Martin, Ingrid Marie; (2025) Hippocampal-Prefrontal Network Oscillations in Schizophrenia and Anxiety. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Theta band oscillations and phase coupling in the hippocampal- medial prefrontal cortex (HPC-mPFC) network play an important role in memory and emotion regulation which well-documented in animal models, but their role in human cognition and psychiatric disorders requires further clarification. This thesis utilizes Magnetoencephalography to investigate theta frequency changes in two different tasks: a contextual fear learning task and an associative memory and inference paradigm. In the first study, healthy participants exhibited increased right HPC theta power when approaching potential threat, which was related to subjective ratings of threat. Additionally, mPFC theta power was increased when approaching safety, reflecting differential roles for these regions in processing threat and safety cues. The differentiation of theta power between threat and safety was positively correlated with anxiety levels, suggesting that theta oscillations play a critical role in regulating contextual fear responses and may relate to individual differences in anxiety. In the second study, patients with Schizophrenia showed significant impairments on recognition memory, including increased rates of false alarms. They also showed impairments on both direct and indirect association tests compared to healthy controls. Both groups displayed increased mPFC theta power and mPFC-HPC theta coupling during the encoding phase of the task. However, during retrieval, patients exhibited a marked loss of mPFC-HPC theta phase coupling. The findings of this thesis build on rodent studies of HPC-PFC function, demonstrating comparable and different theta dynamics in human cognition. Furthermore, this research contributes to our understanding of the role of HPC-PFC network dysfunction in Schizophrenia. Together, these studies offer important insights into the neural mechanisms underlying fear, memory, and psychosis, with implications for advancing therapeutic developments in psychiatric disorders such as Schizophrenia.

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