In the last two decades, a growing number of findings lends support to the idea that physiological levels of cortical arousal can be modulated by inducing changes in specific cortical network via different protocols of transcranial Electrical Stimulation (tES). Specifically, transcranial Direct Current Stimulation (tDCS) has been shown to modulate the firing rate and cortical excitability within the target areas in a polarity-dependent manner, while transcranial Alternating Current Stimulation (tACS) is able to entrain endogenous brain oscillations at specific frequencies. Data from animal/human studies point to the anodal tDCS as the most promising stimulation technique to increase cortical desynchronization and alertness. The general aim of the project is to provide specific setting of tDCS protocols able to modulate cortical arousal levels leading to coherent changes in sleepiness and vigilance in both healthy and clinical populations.
The project will enroll 30 participants: 15 healthy volunteers; 15 patients with Obstructive Sleep Apnea Syndrome (OSAS) with excessive diurnal sleepiness (EDS). Specifically, the project is aimed to enhance daytime vigilance and alertness in healthy subjects undergoing a sleep restriction protocol and in OSAS patients with EDS by using a frontal anodal tDCS protocol to enhance vigilance/alertness.
A multidimensional approach is proposed for the evaluation of the effectiveness of stimulation protocols, considering different measures: objective (EEG Power spectra, PSG parameters), behavioral (Psychomotor Vigilance Task) and subjective (self-report sleepiness questionnaire) measures of sleepiness, sleep propensity and sleep quality will be integrated to provide a multi-level description of changes induced by the specific stimulation along these dimensions. We will evaluate any variability in the magnitude of the effects among different experiments and the impact of the stimulation treatment on patients with OSAS.
Several studies converged toward the definition of a bottom-up model of sleep control, in which the major sleep regulating pathways are integrated in the ascending reticular activating system, originating in the brainstem and relayed to cortical areas. However, recent evidence also points to the existence of top-down mechanisms for the modulation of cortical arousal, underlining the importance of the cortical component and its input to the subcortical structures in the determination of the brain global state. Accordingly, it was proposed that the physiological vigilance states are controlled by a complex cortico-thalamo-cortical feedback loop [2]. In this context, tDCS and tACS represent promising technological tools to evaluate the importance of the cortical component, and of specific patterns of regional cortical activity, in the sleep control.
In fact, the finding of specific stimulation protocols able to induce or block the sleep onset process by mean of an external modulation of cortical activity would provide strong support to the cortico-thalamo-cortical feedback loop model. Actually, manipulating the brain electromagnetic activity, rather than only recording it, has the potential to provide direct evidence for the function of brain processes and to be therapeutically relevant for clinical conditions of decreased arousal or disrupted sleep.
Moreover, basic and clinical sleep research would take important advantage of the possibility to bi-directionally modulate the sleep propensity in healthy subjects by tES, as an alternative to the more expensive sleep deprivation/restriction protocols. The outcomes of the different studies the current project is made of also assume particular relevance from the socio-economic point of view.
On the one hand, given the implications that the level of sleepiness has for the individuals current and near-term ability to safely and efficiently perform operationally-relevant tasks, a tool that is able to manipulate the arousal level (increase and decrease) in healthy subjects could have high social impact. In this contest, this kind of tools could be particularly helpful for shift and night workers as support in the regularization of their wake-sleep cycle.
Actually, this scenario has also important economic implications, since poor sleep quality and excessive diurnal sleepiness are frequently cause of serious accidents linked with high costs in term of human lives, hospitalization and pharmacological spending.
On the other hand, the successful application of tES in clinical populations suffering of arousal disorders, as those involved in this project (i.e. patients with insomnia and patients with OSAS), could be considered another important implication of the outcomes of the project.
It worth noticing that insomnia symptoms are frequently associated with worse physical health and a number of specific conditions, such as respiratory disease, heart disease, and arthritis [14]. Among patients with insomnia who are treated, the large majority receives pharmacotherapy. While the short-term benefits of hypnotics have been reported in several studies, it is recognized that hypnotics should be used with caution and preferably avoided in patients with chronic insomnia [15]. Concerns have been raised over the increasing prescription of benzodiazepines and "Z" drugs for insomnia, with a particular focus on older people due to their increased vulnerability to side effects [15]. Evidence-based non-drug approaches, as the ones that will be evaluated in the current project, are potentially relevant and of interest, being free from the most of the potential risks linked with current pharmacological treatments (i. e. tolerance and dependency, interaction with other drugs) and especially for pharmacological-resistant patients [16].
Similarly, obstructive sleep apnea syndrome (OSAS) may disturb sleep architecture leading to fragmented or decreased sleep duration, which results in excessive daytime sleepiness (EDS) and disturbance of concentration. The EDS is one of the main features responsible for occupational and automobile accidents in this population and also contributes to social engagement impairment [17]. Continuous positive airway pressure (CPAP) is the treatment of choice for patients with OSAS and the most effective method to reduce EDS [18]. Nevertheless, some patients who are regular CPAP users continue to complain of residual EDS [19] and additional pharmacological treatments with CNS stimulants are often administered. However, the use of stimulant drugs for EDS treatment is often associated to abuse potential, interference with sleep, and possible adverse cardiovascular consequences [20]. The possibility to reduce EDS in OSAS patients with a no pharmacological treatment and no sides effects would represent a unique opportunity for this clinical population.