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Fletcher, P.

Publications and source records attributed to Fletcher, P..

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Influence of prior beliefs on perception in early psychosis: effects of illness stage and hierarchical level of belief

Alterations in the balance between prior expectations and sensory evidence may account for faulty perceptions and inferences leading to psychosis. However, uncertainties remain about the nature of altered prior expectations and the degree to which they vary with the emergence of psychosis. We explored how expectations arising at two different levels - cognitive and perceptual - influenced processing of sensory information and whether relative influences of higher and lower level priors differed across people with prodromal symptoms and those with psychotic illness. In two complementary auditory perception experiments, 91 participants (30 with first episode psychosis, 29 at clinical risk for psychosis, and 32 controls) were required to decipher a phoneme within ambiguous auditory input. Expectations were generated in two ways: an accompanying visual input of lip movements observed during auditory presentation, or through written presentation of a phoneme provided prior to auditory presentation. We determined how these different types of information shaped auditory perceptual experience, how this was altered across the prodromal and established phases of psychosis, and how this relates to cingulate glutamate levels assessed by magnetic resonance spectroscopy. The psychosis group relied more on high level cognitive priors compared to both healthy controls and those at clinical risk for psychosis, and more on low level perceptual priors than the clinical risk group. The risk group were marginally less reliant on low level perceptual priors than controls. The results are consistent with previous theory that influences of prior expectations in psychosis in perception differ according to level of prior and illness phase.\n\nGeneral scientific summaryWhat we perceive and believe on any given moment will allow us to form expectations about what we will experience in the next. In psychosis, it is believed that the influence of these so-called perceptual and cognitive prior expectations on perception is altered, thereby giving rise to the symptoms seen in psychosis. However, research thus far has found mixed evidence, some suggesting an increase in the influence of priors and some finding a decrease. Here we test the hypothesis that perceptual and cognitive priors are differentially affected in individuals at-risk for psychosis and individuals with a first episode of psychosis, thereby partially explaining the mixed findings in the literature. We indeed found evidence in favour of this hypothesis, finding weaker perceptual priors in individuals at-risk, but stronger cognitive priors in individuals with first episode psychosis.

neuroscience

Pleiotropic effects drive correlation between body mass index and cortical myelination

BackgroundEpidemiological studies have reported significant associations between obesity and neurocognitive decline. Understanding these associations will require deeper analyses of how body mass index (BMI) and brain structure are related. Here we explore the extent to which shared genetic factors (pleiotropy) govern the association between BMI and cortical myelination.\n\nMethodsStatistical models of bivariate heritability were applied to structural MR image data from a cohort of monozyogotic and dizygotic twins. Estimates of phenotypic and genetic correlation between BMI and cortical myelination were derived. A co-twin control design based on monozygotic twins was used to test the hypothesis of a causal relationship between BMI and myelination. The variation in the genetic correlation across the cortex was compared with the average statistical enrichment of genes associated with obesity derived from data from the Allen brain atlas.\n\nResultsStatistically significant phenotypic and genetic correlation between BMI and cortical myelination was observed across the cortex. Taking the heritability of each trait into account, approximately 80% of the phenotypic correlation between the traits was accounted for by shared genetic factors.\n\nIntra-pair differences between traits in monozygotic twins failed to support a causal relationship. Moreover, variation in genetic correlation across the cortex was significantly associated with the statistical enrichment of genes related to obesity.\n\nConclusionsThese results support the hypothesis that pleiotropic effects drive the association between BMI and cortical myelination. This observation may help to explain the co-occurrence of obesity in neurocognitive decline and mental health disorders characterized by changes in myelination and oligodendrocyte function.

neuroscience