Abstracts

Rationale:
Successful epilepsy surgery relies on the identification of reliable biomarkers for the epileptic focus. We recently found that short-range functional connectivity in the limbic network is increased in patients with temporal lobe epilepsy (TLE) compared to controls, and that TLE patients show signs of premature cerebral aging in fMRI connectivity patterns. Because recent studies have shown that cortical myelin content correlates with fMRI connectivity, and that MRI myelin can track lifetime plastic changes, we hypothesized that MRI myelin markers may be increased in the limbic network of TLE subjects and be correlated with aging. Here we compared T1w/T2w images (a proxy for myelin content) of cortical gray matter between TLE patients and age-matched controls of the Epilepsy Connectome Project (ECP) and Alzheimer’s Disease Connectome Project (ADCP). Because focal seizures also involve deep brain structures, we also investigated myelin changes in subcortical gray matter. In addition to group differences, we also assessed the relationship between changes in myelin and aging in patients and controls.
Method:
51 TLE patients, 48 healthy controls from the ECP and 37 controls from the ADCP underwent 3T MRI Human Connectome Project (HCP) sequences. Image processing used the standard HCP pipeline and Statistical Parametric Mapping (SPM). Patient group mean age was 40.1 ± 11.4 years and control group mean age was 43.1 ± 16.4 years. T1- and T2-weighted MR images were aligned, segmented, corrected for bias, and combined into T1w/T2w images. We compared both average myelin and correlation between myelin and age in the TLE and control groups using two-sample t-tests in SPM and Statistical Nonparametric Mapping (SnPM) toolboxes. Results were corrected for multiple comparisons at p < 0.05 using family-wise error rate (FWE), at the cluster level in SPM and SnPM, and at the voxel level after probabilistic threshold-free cluster enhancement (pTFCE) in SPM.
Results:
Compared to controls, TLE patients showed increased T1w/T2w intensity in medial temporal and limbic areas and the basal ganglia (surviving FWE in SPM, but not SnPM or pTFCE). Patients also showed a positive relationship between myelin and age in limbic cortex and basal ganglia (FWE significant in SPM, SnPM, and pTFCE), and faster myelin increases with age compared to controls in similar regions (surviving SPM, SnPM and pTFCE). In contrast, controls showed decreasing myelin with age in the thalamus (surviving SPM and pTFCE).
Conclusion:
Compared to controls, TLE patients displayed increased T1w/T2w intensity in the limbic network and basal ganglia, and a positive relationship between age and MRI myelin markers in the same areas. Comparison of controls and patients also revealed that the rate at which myelin increases with age in patients is significantly faster in the limbic network, suggesting maladaptive increases in connectivity possibly favoring accelerated aging and cognitive decline.
Funding:
:Epilepsy Connectome Project Alzheimer's Disease Connectome Project Tiny Blue Dot Foundation