Fear Memories and Extinction Memories: Neurophysiological Indicators and the Role of Estradiol and Extinction Timing
Creators: name: Bierwirth, Philipp
Publisher: name: Universität Osnabrück
Year: 2022
Subjects: subject: Fear memories
subject: Extinction memories
subject: Fear conditioning
subject: Fear extinction
subject: Neural oscillations
subject: Estradiol
subject: Extinction timing
subject: 150 - Psychologie

description: Fear memories are necessary to initiate anticipatory fear responses when we are confronted with cues that predict an impending threat. However, when a cue no longer predicts threat, an extinction memory is formed that actively inhibits the expression of the fear memory. Failure to acquire, consolidate, or recall extinction memories causes fear memory expression (i.e., fear responding) in the absence of threat, which is a hallmark characteristic of most anxiety-related disorders and post-traumatic stress disorder (PTSD). Of further importance, these disorders occur approximately twice as often in women than men, which is thought to partially rely on sex hormone mediated differences in fear extinction. Moreover, deficits in extinction memory processing can also hinder the success of extinction-based exposure therapy, which is commonly used to treat these disorders. Thus, a better understanding of the factors determining the quality of extinction memories is of utmost importance. The present thesis focuses on three of these factors including the female sex hormone 17β-estradiol (E2), fear extinction timing, and the noradrenergic arousal system. To examine the role of E2 (Manuscript 1; low E2 levels or high E2 levels) and fear extinction timing (Manuscript 2; either immediately or delayed after the initial fear memory formation), we used a special differential fear conditioning procedure that allowed us to separately assess fear memories and extinction memories via peripheral arousal responses (measured via skin conductance responses [SCR]) and, most importantly, via central neurophysiological indicators (measured via electroencephalography [EEG]). Concerning EEG parameters, we were especially interested in neural oscillations (especially in the theta and gamma range). To further advance the understanding of the neurophysiological foundations of both memory systems, we also aimed at disentangling oscillatory and non-oscillatory brain activity (Manuscript 2). Moreover, the crucial role of the noradrenergic arousal system for the quality of extinction memories is highlighted in a review of relevant rodent and human studies (Manuscript 3). By using the described multi-methodological approach, we were able to demonstrate for the first time that peripheral arousal as well as fear-related theta oscillations are sensitive to E2. This was indicated by less fear responding (attenuated peripheral arousal and attenuated theta oscillations) during the recall of fear and extinction memories under high peripheral E2 levels (Manuscript 1). Concerning the role of fear extinction timing, we demonstrate that delayed extinction is advantageous over immediate extinction in reducing peripheral arousal during the recall of the extinction memory (Manuscript 2). Additionally, by disentangling oscillatory and non-oscillatory brain activity, we demonstrate for the first time that oscillatory and non-oscillatory brain activity is sensitive to fear expression. Moreover, by reviewing different rodent and human studies, we highlight the important role of noradrenergic arousal for the recall of extinction memories and, importantly, provide a detailed mechanistic framework of how extinction deficits might be caused after immediate extinction (Manuscript 3). In sum, the present thesis underscores the important role of E2, fear extinction timing, and the noradrenergic system for the recall quality of fear memories and extinction memories in humans.