effect of acute sleep disruption

in healthy subjects is equivalent to the chronic sleep fragmentation that is typically seen in patients with OSA. Nonetheless, a recent study has shown that reduced motor consolidation in patients with mild OSA was associated with increased arousals during sleep rather this website than the total amount of time spent sleeping, sleep efficiency or sleep architecture (Djonlagic et al., 2012). This, combined with our findings of an increased AI in patients with OSA, suggests that a lack of sleep continuity may contribute to impaired cortical plasticity in patients with see more OSA. Although application of cTBS produces important new information about the neurophysiological consequences of OSA, these results represent

an investigation into LTD-like effects only. The lack of LTD-like synaptic plasticity in OSA could represent an overall reduction in cellular mechanisms of synaptic plasticity, or a shift in the threshold for induction of LTP-like plasticity in accordance with the rules of metaplasticity (Abraham, 2008). However, this latter possibility seems unlikely, as it would contradict findings in animal models of OSA pathology (Xie et al., 2010). Future studies will need to further investigate this prospect by applying intermittent TBS, or other brain stimulation paradigms thought to induce LTP-like plasticity. Finally, due to its cross-sectional design, it is possible that several confounding factors may have contributed to the results observed in our assessment of plasticity. Many factors are known to influence the response to rTMS not (Ridding & Ziemann, 2010). Some of these, such as time of day, age and gender, were well matched between subject groups in the present study. Significant positive correlations between post-intervention MEPs at the 10 and 20 min time point and indices of physical activity during leisure time suggest that reduced physical activity may

have contributed to the response of patients with OSA. This is consistent with a previous study using paired-associative stimulation, which demonstrated reduced neuroplastic modulation in sedentary compared with highly active individuals (Cirillo et al., 2009). However, the strength of associations observed in the present study were relatively weak, suggesting that the extent of physical activity is unlikely to play a large role in the impaired neuroplasticity in patients with OSA. Genetic factors are also known to influence plasticity (Missitzi et al., 2011), for example, a common polymorphism of the brain-derived neurotrophic factor (BDNF) gene can influence the response to rTMS (Cheeran et al., 2008). The prevalence of this BDNF polymorphism may have been different between subject groups.