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.

A time-invariant visco-elastic windkessel model relating blood flow and blood volume

The difference between the rate of change of cerebral blood volume (CBV) and cerebral blood flow (CBF) following stimulation is thought to be due to circumferential stress relaxation in veins (Mandeville, J.B., Marota, J.J.A., Ayata, C., Zaharchuk, G., Moskowitz, M.A., Rosen, B.R., Weisskoff, R.M., 1999. Evidence of a cerebrovascular postarteriole windkessel with delayed compliance. J. Cereb. Blood Flow Metab. 19, 679–689). In this paper we explore the visco-elastic properties of blood vessels, and present a dynamic model relating changes in CBF to changes in CBV. We refer to this model as the visco-elastic windkessel (VW) model. A novel feature of this model is that the parameter characterising the pressure–volume relationship of blood vessels is treated as a state variable dependent on the rate of change of CBV, producing hysteresis in the pressure–volume space during vessel dilation and contraction. The VW model is nonlinear time-invariant, and is able to predict the observed differences between the time series of CBV and that of CBF measurements following changes in neural activity. Like the windkessel model derived by Mandeville, J.B., Marota, J.J.A., Ayata, C., Zaharchuk, G., Moskowitz, M.A., Rosen, B.R., Weisskoff, R.M., 1999. Evidence of a cerebrovascular postarteriole windkessel with delayed compliance. J. Cereb. Blood Flow Metab. 19, 679–689, the VW model is primarily a model of haemodynamic changes in the venous compartment. The VW model is demonstrated to have the following characteristics typical of visco-elastic materials: (1) hysteresis, (2) creep, and (3) stress relaxation, hence it provides a unified model of the visco-elastic properties of the vasculature. The model will not only contribute to the interpretation of the Blood Oxygen Level Dependent (BOLD) signals from functional Magnetic Resonance Imaging (fMRI) experiments, but also find applications in the study and modelling of the brain vasculature and the haemodynamics of circulatory and cardiovascular systems.

The resting-state neurovascular coupling relationship: rapid changes in spontaneous neural activity in the somatosensory cortex are associated with haemodynamic fluctuations that resemble stimulus-evoked haemodynamics

Although promise exists for patterns of resting-state blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) brain connectivity to be used as biomarkers of early brain pathology, a full understanding of the nature of the relationship between neural activity and spontaneous fMRI BOLD fluctuations is required before such data can be correctly interpreted. To investigate this issue, we combined electrophysiological recordings of rapid changes in multi-laminar local field potentials from the somatosensory cortex of anaesthetized rats with concurrent two-dimensional optical imaging spectroscopy measurements of resting-state haemodynamics that underlie fluctuations in the BOLD fMRI signal. After neural ‘events’ were identified, their time points served to indicate the start of an epoch in the accompanying haemodynamic fluctuations. Multiple epochs for both neural ‘events’ and the accompanying haemodynamic fluctuations were averaged. We found that the averaged epochs of resting-state haemodynamic fluctuations taken after neural ‘events’ closely resembled the temporal profile of stimulus-evoked cortical haemodynamics. Furthermore, we were able to demonstrate that averaged epochs of resting-state haemodynamic fluctuations resembling the temporal profile of stimulus-evoked haemodynamics could also be found after peaks in neural activity filtered into specific electroencephalographic frequency bands (theta, alpha, beta, and gamma). This technique allows investigation of resting-state neurovascular coupling using methodologies that are directly comparable to that developed for investigating stimulus-evoked neurovascular responses.

Late Quaternary fire regimes of Australasia

We have compiled 223 sedimentary charcoal records from Australasia in order to examine the temporal and spatial variability of fire regimes during the Late Quaternary. While some of these records cover more than a full glacial cycle, here we focus on the last 70,000 years when the number of individual records in the compilation allows more robust conclusions. On orbital time scales, fire in Australasia predominantly reflects climate, with colder periods characterized by less and warmer intervals by more biomass burning. The composite record for the region also shows considerable millennial-scale variability during the last glacial interval (73.5–14.7 ka). Within the limits of the dating uncertainties of individual records, the variability shown by the composite charcoal record is more similar to the form, number and timing of Dansgaard–Oeschger cycles as observed in Greenland ice cores than to the variability expressed in the Antarctic ice-core record. The composite charcoal record suggests increased biomass burning in the Australasian region during Greenland Interstadials and reduced burning during Greenland Stadials. Millennial-scale variability is characteristic of the composite record of the sub-tropical high pressure belt during the past 21 ka, but the tropics show a somewhat simpler pattern of variability with major peaks in biomass burning around 15 ka and 8 ka. There is no distinct change in fire regime corresponding to the arrival of humans in Australia at 50 ± 10 ka and no correlation between archaeological evidence of increased human activity during the past 40 ka and the history of biomass burning. However, changes in biomass burning in the last 200 years may have been exacerbated or influenced by humans.

High sensitivity recording of afferent nerve activity using ultra-compliant microchannel electrodes: an acutein vivovalidation

Neuroprostheses interfaced with transected peripheral nerves are technological routes to control robotic limbs as well as convey sensory feedback to patients suffering from traumatic neural injuries or degenerative diseases. To maximize the wealth of data obtained in recordings, interfacing devices are required to have intrafascicular resolution and provide high signal-to-noise ratio (SNR) recordings. In this paper, we focus on a possible building block of a three-dimensional regenerative implant: a polydimethylsiloxane (PDMS) microchannel electrode capable of highly sensitive recordings in vivo. The PDMS 'micro-cuff' consists of a 3.5 mm long (100 µm × 70 µm cross section) microfluidic channel equipped with five evaporated Ti/Au/Ti electrodes of sub-100 nm thickness. Individual electrodes have average impedance of 640 ± 30 kΩ with a phase angle of −58 ± 1 degrees at 1 kHz and survive demanding mechanical handling such as twisting and bending. In proof-of-principle acute implantation experiments in rats, surgically teased afferent nerve strands from the L5 dorsal root were threaded through the microchannel. Tactile stimulation of the skin was reliably monitored with the three inner electrodes in the device, simultaneously recording signal amplitudes of up to 50 µV under saline immersion. The overall SNR was approximately 4. A small but consistent time lag between the signals arriving at the three electrodes was observed and yields a fibre conduction velocity of 30 m s−1. The fidelity of the recordings was verified by placing the same nerve strand in oil and recording activity with hook electrodes. Our results show that PDMS microchannel electrodes open a promising technological path to 3D regenerative interfaces.

A 27 day persistence model of near-Earth solar wind conditions: a long lead-time forecast and a benchmark for dynamical models

Geomagnetic activity has long been known to exhibit approximately 27 day periodicity, resulting from solar wind structures repeating each solar rotation. Thus a very simple near-Earth solar wind forecast is 27 day persistence, wherein the near-Earth solar wind conditions today are assumed to be identical to those 27 days previously. Effective use of such a persistence model as a forecast tool, however, requires the performance and uncertainty to be fully characterized. The first half of this study determines which solar wind parameters can be reliably forecast by persistence and how the forecast skill varies with the solar cycle. The second half of the study shows how persistence can provide a useful benchmark for more sophisticated forecast schemes, namely physics-based numerical models. Point-by-point assessment methods, such as correlation and mean-square error, find persistence skill comparable to numerical models during solar minimum, despite the 27 day lead time of persistence forecasts, versus 2–5 days for numerical schemes. At solar maximum, however, the dynamic nature of the corona means 27 day persistence is no longer a good approximation and skill scores suggest persistence is out-performed by numerical models for almost all solar wind parameters. But point-by-point assessment techniques are not always a reliable indicator of usefulness as a forecast tool. An event-based assessment method, which focusses key solar wind structures, finds persistence to be the most valuable forecast throughout the solar cycle. This reiterates the fact that the means of assessing the “best” forecast model must be specifically tailored to its intended use.

The transient atmospheric response to midlatitude SST anomalies

To study the transient atmospheric response to midlatitude SST anomalies, a three-layer quasigeostrophic (QG) model coupled to a slab oceanic mixed layer in the North Atlantic is used. As diagnosed from a coupled run in perpetual winter conditions, the first two modes of SST variability are linked to the model North Atlantic Oscillation (NAO) and eastern Atlantic pattern (EAP), respectively, the dominant atmospheric modes in the Atlantic sector. The two SST anomaly patterns are then prescribed as fixed anomalous boundary conditions for the model atmosphere, and its transient responses are established from a large ensemble of simulations. In both cases, the tendency of the air–sea heat fluxes to damp the SST anomalies results in an anomalous diabatic heating of the atmosphere that, in turn, forces a baroclinic response, as predicted by linear theory. This initial response rapidly modifies the transient eddy activity and thus the convergence of eddy momentum and heat fluxes. The latter transforms the baroclinic response into a growing barotropic one that resembles the atmospheric mode that had created the SST anomaly in the coupled run and is thus associated with a positive feedback. The total adjustment time is as long as 3–4 months for the NAO-like response and 1–2 months for the EAP-like one. The positive feedback, in both cases, is dependent on the polarity of the SST anomaly, but is stronger in the NAO case, thereby contributing to its predominance at low frequency in the coupled system. However, the feedback is too weak to lead to an instability of the atmospheric modes and primarily results in an increase of their amplitude and persistence and a weakening of the heat flux damping of the SST anomaly.

Exposure to parabens at the concentration of maximal proliferative response increases migratory and invasive activity of human breast cancer cells in vitro

Alkyl esters of p–hydroxybenzoic acid (parabens) are widely used as preservatives in personal care products, foods and pharmaceuticals. Their oestrogenic activity, their measurement in human breast tissue and their ability to drive proliferation of oestrogen-responsive human breast cancer cells has opened a debate on their potential to influence breast cancer development. Since proliferation is not the only hallmark of cancer cells, we have investigated the effects of exposure to parabens at concentrations of maximal proliferative response on migratory and invasive properties using three oestrogen-responsive human breast cancer cell lines (MCF-7, T-47-D, ZR-75-1). Cells were maintained short-term (1 week) or long-term (20±2 weeks) in phenol-red-free medium containing 5% charcoal-stripped serum with no addition, 10-8M 17-oestradiol, 1-5x10-4M methylparaben, 10-5M n-propylparaben or 10-5M n-butylparaben. Long-term exposure (20±2 weeks) of MCF-7 cells to methylparaben, n-propylparaben or n-butylparaben increased migration as measured using a scratch assay, time-lapse microscopy and xCELLigence technology: invasive properties were found to increase in matrix degradation assays and migration through matrigel on xCELLigence. Western immunoblotting showed an associated downregulation of E-cadherin and -catenin in the long-term paraben-exposed cells which could be consistent with a mechanism involving epithelial to mesenchymal transition. Increased migratory activity was demonstrated also in long-term paraben-exposed T-47-D and ZR-75-1 cells using a scratch assay and time-lapse microscopy. This is the first report that in vitro, parabens can influence not only proliferation but also migratory and invasive properties of human breast cancer cells.

Postglacial vegetation, fire and climate dynamics at Central Chilean Patagonia (Lake Shaman, 44ºS)

A 19 cal ka BP pollen and charcoal record from Lake Shaman (44°S; 71°W, Chile) was analyzed to establish vegetation, fire and climate dynamics of the forest-steppe ecotone in Central Chilean Patagonia. Lake Shaman record indicates that the upper Río Cisnes valley was free of ice at around 19 cal ka BP. From this date and until 14.8 cal ka BP, a grass steppe with high proportions of shrubs associated to colder and drier conditions than present developed in this area. A continuous increase of Nothofagus accompanied by a decline in the steppe shrubs and sudden dominance of paludal over aquatic plants from 11 cal ka BP was associated to effective moisture increase but still under modern values. The replacement of the cold-dry grass-shrub steppe by a similar-than-present forest-steppe ecotone suggests an increase in temperature indicating the onset of the Holocene. At the same time, moderate fire activity suggested by the charcoal record could be related to major fuel availability as consequence of Nothofagus forest expansion. Between 8 and 3 cal ka BP, the record indicates the easternmost position of the forest-steppe ecotone suggesting the highest effective moisture with the establishment of seasonality between 5 and 3 cal ka BP. From 3 cal ka BP, the record indicates a retraction of the forest-steppe ecotone accompanied by a high pollen record variability and an increased fire activity. These late changes suggest decreased effective moisture associated with a high climatic variability. At regional and extra-regional scale, climatic changes at Lake Shaman's record are mostly associated to changes (latitudinal shifts and/or strengthening/weakening) of past Southern Westerlies that were previously recorded along Patagonia from the Lateglacial to the mid-Holocene. During the Late Holocene, a regional pattern characterized by high record variability emerges throughout Central Chilean Patagonia. This variability would be related to (1) low magnitude Southern Westerlies changes probably associated to ENSO and/or SAM or (2) the complex relationships between vegetation, fire and human occupations during the last 3 cal ka.

Time to decide? Simplicity and congruity in comparative judgment

What is the relationship between magnitude judgments relying on directly available characteristics versus probabilistic cues? Question frame was manipulated in a comparative judgment task previously assumed to involve inference across a probabilistic mental model (e.g., “which city is largest” – the “larger” question – versus “which city is smallest” – the “smaller” question). Participants identified either the largest or smallest city (Experiments 1a, 2) or the richest or poorest person (Experiment 1b) in a three-alternative forced choice (3-AFC) task (Experiment 1) or 2-AFC task (Experiment 2). Response times revealed an interaction between question frame and the number of options recognized. When asked the smaller question, response times were shorter when none of the options were recognized. The opposite pattern was found when asked the larger question: response time was shorter when all options were recognized. These task-stimuli congruity results in judgment under uncertainty are consistent with, and predicted by, theories of magnitude comparison which make use of deductive inferences from declarative knowledge.

MODIS-based vegetation index has sufficient sensitivity to indicate stand-level intra-seasonal climatic stress in oak and beech forests

Context: Variation in photosynthetic activity of trees induced by climatic stress can be effectively evaluated using remote sensing data. Although adverse effects of climate on temperate forests have been subjected to increased scrutiny, the suitability of remote sensing imagery for identification of drought stress in such forests has not been explored fully. Aim: To evaluate the sensitivity of MODIS-based vegetation index to heat and drought stress in temperate forests, and explore the differences in stress response of oaks and beech. Methods: We identified 8 oak and 13 beech pure and mature stands, each covering between 4 and 13 MODIS pixels. For each pixel, we extracted a time series of MODIS NDVI from 2000 to 2010. We identified all sequences of continuous unseasonal NDVI decline to be used as the response variable indicative of environmental stress. Neural Networks-based regression modelling was then applied to identify the climatic variables that best explain observed NDVI declines. Results: Tested variables explained 84–97% of the variation in NDVI, whilst air temperature-related climate extremes were found to be the most influential. Beech showed a linear response to the most influential climatic predictors, while oak responded in a unimodal pattern suggesting a better coping mechanism. Conclusions: MODIS NDVI has proved sufficiently sensitive as a stand-level indicator of climatic stress acting upon temperate broadleaf forests, leading to its potential use in predicting drought stress from meteorological observations and improving parameterisation of forest stress indices.

The development of time-based prospective memory in childhood: the role of working memory updating

This large-scale study examined the development of time-based prospective memory (PM) across childhood and the roles that working memory updating and time monitoring play in driving age effects in PM performance. One hundred and ninety-seven children aged 5 to 14 years completed a time-based PM task where working memory updating load was manipulated within individuals using a dual task design. Results revealed age-related increases in PM performance across childhood. Working memory updating load had a negative impact on PM performance and monitoring behavior in older children, but this effect was smaller in younger children. Moreover, the frequency as well as the pattern of time monitoring predicted children’s PM performance. Our interpretation of these results is that processes involved in children’s PM may show a qualitative shift over development from simple, nonstrategic monitoring behavior to more strategic monitoring based on internal temporal models that rely specifically on working memory updating resources. We discuss this interpretation with regard to possible trade-off effects in younger children as well as alternative accounts.

A numerical model of the ionospheric signatures of time-varying magnetic reconnection: II. Measuring expansions in the ionospheric flow response

A numerical model embodying the concepts of the Cowley-Lockwood (Cowley and Lockwood, 1992, 1997) paradigm has been used to produce a simple Cowley– Lockwood type expanding flow pattern and to calculate the resulting change in ion temperature. Cross-correlation, fixed threshold analysis and threshold relative to peak are used to determine the phase speed of the change in convection pattern, in response to a change in applied reconnection. Each of these methods fails to fully recover the expansion of the onset of the convection response that is inherent in the simulations. The results of this study indicate that any expansion of the convection pattern will be best observed in time-series data using a threshold which is a fixed fraction of the peak response. We show that these methods used to determine the expansion velocity can be used to discriminate between the two main models for the convection response to a change in reconnection.