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Improving Sleep and Cognition in Young Adults and the Elderly Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2014 Improving sleep and cognition in young adults and the elderly Cordi, Maren Abstract: Sleep, particularly slow-wave sleep (SWS), is a critical factor for health and well-being. Fur- thermore, SWS provides a brain state supportive for the spontaneous reactivation, stabilization, and long-term storage of declarative memories. Sleep architecture changes across lifespan and the parallel nascent impairments in SWS, cognition, and other health aspects hint at a deteriorating interplay between these three factors. Thus, a profound understanding of the nature of the relationship between sleep and memory in young and old human participants is fundamental in successfully finding new ways of memory- and sleep-related interventions. The first study was designed to clarify the role of induced reactivations for memory consolidation during sleep in different sleep stages. While reactivation during SWS has been reported to improve memory and stabilize it against future interference, the role of reactivations during rapid eye movement (REM) sleep is less clear. On the one hand, spontaneous reactivations, functionally associated with memory performance, exist in REM sleep. On the other hand, declarative memories have proven stable after sleep which is free from REM sleep. As induction of memory reactivations during REM sleep failed to shelter memory from interference, we concluded that spontaneous reactivations which appear during REM sleep do not contribute to the stabilization of declarative memories. The second study tested hypnosis as a tool to objectively improve sleep as its efficacy had previously been proven for subjective sleep measures. Our data was the first to confirm this effectiveness on an objective levelby revealing a specific increase in SWS and slow-wave activity (SWA) amounts after hypnotic suggestions to deepen sleep in younger adults. Contrary to expectations, SWS-enriched sleep by hypnosis did not improve memory consolidation. As sleep improvements are particularly critical in advanced age, but generalizations from results of younger adults to older adults are not valid, we replicated the study in the third manuscript with older adults. Hypnotic suggestions again proved effective in increasing the amounts of SWS and SWA. Cognition associated with prefrontal activity benefited from this increase. Results for memory consolidation were less pronounced, but promising. Together, data indicated an age-independent effect of hypnotic suggestions on SWS enrichment. They further supported the assump- tion that SWS restores prefrontal cortex (PFC) functionality and benefits consolidation. As an outlook, hypnotic suggestions to increase SWS might be combined with induced memory reactivations during this sleep stage to further improve memory consolidation processes in the elderly. Together, the manuscripts in this thesis investigate the relationship between sleep and memory on a theoretical and a practical level. One study clarifies the role of REM sleep reactivations for memory stability and two studies confirmthe effectiveness of hypnotic suggestions to objectively increase SWS and SWA independent of age.Owing to these insights, the recommendation of hypnosis as a non-pharmacological technique to improve sleep depth, subjective sleep quality and to positively influence cognitive abilities in older adults can bebased on objective and experimentally controlled data. There is great potential inherent in this line of research, which paves the way to positively influence senescence processes in major areas of life and health. Schlaf, vor allem Tiefschlaf (SWS), trägt entscheidend zu Gesundheit und Wohlbefinden bei. Darüber hinaus unterstützt Tiefschlaf spontane Reaktivierungen, sowie die Stabilisierung und Langzeitspeicherung von deklarativen Gedächtnisinhalten. Die Schlafstruktur verändert sich über die Lebensspanne hinweg und die dabei parallel auftretenden Beeinträchtigungen des Tiefschlafs, der Kognition und anderer Gesund- heitsaspekte deuten auf ein zerstörerisches Zusammenspiel zwischen diesen drei Faktoren hin. Daher ist ein tiefgreifendes Verständnis des Wesens der Beziehung zwischen Schlaf und Gedächtnis bei jüngeren und älteren Menschen grundlegend, um erfolgreich neue Interventionsmöglichkeiten zu finden. Die er- ste Studie wurde konzipiert, um die Rolle induzierter Gedächtnisreaktivierungen auf die Konsolidierung im Schlaf während verschiedener Schlafstufen zu klären. Einerseits treten spontane Reaktivierungen, die funktional für die Gedächtnisleistung sind, auch im REM (Rapid Eye Movement) Schlaf auf. Andererseits zeigte sich auch nach einem Schlaf ohne REM Anteil eine Stabilisierung des deklarativen Gedächtnisses. Da die Induktion von Gedächtnisreaktivierungen während des REM Schlafs das Gedächtnis nicht vor Interferenz zu schützen vermochte, schlossen wir auf einen mangelnden Beitrag der Reaktivierungen im REM Schlaf zur Gedächtnisstabilisierung deklarativer Inhalte. Die zweite Studie testete Hypnose als Methode zur Verbesserung des Schlafs, da dessen Wirksamkeit zuvor für subjektive Schlafmaße bestätigt werden konnte. Unsere Daten bestätigten diese Wirksamkeit erstmals an objektiven Maßen, indem sie einen spezifischen Anstieg im Tiefschlafanteil und der Tiefschlafaktivität (SWA) nach einer hypnotischen Suggestion „tiefer zu schlafen“ bei jüngeren Erwachsenen aufwiesen. Entgegen der Erwartung verbesserte der durch Hypnose vertiefte Schlaf die Gedächtniskonsolidierung nicht. Da Verbesserungen des Schlafs besonders im fortgeschrittenen Alter relevant sind, aber Generalisierungen der Ergebnisse von jüngeren auf ältere Erwachsene nicht valide sind, replizierten wir die Studie mit älteren Erwachsenen im drit- ten Manuskript. Die hypnotischen Suggestionen erwiesen sich abermals als förderlich für SWS und SWA. Des Weiteren war die Leistung bei präfrontal abhängigen Gedächtnisaufgaben verbessert. Die Effekte für die Gedächtniskonsolidierung waren geringer, aber vielversprechend. Insgesamt deuteten die Daten auf einen altersunabhängigen Effekt der hypnotischen Suggestionen auf die Tiefschlaferweiterung hin. Sie unterstützen außerdem die Annahme, dass Tiefschlaf präfrontale Areale funktional restauriert und der Gedächtniskonsolidierung zu Gute kommt. Für künftige Studien wird vorgeschlagen, hypnotis- che Suggestionen zur Vertiefung des Schlafs mit der Induktion von Gedächtnisreaktivierungen während dieser Schlafstufe zu kombinieren, um die Gedächtniskonsolidierung bei älteren Erwachsenen weiter zu verbessern. Zusammenfassend untersuchen die drei Manuskripte dieser Dissertation die Beziehung zwis- chen Schlaf und Gedächtnis auf der theoretischen und der praktischen Ebene. Eine Studie klärt die Rolle von Reaktivierungen im REM Schlaf für die Festigung deklarativer Gedächtnisinhalte und zwei Studien bezeugen die altersunabhängige Wirksamkeit hypnotischer Suggestionen zur Erhöhung von SWS und SWA anhand polysomnographischer Daten. Dank dieser Erkenntnisse kann die Empfehlung, Hyp- nose als nichtmedikamentöse Technik zu nutzen, um den Schlaf zu vertiefen, subjektive Schlafqualität zu erhöhen und kognitive Fähigkeiten bei älteren Erwachsenen positiv zu beeinflussen auf objektiv und experimentell kontrollierte Daten gestützt werden. Dieser Forschungssparte wohnt ein großes Potential inne, Altersprozesse in wesentlichen Bereichen des Lebens und der Gesundheit positiv zu beeinflussen. Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-111343 Dissertation Published Version Originally published at: Cordi, Maren. Improving sleep and cognition in young adults and the elderly. 2014, University of Zurich, Faculty of Arts. 2 Improving Sleep and Cognition in Young Adults and the Elderly Thesis (cumulative thesis) Presented to the Faculty of Arts and Social Science of the University of Zurich for the Degree of Doctor of Philosophy by Maren Cordi Accepted in the Autumn Term 2014 on the Recommendation of the Doctoral Committee: Prof. Dr. Björn Rasch, University of Zurich (main advisor) Prof. Dr. Mike Martin, University of Zurich Zürich, 2014 p a g e | II II p a g e | III “It is this potential for plasticity of the relatively stereotyped units of the nervous system that endows each of us with our individuality.” - Eric Kandel, Principles of Neural Science - III p a g e | IV IV Acknowledgements p a g e | V Acknowledgements I would like to thank Prof. Dr. Björn Rasch for giving me the opportunity to write this thesis in his lab of Biopsychology. I particularly appreciate his supportive and motivating nature and his enthusiasm, which inspired the creation of my own ideas and interests, the implementation of which he kindly supported. *** I also want to thank Prof. Dr. Mike Martin for acting as a second supervisor and providing me with some gerontopsychological background and essential organizational information. *** I thank my colleagues for the very friendly and supportive working environment and for having an enjoyable time during conferences. I am also grateful for the support of the Master Students and interns who accompanied me and spent hours and hours in the sleep lab to help me find answers to my research questions. *** Finally, I would like to thank my family, partner and friends for their love and care, establishing a safe and stable background. Thanks for your support and for taking off some of the pressure. V p a g e | VI VI A b s t r a c t p a g e |
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