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Cerebral mechanisms underlying the influence of age-related changes in circadian and homeostatic processes on cognition: a functional neuroimaging approach.

Research Project
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01.04.2010
 - 31.03.2013

1. Summary of the research project 1.1. Background: The circadian and homeostatic sleep-wake regulatory processes interact in a fined tuned manner to modulate human cognitive performance. However, the cerebral mechanisms that underlie this complex interplay remain largely unknown. In a recent neuroimaging approach, we observed that homeostatic sleep-wake processes impact on brain activity in areas implicated in the circadian regulation (i.e. anterior hypothalamus, locus coeruleus). Therefore, we have strong evidence that the circadian and homeostatic interaction directly impinges on cortical activity underlying human sleep-wake behavior. While we could unravel how this complex interplay of circadian and homeostatic processes impact upon brain activity in young individuals, it is still completely unknown what might take place with aging. Ample evidence favors an age-dependent dampening of circadian rhythms and the circadian alertness signal together with less pronounced influence of the homeostatic sleep pressure on neurobehavioral performance, such as sustained attention. Given these prominent age-related changes, the next logical question arises as to which are the cerebral correlates underlying circadian- and homeostatic-related time-of-day modulations on cognition with advanced age. 1.2. General aim: To investigate the cerebral mechanisms underlying the influence of age-related changes in circadian and homeostatic processes on cognition. 1.3. Specific aims: (1) Arousal promoting brain centres (thalamic, brainstem locus coeruleus, hypothalamic regions) will exhibit higher activity profiles during the circadian wake as compared to the circadian sleep promoting part of the 24-hour cycle. (2) A reduced circadian amplitude results in less time-of-day differences with advanced age in arousal promoting brain centres. (3) The circadian alerting signal on task-related brain activity is weaker under high than low sleep pressure. (4) The impact of homeostatic sleep pressure onto circadian wake promoting brain centres and their influence on the entire cortex shows age-related dampening. 1.4. Experimental design/methods: We propose a functional neuroimaging approach (fMRI) to quantify task-related BOLD activity in a cohort of healthy young and old volunteers at very specific time points within the 24-hour cycle. Cognitive domains ranging from sustained attention to higher order executive aspects of attention will be investigated. During a protocol in which the sleep homeostat will be challenged by either an extension (high sleep pressure by sleep deprivation) or a reduction of prior wakefulness (low sleep pressure by interpolated naps), we will focus on the time window in the subjective evening hours which encompasses maximal circadian drive for wake as well as the time window in the subjective morning hours surrounding the maximal circadian drive for sleep. 1.5. Potential value of the project: This pioneering combination of a chronobiological fMRI approach will help to disentangle the cerebral mechanisms underlying time-of-day fluctuations in higher order cognitive behaviors and its age-dependency. This question appears crucial when considering that in our current social context approximately one fifth of all employees are engaged in some form of work that requires timings outside the "standard" 7am to 6pm working day. Furthermore, to understand the contribution of deteriorated circadian arousal promotion at the cerebral level and its detrimental effects on sleep and wakefulness frequently encountered in healthy ageing is decisive in our aging society.

Members (1)

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Christian Cajochen

Principal Investigator