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Spatiotemporal pattern of neuroinflammation after impact-acceleration closed head injury in the rat.

Inflammatory processes have been implicated in the pathogenesis of traumatic brain damage. We analyzed the spatiotemporal expression pattern of the proinflammatory key molecules: interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and inducible nitric oxide synthase in a rat closed head injury (CHI) paradigm. 51 rats were used for RT-PCR analysis after CHI, and 18 for immunocytochemistry. We found an early upregulation of IL-1beta, IL-6, and TNF-alpha mRNA between 1h and 7h after injury; the expression of iNOS mRNA only revealed a significant increase at 4h. After 24h, the expression decreased towards baseline levels, and remained low until 7d after injury. Immunocytochemically, IL-1beta induction was localized to ramified microglia in areas surrounding the primary impact place as well as deeper brain structures. Our study shows rapid induction of inflammatory gene expression that exceeds by far the primary impact site and might therefore contribute to tissue damage at remote sites.

Animals↗

Binocular function in early glaucoma.

PURPOSE: This study investigated whether certain binocular mechanisms are disrupted in early glaucoma. METHODS: Glaucoma patients, suspects, and normals were tested on a battery of psychophysical tests consisting of flicker sensitivity (5 and 34 Hz), temporal cut-off frequency (CFF), contrast sensitivity (Pelli-Robson chart), and stereoacuity. Monocular channels were evaluated with tests of monocular flicker performance and spatial contrast sensitivity. Binocular summation on spatial and temporal tests was used to reflect integrity of binocular neural interactions. Stereoacuity was taken as a measure of performance of disparity processing mechanisms. RESULTS: The groups differed in terms of binocular flicker sensitivity at both temporal rates, binocular and monocular peak contrast sensitivity, and stereoacuity. Binocular summation of both spatial and temporal sensitivity was normal. The glaucoma suspect group was distinguishable from the age-matched normal group on binocular contrast sensitivity and stereoacuity. CONCLUSIONS: The binocular mechanisms that mediate stereoacuity appear to be heavily disrupted, whereas the binocular mechanisms that mediate central neural interaction of monocular inputs are normal. Although monocular spatiotemporal abilities are disrupted, the binocular processes combine the monocular input normally. In addition, our results suggest a benefit of binocular testing for routine assessment of glaucoma patients. The profound disruption of stereoacuity appears to result from disorder in the spatial sampling array at the ganglion-cell level similar to the disorder reported in the normal periphery and the central retina of strabismic amblyopes. These and previous findings were reviewed to evaluate the supposition of preferential M-pathway disruption in early glaucoma. Such a model can not be reconciled with the present findings. We conclude that measurements of temporal modulation sensitivity fit well with such a model, but that the current evidence of spatiotemporal contrast sensitivity disruption is less supportive of such a model.

Analysis of Variance↗

Modulations of the optical flow did not induce locomotor pattern fluctuations in treadmill walking in man.

We report an analysis of gait during human treadmill walking when visual information from the self-displacement velocity was modulated. Removing or sinusoidally modulating the frequency edge information in the optical flow did not induce significant changes in the walking velocity as analyzed using Fast Fourier Transform or in the spatiotemporal gait parameters. While low-frequency fluctuations in displacement speed increased, there was no significant change in locomotor cycle stability, When a constant frequency edge was provided, i.e., when a backward optical flow was added, stride length decreased as compared to the no-optical-flow condition and instantaneous fluctuations in stride amplitude increased. Temporal gait parameters did not change. These partial effects might be better explained by modifications in trunk balance. In humans, modulation of velocity information on self-motion cannot induce unintentional modulation of walking velocity and did not enhance fluctuations in the locomotor pattern. These results argue against the proprioceptive role of sagittal visual-motion information in control of stability of rhythmic leg movement, at least when other proprioceptive feedback sources are available.

Acceleration↗

Topographical analysis of epileptiform potentials in rat somatosensory cortex: the interictal to ictal transition.

Large quantities of penicillin were applied to the face and forelimb region of rat somatosensory cortex, producing an epileptic focus with both electrographic and behavioral signs of seizures that regularly repeated over a period of several minutes. Epicortical potentials were recorded simultaneously from a 64 channel micro-electrode array (8 x 8 platinum electrodes) with inter-electrode distances of 0.5 mm, covering a 3.5 x 3.5 mm2 area centered on the penicillin injection site. Cluster analysis was used to classify successive epileptiform discharges into interictal, transitional, and ictal groups. Principal components analysis (PCA) was used to extract fundamental waveforms producing the spike complex in each group, and to estimate the locations and spatial extent of neuronal populations participating in epileptiform discharge. During all states of epileptic excitability, it was possible to account for over 90% of the variance in the epicortical potential waveforms using a model with only two spatially overlapping populations of cells. The location and spatial extent of the populations remained unchanged by the transition to seizures; the interictal and ictal states were distinguished only by changes in the timing and amplitude of potentials in the two putative neuronal populations. The present model, using only two stationary neuronal populations to reproduce all spatiotemporal patterns in the neocortical epileptogenic focus, is compared to models proposed by others in which epileptic discharge is thought to propagate sequentially through adjacent cortex. It is concluded that the initiation, maintenance, and termination of seizures in neocortex relies on mechanisms that are not necessarily reflected in changes in spatiotemporal interactions among epicortically recorded cell groups within the focus. These mechanisms may be distinguished from those responsible for the spread of seizures within neocortex.

Animals↗

Comparative analysis of gait in Parkinson's disease, cerebellar ataxia and subcortical arteriosclerotic encephalopathy.

Quantitative gait analysis has been used to elucidate characteristic features of neurological gait disturbances. Although a number of studies compared single patient groups with controls, there are only a few studies comparing gait parameters between patients with different neurological disorders affecting gait. In the present study, gait parameters were compared between control subjects, patients with parkinsonian gait due to idiopathic Parkinson's disease, subjects suffering from cerebellar ataxia and patients with gait disturbance due to subcortical arteriosclerotic encephalopathy. In addition to recording of baseline parameters during preferred walking velocity, subjects were required to vary velocity from very slow to very fast. Values of velocity and stride length from each subject were then used for linear regression analysis. Whereas all patient groups showed slower walking velocity and reduced step length compared with healthy controls when assessed during preferred walking, patients with ataxia and subcortical arteriosclerotic encephalopathy had, in addition, increased variability of amplitude and timing of steps. Regression analysis showed that with changing velocity, subjects with Parkinson's disease changed their stride length in the same proportion as that measured in controls. In contrast, patients with ataxia and subcortical arteriosclerotic encephalopathy had a disproportionate contribution of stride length when velocity was increased. Whereas the findings in patients with Parkinson's disease can be explained as a reduction of force gain, the observations for patients with ataxia and subcortical arteriosclerotic encephalopathy reflect an altered spatiotemporal gait strategy in order to compensate for instability. The similarity of gait disturbance in subcortical arteriosclerotic encephalopathy and cerebellar ataxia suggests common mechanisms.

Adult↗

Motion detection in interleaved random dot patterns: evidence for a rectifying nonlinearity preceding motion analysis.

Three experiments examined direction discrimination in temporally interleaved random dot patterns. The stimulus consisted of two or more uncorrelated random patterns presented in a repeating temporal sequence, so that each pattern appeared only once every n frames, separated by uncorrelated patterns. Each pattern shifted either leftward or rightward at each re-appearance (all patterns shifted in the same direction in any one presentation). Subjects could specify shift direction correctly even when eight different patterns were interleaved, provided that the duration of each frame was brief. An explanation based on responses in first-order motion energy detectors tuned to low spatiotemporal frequencies (effectively summating the interleaved patterns over time) was tested using a stimulus in which each pattern inverted in contrast mid-way through each frame. Contrary to predictions based on temporal summation, performance with contrast-inverting patterns was only slightly lower than with non-inverting patterns. An alternative explanation was examined, based on responses in motion detectors that full-wave rectify image contrast before extracting motion energy. Computed responses from such detectors successfully predicted psychophysical performance with interleaved random patterns. Implications for models of motion analysis are discussed.

Discrimination, Psychological↗

Independent component analysis of dynamic brain responses during visuomotor adaptation.

To investigate the spatial and temporal changes in electro-cortical brain activity and hand kinematics during the acquisition of an internal model of a novel screen-cursor transformation, we employed single-trial infomax independent component analysis (ICA), spectral estimation, and kinematics methods. Participants performed center-out drawing movements under normal and rotated visual feedback of pen movements displayed on a computer screen. Clustering of task-related and adaptation-related independent components identified a selective recruitment of brain activation/deactivation foci associated with the exposure to the distorted visual feedback, including networks associated with frontal-, central-, and lateral-posterior alpha rhythms, and frontal-central error-related negativity potential associated with transient theta and low beta rhythms locked to movement onset. Moreover, adaptation to the rotated reference frame was associated with a reduction in the imposed directional bias and decreases in movement path length and movement time by late-exposure trials, as well as after-effects after removal of the visual distortion. The underlying spatiotemporal pattern of activations is consistent with recruitment of frontal-parietal, sensory-motor, and anterior cingulate cortical areas during visuomotor adaptation.

Adaptation, Physiological↗

Developmental expression of perlecan during murine embryogenesis.

Perlecan is a modular heparan sulfate proteoglycan that is an intrinsic constituent of all basement membranes and extracellular matrices. Because of its strategic position and unique structure, perlecan has been implicated in modulating the activity of various growth factors required for normal development and tissue homeostasis. To gain insights into the potential function of perlecan in vivo, we examined the spatiotemporal distribution of its mRNA and protein core during murine embryogenesis. We utilized a new affinity-purified antibody that recognizes specifically the protein core of perlecan together with an in situ RT-PCR approach to perform a systematic analysis of perlecan expression and deposition during murine ontogeny. Perlecan appeared early (E10.5) in tissues of vasculogenesis including heart, pericardium, and major blood vessels. Its early expression coincided with the development of the cardiovascular system. Subsequently (E11-13), the greatest deposition of perlecan occurred within the developing cartilage, especially the cartilage undergoing endochondral ossification, where it remained elevated throughout all the developmental stages, and up to adulthood. Interestingly, the mRNA levels of perlecan were always higher in all the vascularized tissues, principally within endothelial cells, while chondrocytes displayed relatively low mRNA levels. This suggests a higher biosynthesis and turnover rates in the blood vessels vis-à-vis those of cartilaginous and other mesenchymal tissues. During later stages of development (E13-17.5) perlecan mRNA levels progressively increased and its expression correlated with the onset of tissue differentiation of various parenchymal organs including the developing kidneys, lungs, liver, spleen, and gastrointestinal tract. The central nervous system showed no perlecan expression with the exception of the calvaria and choroid plexus. Collectively, the results indicate that perlecan may play crucial roles not only in vasculogenesis but also in the maturation and maintenance of differentiated tissues, including cartilage.

Animals↗

Detailed immunohistology of Pax6 protein and tyrosine hydroxylase in the early zebrafish brain suggests role of Pax6 gene in development of dopaminergic diencephalic neurons.

Spatiotemporal developmental dynamics of Pax6 protein containing (i.e., Pax6) cells were investigated immunohistochemically in embryonic and postembryonic zebrafish brain sections (especially at 2 and 5 day), allowing for a neuroanatomically detailed resolution previously only reported for the mouse. Besides strikingly close correspondences of early Pax6 domains - including many spatiotemporal changes - in mouse and zebrafish brains, some critical differences were noted. There is no pallial (i.e., cortical) Pax6 expression domain in the ventricular proliferative layer in the zebrafish as in the mouse. The main pallial Pax6 domain in the zebrafish is comparable to the migrating stream of Pax6 cells at the pallial-subpallial boundary. This indicates that some developmental functions of Pax6 (i.e., inhibition of subpallial cell migration into pallium by Pax6 migrating stream) might be shared with the mouse and maybe all vertebrates, while others (i.e., control of intrapallial neuronal radial migration via Pax6 expressing radial glia cells) may be special for mammals. Another prominent feature in the early zebrafish forebrain is that the alar plate ventral thalamic Pax6 domain extends far caudolaterally into the periphery of the basal plate posterior tuberculum and hypothalamic inferior lobe. This indicates that the alar plate ventral thalamus invades the forebrain basal plate and contributes to the development of basal forebrain structures. The close spatiotemporal association of Pax6 cells and TH cells of the ventral thalamus indicates a local role of Pax6 in the development of ventral thalamic (as recently demonstrated in the mouse) and, maybe, posterior tubercular TH cells. However, our confocal microscopical analysis of zebrafish brain sections double-immunostained for Pax6 and TH did not reveal cells double-labeled for these two proteins in this location, but rather indicates an inductive interaction of Pax6 cells onto TH cells.

Animals↗

Effects of brisk walking on static and dynamic balance, locomotion, body composition, and aerobic capacity in ageing healthy active men.

This work analyses the short-term physiological and neurophysiological effects of a brisk walking programme in ageing, healthy, active men. Twenty-one men 63 to 72 years of age were recruited and separated into 2 groups. One group performed a walking programme (WP) (n = 11) and another served as control (C) group (n = 10). The walking programme lasted for twelve weeks and included five sessions per week. Several parameters were assessed before and after the programme for the WP group. The same tests were performed (separated by twelve weeks) in group C. During each assessment, the subjects were put through static and dynamic balance tests, spatio-temporal gait analysis, body composition measurements and determination of aerobic capacity and bone mineral density. The statistic analysis showed a significant improvement in dynamic balance performance, especially in lateral sway when the subjects kept their eyes open, an increase of VO(2) max and loss of fat mass in the WP group. However, no alterations appeared in spatiotemporal gait characteristics, static balance performance, lean mass or bone mineral density (total body and hip). According to these results, this walking programme may have positive effects on preventing ageing subjects from falling.

Accidental Falls↗

Analytical solution for the covariance and for the decorrelation time of the angle of arrival of a wave front corrugated by atmospheric turbulence.

The two-dimensional (2D) spatial covariance of the angle-of-arrival (AA) fluctuations is often used to investigate the properties of wave fronts corrugated by the atmosphere for high-angular-resolution techniques. Theoretical series expansions of this covariance are presented. The fast convergence of these series reduces the calculation time of the covariance done by numerical integration. The 2D covariance is a nonradial function. A physical interpretation of this anisotropy is proposed. The spatiotemporal correlation of the AA is deduced from the covariance assuming the "frozen-flow" hypothesis. The impact of the anisotropy on the evaluation of the number of predominant turbulent layers and on the corresponding winds is investigated, and an analysis of temporal correlations is performed. A simple theoretical approximation of the decorrelation time of the AA is given, which is found to be in agreement with experimental results.

Journal Article↗

Control of spatiotemporal chaos in neuronal networks.

Different strategies for the control of chaotic neuronal networks and physical systems are presented. The variables of the dynamics span phase-spaces with very high dimensions. Novel control techniques are introduced that handle these high-dimensional cases. Depending on the system, several orbits with different spatiotemporal symmetries may be stabilized out of the chaotic attractor. The role of chaos control in information processing is pointed out.

Algorithms↗

Analysis of the gait of adults who had residua of congenital dysplasia of the hip.

Twenty-one adult subjects who had symptomatic residua of unilateral congenital dysplasia of the hip, with various degrees of degenerative changes, were studied with respect to the physical and radiographic findings and gait performance. Three-dimensional body reconstruction; the Trendelenburg sign; spatiotemporal parameters of stride; ground-reaction forces; kinematics of the hip, knee, and ankle; moments of forces; and joint powers were evaluated bilaterally. The kinematic and kinetic parameters of the affected limb were compared with those of the unaffected limb and with those of the limbs of normal control subjects. Correlations between changes in selected gait parameters and the clinical and radiographic signs of impairment of the hip were demonstrated. The results are discussed in relation to the possible mechanisms underlying the observed alterations and in view of possible operative interventions.

Adult↗

Early embryonic expression of ion channels and pumps in chick and Xenopus development.

An extensive body of literature implicates endogenous ion currents and standing voltage potential differences in the control of events during embryonic morphogenesis. Although the expression of ion channel and pump genes, which are responsible for ion flux, has been investigated in detail in nervous tissues, little data are available on the distribution and function of specific channels and pumps in early embryogenesis. To provide a necessary basis for the molecular understanding of the role of ion flux in development, we surveyed the expression of ion channel and pump mRNAs, as well as other genes that help to regulate membrane potential. Analysis in two species, chick and Xenopus, shows that several ion channel and pump mRNAs are present in specific and dynamic expression patterns in early embryos, well before the appearance of neurons. Examination of the distribution of maternal mRNAs reveals complex spatiotemporal subcellular localization patterns of transcripts in early blastomeres in Xenopus. Taken together, these data are consistent with an important role for ion flux in early embryonic morphogenesis; this survey characterizes candidate genes and provides information on likely embryonic contexts for their function, setting the stage for functional studies of the morphogenetic roles of ion transport.

Animals↗

Comparison of 3-D stereoscopic MR imaging with pre and post lesion recording in pallidotomy.

OBJECTIVES: A quantitative on-line analysis of electrical activity in the pallidum of Parkinsonian patients has been developed to determine the focal point of lesioning. Additional recordings are made after the lesioning, to assess residual neural activity. A 3-D volume stereoscopic image system is proposed to display the complex anatomy and to superimpose the electrophysiological data into this system. The purpose of this study is to understand the complex pathophysiology in real-time anatomic/image space and determine the location and effect of lesioning residual energy sites. MATERIAL AND METHODS: Thirty patients undergoing 41 pallidotomies are presented. Neuronal activity from the pallidum is recorded using a semi-microelectrode. Based on this activity, lesioning is performed. Post-lesion recordings are made to determine the necessity of additional lesioning. 3-D volume MR images are acquired pre and postoperatively and compared for accuracy of lesion sites. A 3-D stereoscopic image system has been developed to depict basal ganglia geometry in the last 5 patients. Electrophysiological data are superimposed on this image system to show the surgeon the virtual position of the electrode tip. RESULTS: A stereoscopic 3-D volume MR image system has been developed. This system more efficiently and accurately visualizes and records the coordinates of high neural activity in the pallidum and post lesion residual activity. Post-lesion power analysis was carried out in 30 patients. Additional lesions were indicated in 8 and different trajectories in 6. CONCLUSION: Real-time visualization of neural recording, both pre and post-lesioning during pallidotomy, facilitates the surgeon's understanding of the spatiotemporal relationships of pathophysiological properties within the globus pallidus.

Adult↗

Illuminating the landscape of in vivo immunity: insights from dynamic in situ imaging of secondary lymphoid tissues.

A central feature of the immune system is the migratory behavior of its cellular components. Thus, fully understanding the generation and maintenance of immune responses must include consideration of how hematopoietic cells home to, interact within, and exit from secondary lymphoid organs as well as peripheral tissues. Recent advances in in situ imaging techniques now permit direct observation of these events in their physiologic settings with high spatiotemporal resolution. This review summarizes progress in this area of investigation from a lymphocentric perspective. We highlight controversies, point out key unanswered questions, and briefly outline what we believe are some of the near-term directions that in situ microscopic analysis of the immune system will take.

Animals↗

Two forms of apraxia in Alzheimer's disease.

Apraxia was tested in 12 DAT patients with mild to moderate dementia using two assessment procedures: conceptual tasks requiring object use and pantomime knowledge, and tasks based on the imitation of meaningless oral and hand movements. Both object use and pantomime performance were markedly impaired in the DAT group; imitation of hand postures, hand movements and multiple oral movements was also defective while single oral movements could be well imitated. Error analysis revealed several underlying deficits: on conceptual tasks, deficits in object and action knowledge and poor action planning were frequent, whereas impaired recall and coordination of spatial and temporal movement features were found on imitation tasks. A correlation analysis between both types of apraxia showed low and nonsignificant results. These and previous observations suggest that motor control is organized by two functionally separate systems: a conceptual system for purposeful and symbolic motor acts, and a system controlling sensorimotor and spatiotemporal movement features. Both systems may be subject to early damage in Alzheimer's disease.

Aged↗

Two variants of zebrafish p100 are expressed during embryogenesis and regulated by Nodal signaling.

Human p100 protein was first identified as a transcriptional coactivator of Epstein-Barr virus nuclear antigen 2, and has been shown to be a coactivator of other cellular transactivators. Its roles in development of vertebrate embryos, however, have not been reported. We have identified a zebrafish ortholog of the human p100 coactivator. The zebrafish p100 transcript is processed to two alternative variants, long and short forms, referred to as p100L and p100S, respectively. Both GFP-p100L and GFP-p100S fusion proteins are located in the cytoplasm of transfected culture cells and microinjected embryonic cells. Analysis of transcripts with Northern blots revealed the presence of p100L and lower amounts of p100S mRNAs from the one-cell stage throughout the life cycle. Whole-mount in situ hybridization shows that p100L and p100S share the same spatiotemporal expression pattern. Their zygotic expression is initially restricted to axial mesoderm precursors during gastrulation, and then spreads over other tissues during segmentation, and finally is constrained to some internal organs at day 5. We also find that Nodal signaling is essential for the zygotic expression of p100. These studies pave the way to understanding in depth the role of p100 during vertebrate embryogenesis.

Alternative Splicing↗