Present-day sleep research in humans is largely dependent on complex and costly laboratory setups, which require controlled supervision. As it is highly desirable to study sleep and to monitor sleep interventions in a realistic setting at home, new mobile approaches with equivalent performance to lab-based systems are needed. We present here the development and evaluation of a mobile system for sleep-biosignal monitoring and real-time intervention for ambulatory sleep research. We evaluated the system for electroencephalogram (EEG) signal quality and compared it to an established sleep EEG recording system. The real-time EEG signal processing performance was evaluated by implementing a closedloop auditory deep-sleep stimulation algorithm, and we calculated the precision of slow wave (SW) phase targeting during 93 nights. The obtained EEG signals contained similar power spectrograms and high correlations in the delta (0.98) and sigma (0.99) bands when compared to the reference system. The SW phase targeting [mean 44.6°, standard deviation (SD) 46.8°] was comparable to previously published, lab-based approaches. We have, thus, demonstrated that our device is suitable for performing unobtrusive, multinight monitoring and intervention at home. Index Terms-Sensor applications, biosensor sensing and processing, electroencephalogram (EEG), acoustic stimulation, braincomputer interface, sleep, mobile devices.

Background Auditory stimulation has emerged as a promising tool to enhance non-invasively sleep slow waves, deep sleep brain oscillations that are tightly linked to sleep restoration and are diminished with age. While auditory stimulation showed a beneficial effect in lab-based studies, it remains unclear whether this stimulation approach could translate to real-life settings. Methods We present a fully remote, randomized, cross-over trial in healthy adults aged 62–78 years (clinicaltrials.gov: NCT03420677). We assessed slow wave activity as the primary outcome and sleep architecture and daily functions, e.g., vigilance and mood as secondary outcomes, after a two-week mobile auditory slow wave stimulation period and a two-week Sham period, interleaved with a two-week washout period. Participants were randomized in terms of which intervention condition will take place first using a blocked design to guarantee balance. Participants and experimenters performing the assessments were blinded to the condition. Results Out of 33 enrolled and screened participants, we report data of 16 participants that received identical intervention. We demonstrate a robust and significant enhancement of slow wave activity on the group-level based on two different auditory stimulation approaches with minor effects on sleep architecture and daily functions. We further highlight the existence of pronounced inter- and intra-individual differences in the slow wave response to auditory stimulation and establish predictions thereof. Conclusions While slow wave enhancement in healthy older adults is possible in fully remote settings, pronounced inter-individual differences in the response to auditory stimulation exist. Novel personalization solutions are needed to address these differences and our findings will guide future designs to effectively deliver auditory sleep stimulations using wearable technology.

Freezing of gait (FoG) is a motor impairment among patients with advanced Parkinson's disease which is associated with falls and has a negative impact on a patient's quality of life. Wearable systems have been developed to detect FoG and to help patients resume walking by means of rhythmical cueing. A step further is to predict the FoG and start cueing a few seconds before it happens, which might help patients avoid the gait freeze entirely. We characterize the gait parameters continuously with up to 10-12 seconds prior to FoG, observe if and how they change before subjects enter FoG, and compare them with the gait before turns. Moreover, we introduce and discuss new frequency-based features to describe gait and motor anomalies prior to FoG. Using inertial units mounted on the ankles of 5 subjects, we show specific changes in the stride duration and length with up to four seconds prior to FoG on all subjects, compared with turns. Moreover, the dominant frequency migrates towards [3, 8] Hz band with up to six seconds prior to FoG on 3 subjects. These findings open the path to real-time prediction of FoG from inertial measurement units.

OBJECTIVE: In-phase stimulation of EEG slow waves (SW) during deep sleep has shown to improve cognitive function. SW enhancement is particularly desirable in subjects with low-amplitude SW such as older adults or patients suffering from neurodegeneration. However, existing algorithms to estimate the up-phase of EEG suffer from a poor phase accuracy at low amplitudes and when SW frequencies are not constant. METHODS: We introduce two novel algorithms for real-time EEG phase estimation on autonomous wearable devices, a phase-locked loop (PLL) and, for the first time, a phase vocoder (PV). We compared these phase tracking algorithms with a simple amplitude threshold approach. The optimized algorithms were benchmarked for phase accuracy, the capacity to estimate phase at SW amplitudes between 20 and 60 V, and SW frequencies above 1 Hz on 324 home-based recordings from healthy older adults and Parkinson disease (PD) patients. Furthermore, the algorithms were implemented on a wearable device and the computational efficiency and the performance was evaluated in simulation and with a PD patient. RESULTS: All three algorithms delivered more than 70% of the stimulation triggers during the SW up-phase. The PV showed the highest capacity on targeting low-amplitude SW and SW with frequencies above 1 Hz. The hardware testing revealed that both PV and PLL have marginal impact on microcontroller load, while the efficiency of the PV was 4% lower. Active stimulation did not influence the phase tracking. CONCLUSION: This work demonstrated that phase-accurate auditory stimulation can also be delivered during fully remote sleep interventions in populations with low-amplitude SW.

Sufficient recovery during sleep is the basis of physical and psychological well-being. Understanding the physiological mechanisms underlying this restorative function is essential for developing novel approaches to promote recovery during sleep. Phase-targeted auditory stimulation (PTAS) is an increasingly popular technique for boosting the key electrophysiological marker of recovery during sleep, slow-wave activity (SWA, 1–4 Hz EEG power). However, it is unknown whether PTAS induces physiological sleep. In this study, we demonstrate that, when applied during deep sleep, PTAS accelerates SWA decline across the night which is associated with an overnight improvement in attentional performance. Thus, we provide evidence that PTAS enhances physiological sleep and demonstrate under which conditions this occurs most efficiently. These findings will be important for future translation into clinical populations suffering from insufficient recovery during sleep.