Ysbrand van der Werf

The mystery of sleep

While we dream, the brain is working hard. Sleep is an essential part of our lives. However, we know surprisingly little of what is going on in our brains while we sleep. Why do we need sleep? What happens when we have insufficient sleep? To address these issues we monitor the sleeping brains of volunteers in our sleep laboratory. A key issue is understanding the differences between sound and bad sleepers. To further support that, sleep data from the dutch population are collected through a database (www. slaapregister.nl). An international site is being developed to further expand the available dataset.

The neural basis of sleep and sleep disorders

Brain imaging studies are used to elucidate brain mechanisms involved in the favourable and disruptive effects on cognition of, respectively, sleep and sleep disturbances. We focus on (1) the functional significance of the slow oscillations (<4 Hz) typical of ‘deep’ sleep and on (2) the functions and brain areas affected most in insomnia, the most frequently occurring sleep complaint and characterized by ‘shallow’ sleep.

With respect to the functional significance of the slow oscillations we use magneto-encephalography (MEG) to investigate how the spatial map of cortico-cortical synchronization during sleep is affected by pre-sleep cognitive activity. We furthermore apply subtle experimental suppression of slow oscillations and use Magnetic Resonance Imaging (fMRI) to investigate its effects on subsequent task-related activation (blood-oxygen level dependent (BOLD) functional MRI, fMRI) and ‘resting-state’ perfusion (Arterial Spin Labelling, ASL). A new project has started to further investigate the role of slow oscillations on the resting state network. Using novel techniques for manipulation of the sleep slow oscillations we will test the hypothesis that they serve to ‘refresh’ the brain networks used the previous day by evaluating how wake experiences (or rather the accompanying activated brain networks) affect the appearance of slow waves during the night, and secondly, how these slow waves in turn serve to specifically ‘rejuvenate’, or prepare those brain networks for renewed function.

With respect to the functions and brain areas affected most in insomnia, we demonstrated that insomniacs are prone to show a dysbalance of faster responses in simple reaction time tasks and slower responses in a more difficult reaction time task (Altena et al., 2008). We were the first to apply fMRI in insomnia and demonstrated that, in spite of a normal to high performance on verbal fluency tasks, insomniacs show a decreased activation of the dorsolateral prefrontal cortical area typically involved in performing this task (Altena et al., 2008). We presently investigate how insomnia affects performance and BOLD-responses during other tasks that involve prefrontal, parietal and medial temporal lobe activation (fMRI); how it affects ‘resting-state’ perfusion (ASL); how it affects grey and white matter density (voxel-based morphometry, VBM); and how it affects intra-cortical inhibition and facilitation (Transcranial Magnetic Stimulation, TMS).