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Human lab studies: High-Density EEG, MEG, MRI, TMS, eye-tracking, performance and temperature manipulations

Senior scientist Ysbrand Van Der Werf heads the neuroimaging studies in the Sleep & Cognition team. In cooperation with the VU Medical Center and the Academic Medical Center, both located very close to the Netherlands Institute for Neuroscience, we have access to a large number of tools for neuroimaging and their analysis. With respect to the functional significance of the slow oscillations during sleep we use magneto-encephalography (MEG) and high-density EEG; the latter can even be applied ambulatory. We use Magnetic Resonance Imaging (fMRI) to investigate task-related activation (blood-oxygen level dependent (BOLD) functional MRI, fMRI). The resting state network is studied using both BOLD fluctuations and perfusion quantification (Arterial Spin Labelling, ASL). Structural imaging of grey and white matter density applies the voxel-based morphometry (VBM) method. In order to study how sleep and insomnia affects intra-cortical inhibition and facilitation, and in order to apply focal cortical stimulation we own a Transcranial Magnetic Stimulation (TMS) system including Neuronavigation. Cognitive performance tests are implemented in C++, Matlab and E-prime, and can be assessed including eye-tracking. The sleep-lab is equipped with a unique setup for comfortable skin temperature clamping in humans.

Human field studies: web-based psychometrics

Postdoc Jeroen Benjamins has joined the Sleep & Cognition group in order to take responsibility for the implementation of web-based tools for task- and questionnaire assessment. His research program comprises the implementation of the Netherlands Sleep Registry, which uses web-based survey methods to obtain a database of psychometric and sleep data. For a successful implementation, we need a large number of volunteering people, both with sleep complaints and very sound sleepers, that are willing to fill out questionnaires and do game-like tasks at their own computer at home on a regular basis (www.slaapregister.nl). Analyses will aim to identify latent classes (profiles) of subtypes of insomniacs – and of very sound sleepers.

Human field studies: ambulatory monitoring

Our group has an internationally recognized expertise in the field of actigraphic recording and analysis of activity rhythms and sleep in health and disease. Methods have been developed to quantify rhythms in a reliable and clinically relevant way (Van Someren et al., 1999; Van Someren, 2007; Carvalho-Bos et al., 2007), not only in humans, but also in animals (Cayetanot et al., 2005). Furthermore dedicated actigraph has been developed that allows unobtrusive monitoring of the incidence and amplitude of tremor and normal movements in Parkinson’s disease for many weeks, yet at a single minute time resolution. The device can be of great value in the optimization of medication dosage and schedules and in the monitoring of disease progression and treatment response (Van Someren et al., 1993; Van Someren et al., 1998; Van Someren et al., 2006).

We valuated a system for unobtrusive long-term wireless monitoring of skin temperature (van Marken Lichtenbelt et al., 2006). By application of this method we discovered a marked abnormality in thermoregulation in narcolepsy patients, that may even be of diagnostic value (Fronczek et al., 2006) and has led to the innovative treatment strategy of applying mild skin temperature manipulation in order to improve their daytime vigilance and nocturnal sleep (Fronczek et al., 2008; Fronczek et al., 2008).

One of the most valuable markers of the endogenous circadian timing system is the 24-hour profile of melatonin. Radio-immuno-assays and Elisa are available for its determination in plasma and saliva. We promoted the feasibility and reliability of melatonin assessment, also in less-compliant patients like demented elderly, by developing a sparse-sampling assessment protocol and a parsimonious curve-fitting method (Van Someren and Nagtegaal, 2007).

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