Simulation, Implementation and Measurement of Defined Sound Fields for Blood-Brain Barrier Opening in Rats.

The blood-brain barrier (BBB) is the most important obstacle to delivery of therapeutics to the central nervous system. Low-intensity pulsed focused ultrasound (FUS) in combination with microbubbles applied under magnetic resonance imaging (MRI) control provides a non-invasive and safe technique for BBB opening (BBBo). In rodent models, however, settings and application protocols differ significantly. Depending on the strain and size, important variables include ultrasound attenuation and sound field distortion caused by the skull. We examined the ultrasound attenuation of the skull of Wistar rats using a targeted FUS system. By modifying the transducer elements and by varying and simulating the acoustic field of the FUS system, we measured a skull attenuation of about 60%. To evaluate potential application of the targeted FUS system in genetically modified animals with increased sensitivity to brain hemorrhage caused by vascular dysfunction, we assessed safety in healthy animals. Histological and MRI analyses of the central nervous system revealed an increase in the number and severity of hyperacute bleeds with focal pressure. At a pressure of 0.4 MPa, no bleeds were induced, albeit at the cost of a weaker hyperintense MRI signal post BBBo. These results indicate a relationship between pressure and the dimension of permeabilization.

Large EEG amplitude effects are highly similar across Necker cube, smiley, and abstract stimuli.

The information available through our senses is noisy, incomplete, and ambiguous. Our perceptual systems have to resolve this ambiguity to construct stable and reliable percepts. Previous EEG studies found large amplitude differences in two event-related potential (ERP) components 200 and 400 ms after stimulus onset when comparing ambiguous with disambiguated visual information ("ERP Ambiguity Effects"). These effects so far generalized across classical ambiguous figures from different visual categories at lower (geometry, motion) and intermediate (Gestalt perception) levels. The present study aimed to examine whether these ERP Effects are restricted to ambiguous figures or whether they also occur for different degrees of visibility. Smiley faces with low and high visibility of emotional expressions, as well as abstract figures with low and high visibility of a target curvature were presented. We thus compared ambiguity effects in geometric cube stimuli with visibility in emotional faces, and with visibility in abstract figures. ERP Effects were replicated for the geometric stimuli and very similar ERP Effects were found for stimuli with emotional face expressions but also for abstract figures. Conclusively, the ERP amplitude effects generalize across fundamentally different stimulus categories and show highly similar effects for different degrees of stimulus ambiguity and stimulus visibility. We postulate the existence of a high-level/meta-perceptual evaluation instance, beyond sensory details, that estimates the certainty of a perceptual decision. The ERP Effects may reflect differences in evaluation results.