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PubMed2002

A framework for noise-power spectrum analysis of multidimensional images.

A methodological framework for experimental analysis of the noise-power spectrum (NPS) of multidimensional images is presented that employs well-known properties of the n-dimensional (nD) Fourier transform. The approach is generalized to n dimensions, reducing to familiar cases for n = 1 (e.g., time series) and n = 2 (e.g., projection radiography) and demonstrated experimentally for two cases in which n = 3 (viz., using an active matrix flat-panel imager for x-ray fluoroscopy and cone-beam CT to form three-dimensional (3D) images in spatiotemporal and volumetric domains, respectively). The relationship between fully nD NPS analysis and various techniques for analyzing a "central slice" of the NPS is formulated in a manner that is directly applicable to measured nD data, highlights the effects of correlation, and renders issues of NPS normalization transparent. The spatiotemporal NPS of fluoroscopic images is analyzed under varying conditions of temporal correlation (image lag) to investigate the degree to which the NPS is reduced by such correlation. For first-frame image lag of approximately 5-8%, the NPS is reduced by approximately 20% compared to the lag-free case. A simple model is presented that results in an approximate rule of thumb for computing the effect of image lag on NPS under conditions of spatiotemporal separability. The volumetric NPS of cone-beam CT images is analyzed under varying conditions of spatial correlation, controlled by adjustment of the reconstruction filter. The volumetric NPS is found to be highly asymmetric, exhibiting a ramp characteristic in transverse planes (typical of filtered back-rojection) and a band-limited characteristic in the longitudinal direction (resulting from low-pass characteristics of the imager). Such asymmetry could have implications regarding the detectability of structures visualized in transverse versus sagittal or coronal planes. In all cases, appreciation of the full dimensionality of the image data is essential to obtaining meaningful NPS results. The framework may be applied to NPS analysis of image data of arbitrary dimensionality provided the system satisfies conditions of NPS existence.

Algorithms↗
PubMed2001

Abnormalities of the spatiotemporal characteristics of gait at the onset of freezing in Parkinson's disease.

We investigated the spatiotemporal variables of gait leading up to freezing. Gait analysis was carried out on 14 patients with Parkinson's disease in the off phase of the medication cycle. A computerised, three-dimensional gait analysis system was used to measure the walking pattern. After several trials of normal walking with voluntary stopping, distracting manoeuvres and obstacles on the walkway were used to provoke freezing or festination. The gait variables of normal (off phase), festinating, prestop, and prefreezing strides were analysed using analysis of variance for repeated-measures. Cadence was excessively increased (68%) and stride length decreased (69%) during festination compared with normal off walking; a pattern which remained pronounced when comparing prefreezing strides with normal stopping. Analysing in more detail the three steps before a freeze, we found a progressive decrease of stride length and stable cadence rates and proportions of double support phases. The relationship between cadence and stride length exhibited an exponential increase of cadence with a decreasing stride length during festination and freezing. Results suggest that freezing is caused by a combination of an increasing inability to generate stride length superimposed on a dyscontrol of the cadence of walking.

Aged↗
PubMed1997

Visuomotor transformations for reaching to memorized targets: a PET study.

Positron emission tomography (PET) was used to identify cortical and subcortical regions involved in the control of reaching to visual targets. Regional cerebral blood flow (rCBF) was measured in eight healthy subjects using H2(15)O PET during the performance of three different tasks. All tasks required central fixation while a 400-ms target was flashed every 5 s at a random location around a virtual circle centered on the fixation target. Additional instructions differed according to the task: (i) visual detection of the target without overt responses; (ii) immediate pointing to the most recent target in the sequence, and (iii) pointing to the previous target in the sequence. By design, the two motor tasks differed in the cognitive processing required. In each trial of immediate pointing, the spatial location of only the most recent target needed to be processed. In each trial of pointing to the previous, instead, while the most recent target was stored in memory for the movement of the next trial, the previous target had to be retrieved from memory to direct the current movement. Limb trajectories were comparable between the two motor tasks in terms of most spatiotemporal parameters examined. Significant rCBF increases were identified using analysis of covariance and t statistics. Compared with visual detection there was activation of primary sensorimotor cortex, ventrolateral precentral gyrus, inferior frontal gyrus in the opercular region, supramarginal gyrus, and middle occipital gyrus, all these sites in the hemisphere (left) contralateral to the moving limb, and cerebellar vermis, during both immediate pointing and pointing to the previous. During immediate pointing there was additional activation of left inferior parietal lobule close to the intraparietal sulcus, and when compared with pointing to the previous, dorsolateral prefrontal cortex bilaterally. During pointing to the previous, instead, there was additional activation of supplementary motor cortex, anterior and midcingulate, and inferior occipital gyrus in the left hemisphere; superior parietal lobule, supramarginal gyrus, and posterior hippocampus in the right hemisphere; lingual gyri and cerebellar hemispheres bilaterally; anterior thalamus; and pulvinar. The activation of two partially distinct cerebral networks in these two motor tasks reflects the different nature of signal processing involved. In particular, the specific activation of intraparietal sulcus and prefrontal cortex in immediate pointing appears characteristic of a network for visuospatial working memory. By contrast, the corticolimbic network engaged in pointing to the previous could mediate spatial attention and the sequence of encoding, recording, and decoding of spatial memories required by a dual task with two competing targets.

Adult↗
PubMed2005

Chondroitin sulfate proteoglycan phosphacan associates with parallel fibers and modulates axonal extension and fasciculation of cerebellar granule cells.

Phosphacan is a nervous system-specific chondroitin sulfate proteoglycan and one of the major components of extracellular matrix in the brain. In the present study, we examined its spatiotemporal expression, ultrastructural localization, binding manner, and in vitro analysis on cell adhesion, axonal extension, and fasciculation in rat cerebellum. The present light microscopic immunohistochemistry showed that phosphacan immunoreactivity was localized mainly at the molecular layer in the cerebellum, but not at the external granular layer. Further double labeling immunohistochemical and immunoelectron microscopic studies revealed that phosphacan was localized around parallel fibers, but not at synapses. The binding of phosphacan to membrane and/or extracellular matrix partly required Ca2+ and was mediated through its core glycoprotein. Phosphacan inhibited adhesion and axonal extension of cerebellar granule cells in dissociated culture, while it promoted axonal fasciculation of their aggregated culture. These results indicate that phosphacan around parallel fibers may be the repulsive substratum for adhesion and extension of granule cells and promote the fasciculation of parallel fibers.

Animals↗
PubMed2006

Long-range downstream enhancers are essential for Pax6 expression.

Pax6 is a developmental control gene with an essential role in development of the eye, brain and pancreas. Pax6, as many other developmental regulators, depends on a substantial number of cis-regulatory elements in addition to its promoters for correct spatiotemporal and quantitative expression. Here we report on our analysis of a set of mice transgenic for a modified yeast artificial chromosome carrying the human PAX6 locus. In this 420 kb YAC a tauGFP-IRES-Neomycin reporter cassette has been inserted into the PAX6 translational start site in exon 4. The YAC has been further engineered to insert LoxP sites flanking a 35 kb long, distant downstream regulatory region (DRR) containing previously described DNaseI hypersensitive sites, to allow direct comparison between the presence or absence of this region in the same genomic context. Five independent transgenic lines were obtained that vary in the extent of downstream PAX6 locus that has integrated. Analysis of transgenic embryos carrying full-length and truncated versions of the YAC indicates the location and putative function of several novel tissue-specific enhancers. Absence of these distal regulatory elements abolishes expression in specific tissues despite the presence of more proximal enhancers with overlapping specificity, strongly suggesting interaction between these control elements. Using plasmid-based reporter transgenic analysis we provide detailed characterization of one of these enhancers in isolation. Furthermore, we show that overexpression of a short PAX6 isoform derived from an internal promoter in a multicopy YAC transgenic line results in a microphthalmia phenotype. Finally, direct comparison of a single-copy line with the floxed DRR before and after Cre-mediated deletion demonstrates unequivocally the essential role of these long-range control elements for PAX6 expression.

Animals↗
PubMed2001

Is there a relation between neuropsychologic variables and quality of life after stroke?

OBJECTIVES: To describe the quality of life (QOL) of stroke patients and to distill neuropsychologic predictors for poor QOL. DESIGN: A cohort study in which patients were neuropsychologically assessed at a mean of 72.2 days after stroke, with follow-up at a mean of 9.8 months after stroke. SETTING: Research department of a rehabilitation center. PATIENTS: A consecutive sample of 164 stroke patients (mean age, 55.2yr) recruited from a university hospital, a regional hospital, and a rehabilitation center. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Orientation, memory, attention and concentration, visuospatial and visuoconstructive functions, language, and arithmetic skills were assessed with neuropsychologic tests. QOL was assessed with the Sickness Impact Profile (SIP). RESULTS: An overall mean SIP score +/- standard deviation of 20 +/- 11 showed that stroke has a high impact on everyday functioning. Further analyses indicated that QOL is related in particular to tests measuring spatiotemporal and/or sequential aspects of behavior. Forward/backward stepwise regression analysis (n = 106) showed that poor QOL was more likely if patients had a poor result on the Trailmaking Test (TMT) B and/or were women. CONCLUSION: The predictive value of the TMT is most effective and very useful because the TMT is a short and economical procedure. However, the gender-related aspects of recovery deserve more attention, as does the possible bias that can be caused by the composition of a measurement. Further research is needed to refine predictive models that are needed to facilitate the development of more adequate, individual rehabilitation programs.

Adolescent↗
PubMed2006

MEG versus EEG: influence of background activity on interictal spike detection.

The comparative sensitivity of EEG and magnetoencephalography (MEG) in the visual detection of focal epileptiform activity in simultaneous interictal sleep recordings were investigated. The authors examined 14 patients aged 3.5 to 17 years with localization-related epilepsy. Simultaneous 122-channel whole-head MEG and 33-channel EEG were recorded for 20 to 40 minutes during spontaneous sleep. The EEG and MEG data were separated and four blinded independent reviewers marked the presence and timing of epileptic discharges (ED) in the 28 data segments. EEG and MEG data were matched and spikes identified by at least three reviewers were classified in three categories according to the following criteria: type 1 MEG > EEG, type 2 EEG > MEG (type 1/2: difference of three or more raters), and type 3 EEG = MEG (three or more raters each). The presence of simultaneous sleep changes was visually determined for every single EEG-segment. Spikes with high spatiotemporal correlation were averaged and subjected to single dipole analysis of peak activity in EEG. Out of 4704 marked patterns, 1387 spikes fulfilled the above criteria. In fact, more spikes were unique to MEG (689) than to EEG (136) and to the combination of both modalities (562). ED were detected predominantly by MEG in eight patients and by EEG in two patients. The presence of vertex waves and spindles lead to a significantly higher number of spikes identified only in MEG. Averaging of type 1 spikes produced clear spike activity in EEG in 9 of 12 cases. On the contrary, only 2 of 10 type 2 spikes were visible in MEG after averaging. Dipoles of spikes visible in MEG showed a more tangential orientation compared with more radial dipoles of type 2 spikes. Spike characteristics, e.g., dipole orientation, are a key factor for a sole EEG representation. Exclusive MEG detection is more likely influenced by overlapping background activity in EEG. Because MEG is indifferent to radial activity, i.e., sleep changes, a higher ratio of spikes unique to MEG compared with EEG is detected in the case of overlapping sleep changes.

Action Potentials↗
PubMed2004

Whooping cough metapopulation dynamics in tropical conditions: disease persistence and impact of vaccination.

Recent insights in compiling metapopulation models and infectious disease dynamics have enabled a better understanding of spatial and temporal persistence of diseases. The concept of the critical community size (CCS) has been developed with major consideration on analyses of whooping cough and measles dynamics from temperate countries for which large datasets are available. However, few studies have questioned the generality of CCS curves for other regions, i.e. tropical areas, mainly because data are very sparse. This work constitutes, to our knowledge, the first study of whooping cough persistence in a tropical area, in a rural part of Senegal (Western Africa) where the population has been followed for 20 years. In this small community, the CCS is not reached even if we observe CCS-like curves showing persistence increasing with population size. In addition, our analysis supports the idea that vaccination has impacted the spatiotemporal dynamics and persistence of the disease. These findings suggest the need for more comparative analyses of spatio-temporal data series from a wide range of contrasted countries, for example developed and developing nations, so as to have a better understanding of vaccination effects on disease dynamics and persistence.

Humans↗
PubMed2002

Auditory cortical images of cochlear-implant stimuli: coding of stimulus channel and current level.

This study quantified the accuracy with which populations of neurons in the auditory cortex can represent aspects of electrical cochlear stimuli presented through a cochlear implant. We tested the accuracy of coding of the place of stimulation (i.e., identification of the active stimulation channel) and of the stimulus current level. Physiological data came from the companion study, which recorded spike activity of neurons simultaneously from 16 sites along the tonotopic axis of the guinea pig's auditory cortex. In that study, cochlear electrical stimuli were presented to acutely deafened animals through a 6-electrode animal version of the 22-electrode Nucleus banded electrode array (Cochlear). Cochlear electrode configurations consisted of monopolar (MP), bipolar (BP + N) with N inactive electrodes between the active and return electrodes (0 < or = N < or = 3), tripolar (TP) with one active electrode and two flanking return electrodes, and common ground (CG) with one active electrode and as many as five return electrodes. In the present analysis, an artificial neural network was trained to recognize spatiotemporal patterns of cortical activity in response to single presentations of particular stimuli and, thereby, to identify those stimuli. The accuracy of pair-wise discrimination of stimulation channels or of current levels was represented by the discrimination index, d', where d' = 1 was taken as threshold. In many cases, the threshold for discrimination of place of cochlear stimulation was < 0.75 mm, and the threshold for discrimination of current levels was < 1 dB. Cochlear electrode configurations varied in the accuracy with which they signaled to the auditory cortex the place of cochlear stimulation. The BP + N and TP configurations provided considerably greater sensitivity to place of stimulation than did the MP configuration. The TP configuration maintained accurate signaling of place of stimulation up to the highest current levels, whereas sensitivity was degraded at high current levels in BP + N configurations. Electrode configurations also varied in the dynamic range over which they signaled stimulus current level. Dynamic ranges were widest for the BP + 0 configuration and narrowest for the TP configuration. That is, the configuration that showed the most accurate signaling of cochlear place of stimulation (TP) showed the most restricted dynamic range for signaling of current level. These results suggest that the choice of the optimal electrode configuration for use by human cochlear-prosthesis users would depend on the particular demands of the speech-processing strategy that is to be employed.

Action Potentials↗
PubMed2005

Two-photon microscopic analysis of acetylcholine-induced mucus secretion in guinea pig nasal glands.

The spatiotemporal changes in intracellular free Ca(2+) concentration ([Ca(2+)](i)) as well as fluid secretion and exocytosis induced by acetylcholine (ACh) in intact acini of guinea pig nasal glands were investigated by two-photon excitation imaging. Cross-sectional images of acini loaded with the fluorescent Ca(2+) indicator fura-2 revealed that the ACh-evoked increase in [Ca(2+)](i) was immediate and spread from the apical region (the secretory pole) of acinar cells to the basal region. Immersion of acini in a solution containing a fluorescent polar tracer, sulforhodamine B (SRB), revealed that fluid secretion, detected as a rapid disappearance of SRB fluorescence from the extracellular space, occurred exclusively in the luminal region and was accompanied by a reduction in acinar cell volume. Individual exocytic events were also visualized with SRB as the formation of Omega-shaped profiles at the apical membrane. In contrast to the rapidity of fluid secretion, exocytosis of secretory granules occurred with a delay of approximately 70s relative to the increase in [Ca(2+)](i). Exocytic events also occurred deep within the cytoplasm in a sequential manner with the latency of secondary exocytosis being greatly reduced compared with that of primary exocytosis. The delay in sequential compound exocytosis relative to fluid secretion may be important for release of the viscous contents of secretory granules into the nasal cavity.

Acetylcholine↗
PubMed2025

Chromatin accessibility analysis reveals functional cis-regulatory regions related to fruit development and domestication in tomato.

Non-coding DNA sequences harbor vast regulatory programs that ensure the precise spatiotemporal control of gene expression, which is essential for proper plant development and trait formation. Chromatin accessibility analysis could identify functional DNA regions within the extensive non-coding sequences and infer regulatory elements, serving as a crucial approach to unravel the mysteries of non-coding DNA sequences. Tomato fruit, a fleshy organ, provides a special system for studying fruit development and trait formation. However, the role of cis-accessible chromatin regions (cis-ACRs) during tomato fruit development, particularly in comparison with protein-coding DNA sequences, remains poorly understood. Here, we used ATAC-seq to define the landscape of cis-ACRs during fruit development and domestication in tomato. Temporal differential analysis revealed the dynamic opening and closing of cis-ACRs during fruit development. Comparative analysis of cis-ACRs between cultivated and wild tomatoes highlighted their significant contributions to fruit domestication. Combining analysis with genomic structural variations (SVs) suggested that SVs are likely a key factor in the formation of specific accessible cis-ACRs in cultivated tomatoes. Moreover, using gene editing, we identified a functional cis-ACR within the intron of the MBP3 gene that regulates fruit development and size traits. Overall, our findings provide a comprehensive perspective on the roles of cis-ACRs in tomato fruit development and domestication.

Solanum lycopersicum↗
PubMed2002

Linear stability analysis of retrieval state in associative memory neural networks of spiking neurons.

We study associative memory neural networks of the Hodgkin-Huxley type of spiking neurons in which multiple periodic spatiotemporal patterns of spike timing are memorized as limit-cycle-type attractors. In encoding the spatiotemporal patterns, we assume the spike-timing-dependent synaptic plasticity with the asymmetric time window. Analysis for periodic solution of retrieval state reveals that if the area of the negative part of the time window is equivalent to the positive part, then crosstalk among encoded patterns vanishes. Phase transition due to the loss of the stability of periodic solution is observed when we assume fast function for direct interaction among neurons. In order to evaluate the critical point of this phase transition, we employ Floquet theory in which the stability problem of the infinite number of spiking neurons interacting with function is reduced to the eigenvalue problem with the finite size of matrix. Numerical integration of the single-body dynamics yields the explicit value of the matrix, which enables us to determine the critical point of the phase transition with a high degree of precision.

Journal Article↗
PubMed2006

Spatiotemporal expression of four isoforms of Ca2+/calmodulin-dependent protein kinase I in brain and its possible roles in hippocampal dendritic growth.

Among multifunctional Ca(2+)/calmodulin-dependent protein kinases (CaMKs), CaMKI has been shown to comprise a family of four structurally related isoforms (alpha, beta, gamma, and delta) encoded by separate genes with abundant expression in mature brain. In this study, we first examined the developmental gene expression of the four isoforms of CaMKI in mouse brain with special attention to the hippocampal formation by in situ hybridization analysis. The four isoforms of CaMKI were found to exhibit distinct spatiotemporal expression during neuronal development. We also examined the functional involvement of CaMKI in the dendritic formation of cultured hippocampal neurons. The overexpression of kinase-dead mutants of CaMKI reduced the average dendritic length of the transfected neurons without any significant effects on the number of primary dendrites and the branching index. Our present findings provide the detailed anatomical information on the developmental expression of the four isoforms of CaMKI in mouse brain, which represents the possible functional involvement of CaMKI in the basal dendritic growth of hippocampal neurons.

Animals↗
PubMed2001

Experimental and theoretical analysis of phase singularity dynamics in cardiac tissue.

INTRODUCTION: Quantitative analysis of complex self-excitatory wave patterns, such as cardiac fibrillation and other high-order reentry, requires the development of new tools for identifying and tracking the most important features of the activation, such as phase singularities. METHODS AND RESULTS: Image processing operations can be used to detect the phase singularity at the tip of a spiral wave. The phase space behavior of a spatiotemporal sequence of data may be reconstructed using time-series analysis. The phase singularities then are localized efficiently by computing the topologic charge density as the curl of the spatial phase gradient. We analyzed the singularity interaction dynamics of both experimentally observed and numerically simulated instances of quatrefoil reentry and found that the singularity behavior in the experimental preparations can be classified into three categories on the basis of how their separation changes with time. CONCLUSION: Topologic charge densities can be calculated easily and efficiently to reveal phase singularity behavior. However, the differences between theoretical and experimental observations of singularity separation distances indicate the need for more sophisticated numerical models.

Action Potentials↗
PubMed2002

Patterns of hand motion during grasping and the influence of sensory guidance.

This study was aimed at describing temporal synergies of hand movement and determining the influence of sensory cues on the control of these synergies. Subjects were asked to reach to and grasp various objects under three experimental conditions: (1) memory-guided movements, in which the object was not in view during the movement; (2) virtual object, in which a virtual image of the object was in view but the object was not physically present; and (3) real object, in which the object was in view and physically present. Motion of the arm and of 15 degrees of freedom of the hand was recorded. A principal components analysis was developed to provide a concise description of the spatiotemporal patterns underlying the motion. Vision of the object during the reaching movement had no influence on the kinematics, and the effect of the physical presence of the object became manifest primarily after the fingers had contacted the object. Two principal components accounted for >75% of the variance. For both components, there was a strong positive correlation in the rotations of metacarpophalangeal and proximal interphalangeal joints of the fingers. The first principal component exhibited a pattern of finger extension reversing to flexion, whereas the second principal component became important only in the second half of the reaching movement.

Arm↗
PubMed2004

Expression of CD46 in developing rat spermatozoa: ultrastructural localization and utility as a marker of the various stages of the seminiferous tubuli.

Identification of the various stages of the seminal tubule epithelium that are important in spermatogenesis in humans and rodents requires considerable expertise for analysis of ultrastructural appearance under light microscopy. Few good stage-specific markers have been reported to facilitate the process. We recently described characterization of the expression of CD46 (membrane cofactor protein) in the rat using a novel monoclonal antibody. Expression of CD46 was restricted to spermatozoa and their immediate precursors in the testis. In the present study, we used a combination of morphological analyses, known acrosome markers, actin staining, direct nuclear staining, and staining for CD46 to delineate precisely the subcellular location of CD46. Staining of CD46 colocalized with known acrosome markers in late spermatids and mature spermatozoa and was confirmed by electron microscopy to be acrosome-restricted. Expression was first detected in step 7 spermatids, whereas known markers were not expressed until step 9. The CD46 staining pattern differed through spermatid development, and distinct patterns of staining could be identified that, when combined with 4'-6-diamino-2-phenylindole-2HCl nuclear staining, enabled the accurate staging of the seminiferous tubule epithelium in different profiles. This detailed description of the spatiotemporal expression patterns of CD46 provides a valuable tool for analysis of spermatogenesis in the rat. Furthermore, this information will aid ongoing studies regarding the roles of CD46 in acrosome-related spermatozoal functions.

Acrosome↗
PubMed2005

Spatiotemporal clustering of fMRI time series in the spectral domain.

We propose a new method for the analysis of functional magnetic resonance images (fMRI). The decision that a voxel v0 is activated is based not solely on the value of the fMRI signal at v0, but rather on the comparison of all time series s(v)(t) in a small neighborhood Nv0 around v0. Our approach explicitly takes into account the intrinsic spatiotemporal correlations that exist in the data. We focus on experimental designs with periodic stimuli, and therefore we can capture most of the features of the BOLD signal with a low dimensional subspace in the frequency domain. The presence of activated time series can be detected by partitioning the time series in this low dimensional space. Experiments with simulated data, and experimental fMRI data, demonstrate that our approach can outperform standard methods of analysis, such as the t-test.

Brain↗
PubMed2005

Spatiotemporal patterns of expression of IGSF4 in developing mouse nervous system.

IGSF4 is a novel immunoglobulin (Ig)-like intercellular adhesion molecule. Since IGSF4 has been characterized by several independent research groups, this molecule is called by three names, TSLC1, SgIGSF and SynCAM. In the experiments to study global changes of gene expression in fetal murine brains after prenatal exposure to low-doses of X-rays, we have found IGSF4 as one of down-regulated genes after X-irradiation. In order to elucidate the expression of spatiotemporal expression of IGSF4 in the developing brain, we have produced polyclonal antibody against IGSF4 and studied the expression of IGSF4 with immunohistochemistry and Western blot analysis. At embryonic day (E) 12.5, IGSF4-immunoreactivity (IR) was observed diffusely in the telencephalic wall, whereas it became rather confined to the subplate, the cortical plate and the subventricular zone as the development proceeded. Noteworthy was a distinct radial pattern found in the cortical plate of E16.5. IGSF4-IR gradually decreased after birth and disappeared in adulthood. In the cerebellum, IGSF4 was expressed in the molecular layer at postnatal day (P) 0 through P14. By Western blot analysis, IGSF4 remained at low levels throughout embryonic stage, whereas it increased after birth. These spatiotemporal patterns of the expression suggest that IGSF4 plays crucial roles in the development of both telencephalon and cerebellum.

Animals↗