Structural disconnection relates to functional changes after temporal lobe epilepsy surgery

Abstract

Epilepsy surgery consists of surgical resection of the epileptic focus and is recommended for patients with drug-resistant focal epilepsy. However, focal brain lesions can lead to effects in distant brain regions. Similarly, the focal resection in temporal lobe epilepsy surgery has been shown to lead to functional changes distant from the resection. Here we hypothesize that there are changes in brain function caused by temporal lobe epilepsy surgery in regions distant from the resection that are due to their structural disconnection from the resected epileptic focus. Therefore, the goal of this study was to localize changes in brain function caused by temporal lobe epilepsy surgery and relate them to the disconnection from the resected epileptic focus. This study takes advantage of the unique opportunity that epilepsy surgery provides to investigate the effects of focal disconnections on brain function in humans, which has implications in epilepsy and broader neuroscience. Changes in brain function from pre- to post-epilepsy surgery were quantified in a group of temporal lobe epilepsy patients (n = 36) using a measure of resting state functional MRI activity fluctuations. We identified regions with significant functional MRI changes that had high structural connectivity to the resected region in healthy controls (n = 96) and patients based on diffusion MRI. The structural disconnection from the resected epileptic focus was then estimated using presurgical diffusion MRI and related to the functional MRI changes from pre- to post-surgery in these regions. Functional MRI activity fluctuations increased from pre- to post-surgery in temporal lobe epilepsy in the two regions most highly structurally connected to the resected epileptic focus in healthy controls and patients-the thalamus and the fusiform gyrus ipsilateral to the side of surgery (PFWE < 0.05). Broader surgeries led to larger functional MRI changes in the thalamus than more selective surgeries (P < 0.05), but no other clinical variables were related to functional MRI changes in either the thalamus or fusiform. The magnitude of the functional MRI changes in both the thalamus and fusiform increased with a higher estimated structural disconnection from the resected epileptic focus when controlling for the type of surgery (P < 0.05). These results suggest that the structural disconnection from the resected epileptic focus may contribute to the functional changes seen after epilepsy surgery. Broadly, this study provides a novel link between focal disconnections in the structural brain network and downstream effects on function in distant brain regions.

Keywords: ALFF; epilepsy; fMRI; structural connectivity; surgery.

Figure 1

Regional ALFF changes from pre- to post-TLE surgery overlap with high structural connectivity to the anterior hippocampus in the ipsilateral thalamus and fusiform gyrus. (A) Region-wise changes in amplitude of low frequency fluctuations (ALFF) from pre- to post-surgery were tested using paired t-tests. Paired t-test effect size (Cohen's d) of regions with P_FWE < 0.05 are shown. Red regions depict post > pre ALFF while blue regions depict pre > post ALFF. Ipsilateral and contralateral are respective to the side of the epileptic focus. (B) Regions with the highest mean structural connectivity to the anterior hippocampus in healthy controls. Ipsilateral and contralateral are respective to the side of the anterior hippocampus. (C) Regions with the highest mean structural connectivity to the anterior hippocampus before surgery in patients with temporal lobe epilepsy (TLE). Ipsilateral and contralateral are respective to the side of the epileptic focus. (D and E) Relationship between pre- to post-surgical change in ALFF and structural connectivity to the anterior hippocampus across all brain regions with (D) depicting the structural connectivity to the anterior hippocampus in healthy controls, while (E) depicts the presurgical structural connectivity to the anterior hippocampus in patients with TLE. Statistics are from Spearman correlations. Regions with significant post-surgical ALFF changes from (A) are circled in red (increases) and blue (decreases). Ipsilateral anterior and medial temporal regions that were largely removed in some patients during surgery were removed from these analyses. Trend lines are based on a linear model and are shown for visualization purposes only. Inf = inferior; SC = streamline count; TTG = transverse temporal gyrus.

Figure 2

Pre- to post-surgical ALFF increases in thalamus and fusiform gyrus and estimation of structural disconnection from the resected epileptic focus. (A) Clusters of amplitude of low frequency fluctuations (ALFF) increases from pre- to post-surgery were localized within the ipsilateral thalamus (top) and fusiform gyrus (bottom) (P_FWE < 0.05, paired t-tests). (B) These clusters were seeded for tractography using presurgical dMRI data. The structural connectivity to the anterior hippocampus was extracted as an estimate of structural disconnection from the resected epileptic focus for each cluster.

Figure 3

ALFF and structural connectivity differences from controls in the thalamic and fusiform clusters. Amplitude of low frequency fluctuations (ALFF) of healthy controls and temporal lobe epilepsy (TLE) both pre- and post-surgery are shown for the thalamic (A) and fusiform (B) clusters. Control distributions reflect mean between left and right regions. Comparisons to controls were performed with two-sample t-tests, while comparisons from pre- to post-surgery were performed with paired t-tests. TLE and healthy control structural connectivity are shown for the thalamic (C) and fusiform (D) clusters, tested with Wilcoxon rank-sum tests. Control depicts mean between right and left hemisphere, while TLE measures are from the hemisphere ipsilateral to the epileptic focus. *P < 0.01, **P < 0.001, ***P < 0.0001, uncorrected. ATL = anterior temporal lobectomy; SAH = selective amygdalohippocampectomy; SC = streamline count.

Figure 4

Pre- to post-surgical ALFF changes in the thalamus (A) and fusiform (B) are related to the estimated structural disconnection from the epileptic focus. Right-tailed Spearman correlation coefficients are shown for all patients together as well as for only patients who underwent a selective amygdalohippocampectomy (SAH). Surgery type was used as a covariate for the correlations across all patients. Trend lines are based on a linear model and are shown for visualization purposes only. ALFF = amplitude of low frequency fluctuations; ATL = anterior temporal lobectomy; SC = streamline count.