Dynamic multimodal connectivity analysis of brain networks in focal epilepsy

Vanderbilt University, Nashville TN

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Abstract

PROJECT SUMMARY/ABSTRACT Epilepsy is a debilitating neurological disorder that affects 1% of the population worldwide and temporal lobe epilepsy (TLE) is the most common form. Seizure onset in TLE is typically localized to the mesial temporal lobe, however, patients can suffer from distant effects such as loss of consciousness during seizures (ictally) and neurocognitive deficits between seizures (interictally), both of which impair one’s activities of daily living, ability to work, and quality of life. Prior work investigating these global effects have resulted in the Network Inhibition Hypothesis, which states that focal seizure activity observed with stereotactic electroencephalography (SEEG) spreads to subcortical structures responsible for neocortical activation, resulting in ictal loss of consciousness in focal impaired awareness seizures (FIAS). Studies with functional MRI (fMRI) have provided evidence that the same anatomical areas have abnormal functional connectivity (FC). It thought that recurrent FIAS lead to chronic interictal decreases in subcortical to neocortical FC, but this knowledge gap but this knowledge gap has not been addressed. We aim to relate FC of ictal and interictal states using SEEG (Aim 1). I specifically hypothesize during FIAS ictal FC will decrease in the same anatomical regions as those implicated in interictal FC abnormalities. In addition to recurrent seizures, patients can also have devastating interictal neurocognitive deficits. These widespread neurocognitive deficits suggest that there is a common factor, which is thought to be the subcortical arousal structures. It has been shown that fMRI FC abnormalities of subcortical to neocortical structures are associated with neurocognitive deficits, seizure frequency, and can recover after surgery. While general subcortical to neocortical abnormalities have been outlined, there is a gap in understanding of specific brain networks associated with neurocognitive deficits. This could be due in part to not adequately controlling for arousal state. The high vigilance or “sustained attention” state, is a state of cognitive engagement mediated by subcortical arousal structures which fluctuates at rest. It is associated with subcortical to neocortical FC changes, associated with extratemporal neurocognitive deficits, the state active during neurocognitive testing, and thought to be a confounder for resting-state fMRI by some. We aim to link specific subcortical to neocortical network abnormalities with neurocognitive deficits by controlling for the high vigilance state with fMRI-EEG (Aim 2). I specifically hypothesize that during high vigilance states, patients will have significantly decreased FC within subcortical to neocortical networks compared to controls, that the decrease will be associated with extratemporal neurocognitive deficits, and that the network will recover after successful surgery. This proposed fellowship will provide research training in a collaborative research atmosphere with expert mentors. Research training will be conducted in an environment that combines an academic medical center with a level 4 epilepsy center, world class imaging institute, and engineering all on one campus. Studying multiple modalities to characterize epileptic networks may lead to improved neuromodulation targets for TLE.