Semantic Categorization of Naming Responses Based on Prearticulatory Electrical Brain Activity.

PURPOSE: Object naming requires visual decoding, conceptualization, semantic categorization, and phonological encoding, all within 400 to 600 ms of stimulus presentation and before a word is spoken. In this study, we sought to predict semantic categories of naming responses based on prearticulatory brain activity recorded with scalp EEG in healthy individuals. METHODS: We assessed 19 healthy individuals who completed a naming task while undergoing EEG. The naming task consisted of 120 drawings of animate/inanimate objects or abstract drawings. We applied a one-dimensional, two-layer, neural network to predict the semantic categories of naming responses based on prearticulatory brain activity. RESULTS: Classifications of animate, inanimate, and abstract responses had an average accuracy of 80%, sensitivity of 72%, and specificity of 87% across participants. Across participants, time points with the highest average weights were between 470 and 490 milliseconds after stimulus presentation, and electrodes with the highest weights were located over the left and right frontal brain areas. CONCLUSIONS: Scalp EEG can be successfully used in predicting naming responses through prearticulatory brain activity. Interparticipant variability in feature weights suggests that individualized models are necessary for highest accuracy. Our findings may inform future applications of EEG in reconstructing speech for individuals with and without speech impairments.

VasoMetrics: unbiased spatiotemporal analysis of microvascular diameter in multi-photon imaging applications.

BACKGROUND: Multi-photon imaging of the cerebrovasculature provides rich data on the dynamics of cortical arterioles, capillaries, and venules. Vascular diameter is the major determinant of blood flow resistance, and is the most commonly quantified metric in studies of the cerebrovasculature. However, there is a lack of accessible and easy-to-use methods to quantify vascular diameter in imaging data. METHODS: We created VasoMetrics, a macro written in ImageJ/Fiji for spatiotemporal analysis of microvascular diameter. The key feature of VasoMetrics is rapid analysis of many evenly spaced cross-sectional lines along the vessel of interest, permitting the extraction of numerous diameter measurements from individual vessels. Here we demonstrated the utility of VasoMetrics by analyzing in vivo multi-photon imaging stacks and movies collected from lightly sedated mice, as well as data from optical coherence tomography angiography (OCTA) of human retina. RESULTS: Compared to the standard approach, which is to measure cross-sectional diameters at arbitrary points along a vessel, VasoMetrics accurately reported spatiotemporal features of vessel diameter, reduced measurement bias and time spent analyzing data, and improved the reproducibility of diameter measurements between users. VasoMetrics revealed the dynamics in pial arteriole diameters during vasomotion at rest, as well as changes in capillary diameter before and after pericyte ablation. Retinal arteriole diameter was quantified from a human retinal angiogram, providing proof-of-principle that VasoMetrics can be applied to contrast-enhanced clinical imaging of microvasculature. CONCLUSIONS: VasoMetrics is a robust macro for spatiotemporal analysis of microvascular diameter in imaging applications.

Brain capillary pericytes exert a substantial but slow influence on blood flow.

The majority of the brain's vasculature is composed of intricate capillary networks lined by capillary pericytes. However, it remains unclear whether capillary pericytes influence blood flow. Using two-photon microscopy to observe and manipulate brain capillary pericytes in vivo, we find that their optogenetic stimulation decreases lumen diameter and blood flow, but with slower kinetics than similar stimulation of mural cells on upstream pial and precapillary arterioles. This slow vasoconstriction was inhibited by the clinically used vasodilator fasudil, a Rho-kinase inhibitor that blocks contractile machinery. Capillary pericytes were also slower to constrict back to baseline following hypercapnia-induced dilation, and slower to dilate towards baseline following optogenetically induced vasoconstriction. Optical ablation of single capillary pericytes led to sustained local dilation and a doubling of blood cell flux selectively in capillaries lacking pericyte contact. These data indicate that capillary pericytes contribute to basal blood flow resistance and slow modulation of blood flow throughout the brain.

Mild pericyte deficiency is associated with aberrant brain microvascular flow in aged PDGFRß+/- mice.

The receptor tyrosine kinase PDGFRß is essential for pericyte migration to the endothelium. In mice lacking one allele of PDGFRß (PDGFRß+/-), previous reports have described an age-dependent loss of pericytes in the brain, leading to cerebrovascular dysfunction and subsequent neurodegeneration reminiscent of that seen in Alzheimer's disease and vascular dementia. We examined 12-20-month-old PDGFRß+/- mice to better understand how pericyte loss affects brain microvascular structure and perfusion in vivo. We observed a mild reduction of cortical pericyte number in PDGFRß+/- mice (27% fewer cell bodies) compared to controls, but no decrease in pericyte coverage of the endothelium. This mild degree of pericyte loss caused no discernable change in cortical microvascular density, length, basal diameter or reactivity to hypercapnia. Yet, it was associated with an increase in basal blood cell velocity, primarily in pre-capillary arterioles. Taken together, our results suggest that mild pericyte loss can lead to aberrant cerebral blood flow despite a lack of apparent effect on microvascular structure and reactivity.

Dynamic Remodeling of Pericytes In Vivo Maintains Capillary Coverage in the Adult Mouse Brain.

Direct contact and communication between pericytes and endothelial cells is critical for maintenance of cerebrovascular stability and blood-brain barrier function. Capillary pericytes have thin processes that reach hundreds of micrometers along the capillary bed. The processes of adjacent pericytes come in close proximity but do not overlap, yielding a cellular chain with discrete territories occupied by individual pericytes. Little is known about whether this pericyte chain is structurally dynamic in the adult brain. Using in vivo two-photon imaging in adult mouse cortex, we show that while pericyte somata were immobile, the tips of their processes underwent extensions and/or retractions over days. The selective ablation of single pericytes provoked exuberant extension of processes from neighboring pericytes to contact uncovered regions of the endothelium. Uncovered capillary regions had normal barrier function but were dilated until pericyte contact was regained. Pericyte structural plasticity may be critical for cerebrovascular health and warrants detailed investigation.