Biology subjects

Murray, G.

Publications and source records attributed to Murray, G..

4 recordsLinked to original sources

bioRxiv2018

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↗

bioRxiv2018

Meta-analytic evidence for the plurality of mechanisms in transdiagnostic structural MRI studies of hallucination status

BACKGROUNDHallucinations are transmodal and transdiagnostic phenomena, occurring across sensory modalities and presenting in psychiatric, neurodegenerative, neurological, and non-clinical populations. Despite their cross-category occurrence, little empirical work has directly compared between-group neural correlates of hallucinations.\n\nMETHODSWe performed whole-brain voxelwise meta-analyses of hallucination status across diagnoses using AES-SDM, and conducted a comprehensive systematic review in PubMed and Web of Science until May 2018 on other structural correlates of hallucinations, including cortical thickness and gyrification.\n\nFINDINGS3214 abstracts were identified. Patients with psychiatric disorders and hallucinations (eight studies) exhibited reduced gray matter (GM) in the left insula, right inferior frontal gyrus, left anterior cingulate/paracingulate gyrus, left middle temporal gyrus, and increased in the bilateral fusiform gyrus, while patients with neurodegenerative disorders with hallucinations (eight studies) showed GM decreases in the left lingual gyrus, right supramarginal gyrus/parietal operculum, left parahippocampal gyrus, left fusiform gyrus, right thalamus, and right lateral occipital gyrus. Group differences between meta-analyses were formally confirmed and a jackknife sensitivity analysis established the reproducibility of results across nearly all study combinations. For other measures (28 studies), the most consistent findings associated with hallucination status were reduced cortical thickness in temporal gyri in schizophrenia and altered hippocampal volume in Parkinsons disease and dementia.\n\nINTERPRETATIONDistinct patterns of neuroanatomical alteration characterize hallucination status in patients with psychiatric and neurodegenerative diseases, suggesting a plurality of anatomical signatures. This approach has implications for treatment, theoretical frameworks, and generates refutable predictions for hallucinations in other diseases and their occurrence within the general population.\n\nFUNDINGNone.\n\nResearch in contextO_ST_ABSEvidence before this studyC_ST_ABSThere is increasing recognition that hallucinations occur beyond the archetype of schizophrenia, presenting in other psychiatric disorders, neurological and neurodegenerative conditions, and among the general population. Not only are hallucinations a transdiagnostic phenomenon, but also the experience of hallucinating is phenomenologically diverse, varying in modality, content, frequency, and affect. It has been suggested that no one type of hallucination is pathognomic to any one disorder, but rather that hallucinations may exist on a continuum. However, limited research has been done to directly compare the underlying neuroanatomy of hallucinations between different disorders. With this aim, we conducted a meta-analysis and systematic review of structural MRI studies comparing individuals who experience hallucinations with those who do not, to investigate the brain morphology related to the transdiagnostic presentation of hallucinations. We searched PubMed and Web of Science with no start date limit, up to May 2018 using the keyword combination (hallucinat*) AND (MRI OR magnetic resonance imaging OR morphology OR voxel?based OR morphometr* OR neural correlate OR structur*). We included only studies with a within-group no-hallucination control to tease out structural changes specific to hallucinations from effects of the broader pathology. Neuroimaging meta-analyses were conducted on studies performing whole-brain voxelwise gray matter differences, while studies assessing other structural correlates were qualitatively synthesized.\n\nAdded value of this studyThis is the first meta-analysis to illustrate the brain structural correlates of hallucination occurrence derived from T1-weighted MRI, and to do so in a comparative manner across clinical groups. We identified two distinct gray matter substrates for hallucination presence in psychiatric compared to neurodegenerative diseases, which we hypothesise constitute at least two distinct mechanisms. In addition, we qualitatively assessed other structural neuroimaging studies over a variety of morphometric indices. We therefore provide a complete characterization of current knowledge of the brain morphology associated with hallucinations across clinical status and modality.\n\nImplications of all the available evidenceOur findings show at least two structural substrates that link to the hallucinatory experience. This informs theoretical work on hallucinations which have to date been limited in generating unifying direction-specific predictions of brain structure and function. Understanding the plurality of anatomical signatures of hallucinations may also inform treatment strategies. We predict that other disorders in which patients experience hallucinations can be categorised by our approach based on the broader phenotype; for example, hallucinations in personality disorder may be of the psychiatric type, and similarly for early onset hallucinations in the general population, whilst later onset will be neurodegenerative. Moreover, by differentiating the mechanisms of hallucinations we recommend the contextualising of research by the appropriate phenotype.

neuroscience↗

bioRxiv2018

Altered cingulate and substantia nigra/ventral tegmental activation to novelty and emotional salience in antipsychotic naive first episode psychosis patients

Abnormal salience processing has been suggested to contribute to the formation of positive psychotic symptoms in schizophrenia and related conditions. Previous research utilising reward learning or anticipation paradigms has demonstrated cortical and subcortical abnormalities in people with psychosis, specifically in the prefrontal cortex, the dopaminergic midbrain and the striatum. In these paradigms, reward prediction errors attribute motivational salience to stimuli. However, little is known about possible abnormalities across different forms of salience processing in psychosis patients, and whether any such abnormalities involve the dopaminergic midbrain. The aim of our study was, therefore, to investigate possible alterations in psychosis in neural activity in response to various forms of salience: novelty, negative emotion, targetness (task-driven salience) and rareness/deviance. We studied 14 antipsychotic naive participants with first episode psychosis, and 37 healthy volunteers. During fMRI scanning, participants performed a visual oddball task containing these four forms of salience. Psychosis patients showed abnormally reduced signalling in the substantia nigra/ventral tegmental area (SN/VTA) for novelty, negative emotional salience and targetness; reduced striatal and occipital (lingual gyrus) signalling to novelty and negative emotional salience, reduced signalling in the amygdala, anterior cingulate cortex and parahippocamal gyrus to negative emotional salience, and reduced cerebellar signalling to novelty and negative emotional salience. Our results indicate alterations of several forms of salience processing in patients with psychosis in the midbrain SN/VTA, with additional subcortical and cortical regions also showing alterations in salience signalling, the exact pattern of alterations depending on the form of salience in question.

neuroscience↗

bioRxiv2017

Cost evaluation during decision making in patients at early stages of psychosis

Jumping to conclusions during probabilistic reasoning is a cognitive bias reliably observed in psychosis, and linked to delusion formation. Although the reasons for this cognitive bias are unknown, one suggestion is that psychosis patients may view sampling information as more costly. However, previous computational modelling has provided evidence that patients with chronic schizophrenia jump to conclusion because of noisy decision making. We developed a novel version of the classical beads-task, systematically manipulating the cost of information gathering in four blocks. For 31 individuals with early symptoms of psychosis and 31 healthy volunteers, we examined the numbers of draws to decision when information sampling had no, a fixed, or an escalating cost. Computational modelling involved estimating a cost of information sampling parameter and a cognitive noise parameter. Overall patients sampled less information than controls. However, group differences in numbers of draws became less prominent at higher cost trials, where less information was sampled. The attenuation of group difference was not due to floor effects, as in the most costly block participants sampled more information than an ideal Bayesian agent. Computational modelling showed that, in the condition with no objective cost to information sampling, patients attributed higher costs to information sampling than controls (Mann-Whiney U=289, p=0.007), with marginal evidence of differences in noise parameter estimates (t=1.86 df=60, p=0.07). In patients, individual differences in severity of psychotic symptoms were statistically significantly associated with higher cost of information sampling (rho=0.6, p=0.001) but not with more cognitive noise (rho=0.27, p=0.14); in controls cognitive noise predicted aspects of schizotypy (preoccupation and distress associated with delusion-like ideation on the Peters Delusion Inventory). Using a psychological manipulation and computational modelling, we provide evidence that early psychosis patients jump to conclusions because of attributing higher costs to sampling information, not because of being primarily noisy decision makers.

neuroscience↗