164 research outputs found
Familiarization: A theory of repetition suppression predicts interference between overlapping cortical representations
Repetition suppression refers to a reduction in the cortical response to a novel stimulus that
results from repeated presentation of the stimulus. We demonstrate repetition suppression
in a well established computational model of cortical plasticity, according to which the relative
strengths of lateral inhibitory interactions are modified by Hebbian learning. We present
the model as an extension to the traditional account of repetition suppression offered by
sharpening theory, which emphasises the contribution of afferent plasticity, by instead
attributing the effect primarily to plasticity of intra-cortical circuitry. In support, repetition suppression
is shown to emerge in simulations with plasticity enabled only in intra-cortical connections.
We show in simulation how an extended ‘inhibitory sharpening theory’ can explain
the disruption of repetition suppression reported in studies that include an intermediate
phase of exposure to additional novel stimuli composed of features similar to those of the
original stimulus. The model suggests a re-interpretation of repetition suppression as a manifestation
of the process by which an initially distributed representation of a novel object
becomes a more localist representation. Thus, inhibitory sharpening may constitute a more
general process by which representation emerges from cortical re-organisation
Interpreting BOLD: towards a dialogue between cognitive and cellular neuroscience
Cognitive neuroscience depends on the use of blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to probe brain function. Although commonly used as a surrogate measure of neuronal activity, BOLD signals actually reflect changes in brain blood oxygenation. Understanding the mechanisms linking neuronal activity to vascular perfusion is, therefore, critical in interpreting BOLD. Advances in cellular neuroscience demonstrating differences in this neurovascular relationship in different brain regions, conditions or pathologies are often not accounted for when interpreting BOLD. Meanwhile, within cognitive neuroscience, increasing use of high magnetic field strengths and the development of model-based tasks and analyses have broadened the capability of BOLD signals to inform us about the underlying neuronal activity, but these methods are less well understood by cellular neuroscientists. In 2016, a Royal Society Theo Murphy Meeting brought scientists from the two communities together to discuss these issues. Here we consolidate the main conclusions arising from that meeting. We discuss areas of consensus about what BOLD fMRI can tell us about underlying neuronal activity, and how advanced modelling techniques have improved our ability to use and interpret BOLD. We also highlight areas of controversy in understanding BOLD and suggest research directions required to resolve these issues
Effects of oxidized low density lipoprotein, lipid mediators and statins on vascular cell interactions
The integrin heterodimer CD11b/CD18 (alpha M beta 2, Mac-1, CR3) expressed on monocytes or polymorphonuclear leukocytes (PMN) is a receptor for iC3b, fibrinogen, heparin, and for intercellular adhesion molecule (ICAM)-1 on endothelium, crucially contributing to vascular cell interactions in inflammation and atherosclerosis. In this report, we summarize our findings on the effects of lipid mediators and lipid-lowering drugs. Exposure of endothelial cells to oxidized low density lipoprotein (oxLDL) induces upregulation of ICAM-1 and increases adhesion of monocytic cells expressing Mac-1. Inhibition experiments show that monocytes use distinct ligands, i.e. ICAM-1 and heparan sulfate proteoglycans for adhesion to oxLDL-treated endothelium. An albumin-transferable oxLDL activity is inhibited by the antioxidant pyrrolidine dithiocarbamate (PDTC), while 8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) or lysophosphatidylcholine had no effect, implicating yet unidentified radicals. Sequential adhesive! and signaling events lead to the firm adhesion of rolling PMN on activated and adherent platelets, which may occupy areas of endothelial denudation. Shear resistant arrest of PMN on thrombin-stimulated platelets in flow conditions requires distinct regions of Mac-1, involving its interactions with fibrinogen bound to platelet alpha llb beta 3, and with other platelet ligands. Both arrest and adhesion strengthening under flow are stimulated by platelet-activating factor and leukotriene B4, but not by the chemokine receptor CXCR2. We tested whether Mac-1-dependent monocyte adhesiveness is affected by inhibitors of hydroxy-methylglutaryl-Coenzyme A reductase (statins) which improve morbidity and survival of patients with coronary heart disease. As compared to controls, adhesion of isolated monocytes to endothelium ex vivo was increased in patients with hypercholesterolemia. Treatment with statins decreased total and low density lipoprotein (LDL) cholesterol plasma levels, surface expression of Mac-1, and resulted in a dramatic reduction of Mac,mediated monocyte adhesion to endothelium. The inhibition of monocyte adhesion was reversed by mevalonate but not LDL in vitro,indicating that isoprenoid precursors are crucial for adhesiveness of Mac-1. Such effects may crucially contribute to the clinical benefit of statins, independent of cholesterol-lowering, and may represent a paradigm for novel, anti-inflammatory mechanisms of action by this class of drugs
Self-organising Thermoregulatory Huddling in a Model of Soft Deformable Littermates
Thermoregulatory huddling behaviours dominate the early experiences of developing rodents, and constrain the patterns of sensory and motor input that drive neural plasticity. Huddling is a complex emergent group behaviour, thought to provide an early template for the development of adult social systems, and to constrain natural selection on metabolic physiology. However, huddling behaviours are governed by simple rules of interaction between individuals, which can be described in terms of the thermodynamics of heat exchange, and can be easily controlled by manipulation of the environment temperature. Thermoregulatory huddling thus provides an opportunity to investigate the effects of early experience on brain development in a social, developmental, and evolutionary context, through controlled experimentation. This paper demonstrates that thermoregulatory huddling behaviours can self-organise in a simulation of rodent littermates modelled as soft-deformable bodies that exchange heat during contact. The paper presents a novel methodology, based on techniques in computer animation, for simulating the early sensory and motor experiences of the developing rodent
Coordinated optimization of visual cortical maps (II) Numerical studies
It is an attractive hypothesis that the spatial structure of visual cortical
architecture can be explained by the coordinated optimization of multiple
visual cortical maps representing orientation preference (OP), ocular dominance
(OD), spatial frequency, or direction preference. In part (I) of this study we
defined a class of analytically tractable coordinated optimization models and
solved representative examples in which a spatially complex organization of the
orientation preference map is induced by inter-map interactions. We found that
attractor solutions near symmetry breaking threshold predict a highly ordered
map layout and require a substantial OD bias for OP pinwheel stabilization.
Here we examine in numerical simulations whether such models exhibit
biologically more realistic spatially irregular solutions at a finite distance
from threshold and when transients towards attractor states are considered. We
also examine whether model behavior qualitatively changes when the spatial
periodicities of the two maps are detuned and when considering more than 2
feature dimensions. Our numerical results support the view that neither minimal
energy states nor intermediate transient states of our coordinated optimization
models successfully explain the spatially irregular architecture of the visual
cortex. We discuss several alternative scenarios and additional factors that
may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with
arXiv:1102.335
Coordinated optimization of visual cortical maps (I) Symmetry-based analysis
In the primary visual cortex of primates and carnivores, functional
architecture can be characterized by maps of various stimulus features such as
orientation preference (OP), ocular dominance (OD), and spatial frequency. It
is a long-standing question in theoretical neuroscience whether the observed
maps should be interpreted as optima of a specific energy functional that
summarizes the design principles of cortical functional architecture. A
rigorous evaluation of this optimization hypothesis is particularly demanded by
recent evidence that the functional architecture of OP columns precisely
follows species invariant quantitative laws. Because it would be desirable to
infer the form of such an optimization principle from the biological data, the
optimization approach to explain cortical functional architecture raises the
following questions: i) What are the genuine ground states of candidate energy
functionals and how can they be calculated with precision and rigor? ii) How do
differences in candidate optimization principles impact on the predicted map
structure and conversely what can be learned about an hypothetical underlying
optimization principle from observations on map structure? iii) Is there a way
to analyze the coordinated organization of cortical maps predicted by
optimization principles in general? To answer these questions we developed a
general dynamical systems approach to the combined optimization of visual
cortical maps of OP and another scalar feature such as OD or spatial frequency
preference.Comment: 90 pages, 16 figure
How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers
Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program
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