Multimodal Imaging of the Salience Network in Schizophrenia
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 unanswere...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
| Published: |
2018
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| Online Access: | https://eprints.nottingham.ac.uk/49739/ |
| _version_ | 1848798065868144640 |
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| author | Kumar, Jyothika |
| author_facet | Kumar, Jyothika |
| author_sort | Kumar, Jyothika |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:13:51Z |
| format | Thesis (University of Nottingham only) |
| id | nottingham-49739 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T20:13:51Z |
| publishDate | 2018 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-497392025-02-28T14:00:11Z https://eprints.nottingham.ac.uk/49739/ Multimodal Imaging of the Salience Network in Schizophrenia Kumar, Jyothika 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. 2018-07-12 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en cc_by_nc_sa https://eprints.nottingham.ac.uk/49739/1/JK_Thesis_Final_Revised.pdf Kumar, Jyothika (2018) Multimodal Imaging of the Salience Network in Schizophrenia. PhD thesis, University of Nottingham. Salience Network; Pathophysiology of schizophrenia; Neuroimaging; Neurochemistry; NMDA receptor hypofunction hypothesis; Oxidative stress |
| spellingShingle | Salience Network; Pathophysiology of schizophrenia; Neuroimaging; Neurochemistry; NMDA receptor hypofunction hypothesis; Oxidative stress Kumar, Jyothika Multimodal Imaging of the Salience Network in Schizophrenia |
| title | Multimodal Imaging of the Salience Network in Schizophrenia |
| title_full | Multimodal Imaging of the Salience Network in Schizophrenia |
| title_fullStr | Multimodal Imaging of the Salience Network in Schizophrenia |
| title_full_unstemmed | Multimodal Imaging of the Salience Network in Schizophrenia |
| title_short | Multimodal Imaging of the Salience Network in Schizophrenia |
| title_sort | multimodal imaging of the salience network in schizophrenia |
| topic | Salience Network; Pathophysiology of schizophrenia; Neuroimaging; Neurochemistry; NMDA receptor hypofunction hypothesis; Oxidative stress |
| url | https://eprints.nottingham.ac.uk/49739/ |