Dynamics of the cortical responsiveness during extended wakefulness, in young and older participants.

Although it has been established that human brain physiology and cognition are under the joint effect of the sleep homeostasis and the circadian alerting signal, the detrimental effect of sleep deprivation is still mostly seen as merely a consequence of a lack of sleep. While this approach is valuable, in order to develop a complete understanding, a circadian perspective needs to be integrated. However, a major difficulty of measuring circadian rhythmicity stems from the complexity of assessing it, because confounders such as light, activity, meals etc. could mask the underlying circadian regulation. Here, we performed two constant routine studies that allow us to measure the interaction between sleep homeostasis and the circadian processes at the cortical level. During the studies, three complementary aspects of the cortical function were investigated, as well as their associations with behavioural performance, and age-related changes of the cortical dynamics. In phase I of the study, the dynamics of cortical excitability, and of response scattering and complexity were described during a 28 hour wake extension protocol in young participants (18-30 y). In phase II, the dynamics of cortical excitability and response complexity were investigated during a 34 hour wake extension in young (18-30 y) and older (50-70 y) participants in order to address lifetime changes. Overall, the results of this thesis demonstrated an age-dependent homeostatic and circadian regulation of basic cortical function. That was especially evident at the local level, when focusing on cortical excitability profile: young participants showed a clear circadian rhythmicity and sleep homeostasis regulation, the dynamic of which was dampened in the older participants. At the global level, cortical response scattering and complexity changed with time spent awake, i.e. according to the circadian phase Furthermore, cortical complexity response was higher in the older group, showing a simple age effect, but the dynamic did not differ between the two age groups. Preliminary analyses demonstrated that these cortical dynamics sustain part of the profile of behavioural performance across the circadian cycle. Importantly, older people with higher cortical excitability, particularly during the biological night, were performing better at higher order tasks, possibly indicating that older people that maintain a degree of sensitivity toward sleep homeostasis and circadian processes perform better. Understanding the principal forces that regulate the dynamics of cortical neurophysiology in two age groups –and their impact on cognition– is of uppermost importance for our ageing society, in which sleep deprivation and circadian misalignment are commonplace

Time course of cortical response complexity during extended wakefulness and its differential association with vigilance in young and older individuals

peer reviewe

Changes in EEG Permutation Entropy in the evening and in the transition from wake to sleep

Peer reviewe

Time course of cortical response complexity during extended wakefulness and its differential association with vigilance in young and older individuals

peer reviewe

Circadian regulation of human cortical excitability

peer reviewe

Circadian dynamics in measures of cortical excitation and inhibition balance

Several neuropsychiatric and neurological disorders have recently been characterized as dysfunctions arising from a ‘final common pathway’ of imbalanced excitation to inhibition within cortical networks. How the regulation of a cortical E/I ratio is affected by sleep and the circadian rhythm however, remains to be established. Here we addressed this issue through the analyses of TMS-evoked responses recorded over a 29h sleep deprivation protocol conducted in young and healthy volunteers. Spectral analyses of TMS-evoked responses in frontal cortex revealed non-linear changes in gamma band evoked oscillations, compatible with an influence of circadian timing on inhibitory interneuron activity. In silico inferences of cell-to-cell excitatory and inhibitory connectivity and GABA/Glutamate receptor time constant based on neural mass modeling within the Dynamic causal modeling framework, further suggested excitation/inhibition balance was under a strong circadian influence. These results indicate that circadian changes in EEG spectral properties, in measure of excitatory/inhibitory connectivity and in GABA/glutamate receptor function could support the maintenance of cognitive performance during a normal waking day, but also during overnight wakefulness. More generally, these findings demonstrate a slow daily regulation of cortical excitation/inhibition balance, which depends on circadian-timing and prior sleep-wake history

Age-related changes in circadian sleep-wake regulation: Impact on cognitive performance and cerebral correlates

peer reviewe

Neuronal excitation/inhibition balance is set by the need for sleep and the biological clock

peer reviewe

The two-process model of sleep regulation: a reappraisal

In the last three decades the two-process model of sleep regulation has served as a major conceptual framework in sleep research. It has been applied widely in studies on fatigue and performance and to dissect individual differences in sleep regulation. The model posits that a homeostatic process (Process S) interacts with a process controlled by the circadian pacemaker (Process C), with time-courses derived from physiological and behavioural variables. The model simulates successfully the timing and intensity of sleep in diverse experimental protocols. Electrophysiological recordings from the suprachiasmatic nuclei (SCN) suggest that S and C interact continuously. Oscillators outside the SCN that are linked to energy metabolism are evident in SCN-lesioned arrhythmic animals subjected to restricted feeding or methamphetamine administration, as well as in human subjects during internal desynchronization. In intact animals these peripheral oscillators may dissociate from the central pacemaker rhythm. A sleep/fast and wake/feed phase segregate antagonistic anabolic and catabolic metabolic processes in peripheral tissues. A deficiency of Process S was proposed to account for both depressive sleep disturbances and the antidepressant effect of sleep deprivation. The model supported the development of novel non-pharmacological treatment paradigms in psychiatry, based on manipulating circadian phase, sleep and light exposure. In conclusion, the model remains conceptually useful for promoting the integration of sleep and circadian rhythm research. Sleep appears to have not only a short-term, use-dependent function; it also serves to enforce rest and fasting, thereby supporting the optimization of metabolic processes at the appropriate phase of the 24-h cycle