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PubMed2005

Hierarchical nature of morphological integration and modularity in the human posterior face.

Morphological integration and modularity are important points of intersection between evolution and the development of organismal form. Identification and quantification of integration are also of increasing paleoanthropological interest. In this study, the "posterior face," i.e., the mandibular ramus and its integration with the associated midline and lateral basicranium, is analyzed in lateral radiographs of 144 adult humans from three different geographic regions. The null hypothesis of homogenously pervasive morphological integration among "posterior-face" components is tested with Procrustes geometric morphometrics, partial least squares, and singular warps analysis. The results reveal statistically significant differences in integration. Only loose integrative relationships are found between midline and lateral components of the basicranium, which may indicate the presence of at least two different basicranial modules. This modularity can be interpreted in terms of spatiotemporal dissociation in the development of those basicranial structures, and gives support to hypotheses of independent phylogenetic modifications at the lateral and midline basicranium in humans. In addition, morphological integration was statistically significantly stronger between the middle cranial fossa and the mandibular ramus than between the ramus and the midline cranial base. This finding confirms previous hypotheses of a "petroso-mandibular unit," which could be a developmental consequence of well-known phylogenetic modifications in coronal topology of the posterior face and base in hominoid evolution, related to middle cranial fossa expansion. This unit could be involved in later evolutionary tendencies in the hominid craniofacial system.

Adult↗
PubMed2003

Hemodynamic segmentation of MR brain perfusion images using independent component analysis, thresholding, and Bayesian estimation.

Dynamic-susceptibility-contrast MR perfusion imaging is a widely used imaging tool for in vivo study of cerebral blood perfusion. However, visualization of different hemodynamic compartments is less investigated. In this work, independent component analysis, thresholding, and Bayesian estimation were used to concurrently segment different tissues, i.e., artery, gray matter, white matter, vein and sinus, choroid plexus, and cerebral spinal fluid, with corresponding signal-time curves on perfusion images of five normal volunteers. Based on the spatiotemporal hemodynamics, sequential passages and microcirculation of contrast-agent particles in these tissues were decomposed and analyzed. Late and multiphasic perfusion, indicating the presence of contrast agents, was observed in the choroid plexus and the cerebral spinal fluid. An arterial input function was modeled using the concentration-time curve of the arterial area on the same slice, rather than remote slices, for the deconvolution calculation of relative cerebral blood flow.

Adolescent↗
PubMed2000

Proliferation pattern changes in the zebrafish brain from embryonic through early postembryonic stages.

Proliferating cell nuclear antigen (PCNA)-immunohistochemistry was used for demonstrating the spatiotemporal course of proliferation in the brains of embryonic (24 h) through postembryonic (5 days) zebrafish (Danio rerio). Parallel series of the same stages prepared according to the combined Bodian fiber silver-stain/cresyl Nissl-stain were used for improved morphogenetic analysis (i.e., in detecting critical neuroanatomical landmarks). Starting from an essentially ubiquituous proliferation throughout the neural tube before 24 h, PCNA-immunoreactive cells become successively more restricted to a subset of gray matter cells around 48 h and even more distinct proliferation zones become apparent around 72 h. Both hindbrain and forebrain reveal a segmental organization with regard to the distribution of proliferation zones, but the rhombomeric pattern of PCNA-immunoreactive cells emerging between 48 h and 72 h precedes a similar prosomeric pattern by about 48 h. Two divisions of the midbrain-hindbrain boundary are described here morphologically and both are demonstrated to show sustained proliferation throughout the investigated time frame. In contrast, proliferation in the adjacent mesencephalic and cerebellar domains is rapidly down-regulated during the first 5 days of development.

Animals↗
PubMed1983

Effect of viscosity on enzyme-ligand dissociation. II. Role of the microenvironment.

A theoretical treatment, describing a novel viscosity effect on decomposition of enzyme-ligand complexes, recently appeared (Somogyi et al., 1978). From this approach emerged a mechanistic picture of the manner in which increased viscosity lowers the value of the decomposition rate constant. A refined version of this model is presented herein. The analysis is extended to the molecular microenvironment ultimately responsible for mediating the "viscosity effect." Consideration is given to two major factors: (1) the role of viscosity in attenuating the excess chemical energy and (2) the statistical features of the microviscosity. In view of spatiotemporal inhomogeneity in the liquid structure, the concept of averaged microviscosity is introduced to parametrize the enzyme-ligand recombination probability. Quantitative predictions are consistent with models of liquid structure and with results from enzyme studies. The "viscosity effect" may contribute to substrate compartmentation in organized multi-enzyme systems in vivo.

Enzymes↗
PubMed1994

Electrical source localization of human movement-related cortical potentials.

Movement-related cortical potentials (MRCP) of healthy humans were analyzed with a brain electrical source analysis program for modelling equivalent electrical dipoles in order to suggest the generators of the MRCP. Both right and left voluntary self-paced index finger movements were performed by 14 subjects and MRCP were recorded on the scalp with 29 electrodes. A spatiotemporal three-dipole model was developed and it explained 94.1% of the right-hand data and 96.4% of the left-hand data. The models for right- and left-hand data were almost similar except for the different hemispheres. A midline dipole was most active during the preparatory period before the onset of voluntary movement and two contralaterally locating dipoles were most active during and immediately after the motor act. The present model did not support recently suggested bilateral activation of primary motor cortices preceding the voluntary movement. The locations, orientations and the time course of activation of the dipoles suggest the involvement of the supplementary motor area in preparation of the movement and the contralateral primary motor cortex during the execution of the movement and the contralateral primary sensory cortex following the movement.

Adult↗
PubMed1995

Distribution of a brain-specific proteoglycan, neurocan, and the corresponding mRNA during the formation of barrels in the rat somatosensory cortex.

Neurocan is a developmentally regulated chondroitin sulphate proteoglycan in the rat brain. In the present study, spatiotemporal patterns of expression of neurocan and the corresponding mRNA were examined in the developing cortical barrel field of the rat brain by using a monoclonal antibody that was highly specific to neurocan and a riboprobe for a portion of the mRNA. Immunohistochemical analysis revealed that neurocan was distributed throughout the cerebral cortex during early postnatal development but was excluded from the centres of cortical barrels at the time of entry and arborization of thalamocortical axons. At this developmental stage, expression of neurocan mRNA was shown by in situ hybridization to be down-regulated in the barrel centres. When a row of whisker follicles was laser-cauterized on postnatal day 1, the pattern of expression of neurocan was disturbed in the row of barrels that corresponded to the lesioned whisker follicles in the contralateral somatosensory cortex. From these observations, it appears that neuronal stimuli through early thalamocortical fibres from the sensory periphery cause reduced expression of neurocan mRNA in neurocan-producing cells in the presumptive barrel centres. Our findings also suggest that the pattern of distribution of neurocan in early postnatal barrel fields may be due mainly to the down-regulation of expression of neurocan mRNA.

Animals↗
PubMed1996

Forebrain patterning defects in Small eye mutant mice.

Pax6 is a member of the Pax gene family of transcriptional regulators that exhibits a restricted spatiotemporal expression in the developing central nervous system, eye and nose. Mutations in Pax6 are responsible for inherited malformations in man, rat and mouse. To evaluate the role of Pax6 in forebrain development, we studied in detail mouse Small eye/Pax6 mutant brains. This analysis revealed severe defects in forebrain regions where Pax6 is specifically expressed. The establishment of some expression boundaries along the dorsoventral axis of the secondary prosencephalon is distorted and the specification of several ventral structures and nuclei is abolished. Specifically, the development of the hypothalamo-telencephalic transition zone and the ventral thalamus is distorted. Our detailed analysis included a comparison of the expression of Pax6, Dlx1 and several other genes during embryonic mouse brain development in wild-type and in the mutant Small eye (Sey) brain. The results from the analysis of normal brain development show that the restricted expression of Pax6 and Dlx1 at E12.5 dpc respect domains within the forebrain, consistent with the implications of the prosomeric model for the organisation of the forebrain (L. Puelles and J. L. R. Rubenstein (1993) Trends Neurosci. 16, 472-479). Furthermore, we found an early restriction of Pax6 and Dlx1 expression into presumptive histogenetic fields that correlate with the formation of distinct forebrain structures and nuclei. Our results are discussed in light of changes in adhesive properties in the Sey brain that might control segregation, assembly and cell migration of progenitors of specific forebrain regions.

Animals↗
PubMed2004

Analysis of Dscam diversity in regulating axon guidance in Drosophila mushroom bodies.

Dscam is an immunoglobulin (Ig) superfamily member that regulates axon guidance and targeting in Drosophila. Alternative splicing potentially generates 38,016 isoforms differing in their extracellular Ig and transmembrane domains. We demonstrate that Dscam mediates the sorting of axons in the developing mushroom body (MB). This correlates with the precise spatiotemporal pattern of Dscam protein expression. We demonstrate that MB neurons express different arrays of Dscam isoforms and that single MB neurons express multiple isoforms. Two different Dscam isoforms differing in their extracellular domains introduced as transgenes into single mutant cells partially rescued the mutant phenotype. Expression of one isoform of Dscam in a cohort of MB neurons induced dominant phenotypes, while expression of a single isoform in a single cell did not. We propose that different extracellular domains of Dscam share a common function and that differences in isoforms expressed on the surface of neighboring axons influence interactions between them.

Alternative Splicing↗
PubMed2004

Spatiotemporal structures in a model with delay and diffusion.

Pattern formation described by differential-difference equations with diffusion is investigated. It is shown that an arbitrarily small diffusion induces space-time turbulence just at the instability threshold of the homogeneous stationary solution. We prove this property by deriving a complex Ginzburg-Landau equation on the basis of normal form analysis. Well above threshold, such turbulent structures give way to synchronized states ordered by spirals and targets. This secondary instability can be understood with an asymptotic method representing the system as a cellular automaton network.

Biophysics↗
PubMed2003

When the target becomes the mask: using apparent motion to isolate the object-level component of object substitution masking.

J. T. Enns and V. Di Lollo (1997) discovered a new form of visual masking that they labeled object substitution masking (OSM). OSM occurs when 4 dots, presented around a target, trail in the display after target offset. The present study showed that the physical presence of the masking dots after target offset is not necessary for OSM. Instead, the continued presence of a changing high-level representation associated with the target suffices to yield OSM. Apparent motion was used to define such representation. In these experiments, the initial display offset and was followed by a 2nd display where masks appeared at new locations. Only when the spatiotemporal properties of the stimuli on the 2nd display supported the perception of the target moving and turning into the mask was OSM observed.

Analysis of Variance↗
PubMed1997

A subspace reverse-correlation technique for the study of visual neurons.

A new discrete-time reverse-correlation scheme for the study of visual neurons is proposed. The visual stimulus is generated by drawing with uniform probability, at each refresh time, an image from a finite set S of orthonormal images. We show that if the neuron can be modeled as a spatiotemporal linear filter followed by a static nonlinearity, the cross-correlation between the input image sequence and the cell's spike train output gives the projection of the receptive field onto the subspace spanned by S. The technique has been applied to the analysis of simple cells in the primary visual cortex of cats and macaque monkeys. Experimental results are presented where S spans a subspace of spatially low-pass signals. Advantages of the proposed scheme over standard white-noise techniques include improved signal to noise ratios, increased spatial resolution, and the possibility to restrict the study to particular subspaces of interest.

Animals↗
PubMed2000

Précis of Neural organization: structure, function, and dynamics.

NEURAL ORGANIZATION: Structure, function, and dynamics shows how theory and experiment can supplement each other in an integrated, evolving account of the brain's structure, function, and dynamics. (1) STRUCTURE: Studies of brain function and dynamics build on and contribute to an understanding of many brain regions, the neural circuits that constitute them, and their spatial relations. We emphasize Szentágothai's modular architectonics principle, but also stress the importance of the microcomplexes of cerebellar circuitry and the lamellae of hippocampus. (2) FUNCTION: Control of eye movements, reaching and grasping, cognitive maps, and the roles of vision receive a functional decomposition in terms of schemas. Hypotheses as to how each schema is implemented through the interaction of specific brain regions provide the basis for modeling the overall function by neural networks constrained by neural data. Synthetic PET integrates modeling of primate circuitry with data from human brain imaging. (3) DYNAMICS: Dynamic system theory analyzes spatiotemporal neural phenomena, such as oscillatory and chaotic activity in both single neurons and (often synchronized) neural networks, the self-organizing development and plasticity of ordered neural structures, and learning and memory phenomena associated with synaptic modification. Rhythm generation involves multiple levels of analysis, from intrinsic cellular processes to loops involving multiple brain regions. A variety of rhythms are related to memory functions. The Précis presents a multifaceted case study of the hippocampus. We conclude with the claim that language and other cognitive processes can be fruitfully studied within the framework of neural organization that the authors have charted with John Szentágothai.

Brain↗
PubMed1998

Stability and patterning of speech movement sequences in children and adults.

Children (aged 4 and 7 years) and young adults produced a six-syllable utterance 15 times. The displacement of the lower lip was recorded with an Optotrak system and analyzed in a number of ways. First, using a procedure recently developed in our laboratory, displacement records from the 15 repetitions were amplitude- and time-normalized, and the spatiotemporal index (the STI) was computed. The STI reflects the degree to which repeated performance of a task produces movement trajectories that converge on a single pattern. Children produced less stable movement trajectories, as reflected in higher values on the STI. In a second analysis, standard measurements of amplitude and peak velocity were made for two opening and two closing lip movements. These measures suggested that, relative to the size of their oral structures, children have large movement ranges in speech. Also, children tend to move with a lower peak velocity. This large-amplitude, low-velocity movement style may reflect different underlying control processes. Finally, another analysis focused on open-close movement sequences associated with two words of the utterance. A pattern-recognition algorithm applied to the normalized waveforms from the open-close sequences revealed that children and adults produced equally distinctive movement trajectories for the two syllables. Taken together, these preliminary results suggest that nonlinear and nonuniform changes occur in components of the speech motor system during development.

Adult↗
PubMed2001

Controlling spatiotemporal chaos in coupled map lattices.

A simple method is presented for controlling spatiotemporal chaos in coupled map lattices to a homogeneous state. This method can be applied to many kinds of models such as coupled map lattices (CML), one-way open CML (the open-flow model), and globally coupled map. We offer the stability analysis of the homogeneous state. Simple and sufficient conditions are obtained for controlling the above mentioned models. Our theoretical results agree well with numerical simulations.

Journal Article↗
PubMed2003

Quantitative echocardiographic assessment of regional wall motion and left ventricular asynchrony with color kinesis in cardiac surgery patients.

UNLABELLED: Conventional echocardiographic interpretation of regional wall motion abnormalities is subjective and experience dependent. Delayed contraction in the ejection phase (tardokinesis) and regional systolic asynchrony, sensitive markers of myocardial ischemia, cannot be accurately assessed visually. We used color kinesis (CK), a technique that evaluates spatiotemporal patterns of endocardial motion, to objectively detect regional wall motion abnormalities in patients undergoing coronary bypass surgery, and we compared it with conventional assessment of grayscale images by less experienced reviewers; we used expert grading as the gold standard for comparisons. Quantitative CK analysis agreed more closely with expert grading than less experienced reviewers (kappa coefficients, 0.74 versus 0.52 and 0.5). Global tardokinesis, identified in 9 of 26 patients (2 with normal fractional area change), was associated with an increased index of systolic asynchrony. Regional tardokinesis was identified in 48 of 150 segments: 27 segments had a normal magnitude of wall motion, 18 were hypokinetic, and 3 were severely hypokinetic/akinetic. Mildly hypokinetic segments showed delayed systolic motion, whereas residual motion of severely hypokinetic/akinetic segments occurred in early systole, reflecting passive effects produced by adjacent myocardial contraction. Quantitative CK may be a useful supplement to visual assessment, particularly for less experienced readers. By diagnosing tardokinesis, common among cardiac surgical patients even with normal standard ejection phase indices, quantitative CK may improve the intraoperative detection of regional ischemic changes. IMPLICATIONS: Quantitative color kinesis allows for objective and sensitive intraoperative echocardiographic assessment of abnormal spatial and temporal patterns of regional ventricular wall motion, with potentially important implications for improving myocardial ischemia detection in patients undergoing cardiac surgery.

Cardiac Surgical Procedures↗
PubMed2006

Development of the mesencephalic dopaminergic neuron system is compromised in the absence of neurogenin 2.

Neurogenin 2 (Ngn2) is a proneural gene involved in neuronal differentiation and subtype specification in various regions of the nervous system. In the ventral midbrain, Ngn2 is expressed in a spatiotemporal pattern that correlates with the generation of mesencephalic dopaminergic (mesDA) neurons. We show here that lack of Ngn2 impairs the development of mesDA neurons, such that less than half of the normal mesDA neuron number remain in Ngn2 mutant mice at postnatal stages. Analysis of Ngn2 mutant mice during mesDA neurogenesis show that medially located precursors are formed but are arrested in their differentiation at a stage when they have not yet acquired the characteristics of mesDA neuron precursors. Loss of Ngn2 function appears to specifically affect the generation of DA neurons, as the development of other types of neurons within the ventral midbrain is unaltered. Ngn2 is the first example of a gene expressed in progenitors in the ventricular zone of the mesDA neuron domain that is essential for proper mesDA neuron differentiation, and whose loss of function causes impaired mesDA neurogenesis without other major abnormalities in the ventral midbrain.

Animals↗
PubMed2005

[Confocal laser scanning microscopy to study molecular mechanism of mast cell activation].

In the immune system, mast cells are a key cell type in the pathogenesis of immunoglobulin E (IgE)-dependent hypersensitivity reactions. Engagement of the high-affinity IgE receptors by multivalent antigens initiates the downstream activation of signal-transducing enzymes and evokes degranulation and cytokine production via an increase in the intracellular Ca2+ concentration. In addition, mast cells also play a prominent role in non-IgE-mediated hypersensitivity reactions. Mast cells are closely apposed to nerves in vivo and are likely to be regulated functionally by nerves. However, the molecular mechanisms for mast cell activation in an IgE-dependent and -independent manner have not been fully clarified. Confocal laser scanning microscopy has played an essential role in cell biology by allowing visualization of specific intracellular signaling molecules with high spatiotemporal resolution in living cells. We have studied intracellular movements of Ca2+ using a specific fluorescent probe and several types of signaling molecules using derivatives of green fluorescent protein in a living single mast cell using a microscopic strategy. We here describe our imaging analysis of the calcium signals to the nucleus, the movement of secretory granules in the degranulation process, and the nucleocytoplasmic shuttling of mitogen-activated protein kinase in mast cells. Further, we demonstrate that direct communication between mast cells and nerves occurs. These findings provide useful information from a new perspective to understand the molecular mechanisms of allergic reaction and inflammation.

Animals↗
PubMed2000

Spatiotemporal expression of BDNF in the hippocampus induced by the continuous intracerebroventricular infusion of beta-amyloid in rats.

The beta-amyloid protein (Abeta) is the major component of senile plaques found in the brain in Alzheimer's disease (AD). Its neurotoxic properties in vivo, however, are not well defined. Since the expression of neurotrophin genes is considered an important component of the intrinsic neuroprotective response to insults, we analyzed the gene expression of neurotrophins in the brains of rats which received a continuous infusion of Abeta-(1-42) into the cerebroventricle. Northern blot analysis revealed a significant increase in brain-derived neurotrophic factor (BDNF) expression in the hippocampus but no change in the cerebral cortices. The alteration peaked on days 3-7 and returned to the basal level on day 14 after the start of Abeta-(1-42) infusion. No significant changes in nerve growth factor or neurotrophin-3 mRNA expression were observed. The infusion of Abeta-(1-40) and (25-35) also triggered the expression of BDNF mRNA, whereas neither Abeta-(40-1) nor (1-16) had any effect. In situ hybridization histochemistry revealed that the expression mainly occurred in the hilus and granular layer of the dentate gyrus and to a lesser extent in the pyramidal neurons of the CA1 region. These results demonstrate that the continuous intracerebroventricular infusion of Abeta induces selective and spatiotemporal expression of BDNF mRNA in the hippocampus.

Alzheimer Disease↗