Neuroimaging and psychophysiological markers of fear-related disorders

Pöhlchen, Dorothee (2023): Neuroimaging and psychophysiological markers of fear-related disorders. Dissertation, LMU München: Medizinische Fakultät

Abstract

Fear-related disorders such as panic disorder, specific phobias, or post-traumatic stress disorder, are highly burdensome and prevalent, making research on their pathogenic mechanisms an imperative. One of the central etiologic models of fear-related disorders is that they arise and manifest based on differences in associative fear-learning mechanisms, presenting a unifying mechanism underlying currently distinct diagnoses. This suggests that capturing learning-related deficits indicates pathology and may thereby serve as an informative diagnostic biomarker. Importantly, no studies up to date have compared different psychophysiological readouts regarding their ability to index specific fear-conditioning subprocesses with regard to fear-related pathology. Consequently, this thesis aimed at uncovering learning-related psychophysiological markers of fear-related disorders. In the first study of this thesis, patients with fear-related disorders and healthy controls showed similar learning trajectories and there was also no evidence for a dimensional association between the severity of the disorder and learning or memory-related markers. In the context of an increasing number of studies reporting similar null findings, our results therefore question the diagnostic validity of the associative fear learning model of fear-related disorders. In the second study of this thesis, patients with fear-related disorders and healthy controls were compared regarding their startle reflex, a basal measure of threat reactivity if probed in an aversive context. Patients with fear-related disorders showed a significantly faster initiation of the startle reflex. As startle under threat depends on modulatory inputs of the amygdala and as shorter startle latencies were associated with smaller amygdala volumes, patients with fear-related disorders may be characterized by an increased readiness, or hyperarousal, of amygdala-modulated startle circuits. The third study of this thesis investigated fear memory formation using an experimental trauma film paradigm in healthy participants, increasing the ecological validity of the classical fear conditioning setups used in the first two studies. There was no evidence for learning-related differences in predicting intrusion formation or loss of contextual memory, two core mnemonic symptoms of post-traumatic stress disorder. However, hippocampal deactivation towards highly aversive films predicted less severe intrusive memory formation. Such a distinct hippocampal stress-related signature may therefore be a correlate of adaptive stress signaling. Together, the results of all three studies speak against learning-related differences as key characteristics of fear-related pathology and thereby against one of the dominant theories on the emergence and maintenance of fear-related disorders. Even if small differences in fear-conditioning existed, they would therefore be too small to be suited as a cross-diagnostic biomarker. Instead, results provide evidence for a sympathetic hyperarousal-account of fear-related disorders. Our findings therefore suggest a paradigm shift away from very specific fear-conditioning paradigms toward more basic fear-eliciting paradigms that prioritize the extraction of stable and reliable biological markers.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 26. Mai 2023
• 1. Bericht­erstatter:in: Binder, Elisabeth