Investigating the Neural Correlates of Cervical Dystonia and Temporal Discrimination using Neuroimaging based Computational Modelling and Multimodal Pattern Recognition
Citation:
NARASIMHAM, SHRUTI, Investigating the Neural Correlates of Cervical Dystonia and Temporal Discrimination using Neuroimaging based Computational Modelling and Multimodal Pattern Recognition, Trinity College Dublin.School of Engineering, 2020Download Item:
Abstract:
Movement disorders, such as Parkinson s disease and Dystonia, have traditionally been considered as disorders of impaired motor control resulting predominantly from dysfunction of the Basal Ganglia. However, there has been increased recognition lately of associated behavioural, psychiatric, autonomic, and other non-motor symptoms. The sensory aspects include fundamental sensory abnormalities and the effects of external sensory input on the underlying motor abnormality. The Basal Ganglia, Cerebellum, Thalamus, and their connections, coupled with altered sensory input, seem to play a role in abnormal sensorimotor integration. However, the physiological basis of sensory abnormalities, the role of the Basal Ganglia, Cerebellum, and related structures on sensory processing, and their effects on movement disorders is poorly understood.
Dystonia is the third most common movement disorder characterized by sustained muscle contractions and sometimes painful postures. Although an exact prevalence remains a challenge, Primary Dystonia has been estimated with a prevalence of 16.43 per 100,000. In Ireland, it affects 592 individuals, of which 410 are Cervical Dystonia patients. Cervical Dystonia involves muscles of the head, neck and shoulders, with no precise cause attributed to date. A dysfunction in the midbrain network for covert attention has been recently implicated in Cervical Dystonia with the Superior Colliculus as a significant node in this process. Concurrently, the paucity of genetic discovery has stimulated the search for endophenotypes, of which the temporal discrimination threshold has been proposed as a potential mediational endophenotype. However, the neural substrates of abnormal temporal discrimination are poorly understood.
The primary aim of this research was to localize specific regions in the subcortical midbrain network that play a crucial role in the pathomechanisms of Cervical Dystonia, via novel neuroimaging based computational methods. Furthermore, since first-degree relatives harbour sensory abnormalities similar to patients, the objective was to probe the neural substrates of abnormal temporal discrimination in a cohort of unaffected relatives of dystonia patients.
The main findings of this thesis are as follows:
1. Subjects with an abnormal temporal discrimination threshold (patients and unaffected relatives) have a significantly reduced superior collicular activation to looming visual stimuli. As TDT Z-score worsens, superior collicular activation diminishes, indicating the crucial role of this node in the shared pathomechanisms of both Cervical Dystonia and abnormal temporal discrimination.
2. The intrinsic connectivity within the Superior Colliculus as well as between the Substantia Nigra and the Superior Colliculus is significantly altered under the influence of the loom visual stimulus, in subjects with an abnormal temporal discrimination threshold (patients and unaffected relatives). The bottom-up attentional network is dysfunctional, providing evidence for involvement of the midbrain network for covert attention.
3. Local, regional as well as global resting-state connectivity properties are altered in
relatives with abnormal temporal discrimination when compared to relatives with normal temporal discrimination threshold. The existence of differences along with similarities in large-scale network architecture and topology, suggests that these discrepancies may be indicative of a subclinical pre-symptomatic phase due to the expression of an abnormal gene or a protective neuroplastic response to that gene.
4. Multivoxel pattern analysis and multimodal combination of abnormalities in adult-onset idiopathic focal dystonia, facilitate a more sensitive, robust and comprehensive approach towards analyzing this network disorder. An increase in classification performance using a multivariate approach in comparison to the previously employed univariate and unimodal analysis cautiously suggests the need for the existence of both structural as well as functional abnormalities for disorder manifestation.
In conclusion, key insights about Cervical Dystonia pathomechanisms have been uncovered by designing, developing and deploying novel neuroimaging based experimental paradigms, computational models and multimodal pattern analysis. The incorporation of a cohort of unaffected relatives of Cervical Dystonia patients in the investigation has resulted in a more comprehensive assessment of the mediational endophenotype concept in this disorder. Additionally, there is potential in an improved automated diagnosis of dystonia patients via mutlivoxel and multimodal neuroimaging analysis.
Sponsor
Grant Number
Health Research Board (HRB)
Irish Research Council (IRC)
Dystonia Ireland
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https://tcdlocalportal.tcd.ie/pls/EnterApex/f?p=800:71:0::::P71_USERNAME:NARASIMSDescription:
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Author: NARASIMHAM, SHRUTI
Advisor:
Reilly, RichardPublisher:
Trinity College Dublin. School of Engineering. Discipline of Electronic & Elect. EngineeringType of material:
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Full text availableKeywords:
TDT, Pattern Recognition, Multimodal, Cervical Dystonia, AOIFD, NeuroimagingMetadata
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