Poster No:
339
Submission Type:
Abstract Submission
Authors:
Leigh Sepeta1, Hua Xie2, Venkata Sita Priyanka Illapani2, Samantha Werner2, Sonya Leikin2, Lauren Reppert3, Arini Bhargava4, Andrei Poliakov5, Hannah Goldstein5, Chima Oluigbo2, Kristina Patrick6, Daniel Drane7, Kartik Reddy8, Don Bearden9, Carla Ammons9, Eswar Damaraju9, Carrie McDonald10, Madison Berl2, William Gaillard2, Mohamad Koubeissi11
Institutions:
1Children's National Hospital, Washington DC, DC, 2Children's National Hospital, Washington, DC, DC, 3Baylor College of Medicine, Houston, TX, 4Carnegie Mellon University, Pittsburgh, PA, 5Seattle Children's, Seattle, WA, 6Seattle Children's Hospital, Seattle, WA, 7Emory School of Medicine, Department of Neurology, Department of Neurosurgery, Atlanta, GA, 8Emory University, Atlanta, GA, 9Children's Hospital of Atlanta, Atlanta, GA, 10University of California, San Diego, San Diego, CA, 11George Washington University, Washington, DC, DC
First Author:
Co-Author(s):
Hua Xie, PhD
Children's National Hospital
Washington, DC, DC
Daniel Drane, PhD
Emory School of Medicine, Department of Neurology, Department of Neurosurgery
Atlanta, GA
Introduction:
Epilepsy affects 1 in 26 individuals, with the highest onset in childhood (Institute of Medicine (US) Committee on the Public Health Dimensions of the Epilepsies, 2012). It is a debilitating neurological disorder affecting millions worldwide. Despite advances in treatment, a significant proportion of patients remain refractory to conventional therapies. Resection can be effective in treating pharmaco-resistant focal epilepsy, such as temporal lobe epilepsy (TLE)(Engel, 1993; Wiebe, 2000), however, it is invasive and carries substantial cognitive risks (Bonelli et al., 2010; Hermann et al., 1995; Janszky et al., 2005; Powell et al., 2008; Wyllie et al., 1998). Therefore, new treatment options are necessary. The piriform cortex is a region implicated in seizure generation and propagation, which has made it a potential therapeutic target (Bayat et al., 2017; Henke et al., 2003; Skopin et al., 2020). Despite its promise, connectivity of this region to the seizure onset zone has not been studied in childhood focal epilepsy.
Methods:
This study leverages the success of collaboration of the epilepsy program at George Washington University (GWU) and Children's National Hospital (CNH), as well our pediatric epilepsy neuroimaging consortium with data from three sites (CNH, Seattle Children's and Emory) to examine piriform connectivity throughout childhood (age 6 to 17) and how this is affected by focal epilepsy. We initially used graph theory metrics during resting-state fMRI in focal epilepsy patients (n=152) and a subset of typically developing controls (TD; n=17; see Figure 1 for details). Firstly, the raw resting-state fMRI data underwent preprocessing and denoising using fMRIprep, including motion correction, slice timing correction, low-pass filtering and normalization to a template MNI space, and smoothed with 6mm full width at half maximum (FWHM) Gaussian kernel. The preprocessed fMRI data were parcellated into ROIs using a Schafer 400 atlas and spherical piriform masks will be created from previously reported coordinates. The timeseries was averaged within each ROI. Functional connectivity was quantified as the correlation between time courses across ROIs within a given subject. We employed Brain Connectivity Toolbox to study the hubness using patients and controls functional connectivity data, where hubness is characterized as the summed nodal degree. We compared the hubness measures of TDs vs children with TLE. We hypothesized that while all participants would show the piriform as a hub (or central node) of connectivity, patients would show atypical hubness in this region.
Results:
Patients with focal epilepsy had altered whole-brain connectivity of the piriform compared to controls (p<0.001), with age positively predicting piriform connectivity (p<0.001). Hippocampal-piriform connectivity was significantly decreased in patients for both left and right hippocampus using 2-sample t tests (p<0.001).
Conclusions:
In our preliminary analyses, we found that children with epilepsy have altered whole-brain connectivity of the piriform compared to controls. Our central hypothesis is that the piriform cortex will be identified as a hub for seizure generation and propagation through fMRI, likely due to its connectivity with the hippocampus, and these results supported that hypothesis. Future analysis will include more patients from the consortium which is important because a better understanding of piriform connectivity will advance our understanding of epilepsy pathophysiology.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Novel Imaging Acquisition Methods:
BOLD fMRI 2
Keywords:
Epilepsy
FUNCTIONAL MRI
1|2Indicates the priority used for review
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Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
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Was this research conducted in the United States?
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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
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Functional MRI
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fMRI Prep
Provide references using APA citation style.
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