Semantic priming, schizophrenia and the ketamine model of psychosis

Abstract

The central aim of the studies presented in my thesis was to investigate the modulation of semantic memory function and its neural correlates in relation to schizophrenia. Semantic information is stored information that is impersonal, and includes knowledge of words and their meaning, and general knowledge about the world. Semantic memory deficits are thought to underlie core symptoms of schizophrenia, including delusions, thought disorder and alogia. The semantic priming (SP) paradigm has been used extensively to assess semantic memory function. In SP experiments, healthy individuals usually respond faster to target words (e.g. atlas) when these are preceded by semantically related prime words (e.g. map) than when preceded by unrelated prime words (e.g. chess)—referred to as the SP effect. My thesis combined several approaches, using SP as the main tool. First, a behavioural study was conducted with patients with schizophrenia. Second, two neuroimaging experiments investigated modulation of neural correlates of SP in schizophrenia. Last, two studies utilised the ketamine model of psychosis in healthy volunteers to investigate: (i) the effects of acute ketamine administration on semantic memory function in drug‐naïve participants, and (ii) the effects of repeated ketamine administration, seen in those who use ketamine recreationally. In summary, three key findings indicate that the employment of conscious strategies during semantic processing is impaired (i) by acute ketamine administration to healthy volunteers, and (ii) in schizophrenia patients as indicated firstly by behavioural results, and (iii) secondly by altered prefrontal haemodynamic activation. None of my studies found any modulation of SP when strategic influences were limited i.e. under automatic conditions. My findings suggest that the disrupted semantic processing in schizophrenia is associated with the modulation of the so‐called ‘executive functions’ and prefrontal haemodynamic responses. Future research should explore whether or not this impairment is specific to semantic memory processing