Modulating fear: The impact of tDCS on fear extinction memory consolidation during REM sleep

This thesis aims to present a research and analysis project focused on enhancing the consolidation of fear extinction memories, acquired through conditioning, by applying transcranial direct current stimulation (tDCS) during the REM sleep phase. To achieve this, the initial step was to establish a theoretical framework that serves as an introduction, helping to explain the rationale behind this research hypothesis, which could have important clinical implications for the treatment of post-traumatic stress disorder (PTSD) and anxiety disorders. The first chapter focuses on the study of the neural circuits involved in fear, with particular emphasis on the neurophysiological components and their connections to psychopathological aspects. Detailed attention is given to the central role of key structures like the amygdala, hippocampus, and prefrontal cortex in the fear response and the dysfunctions linked to anxiety disorders and PTSD. A discussion will follow on the current treatment options available, both pharmacological and psychotherapeutic, highlighting the limitations of conventional approaches and the need for more effective therapeutic strategies. The second chapter examines the physiology of stress, particularly focusing on the hypothalamic-pituitary-adrenal (HPA) axis and its significance in maintaining homeostasis and responding to stress. The chapter will analyze the mechanisms by which chronic stress can affect the functioning of limbic circuits, leading to significant mental health consequences. In the third chapter, the fear conditioning paradigm will be explored. This is an associative learning process, based on Pavlovian principles, through which organisms learn to associate a neutral stimulus with an aversive event. The chapter will describe the experimental protocols used to study fear conditioning, the phases involved, and the physiological measures employed to quantify conditioned fear responses. The fourth chapter will address the relationship between sleep and memory, with a particular focus on sleep structure and its various stages. It will examine the processes involved in memory consolidation during sleep, analyzing the primary hypotheses regarding the role of different sleep stages in the stabilization of memory traces. In the fifth chapter, the discussion will turn to the use of tDCS during sleep and its significant impact on memory consolidation, with special attention given to its potential in enhancing the extinction of fear memories. Recent studies exploring the effectiveness of tDCS in modulating brain plasticity and reducing fear responses will be reviewed. Finally, the sixth chapter will detail the experimental project carried out, titled "Exploring the effects of tDCS during REM sleep in fear extinction learning." The chapter will outline the experimental procedures and timelines followed, as well as the data analysis methods and a discussion of the findings. This project represents an innovative attempt to use tDCS to strengthen the extinction of fear memories during REM sleep, supported by functional neuroimaging, thereby opening new avenues for the treatment of anxiety disorders and PTSD.