A neuroimaging perspective on the emotional sleepy brain

Sleep has been shown to be important for a number of emotional functions. Brain correlates to the effect of sleep deprivation on emotion have been studied in the last decades and increased amygdala reactivity has been proposed as one possible mechanism. However, existing literature shows inconsistent consequences of sleep loss, both in terms of behavioral outcomes and measures of brain activity. Age is one factor that could modulate effects of sleep deprivation on emotional functions, since both sleep patterns and emotional reactivity change with aging. Beyond changes in amygdala reactivity, changes in the brain’s intrinsic connectivity or immune factors could be possible mechanisms through which insufficient sleep affects specific emotional functions as well as fatigue and sleepiness. The aim of this thesis was to investigate mechanisms underlying effects of insufficient sleep on emotional functions, including emotional contagion, empathy, emotional regulation, and mood, as well as sleepiness and fatigue. The thesis consists of five studies using different brain imaging methods and investigating both younger and older adults. Studies I and III show that one night of restricted sleep was sufficient to cause changes in emotional behavior, i.e. a negativity bias, negative mood, and a decreased ability to regulate emotions (in young). However, increased amygdala reactivity was not shown to be increased after sleep restriction. Study II shows that empathic behavior was affected in older but not in young subjects after sleep restriction. Study IV shows that sleep restriction was associated with increased global signal variability in the brain, as a potential marker of wake-state instability and sleepiness. However, no significant effects on the brain’s default mode network were found. Study V shows that patients with severe seasonal allergy had increased fatigue, sleepiness and disturbed sleep, and signs of peripheral inflammation. However, the study does not implicate increased translocator protein binding, as measured with positron emission tomography, and indicating possible microglia cell activation, as involved in these non-specific symptoms. In conclusion, this thesis shows that restricted sleep is associated with a negativity bias and a decreased ability to regulate emotions, at least in young. Increased global signal variability in the brain’s gray matter could be one possible correlate to the behavioral effects of sleep restriction. However, other brain mechanisms underlying emotional dysfunction related to poor sleep need further investigation, using reliable methods in large samples. LIST OF SCIENTIFIC PAPERS I. Tamm, S. , Schwarz, J., Thuné, H. , Kecklund, G. , Petrovic, P., Åkerstedt, T. , Fischer, H. , Lekander, M. , Nilsonne, G. Effects of partial sleep deprivation on emotional contagion in humans: a combined fMRI and EMG study in young and older individuals (manuscript) II. Tamm S. , Nilsonne G. , Schwarz J., Lamm C. , Kecklund G. , Petrovic P., Fischer H. , Åkerstedt T. , Lekander M. The effect of sleep restriction on empathy for pain: An fMRI study in younger and older adults. Sci Rep. 2017 Sep 25;7(1):12236. III. Tamm, S. , Nilsonne, G. , Schwarz, J., Golkar, A. , Kecklund, G. , Petrovic, P., Fischer, H. , Åkerstedt, T. , Lekander, M. Sleep restriction caused impaired emotional regulation without detectable brain activation changes a functional magnetic resonance imaging study. Royal Society Open Science (accepted). IV. Nilsonne G. , Tamm S. , Schwarz J., Almeida R. , Fischer H. , Kecklund G. , Lekander M. , Fransson P., Åkerstedt T. Intrinsic brain connectivity after partial sleep deprivation in young and older adults: results from the Stockholm Sleepy Brain study. Sci Rep. 2017 Aug 25;7(1):9422. V. Tamm S. , Cervenka S. , Forsberg A. , Estelius J., Grunewald J., Gyllfors P.,. Karshikoff B. , Kosek E. , Lampa J., Lensmar C. , Strand V. , Åkerstedt T. , Halldin C. , Ingvar M. , Olgart Höglund C. , Lekander M. Evidence of fatigue, disordered sleep and peripheral inflammation, but not increased brain TSPO expression, in seasonal allergy: A [(11)C]PBR28 PET study. Brain Behav Immun. 2018 Feb;68:146-157. CONTENTS 1 Preface . 1 2 Theoretical introduction . 2 3 Literature overview . 5 3.1 Sleep . 5 3.2 Sleepiness and fatigue. 6 3.3 Sleep, emotion and cognition . 6 3.4 Emotional contagion . 9 3.5 Empathy. 10 3.6 Emotional regulation . 11 3.7 The aging brain and emotion . 13 3.8 Aging and sleep . 15 3.9 Sleep and resting state connectivity . 15 3.10 Inflammation and sickness behavior . 17 3.11 Sleep and inflammation . 17 3.12 Sleep and depressive symptoms in chronic inflammation . 18 4 Aims . 19 4.1 Overall aim . 19 4.2 Specific aims and hypotheses . 20 4.2. 1 Study 1 . 20 4.2. 2 Study 2 . 20 4.2. 3 Study 3 . 20 4.2. 4 Study 4 . 21 4.2. 5 Study 5 . 21 5 Methods and materials . 23 5.1 Overview of the data collections . 23 5.1. 1 The Sleepy Brain Study . 23 5.1. 2 The RAALLPET study . 28 5.2 Overview of studies I-V . 31 6 Main results. 34 7 Summary of findings . 35 8 Methodological and ethical limitations, advantages and reflections . 38 8.1 Brain imaging methods . 38 8.2 Emotional tasks . 39 8.3 Methods to study empathy . 40 8.4 The type of sleep manipulation . 41 8.5 Reflections on reproducible research . 43 8.6 Ethical considerations . 44 9 General discussion . 46 9.1 Does sleep restriction affect emotional behavior? 46 9.2 What effects does sleep restriction have on measures of brain function? 46 9.3 Variability in brain and behavior after sleep restriction . 47 9.4 Emotional contagion, empathy and emotional regulation in aging . 48 9.5 Does aging affect the response to sleep restriction? 49 9.6 What else causes the inconsistency in the effects of sleep deprivation on emotion? 50 9.7 Sleepiness, depression and fatigue – the role of sleep and inflammation . 50 10 Conclusions . 52 11 Future directions and implications for mental health . 53 12 A look back . 53 13 Acknowledgements . 55 14 References . 58 LIST OF ABBREVIATIONS EEG Electroencephalography EOG Electrooculography EMG Electromyography