Negative blood oxygen level dependence in the rat: a model for investigating the role of suppression in neurovascular coupling

Modern neuroimaging techniques rely on neurovascular coupling to show regions of increased brain activation. However, little is known of the neurovascular coupling relationships that exist for inhibitory signals. To address this issue directly we developed a preparation to investigate the signal sources of one of these proposed inhibitory neurovascular signals, the negative blood oxygen level-dependent (BOLD) response (NBR), in rat somatosensory cortex. We found a reliable NBR measured in rat somatosensory cortex in response to unilateral electrical whisker stimulation, which was located in deeper cortical layers relative to the positive BOLD response. Separate optical measurements (two-dimensional optical imaging spectroscopy and laser Doppler flowmetry) revealed that the NBR was a result of decreased blood volume and flow and increased levels of deoxyhemoglobin. Neural activity in the NBR region, measured by multichannel electrodes, varied considerably as a function of cortical depth. There was a decrease in neuronal activity in deep cortical laminae. After cessation of whisker stimulation there was a large increase in neural activity above baseline. Both the decrease in neuronal activity and increase above baseline after stimulation cessation correlated well with the simultaneous measurement of blood flow suggesting that the NBR is related to decreases in neural activity in deep cortical layers. Interestingly, the magnitude of the neural decrease was largest in regions showing stimulus-evoked positive BOLD responses. Since a similar type of neural suppression in surround regions was associated with a negative BOLD signal, the increased levels of suppression in positive BOLD regions could importantly moderate the size of the observed BOLD response.

A dynamic causal model of the coupling between pulse stimulation and neural activity

We present a dynamic causal model that can explain context-dependent changes in neural responses, in the rat barrel cortex, to an electrical whisker stimulation at different frequencies. Neural responses were measured in terms of local field potentials. These were converted into current source density (CSD) data, and the time series of the CSD sink was extracted to provide a time series response train. The model structure consists of three layers (approximating the responses from the brain stem to the thalamus and then the barrel cortex), and the latter two layers contain nonlinearly coupled modules of linear second-order dynamic systems. The interaction of these modules forms a nonlinear regulatory system that determines the temporal structure of the neural response amplitude for the thalamic and cortical layers. The model is based on the measured population dynamics of neurons rather than the dynamics of a single neuron and was evaluated against CSD data from experiments with varying stimulation frequency (1–40 Hz), random pulse trains, and awake and anesthetized animals. The model parameters obtained by optimization for different physiological conditions (anesthetized or awake) were significantly different. Following Friston, Mechelli, Turner, and Price (2000), this work is part of a formal mathematical system currently being developed (Zheng et al., 2005) that links stimulation to the blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal through neural activity and hemodynamic variables. The importance of the model described here is that it can be used to invert the hemodynamic measurements of changes in blood flow to estimate the underlying neural activity.

Theory and generalization of Monte Carlo models of the BOLD signal source

The dependency of the blood oxygenation level dependent (BOLD) signal on underlying hemodynamics is not well understood. Building a forward biophysical model of this relationship is important for the quantitative estimation of the hemodynamic changes and neural activity underlying functional magnetic resonance imaging (fMRI) signals. We have developed a general model of the BOLD signal which can model both intra- and extravascular signals for an arbitrary tissue model across a wide range of imaging parameters. The model of the BOLD signal was instantiated as a look-up-table (LuT), and was verified against concurrent fMRI and optical imaging measurements of activation induced hemodynamics. Magn Reson Med, 2008. © 2008 Wiley-Liss, Inc.

A model of the dynamic relationship between blood flow and volume changes during brain activation

The temporal relationship between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is important in the biophysical modeling and interpretation of the hemodynamic response to activation, particularly in the context of magnetic resonance imaging and the blood oxygen level-dependent signal. Grubb et al. (1974) measured the steady state relationship between changes in CBV and CBF after hypercapnic challenge. The relationship CBV proportional to CBFPhi has been used extensively in the literature. Two similar models, the Balloon (Buxton et al., 1998) and the Windkessel (Mandeville et al., 1999), have been proposed to describe the temporal dynamics of changes in CBV with respect to changes in CBF. In this study, a dynamic model extending the Windkessel model by incorporating delayed compliance is presented. The extended model is better able to capture the dynamics of CBV changes after changes in CBF, particularly in the return-to-baseline stages of the response.

Sparse model construction using coordinate descent optimization

We propose a new sparse model construction method aimed at maximizing a model’s generalisation capability for a large class of linear-in-the-parameters models. The coordinate descent optimization algorithm is employed with a modified l1- penalized least squares cost function in order to estimate a single parameter and its regularization parameter simultaneously based on the leave one out mean square error (LOOMSE). Our original contribution is to derive a closed form of optimal LOOMSE regularization parameter for a single term model, for which we show that the LOOMSE can be analytically computed without actually splitting the data set leading to a very simple parameter estimation method. We then integrate the new results within the coordinate descent optimization algorithm to update model parameters one at the time for linear-in-the-parameters models. Consequently a fully automated procedure is achieved without resort to any other validation data set for iterative model evaluation. Illustrative examples are included to demonstrate the effectiveness of the new approaches.

The vertical structure of oceanic Rossby waves: a comparison of high-resolution model data to theoretical vertical structures

Tests of the new Rossby wave theories that have been developed over the past decade to account for discrepancies between theoretical wave speeds and those observed by satellite altimeters have focused primarily on the surface signature of such waves. It appears, however, that the surface signature of the waves acts only as a rather weak constraint, and that information on the vertical structure of the waves is required to better discriminate between competing theories. Due to the lack of 3-D observations, this paper uses high-resolution model data to construct realistic vertical structures of Rossby waves and compares these to structures predicted by theory. The meridional velocity of a section at 24° S in the Atlantic Ocean is pre-processed using the Radon transform to select the dominant westward signal. Normalized profiles are then constructed using three complementary methods based respectively on: (1) averaging vertical profiles of velocity, (2) diagnosing the amplitude of the Radon transform of the westward propagating signal at different depths, and (3) EOF analysis. These profiles are compared to profiles calculated using four different Rossby wave theories: standard linear theory (SLT), SLT plus mean flow, SLT plus topographic effects, and theory including mean flow and topographic effects. Our results support the classical theoretical assumption that westward propagating signals have a well-defined vertical modal structure associated with a phase speed independent of depth, in contrast with the conclusions of a recent study using the same model but for different locations in the North Atlantic. The model structures are in general surface intensified, with a sign reversal at depth in some regions, notably occurring at shallower depths in the East Atlantic. SLT provides a good fit to the model structures in the top 300 m, but grossly overestimates the sign reversal at depth. The addition of mean flow slightly improves the latter issue, but is too surface intensified. SLT plus topography rectifies the overestimation of the sign reversal, but overestimates the amplitude of the structure for much of the layer above the sign reversal. Combining the effects of mean flow and topography provided the best fit for the mean model profiles, although small errors at the surface and mid-depths are carried over from the individual effects of mean flow and topography respectively. Across the section the best fitting theory varies between SLT plus topography and topography with mean flow, with, in general, SLT plus topography performing better in the east where the sign reversal is less pronounced. None of the theories could accurately reproduce the deeper sign reversals in the west. All theories performed badly at the boundaries. The generalization of this method to other latitudes, oceans, models and baroclinic modes would provide greater insight into the variability in the ocean, while better observational data would allow verification of the model findings.

Type-1 error inflation in the traditional by-participant analysis to metamemory accuracy: a generalized mixed-effects model perspective

In order to examine metacognitive accuracy (i.e., the relationship between metacognitive judgment and memory performance), researchers often rely on by-participant analysis, where metacognitive accuracy (e.g., resolution, as measured by the gamma coefficient or signal detection measures) is computed for each participant and the computed values are entered into group-level statistical tests such as the t-test. In the current work, we argue that the by-participant analysis, regardless of the accuracy measurements used, would produce a substantial inflation of Type-1 error rates, when a random item effect is present. A mixed-effects model is proposed as a way to effectively address the issue, and our simulation studies examining Type-1 error rates indeed showed superior performance of mixed-effects model analysis as compared to the conventional by-participant analysis. We also present real data applications to illustrate further strengths of mixed-effects model analysis. Our findings imply that caution is needed when using the by-participant analysis, and recommend the mixed-effects model analysis.

A simple model of the effects of the mid-latitude total ion trough in the bottomsideFlayer on HF radiowave propagation

Observations of the amplitudes and Doppler shifts of received HF radio waves are compared with model predictions made using a two-dimensional ray-tracing program. The signals are propagated over a sub-auroral path, which is shown to lie along the latitudes of the mid-latitude trough at times of low geomagnetic activity. Generalizing the predictions to include a simple model of the trough in the density and height of the F2 peak enables the explanation of the anomalous observed diurnal variations. The behavior of received amplitude, Doppler shift, and signal-to-noise ratio as a function of the Kp index value, the time of day, and the season (in 17 months of continuous recording) is found to agree closely with that predicted using the statistical position of the trough as deduced from 8 years of Alouette satellite soundings. The variation in the times of the observation of large signal amplitudes with the Kp value and the complete absence of such amplitudes when it exceeds 2.75 are two features that implicate the trough in these effects.

Evidence of a topographic signal in surface soil moisture derived from ENVISAT ASAR wide swath data

The susceptibility of a catchment to flooding is affected by its soil moisture prior to an extreme rainfall event. While soil moisture is routinely observed by satellite instruments, results from previous work on the assimilation of remotely sensed soil moisture into hydrologic models have been mixed. This may have been due in part to the low spatial resolution of the observations used. In this study, the remote sensing aspects of a project attempting to improve flow predictions from a distributed hydrologic model by assimilating soil moisture measurements are described. Advanced Synthetic Aperture Radar (ASAR) Wide Swath data were used to measure soil moisture as, unlike low resolution microwave data, they have sufficient resolution to allow soil moisture variations due to local topography to be detected, which may help to take into account the spatial heterogeneity of hydrological processes. Surface soil moisture content (SSMC) was measured over the catchments of the Severn and Avon rivers in the South West UK. To reduce the influence of vegetation, measurements were made only over homogeneous pixels of improved grassland determined from a land cover map. Radar backscatter was corrected for terrain variations and normalized to a common incidence angle. SSMC was calculated using change detection. To search for evidence of a topographic signal, the mean SSMC from improved grassland pixels on low slopes near rivers was compared to that on higher slopes. When the mean SSMC on low slopes was 30–90%, the higher slopes were slightly drier than the low slopes. The effect was reversed for lower SSMC values. It was also more pronounced during a drying event. These findings contribute to the scant information in the literature on the use of high resolution SAR soil moisture measurement to improve hydrologic models.

A model analysis of climate and CO2 controls on tree growth in a semi-arid woodland

We used a light-use efficiency model of photosynthesis coupled with a dynamic carbon allocation and tree-growth model to simulate annual growth of the gymnosperm Callitris columellaris in the semi-arid Great Western Woodlands, Western Australia, over the past 100 years. Parameter values were derived from independent observations except for sapwood specific respiration rate, fine-root turnover time, fine-root specific respiration rate and the ratio of fine-root mass to foliage area, which were estimated by Bayesian optimization. The model reproduced the general pattern of interannual variability in radial growth (tree-ring width), including the response to the shift in precipitation regimes that occurred in the 1960s. Simulated and observed responses to climate were consistent. Both showed a significant positive response of tree-ring width to total photosynthetically active radiation received and to the ratio of modeled actual to equilibrium evapotranspiration, and a significant negative response to vapour pressure deficit. However, the simulations showed an enhancement of radial growth in response to increasing atmospheric CO2 concentration (ppm) ([CO2]) during recent decades that is not present in the observations. The discrepancy disappeared when the model was recalibrated on successive 30-year windows. Then the ratio of fine-root mass to foliage area increases by 14% (from 0.127 to 0.144 kg C m-2) as [CO2] increased while the other three estimated parameters remained constant. The absence of a signal of increasing [CO2] has been noted in many tree-ring records, despite the enhancement of photosynthetic rates and water-use efficiency resulting from increasing [CO2]. Our simulations suggest that this behaviour could be explained as a consequence of a shift towards below-ground carbon allocation.

Serial clustering of extratropical cyclones in a multi-model ensemble of historical and future simulations

This study has investigated serial (temporal) clustering of extra-tropical cyclones simulated by 17 climate models that participated in CMIP5. Clustering was estimated by calculating the dispersion (ratio of variance to mean) of 30 December-February counts of Atlantic storm tracks passing nearby each grid point. Results from single historical simulations of 1975-2005 were compared to those from historical ERA40 reanalyses from 1958-2001 ERA40 and single future model projections of 2069-2099 under the RCP4.5 climate change scenario. Models were generally able to capture the broad features in reanalyses reported previously: underdispersion/regularity (i.e. variance less than mean) in the western core of the Atlantic storm track surrounded by overdispersion/clustering (i.e. variance greater than mean) to the north and south and over western Europe. Regression of counts onto North Atlantic Oscillation (NAO) indices revealed that much of the overdispersion in the historical reanalyses and model simulations can be accounted for by NAO variability. Future changes in dispersion were generally found to be small and not consistent across models. The overdispersion statistic, for any 30 year sample, is prone to large amounts of sampling uncertainty that obscures the climate change signal. For example, the projected increase in dispersion for storm counts near London in the CNRMCM5 model is 0.1 compared to a standard deviation of 0.25. Projected changes in the mean and variance of NAO are insufficient to create changes in overdispersion that are discernible above natural sampling variations.

Vehicle subtype, make and model classification from side profile video

This paper addresses the challenging domain of vehicle classification from pole-mounted roadway cameras, specifically from side-profile views. A new public vehicle dataset is made available consisting of over 10000 side profile images (86 make/model and 9 sub-type classes). 5 state-of-the-art classifiers are applied to the dataset, with the best achieving high classification rates of 98.7% for sub-type and 99.7- 99.9% for make and model recognition, confirming the assertion made that single vehicle side profile images can be used for robust classification.

Regulation of early steps of GPVI signal transduction by phosphatases: a systems biology approach

We present a data-driven mathematical model of a key initiating step in platelet activation, a central process in the prevention of bleeding following Injury. In vascular disease, this process is activated inappropriately and causes thrombosis, heart attacks and stroke. The collagen receptor GPVI is the primary trigger for platelet activation at sites of injury. Understanding the complex molecular mechanisms initiated by this receptor is important for development of more effective antithrombotic medicines. In this work we developed a series of nonlinear ordinary differential equation models that are direct representations of biological hypotheses surrounding the initial steps in GPVI-stimulated signal transduction. At each stage model simulations were compared to our own quantitative, high-temporal experimental data that guides further experimental design, data collection and model refinement. Much is known about the linear forward reactions within platelet signalling pathways but knowledge of the roles of putative reverse reactions are poorly understood. An initial model, that includes a simple constitutively active phosphatase, was unable to explain experimental data. Model revisions, incorporating a complex pathway of interactions (and specifically the phosphatase TULA-2), provided a good description of the experimental data both based on observations of phosphorylation in samples from one donor and in those of a wider population. Our model was used to investigate the levels of proteins involved in regulating the pathway and the effect of low GPVI levels that have been associated with disease. Results indicate a clear separation in healthy and GPVI deficient states in respect of the signalling cascade dynamics associated with Syk tyrosine phosphorylation and activation. Our approach reveals the central importance of this negative feedback pathway that results in the temporal regulation of a specific class of protein tyrosine phosphatases in controlling the rate, and therefore extent, of GPVI-stimulated platelet activation.

Investigation of the impact of anthropogenic heat flux within an urban land surface model and PILPS-urban

Results from the first international urban model comparison experiment (PILPS-Urban) suggested that models which neglected the anthropogenic heat flux within the surface energy balance performed at least as well as models that include the source term, but this could not be explained. The analyses undertaken show that the results from PILPS-Urban were masked by the signal from including vegetation, which was identified in PILPS-Urban as being important. Including the anthropogenic heat flux does give improved performance, but the benefit is small for the site studied given the relatively small magnitude of this flux relative to other terms in the surface energy balance. However, there is no further benefit from including temporal variations in the flux at this site. The importance is expected to increase at sites with a larger anthropogenic heat flux and greater temporal variations.

Mitochondrial sequence data and Dipsacales phylogeny: Mixed models, partitioned Bayesian analyses, and model selection

Phylogenetic analyses of chloroplast DNA sequences, morphology, and combined data have provided consistent support for many of the major branches within the angiosperm, clade Dipsacales. Here we use sequences from three mitochondrial loci to test the existing broad scale phylogeny and in an attempt to resolve several relationships that have remained uncertain. Parsimony, maximum likelihood, and Bayesian analyses of a combined mitochondrial data set recover trees broadly consistent with previous studies, although resolution and support are lower than in the largest chloroplast analyses. Combining chloroplast and mitochondrial data results in a generally well-resolved and very strongly supported topology but the previously recognized problem areas remain. To investigate why these relationships have been difficult to resolve we conducted a series of experiments using different data partitions and heterogeneous substitution models. Usually more complex modeling schemes are favored regardless of the partitions recognized but model choice had little effect on topology or support values. In contrast there are consistent but weakly supported differences in the topologies recovered from coding and non-coding matrices. These conflicts directly correspond to relationships that were poorly resolved in analyses of the full combined chloroplast-mitochondrial data set. We suggest incongruent signal has contributed to our inability to confidently resolve these problem areas. (c) 2007 Elsevier Inc. All rights reserved.