Disrupted Global and Regional Structural Networks and Subnetworks in Children with Localization-Related Epilepsy.

BACKGROUND AND PURPOSE: Structural connectivity has been thought to be a less sensitive measure of network changes relative to functional connectivity in children with localization-related epilepsy. The aims of this study were to investigate the structural networks in children with localization-related epilepsy and to assess the relation among structural connectivity, intelligence quotient, and clinical parameters. MATERIALS AND METHODS: Forty-five children with nonlesional localization-related epilepsy and 28 healthy controls underwent DTI. Global network (network strength, clustering coefficient, characteristic path length, global efficiency, and small-world parameters), regional network (nodal efficiency), and the network-based statistic were compared between patients and controls and correlated with intelligence quotient and clinical parameters. RESULTS: Patients showed disrupted global network connectivity relative to controls, including reduced network strength, increased characteristic path length and reduced global efficiency, and reduced nodal efficiency in the frontal, temporal, and occipital lobes. Connectivity in multiple subnetworks was reduced in patients, including the frontal-temporal, insula-temporal, temporal-temporal, frontal-occipital, and temporal-occipital lobes. The frontal lobe epilepsy subgroup demonstrated more areas with reduced nodal efficiency and more impaired subnetworks than the temporal lobe epilepsy subgroup. Network parameters were not significantly associated with intelligence quotient, age at seizure onset, or duration of epilepsy. CONCLUSIONS: We found disruption in global and regional networks and subnetworks in children with localization-related epilepsy. Regional efficiency and subnetworks were more impaired in frontal lobe epilepsy than in temporal lobe epilepsy. Future studies are needed to evaluate the implications of disrupted networks for surgical resection and outcomes for specific epileptogenic zones and the relation of disrupted networks to more complex cognitive function.

Abnormal functional network connectivity among resting-state networks in children with frontal lobe epilepsy.

BACKGROUND AND PURPOSE: Epilepsy is considered a disorder of neural networks. The aims of this study were to assess functional connectivity within resting-state networks and functional network connectivity across resting-state networks by use of resting-state fMRI in children with frontal lobe epilepsy and to relate changes in resting-state networks with neuropsychological function. MATERIALS AND METHODS: Fifteen patients with frontal lobe epilepsy and normal MR imaging and 14 healthy control subjects were recruited. Spatial independent component analysis was used to identify the resting-state networks, including frontal, attention, default mode network, sensorimotor, visual, and auditory networks. The Z-maps of resting-state networks were compared between patients and control subjects. The relation between abnormal connectivity and neuropsychological function was assessed. Correlations from all pair-wise combinations of independent components were performed for each group and compared between groups. RESULTS: The frontal network was the only network that showed reduced connectivity in patients relative to control subjects. The remaining 5 networks demonstrated both reduced and increased functional connectivity within resting-state networks in patients. There was a weak association between connectivity in frontal network and executive function (P = .029) and a significant association between sensorimotor network and fine motor function (P = .004). Control subjects had 79 pair-wise independent components that showed significant temporal coherence across all resting-state networks except for default mode network-auditory network. Patients had 66 pairs of independent components that showed significant temporal coherence across all resting-state networks. Group comparison showed reduced functional network connectivity between default mode network-attention, frontal-sensorimotor, and frontal-visual networks and increased functional network connectivity between frontal-attention, default mode network-sensorimotor, and frontal-visual networks in patients relative to control subjects. CONCLUSIONS: We found abnormal functional connectivity within and across resting-state networks in children with frontal lobe epilepsy. Impairment in functional connectivity was associated with impaired neuropsychological function.

Impaired default mode network on resting-state FMRI in children with medically refractory epilepsy.

BACKGROUND AND PURPOSE: Resting-state networks including the DMN have been shown to be abnormal in adults with temporal lobe epilepsy. However, little is known about the DMN in children with medically refractory epilepsy. The aim was to determine whether there was a difference in the DMN in children with medically refractory epilepsy relative to controls. MATERIALS AND METHODS: Eleven children with medically refractory epilepsy and 11 age-matched healthy controls underwent resting-state fMRI. IC analysis was used to identify the DMN. A random-effects analysis was performed on the Z-maps of the DMN within each group and between groups. We calculated the temporal correlation coefficients of pairs of ROIs: PCC/PCUN, mPFC, and left and right lateral parietal cortices. The relations between z scores of temporal correlation coefficients of pairs of ROIs and clinical seizure parameters and IQ were assessed. RESULTS: The patients demonstrated decreased DMN connectivity in the PCC/PCUN, bilateral lateral parietal cortex, and anterior and midcingulate relative to controls. There was reduced connectivity between the mPFC-right lateral parietal cortex, the PCC/PCUN-left lateral parietal cortex, and the PCC/PCUN-right lateral parietal cortex pairs of ROIs in patients compared with controls. There were no significant correlations between the z scores of temporal correlation coefficients of the 6 pairs of ROIs in patients and age of seizure onset, duration of epilepsy, number of medications, seizure frequency, and IQ. CONCLUSIONS: We have found reduced connectivity in the DMN in children with medically refractory epilepsy. Further studies are needed to determine whether different seizure types have different effects on the DMN and whether the impaired connectivity is related to cognitive functions subserved by the DMN.

Mouse embryonic phenotyping by morphometric analysis of MR images.

A new method is described for automatic detection of subtle morphological phenotypes in mouse embryos. Based on high-resolution magnetic resonance imaging scanning and nonlinear image alignment, this method is demonstrated by comparing the morphology of two inbred strains, C57BL/6J and 129Sv/S1ImJ, at 15.5 days postconception. Mouse embryo morphology was found to be highly amenable to this kind of analysis with very low levels (on average 110 µm) of residual anatomical variation within strains after linear differences in pose and scale are removed. Mapping of local size differences showed that C57BL/6J embryos were larger than 129Sv/S1ImJ embryos, although these differences were not uniformly distributed across the anatomy. Expressed in terms of organ volumes, heart and lung were larger in C57BL/6J embryos, while brain and liver were comparable in volume between strains. The positive relationship between organ size and embryo size was consistent for the two strains but differed by organ, with the brain and liver being the least variable. Together these findings suggest the power of this technique for detecting subtle phenotypic differences arising from mutated genes.