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PubMed1999

A primer of magnetic stimulation as a tool for neuropsychology.

Transcranial magnetic stimulation (TMS) offers the neuropsychologist a 'virtual lesion' method of investigating the effects of cortical dysfunction. Classical neuropsychology relies on patients with irreversible, and often diffuse brain lesions and these factors place limitations on the inferences that can be drawn about normal brain function. Thus the neuropsychologist is constrained by the extent to which the damaged brain undergoes reorganisation and by the inability to address questions regarding the timing of cognitive functions. TMS can disrupt cognitive functions for a few tens of milliseconds (although some effects of TMS can be seen for longer), with spatial resolution in the order of a centimetre and therefore allows one to study the role of brain areas without the masking effects of cortical reorganisation. The spatial and temporal resolutions are not unique to TMS but because TMS can be used as a temporary interference technique, it has a functional resolution with which one can address questions beyond the range of other neuroimaging and patient studies. Here we outline how TMS produces transitory 'lesion' effects, examine how the effects of stimulation spread in depth and breadth across the cortex and discuss the principles of the use of TMS in neuropsychology. Finally, we also itemise some issues of safety.

Cerebral Cortex↗
PubMed1988

An experimental study of the relationship between image quality and spatial resolution for the gamma camera.

Many centres make regular measures of gamma camera performance as part of routine quality assurance programmes. Such measures may detect gradual deterioration in the camera but provide no basis on which to decide when corrective action should be taken. It is necessary to know when changes in camera performance are significant in terms of perceived image quality. In this work, one index of performance, the full width half maximum (FWHM) of the line spread function, was degraded in a controlled manner and the ability of observers to detect this change in the images produced was examined. Both simple and complex objects were investigated. A suitable decision criterion was suggested which indicated that changes of about 0.3 mm in the FWHM of the camera could be detected in the image. This figure was essentially independent of the complexity of the image, the initial FWHM of the camera and, above 300 k, the number of counts in the image. The way in which this type of experiment can help to establish a rational basis for gamma camera quality assurance programmes is discussed.

Bone and Bones↗
PubMed2003

Spatially resolved wavefront aberrations of ophthalmic progressive-power lenses in normal viewing conditions.

PURPOSE: To measure the wavefront aberration at different locations in progressive-power lenses (PPL's) isolated and in situ (PPL's plus eye). METHODS: A Hartmann-Shack wavefront sensor was used to measure progressive-power lenses and human eyes either independently or in combination. In each selected zone, the lens was placed and tilted accordingly to simulate natural viewing conditions. We measured 21 relevant locations across an isolated PPL (plano lens of power addition of 2 D). In six of the locations, the wavefront aberration of the eye plus PPL were obtained in two ways: (1) by direct measurement of the system and (2) by adding the individual wavefront aberrations of the eye and the lens for each appropriate zone. In every case, we obtained the wavefront aberration as Zernike polynomials expansions, the root mean square error, the point-spread function, and the Strehl ratio. RESULTS: Along the corridor of the PPL, third-order coma and trefoil, and astigmatism were the dominant aberrations. In areas of the PPL outside the corridor, astigmatism increased, whereas other aberrations remained similar to the lens center. Small differences were found between the direct and calculated methods used to obtain the wavefront aberration of the eye with the lens, and the possible sources of errors were discussed. In some lenses zones, the aberrations of the lens may be compensated by the particular aberrations of the eye, yielding improved optical performance over that present in the lens alone. CONCLUSIONS: We designed and built a wavefront sensor to perform spatially resolved aberration measurements in ophthalmic lenses, in particular in PPL's, either isolated or in combination with the eye. The aberrations appearing in the PPL were compared with those in normal aged eyes.

Adult↗
PubMed1998

Variable TE gradient and spin echo sequences for in vivo MR microscopy of short T2 species.

Collagen-rich tissues such as skin or fibrous cartilage have very short T2 and thus, in order to be visible, demand a commensurate reduction in echo time. Whereas short echo time for imaging of humans is straightforward at large fields of view with currently available whole body gradient hardware, the problem is more challenging in the microscopic resolution regime (<100 microm). In this work a simple approach consisting of shortening the echo time dynamically toward the lower spatial frequencies is described for three-dimensional partial flip-angle gradient and spin-echo sequences. Microimages obtained in vivo at 50 microm resolution on a 1.5 T whole body scanner are shown to afford a signal-to-noise gain of over 100% in the dermis of the human skin. A point-spread function analysis indicates that the variable echo time gradient-echo sequence produces a unique not previously reported off-resonance artifact in the phase-encoding direction. The artifact results from the phase modulation occurring during the variable echo time and can manifest as both blurring and intensity fluctuations, as well as shifts of boundaries in the phase-encoding direction. However, for the on-resonance condition, the images are free from these artifacts and exhibit significantly improved signal-to-noise ratio.

Artifacts↗
PubMed1985

Observations on the astrocyte response to a cerebral stab wound in adult rats.

The temporal and spatial distribution of immunocytochemically identified reactive astrocytes is described following a cerebral stab wound in adult rats. Different patterns of reactivity were observed in the cerebral cortex, the corpus callosum and the deep structures of the hemisphere. In the cerebral cortex, the zone of astrocytic reactivity was initially limited to the vicinity of the wound but spread with time to encompass the entire ipsilateral cortex, then regressed; in the deep structures only a spreading phase was observed and this was slower than in the cortex; reactivity in the corpus callosum was slight and always restricted to the immediate vicinity of the lesion. Reactive astrocytes were never observed in the hemisphere contralateral to the lesion. The reorganization of reactive astrocytes in the immediate vicinity of the lesion into a membrana gliae limitans accessoria was also observed. On the basis of these observations, the hypothesis is proposed that astrocytes respond primarily to the mechanical disruption consequent to injury and that the response promotes the restoration of the structural integrity of the lesioned tissue.

Animals↗
PubMed1997

Synapse specificity of long-term potentiation breaks down at short distances.

Long-term potentiation (LTP), the long-lasting increase in synaptic transmission, has been proposed to be a cellular mechanism essential for learning and memory, neuronal development, and circuit reorganization. In the original theoretical and experimental work it was assumed that only synapses that had experienced concurrent pre- and postsynaptic activity are subject to synaptic modification. It has since been shown, however, that LTP is also expressed in synapses on neighbouring neurons that have not undergone the induction procedure. Yet, it is still believed that this spread of LTP is limited to adjacent postsynaptic cells, and does not occur for synapses on neighbouring input fibres. However, for technical reasons, tests for 'input specificity' were always done for synapses relatively far apart. Here we have used a new local superfusion technique, which allowed us to assess the synaptic specificity of LTP with a spatial resolution of approximately 30 microm. Our results indicate that there is no input specificity at a distance of less than 70 microm. Synapses in close proximity to a site of potentiation are also potentiated regardless of their own history of activation, whereas synapses far away show no potentiation.

Animals↗
PubMed1989

Chromosomal inversion patterning and population differentiation in a young insular species, Drosophila silvestris.

The recently evolved Hawaiian species Drosophila silvestris has a subdivided population structure and shows great spatial heterogeneity in chromosome inversion distributions and frequencies within its extremely limited geographic range. Pattern analysis of the 11 chromosomal polymorphisms in the context of the recently discovered morphological and behavioral divergence within the species has elucidated the history of the chromosomal differentiation. We identify four chronological groups of inversions and their probable sites of origin. Spread of the derived "3-row" bristle morphotype on the Hilo side of the Island of Hawaii has been accompanied by the acquisition of six new inversion polymorphisms. Three phylogenetically old inversions show correlations with altitude, and there are multiple cross-correlations between inversions on the same and different chromosomes, reflecting complex interaction systems. Quantification of the genetic population structure of D. silvestris by hierarchical F statistics reveals a dramatic level of genetic differentiation for an evolutionarily new species of such restricted range. This level exceeds that of older, continental Drosophila species. There is, however, minimal concordance between the chromosomal variation and the morphological-behavioral discontinuity, a consequence of the extensive cytological variation within each morphotype. Such a fragmented gene pool favors the rapid evolution and continued divergence of this insular species.

Animals↗
PubMed1986

Quantitative electron microscope autoradiography: application of multiple linear regression analysis.

A new method for the analysis of high resolution EM autoradiographs is described. It identifies labelled cell organelle profiles in sections on a strictly statistical basis and provides accurate estimates for their radioactivity without the need to make any assumptions about their size, shape and spatial arrangement. The radioactivity in interfacial membranes and transitional junctional regions between pairs of adjoining cell structures can be determined without any additional measurements. The uniformity of internal labelling of large cell organelles can be also assessed. Correcting for cross-fire does not need any predictive information from a frequency distribution function describing the image spread about a radioactive point source. Instead, the section area is subdivided into regions in such a way that each region with cross-fired silver grains over it includes also the sites of the radioactive disintegrations that have produced them. The method is based on the quantitative regression relationship between the number of developed silver grains overlying any given region and the size of the cell organelle profiles included. A transparent overlay screen bearing a regular array of circles and a point-counting procedure are applied to divide the section area into regions and to measure their area and the size of the cell organelle profiles. The least squares method is used for the simple and rapid calculation of specific activity estimates and exact standard errors to be attached to them. A modest computing facility and a standard library program are required. Simulation modelling and analysis of residuals were used to lend support to the validity of the method.

Animals↗
PubMed2000

Voltage- and ligand-gated ryanodine receptors are functionally separated in developing C2C12 mouse myotubes.

In order to further understand the role of voltage- and ligand-gated ryanodine receptors in the control of intracellular Ca2+ signalling during myogenesis, changes in cytosolic free calcium concentration ([Ca2+]i) were investigated by fura-2 videoimaging in C2C12 mouse myotubes developing in vitro. A synchronous [Ca2+]i increase was observed after depolarisation with high [K+], while the Ca2+ response propagated as a wave following caffeine administration. Application of the two stimuli to the same myotube often revealed the existence of cellular zones that were responsive to depolarisation but not to caffeine. Focal application of high [K+] promoted a [Ca2+]i response detectable only in the cellular areas close to the pipette tip, while focal application of caffeine elicited a [Ca2+]i increase which spread as a Ca2+ wave. Buffering of [Ca2+]i by BAPTA did not affect the pattern of the depolarisation-induced [Ca2+]i transient but abolished the Ca2+ waves elicited by caffeine. When high [K+] and caffeine were applied in sequence, reciprocal inhibition of the [Ca2+]i responses was observed. Our results suggest that the different spatial patterns of [Ca2+]i responses are due to uneven distribution of voltage- and ligand-gated ryanodine receptors within the myotube. These two types of receptor control two functionally distinct Ca2+ pools which are part of a common intracellular compartment. Finally, the two differently operated ryanodine receptor channels appear to be independently activated, so that a mechanism of Ca2+-induced Ca2+ release is not required to sustain the global response in C2C12 myotubes.

Animals↗
PubMed2004

The spatial pattern of atrial cardiomyocyte calcium signalling modulates contraction.

We examined the regulation of calcium signalling in atrial cardiomyocytes during excitation-contraction coupling, and how changes in the distribution of calcium impacts on contractility. Under control conditions, calcium transients originated in subsarcolemmal locations and showed local regeneration through activation of calcium-induced calcium release from ryanodine receptors. Despite functional ryanodine receptors being expressed at regular (approximately 2 microm) intervals throughout atrial myocytes, the subsarcolemmal calcium signal did not spread in a fully regenerative manner through the interior of a cell. Rather, there was a diminishing centripetal propagation of calcium. The lack of regeneration was due to mitochondria and SERCA pumps preventing the inward movement of calcium. Inhibiting these calcium buffering mechanisms allowed the globalisation of action potential-evoked responses. In addition, physiological positive inotropic agents, such as endothelin-1 and beta-adrenergic agonists, as well as enhanced calcium current, calcium store loading and inositol 1,4,5-trisphosphate infusion also led to regenerative global responses. The consequence of globalising calcium signals was a significant increase in cellular contraction. These data indicate how calcium signals and their consequences are determined by the interplay of multiple subcellular calcium management systems.

Animals↗
PubMed2000

A Spatially Resolved Plerionic X-Ray Nebula around PSR B0540-69.

We present a high-resolution Chandra X-ray observation of PSR B0540-69, the Crab-like 50 ms pulsar in the Large Magellanic Cloud. We use phase-resolved imaging to decompose the extended X-ray emission, as expected of a synchrotron nebula, from the pointlike emission of the pulsar. The image of the pulsed X-ray emission shows a well-defined point-spread function of the observation, while the resolved nebula has a morphology and size remarkably similar to the Crab nebula, including evidence for a jetlike feature from PSR B0540-69. The patchy outer shell, which most likely represents the expanding blast wave of the supernova, is reminiscent of that seen in radio. Based on morphology, size, and energetics, there can be little doubt that SNR B0540-69 is an analogous system to the Crab but located in our neighboring galaxy.

Journal Article↗
PubMed2006

An LNG release, transport, and fate model system for marine spills.

LNGMAP, a fully integrated, geographic information based modular system, has been developed to predict the fate and transport of marine spills of LNG. The model is organized as a discrete set of linked algorithms that represent the processes (time dependent release rate, spreading, transport on the water surface, evaporation from the water surface, transport and dispersion in the atmosphere, and, if ignited, burning and associated radiated heat fields) affecting LNG once it is released into the environment. A particle-based approach is employed in which discrete masses of LNG released from the source are modeled as individual masses of LNG or spillets. The model is designed to predict the gas mass balance as a function of time and to display the spatial and temporal evolution of the gas (and radiated energy field). LNGMAP has been validated by comparisons to predictions of models developed by ABS Consulting and Sandia for time dependent point releases from a draining tank, with and without burning. Simulations were in excellent agreement with those performed by ABS Consulting and consistent with Sandia's steady state results. To illustrate the model predictive capability for realistic emergency scenarios, simulations were performed for a tanker entering Block Island Sound. Three hypothetical cases were studied: the first assumes the vessel continues on course after the spill starts, the second that the vessel stops as soon as practical after the release begins (3 min), and the third that the vessel grounds at the closest site practical. The model shows that the areas of the surface pool and the incident thermal radiation field (with burning) are minimized and dispersed vapor cloud area (without burning) maximized if the vessel continues on course. For this case the surface pool area, with burning, is substantially smaller than for the without burning case because of the higher mass loss rate from the surface pool due to burning. Since the vessel speed substantially exceeds the spill spreading rate, both the thermal radiation fields and surface pool trail the vessel. The relative directions and speeds of the wind and vessel movement govern the orientation of the dispersed plume. If the vessel stops, the areas of the surface pool and incident radiation field (with burning) are maximized and the dispersed cloud area (without burning) minimized. The longer the delay in stopping the vessel, the smaller the peak values are for the pool area and the size of the thermal radiation field. Once the vessel stops, the spill pool is adjacent to the vessel and moving down current. The thermal radiation field is oriented similarly. These results may be particularly useful in contingency planning for underway vessels.

Accidents↗
PubMed1994

Genetic variation in North Africa and Eurasia: neolithic demic diffusion vs. Paleolithic colonisation.

The hypothesis that both genetic and linguistic similarities among Eurasian and North African populations are due to demic diffusion of neolithic farmers is tested against a wide database of allele frequencies. Demic diffusion of farming and languages from the Near East should have determined clines in areas defined by linguistic criteria; the alternative hypothesis of cultural transmission does not predict clines. Spatial autocorrelation analysis shows significant gradients in three of the four linguistic families supposedly affected by neolithic demic diffusion; the Afroasiatic family is the exception. Many such gradients are not observed when populations are jointly analyzed, regardless of linguistic classification. This is incompatible with the hypothesis that major cultural transformations in Eurasia (diffusion of related languages and spread of agriculture) took place without major demographic changes. The model of demic diffusion seems therefore to provide a mechanism explaining coevolution of linguistic and biological traits in much of the Old World. Archaeological, linguistic, and genetic evidence agree in suggesting a multidirectional process of gene flow from the Near East in the neolithic. However, the possibility should be envisaged that some allele frequency patterns can predate the neolithic and depend on the initial spread of Homo sapiens sapiens from Africa into Eurasia.

Agriculture↗
PubMedDate not supplied

Hydro-MRI for the visualization of gastric wall motility using RARE magnetic resonance imaging sequences.

BACKGROUND: Although different imaging techniques such as conventional X-ray, ultrasonography, and hydro-computed tomography are available for the imaging of the stomach, none can depict this organ in full size without radiation. Therefore, the study of the entire gastric wall motility of the stomach is difficult and in principle only performable with rapid magnetic resonance imaging (MRI) techniques. T1-weighted imaging sequences have been used for the dynamic study of gastric wall motility. This technique was combined with the oral intake of para- or superparamagnetic contrast agents to achieve sufficient intraluminal contrast. The technique described in the present study is based on a different contrast mechanism. METHODS: The stomach was filled with 500 mL of 10% of aqueous dextrose solution, and a strongly T2-weighted fast rapid acquisition with relaxation enhancement (RARE) type imaging sequence was used for data acquisition. No other contrast agents were applied. An ultrafast RARE imaging sequence with an asymmetric phase-encoding scheme was developed to achieve a high temporal and spatial resolution. The scanning time per image was approximately 1 s. RESULTS: The stomach was imaged in full size. The concentric constrictor rings moved from the proximal part of the body toward the antrum. The mean duration for one contraction cycle was approximately 17.9 +/- 2.5 s, the mean contractile frequency was 3.4 +/- 0.5 s, and the mean spreading velocity was 65.5 +/- 3.6 cm/min. CONCLUSIONS: The purpose of this study was to demonstrate a new technical approach for a noninvasive dynamic study of gastric motor function with hydro-MRI. This robust method may have clinical application, e.g., in the diagnosis of gastroparesis, and may be extended to the rest of the gastrointestinal tract.

Administration, Oral↗
PubMed2000

Center surround receptive field structure of cone bipolar cells in primate retina.

In non-mammalian vertebrates, retinal bipolar cells show center-surround receptive field organization. In mammals, recordings from bipolar cells are rare and have not revealed a clear surround. Here we report center-surround receptive fields of identified cone bipolar cells in the macaque monkey retina. In the peripheral retina, cone bipolar cell nuclei were labeled in vitro with diamidino-phenylindole (DAPI), targeted for recording under microscopic control, and anatomically identified by intracellular staining. Identified cells included 'diffuse' bipolar cells, which contact multiple cones, and 'midget' bipolar cells, which contact a single cone. Responses to flickering spots and annuli revealed a clear surround: both hyperpolarizing (OFF) and depolarizing (ON) cells responded with reversed polarity to annular stimuli. Center and surround dimensions were calculated for 12 bipolar cells from the spatial frequency response to drifting, sinusoidal luminance modulated gratings. The frequency response was bandpass and well fit by a difference of Gaussians receptive field model. Center diameters were all two to three times larger than known dendritic tree diameters for both diffuse and midget bipolar cells in the retinal periphery. In one instance intracellular staining revealed tracer spread between a recorded cell and its nearest neighbors, suggesting that homotypic electrical coupling may contribute to receptive field center size. Surrounds were around ten times larger in diameter than centers and in most cases the ratio of center to surround strength was approximately 1. We suggest that the center-surround receptive fields of the major primate ganglion cell types are established at the bipolar cell, probably by the circuitry of the outer retina.

Animals↗
PubMedDate not supplied

Direction selectivity in a model of the starburst amacrine cell.

The starburst amacrine cell (SBAC), found in all mammalian retinas, is thought to provide the directional inhibitory input recorded in On-Off direction-selective ganglion cells (DSGCs). While voltage recordings from the somas of SBACs have not shown robust direction selectivity (DS), the dendritic tips of these cells display direction-selective calcium signals, even when gamma-aminobutyric acid (GABAa,c) channels are blocked, implying that inhibition is not necessary to generate DS. This suggested that the distinctive morphology of the SBAC could generate a DS signal at the dendritic tips, where most of its synaptic output is located. To explore this possibility, we constructed a compartmental model incorporating realistic morphological structure, passive membrane properties, and excitatory inputs. We found robust DS at the dendritic tips but not at the soma. Two-spot apparent motion and annulus radial motion produced weak DS, but thin bars produced robust DS. For these stimuli, DS was caused by the interaction of a local synaptic input signal with a temporally delayed "global" signal, that is, an excitatory postsynaptic potential (EPSP) that spread from the activated inputs into the soma and throughout the dendritic tree. In the preferred direction the signals in the dendritic tips coincided, allowing summation, whereas in the null direction the local signal preceded the global signal, preventing summation. Sine-wave grating stimuli produced the greatest amount of DS, especially at high velocities and low spatial frequencies. The sine-wave DS responses could be accounted for by a simple mathematical model, which summed phase-shifted signals from soma and dendritic tip. By testing different artificial morphologies, we discovered DS was relatively independent of the morphological details, but depended on having a sufficient number of inputs at the distal tips and a limited electrotonic isolation. Adding voltage-gated calcium channels to the model showed that their threshold effect can amplify DS in the intracellular calcium signal.

Amacrine Cells↗
PubMed2006

Quantum optimal control of molecular isomerization in the presence of a competing dissociation channel.

The quantum optimal control of isomerization in the presence of a competing dissociation channel is simulated on a two-dimensional model. The control of isomerization of a hydrogen atom is achieved through vibrational transitions on the ground-state surface as well as with the aid of an excited-state surface. The effects of different competing dissociation channel configurations on the isomerization control are explored. Suppression of the competing dissociation dynamics during the isomerization control on the ground-state surface becomes easier with an increase in the spatial separation between the isomerization and dissociation regions and with a decrease in the dissociation channel width. Isomerization control first involving transfer of amplitude to an excited-state surface is less influenced by the dissociation channel configuration on the ground-state surface, even in cases where the excited-state surface allows for a moderate spreading of the excited wave packet.

Journal Article↗
PubMed2004

Contribution of somatosensory cortex to evoked cerebellar blood flow responses.

Projections from the trigeminocerebellar pathway and the somatosensory cortex coincide spatially in the granule cell layer of Crus I/II of the cerebellar hemisphere. A biphasic field potential was seen: one peak at 10 ms (trigeminal input) and another at 20 ms (somatosensory input). Linear correlation analysis revealed only a weak coupling between somatosensory input and cerebellar blood flow responses to infraorbital nerve stimulation. In separate experiments, cortical spreading depression attenuated the field potential peak at 20 ms while blood flow responses remained unaltered. Thus, trigeminocerebellar activity explained the evoked blood flow responses. Our data provide further evidence that activity-dependent blood flow responses are context-sensitive and that interaction between excitatory neuronal circuits targeting the same cells may occlude vascular responses.

Action Potentials↗