Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.785175
Title: Neuroimaging of epilepsy : disease severity, cognitive comorbidities and endophenotypes
Author: Caciagli, Lorenzo
ISNI:       0000 0004 7970 7171
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Abstract:
Epilepsy is a common neurological disorder complicated by cognitive and psycho- social comorbidities. Magnetic resonance imaging (MRI) investigations characterise brain networks in vivo, providing measurable traits (biomarkers) of pathological processes with biological validity and high reproducibility, thereby shedding light on the pathological mechanisms of epilepsy and its comorbidities. In this PhD thesis, functional and structural MRI have been employed to detect potential biomarkers in relation to three specific domains of epilepsy: (1) disease severity in temporal lobe epilepsy (TLE), (2) cognitive network dysfunction in frontal lobe epilepsy (FLE), and (3) heritable phenotypes (endophenotypes) in the prototypical generalised epilepsy syndrome, juvenile myoclonic epilepsy (JME). The first project focused on determinants of disease severity in TLE: (a) disease progression and (b) secondary generalised (focal to bilateral) tonic-clonic seizures. In Study 1, I applied a meta-analytical approach on previous structural MRI studies in TLE (n > 1500), providing comprehensive evidence for hippocampal and extra- hippocampal cumulative atrophy. In Study 2, I captured functional MRI (fMRI) markers of secondarily-generalised tonic-clonic seizures in TLE, identifying abnormal activation, task-modulated connectivity and network-based centrality of the thalamus. The second project investigated the neural correlates of cognitive dysfunction in FLE. Using neuropsychometry and four fMRI tasks addressing working memory and expressive language, I detected derangements of fronto-temporo-parietal activation, independent of seizure focus lateralisation, and impaired deactivation of task- negative networks. The third project investigated patients with JME and their unaffected siblings to identify imaging endophenotypes of JME, i.e. heritable traits associated with the disease at the population-level, co-segregating in families with affected members. Study 1 validated indicators of motor system activation during language and episodic memory fMRI as suitable endophenotypes. Study 2 investigated structure and function of the mesiotemporal lobe, showing abnormalities of hippocampal morphometry common to patients and siblings and associated with reorganisation of memory fMRI activation, implying prenatal neurodevelopmental mechanisms.
Supervisor: Koepp, M. ; Winston, G. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.785175  DOI: Not available
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