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Typical childhood development is characterized by the emergence of intrinsic connectivity networks (ICNs) by way of internetwork segregation and intranetwork integration. The impact of childhood epilepsy on the maturation of ICNs is, however, poorly understood. The developmental trajectory of ICNs in 26 children (8-17 years) with localization-related epilepsy and 28 propensity-score matched controls was evaluated using graph theoretical analysis of whole brain connectomes from resting-state functional magnetic resonance imaging (fMRI) data. Children with epilepsy demonstrated impaired development of regional hubs in nodes of the salience and default mode networks (DMN). Seed-based connectivity and hierarchical clustering analysis revealed significantly decreased intranetwork connections, and greater internetwork connectivity in children with epilepsy compared to controls. Significant interactions were identified between epilepsy duration and the expected developmental trajectory of ICNs, indicating that prolonged epilepsy may cause progressive alternations in large-scale networks throughout childhood. DMN integration was also associated with better working memory, whereas internetwork segregation was associated with higher full-scale intelligence quotient scores. Furthermore, subgroup analyses revealed the thalamus, hippocampus, and caudate were weaker hubs in children with secondarily generalized seizures, relative to other patient subgroups. Our findings underscore that epilepsy interferes with the developmental trajectory of brain networks underlying cognition, providing evidence supporting the early treatment of affected children.

SUMMARYPurpose: Combining intracranial electroencephalography (iEEG) with functional magnetic resonance imaging (fMRI) is of interest in epilepsy studies as it would allow the detection of much smaller interictal epileptiform discharges than can be recorded using scalp EEG-fMRI. This may help elucidate the spatiotemporal mechanisms underlying the generation of interictal discharges. To our knowledge, iEEG-fMRI has never been performed at 3 Tesla (3T) in humans. We report our findings relating to spike-associated blood oxygen level-dependent (BOLD) signal changes in two subjects. Methods: iEEG-fMRI at 3T was performed in two subjects. Twelve channels of iEEG were recorded from subdural strips implanted on the left posterior temporal and middle frontal lobes in a 20-year-old female with bilateral periventricular gray matter heterotopia. Twenty channels of iEEG were recorded bilaterally from two subdural strips laid anterior-posterior along mesial temporal surfaces in a 29-year-old woman with bilateral temporal seizures and mild left amygdalar enlargement on MRI. Functional MRI (fMRI) statistical maps were generated and thresholded at p = 0.01. Key Findings: No adverse events were noted. A total of 105 interictal discharges were recorded in the posterior middle temporal gyrus of Subject 1. In Subject 2, 478 discharges were recorded from both mesial temporal surfaces (n = 194 left, 284 right). The right and left discharges were modeled separately, as they were independent. Subject 1 showed spike-associated BOLD signal increases in the left superior temporal region, left middle frontal gyrus, and right parietal lobe. BOLD decreases were seen in the right frontal and parietal lobes. In Subject 2, BOLD signal increases were seen in both mesial temporal lobes, which when left and right spikes were modeled independently, were greater on the side of the discharge. In addition, striking BOLD signal decreases were observed in the thalamus and posterior cingulate gyrus. Significance: iEEG-fMRI can be performed at 3T with low risk. Notably, runs of only 5 or 10 min of EEG-fMRI were performed as part of our implementation protocol, yet a significant number of epileptiform discharges were recorded, allowing meaningful analyses. With these studies, we have shown that deactivation can be seen in individual subjects with focal epileptiform discharges. These preliminary observations suggest a novel mechanism through which focal interictal discharges may have widespread cortical and subcortical influences. KEY WORDS: Intracranial EEG, Functional MRI, EEGfMRI, Focal epilepsy.Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been combined successfully to help localize changes in brain activity associated with interictal discharges (Cunningham et al., 2008;Gotman, 2008). Despite the success of scalp EEG-fMRI, scalp EEG has limited ability to detect discharges involving a small cortical area (<10 cm 2 ) or from deeper brain structures (Ebersole, 1997). The ability to detect low amplitude, deeply originat...

ObjectivesSimultaneous scalp EEG-fMRI can identify hemodynamic changes associated with the generation of interictal epileptiform discharges (IEDs), and it has the potential of becoming a standard, non-invasive technique for pre-surgical assessment of patients with medically intractable epilepsy. This study was designed to assess the BOLD response to focal IEDs recorded via simultaneous intracranial EEG-functional MRI (iEEG-fMRI).MethodsTwelve consecutive patients undergoing intracranial video EEG monitoring were recruited for iEEG-fMRI studies at 3 T. Depth, subdural strip, or grid electrodes were implanted according to our standard clinical protocol. Subjects underwent 10–60 min of continuous iEEG-fMRI scanning. IEDs were marked, and the most statistically significant clusters of BOLD signal were identified (Z-score 2.3, p value < 0.05). We assessed the concordance between the locations of the BOLD response and the IED. Concordance was defined as a distance <1.0 cm between the IED and BOLD response location. Negative BOLD responses were not studied in this project.ResultsNine patients (7 females) with a mean age of 31 years (range 22–56) had 11 different types of IEDs during fMR scanning. The IEDs were divided based on the location of the active electrode contact into mesial temporal, lateral temporal, and extra-temporal. Seven (5 left) mesial temporal IED types were recorded in 5 patients (110–2092 IEDs per spike location). Six of these IEDs had concordant BOLD response in the ipsilateral mesial temporal structures, <1 cm from the most active contact. One of the two subjects with left lateral temporal IEDs had BOLD responses concordant with the location of the most active contact, as well other ipsilateral and contralateral sites. Notably, the remaining two subjects with extratemporal discharges showed no BOLD signal near the active electrode contact.ConclusionsiEEG-fMRI is a feasible and low-risk method for assessment of hemodynamic changes of very focal IEDs that may not be recorded by scalp EEG. A high concordance rate between the location of the BOLD response and IEDs was seen for mesial temporal (6/7) IEDs. Significant BOLD activation was also seen in areas distant from the active electrode and these sites exhibited maximal BOLD activation in the majority of cases. This implies that iEEG-fMRI may further describe the areas involved in the generation of IEDs beyond the vicinity of the electrode(s).