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At least 307 records · Page 17Linked to original sources

Spatial distribution of neuronal complexity loss in neocortical lesional epilepsies.

PURPOSE: Nonlinear EEG analysis is valuable in characterizing the spatiotemporal dynamics of the epileptogenic process in mesial temporal lobe epilepsy. We examined the ability of the measure neuronal complexity loss (L*) to characterize the primary epileptogenic area of neocortical lesional epilepsies during the interictal state. METHODS: Spatial distribution of L* (L* map) was extracted from electrocorticograms (n = 52) recorded during presurgical assessment via subdural 64-contact grid electrodes covering lesions in either frontal, parietal, or temporal neocortex in 15 patients. The exact location of recording contacts on the brain surface was identified by matching a postimplant lateral x-ray of the skull with a postoperatively obtained sagittal MRI scan. Reprojecting L* maps onto the subject's brain surface allowed us to compare the spatial distribution of L* with the resection range of the extended lesionectomy. RESULTS: In each of the six patients who became seizure-free, maximum values of L* were restricted to recording sites coinciding with the area of resection. In contrast, L* maps of most patients who had no benefit from the resection indicated a more widespread extent or the existence of additional, probably autonomous, foci. The mean of L* values obtained from recording sites outside the area of resection correctly distinguished 13 patients (86.7 %) with respect to seizure outcome. CONCLUSIONS: Relevant information obtained from long-lasting interictal electrocorticographic recordings can be compressed to a single L* map that contributes to a spatial characterization of the primary epileptogenic area. In neocortical lesional epilepsies, L* allows for identification and characterization of epileptogenic activity and thus provides an additional diagnostic tool for presurgical assessment.

Adolescent↗

A recombinogenic targeting method to modify large-inserts for cis-regulatory analysis in transgenic mice: construction and expression of a 100-kb, zebrafish Hoxa-11b-lacZ reporter gene.

The identification of cis-sequences responsible for spatiotemporal patterns of gene expression often requires the functional analysis of large genomic regions. In this study a 100-kb zebrafish Hoxa-11b-lacZ reporter gene was constructed and expressed in transgenic mice. PAC clone 10-O19, containing a portion of the zebrafish HoxA-b cluster, was captured into the yeast-bacterial shuttle vector, pPAC-ResQ, by recombinogenic targeting. A lacZ reporter gene was then inserted in-frame into exon 1 of the zfHoxa-11b locus by a second round of recombinogenic targeting. Expression of the zfHoxa-11b-lacZ reporter gene in 10.5 d.p.f. transgenic mouse embryos was observed only in the posterior portion of the A-P axis, in the paraxial mesoderm, neural tube, and somites. These findings demonstrate the utility of recombinogenic targeting for the modification and expression of large inserts captured from P1/PAC clones.

Animals↗

A biomechanical study of gait initiation in Huntington's disease.

BACKGROUND: Akinesia in basal ganglia disorders is essentially defined by delayed movement initiation; the reaction time increases and it becomes difficult (or even impossible) for the subject to initiate movement. A biomechanical study of gait initiation would help evaluate the role of akinesia in early stage Huntington's disease (HD) patients. METHODS: We recorded kinematic, spatiotemporal and angular parameters (using video motion analysis, a force platform and an optoelectronic system) for the first two steps taken by 15 HD patients and 15 gender- and age-matched controls. In order to evaluate the influence of an external cue on gait initiation parameters, we studied two movement paradigms: self-triggered initiation and initiation triggered (cued) by a "beep" sound. We analyzed kinematic, spatiotemporal (the speed, length and duration of the two first steps) and angular parameters (range of joint angles) as well as kinetic data (the trajectory of the centre of pressure (COP); the speed and trajectory of the centre of mass (COM)). RESULTS: HD patients presented akinesia in both externally triggered and self-triggered conditions. Patients had more difficulties with self-triggered gait than with triggered gait. In HD, anticipatory postural adjustments (APAs) were more impaired in self-triggered gait initiation than in cued initiation. Indeed, an alteration in the kinetic parameters revealed a reduction in first step speed in both conditions. Hypokinesia (as assessed by a reduction in the range of angle joints) played an important role in this reduction. CONCLUSION: Akinesia is a major feature of impaired gait initiation in HD. The deficiencies in self-triggered initiation in HD seen here fit with a hypothesis whereby deficient internal cueing can be replaced by an external trigger.

Biomechanical Phenomena↗

Application of color Doppler M-mode echocardiography in the assessment of ventricular diastolic function: potential for quantitative analysis.

Color Doppler M-mode echocardiography provides a spatiotemporal map of blood distribution (v(s,t)) within the heart, with a typical temporal resolution of 5 ms, a spatial resolution of 300 microns, and a velocity resolution of 3 cm/s. M-mode echocardiographic data can be obtained along a streamline from the mid-left atrium to the mid-left ventricle from either the apical transthoracic window or the basal transesophageal window. A key parameter of the color Doppler M-mode is the transmitral propagation velocity, the slope of the leading edge of the M-mode derived E-wave. This propagation velocity is significantly less than the velocities measured within the E-wave by pulsed Doppler echocardiography and appears to provide important independent information about left ventricular filling pressures and diastolic function. Furthermore, color M-mode velocities can be processed quantitatively by the Euler equation to yield estimates of the small (< 2 mmHg) pressure gradients between the base and apex during filling, the first time such gradients have been measured noninvasively.

Diastole↗

Neural mechanisms generating respiratory pattern in mammalian brain stem-spinal cord in vitro. I. Spatiotemporal patterns of motor and medullary neuron activity.

1. An analysis of the spatial and temporal patterns of activity of neurons of the respiratory motor-pattern generation system in an in vitro neonatal rat brain stem-spinal cord preparation is presented. Impulse discharge patterns of spinal and cranial moto-neurons as well as respiratory neurons in the medulla were analyzed. Patterns of motoneuronal discharge were characterized at the population level from recordings of motor-nerve discharge and at the single-cell level from intracellular recordings. These patterns were compared to patterns generated in the neonatal rat and adult mammal in vivo to establish the correspondence between in vitro and in vivo states. 2. The in vitro system generated a complex spatiotemporal pattern of spinal and cranial motoneuron activity during inspiratory (I) and expiratory (E) phases of the respiratory cycle. The respiratory cycle consisted of three distinct phases of neuronal activity (I, early E, and late E phase) similar to the temporal organization of the cycle in the intact mammal. The spike discharge pattern of motoneurons during the I phase consisted of a rapidly peaking-slowly decrementing discharge envelope with a high degree of synchronization on a time scale of 25-50 ms (approximately 20-40 Hz). A similar pattern was generated in the neonate in vivo under conditions comparable with the in vitro state (i.e., nervous system isolated from mechanosensory afferent inputs). However, the I-phase-motoneuron discharge pattern and cycle-phase durations differed from those characteristic of the intact neonatal or adult systems in vivo. This difference could be accounted for primarily by removal of vagal mechanosensory afferent inputs. 3. The synaptic drive potentials of spinal motoneurons during the I phase in vitro consisted of a rapidly peaking-slowly decrementing potential envelope similar in shape to the spike-frequency histogram of single motoneurons and the envelope of the motoneuron-population discharge. The drive potentials had prominent high-frequency amplitude fluctuations superimposed on the slower drive-potential envelope that were temporally correlated with the generation of motoneuron action potentials. The dominant frequency components of these fast-membrane-potential oscillations (20-35 Hz) were similar to the frequency components of the amplitude fluctuations in the motoneuron-population discharge. One class of medullary neurons with I-phase discharge also exhibited a rapidly peaking-slowly decrementing pattern of impulse discharge and synaptic drive potential with similar high-frequency components.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Tuning of a basic coordination pattern constructs straight-ahead and curved walking in humans.

We tested the hypothesis that common principles govern the production of the locomotor patterns for both straight-ahead and curved walking. Whole body movement recordings showed that continuous curved walking implies substantial, limb-specific changes in numerous gait descriptors. Principal component analysis (PCA) was used to uncover the spatiotemporal structure of coordination among lower limb segments. PCA revealed that the same kinematic law accounted for the coordination among lower limb segments during both straight-ahead and curved walking, in both the frontal and sagittal planes: turn-related changes in the complex behavior of the inner and outer limbs were captured in limb-specific adaptive tuning of coordination patterns. PCA was also performed on a data set including all elevation angles of limb segments and trunk, thus encompassing 13 degrees of freedom. The results showed that both straight-ahead and curved walking were low dimensional, given that 3 principal components accounted for more than 90% of data variance. Furthermore, the time course of the principal components was unchanged by curved walking, thereby indicating invariant coordination patterns among all body segments during straight-ahead and curved walking. Nevertheless, limb- and turn-dependent tuning of the coordination patterns encoded the adaptations of the limb kinematics to the actual direction of the walking body. Absence of vision had no significant effect on the intersegmental coordination during either straight-ahead or curved walking. Our findings indicate that kinematic laws, probably emerging from the interaction of spinal neural networks and mechanical oscillators, subserve the production of both straight-ahead and curved walking. During locomotion, the descending command tunes basic spinal networks so as to produce the changes in amplitude and phase relationships of the spinal output, sufficient to achieve the body turn.

Adaptation, Physiological↗

Architectural dynamics of F-actin in eupodia suggests their role in invasive locomotion in Dictyostelium.

Eupodia are F-actin-containing cortical structures similar to vertebrate podosomes or invadopodia found in metastatic cells. Eupodia are rich in alpha-actinin and myosin IB/D, but not a Dictyostelium homologue of talin. In the present study, we localized other actin-binding proteins, ABP120, cofilin, coronin, and fimbrin, in the eupodia and examined the three-dimensional organization of their F-actin system by confocal microscopy and transmission electron microscopy. To examine their function, we analyzed the assembly and disassembly dynamics of the F-actin system in eupodia and its relation to lamellipodial protrusion. Actin dynamics was examined by monitoring S65T-GFP-coronin and rhodamine-actin using a real-time confocal unit and a digital microscope system. Fluorescence morphometric analysis demonstrates the presence of a precise spatiotemporal coupling between F-actin assembly in eupodia and lamellipodial protrusion. When a lamellipodium advances to invade a tight space, additional rows of eupodia are sequentially formed at the base of that lamellipodium. These results indicate that mechanical stress at the leading edge modulates the structural integrity of actin and its binding proteins, such that eupodia are formed when anchorage is needed to boost for invasive protrusion of the leading edge.

Actin Depolymerizing Factors↗

Efficient mapping of California mortality fields at different spatial scales.

A meaningful characterization of epidemiologic fields (mortality, incidence rate, etc.) often involves the assessment of their spatiotemporal variation at multiple scales. An adequate analysis should depend on the scale at which the epidemiologic field is considered rather than being limited by the scale at which the data are available. In many studies, for example, data are available at a larger scale (say, counties), whereas the epidemiologist is interested in a smaller-scale analysis (say, residential neighborhoods). We propose a mathematically rigorous and epidemiologically meaningful multiscale approach that uses the well-known BME theory to study important scale effects and generate informative scale-dependent maps. The approach is applied to a real-world case study involving daily mortality counts in the state of California. The approach accounts for scale effects and produces mortality predictions at the zip-code scale by downscaling data from the county scale. The multiscale approach is tested by means of a verification data set with detailed mortality information at the zip-code level for 1 day. A measure of mapping accuracy is used to demonstrate that the multiscale approach offers more accurate mortality predictions at the local scale than existing approaches, which do not account for scale effects.

California↗

Evidence implicating BRD1 with brain development and susceptibility to both schizophrenia and bipolar affective disorder.

Linkage studies suggest that chromosome 22q12-13 may contain one or more shared susceptibility genes for schizophrenia (SZ) and bipolar affective disorder (BPD). In a Faeroese sample, we previously reported association between microsatellite markers located at 22q13.31-qtel and both disorders. The present study reports an association analysis across five genes (including 14 single nucleotide and two microsatellite polymorphisms) in this interval using a case-control sample of 162 BPD, 103 SZ patients and 200 controls. The bromodomain-containing 1 gene (BRD1), which encodes a putative regulator of transcription showed association with both disorders with minimal P-values of 0.0046 and 0.00001 for single marker and overall haplotype analysis, respectively. A specific BRD1 2-marker 'risk' haplotype showed a frequency of approximately 10% in the combined case group versus approximately 1% in controls (P-value 2.8 x 10(-7)). Expression analysis of BRD1 mRNA revealed widespread expression in mammalian brain tissue, which was substantiated by immunohistochemical detection of BRD1 protein in the nucleus, perikaryal cytosol and proximal dendrites of the neurons in the adult rat, rabbit and human CNS. Quantitative mRNA analysis in developing fetal pig brain revealed spatiotemporal differences with high expression at early embryonic stages, with intense nuclear and cytosolar immunohistochemical staining of the neuroepithelial layer and early neuroblasts, whilst more mature neurons at later embryonic stages had less nuclear staining. The results implicate BRD1 with SZ and BPD susceptibility and provide evidence that suggests a role for BRD1 in neurodevelopment.

Animals↗

kltool: A tool to analyze spatiotemporal complexity.

We announce the availability of a software package, called kltool, that can extract phase space information from complex spatiotemporal data via the Karhunen-Loeve analysis. Data generated by the periodic, quasiperiodic or chaotic evolution of a small number of spatially coherent structures can be processed. A key feature of kltool is that it allows the user to interact easily with the data processing and its graphical display. We illustrate the use of kltool on numerical data from the Kuramoto-Sivashinsky equation and laboratory data from a flame experiment.

Journal Article↗

Partial synchronization and spontaneous spatial ordering in coupled chaotic systems.

A model of many symmetrically and locally coupled chaotic oscillators is studied. Partial chaotic synchronizations associated with spontaneous spatial ordering are demonstrated. Very rich patterns of the system are revealed, based on partial synchronization analysis. The stabilities of different partially synchronous spatiotemporal structures and some dynamical behaviors of these states are discussed both numerically and analytically.

Journal Article↗

Stroke surfaces: temporally coherent artistic animations from video.

The contribution of this paper is a novel framework for synthesizing nonphotorealistic animations from real video sequences. We demonstrate that, through automated mid-level analysis of the video sequence as a spatiotemporal volume--a block of frames with time as the third dimension--we are able to generate animations in a wide variety of artistic styles, exhibiting a uniquely high degree of temporal coherence. In addition to rotoscoping, matting, and novel temporal effects unique to our method, we demonstrate the extension of static nonphotorealistic rendering (NPR) styles to video, including painterly, sketchy, and cartoon shading. We demonstrate how this novel coherent shading framework may be combined with our earlier motion emphasis work to produce a comprehensive "Video Paintbox" capable of rendering complete cartoon-styled animations from video clips.

Algorithms↗

Magnetoencephalography as a research tool in neuroscience: state of the art.

Magnetoencephalography (MEG) is a noninvasive neuroimaging method for detecting, analyzing, and interpreting the magnetic field generated by the electrical activity in the brain. Modern hardware can capture the MEG signal at hundreds of points around the head in a snapshot lasting only a fraction of a millisecond. The sensitivity of modern hardware is high enough to permit the extraction of a clean signal generated by the brain well above the noise level of the MEG hardware. It is possible to identify signatures of superficial and often deep generators in the raw MEG signal, even in snapshots of data. In a more quantitative way, tomographic images of the electrical current density in the brain can be extracted from each snapshot of MEG signal, providing a direct correlate of coherent collective neuronal activity. A number of recent studies have scrutinized brain function in the new spatiotemporal window that real-time tomographic analysis of MEG signals has opened. The results have allowed the variability in a single area to be seen in the context of activity in other areas and background rhythmic activity. In this view, normal brain function is seen as a cascade of extremely fast events and the unfolding of specialized processes, segregated in space and time and organized into well-defined stages of processing.

Animals↗

Dissection of NT3 functions in vivo by gene replacement strategy.

The development of the peripheral nervous system is governed in part by a family of neurotrophic factors that signal through Trk tyrosine kinase receptors. Neurotrophin 3 (NT3) ablation in mice causes a more severe neuronal phenotype than deletion of its receptor TrkC, suggesting that NT3 acts also through other non-preferred Trk receptors. To study the role of low-affinity ligand receptor interactions in vivo, we have replaced the Nt3 gene with the gene for brain-derived neurotrophic factor (BDNF), a TrkB ligand. As in NT3 and TrkC null mice, the proprioception system of these mutants failed to assemble. However, sensory fiber projections in the embryonic spinal cord suggest chemotropic effects of BDNF in vivo. In the dorsal root ganglia, the developmental dynamic of neuron numbers demonstrates that NT3 is required for activation of TrkB during neurogenesis and that TrkA is required during target tissue innervation. In the inner ear, the ectopic BDNF rescued the severe neuronal deficits caused by NT3 absence, indicating that TrkB and TrkC activate equivalent pathways to promote survival of cochlear neurons. However, specific increased innervation densities suggest unique functions for BDNF and NT3 beyond promoting neuronal survival. This mouse model has allowed the dissection of specific spatiotemporal Trk receptor activation by NT3. Our analysis provides examples of how development can be orchestrated by complex high- and low-affinity interactions between ligand and receptor families.

Animals↗

Genotyping of Cre-lox mice and detection of tissue-specific recombination by multiplex PCR.

Conditional gene targeting, based on Cre-lox or other systems, requires frequent genotyping of transgenic mouse populations and monitoring of tissue-specific Cre recombinatory efficiency. This is currently achieved by Southern analysis from tail- and tissue-derived DNA. Multiplex PCR amplification of the floxed (flanked by loxP sites) genomic region, combined with the PCR detection of the Cre transgene, simplifies this task. Here, we show that complete genotyping of a floxed locus is possible with three appropriately placed primers and that this triplex PCR can be performed simultaneously with a universal PCR assay for the detection of Cre transgenes. Using this approach, we also determined the ratios of recombined versus non-recombined floxed genomic segments in genomic DNA samples. This allowed us to estimate the efficiency of in vivo conditional inactivation from biopsy material and tissue samples that were too small for Southern analysis. As many new conditional knockouts are spatiotemporally restricted, such assays will become increasingly useful. The proposed PCR strategy is flexible and may be adapted to the structural specificities of any target gene.

Alleles↗

Spatiotemporal profile of synaptic activation produced by the electrical and visual stimulation of retinal inputs to the optic tectum: a current source density analysis in the pigeon (Columba livia).

The optic tectum of the pigeon is a highly organized, multilayered structure that receives a massive polystratified afference of at least five different populations of retinal ganglion cells and gives rise to various anatomically segregated efferent systems. The synaptic organization of retino-tectal circuitry is, at present, mostly unknown. To investigate the spatiotemporal profile of synaptic activation produced by differential (electrical and visual) stimulation of the retinal inputs, we performed a high-spatial-resolution current source density analysis in the optic tectum of the anaesthetized pigeon. Electrical stimuli consisted of brief pulses of different durations applied to the optic nerve head, while visual stimuli consisted of light flashes of different intensities. Electrical stimulation generated sinks confined to retinorecipient layers. The temporal structure, spatial location and thresholds of these sinks indicated that they are all due to primary tectal synapses of retinal fibers with different conduction velocities. Sinks evoked by the fastest retinal axons were more superficially located than sinks produced by slower retinal fibers. Visual stimulation, on the other hand, resulted in a more complex pattern of current sinks, with various sinks located in the retinorecipient layers and also well below. Visual stimulation induced action potentials at superficial as well as deep tectal levels. We conclude that electrical stimulation activates most of the populations of ganglion cells as well as their primary tectal synapses, but is unable to elicit a significant activation of secondary tectal synapses. Visual stimulation, on the contrary, activates just some of the incoming retinal populations, but in a way that produces noticeable secondary activation of intratectal circuits. Laminar segregation of retinally evoked tectal activity, as reported here, has also been found in other vertebrates. Similarities and differences with previous studies are discussed.

Animals↗

Single quantum dot tracking based on perceptual grouping using minimal paths in a spatiotemporal volume.

Semiconductor quantum dots (QDs) are new fluorescent probes with great promise for ultrasensitive biological imaging. When detected at the single-molecule level, QD-tagged molecules can be observed and tracked in the membrane of live cells over unprecedented durations. The motion of these individual molecules, recorded in sequences of fluorescence images, can reveal aspects of the dynamics of cellular processes that remain hidden in conventional ensemble imaging. Due to QD complex optical properties, such as fluorescence intermittency, the quantitative analysis of these sequences is, however, challenging and requires advanced algorithms. We present here a novel approach, which, instead of a frame by frame analysis, is based on perceptual grouping in a spatiotemporal volume. By applying a detection process based on an image fluorescence model, we first obtain an unstructured set of points. Individual molecular trajectories are then considered as minimal paths in a Riemannian metric derived from the fluorescence image stack. These paths are computed with a variant of the fast marching method and few parameters are required. We demonstrate the ability of our algorithm to track intermittent objects both in sequences of synthetic data and in experimental measurements obtained with individual QD-tagged receptors in the membrane of live neurons. While developed for tracking QDs, this method can, however, be used with any fluorescent probes.

Algorithms↗