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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Sensory and motor networks in psychotic disorders: from brain structure and function to phenomenology

Alternative title: Sanse- og motornett i psykotiske lidelser: fra hjernestruktur og funksjon til fenomenologi

Awarded: NOK 8.6 mill.

Psychotic disorders disrupt the core of our sense of reality, and include experiences such as hallucinations and delusions, feelings of unrealness, and of being overwhelmed by perceptual stimuli. Many of these symptoms can be understood as deficits in sensory processing. Despite the immense costs of these disorders - both for affected individuals and society - decades of extensive research have failed to identify the underlying mechanisms, severely hindering the development of new and effective treatments. One promising causal factor in psychosis is aberrant brain myelination. Myelin is a fatty white substance surrounding nerve cells and is of crucial of importance for the propagation of electric signals in the nervous system. However, while there is ample evidence of both myelination deficits and sensory processing deficits in psychotic disorders, it is unknown how they relate to each other, and whether they constitute a common pathophysiological mechanism for a specific subgroup of patients. We propose that disruptions in basic sensory processing - caused by temporal dys-regulation (or de-synchronization) of neural activity due to altered myelination within and between primary sensory areas of the brain - may provide such a link between brain anatomy and psychotic experiences.

Psychotic disorders disrupt the core of human experience, and the cost for affected individuals and society is high. There is evidence of both myelination deficits and sensory processing deficits in psychotic disorders, but it is unknown how they relate to each other, and whether they constitute a common pathophysiological mechanism for a specific subgroup of patients. Since 2004 patients with psychosis (n=1600) and control subjects (n=1000) have been investigated thoroughly including clinical, neuropsychological, genetic as well as magnetic resonance imaging (MRI), since 2012 including diffusion tensor imaging assessments within an ongoing project (NORMENT-TOP). Since 2016 subjects are also investigated with electroencephalography (EEG) including three different event-related potential (ERP) and one resting state paradigm. Myelin-related alterations of grey and white matter will be examined by MRI. Potential genetic associations with intracortical myelination will be investigated. EEG auditory paradigms will be analyzed with regard to myelination status in auditory cortical regions, the visual paradigm in conjunction with myelination status in visual cortex and oscillatory resting paradigm will be examined in relation to myelination status of regions with attenuated long-range correlations in patients. Psychotic symptoms already assessed, as well as novel measures capturing more subtle phenomena, will be analysed in relation to EEG and MRI examinations. In order to further test the corollary discharge hypothesis, an ERP button-pressing paradigm and a new functional MRI paradigm, possible to use examining BOLD activation in self-generated versus passive/distorted conditions, will be piloted. The project will give further knowledge about the myelination and delayed corollary discharge hypothesis of psychosis, which may provide targets for new drugs, biomarkers for earlier detection, and better individualization of medical and non-medical treatment.

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FRIMEDBIO-Fri prosj.st. med.,helse,biol

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