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The multiscale character of evoked cortical activity.

Both the architecture and the dynamics of the brain have characteristic features at different spatial scales. However, the existence, nature and function of dynamical interdependencies between such scales have not been investigated. We studied the multiscale properties of functional magnetic resonance imaging (fMRI) data acquired while human subjects viewed a visual image. Traditional "region of interest" analysis of this data set revealed evoked activity in primary and extrastriate visual cortex. Wavelet transform in the spatial domain provides a multiscale representation of this evoked brain activity. Studying the correlation structure of this representation revealed strong and novel interdependencies in these data within and between different spatial scales. We found that such correlations are stronger than those evident in the original data and comparable in magnitude to those obtained after Gaussian smoothing. However, analysis of the data in the wavelet domain revealed additional structure such as positive correlations, strong anti-correlations and phase-lagged interdependencies. Statistical significance of these effects was inferred through nonparametric bootstrap techniques. We conclude that the spatial analysis of functional neuroimaging data in the wavelet domain provides novel information which may reflect complex spatiotemporal neuronal activity and information encoding. It also affords a quantitative means of testing hierarchical and multiscale models of cortical activity.

Adult↗

Long-range control of gene expression: emerging mechanisms and disruption in disease.

Transcriptional control is a major mechanism for regulating gene expression. The complex machinery required to effect this control is still emerging from functional and evolutionary analysis of genomic architecture. In addition to the promoter, many other regulatory elements are required for spatiotemporally and quantitatively correct gene expression. Enhancer and repressor elements may reside in introns or up- and downstream of the transcription unit. For some genes with highly complex expression patterns--often those that function as key developmental control genes--the cis-regulatory domain can extend long distances outside the transcription unit. Some of the earliest hints of this came from disease-associated chromosomal breaks positioned well outside the relevant gene. With the availability of wide-ranging genome sequence comparisons, strong conservation of many noncoding regions became obvious. Functional studies have shown many of these conserved sites to be transcriptional regulatory elements that sometimes reside inside unrelated neighboring genes. Such sequence-conserved elements generally harbor sites for tissue-specific DNA-binding proteins. Developmentally variable chromatin conformation can control protein access to these sites and can regulate transcription. Disruption of these finely tuned mechanisms can cause disease. Some regulatory element mutations will be associated with phenotypes distinct from any identified for coding-region mutations.

Animals↗

Ring formation in nanoliter cups: quantitative measurements of flow in micromachined wells.

Drying of DNA spots on microarrays and spilled coffee yields ringlike stains, because the outward flow transports dissolved particles to the border. Contact line pinning and diffusion limited evaporation of a liquid sample are the two necessary conditions to induce an outward directed liquid flow during evaporation. In this paper we present quantitative measurements of this flow field visualized by microspheres which are injected into a liquid sample in circular wells with a radius of 100-150 micro m and a depth of 6 micro m. The motion, including Brownian motion, of these microspheres with a radius of 0.25 micro m is recorded using digital fluorescence microscopy. Our analysis, using optic flow, does not require object identification, nor tracking of the individual objects. The spatiotemporal measurement space is sparsely filled at only those space/time positions where a microsphere is present. A confidence measure is computed indicating the presence of microspheres in this measurement space. The circular well shape allows us to transform the sparse measurement space into a denser, averaged radial velocity field. In this transformation we "interpolate" the radial velocity between values with a high confidence, which results in quantitative measurements of this outward flow field during the complete time interval of the evaporation process and at all radial positions in the circular wells. This allows for a quantitative validation of the elegant theory of ring formation.

Journal Article↗

Generation of dynamic structures in nonequilibrium reactive bilayers.

We present a nonequlibrium approach for the study of a flexible bilayer whose two components induce distinct curvatures. In turn, the two components are interconverted by an externally promoted reaction. Phase separation of the two species in the surface results in the growth of domains characterized by different local composition and curvature modulations. This domain growth is limited by the effective mixing due to the interconversion reaction, leading to a finite characteristic domain size. In addition to these effects, first introduced in our earlier work [Phys. Rev. E 71, 051906 (2005)], the important new feature is the assumption that the reactive process actively affects the local curvature of the bilayer. Specifically, we suggest that a force energetically activated by external sources causes a modification of the shape of the membrane at the reaction site. Our results show the appearance of a rich and robust dynamical phenomenology that includes the generation of traveling and/or oscillatory patterns. Linear stability analysis, amplitude equations, and numerical simulations of the model kinetic equations confirm the occurrence of these spatiotemporal behaviors in nonequilibrium reactive bilayers.

Computer Simulation↗

Postural performance and strategy in the unipedal stance of soccer players at different levels of competition.

CONTEXT: Sport training enhances the ability to use somatosensory and otolithic information, which improves postural capabilities. Postural changes are different according to the sport practiced, but few authors have analyzed subjects' postural performances to discriminate the expertise level among highly skilled athletes within a specific discipline. OBJECTIVE: To compare the postural performance and the postural strategy between soccer players at different levels of competition (national and regional). DESIGN: Repeated measures with 1 between-groups factor (level of competition: national or regional) and 1 within-groups factor (vision: eyes open or eyes closed). Dependent variables were center-of-pressure surface area and velocity; total spectral energy; and percentage of low-, medium-, and high-frequency band. SETTING: Sports performance laboratory. PATIENTS OR OTHER PARTICIPANTS: Fifteen national male soccer players (age = 24 +/- 3 years, height = 179 +/- 5 cm, mass = 72 +/- 3 kg) and 15 regional male soccer players (age = 23 +/- 3 years, height = 174 +/- 4 cm, mass = 68 +/- 5 kg) participated in the study. INTERVENTION(S): The subjects performed posturographic tests with eyes open and closed. MAIN OUTCOME MEASURE(S): While subjects performed static and dynamic posturographic tests, we measured the center of foot pressure on a force platform. Spatiotemporal center-of-pressure measurements were used to evaluate the postural performance, and a frequency analysis of the center-of-pressure excursions (fast Fourier transform) was conducted to estimate the postural strategy. RESULTS: Within a laboratory task, national soccer players produced better postural performances than regional players and had a different postural strategy. The national players were more stable than the regional players and used proprioception and vision information differently. CONCLUSIONS: In the test conditions specific to playing soccer, level of playing experience influenced postural control performance measures and strategies.

Journal Article↗

A qualitative dynamic analysis of reiterant speech production: phase portraits, kinematics, and dynamic modeling.

The departure point of the present paper is our effort to characterize and understand the spatiotemporal structure of articulatory patterns in speech. To do so, we removed segmental variation as much as possible while retaining the spoken act's stress and prosodic structure. Subjects produced two sentences from the "rainbow passage" using reiterant speech in which normal syllables were replaced by /ba/ or /ma/. This task was performed at two self-selected rates, conversational and fast. Infrared LEDs were placed on the jaw and lips and monitored using a modified SELSPOT optical tracking system. As expected, when pauses marking major syntactic boundaries were removed, a high degree of rhythmicity within rate was observed, characterized by well-defined periodicities and small coefficients of variation. When articulatory gestures were examined geometrically on the phase plane, the trajectories revealed a scaling relation between a gesture's peak velocity and displacement. Further quantitative analysis of articulator movement as a function of stress and speaking rate was indicative of a language-modulated dynamical system with linear stiffness and equilibrium (or rest) position as key control parameters. Preliminary modeling was consonant with this dynamical perspective which, importantly, does not require that time per se be a controlled variable.

Female↗

Nonlinear dynamics of direction-selective recurrent neural media.

The direction selectivity of cortical neurons can be accounted for by asymmetric lateral connections. Such lateral connectivity leads to a network dynamics with characteristic properties that can be exploited for distinguishing in neurophysiological experiments this mechanism for direction selectivity from other possible mechanisms. We present a mathematical analysis for a class of direction-selective neural models with asymmetric lateral connections. Contrasting with earlier theoretical studies that have analyzed approximations of the network dynamics by neglecting nonlinearities using methods from linear systems theory, we study the network dynamics with nonlinearity taken into consideration. We show that asymmetrically coupled networks can stabilize stimulus-locked traveling pulse solutions that are appropriate for the modeling of the responses of direction-selective neurons. In addition, our analysis shows that outside a certain regime of stimulus speeds the stability of these solutions breaks down, giving rise to lurching activity waves with specific spatiotemporal periodicity. These solutions, and the bifurcation by which they arise, cannot be easily accounted for by classical models for direction selectivity.

Animals↗

Analysis of Krüppel control elements reveals that localized expression results from the interaction of multiple subelements.

The Drosophila gap gene Krüppel (Kr) displays a complex spatiotemporal pattern of expression during embryogenesis. Using P-element transformation experiments, we demonstrate that control elements guiding Kr expression in the central or in the anterior domain at the blastoderm stage are each composed of multiple subelements that interact synergistically. We provide evidence that bicoid (bcd) and hunch-back (hb) gene products, as well as at least one other activator, are needed to activate Kr expression in the central domain. We localize and describe regulatory elements within the 4.1-kilobase region proximal to the Kr promoter that are responsible for expression in the ectoderm, mesoderm, amnioserosa, and nervous system. Finally, a protein instability motif encoded in the second exon appears to be important for resetting the dynamic Kr pattern.

Animals↗

Second-order reversed phi.

In a first-order reversed-phi motion stimulus (Anstis, 1970), the black-white contrast of successive frames is reversed, and the direction of apparent motion may, under some conditions, appear to be reversed. It is demonstrated here that, for many classes of stimuli, this reversal is a mathematical property of the stimuli themselves, and the real problem is in perceiving forward motion, which involves the second- or third-order motion systems or both. Three classes of novel second-order reversed-phi stimuli (contrast, spatial frequency, and flicker modulation) that are invisible to first-order motion analysis were constructed. In these stimuli, the salient stimulus features move in the forward (feature displacement) direction, but the second-order motion energy model predicts motion in the reversed direction. In peripheral vision, for all stimulus types and all temporal frequencies, all the observers saw only the reversed-phi direction of motion. In central vision, the observers also perceived reversed motion at temporal frequencies above about 4 Hz, but they perceived movement in the forward direction at lower temporal frequencies. Since all of these stimuli are invisible to first-order motion, these results indicate that the second-order reversed-phi stimuli activate two subsequent competing motion mechanisms, both of which involve an initial stage of texture grabbing (spatiotemporal filtering, followed by fullwave rectification). The second-order motion system then applies a Reichardt detector (or equivalently, motion energy analysis) directly to this signal and arrives at the reversed-phi direction. The third-order system marks the location of features that differ from the background (the figure) in a salience map and computes motion in the forward direction from the changes in the spatiotemporal location of these marks. The second-order system's report of reversed movement dominates in peripheral vision and in central vision at higher temporal frequencies, because it has better spatial and temporal resolution than the third-order system, which has a cutoff frequency of 3-4 Hz (Lu & Sperling, 1995b). In central vision, below 3-4 Hz, the third-order system's report of resolvable forward movement of something salient (the figure) dominates the second-order system's report of texture contrast movement.

Adult↗

The effect of pacing strategies on the variability of speech movement sequences in dysarthria.

There are many potential sources of variability in speech production, particularly in individuals with dysarthria. The degree and time course of stabilization of the speech production system during recovery from a neurological insult is not constant across individuals. Another source of variability in speech production is speaking rate. Although individuals with no neurological impairments typically show increased variability at reduced speaking rates, this phenomenon has not been explored extensively in individuals with dysarthria. Because rate control strategies are commonly used in dysarthria treatment, it is of clinical importance to know if individuals with dysarthria produce less variable speech with rate reduction. Six individuals with mild dysarthria, 6 with moderate-to-severe dysarthria, and 6 matched normal controls repeated an utterance in four speaking rate conditions: habitual, fast, breaks between words, and stretched. Data were analyzed using the spatiotemporal index (STI), a composite measure of spatial and temporal variability across token repetitions. The normal controls consistently demonstrated the least variability, regardless of rate condition. Both groups with dysarthria were the least variable in the stretched condition and the most variable in the fast condition. The STI values of the group with moderate-to-severe dysarthria were significantly different from both the individuals with mild dysarthria and the normal controls. There were no significant differences between the group with mild dysarthria and the normal controls. In general, slowing the speaking rate in individuals with dysarthria reduces spatiotemporal variability; however, the effect of reduced spatiotemporal variability on intelligibility requires further investigation.

Adult↗

Effects of an actuated ankle exoskeleton on walking stability in healthy adults: a controlled laboratory study.

BACKGROUND: Ankle exoskeletons are widely used to reduce the metabolic cost of walking, yet their effects on walking stability during unperturbed gait remain insufficiently understood. Walking stability can be characterized using complementary measures that capture stride-to-stride variability, global temporal organization, and local dynamic stability. Understanding how walking with an actuated ankle exoskeleton system influences these different aspects of gait stability is essential for the safe design and control of wearable robotic devices. METHODS: Eighteen healthy adults walked on a treadmill at a constant speed (1.1&#xa0;m/s) with and without an actuated bilateral ankle exoskeleton in a randomized crossover design. Spatiotemporal variability was quantified using coefficients of variation (CoV) of stride length, step width, and stance ratio. Global gait stability was assessed using detrended fluctuation analysis of stride time. Local dynamic stability was evaluated using maximum Lyapunov exponent calculated for the trunk, hip, upper leg, lower leg, and foot. Paired-samples two-sided t-tests were used to compare conditions. RESULTS: Walking with the ankle exoskeleton resulted in increased stride-to-stride spatiotemporal variability, reflected by higher CoV values for stride length (p&#x2009;<&#x2009;0.001) and stance ratio (p&#x2009;=&#x2009;0.005), while mean stride length and step width remained unchanged. Mean stance ratio was reduced in the exoskeleton condition (p&#x2009;<&#x2009;0.001). Global gait stability did not differ between conditions, indicating preserved long-range temporal gait organization. Local dynamic stability increased at the lower leg (p&#x2009;<&#x2009;0.001) and foot (p&#x2009;=&#x2009;0.019) when walking with the exoskeleton. CONCLUSIONS: Walking with the actuated ankle exoskeleton alters gait control across multiple levels during steady walking. While stride-to-stride variability in stride length and stance ratio increased, global gait stability remained unchanged. Local dynamic stability was increased at the lower leg and foot, suggesting segment-specific effects of ankle-level assistance close to the assisted joint. However, these findings should be interpreted as the combined effect of wearing the exoskeleton and receiving active assistance, rather than the isolated effect of plantarflexion assistance. These&#xa0;results provide insight for the design and control of ankle exoskeletons with respect to stability-related effects during walking.

Humans↗

A new concept for EEG/MEG signal analysis: detection of interacting spatial modes.

We propose a new concept for analyzing EEG/MEG data. The concept is based on a projection of the spatiotemporal signal into the relevant phase space and the interpretation of the brain dynamics in terms of dynamical systems theory. The projection is obtained by a simultaneous determination of spatial modes and coefficients of differential equations. The resulting spatiotemporal model can be characterized by stationary points and corresponding potential field maps. Brain information processing can be interpreted by attraction and repulsion of spatial field distributions given by these stationary points. This allows an objective and quantitative characterization of the brain dynamics. We outline this concept and the underlying algorithm. Results of the application of this method to an event related potential (ERP) study of auditory memory processes are discussed.

Algorithms↗

Expression of ADAMTS-5/implantin in human decidual stromal cells: regulatory effects of cytokines.

BACKGROUND: The restricted expression of ADAMTS-5 (A Disintegrin And Metalloproteinase with ThromboSpondin repeats-5) to the maternal-fetal interface in mice has led to this novel metalloproteinase being assigned the trivial name 'implantin'. METHODS: As a first step in determining whether ADAMTS-5 also contributes to the implantation process in humans, we have examined the spatiotemporal expression of this ADAMTS subtype in the endometrium during the menstrual cycle and pregnancy by immunohistochemical analysis. A quantitative competitive PCR (QC-PCR) strategy and western blotting were subsequently used to determine whether interleukin (IL)-1beta and transforming growth factor (TGF)-beta1, two cytokines involved in the formation of the maternal-fetal interface, were capable of regulating ADAMTS-5 messenger RNA (mRNA) and protein levels in primary cultures of stromal cells isolated from first trimester decidual tissues. RESULTS: ADAMTS-5 expression in the stroma of the human endometrium correlates with decidualization of this cellular compartment in vivo. IL-1beta was found to increase (P < 0.05) whereas TGF-beta1 decreased (P < 0.05) ADAMTS-5 mRNA and protein levels in decidual stromal cell cultures in a concentration- and time-dependent manner. These regulatory effects were attenuated by function-perturbing antibodies directed against either cytokine. CONCLUSIONS: ADAMTS-5 expression is restricted to decidualized stromal cells of the human endometrium in vivo and is subject to regulation by cytokines in vitro.

ADAM Proteins↗

Magnetoencephalographic characterization of sleep spindles in humans.

Sleep spindles in EEG recordings of adults are most prominent over the central and frontal midline regions. Early magnetoencephalographic recordings agreed with conventional EEG findings. However, more recent small-array magnetoencephalography and quantitative EEG studies suggest that the source areas for spindles are more widespread. We used a whole-head 122-channel biomagnetometer to characterize the sources of sleep spindles in four normal volunteers. Parallel interactive and automated multiple dipole spatiotemporal source modeling was conducted on the data sets of 10 spindles from each subject. Principal component analysis was used to estimate the number of sources in interactive source modeling, and singular value decomposition was used in automated dipole modeling. Spectral analysis of the epochs containing sleep spindles was performed. Principal component analysis and singular value decomposition suggested that all sleep spindles were made up of activity from multiple sources. Similarly, interactive and automated multiple dipole source modeling showed that three or more sources were present in 75% of spindle bursts. The sources for sleep spindles localized to all four cerebral lobes. Parietal and frontal lobes were the areas most frequently involved. Interactive source modeling resulted in more frequent temporal lobe than occipital dipole localizations; automated source modeling showed more frequent occipital than temporal sources. Spindle source localizations varied across subjects and across different spindles within subjects. Our results indicate that individual sleep spindles are generated by multiple cortical sources that are widespread within and across individuals.

Adolescent↗

Multifrequency control of Faraday wave patterns.

We show how pattern formation in Faraday waves may be manipulated by varying the harmonic content of the periodic forcing function. Our approach relies on the crucial influence of resonant triad interactions coupling pairs of critical standing wave modes with damped, spatiotemporally resonant modes. Under the assumption of weak damping and forcing, we perform a symmetry-based analysis that reveals the damped modes most relevant for pattern selection, and how the strength of the corresponding triad interactions depends on the forcing frequencies, amplitudes, and phases. In many cases, the further assumption of Hamiltonian structure in the inviscid limit determines whether the given triad interaction has an enhancing or suppressing effect on related patterns. Surprisingly, even for forcing functions with arbitrarily many frequency components, there are at most five frequencies that affect each of the important triad interactions at leading order. The relative phases of those forcing components play a key role, sometimes making the difference between an enhancing and suppressing effect. In numerical examples, we examine the validity of our results for larger values of the damping and forcing. Finally, we apply our findings to one-dimensional periodic patterns obtained with impulsive forcing and to two-dimensional superlattice patterns and quasipatterns obtained with multifrequency forcing.

Journal Article↗

Strategies optimize the detection of motion transients.

Strategies are implicitly formed when a task is consistent and can be used to improve performance. To investigate how strategies can alter perceptual performance, I trained animals in a reaction time (RT) detection task in which the probability of a fixed duration motion pulse appearing varied over time in a consistent manner. Consistent with previous studies suggesting the implicit representation of task timing, I found that RTs were inversely related to the probability of the pulse appearing and decreased with training. I then inferred the sensory integration underlying responses using behavioral reverse correlation analysis. This analysis revealed that training and anticipation optimized detection by improving the correlation between sensory integration and the spatiotemporal extent of the motion pulse. Moreover, I found that these improvements in sensory integration could largely explain observed changes in the distribution of RT with training and anticipation. These results suggest that training can increase detection performance by optimizing sensory integration according to implicitly formed representations of the likelihood and nature of the stimulus.

Animals↗

Stanniocalcin 1 (STC1) protein and mRNA are developmentally regulated during embryonic mouse osteogenesis: the potential of stc1 as an autocrine/paracrine factor for osteoblast development and bone formation.

STC1, a mammalian homologue of stanniocalcin (STC) which plays a major role in calcium/phosphate homeostasis in fish, has been recently isolated. We have characterized the spatiotemporal distribution of STC1 mRNA and protein during mouse embryonic development generally and osteogenesis specifically. Northern blotting analysis of whole embryos showed that STC1 mRNA is highly and differentially expressed during embryogenesis. By in situ hybridization, STC1 mRNA was detected early in mesenchymal condensations and was then found to be highly expressed in perichondrial cells, periosteal cells, and then osteoblasts during endochondral bone formation. In bones forming by intramembranous ossification, STC1 mRNA was not detected until osteogenic cells appeared. The cellular distribution of STC1 protein closely corresponded to that of its mRNA, but the protein was also detected in hypertrophic chondrocytes. In the MC3T3-E1 osteogenic cell model, STC1 protein and mRNA were detectable throughout proliferation and differentiation stages but levels were relatively higher late during nodule formation/mineralization phases. For comparison, STC1 mRNA was also found in epithelial cells of both embryonic and adult intestine that had not previously been described among tissues responsive to calcium/phosphate transport. These results suggest that STC1 is expressed in a time- and cell-specific manner and may play an autocrine/paracrine role during osteoblast development and bone formation.

Animals↗

The evolutionary origin of animal cellulose synthase.

Urochordates are the only animals that produce cellulose, a polysaccharide existing primarily in the extracellular matrices of plant, algal, and bacterial cells. Here we report a Ciona intestinalis homolog of cellulose synthase, which is the core catalytic subunit of multi-enzyme complexes where cellulose biosynthesis occurs. The Ciona cellulose synthase gene, Ci-CesA, is a fusion of a cellulose synthase domain and a cellulase (cellulose-hydrolyzing enzyme) domain. Both the domains have no animal homologs in public databases. Exploiting this fusion of atypical genes, we provided evidence of a likely lateral transfer of a bacterial cellulose synthase gene into the urochordate lineage. According to fossil records, this likely lateral acquisition of the cellulose synthase gene may have occurred in the last common ancestor of extant urochordates more than 530 million years ago. Whole-mount in situ hybridization analysis revealed the expression of Ci-CesA in C. intestinalis embryos, and the expression pattern of Ci-CesA was spatiotemporally consistent with observed cellulose synthesis in vivo. We propose here that urochordates may use a laterally acquired "homologous" gene for an analogous process of cellulose synthesis.

Amino Acid Sequence↗