Multi-spectral diffusion MRI mega-analysis in genetic generalized epilepsy: Relation to outcomes.

BACKGROUND AND OBJECTIVES: Genetic generalized epilepsy (GGE) is the most common form of generalized epilepsy. Although individual patients with GGE typically present without structural alterations, group differences have been demonstrated in GGE and some GGE subtypes like juvenile myoclonic epilepsy (GGE-JME). Previous studies usually involved only small cohorts from single centers and therefore could not assess imaging markers of multiple GGE subtypes. METHODS: We performed a diffusion MRI mega-analysis in 192 participants consisting of 126 controls and 66 patients with GGE from four different cohorts and two different epilepsy centers. We applied whole-brain multi-site harmonization and analyzed fractional anisotropy (FA), as well as mean, radial and axial diffusivity (MD/RD/AD) to assess differences between controls, patients with GGE and the common GGE subtypes, i.e. GGE with generalized tonic-clonic seizures only (GGE-GTCS), GGE-JME and absence epilepsy (GGE-AE). We also analyzed relationships with patients' response to anti-seizure-medication (ASM). RESULTS: Relative to controls, we identified decreased anisotropy and increased RD in patients with GGE. We found no significant effects of disease duration, age of onset or seizure frequency on diffusion metrics. Patients with JME had increased MD and RD when compared to controls, while patients with GGE-GTCS showed decreased MD/AD when compared to controls. Compared to patients with GGE-AE, patients with GGE-GTCS had lower AD/MD. Compared to patients with GGE-GTCS, patients with GGE-JME had higher MD/RD and AD. Moreover, we found lower FA in patients with refractory when compared to patients with non-refractory GGE in the right cortico-spinal tract, but no significant differences in patients with active versus controlled epilepsy. DISCUSSION: We provide evidence that clinically defined GGE as a whole and GGE-subtypes harbor marked microstructural differences detectable with diffusion MRI. Moreover, we found an association between microstructural changes and treatment resistance. Our findings have important implications for future full-resolution multi-site studies when assessing GGE, its subtypes and ASM refractoriness.

Big Field of View MRI T1w and FLAIR Template - NMRI225.

Image templates are a common tool for neuroscience research. Often, they are used for spatial normalization of magnetic resonance imaging (MRI) data, which is a necessary procedure for analyzing brain morphology and function via voxel-based analysis. This allows the researcher to reduce individual shape differences across images and make inferences across multiple subjects. Many templates have a small field-of-view typically focussed on the brain, limiting the use for applications requiring detailed information about other extra-cranial structures in the head and neck area. However, there are several applications where such information is important, for example source reconstruction of electroencephalography (EEG) and/or magnetoencephalography (MEG). We have constructed a new template based on 225 T1w and FLAIR images with a big field-of-view that can serve both as target for across subject spatial normalization as well as a basis to build high-resolution head models. This template is based on and iteratively re-registered to the MNI152 space to provide maximal compatibility with the most commonly used brain MRI template.

Resolving different presynaptic activity patterns within single olfactory glomeruli of Xenopus laevis larvae.

Olfactory sensing is generally organized into groups of similarly sensing olfactory receptor neurons converging into their corresponding glomerulus, which is thought to behave as a uniform functional unit. It is however unclear to which degree axons within a glomerulus show identical activity, how many converge into a glomerulus, and to answer these questions, how it is possible to visually separate them in live imaging. Here we investigate activity of olfactory receptor neurons and their axon terminals throughout olfactory glomeruli using electrophysiological recordings and rapid 4D calcium imaging. While single olfactory receptor neurons responsive to the same odor stimulus show a diversity of responses in terms of sensitivity and spontaneous firing rate on the level of the somata, their pre-synaptic calcium activity in the glomerulus is homogeneous. In addition, we could not observe the correlated spontaneous calcium activity that is found on the post-synaptic side throughout mitral cell dendrites and has been used in activity correlation imaging. However, it is possible to induce spatio-temporal presynaptic response inhomogeneities by applying trains of olfactory stimuli with varying amino acid concentrations. Automated region-of-interest detection and correlation analysis then visually distinguishes at least two axon subgroups per glomerulus that differ in odor sensitivity.