Characterization of postsurgical functional connectivity changes in temporal lobe epilepsy

Abstract

Objective: Seizure outcome after mesial temporal lobe epilepsy (mTLE) surgery is complex and diverse, even across patients with homogeneous presurgical clinical profiles. The authors hypothesized that this is due in part to variations in network connectivity across the brain before and after surgery. Although presurgical network connectivity has been previously characterized in these patients, the objective of this study was to characterize presurgical to postsurgical functional network connectivity changes across the brain after mTLE surgery.

Methods: Twenty patients with drug-refractory unilateral mTLE (5 left side, 10 female, age 39.3 ± 13.5 years) who underwent either selective amygdalohippocampectomy (n = 13) or temporal lobectomy (n = 7) were included in the study. Presurgical and postsurgical (36.6 ± 14.3 months after surgery) functional connectivity (FC) was measured with 3-T MRI and compared with findings in age-matched healthy controls (n = 44, 21 female, age 39.3 ± 14.3 years). Postsurgical connectivity changes were then related to seizure outcome, type of surgery, and presurgical disease parameters.

Results: The results demonstrated significant decreases of FC from control group values across the brain after surgery that were not present before surgery, including many contralateral hippocampal connections distal to the surgical site. Postsurgical impairment of contralateral precuneus to ipsilateral occipital connectivity was associated with seizure recurrence. Presurgical impairment of the contralateral precuneus to contralateral temporal lobe connectivity was associated with those who underwent selective amygdalohippocampectomy compared to those who had temporal lobectomy. Finally, changes in thalamic connectivity after surgery were linearly related to duration of epilepsy and frequency of consciousness-impairing seizures prior to surgery.

Conclusions: The widespread contralateral hippocampal FC changes after surgery may be a reflection of an ongoing epileptogenic progression that has been altered by the surgery, rather than a direct result of the surgery itself. This network evolution may contribute to long-term seizure outcome. Therefore, the combination of presurgical network mapping with the understanding of the dynamic effects of surgery on the networks may ultimately be used to create predictors of the likelihood of long-term seizure recurrence in individual patients after mTLE surgery.

Keywords: MRI; connectivity; epilepsy surgery; functional neuroimaging; functional neurosurgery; temporal lobe epilepsy.

FIG. 1.

FC in patients with mTLE before and after surgery related to age-matched healthy controls. A: FC in mTLE before surgery compared to age-matched healthy controls (represented by zero). B: FC in mTLE after surgery compared to age-matched healthy controls. Values in panels A and B reflect the mean of the 95% confidence interval of the t-test between FC and zero. Units are standard deviations from age-matched healthy controls. C: Presurgical regions (dark colors) and lobes (light colors) were significantly different from age-matched controls (p < 0.05, Bonferroni correction). D: Postsurgical regions (dark colors) and lobes (light colors) were significantly different from age-matched controls (p < 0.05, Bonferroni correction). Seed regions are represented by each row and the first 12 columns. The remaining columns are arranged according to lobes of the brain, separated by thick black lines. Within lobes, all regions ipsilateral and contralateral to seizure focus are on the left and right side of the thin black lines, respectively. Connections involving the ipsilateral hippocampus and temporal lobe are gray to indicate that these were excluded from postsurgical analyses. i (following abbreviation) = ipsilateral to seizure focus; c (following abbreviation) = contralateral to seizure focus; HIP = hippocampus; THAL = thalamus; PREC = precuneus; A_INS = anterior insula; P_INS = posterior insula; M_CING = mid-cingulate; PREF = prefrontal; PAR = parietal; OCC = occipital; TEMP = temporal; MOT = motor; SOM = somatosensory; SUB = subcortical.

FIG. 2.

FC decreases after surgery in mTLE. Postsurgical decreases in FC compared to presurgical FC are found (A) from the ipsilateral precuneus to the ipsilateral posterior cingulate (p < 0.01, Bonferroni correction); (B) from the contralateral hippocampus to the contralateral subcortical lobe (p < 0.01, Bonferroni correction); and (C) from the contralateral hippocampus to the contralateral parietal lobe (p < 0.01, Bonferroni correction). D: All regional connections with a postsurgical decrease in FC compared to presurgical FC (p < 0.05, Bonferroni correction) are depicted on the brain to indicate the spatial distribution of the changes, excluding those involving the ipsilateral temporal lobe. All statistics are adjusted for months after surgery at which postsurgical scan was obtained. Value of FC = 0 represents age-matched healthy control. ipsi, I (following abbreviation) = ipsilateral to seizure focus; contra, C (following abbreviation) = contralateral to seizure focus; corr = Bonferroni correction; ACG = anterior cingulate gyrus; BF = basal forebrain; CING = mid-cingulate gyrus; FFG = fusiform gyrus; HIP = hippocampus; LING = lingual gyrus; PCG = posterior cingulate gyrus; PREC = precuneus; SMG = supramarginal gyrus; SPL = superior parietal lobule; THAL = thalamus; VDC = ventral diencephalon.

FIG. 3.

Postsurgical change in FC between the contralateral precuneus and the ipsilateral occipital lobe is related to seizure outcome. A: Presurgical - postsurgical FC is lower in those patients who are seizure free (group 1) compared to those with recurring seizures (groups 2 and 3) at postsurgical scan (ANOVA, p < 0.05, Bonferroni correction). Change in FC is adjusted for months after surgery at which postsurgical scan was obtained. B: Group 1 patients (n = 9) show no difference from control before or after surgery (1-sample t-test, p > 0.05). C: Groups 2 and 3 patients (n = 11) show no difference from control prior to surgery (1-sample t-test, p > 0.05), but a decrease from control after surgery (1-sample t-test, p < 0.01, uncorrected). Value of FC = 0 represents age-matched healthy control. contra = contralateral to seizure focus. * 2-sample t-test (p < 0.05, uncorrected); ^** 2-sample t-test (p < 0.001, uncorrected).

FIG. 4.

Postsurgical change in FC between the contralateral precuneus and the contralateral temporal lobe is related to type of surgery. A: Presurgical - postsurgical FC is higher in those patients who underwent right temporal lobectomy compared to those who underwent selective amygdalohippocampectomy (Sel AH) (ANOVA, p < 0.05, Bonferroni correction). Change in FC is adjusted for months after surgery at which postsurgical scan was obtained. B: Patients with selective AH (n = 13) show a decrease from control before (1-sample t-test, p < 0.01, uncorrected) but not after surgery. C: Patients with temporal lobectomy (n = 13) show no difference from control prior to or after surgery (1-sample t-test, p > 0.05). Value of FC = 0 represents age-matched healthy control. * 2-sample t-test (p < 0.01, uncorrected); ^** 2-sample t-test (p < 0.001, uncorrected).

FIG. 5.

Thalamic postsurgical changes in FC related to presurgical disease parameters. A: Positive correlation between duration of disease prior to surgery and FC change from contralateral thalamus to ipsilateral and contralateral posterior cingulate (Pearson correlation, p < 0.01, corrected). B: Presurgical and postsurgical FC between contralateral thalamus and ipsilateral posterior cingulate related to duration of disease prior to surgery. C: Presurgical and postsurgical FC between contralateral thalamus and contralateral posterior cingulate related to duration of disease prior to surgery. D: Negative correlation between frequency of consciousness-impairing seizures per month prior to surgery and FC change from the ipsilateral thalamus to the ipsilateral prefrontal lobe (Pearson correlation, p < 0.05, corrected). E: Presurgical and postsurgical FC between ipsilateral thalamus and ipsilateral prefrontal lobe related to frequency of presurgical seizures. Value of FC = 0 represents age-matched healthy control. Linear trend lines are shown. corr = Bonferroni correction; PC = posterior cingulate; Pref = prefrontal lobe.