Investigating Epileptic and Functional Networks in Patients with Drug Resistant Focal Epilepsy

National Institute Of Neurological Disorders And Stroke

Investigators

Linked publications, trials & patents

Abstract

Over the past year, we have continued to devote significant effort to this project, continuing to acquire functional and structural neuroimaging data, electroencephalography (EEG) and magnetoencephalography (MEG) data, and clinical and neuropsychological data in patients undergoing clinical pre-surgical evaluations. We have continued our work in developing novel imaging biomarkers for seizure focus lateralization and/or localization. We previously developed an MRI postprocessing method to aid with detection of focal cortical dysplasias, which often lead to seizures and epilepsy. This has continued to prove an important clinical tool for our patients undergoing presurgical evaluation. We are also using similar image processing tools to improve tissue segmentation in structurally abnormal brains and using these segmentations to create improved resection masks in patients who undergo epilepsy surgery. We are working to publish this over the coming year. Over the past year, we primarily focused our imaging research on exploring the utility of arterial spin labeling (ASL) MRI in lateralizing the seizure focus in patients with temporal lobe epilepsy. ASL MRI is a widely available, safe, noninvasive imaging modality used to study cerebral blood flow and perfusion. In our cohort, we found that those with lesional epilepsy on MRI (most often medial temporal sclerosis), show significant hypoperfusion in the medial temporal lobe, particularly in the hippocampus and parahippocampal gyrus, as well as the lateral temporal lobe, primarily driven by asymmetries in the anterior temporal neocortex, compared to healthy volunteers. Although non-lesional TLE patients demonstrate similar degrees of ipsilateral brain perfusion to lesional TLE patients, these findings are less asymmetric, yielding similar asymmetry indices to healthy volunteers, making abnormalities more difficult to detect in this patient group. This work was carried out in collaboration with Lalith Talagala in the NINDS NMR Center Core Facility. Our manuscript describing these findings was published in Epilepsy Research (Rentzeperis et al. 2023). The second goal of this project is related to exploring the relationship between propagation of epileptiform activity and underlying structural and functional networks in individual patients with epilepsy. We have actively participated in an ongoing collaboration with Kareem Zaghloul's lab in the NINDS Surgical Neurology Branch, and their development of a novel method to identify local sources of epileptiform activity during seizures using phase differences observed across electrodes during seizures (Diamond et al., 2021). Over the past year, as described in Diamond et al. 2023, this approach was extended to use differences in time of arrival to also localize potential sources of interictal epileptiform activity. The methods used in this work are based on propagation of epileptiform activity over the gray matter cortical surface in the form of traveling waves. In our lab, we have now developed an approach that allows us to incorporate the additional possibility of white matter propagation of interictal epileptiform activity using MRI diffusion tensor imaging obtained in our cohort of patients. This approach frequently identifies unique and at times more distant potential sources of epileptiform activity. It also highlights that white matter propagation may underlie mislocalization in the setting of sparse electrode sampling using intracranial EEG recordings, with earlier spiking at times occurring distantly from the source due to the faster conduction velocities of white matter versus local traveling wave propagation. This work has been accepted for publication in Brain (Withers et al, 2023), and will appear on next years annual report. Over the past year, we have also devoted significant effort to enhancing our analysis of magnetoencephalography (MEG) recordings in our patient cohort. Compared to invasive EEG recordings, MEG is complementary, retaining excellent temporal resolution and allowing for more widespread coverage across the cortical surface, although only obtained over minutes to hours. Over the past year, we have been able to develop processing pipelines to implement additional source localization techniques, allowing us to compare results in our patient population between the gold standard equivalent current dipole (ECD) approach, areas of resection, and beamforming and dynamic statistical parametric mapping (dSPM) approaches. We are also working to use MEG to increase our understanding of propagation of interictal epileptiform activity, exploring whether traveling wave and white matter propagation can also be observed and used to better understand propagation of this activity and its relationship to structural and functional connectivity patterns. Finally, as part of our ongoing epilepsy imaging study, we have continued to prospectively obtain pre- and post-operative language and resting state functional MRI (fMRI) data. Several of our close collaborators continue to make use of this data over the past year to study both language and memory. Leigh Sepeta, collaborator from Children's National Medical Center, is investigating the use of language fMRI activations to predict memory outcomes following temporal lobe epilepsy surgery and is implementing a novel memory task to further identify potential asymmetries in memory-related activation in the mesial temporal regions. She is also analyzing this fMRI data to explore the presence of gradients of functional connectivity to the hippocampus. Nadia Biassou and her group are also using this data to explore dynamic functional connectivity in relation to language tasks, presenting this work in several posters and talks, and are working to prepare a manuscript describing their findings.