Seizures are often followed by sensory, cognitive or motor impairments during the postictal phase that show striking similarity to transient hypoxic/ischemic attacks. Here we show that seizures result in a severe hypoxic attack confined to the postictal period. We measured brain oxygenation in localized areas from freely-moving rodents and discovered a severe hypoxic event (pO2 < 10 mmHg) after the termination of seizures. This event lasted over an hour, is mediated by hypoperfusion, generalizes to people with epilepsy, and is attenuated by inhibiting cyclooxygenase-2 or L-type calcium channels. Using inhibitors of these targets we separated the seizure from the resulting severe hypoxia and show that structure specific postictal memory and behavioral impairments are the consequence of this severe hypoperfusion/hypoxic event. Thus, epilepsy is much more than a disease hallmarked by seizures, since the occurrence of postictal hypoperfusion/hypoxia results in a separate set of neurological consequences that are currently not being treated and are preventable.DOI: http://dx.doi.org/10.7554/eLife.19352.001

Diffusion tensor imaging (DTI) studies have provided much evidence of white and subcortical gray matter changes during late childhood and early adolescence that suggest increasing myelination, axon density, and/or fiber coherence. Neurite orientation dispersion and density imaging (NODDI) can be used to further characterize development in white and subcortical grey matter regions in the brain by improving specificity of the MRI signal compared to conventional DTI. We used measures from NODDI and DTI to examine white and subcortical gray matter development in a group of 27 healthy participants aged 8–13 years. Neurite density index (NDI) was strongly correlated with age in nearly all regions, and was more strongly associated with age than fractional anisotropy (FA). No significant correlations were observed between orientation dispersion index (ODI) and age. This suggests that white matter and subcortical gray matter changes during late childhood and adolescence are dominated by changes in neurite density (i.e., axon density and myelination), rather than increasing coherence of axons. Within brain regions, FA was correlated with both ODI and NDI while mean diffusivity was only related to neurite density, providing further information about the structural variation across individuals. Data-driven clustering of the NODDI parameters showed that microstructural profiles varied along layers of white matter, but that that much of the white and subcortical gray matter matured in a similar manner. Clustering highlighted isolated brain regions with decreasing NDI values that were not apparent in region-of-interest analysis. Overall, these results help to more specifically understand patterns of white and gray matter development during late childhood and early adolescence.

Sensitive and specific biomarkers of myelin can help define baseline brain health and development, identify and monitor disease pathology, and evaluate response to treatment where myelin content is affected. Diffusion measures such as radial diffusivity (RD) are commonly used to assess myelin content, but are not specific to myelin. Inhomogeneous magnetization transfer (ihMT) and multicomponent driven equilibrium single-pulse observation of T1 and T2 (mcDESPOT) offer quantitative parameters (qihMT and myelin volume fraction/VF, respectively) which are suggested to have improved sensitivity to myelin. We compared RD, qihMT, and VF in a cohort of 23 healthy children aged 8-13 years to evaluate the similarities and differences across these measures. All 3 measures were significantly related across brain voxels, but VF and qihMT were significantly more strongly correlated (qihMT-VF r = 0.89) than either measure was with RD (RD-qihMT r = -0.66, RD-VF r = -0.74; all p < 0.001). Mean parameters differed in several regions, especially in subcortical gray matter. These differences can likely be explained by unique sensitivities of each measure to non-myelin factors, such as crossing fiber geometry, axonal packing, fiber orientation, glial density, or magnetization transfer effects in a voxel. We also observed an orientation dependence of qihMT in white matter, such that qihMT decreased as fiber orientation went from parallel to perpendicular to B. All measures appear to be sensitive to myelin content, though qihMT and VF appear to be more specific to it than RD. Scan time, noise tolerance, and resolution requirements may inform researchers of the appropriate measure to choose for a specific application.