Widespread, depth-dependent cortical microstructure alterations in pediatric focal epilepsy.

OBJECTIVE: Tissue abnormalities in focal epilepsy may extend beyond the presumed focus. The underlying pathophysiology of these broader changes is unclear, and it is not known whether they result from ongoing disease processes or treatment-related side effects, or whether they emerge earlier. Few studies have focused on the period of onset for most focal epilepsies, childhood. Fewer still have utilized quantitative magnetic resonance imaging (MRI), which may provide a more sensitive and interpretable measure of tissue microstructural change. Here, we aimed to determine common spatial modes of changes in cortical architecture in children with heterogeneous drug-resistant focal epilepsy and, secondarily, whether changes were related to disease severity. METHODS: To assess cortical microstructure, quantitative T1 and T2 relaxometry (qT1 and qT2) was measured in 43 children with drug-resistant focal epilepsy (age range = 4-18 years) and 46 typically developing children (age range = 2-18 years). We assessed depth-dependent qT1 and qT2 values across the neocortex, as well as their gradient of change across cortical depths. We also determined whether global changes seen in group analyses were driven by focal pathologies in individual patients. Finally, as a proof-of-concept, we trained a classifier using qT1 and qT2 gradient maps from patients with radiologically defined abnormalities (MRI positive) and healthy controls, and tested whether this could classify patients without reported radiological abnormalities (MRI negative). RESULTS: We uncovered depth-dependent qT1 and qT2 increases in widespread cortical areas in patients, likely representing microstructural alterations in myelin or gliosis. Changes did not correlate with disease severity measures, suggesting they may represent antecedent neurobiological alterations. Using a classifier trained with MRI-positive patients and controls, sensitivity was 71.4% at 89.4% specificity on held-out MRI-negative patients. SIGNIFICANCE: These findings suggest the presence of a potential imaging endophenotype of focal epilepsy, detectable irrespective of radiologically identified abnormalities.

Prediction of behavioral deficits in acute stroke from lesion and structural disconnection mapping.

Prediction of behavioral deficits in stroke relies on understanding the distribution of focal damage as well as the distribution of the underlying functional anatomy. Using structural or functional magnetic resonance imaging, previous studies investigated the predictive performance of imaging biomarkers for behavioral deficits in stroke patients. However, only focal lesion information or functional connectivity information alone was used in the modelling, with a small sample size and on a specific behavioral deficit domain. In this study, we investigated the prediction of behavioral deficits in acute stroke using both focal lesion patterns and structural disconnection mapping on a cohort of 551 ischemic stroke patients within one week post symptom onset. Five behavioral deficits domains, including motor, cognitive, visual, somatosensory and coordination deficits, were investigated. A probabilistic map of lesion-induced structural "disconnectome" map was created to estimate the degree of structural disconnection due to lesions. In the predictive modelling, both lesion volume and location and distant structural disconnections were included in combination with the clinical information. The results showed that improved prediction performance was achieved when considering both focal lesion patterns and global lesion-induced structural disconnections for all five behavioral deficits groups. Distinct lesion maps were obtained for each behavioral deficit, providing insights into neurobiological mechanisms of stroke functional impairment.

Atomic force microscopy-based single-molecule force spectroscopy detects DNA base mismatches.

Atomic force microscopy-based single-molecule-force spectroscopy is limited by low throughput. We introduce addressable DNA origami to study multiple target molecules. Six target DNAs that differed by only a single base-pair mismatch were clearly differentiated a rupture force of only 4 pN.