Electromagnetic source imaging predicts surgical outcome in children with focal cortical dysplasia.

OBJECTIVE: To evaluate the diagnostic accuracy of electromagnetic source imaging (EMSI) in localizing spikes and predict surgical outcome in children with drug resistant epilepsy (DRE) due to focal cortical dysplasia (FCD). METHODS: We retrospectively analyzed magnetoencephalography (MEG) and high-density (HD-EEG) data from 23 children with FCD-associated DRE who underwent intracranial EEG and surgery. We localized spikes using equivalent current dipole (ECD) fitting, dipole clustering, and dynamical statistical parametric mapping (dSPM) on EMSI, electric source imaging (ESI), and magnetic source imaging (MSI). We calculated the distance from the seizure onset zone (DSOZ) and resection (DRES). We estimated receiver operating characteristic (ROC) curves with Youden's index (J) to predict outcome. RESULTS: EMSI presented shorter DSOZ (15.18 ± 9.06 mm) and DRES (8.56 ± 6.24 mm) compared to ESI (DSOZ: 25.04 ± 16.20 mm, p < 0.009; DRES: 18.88 ± 17.30 mm, p < 0.03) and MSI (DSOZ: 23.37 ± 8.98 mm, p < 0.03; DRES: 15.51 ± 10.11 mm, p < 0.02) for clustering in patients with good outcome. Clustering showed shorter DSOZ and DRES compared to ECD fitting and dSPM (p < 0.05). EMSI had higher performance as outcome predictor (J = 70.63%) compared to ESI (J = 41.27%) and MSI (J = 33.33%) for clustering. CONCLUSIONS: EMSI provides superior localization and improved predictive performance than individual modalities. SIGNIFICANCE: EMSI can help the surgical planning and facilitate the localization of epileptogenic foci.

Non-invasive mapping of epileptogenic networks predicts surgical outcome.

Epilepsy is increasingly considered a disorder of brain networks. Studying these networks with functional connectivity can help identify hubs that facilitate the spread of epileptiform activity. Surgical resection of these hubs may lead patients who suffer from drug-resistant epilepsy to seizure freedom. Here, we aim to map non-invasively epileptogenic networks, through the virtual implantation of sensors estimated with electric and magnetic source imaging, in patients with drug-resistant epilepsy. We hypothesize that highly connected hubs identified non-invasively with source imaging can predict the epileptogenic zone and the surgical outcome better than spikes localized with conventional source localization methods (dipoles). We retrospectively analysed simultaneous high-density electroencephalography (EEG) and magnetoencephalography data recorded from 37 children and young adults with drug-resistant epilepsy who underwent neurosurgery. Using source imaging, we estimated virtual sensors at locations where intracranial EEG contacts were placed. On data with and without spikes, we computed undirected functional connectivity between sensors/contacts using amplitude envelope correlation and phase locking value for physiologically relevant frequency bands. From each functional connectivity matrix, we generated an undirected network containing the strongest connections within sensors/contacts using the minimum spanning tree. For each sensor/contact, we computed graph centrality measures. We compared functional connectivity and their derived graph centrality of sensors/contacts inside resection for good (n = 22, ILAE I) and poor (n = 15, ILAE II-VI) outcome patients, tested their ability to predict the epileptogenic zone in good-outcome patients, examined the association between highly connected hubs removal and surgical outcome and performed leave-one-out cross-validation to support their prognostic value. We also compared the predictive values of functional connectivity with those of dipoles. Finally, we tested the reliability of virtual sensor measures via Spearman's correlation with intracranial EEG at population- and patient-level. We observed higher functional connectivity inside than outside resection (P < 0.05, Wilcoxon signed-rank test) for good-outcome patients, on data with and without spikes across different bands for intracranial EEG and electric/magnetic source imaging and few differences for poor-outcome patients. These functional connectivity measures were predictive of both the epileptogenic zone and outcome (positive and negative predictive values ≥55%, validated using leave-one-out cross-validation) outperforming dipoles on spikes. Significant correlations were found between source imaging and intracranial EEG measures (0.4 ≤ rho ≤ 0.9, P < 0.05). Our findings suggest that virtual implantation of sensors through source imaging can non-invasively identify highly connected hubs in patients with drug-resistant epilepsy, even in the absence of frank epileptiform activity. Surgical resection of these hubs predicts outcome better than dipoles.

Noninvasive Mapping of Ripple Onset Predicts Outcome in Epilepsy Surgery.

OBJECTIVE: Intracranial electroencephalographic (icEEG) studies show that interictal ripples propagate across the brain of children with medically refractory epilepsy (MRE), and the onset of this propagation (ripple onset zone [ROZ]) estimates the epileptogenic zone. It is still unknown whether we can map this propagation noninvasively. The goal of this study is to map ripples (ripple zone [RZ]) and their propagation onset (ROZ) using high-density EEG (HD-EEG) and magnetoencephalography (MEG), and to estimate their prognostic value in pediatric epilepsy surgery. METHODS: We retrospectively analyzed simultaneous HD-EEG and MEG data from 28 children with MRE who underwent icEEG and epilepsy surgery. Using electric and magnetic source imaging, we estimated virtual sensors (VSs) at brain locations that matched the icEEG implantation. We detected ripples on VSs, defined the virtual RZ and virtual ROZ, and estimated their distance from icEEG. We assessed the predictive value of resecting virtual RZ and virtual ROZ for postsurgical outcome. Interictal spike localization on HD-EEG and MEG was also performed and compared with ripples. RESULTS: We mapped ripple propagation in all patients with HD-EEG and in 27 (96%) patients with MEG. The distance from icEEG did not differ between HD-EEG and MEG when mapping the RZ (26-27mm, p = 0.6) or ROZ (22-24mm, p = 0.4). Resecting the virtual ROZ, but not virtual RZ or the sources of spikes, was associated with good outcome for HD-EEG (p = 0.016) and MEG (p = 0.047). INTERPRETATION: HD-EEG and MEG can map interictal ripples and their propagation onset (virtual ROZ). Noninvasively mapping the ripple onset may augment epilepsy surgery planning and improve surgical outcome of children with MRE. ANN NEUROL 2021;89:911-925.

Eye movements modulate the spatiotemporal dynamics of word processing.

Active reading requires coordination between frequent eye movements (saccades) and short fixations in text. Yet, the impact of saccades on word processing remains unknown, as neuroimaging studies typically employ constant eye fixation. Here we investigate eye-movement effects on word recognition processes in healthy human subjects using anatomically constrained magnetoencephalography, psychophysical measurements, and saccade detection in real time. Word recognition was slower and brain responses were reduced to words presented early versus late after saccades, suggesting an overall transient impairment of word processing after eye movements. Response reductions occurred early in visual cortices and later in language regions, where they colocalized with repetition priming effects. Qualitatively similar effects occurred when words appeared early versus late after background movement that mimicked saccades, suggesting that retinal motion contributes to postsaccadic inhibition. Further, differences in postsaccadic and background-movement effects suggest that central mechanisms also contribute to postsaccadic modulation. Together, these results suggest a complex interplay between visual and central saccadic mechanisms during reading.

An intraoperative multimodal neurophysiologic approach to successful resection of precentral gyrus epileptogenic lesions.

Cortical dysplasias (CDs) are highly epileptogenic lesions with a good prognosis of seizure freedom, if totally resected. However, their accurate delineation and resection can be difficult, and depend on the extent of pathology and lesion location. Intraoperative neurophysiologic assessments are valuable in these situations. We present an illustrative case of intractable epilepsy where judicious use of intraoperative neurophysiologic-techniques guided resection of precentral CD, under general anesthesia and in the absence of preoperative electrophysiologic mapping data. Ictal onset was accurately delineated using electrocorticography (ECoG). Phase reversal of the median somatosensory-evoked potentials (MSSEPs) localized the central sulcus (CS). Motor evoked potentials (MEPs) triggered by high-frequency monopolar anodal electrical cortical stimulation at the primary motor cortex (PMC) threshold delineated the PMC. Using this technique, PMC and the corticospinal tract (CST) were continuously monitored during resection. No changes in MEPs from the preresection baseline were seen; no residual abnormal activity was present in the postresection ECoG. The patient emerged from surgery without deficits and has been seizure free during a 10-month follow-up. Staged multimodal intraoperative neurophysiology can be used successfully under general anesthesia to guide resection of epileptogenic lesions within the precentral gyrus, as an add-on or, in certain situations, as a viable alternative to preoperative electrophysiologic mapping.