Growing evidence suggests that the Salience Network, anchored on the bilateral anterior insula and dorsal anterior cingulate cortex plays a key role in the pathophysiology of schizophrenia. However, several questions regarding the exact nature of these abnormalities in schizophrenia remain unanswered. This thesis examines the neurobiological basis of Salience Network dysfunction in patients with schizophrenia. Specifically, in this work, we use multi-modal neuroimaging techniques to investigate abnormalities in the functioning, connectivity and neurochemistry of the Salience Network in schizophrenia. Chapter 1 introduces the concept of schizophrenia as a disorder of salience and the role of the Salience Network in this context. Chapter 2 describes participant recruitment, data collection and the neuroimaging techniques used in this work. Chapters 3 to 5 present the results from three research studies. In the first study, using functional Magnetic Resonance Imaging (fMRI) and Magnetoencephalography (MEG), we investigate regional brain activity in response to a task designed to engage the Salience Network. We report evidence demonstrating inefficient cerebral recruitment in patients with schizophrenia i.e. aberrant activity in task positive and task negative brain regions; along with reduced beta response to relevant stimuli in the Salience Network. These findings are reported in chapter 3. In chapter 4, we use high resolution 7T Magnetic Resonance Spectroscopy (MRS) and demonstrate that neurochemical abnormalities in schizophrenia vary between patients depending on their clinical status. Specifically, we show that glutathione and glutamate concentrations in the Anterior Cingulate Cortex are prominently reduced in patients with residual schizophrenia. We also provide evidence linking two popular neurochemical theories of schizophrenia – the NMDA receptor hypofunction hypothesis and the theory of oxidative stress. Chapter 5 explores the question of disrupted effective connectivity within the Salience Network in schizophrenia using resting-state fMRI. In this chapter, we report abnormalities in effective connectivity within the Salience Network in patients with schizophrenia. We also demonstrate that these aberrant causal interactions are related to the neurochemical abnormalities reported in chapter 4. Finally, in Chapter 6, we discuss the significance and translational potential of these findings and offer recommendations for future work. Overall, using a multimodal imaging study design and a wide range of measures, this thesis reports novel findings which further our understanding of Salience Network dysfunction in schizophrenia and provides a good foundation for future research studies in this area.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:757387 |
| Date | January 2018 |
| Creators | Kumar, Jyothika |
| Publisher | University of Nottingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.nottingham.ac.uk/49739/ |
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