Understanding and Enhancing the Therapeutic Function of Sleep

Memories of intense, traumatic and unpleasant experiences are hard to forget. This persistence of so called 'emotional memories' is typically beneficial as it allows us to reflect on significant personal events and respond to future challenges effectively. However, if negative thoughts and experiences dominate our everyday lives, as is the case in major depression, then emotional memories can engulf our autobiographical histories, creating a chronic state of anxiety. Research suggests that sleep is crucial for emotional memory management. Restricted sleep impairs memory performance and psychological stability in healthy adults, while sleep disturbances are commonplace in major depression, affecting up to 90% of patients. A full understanding of the relationship between sleep, memory and emotion is therefore vital for gaining scientific insights into the mind, learning more about the fundamental biology of mental health and disease, and identifying innovative targets for therapeutic intervention.

This research project will systematically investigate the role of sleep in emotional memory management. I will combine experimental psychology, cognitive neuroscience and neurophysiology to understand the mechanisms by which the sleeping brain processes memories of emotional experiences. To optimise the associated, scientific and medical benefits, the planned experiments will involve both healthy adults and patients with major depression.

The starting point is to determine the necessity of sleep for emotional memory management. I will first compare the effects of sleep and sleep deprivation on emotional memory retention, physiological arousal and functional responses in emotional centres of the brain. Importantly, sleep consists of various stages, which each have distinct patterns of brain activity. Therefore, the second step will assess how boosting brain activity in different stages of sleep (via auditory stimulation) influences emotional memory. The third step is concerned with gaining deeper insights into the underlying mechanisms of the brain's emotional memory system. As such, I will use sophisticated brain imaging techniques to examine real-time changes in brain activity as emotional memories are reactivated in sleep.

The transition of scientific research from bench to bedside is contingent on tangible benefits in clinical patients. Therefore, the fourth step will be to evaluate the effects of boosting sleeping brain activity on emotional memory management in patients with major depression. This will offer new headway in disentangling the links between chronic sleep disturbances and emotional memory impairments in psychiatric conditions, and may lay the groundwork for innovative therapeutic interventions.

This research programme has strong potential to generate many societal benefits, both nationally and internationally. The World Health Organisation estimates that there are upwards of 350 million people worldwide suffering from a depressive mood disorder. Better understanding of the role of sleep in emotional memory may lead to new treatments, preventative strategies and diagnostic tools for major depression, potentially reducing the £105 billion annual economic cost of mental illness in England alone. Furthermore, enhancing knowledge of the mechanisms by which sleep supports learning and memory may lead to the development of novel educational aids for adults and children. Importantly, this research will raise public awareness of the value of sleep for memory and psychological stability, translating into better sleep practices and improved health and wellbeing.

Although evidence from healthy adults and clinical patients suggests that sleep deprivation impairs our ability to manage memories of intense emotional experiences, little is known about the role of sleep in emotional memory processing. The proposed research consists of four sections (A to D), which are designed to provide converging evidence on the mechanisms by which emotional memories are supported by sleep. The aim of Section A is to determine the necessity of sleep for emotional memory. To this end, the planned experiments will employ behavioural testing, electrodermal activity (EDA), electrocardiography (ECG) and functional magnetic resonance imaging (fMRI) to compare the brain's ability to manage emotionally salient memories after sleep and sleep deprivation. Section B will proceed to examining the roles of distinct components of sleep. In particular, an auditory stimulation technique will be used to boost the expression of sleeping brain oscillations previously linked to emotional memory. Behavioural testing, EDA, ECG and fMRI will then be employed to determine the emotional memory effects of such oscillatory enhancement. Section C will seek to foster our understanding of the mechanisms by which the sleeping brain supports emotional memory. Intracranial electroencephalography (iEEG) will be used to study interactions between hippocampal oscillations during auditory stimulation, whereas simultaneous EEG-fMRI will be used to study emotional memory reactivation and reinstatement in sleep. Finally, Section D is aimed at evaluating the clinical impacts of enhancing sleeping brain oscillations via auditory stimulation. As such, the experiments of Section B will be repeated in MD patients, opening a potential door to a novel therapeutic intervention. In sum, this research will provide unique insights into the emotional memory function of sleep and, in turn, the fundamental biology of mental health and disease.

The planned research has strong potential to generate societal impact in a number of areas, with a medium- to long-term time scale.

Mental Health: This research will directly contribute to our understanding of the link between sleep and emotional memory management. Many mental illnesses, particularly mood disorders such as major depression (MD), are characterised by severe sleep disturbances. By enhancing knowledge of sleep's role in the mechanisms of mental health and disease, it may be possible to identify novel, sleep-specific targets for therapeutic intervention, potentially reducing the estimated £105 billion annual economic cost of mental illness in England alone. Notably, many of the planned experiments employ auditory brain stimulation to enhance neural oscillations in sleep and investigate the effects for emotional memory processing, both in healthy adults and patients with MD. These experiments may lay the groundwork for new treatments and preventative strategies in the clinical sector, fostering improved health and wellbeing. Broadly speaking, this research will provide unique insights into how the breakdown of sleep relates to the onset of mental illness, symptom severity, recovery rates and risk of relapse.

Education: This research will also advance our understanding of how sleep facilitates the retention of newly-formed memories more generally. This understanding may promote better sleep practices among university students (e.g. through the optimisation of learning schedules and avoidance of the "all-nighter" during exam revision periods). Raising awareness of the roles of distinct sleep parameters that prevail in different periods of the night also has the potential to discourage partial sleep restriction among students with demanding personal routines (e.g. as may arise when trying to balance paid jobs with full-time education). Despite its focus on adults, this research may have important ramifications for primary and secondary education. Previous studies on pedagogical methods for enhancing learning in school have focused on the factors that benefit encoding rather than retention. Demonstrating the importance of sleep for offline memory retention may impact on policymaking regarding the availability of sleep and rest opportunities in the school day.

Wider Public: There is increasing worldwide concern about the impacts of restricted sleep on adults' cognitive capacities and mental health. The United States Centers for Disease Control and Prevention, for example, describe sleep deprivation as a "Public Health Epidemic". This research has strong potential to benefit the wider public in terms of understanding the value of sleep for memory and psychological stability. This may translate into better public sleep practices (e.g. defining set sleep routines), and thus better quality of life. Tangible cognitive and emotional benefits of auditory brain stimulation may translate into commercially available devices or smartphone apps to enhance the affective memory function of sleep.

Research Staff: The postdoctoral researchers and research technician on this project will gain valuable experience in using an array of sophisticated experimental techniques, as well as the full range of academic tasks required for a career in academic research. Departmentally-funded summer bursary students will gain experience in research and the laboratory environment, which is becoming almost a pre-requisite for PhD funding. The opportunities and experiences gained by the staff and students will also be applicable to a number of non-academic employment sectors (e.g., public liaison, communication and social awareness; problem solving; creativity and innovation; application of IT and numeracy).