• sleep
• chronotype
• social jetlag
• lifestyle
• sport performance
• melatonin
• TMS-EEG

Sleep is an integral part of the cyclical nature of our lives, constituting approximately a third of our daily existence. The repercussions of sleep deprivation can be dramatic and are inevitable, although its precise function remains elusive. Several theories posit that sleep plays a pivotal role in regulating crucial biological functions essential for animal life. These include memory consolidation, synaptic homeostasis, and the elimination of neurotoxins within the central nervous system.
In our day-to-day experiences, the impact of inadequate sleep duration or quality on physical and cognitive performance is evident. In specific conditions, such as engaging in extreme sports, compromised sleep can even lead to physical harm. Common causes of sleep disturbances include externally imposed social schedules dictated by work or school start times, which may be mismatched with individual circadian preference, thus significantly and negatively affecting waking functioning.
Within the realm of pathophysiology, research indicates that dysregulations in sleep/wake rhythms are emerging risk factors for Non-Communicable Diseases. The negative effects of poor sleep on emotion regulation may contribute to the adoption of unhealthy lifestyle habits in response to stressors, possibly partially explaining the link between sleep disturbances and chronic diseases.
Given the widespread prevalence of sleep disturbances, there is a critical need to identify effective treatments. Exogenous melatonin, with its combined chronobiotic and sleep-promoting properties, emerges as a promising candidate. However, the optimal administration schedule for maximizing its sleep-promoting effects in both adults and pediatric populations remains unclear.
The use of Transcranial Magnetic Stimulation (TMS-EEG) during sleep has significantly contributed to understanding the mechanisms underlying the loss of consciousness. The Perturbational Complexity Index (PCI), quantifying the complexity of TMS-Evoked Potentials, has been validated as a valuable diagnostic tool for assessing capacity for consciousness in patients with Disorders of Consciousness. Its use in clinical practice relies on the possibility of simplifying TMS-EEG data collection, also through the acceleration of data acquisition. Reducing the InterStimulus Interval (ISI) is a viable strategy for reducing data collection time without decreasing signal quality. However, the impact of stimulation frequency on TMS-Evoked Potentials and PCI values is still not known.

The research project aimed to:
1) Explore the association between sleep disturbances and an unhealthy lifestyle under chronic stress conditions and normal circumstances.
2) Investigate how circadian rhythm conflicts can influence sports performance.
3) Identify the most effective melatonin treatment schedule for promoting sleep in both children and adults.
4) Examine the effect of a short InterStimulus Interval (ISI) on TMS-EEG response and a derived measure of complexity (PCI).

For aim 1, data on lifestyle and sleep habits were collected through an online questionnaire during the COVID-19 first-wave lockdown (stress condition) and after the end of the pandemic, with 1297 and 465 participants, respectively. Wrist actigraphy assessed the sleep/wake rhythm of 245 participants in the second group. Results indicated that poor sleep quality predicts the adoption of several unhealthy lifestyle habits, summarized in a score, independently of wide set of variables measuring demographics, attitude towards the pandemic, circadian misalignment, pandemic burden on the geographical area. Beyond the pandemic, a multidimensional sleep health index, derived by the combination of objective sleep metrics and subjective perception of sleep quality, predicted the Body Mass Index, the weekly consumption of cigarettes and alcoholic beverages, in parallel partially explaining the association between eveningness and drinking and smoking intensity. These findings demonstrated the importance of sleep health as a target for health promotion.
For aim 2, a questionnaire investigating the night shift sleep management was administered to 190 crews participating in an overnight sleep regatta. Shift schedule was used to identify predictors of the final placement. Results support the hypothesis that allowing crew members to self-manage the time to devote to sleep and the time to devote to wakefulness is associated with a global improved team performance. These results have potential implication for the management of several types of continuous cycle activity, whose organization should take in account individual biological rhythm. In a separate study with high school basketball athletes, a sample of 93 high school students-basketball athletes performed several sessions of free throws (number of free throws = 7880) both during the school and the holiday periods. When attending school, but not on holiday, chronotype significantly interacted with the day of the week in predicting sport performance. In particular, the most evening types showed a weekly performance trend consistent with their increased likelihood of experiencing a cumulative sleep debt due to early school start time. Moreover, the participants who did not complete the free throw motor scheme learning worsened their performance when attending school compared to the holiday period, possibly reflecting how early school start time-related sleep deprivation negatively influence motor learning. These results suggest that matching social schedule with circadian preference might grant several benefits to adolescents, in parallel confirming sleep importance for learning in a naturalistic setting.
For aim 3, two systematic reviews and dose-response metanalyses were conducted: one considering only studies conducted in adults, one in prepubertal children. Both studies showed that the optimal melatonin dose for sleep promotion ranges between 2 and 5 mg, and that the time of administration with respect to bedtime plays the most important role in predicting melatonin efficiency. In particular, melatonin reaches the maximal efficacy in reducing sleep onset latency when administered 2-3 hours before bedtime. Our findings suggest that the melatonin administration schedules most commonly advised in clinic and by the manufacturers of over-the-counter formulations (2 mg before bedtime) may not be the most effective and, if confirmed by clinical trials, might lead to reconsider melatonin role in the treatment of sleep disturbances.
For aim 4, 14 participants were stimulated twice on the left hemisphere in 3 cortical spots (premotor, parietal, occipital) keeping the stimulation parameters constant with exception of the InterStimulus Interval (ISI). ISI jittered between 2-2.3 s in the ISI2 condition, and between 1-1.3 s in the ISI1 condition. While the ISI2 condition represents the most commonly adopted when stimulating non-motor areas, shortening the ISI to 1-1.3 s would allow to cut in half the time required for data acquisition. Visual inspection of the grand average TEP showed that stimulation frequency does not impact the topography and timing of the major peaks of the response. Moreover, no significant difference emerged when comparing ISI2 and ISI1 peak-to-peak amplitude, suggesting that increasing the stimulation frequency does not affect cortical excitability. Instead, the amplitude of the late component (80-220 ms) was higher at ISI2 compared to ISI1 at premotor and parietal level. In the premotor area only, power loss in the late component was paralleled by a decrease in signal entropy, suggesting that the reduction in amplitude may be due to the loss of non-redundant information. The loss of information was coupled with a significant drop in the complexity of the response, as measured by PCI. Stimulating posterior cortices, rather than frontal, may be hence preferable to minimize alterations in TEP characteristics and facilitate the interpretation of PCI using established reference values.