Abstract

BackgroundEpilepsy is one of the most prevalent neurological disorders. It remains medically intractable for about one-third of patients with focal epilepsy, for whom precise localization of the epileptogenic zone responsible for seizure initiation may be critical for successful surgery. Existing fMRI literature points to widespread network disturbances in functional connectivity. Per previous scalp and intracranial EEG studies and consistent with excessive local synchronization during interictal discharges, we hypothesized that, relative to same regions in healthy controls, epileptogenic foci would exhibit less chaotic dynamics, identifiable via entropic analyses of resting state fMRI time series.MethodsIn order to first validate this hypothesis on a cohort of patients with known ground truth, here we test individuals with well-defined epileptogenic foci (left mesial temporal lobe epilepsy). We analyzed voxel-wise resting-state fMRI time-series using the autocorrelation function (ACF), an entropic measure of regulation and feedback, and performed follow-up seed-to-voxel functional connectivity analysis. Disruptions in connectivity of the region exhibiting abnormal dynamics were examined in relation to duration of epilepsy and patients’ cognitive performance using a delayed verbal memory recall task.ResultsACF analysis revealed constrained (less chaotic) functional dynamics in left temporal lobe epilepsy patients, primarily localized to ipsilateral temporal pole, proximal to presumed focal points. Autocorrelation decay rates differentiated, with 100 % accuracy, between patients and healthy controls on a subject-by-subject basis within a leave-one-subject out classification framework. Regions identified via ACF analysis formed a less efficient network in patients, as compared to controls. Constrained dynamics were linked with locally increased and long-range decreased connectivity that, in turn, correlated significantly with impaired memory (local left temporal connectivity) and epilepsy duration (left temporal – posterior cingulate cortex connectivity).ConclusionsOur current results suggest that data driven functional MRI methods that target network dynamics hold promise in providing clinically valuable tools for identification of epileptic regions.

Highlights

  • Epilepsy is one of the most prevalent neurological disorders

  • We identified clusters of voxels that were significantly differently connected to the region exhibiting constrained dynamics in patients relative to controls

  • Connectivity abnormalities correlate with epilepsy duration In linking neural and clinical features, for the latter we focused on duration rather than seizure frequency since our patient sample did not provide significant variance in the latter

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Summary

Introduction

Epilepsy is one of the most prevalent neurological disorders It remains medically intractable for about one-third of patients with focal epilepsy, for whom precise localization of the epileptogenic zone responsible for seizure initiation may be critical for successful surgery. Epilepsy is one of the most prevalent neurological disorders, affecting approximately 50 million people worldwide [1] It is characterized by seizures, resulting from abnormal transient change in the synchronized firing of neurons [2]. The current gold standard for localization of focal regions includes identification of an epileptogenic zone on intracranial EEG recordings combined with postoperative seizure freedom following its resection; invasive pre-surgical workup carries additional risks and has been associated with complications in about 23 % of patients [5]. The development of noninvasive techniques capable of accurately localizing epileptogenic regions on a subject-by-subject basis will be critical for improving surgical outcomes

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