Cognitive and Neural Map Representations in Schizophrenia

Abstract

An ability to build structured cognitive maps of the world may lie at the heart of understanding cognitive features of schizophrenia. In rodents, cognitive map representations are supported by sequential hippocampal place cell reactivations during rest (offline), known as replay. These events occur in the context of local high frequency ripple oscillations, and whole-brain default mode network (DMN) activation. Genetic mouse models of schizophrenia also report replay and ripple abnormalities. Here, I investigate the behavioural and neural signatures of structured internal representations in people with a diagnosis of schizophrenia (PScz, n = 29) and matched control participants (n = 28) using magnetoencephalography (MEG). Participants were asked to infer correct sequential relationships between task pictures by applying a pre-learned task template to visual experiences containing these pictures. In Chapter 3 I show that, during a post-task rest session, controls exhibited fast spontaneous neural reactivation of task state representations that replayed inferred relationships. Replay was coincident with increased ripple power in hippocampus, which may be related to NMDAR availability (Chapter 4). PScz showed both reduced replay and augmented ripple power, convergent with genetic mouse models. These abnormalities were linked to impairments in behavioural acquisition of task structure, and to its subsequent representation in visually evoked neural responses. In Chapter 5 I explore the temporal coupling between replay onsets and DMN activation. I show an impairment in this association in PScz, which related to subsequent mnemonic maintenance of learned task structure, complementing previous reports of DMN abnormalities in the condition. Finally, in Chapter 6, using a separate verbal fluency task, I show that PScz exhibit evidence of reduced use of (semantic) associative information when sampling concepts from memory. Together, my results provide support for a hypothesis that schizophrenia is associated with abnormalities in neural and behavioural correlates of cognitive map representation

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