Lowther, Millie; (2024) The effect of common interventions on the cognitive and neural mechanisms underlying negative bias in anxiety. Doctoral thesis (Ph.D), UCL (University College London).

Text Thesis_MillieLowther.pdf - Accepted Version Access restricted to UCL open access staff until 1 October 2025. Download (17MB)

Abstract

This thesis investigates the neural and cognitive mechanisms driving negative bias within anxiety and mood disorders, aiming to elucidate the impact of common interventions on these mechanisms. Negative bias is a core feature of anxiety and mood disorders, contributing to the development and maintenance of symptoms, and modification of negative bias is thought to be a mechanism underlying treatment response. This thesis specifically focuses on pessimistic interpretation of ambiguity, which is relatively understudied and the cognitive and neural mechanisms underlying this type of negative bias are not well understood. Throughout the thesis, I use a translational task to measure interpretation of ambiguity in order to bridge the gap between basic and clinical research. The first experimental chapter explores the neural circuitry underlying interpretation of ambiguity in healthy controls, using fMRI. A smaller discovery sample is used for exploratory analyses, and results are replicated in an independent larger sample. The second experimental chapter compares the neural circuitry underlying task behaviour in individuals with generalised anxiety disorder symptoms and asymptomatic controls. The third study investigates how escitalopram (a Selective Serotonin Reuptake Inhibitor), compared to placebo, modulates this bias and the underlying neural circuitry, and the fourth investigates how Cognitive Behavioural Therapy modulates the bias. The final experimental chapter investigates the cognitive mechanisms contributing to bias in the task, with a focus on potential feedback-based learning processes. The general discussion chapter discusses these findings in relation to contemporary models of antidepressant action and cognitive behavioural therapy, considering implications of the results, limitations of the work presented, and possible future directions.

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