Resting-state fMRI seizure onset localization meta-analysis: comparing rs-fMRI to other modalities including surgical outcomes

Abstract

Objective: Resting-state functional MRI (rs-fMRI) may localize the seizure onset zone (SOZ) for epilepsy surgery, when compared to intracranial EEG and surgical outcomes, per a prior meta-analysis. Our goals were to further characterize this agreement, by broadening the queried rs-fMRI analysis subtypes, comparative modalities, and same-modality comparisons, hypothesizing SOZ-signal strength may overcome this heterogeneity.

Methods: PubMed, Embase, Scopus, Web of Science, and Google Scholar between April 2010 and April 2020 via PRISMA guidelines for SOZ-to-established-modalities were screened. Odd ratios measured agreement between SOZ and other modalities. Fixed- and random-effects analyses evaluated heterogeneity of odd ratios, with the former evaluating differences in agreement across modalities and same-modality studies.

Results: In total, 9,550 of 14,384 were non-duplicative articles and 25 met inclusion criteria. Comparative modalities were EEG 7, surgical outcome 6, intracranial EEG 5, anatomical MRI 4, EEG-fMRI 2, and magnetoencephalography 1. Independent component analysis 9 and seed-based analysis 8 were top rs-fMRI methods. Study-level odds ratio heterogeneity in both the fixed- and random-effects analysis was significant (p < 0.001). Marked cross-modality and same-modality systematic differences in agreement between rs-fMRI and the comparator were present (p = 0.005 and p = 0.002), respectively, with surgical outcomes having higher agreement than EEG (p = 0.002) and iEEG (p = 0.007). The estimated population mean sensitivity and specificity were 0.91 and 0.09, with predicted values across studies ranging from 0.44 to 0.96 and 0.02 to 0.67, respectively.

Significance: We evaluated centrality and heterogeneity in SOZ agreement between rs-fMRI and comparative modalities using a wider variety of rs-fMRI analyzing subtypes and comparative modalities, compared to prior. Strong evidence for between-study differences in the agreement odds ratio was shown by both the fixed- and the random-effects analyses, attributed to rs-fMRI analysis variability. Agreement with rs-fMRI differed by modality type, with surgical outcomes having higher agreement than EEG and iEEG. Overall, sensitivity was high, but specificity was low, which may be attributed in part to differences between other modalities.

Keywords: epilepsy surgery; meta-analysis; neuroimaging; resting-state functional MRI; seizure network.

Figure 1

PRISMA flow diagram for the current meta-analysis. *Animal studies, patients without epilepsy; **study design (n = 141), indication (n = 25), comparator (n = 12), publication type (n = 20), intervention (n = 9), outcomes (n = 9), patient population (n = 4), setting (n = 3), language (n = 4), manuscript unavailable (n = 11), duplicate paper (n = 8), duplicate population (n = 14), and unavailable subject level SOZ data (n = 52).

Figure 2

Fixed-effects analysis odd ratios. Each study was summarized into a 2×2 table, and conditional likelihood-based estimates were obtained if there are no zero cells. In five studies, one cell was zero, and median unbiased estimates were obtained (as marked by *). If any margin is zero, the study is non-informative. This left the 10 studies shown in this figure. The analysis presented very strong evidence against the existence of a common odds ratio. Red line indicates an odds ratio of 1 of no association.

Figure 3

Fixed-effects analysis sensitivities and specificities. Each study was summarized into a 2×2 table. Sensitivities and specificities were calculated, and exact 95% confidence intervals were obtained.

Figure 4

Random-effects analysis odd ratios. Random-effects model includes a random study-specific log odds ratio measuring the agreement between fs-MRI and the comparative. Predicted study-specific odds ratios and prediction intervals are depicted. The study-specific odds ratios, assumed normally distributed, are estimated to have a mean (and median) of 1.007 and with a standard deviation of 3. The analysis presented very strong evidence against the existence of a common odds ratio.

Figure 5

Random-effects sensitivities and specificities. Random-effects model includes a random study-specific log odds ratio measuring the agreement between fs-MRI and the comparative. Predicted study-specific odds ratios and prediction intervals are depicted. The study-specific sensitivity and specificity assumed normality are assumed to have a mean of 0.91 and 0.09, respectively.