Abstracts

Rationale: In addition to recurrent seizures, patients with focal epilepsy can experience neurocognitive deficits, including decreased attention, executive function, and concentration. These neurocognitive can greatly affect the quality of life for many patients. Neuromodulation of subcortical networks has demonstrated preliminary success in the restoration of consciousness for consciousness-impairing seizures and similar strategies may aid in improving neurocognitive functioning in patients with focal epilepsy. The Extended Network Inhibition Hypothesis posited that subcortical-to-neocortical networks may contribute to these neurocognitive deficits, but prior studies have been confounded by arousal level, termed vigilance. Thus, we sought to analyze subcortical networks while controlling for vigilance state to identify neuromodulation targets for neurocognition in focal epilepsy.


Methods: 20-minutes of resting-state functional MRI (fMRI) data were obtained for 46 age-matched patients with focal epilepsy and healthy controls. Vigilance was computed using an fMRI based template for all windows, with high and low vigilance windows selected for analysis. These data were parcellated into subcortical and cortical regions with the Harvard-Oxford atlas and a patient-specific atlas of nucleus basalis of Meynert (NBM), a key subcortical nucleus. Functional connectivity was computed between all regions using a sliding window technique with a 2-minute length and 2-second stride. The first 10 windows and the last 10 windows of each fMRI acquisition sequence were excluded. Degree, a network measure of the number of connections of a brain region, was used to assess connectivity of subcortical arousal structures.


Results: We found that degree of the ipsilateral NBM was increased in the high vigilance state in patients (paired t-test, p=0.007), but not for controls (p=0.301, Fig. 1A-B). This may represent decreased activating output from subcortical arousal structures. Additionally, we found that the NBM degree is lower in patients than controls in the low vigilance state (p=0.005), but not in the high vigilance state (p=0.150, Fig. 1C-D). This may indicate that patients have decreased activation of subcortical structures at baseline which may contribute to long-term neurocognitive deficits.


Conclusions: Impaired neurocognition can be devastating to patients with epilepsy and neuromodulation of subcortical networks may help these patients. We found that subcortical networks are disrupted in patients during low vigilance states but begin to resemble healthy controls in high vigilance states. This suggests that subcortical networks function abnormally in patients with epilepsy and these subcortical network abnormalities may be related to vigilance state. Such work may lead to identification of targets for neuromodulation to improve neurocognitive deficits.


Funding: This work was funded by NIH grants T32EB021937, T32GM007347, F31NS120401, R01NS112252, R0INS110130, and R01NS108445