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

English title Cerebral mechanisms underlying the influence of age-related changes in circadian and homeostatic processes on cognition: a functional neuroimaging approach
Applicant Cajochen Christian
Number 130689
Funding scheme Project funding (Div. I-III)
Research institution Abteilung Chronobiologie Universitäre Psychiatrische Kliniken Basel
Institution of higher education University of Basel - BS
Main discipline Neurophysiology and Brain Research
Start/End 01.04.2010 - 31.03.2013
Approved amount 532'630.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Physiology : other topics

Keywords (9)

Circadian; Homeostatic; Ageing; Cognition; fMRI; circadian clock; homeostatic sleep-wake regulation; functional magnetic resonance imaging; aging

Lay Summary (German)

Lead
Lay summary
Wichtigstes Ziel dieser Studie ist es, den Einfluss der inneren Uhr und des Schlafdruckes auf die zerebralen Korrelate kognitiver Leistungsfähigkeit bei gesunden jungen und älteren Probanden zu erheben. Die innere Uhr des Menschen sorgt dafür, dass die täglichen Schwankungen verschiedener Körperrhythmen (z.B. Hormone, Müdigkeit, Leistungsfähigkeit) mit dem Rhythmus des Tag-Nacht Wechsels synchronisiert bleiben. Die Periodik der inneren Uhr beträgt beim Menschen ungefähr 24 Stunden. Gleichzeitig nimmt die Schlafbereitschaft (Schlafdruck) während des Wachseins kontinuierlich zu. Die Stärke dieses Schlafdruckes spüren wir vor allem dann, wenn wir lange Zeit wach bleiben wollen. Die Qualität des Schlafes und der Leistungsfähigkeit während des Wachseins hängt erheblich von diesen zwei Faktoren ab. Im Alter verändert sich der Aufbau der Schlafbereitschaft und die Stärke des von der inneren Uhr gesendeten Wachsignals. Wie und auf welcher Ebene die innere Uhr und der Schlafdruck zusammen arbeiten um die Leistungsfähigkeit ja nach Tageszeitpunkt zu begutachten ist jedoch noch unklar. Das Ziel dieser Studie ist, Einflüsse der inneren Uhr und der Schlaf-Wachhomöostase auf die zerebralen Korrelate kognitiver Leistungsfähigkeit bei gesunden jungen und älteren Probanden zu untersuchen. Die zerebralen Korrelate kognitiver Leistungsfähigkeit werden anhand funktioneller Kernspintomographie ermittelt. Diese Messungen werden regelmässig an verschiedenen Tageszeitpunkten und unter verschiedenen Schlafdruckniveaus erhoben. Im Langtagprotokoll wird die "Tageslänge" auf 40 Stunden ausgedehnt werden, während im Kurztagprotokoll viele kurze Nickerchen geplant sind. Dieses Projekt soll dazu beitragen, die zerebralen Mechanismen, die der tageszeitabhängigen Variation unserer kognitiven Leistungsfähigkeit unterliegen weiterhin zu entschlüsseln. Zudem können wir den Einfluss des Altersprozesses auf diese Parameter testen. Diese Frage erscheint von entscheidender Bedeutung, wenn man bedenkt, dass wir immer älter werden und in unserer Gesellschaft etwa ein Fünftel aller Arbeitnehmer in irgendeiner Form von Schichtarbeitarbeit engagiert sind.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Age-related changes in sleep and circadian rhythms: impact on cognitive performance and underlying neuroanatomical networks.
Schmidt Christina, Peigneux Philippe, Cajochen Christian (2012), Age-related changes in sleep and circadian rhythms: impact on cognitive performance and underlying neuroanatomical networks., in Front. Neur., 3, 118.
Sleep-wake rhythms and cognition
Maire Micheline, Reichert Carolin, Schmidt Christina, Sleep-wake rhythms and cognition, in Journal of Cognitive and Behavioral Psychotherapy.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Meeting Swiss Society for Sleep Research, Sleep Medecine and Chronobiology 16.05.2013 Aarau
Deutsche Gesellschaft für Schlafmedizin 06.12.2012 Berlin
European Sleep Research Society (ESRS) 12.09.2012 Paris
Meeting Swiss Society of Sleep Research, Sleep Medecine and Chronobiology 12.04.2012 Zürich


Awards

Title Year
Jacobs Young Researcher Grant 2012
Poster Prize 2010

Associated projects

Number Title Start Funding scheme
55385 Very short and very long days: new techniques to measure circa- dian and sleep dependent processes in Alzheimer's disease and depression (zu START) 01.01.2000 Project funding (Div. I-III)
143736 Inter-individual differences underlying circadian and sleep-wake dependent modulations in cognitive performance : an electrophysiological, behavioural and functional neuroimaging approach. 01.04.2013 Project funding (Div. I-III)
163058 Influence of Caffeine Consumption on the Human Circadian System: Neurobehavioral, Hormonal and Cerebral Mechanisms 01.02.2016 Project funding (Div. I-III)
108108 The role of the circadian clock and the sleep homeostat in major depression 01.01.2006 Project funding (Div. I-III)

Abstract

1.Summary of the research project1.1. 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.
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