Multiscale Functional Deviation Mapping in Temporal Lobe Epilepsy
Poster No:
278
Submission Type:
Abstract Submission
Authors:
Ke Xie1, Jessica Royer1, Ella Sahlas1, Judy Chen1, Alexander Ngo1, Thaera Arafat1, Yigu Zhou1, Raúl Rodríguez-Cruces1, Raluca Pana1, Alexander Weil2, Dewi Schrader3, Zhiqiang Zhang4, Luis Concha5, Andrea Bernasconi1, Neda Bernasconi1, Boris Bernhardt1
Institutions:
1McGill University, Montreal, QC, 2Sainte-Justine University Hospital Centre, Montreal, QC, 3British Columbia Children's Hospital, Vancouver, BC, 4Nanjing University School of Medicine, Nanjing, Jiangsu, 5Universidad Nacional Autónoma de Mexico, Mexico, Queretaro
First Author:
Co-Author(s):
Introduction:
Temporal lobe epilepsy (TLE) is the most prevalent pharmaco-resistant focal epilepsy. Increasing number of studies highlight variability in the distribution and severity of whole-brain brain structural and functional anomalies associated with this condition. Heterogeneity challenges the understanding of disease mechanisms and the design of individual clinical predictors. Indeed, conventional case-control analyses may obscure individual differences as they rely on group averages. This study assessed inter-individual variability of spatial patterns of brain function at rest using normative modeling across multiple scales of brain organization applied to multisite data.[1]
Methods:
We analyzed 3T MRI data from 305 individuals with unilateral TLE (142 male; mean age ± SD = 31.5±10.5 years [16–68]; 156 with a left-sided focus) and 300 age- and sex-matched healthy controls (153 male; mean age ± SD = 29.3±8.0 years [17–60]) aggregated three independent sites (Figure 1A). To assess cortical functions at local, regional and global levels, we calculated signal variability (SV), regional homogeneity (ReHo), and node strength (NS) at the node level from resting-state fMRI time series (Figure 1B). For each fMRI metric and brain region, a W-score map was generated for each patient using the healthy control group as a reference (Figure 1C). With a mean value of 0 and a standard deviation of 1 relative to the control group, the W-score is analogous to the Z-score but adjusted for age and sex. A cut-off of 2 standard deviations (i.e., |W-score| ≥ 1.96, corresponding to the 97.5th and 2.5th percentiles) was applied to identify regions of extreme deviations and group-level prevalence maps were created.[2]
Results:
Compared to healthy controls, the median proportion of regional deviations of signal variability, regional homogeneity, and node strength in the TLE group was 9.5%, 7.5%, and 5.9%, respectively (Figure 2A). The temporal, parietal, and occipital lobes showed the highest deviations for signal variability and regional homogeneity, while the parietal and insular lobes had the highest deviations for node strength. These deviations were more pronounced ipsilateral to the seizure focus. Spatial correlations were observed only between signal variability and regional homogeneity, suggesting that these fMRI metrics provide distinct information (Figure 2B). Aggregation of the three metrics through multivariate Mahalanobis distance revealed a diffuse pattern of functional deviations across the cortex in TLE patients (median = 23.1%, Figure 2C), with the highest prevalence in both temporal lobes. Findings were consistent across all sites (rho > 0.39, Pspin < 0.001). Patients with MRI-informed hippocampal atrophy (61.3%) exhibited more extreme deviations, particularly in the ipsilateral temporal lobe, compared to those with normal hippocampal volume. Similarly, patients with longer disease duration (median = 12 years) had more extreme deviations in the ipsilateral temporal and insular lobes than those with shorter duration.
Conclusions:
By leveraging large, multi-site resting-state fMRI data and normative modeling, this study mapped cortex-wide prevalences of multiscale functional alterations in patients with TLE. Peak prevalences in medial and lateral temporal regions reinforce their role as disease epicenters, while associations to hippocampal atrophy and disease duration indicate determinants of patient-to-patient phenotypic variations. Our findings provide new evidence on the spectrum of multiscale functional imbalances in TLE, and may ultimately guide the development of individualized therapeutic targets.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems 2
Normal Development
Keywords:
Cortex
Epilepsy
FUNCTIONAL MRI
Modeling
1|2Indicates the priority used for review
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2. Bethlehem, R.A.I. (2020). A normative modelling approach reveals age-atypical cortical thickness in a subgroup of males with autism spectrum disorder. Commun Biol, 3(1), 486.