Presurgical temporal lobe epilepsy connectome fingerprint for seizure outcome prediction.

Temporal lobe epilepsy presents a unique situation where confident clinical localization of the seizure focus does not always result in a seizure-free or favourable outcome after mesial temporal surgery. In this work, magnetic resonance imaging derived functional and structural whole-brain connectivity was used to compute a network fingerprint that captures the connectivity profile characteristics that are common across a group of nine of these patients with seizure-free outcome. The connectivity profile was then computed for 38 left-out patients with the hypothesis that similarity to the fingerprint indicates seizure-free surgical outcome. Patient profile distance to the fingerprint was compared with 1-year seizure outcome and standard clinical parameters. Distance to the fingerprint was higher for patients with Engel III-IV 1-year outcome compared with those with Engel Ia, Ib-d, and II outcome (Kruskal-Wallis, P < 0.01; Wilcoxon rank-sum p corr <0.05 Bonferroni-corrected). Receiver operator characteristic analysis revealed 100% sensitivity and 90% specificity in identifying patients with Engel III-IV outcome based on distance to the fingerprint in the left-out patients. Furthermore, distance to the fingerprint was not related to any individual clinical parameter including age at scan, duration of disease, total seizure frequency, presence of mesial temporal sclerosis, lateralizing ictal, interictal scalp electroencephalography, invasive stereo-encephalography, or positron emission tomography. And two published algorithms utilizing multiple clinical measures for predicting seizure outcome were not related to distance to the fingerprint, nor predictive of seizure outcome in this cohort. The functional and structural connectome fingerprint provides quantitative, clinically interpretable and significant information not captured by standard clinical assessments alone or in combinations. This automated and simple method may improve patient-specific prediction of seizure outcome in patients with a clinically identified focus in the mesial temporal lobe.

Characterization of resting functional MRI activity alterations across epileptic foci and networks.

Brain network alterations have been studied extensively in patients with mesial temporal lobe epilepsy (mTLE) and other focal epilepsies using resting-state functional magnetic resonance imaging (fMRI). However, little has been done to characterize the basic fMRI signal alterations caused by focal epilepsy. Here, we characterize how mTLE affects the fMRI signal in epileptic foci and networks. Resting-state fMRI and diffusion MRI were collected from 47 unilateral mTLE patients and 96 healthy controls. FMRI activity, quantified by amplitude of low-frequency fluctuations, was increased in the epileptic focus and connected regions in mTLE. Evidence for spread of this epileptic fMRI activity was found through linear relationships of regional activity across subjects, the association of these relationships with functional connectivity, and increased activity along white matter tracts. These fMRI activity increases were found to be dependent on the epileptic focus, where the activity was related to disease severity, suggesting the focus to be the origin of these pathological alterations. Furthermore, we found fMRI activity decreases in the default mode network of right mTLE patients with different properties than the activity increases found in the epileptic focus. This work provides insights into basic fMRI signal alterations and their potential spread across networks in focal epilepsy.

Resting-state hippocampal networks related to language processing reveal unique patterns in temporal lobe epilepsy.

OBJECTIVE: Patients with temporal lobe epilepsy (TLE) commonly experience a broad range of language impairments. These deficits are thought to arise from repeated seizure activity that damages language regions. However, connectivity between the seizure onset region in the hippocampus and regions related to language processing has rarely been studied, and could also have a strong impact on language function. The purpose of this study was to use resting-state functional connectivity (FC) measures to assess hippocampal network patterns and their relation to language abilities in patients with right TLE (RLTE), left TLE (LTLE), and healthy controls. METHODS: Presurgical resting-state 3T functional MRI data were acquired from 40 patients with mesial TLE (27 RTLE, 13 LTLE) and 54 controls. The regions of interest were the anterior and posterior bilateral hippocampi and eleven regions grouped by frontal or temporo-parietal locations, including large areas of language-related cortex. FC values were computed with the right/left anterior and posterior hippocampi as the seeds and frontal and temporo-parietal regions as targets. Resting-state lateralization indices were also calculated (LI-Rest), and all FC measures were correlated to neuropsychological language scores and measures related to manifestation of epilepsy including age of onset, duration of disease, monthly seizure frequency, and hippocampal volume. RESULTS: We found significant group differences between the anterior hippocampi and temporo-parietal regions closest to the seizure focus, in which RTLE and LTLE showed stronger connectivity to their contralateral hippocampus, while controls showed similar connectivity to both hippocampi. In addition, LI-Rest demonstrated significantly more right lateralization in LTLE compared to RTLE for temporo-parietal regions only. In LTLE, we found significant associations between stronger hippocampal network resting-state FC and later age of onset and decreased left anterior hippocampal volume. SIGNIFICANCE: The results of our study indicate that the presence of TLE impacts hippocampal-temporo-parietal networks relevant to language processing.