Resting-State Functional Connectivity in Treatment-Resistant Idiopathic Generalized Epilepsy
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University of Cincinnati / OhioLINK
2013
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ndltd-OhioLink-oai-etd.ohiolink.edu-ucin13806129372021-08-03T06:19:53Z Resting-State Functional Connectivity in Treatment-Resistant Idiopathic Generalized Epilepsy Kay, Benjamin P. Neurology IGE GGE epilepsy default mode resting state connectivity Three million Americans live with epilepsy at an annual cost of over $12 billion per year. Idiopathic generalized epilepsy (IGE) is a primary seizure disorder that accounts for 15-20% of all epilepsies and is associated with high rates of cognitive and psychiatric comorbidities in addition to seizures. Approximately 20% of IGE patients experience refractory seizures despite appropriate therapy. Uncontrolled seizures are a significant cause of poor quality of life, morbidity, and mortality. Although treatment-resistance is common and associated with poor clinical outcome, there are few reliable biomarkers for it and its neuronal correlates are not well understood. Therefore, the aim of this study was to investigate the neuronal correlates of treatment-resistance using data collected from 100 IGE patients and 40 healthy control subjects.We used simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to measure resting-state functional connectivity, a recent technique for detecting abnormal neuronal connectivity in epilepsy. We found increased connectivity in a thalamocortical circuit thought to give rise to epileptic discharges in IGE patients vs. healthy controls. A separate circuit involving cerebellum, thalamus, basal ganglia, and cortex was found to have reduced connectivity in treatment-resistant vs. responsive IGE patients. This previously unknown cerebellar circuit was not significantly different between IGE patients vs. healthy controls and may be altered specifically in treatment-resistant patients.We also found reduced connectivity in the default-mode network (DMN), a set of brain regions thought to be important for maintaining consciousness. The DMN is deactivated by epileptic discharges, and its inhibition may cause loss of consciousness during seizures. DMN connectivity was found to be reduced in IGE patients vs. healthy controls, and it was further reduced in treatment resistant vs. responsive IGE patients. Loss of DMN connectivity was also correlated with disease duration. Therefore, DMN connectivity may be a biomarker for treatment-resistance. Patients with a high frequency of epileptic discharges were found to have increased connectivity between a motor, seizure-related network and the DMN. This finding provides a plausible mechanism by which the DMN is disrupted in IGE.The discovery of biomarkers for treatment-resistant IGE is clinically important and adds to the scientific understanding of epilepsy. Future studies may further elucidate the mechanisms underlying these altered neuronal circuits, establish a causal relationship between these biomarkers and clinical outcome, and investigate new pharmaceutical agents for the treatment of refractory IGE. 2013 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1380612937 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1380612937 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Neurology IGE GGE epilepsy default mode resting state connectivity |
| spellingShingle |
Neurology IGE GGE epilepsy default mode resting state connectivity Kay, Benjamin P. Resting-State Functional Connectivity in Treatment-Resistant Idiopathic Generalized Epilepsy |
| author |
Kay, Benjamin P. |
| author_facet |
Kay, Benjamin P. |
| author_sort |
Kay, Benjamin P. |
| title |
Resting-State Functional Connectivity in Treatment-Resistant Idiopathic Generalized Epilepsy |
| title_short |
Resting-State Functional Connectivity in Treatment-Resistant Idiopathic Generalized Epilepsy |
| title_full |
Resting-State Functional Connectivity in Treatment-Resistant Idiopathic Generalized Epilepsy |
| title_fullStr |
Resting-State Functional Connectivity in Treatment-Resistant Idiopathic Generalized Epilepsy |
| title_full_unstemmed |
Resting-State Functional Connectivity in Treatment-Resistant Idiopathic Generalized Epilepsy |
| title_sort |
resting-state functional connectivity in treatment-resistant idiopathic generalized epilepsy |
| publisher |
University of Cincinnati / OhioLINK |
| publishDate |
2013 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1380612937 |
| work_keys_str_mv |
AT kaybenjaminp restingstatefunctionalconnectivityintreatmentresistantidiopathicgeneralizedepilepsy |
| _version_ |
1719435106939043840 |