137 research outputs found
DMSO-free methods of preserving mesenchymal stem cells (MSCs) that retain high levels of post thaw function
A novel, biologically-inspired strategy was developed to improve the preservation of mesenchymal stem cells (MSCs). MSCs are being investigated for the treatment of cardiovascular disorders, diabetes, connective tissue disorders, acute lung injury, amyotrophic lateral sclerosis, kidney diseases and more. To date, over 300 clinical trials involve the use of MSCs, with well over 2000 patients safely treated.Current methods of preserving MSCs are inadequate/ suboptimal. Concerns over poor post thaw function have become so pervasive that it is now common for MSCs to be cultured for 24-72 h prior to administration. These MSCs have a short shelf life (\u3c 24 hours), require special FDA permission, and the process increases cost and reduces access.
The research described here utilizes an evolutionary algorithm to identify combinations of naturally occurring osmolytes that yield high cell recovery post thaw and optimize the composition of a DMSO-free, protein-free medium for cryopreservation of the cells. Additionally, we demonstrate that these novel solutions maintain MSC functionality when evaluated using surface markers, attachment, proliferation, actin alignment, RNA expression, and DNA hydroxymethlyation.
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Elastic net model of ocular dominance - overall stripe pattern and monocular deprivation
The elastic net (Durbin and Willshaw 1987) can account for the development of both topography and ocular dominance in the mapping from the lateral geniculate nucleus to primary visual cortex (Goodhill and Willshaw 1990). Here it is further shown for this model that (1) the overall pattern of stripes produced is strongly influenced by the shape of the cortex: in particular, stripes with a global order similar to that seen biologically can be produced under appropriate conditions, and (2) the observed changes in stripe width associated with monocular deprivation are reproduced in the model
Perceptual Context in Cognitive Hierarchies
Cognition does not only depend on bottom-up sensor feature abstraction, but
also relies on contextual information being passed top-down. Context is higher
level information that helps to predict belief states at lower levels. The main
contribution of this paper is to provide a formalisation of perceptual context
and its integration into a new process model for cognitive hierarchies. Several
simple instantiations of a cognitive hierarchy are used to illustrate the role
of context. Notably, we demonstrate the use context in a novel approach to
visually track the pose of rigid objects with just a 2D camera
Reconstructing Speech from Human Auditory Cortex
Direct brain recordings from neurosurgical patients listening to speech reveal that the acoustic speech signals can be reconstructed from neural activity in auditory cortex
When Two Become One: The Limits of Causality Analysis of Brain Dynamics
Biological systems often consist of multiple interacting subsystems, the brain being a prominent example. To understand the functions of such systems it is important to analyze if and how the subsystems interact and to describe the effect of these interactions. In this work we investigate the extent to which the cause-and-effect framework is applicable to such interacting subsystems. We base our work on a standard notion of causal effects and define a new concept called natural causal effect. This new concept takes into account that when studying interactions in biological systems, one is often not interested in the effect of perturbations that alter the dynamics. The interest is instead in how the causal connections participate in the generation of the observed natural dynamics. We identify the constraints on the structure of the causal connections that determine the existence of natural causal effects. In particular, we show that the influence of the causal connections on the natural dynamics of the system often cannot be analyzed in terms of the causal effect of one subsystem on another. Only when the causing subsystem is autonomous with respect to the rest can this interpretation be made. We note that subsystems in the brain are often bidirectionally connected, which means that interactions rarely should be quantified in terms of cause-and-effect. We furthermore introduce a framework for how natural causal effects can be characterized when they exist. Our work also has important consequences for the interpretation of other approaches commonly applied to study causality in the brain. Specifically, we discuss how the notion of natural causal effects can be combined with Granger causality and Dynamic Causal Modeling (DCM). Our results are generic and the concept of natural causal effects is relevant in all areas where the effects of interactions between subsystems are of interest
Hemodynamic Traveling Waves in Human Visual Cortex
Functional MRI (fMRI) experiments rely on precise characterization of the blood oxygen level dependent (BOLD) signal. As the spatial resolution of fMRI reaches the sub-millimeter range, the need for quantitative modelling of spatiotemporal properties of this hemodynamic signal has become pressing. Here, we find that a detailed physiologically-based model of spatiotemporal BOLD responses predicts traveling waves with velocities and spatial ranges in empirically observable ranges. Two measurable parameters, related to physiology, characterize these waves: wave velocity and damping rate. To test these predictions, high-resolution fMRI data are acquired from subjects viewing discrete visual stimuli. Predictions and experiment show strong agreement, in particular confirming BOLD waves propagating for at least 5β10 mm across the cortical surface at speeds of 2β12 mm s-1. These observations enable fundamentally new approaches to fMRI analysis, crucial for fMRI data acquired at high spatial resolution
Mapping the Organization of Axis of Motion Selective Features in Human Area MT Using High-Field fMRI
Functional magnetic resonance imaging (fMRI) at high magnetic fields has made it possible to investigate the columnar organization of the human brain in vivo with high degrees of accuracy and sensitivity. Until now, these results have been limited to the organization principles of early visual cortex (V1). While the middle temporal area (MT) has been the first identified extra-striate visual area shown to exhibit a columnar organization in monkeys, evidence of MT's columnar response properties and topographic layout in humans has remained elusive. Research using various approaches suggests similar response properties as in monkeys but failed to provide direct evidence for direction or axis of motion selectivity in human area MT. By combining state of the art pulse sequence design, high spatial resolution in all three dimensions (0.8 mm isotropic), optimized coil design, ultrahigh field magnets (7 Tesla) and novel high resolution cortical grid sampling analysis tools, we provide the first direct evidence for large-scale axis of motion selective feature organization in human area MT closely matching predictions from topographic columnar-level simulations
Mechanisms underlying a thalamocortical transformation during active tactile sensation
During active somatosensation, neural signals expected from movement of the sensors are suppressed in the cortex, whereas information related to touch is enhanced. This tactile suppression underlies low-noise encoding of relevant tactile features and the brainβs ability to make fine tactile discriminations. Layer (L) 4 excitatory neurons in the barrel cortex, the major target of the somatosensory thalamus (VPM), respond to touch, but have low spike rates and low sensitivity to the movement of whiskers. Most neurons in VPM respond to touch and also show an increase in spike rate with whisker movement. Therefore, signals related to self-movement are suppressed in L4. Fast-spiking (FS) interneurons in L4 show similar dynamics to VPM neurons. Stimulation of halorhodopsin in FS interneurons causes a reduction in FS neuron activity and an increase in L4 excitatory neuron activity. This decrease of activity of L4 FS neurons contradicts the "paradoxical effect" predicted in networks stabilized by inhibition and in strongly-coupled networks. To explain these observations, we constructed a model of the L4 circuit, with connectivity constrained by in vitro measurements. The model explores the various synaptic conductance strengths for which L4 FS neurons actively suppress baseline and movement-related activity in layer 4 excitatory neurons. Feedforward inhibition, in concert with recurrent intracortical circuitry, produces tactile suppression. Synaptic delays in feedforward inhibition allow transmission of temporally brief volleys of activity associated with touch. Our model provides a mechanistic explanation of a behavior-related computation implemented by the thalamocortical circuit
Common Cortical Loci Are Activated during Visuospatial Interpolation and Orientation Discrimination Judgements
There is a wealth of literature on the role of short-range interactions between low-level orientation-tuned filters in the perception of discontinuous contours. However, little is known about how spatial information is integrated across more distant regions of the visual field in the absence of explicit local orientation cues, a process referred to here as visuospatial interpolation (VSI). To examine the neural correlates of VSI high field functional magnetic resonance imaging was used to study brain activity while observers either judged the alignment of three Gabor patches by a process of interpolation or discriminated the local orientation of the individual patches. Relative to a fixation baseline the two tasks activated a largely over-lapping network of regions within the occipito-temporal, occipito-parietal and frontal cortices. Activated clusters specific to the orientation task (orientation>interpolation) included the caudal intraparietal sulcus, an area whose role in orientation encoding per se has been hotly disputed. Surprisingly, there were few task-specific activations associated with visuospatial interpolation (VSI>orientation) suggesting that largely common cortical loci were activated by the two experimental tasks. These data are consistent with previous studies that suggest higher level grouping processes -putatively involved in VSI- are automatically engaged when the spatial properties of a stimulus (e.g. size, orientation or relative position) are used to make a judgement
Synchronous chaos and broad band gamma rhythm in a minimal multi-layer model of primary visual cortex
Visually induced neuronal activity in V1 displays a marked gamma-band
component which is modulated by stimulus properties. It has been argued that
synchronized oscillations contribute to these gamma-band activity [...
however,] even when oscillations are observed, they undergo temporal
decorrelation over very few cycles. This is not easily accounted for in
previous network modeling of gamma oscillations. We argue here that
interactions between cortical layers can be responsible for this fast
decorrelation. We study a model of a V1 hypercolumn, embedding a simplified
description of the multi-layered structure of the cortex. When the stimulus
contrast is low, the induced activity is only weakly synchronous and the
network resonates transiently without developing collective oscillations. When
the contrast is high, on the other hand, the induced activity undergoes
synchronous oscillations with an irregular spatiotemporal structure expressing
a synchronous chaotic state. As a consequence the population activity undergoes
fast temporal decorrelation, with concomitant rapid damping of the oscillations
in LFPs autocorrelograms and peak broadening in LFPs power spectra. [...]
Finally, we argue that the mechanism underlying the emergence of synchronous
chaos in our model is in fact very general. It stems from the fact that gamma
oscillations induced by local delayed inhibition tend to develop chaos when
coupled by sufficiently strong excitation.Comment: 49 pages, 11 figures, 7 table
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