fMRI-Based Effective Connectivity in Surgical Remediable Epilepsies: A Pilot Study

Abstract

Simultaneous EEG-fMRI can contribute to identify the epileptogenic zone (EZ) in focal epilepsies.However, fMRI maps related to Interictal Epileptiform Discharges (IED) commonly show multiple regions of signal change rather than focal ones. Dynamic causal modeling (DCM) can estimate effective connectivity, i.e. the causal effects exerted by one brain region over another, based on fMRI data. Here, we employed DCM on fMRI data in 10 focal epilepsy patients with multiple IED-related regions of BOLD signal change, to test whether this approach can help the localization process of EZ. For each subject, a family of competing deterministic, plausible DCM models were constructed using IED as autonomous input at each node, one at time. The DCM findings were compared to the presurgical evaluation results and classified as: "Concordant" if the node identified by DCM matches the presumed focus, "Discordant" if the node is distant from the presumed focus, or "Inconclusive" (no statistically significant result). Furthermore, patients who subsequently underwent intracranial EEG recordings or surgery were considered as having an independent validation of DCM results. The effective connectivity focus identified using DCM was Concordant in 7 patients, Discordant in two cases and Inconclusive in one. In four of the 6 patients operated, the DCM findings were validated.Notably, the two Discordant and Invalidated results were found in patients with poor surgical outcome. Our findings provide preliminary evidence to support the applicability of DCM on fMRI data to investigate the epileptic networks in focal epilepsy and, particularly, to identify the EZ in complex cases.

Noninvasive Epileptogenic Signal Direction Determination by Effective Connectivity of Resting State Functional MRI - Independent of EEG

“…Before application to the more heterogeneously localized SOZ of the general DRE population, it was necessary to perform this analysis in such a homogenous and well established SOZ location of the HH to understand the potential of this tool for narrowing ROI for SOZ location determination. Importantly, polarity of SOZ and pZ connections were consistent in both individual and group analyses , increasing confidence in individual application, similar to prior RSFC (Boerwinkle et al, 2019a; Boerwinkle et al, 2018a; Boerwinkle et al, 2017; Boerwinkle et al, 2016) and RSEC work (Vaudano et al, 2021).…”

“…Our hypothesis that, from rs-fMRI alone, intrinsic modulation from the SOZ is excitatory and modulation from the pZ is inhibitory is supported by our results. Unlike previous studies, we did not time lock or model around ictal onset or known periods of interictal discharge (Daunizeau et al, 2012; Hamandi et al, 2008; Klamer et al, 2018; Klamer et al, 2015; Murta et al, 2012; Vaudano et al, 2013; Vaudano et al, 2009; Vaudano et al, 2021; Warren et al, 2019). Instead, we assumed, that in DRE, markers of epileptic signal are present in resting-state networks regardless of known or unknown ictal and interictal activity at time of data capture and without time-locking to ictal/interictal activity.…”

“…The fundamental limitation of static rs-fMRI ICA is overcome to some extent by employing simultaneous EEG-fMRI, though this method only identifies the SOZ in a small proportion of cases, alone (Vaudano et al, 2021). The interictal epileptogenic discharges (IED) detected by EEG inform the time point at which pre-to-post blood oxygenation level dependent (BOLD) imaging maximal regions of interest (IED-BOLD ROI) are identified.…”

“…The interictal epileptogenic discharges (IED) detected by EEG inform the time point at which pre-to-post blood oxygenation level dependent (BOLD) imaging maximal regions of interest (IED-BOLD ROI) are identified. A possible advance on this method, subsequent dynamic causal modeling (DCM) of the IED-BOLD ROI, has differentiated the epileptogenic driver from propagation regions in four cases as determined by good surgical outcomes (Engel class I and II) (Engel, 1993; Vaudano et al, 2021). However, this limited series highlighted the dependency of EEG-fMRI on requires additional specialized equipment, EEG technician staff, and epileptiform events to occur during the scan; all of which are cumbersome features limiting clinical utility.…”

Mapping of Language-and-Memory Networks in Patients With Temporal Lobe Epilepsy by Using the GE2REC Protocol

“…Nevertheless, other mapping methods using fMRI can also be used in the presurgical evaluation. For instance, studies show clinical application of functional connectivity ( Bettus et al, 2010 ; Pravatà et al, 2014 ; Tracy and Doucet, 2015 ; DeSalvo et al, 2020 ; Foesleitner et al, 2021 ) and effective connectivity ( Vaudano et al, 2021 ).…”