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PubMed2003

[Application of synthetic aperture magnetometry for epilepsy surgery].

Recently developed synthetic aperture magnetometry (SAM) is a new MEG signal analysis introducing a high performance spatial filtering technique. SAM is not an inverse solution like dipole analysis, but rather an adaptive beamformer for estimating source activity at each selected voxel inside of the brain. SAM can estimate source changes as a function of time, or power changes subjected to statistical analysis from the non-averaged raw MEG data. Thus this method enables to display the regional currentodensitogram of the arbitrary selected brain tissue as if depth electrodes were inserted (SAM virtual sensor), and to detect the origin of epileptic discharges and their spread. By applying statistical discrimination, SAM can also demonstrate the spatial distribution of event-related changes of brain rhythm (SAM statistical method), in other words activated cerebral cortex during task performance. We will present the usefulness of noninvasive SAM methods in epilepsy surgery detecting the epileptogenic zone by SAM virtual sensor method as well as eloquent brain by SAM statistical method.

Cerebral Cortex↗
PubMed2005

Disruption of actin cytoskeleton and anchorage-dependent cell spreading induces apoptotic death of mouse neural crest cells cultured in vitro.

In vertebrate embryos, neural crest cells emigrate out of the neural tube and contribute to the formation of a variety of neural and nonneural tissues. Some neural crest cells undergo apoptotic death during migration, but its biological significance and the underlying mechanism are not well understood. We carried out an in vitro study to examine how the morphology and survival of cranial neural crest (CNC) cells of the mouse embryo are affected when their actin cytoskeleton or anchorage-dependent cell spreading is perturbed. Disruption of actin fiber organization by cytochalasin D (1 microg/ml) and inhibition of cell attachment by matrix metalloproteinase-2 (MMP-2; 2.0 units/ml) were followed by morphologic changes and apoptotic death of cultured CNC cells. When the actin cytoskeleton was disrupted by cytochalasin D, the morphologic changes of cultured CNC cells preceded DNA fragmentation. These results indicate that the maintenance of cytoskeleton and anchorage-dependent cell spreading are required for survival of CNC cells. The spatially and temporally regulated expression of proteinases may be essential for the differentiation and migration of neural crest cells.

Actins↗
PubMed1991

Experimental analysis of scattered photons in Tc-99m imaging with a gamma camera.

The amount of scattered photons in a clinical imaging window of Tc-99m was experimentally measured by means of a line source with scattering materials and a gamma camera. A symmetrical photopeak energy window centered at 140 keV with a width of 20% (126-154 keV) was partitioned into several small windows. Energy spectra were analyzed to determine the scatter fraction and the attenuation coefficient for each window. Line spread functions (LSF) were also obtained to characterize the spatial scatter distribution. The results of analysis of energy spectra show that scattered photons are included over the symmetric 20% window (SW) and scatter fractions increase linearly with the increasing thickness of the scattering material in all energy windows investigated. In addition, the results for the LSF show that the scatter distribution within the SW is represented as a mono-exponential function. Experimental measurements obtained with a phantom and a gamma camera simplify accurate quantification of scattered photons. Such quantitative analysis of scattered photons is important in developing and evaluating a scatter correction technique.

Models, Structural↗
PubMed1983

UV micro-irradiation of the Chinese hamster cell nucleus and caffeine post-treatment. Immunocytochemical localization of DNA photolesions in cells with partial and generalized chromosome shattering.

UV micro-irradiation of a small part of the Chinese hamster nucleus and caffeine post-incubation often results in shattered chromosomes at the first post-irradiation mitosis. In some of these mitotic cells, chromosome shattering is restricted to a few chromosomes spatially related in a small area of the metaphase spread; in others, shattering includes the whole chromosome complement. These 2 types of damage have been called partial and generalized chromosome shattering (PCS and GCS). Using antisera that specifically react with UV-irradiated DNA, we identified micro-irradiated chromatin in interphase nuclei and in mitotic cells with PCS or GCS by indirect immunofluorescence microscopy. In PCS, immunofluorescence staining was found in the damaged area, while the surrounding intact chromosomes were not stained. In GCS, staining was also restricted to a small region of the shattered chromosome complement. In other experiments, cells synchronized in G1 were micro-irradiated in the nucleus, pulse-labelled with [3H]thymidine and post-incubated with caffeine. Autoradiographs of cells with GCS showed unscheduled DNA synthesis restricted to a small chromatin region. Our data present direct evidence that the distribution of DNA photolesions does not coincide with the sites of chromosomal damage in GCS. As a working, hypothesis, we propose that an indirect mechanism is involved in the induction of GCS by which DNA photolesions in a small nuclear segment induce shattering of both micro-irradiated and non-irradiated chromosomes.

Animals↗
PubMed1995

The spatiotemporal range of inhibitory interaction in flicker detection.

The flicker thresholds of luminous bars were measured as a function of the spatial and/or temporal separation of two flickering stimuli. Each of the bars had an intensity profile of one-half cycle of a sinusoidal wave subtending 2.26 x 0.45 arc deg and each bar was presented twice at two positions with a duration of 10 msec. The spatial separation was defined as the distance between the adjacent flanks of two flickering stimuli, while the temporal separation was determined as the time-lag between the offset of the first flickering stimulus and the onset of the second. We found that the thresholds increased asymptotically with the spatial separation in such a way as to suggest that the spatial extent over which inhibitory interaction could be effective was as large as about 2 arc deg. We also found that the threshold gradually decreased with greater temporal separation; this indicated that the temporal proximity of successive stimuli effects less suppression on the temporal response. These two effects were seemingly additive. These findings suggest that the visual system involves not only local spatial interaction, but also a global mechanism capable of spreading inhibition over several local units after a delay of several msec.

Flicker Fusion↗
PubMed1996

Introducing spatio-temporal reasoning into the inverse problem in electroencephalography.

Studying the Brain's Electrical and Magnetic Signals (BEMS) requires the contribution of many area of research that include anatomy, neurophysiology and electromagnetic theory. NEUROLAB is a framework dedicated to the study of brain disorders. Upon completion, it should provide users with an intelligent computational environment that incorporates qualitative and quantitative models of the brain and head, and a model for representing and reasoning about time and space. Spatio-temporal knowledge of a given problem is represented as a constraint network where to each node of the network are attached temporal and spatial variables that must satisfy the constraints defined by the arch labels connecting the nodes. In this paper, we show how temporal reasoning can be combined with spatial descriptions to produce different scenarios of possible seizure spread. These scenarios can provide a priori information for the inverse problem the role of which is to localise the sources of the observed BEMS.

Artificial Intelligence↗
PubMed1988

Analytical theory for extracellular electrical stimulation of nerve with focal electrodes. I. Passive unmyelinated axon.

The cable model of a passive, unmyelinated fiber in an applied extracellular field is derived. The solution is valid for an arbitrary, time-varying, applied field, which may be determined analytically or numerically. Simple analytical computations are presented. They explain a variety of known phenomena and predict some previously undescribed properties of extracellular electrical stimulation. The polarization of a fiber in an applied field behaves like the output of a spatial high-pass and temporal low-pass filter of the stimulus. High-frequency stimulation results in a more spatially restricted region of fiber excitation, effectively reducing current spread relative to that produced by low-frequency stimulation. Chronaxie measured extracellularly is a function of electrode position relative to the stimulated fiber, and its value may differ substantially from that obtained intracellularly. Frequency dependence of psychophysical threshold obtained by electrical stimulation of the macaque cochlea closely follows the frequency dependence of single-fiber passive response.

Animals↗
PubMed2006

A molecular epidemiological study of rabies in Cuba.

To investigate the emergence and current situation of terrestrial rabies in Cuba, a collection of rabies virus specimens was employed for genetic characterization. These data supported the monophyletic nature of all terrestrial rabies viruses presently circulating in Cuba but additionally delineated several distinct variants exhibiting limited spatial distribution which may reflect the history of rabies spread on the island. The strain of rabies currently circulating in Cuba, which emerged on the island in the early 20th century, has very close evolutionary ties to the Mexican dog type and is a member of the cosmopolitan lineage widely distributed during the colonial period. The Cuban rabies viruses, which circulate predominantly within the mongoose population, are phylogenetically distant from viruses circulating in mongooses in other parts of the world. These studies illustrate, at a global level, the adaptation of multiple strains of rabies to mongoose species which should be regarded as important wildlife hosts for rabies re-emergence. Given the recent emergence of human cases due to bat contact in Cuba, this study also included a single insectivorous bat specimen which was found to most closely resemble the rabies viruses known to circulate in Mexican vampire bats.

Animals↗
PubMed2002

Proteolysis and its regulation at the surface of Streptococcus pyogenes.

Pathogenic bacteria often produce proteinases that are believed to be involved in virulence. Moreover, several host defence systems depend on proteolysis, demonstrating that proteolysis and its regulation play an important role during bacterial infections. Here, we discuss how proteolytical events are regulated at the surface of Streptococcus pyogenes during infection with this important human pathogen. Streptococcus pyogenes produces proteinases, and host proteinases are produced and released as a result of the infection. Streptococcus pyogenes also recruits host proteinase inhibitors to its surface, suggesting that proteolysis is tightly regulated at the bacterial surface. We propose that the initial phase of a S. pyogenes infection is characterized by inhibition of proteolysis and complement activity at the bacterial surface. This is achieved mainly through binding of host proteinase inhibitors and complement regulatory proteins to bacterial surface proteins. In a later phase of the infection, massive proteolytic activity will release bacterial surface proteins and degrade human tissues, thus facilitating bacterial spread. These proteolytic events are regulated both temporally and spatially, and should influence virulence and the outcome of S. pyogenes infections.

Bacterial Proteins↗
PubMed2006

Regulation of outside-in signaling and affinity by the beta2 I domain of integrin alphaLbeta2.

The adhesiveness of integrin alpha(L)beta(2) is modulated by divalent cations. We mutated three metal ion-binding sites in the beta(2) I domain. The metal ion-dependent adhesion site (MIDAS) and the ligand-induced metal-binding site are required for ligand binding and sufficient for synergism between Ca(2+) and Mg(2+). Adjacent to MIDAS (ADMIDAS) mutants are constitutively active but remain bent, with poor exposure of a beta(2) stalk region epitope. Fluorescence resonance energy transfer between fluorescent protein-fused alpha(L) and beta(2) cytoplasmic domains showed that ADMIDAS mutation abrogated ligand binding-induced spatial separation of cytoplasmic domains. Furthermore, ADMIDAS mutation abolished spreading on ligand-bearing substrates. Thus, beta(2) I domain metal ion-binding sites regulate alpha(L) I domain affinity, and the ADMIDAS is required for outside-in signaling.

Amino Acid Sequence↗
PubMed2001

Collimator scatter and 2D dosimetry in small proton beams.

Monte Carlo simulations have been performed to determine the influence of collimator-scattered protons from a 150 MeV proton beam on the dose distribution behind a collimator. Slit-shaped collimators with apertures between 2 and 20 mm have been simulated. The Monte Carlo code GEANT 3.21 has been validated against one-dimensional dose measurements with a scintillating screen, observed by a CCD camera. In order to account for the effects of the spatial response of the CCD/scintillator system, the line-spread function was determined by comparison with measurements made with a diamond detector. The line-spread function of the CCD/scintillator system is described by a Gaussian distribution with a standard deviation of 0.22 mm. The Monte Carlo simulations show that protons that hit the collimator on the entrance face and leave it through the wall of the aperture make the largest scatter contribution. Scatter on air is the major contribution to the extent of the penumbra. From the energy spectra it is derived that protons with a relative biological effectiveness greater than 1 cause at most 1% more damage in tissue than what would be expected from the physical dose.

Computer Simulation↗
PubMed2000

Experimental observation of localization in the spatial frequency domain of a kicked optical system

An experimental realization of an optical "kicked" system is presented. It exhibits localization analogous to that of the quantum "kicked-rotor." In the experiment, free space propagating light is periodically kicked by thin sinusoidal phase gratings, which produce high order diffractions and tend to increase the spatial frequency band. The wave property suppresses this diffusive spread. The localization is realized in a regime near anti-resonance of the system, which is also studied theoretically. The behavior in this regime is similar to that of electronic motion in incommensurate potentials. A crucial part of the experimental system is the grating in-phase positioning, which is done by using the Talbot effect.

Journal Article↗
PubMed2004

Influence of volcanic activity on the population genetic structure of Hawaiian Tetragnatha spiders: fragmentation, rapid population growth and the potential for accelerated evolution.

Volcanic activity on the island of Hawaii results in a cyclical pattern of habitat destruction and fragmentation by lava, followed by habitat regeneration on newly formed substrates. While this pattern has been hypothesized to promote the diversification of Hawaiian lineages, there have been few attempts to link geological processes to measurable changes in population structure. We investigated the genetic structure of three species of Hawaiian spiders in forests fragmented by a 150-year-old lava flow on Mauna Loa Volcano, island of Hawaii: Tetragnatha quasimodo (forest and lava flow generalist), T. anuenue and T. brevignatha (forest specialists). To estimate fragmentation effects on population subdivision in each species, we examined variation in mitochondrial and nuclear genomes (DNA sequences and allozymes, respectively). Population subdivision was higher for forest specialists than for the generalist in fragments separated by lava. Patterns of mtDNA sequence evolution also revealed that forest specialists have undergone rapid expansion, while the generalist has experienced more gradual population growth. Results confirm that patterns of neutral genetic variation reflect patterns of volcanic activity in some Tetragnatha species. Our study further suggests that population subdivision and expansion can occur across small spatial and temporal scales, which may facilitate the rapid spread of new character states, leading to speciation as hypothesized by H. L. Carson 30 years ago.

Animals↗
PubMed1995

Collimator optimization for lesion detection incorporating prior information about lesion size.

A Bayesian estimator has been developed as a paradigm for human observer performance in detecting lesions of unknown size in a uniform noisy background. The Bayesian observer used knowledge of the range of possible lesion sizes as a prior; its predictions agreed well with the results of a six-observer perceptual study. The average human response to changes in collimator resolution, as measured by the detectability index, dA, was tracked by the Bayesian detector's signal-to-noise ratio (SNR) somewhat better than by two other estimation models based, respectively, on lesser and greater degrees of lesion size uncertainty. As the range of possible lesion sizes increased, the Bayesian detector's SNR decreased and the optimal collimator resolution shifted towards better resolution. An analytic approximation for the variance of lesion activity estimates (which included the same prior) was shown to predict the variance of the Bayesian estimator over a wide range of collimator resolution values. Because the bias of the Bayesian estimator was small (< 1%), the analytic variance estimate permitted a rapid and convenient prediction of the Bayesian detection SNR. This calculation was then used to optimize the geometric parameters of a two-layer tungsten collimator being constructed from crossed grids for a new imaging detector. A Monte Carlo program was first run to estimate all contributions to the radial point-spread function for collimators of differing tungsten contents and spatial resolution values, imaging 140-keV photons emitted from the center of a 15-cm-diameter, water-filled attenuator. The optimal collimator design for detecting lesions with unknown diameters in the range 2.5-7.5 mm yielded a system resolution of approximately 8.5-mm FWHM, a geometric collimator efficiency of 1.21 x 10(-4), and a single-septum penetration probability of 1%.

Bayes Theorem↗
PubMed1998

Spatio-temporal subthreshold receptive fields in the vibrissa representation of rat primary somatosensory cortex.

Spatio-temporal subthreshold receptive fields in the vibrissa representation of rat primary somatosensory cortex. J. Neurophysiol. 80: 2882-2892, 1998. Whole cell recordings of synaptic responses evoked by deflection of individual vibrissa were obtained from neurons within adult rat primary somatosensory cortex. To define the spatial and temporal properties of subthreshold receptive fields, the spread, amplitude, latency to onset, rise time to half peak amplitude, and the balance of excitation and inhibition of subthreshold input were quantified. The convergence of information onto single neurons was found to be extensive: inputs were consistently evoked by vibrissa one- and two-away from the vibrissa that evoked the largest response (the "primary vibrissa"). Latency to onset, rise time, and the incidence and strength of inhibitory postsynaptic potentials (IPSPs) varied as a function of position within the receptive field and the strength of evoked excitatory input. Nonprimary vibrissae evoked smaller amplitude subthreshold responses [primary vibrissa, 9.1 +/- 0.84 (SE) mV, n = 14; 1-away, 5. 1 +/- 0.5 mV, n = 38; 2-away, 3.7 +/- 0.59 mV, n = 22; 3-away, 1.3 +/- 0.70 mV, n = 8] with longer latencies (primary vibrissa, 10.8 +/- 0.80 ms; 1-away, 15.0 +/- 1.2 ms; 2-away, 15.7 +/- 2.0 ms). Rise times were significantly faster for inputs that could evoke action potential responses (suprathreshold, 4.1 +/- 1.3 ms, n = 8; subthreshold, 12.4 +/- 1.5 ms, n = 61). In a subset of cells, sensory evoked IPSPs were examined by deflecting vibrissa during injection of hyperpolarizing and depolarizing current. The strongest IPSPs were evoked by the primary vibrissa (n = 5/5), but smaller IPSPs also were evoked by nonprimary vibrissae (n = 8/13). Inhibition peaked by 10-20 ms after the onset of the fastest excitatory input to the cortex. This pattern of inhibitory activity led to a functional reversal of the center of the receptive field and to suppression of later-arriving and slower-rising nonprimary inputs. Together, these data demonstrate that subthreshold receptive fields are on average large, and the spatio-temporal dynamics of these receptive fields vary as a function of position within the receptive field and strength of excitatory input. These findings constrain models of suprathreshold receptive field generation, multivibrissa interactions, and cortical plasticity.

Animals↗
PubMed2005

Temporal dependence in uncoupling of blood volume and oxygenation during interictal epileptiform events in rat neocortex.

We investigated the dynamic spatiotemporal relationships of cerebral blood volume (CBV), deoxygenated hemoglobin (Hbr), and light scatter (LS) associated with interictal epileptiform events with multiwavelength optical recording of intrinsic signals and simultaneous field potential recording. Interictal spikes (IISs) were induced with iontophoresis of bicuculline methiodide in rat neocortex. Intrinsic signal changes appeared as early as 100 msec after the IIS at all wavelengths and could be appreciated after only a single IIS. Initially, the largest signal arose from a focal increase in deoxygenation, which lasted for approximately 2 sec, consistent with an "initial dip." An equally early focal increase in CBV had a smaller amplitude than the Hbr signal until >2 sec after the IIS, when its amplitude surpassed that of the Hbr signal but also spread to a larger, less focal area. The most spatially restricted and smallest amplitude signal was produced by LS. A later hyperoxygenation, or increase in blood oxygenation level-dependent signal, was often seen in the draining veins but inconsistently seen in the IIS focus. An inverted optical signal was recorded at all wavelengths from multiple regions in the surrounding cortex within 100 msec of the IIS. We therefore conclude that the IIS induces a rapid increase in metabolic demand, which cannot be met by a rapid, initially focal but small increase in CBV that results in a prolonged increase in Hbr (epileptic dip in oxygenated hemoglobin). The inverted optical signal in the surround arises from a decrease in CBV and a decrease in Hbr, likely resulting from a combination of shunting of CBV to the focus and decreased metabolic demand resulting from decreased neuronal activity, consistent with "surround inhibition."

Action Potentials↗
PubMed2004

Topographical pattern dynamics in passive adhesion of cell membranes.

Strong adhesion of highly active cells often nucleates focal adhesions, synapses, and related structures. Red cells lack such complex adhesion systems and are also nonmotile, but they are shown here to dynamically evolve complex spatial patterns beyond an electrostatic threshold for strong adhesion. Spreading of the cell onto a dense, homogeneous poly-L-lysine surface appears complete in <1 s with occasional blisters that form and dissipate on a similar timescale; distinct rippled or stippled patterns in fluorescently labeled membrane components emerge later, however, on timescales more typical of long-range lipid diffusion (approximately minutes). Within the contact zone, the anionic fluorescent lipid fluorescein phosphoethanolamine is seen to rearrange, forming worm-like rippled or stippled domains of <500 nm that prove independent of whether the cell is intact and sustaining a tension or ruptured. Lipid patterns are accompanied by visible perturbations in Band 3 distribution and weaker perturbations in membrane skeleton actin. Pressing down on the membrane quenches the lipid patterns, revealing a clear topographical basis for pattern formation. Counterion screening and membrane fluctuations likely contribute, but the results primarily highlight the fact that even in adhesion of a passive red cell, regions of strong contact slowly evolve to become interspersed with regions where the membrane is more distant from the surface.

Cell Adhesion↗
PubMed1996

Intrinsic optical signals in rat neocortical slices measured with near-infrared dark-field microscopy reveal changes in extracellular space.

In the last decade, the measurement of activity-dependent intrinsic optical signals (IOSs) in excitable tissues has become a useful tool for collecting data about spatial patterns of information processing in mammalian brain and spread of excitation. Although the extent of the IOS correlates well with the extent of electrical excitation, its time course is much slower, suggesting that it does not directly monitor the electrical activity. The aim of this study was to investigate the mechanisms responsible for generation of IOSs. Coronal neocortical brain slices of juvenile rats were electrically stimulated at the border of layer VI and the white matter. The induced columnar-shaped IOSs were recorded using dark-field video microscopy. At corresponding locations, alterations in extracellular K+ concentration and extracellular space (ECS) volume were registered using ion-selective microelectrodes. After stimulation, a transient increase of extracellular K+ concentration up to 10 mM and a transient decrease of ECS volume by approximately 4% could be observed. The comparison of the time courses of these parameters yielded considerable differences between extracellular K+ concentration increase and IOS, but obvious similarities between alterations in ECS volume and IOS. To test the hypothesis that changes in IOS reflect changes in ECS, but not extracellular K+ concentration, we recorded under conditions that are known to prevent activity-induced changes in ECS, i.e., in low Cl- solutions and in the presence of furosemide. Both treatments similarly decreased stimulation-induced IOSs and alterations of ECS. However, the effect of these treatments on changes of extracellular K+ was different and did not correspond to the changes of IOS. We conclude that activity-dependent IOSs in rat neocortical slices measured by near-infrared video microscopy reveal changes in ECS. Furthermore, the pharmacological and ion substitutional experiments make it likely that activity-induced IOSs are attributable to cell swelling via a net KCI uptake and a concomitant water influx.

Animals↗