Abnormal Capillary Vasodynamics Contribute to Ictal Neurodegeneration in Epilepsy.

Seizure-driven brain damage in epilepsy accumulates over time, especially in the hippocampus, which can lead to sclerosis, cognitive decline, and death. Excitotoxicity is the prevalent model to explain ictal neurodegeneration. Current labeling technologies cannot distinguish between excitotoxicity and hypoxia, however, because they share common molecular mechanisms. This leaves open the possibility that undetected ischemic hypoxia, due to ictal blood flow restriction, could contribute to neurodegeneration previously ascribed to excitotoxicity. We tested this possibility with Confocal Laser Endomicroscopy (CLE) and novel stereological analyses in several models of epileptic mice. We found a higher number and magnitude of NG2+ mural-cell mediated capillary constrictions in the hippocampus of epileptic mice than in that of normal mice, in addition to spatial coupling between capillary constrictions and oxidative stressed neurons and neurodegeneration. These results reveal a role for hypoxia driven by capillary blood flow restriction in ictal neurodegeneration.

White matter structure changes as adults learn a second language.

Traditional models hold that the plastic reorganization of brain structures occurs mainly during childhood and adolescence, leaving adults with limited means to learn new knowledge and skills. Research within the last decade has begun to overturn this belief, documenting changes in the brain's gray and white matter as healthy adults learn simple motor and cognitive skills [Lövdén, M., Bodammer, N. C., Kühn, S., Kaufmann, J., Schütze, H., Tempelmann, C., et al. Experience-dependent plasticity of white-matter microstructure extends into old age. Neuropsychologia, 48, 3878-3883, 2010; Taubert, M., Draganski, B., Anwander, A., Müller, K., Horstmann, A., Villringer, A., et al. Dynamic properties of human brain structure: Learning-related changes in cortical areas and associated fiber connections. The Journal of Neuroscience, 30, 11670-11677, 2010; Scholz, J., Klein, M. C., Behrens, T. E. J., & Johansen-Berg, H. Training induces changes in white-matter architecture. Nature Neuroscience, 12, 1370-1371, 2009; Draganski, B., Gaser, C., Busch, V., Schuirer, G., Bogdahn, U., & May, A. Changes in grey matter induced by training. Nature, 427, 311-312, 2004]. Although the significance of these changes is not fully understood, they reveal a brain that remains plastic well beyond early developmental periods. Here we investigate the role of adult structural plasticity in the complex, long-term learning process of foreign language acquisition. We collected monthly diffusion tensor imaging scans of 11 English speakers who took a 9-month intensive course in written and spoken Modern Standard Chinese as well as from 16 control participants who did not study a language. We show that white matter reorganizes progressively across multiple sites as adults study a new language. Language learners exhibited progressive changes in white matter tracts associated with traditional left hemisphere language areas and their right hemisphere analogs. Surprisingly, the most significant changes occurred in frontal lobe tracts crossing the genu of the corpus callosum-a region not generally included in current neural models of language processing. These results indicate that plasticity of white matter plays an important role in adult language learning and additionally demonstrate the potential of longitudinal diffusion tensor imaging as a new tool to yield insights into cognitive processes.

BOLD activation varies parametrically with corner angle throughout human retinotopic cortex.

The Alternating Brightness Star (ABS) is an illusion that provides insight into the relationship between brightness perception and corner angle. Recent psychophysical studies of this illusion have shown that corner salience varies parametrically with corner angle, with sharp angles leading to strong illusory percepts and shallow angles leading to weak percepts. It is hypothesized that the illusory effects arise because of an interaction between surface corners and the shape of visual receptive fields: sharp surface corners may create hotspots of high local contrast due to processing by center-surround and other early receptive fields. If this hypothesis is correct, early visual neurons should respond powerfully to sharp corners and curved portions of surface edges. Indeed, the primary role of early visual neurons may be to localize the discontinuities along the edges of surfaces. If so, all early visual areas should show greater BOLD responses to sharp corners than to shallow corners. On the other hand, if corner processing is exclusively constrained to certain areas of the brain, only those specific areas will show greater responses to sharp vs shallow corners. To address this we explored the BOLD correlates of the ABS illusion in the human visual cortex using fMRI. We found that BOLD signal varies parametrically with corner angle throughout the visual cortex, offering the first neurophysiological correlates of the ABS illusion. This finding provides a neurophysiological basis for the previously reported psychophysical data that showed that corner salience varied parametrically with corner angle. We propose that all early visual areas localize discontinuities along the edges of surfaces, and that specific cortical corner-processing circuits further establish the specific nature of those discontinuities, such as their orientation.

Visibility, visual awareness, and visual masking of simple unattended targets are confined to areas in the occipital cortex beyond human V1/V2.

In visual masking, visible targets are rendered invisible by modifying the context in which they are presented, but not by modifying the targets themselves. Here, we localize the neuronal correlates of visual awareness in the human brain by using visual masking illusions. We compare monoptic visual masking activation, which we find within all retinotopic visual areas, with dichoptic masking activation, which we find only in those retinotopic areas downstream of V2. Because monoptic and dichoptic masking are equivalent in magnitude perceptually, the present results establish a lower bound for maintenance of visual awareness of simple unattended targets. Moreover, we find that awareness-correlated circuits for simple targets are restricted to the occipital lobe. This finding provides evidence of an upper boundary in the visual hierarchy for visual awareness of simple unattended targets, thus constraining the location of circuits that maintain the visibility of simple targets to occipital areas beyond V1/V2.