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Determining and visualizing uncertainty in estimates of fiber orientation from diffusion tensor MRI.

Diffusion tensor MRI (DT-MRI) permits determination of the dominant orientation of structured tissue within an image voxel. This has led to the development of 2D graphical methods for representing fiber orientation and DT-MRI "tractography," which aims to reconstruct the 3D trajectories of white matter fasciculi. Most contemporary fiber orientation mapping schemes and tractography algorithms employ the directional information contained in the eigenvectors of the diffusion tensor to approximate white matter fiber orientation. However, while the uncertainty associated with every estimate of an eigenvector has long been recognized, no attempts to quantify this uncertainty in vivo have been reported. Here, a method is proposed for determining confidence intervals in fiber orientation from real DT-MRI data using the bootstrap method. This is used to construct maps of the "cone of uncertainty," allowing simultaneous viewing of fiber orientation and its uncertainty, and to examine the relationship between orientation uncertainty and tissue anisotropy.

Anisotropy↗

Structure and orientation of the mammalian antibacterial peptide cecropin P1 within phospholipid membranes.

Cecropins are positively charged antibacterial peptides that act by permeating the membrane of susceptible bacteria. To gain insight into the mechanism of membrane permeation, the secondary structure and the orientation within phospholipid membranes of the mammalian cecropin P1 (CecP) was studied using attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy and molecular dynamics simulations. The shape and frequency of the amide I and II absorption peaks of CecP within acidic PE/PG multibilayers (phosphatidylethanolamine/phosphatidylglycerol) in a 7:3 (w/w) ratio (a phospholipid composition similar to that of many bacterial membranes), indicated that the peptide is predominantly alpha-helical. Polarized ATR-FTIR spectroscopy was used to determine the orientation of the peptide relative to the bilayer normal of phospholipid multibilayers. The ATR dichroic ratio of the amide I band of CecP peptide reconstituted into oriented PE/PG phospholipid membranes indicated that the peptide is preferentially oriented nearly parallel to the surface of the lipid membranes. A similar secondary structure and orientation were found when zwitterionic phosphatidylcholine phospholipids were used. The incorporation of CecP did not significantly change the order parameters of the acyl chains of the multibilayer, further suggesting that CecP does not penetrate the hydrocarbon core of the membranes. Molecular dynamics simulations were used to gain insight into possible effects of transmembrane potential on the orientation of CecP relative to the membrane. The simulations appear to confirm that CecP adopts an orientation parallel to the membrane surface and does not insert into the bilayer in response to a cis positive transmembrane voltage difference. Taken together, the results further support a "carpet-like" mechanism, rather than the formation of transmembrane pores, as the mode of action of CecP. According to this model, formation of a layer of peptide monomers on the membrane surface destablizes the phospholipid packing of the membrane leading to its eventual disintegration.

Amino Acid Sequence↗

Refining the overall structure and subdomain orientation of ribosomal protein S4 delta41 with dipolar couplings measured by NMR in uniaxial liquid crystalline phases.

Prokaryotic protein S4 initiates assembly of the small ribosomal subunit by binding to 16 S rRNA. Residues 43-200 of S4 from Bacillus stearothermophilus (S4 Delta41) bind to both 16 S rRNA and to a mRNA pseudoknot. In order to obtain structure-based insights regarding RNA binding, we previously determined the solution structure of S4 Delta41 using NOE, hydrogen bond, and torsion angle restraints. S4 Delta41 is elongated, with two distinct subdomains, one all helical, the other including a beta-sheet. In contrast to the high resolution structures obtained for each individual subdomain, their relative orientation was not precisely defined because only 17 intersubdomain NOE restraints were determined. Compared to the 1.7 A crystal structure, when the sheet-containing subdomains are superimposed, the helical subdomain is twisted by almost 45 degrees about the long axis of the molecule in the solution structure. Because variations in subdomain orientation may explain how the protein recognizes multiple RNA targets, our current goal is to determine the orientation of the subdomains in solution with high precision. To this end, NOE assignments were re-examined. NOESY experiments on a specifically labeled sample revealed that one of the intersubdomain restraints had been misassigned. However, the revised set of NOE restraints produces solution structures that still have imprecisely defined subdomain orientations and that lie between the original NMR structure and the crystal structure. In contrast, augmenting the NOE restraints with N-H dipolar couplings, measured in uniaxial liquid crystalline phases, clearly establishes the relative orientation of the subdomains. Data obtained from two independent liquid crystalline milieux, DMPC/DHPC bicelles and the filamentous bacteriophage Pf1, show that the relative orientation of the subdomains in solution is quite similar to the subdomain orientation in the crystal structure. The solution structure, refined with dipolar data, is presented and its implications for S4's RNA binding activity are discussed.

Geobacillus stearothermophilus↗

Horizontal organization of orientation-sensitive cells in primate visual cortex.

In the visual cortex of the monkey the horizontal organization of the preferred orientations of orientation-selective cells follows two opposing rules: (1) neighbors tend to have similar orientation preferences, and (2) many different orientations are observed in a local region. We have described a classification for orientation maps based on the types of topological singularities and the spacing of these singularities relative to the cytochrome oxidase blobs. Using the orientation drift rate as a measure we have compared simulated orientation maps to published records of horizontal electrode recordings.

Animals↗

GABA-induced remote inactivation reveals cross-orientation inhibition in the cat striate cortex.

We investigated the contributions of lateral intracortical connections to the orientation tuning of area 17 cells using micro-iontophoresis of the inhibitory transmitter gamma-aminobutyric acid (GABA) to inactivate small cortical sites in the vicinity of a recorded cell. GABA was ejected from an array of micropipettes each with an average horizontal distance of 500 microns from the recording site. Of 54 cells tested, 33 showed a reduction and 3 a loss of orientation selectivity due to an increase in responses to non-optimal orientations during GABA inactivation. The response to the optimal orientation remained constant in more than half of the cells and increased or decreased in others. Given that a complete cycle of orientations occupies a tangential distance of 1000 microns, the observed broadening of orientation tuning is presumably due to GABA-mediated inactivation of inhibitory interneurones with different preferred orientations from those of their target cell.

Animals↗

Orientation of dendrites in the lateral geniculate nucleus of the monkey.

Quantitative analysis of dendritic orientation in rapid Golgi sections of the lateral geniculate nucleus of Old World monkeys was performed with the help of a computer-microscope and a tree-analysing program. The orientation of intermediate and terminal dendritic segments of parvocellular and magnocellular multipolar neurons was measured at different ages in relationship to a reference line defined by the major direction of afferent fibres visualized in Golgi preparations and by silver staining. The direction of fibre bundles crossing the nucleus is approximately perpendicular to the layers near their apex, but more oblique laterally and medially. There is a clear tendency for terminal dendritic segments of both parvocellular and magnocellular neurons to be oriented preferentially along these fibres and fewer are perpendicular to them. The orientation of intermediate segments is much less clear, showing a more random orientation with regard to the fibres. There is no obvious influence of the order of branching or of the age of the animal (between late gestation and maturity) on the orientation of terminal and intermediate dendritic segments. A parallel study (Leuba and Garey 1984) suggests that there is greater plasticity in the terminal part of the dendritic tree, and it is possible that the maturation of afferent fibres causes these terminal segments to orient along them very early during normal development.

Age Factors↗

Alcohol consumption by orientals in North America is predicted largely by a single gene.

Orientals consume significantly less alcohol, and show a lower prevalence of alcohol abuse and dependence, than Caucasians. Sociological theories propose that this difference is due mainly to cultural factors. Physiological theories have suggested that the flushing reaction experienced by some Orientals serves as a deterrent to ethanol consumption. The flushing reaction is observed mainly in individuals who possess a mutation in the high-affinity aldehyde dehydrogenase (ALDH2) which renders the enzyme inactive. However, the tendency to flush correlates poorly with alcohol consumption, thus casting doubt on the physiological interpretations. The present study investigates the influence of the ALDH2 allele and of acculturation in North America on alcohol consumption by Orientals born in Canada or the United States. Oriental males carrying the inactive ALDH2(-) allele drink two-thirds less alcohol (6.1 +/- 1.5 vs. 18.2 +/- 2.8 drinks/4 weeks; p < 0.001), show one-third the prevalence of binge drinking (15.2 vs. 42.2%; p < 0.01), and are three times more likely to be abstainers (39.4 vs. 13.3%; p < 0.01) than Oriental ALDH2(+) males carrying the gene for the active enzyme. There were no significant differences in binge drinking or abstinence rates between ALDH2(+) Orientals and Caucasian males. Acculturation in North American society accounted for only 7-11% of the variance in overall consumption (p < 0.02). It is concluded that a single mutation in the high-affinity aldehyde dehydrogenase (ALDH2) gene predicts two-thirds of the alcohol consumption and excessive alcohol use by Oriental males born in North America.

Acculturation↗

Consequences of chemosensory phenomena for leukocyte chemotactic orientation.

The stochastic nature of cell surface receptor-ligand binding is known to limit the accuracy of detection of chemoattractant gradients by leukocytes, thus limiting the orientation ability that is crucial to the chemotactic response in host defense. The probabilistic cell orientation model of Lauffenburger is extended here to assess the consequences of recently discovered receptor phenomena: "down-regulation" of total surface receptor number, spatial asymmetry of surface receptors, and existence of a higher-affinity receptor subpopulation. In general, a reduction in orientation accuracy is predicted by inclusion of these phenomena. An orientation signal based on a simple model of chemosensory adaptation (i.e., a spatial difference in relative receptor occupancy) is found to be functionally different from the signal suggested by an experimental correlation (i.e., a spatial difference in absolute receptor occupancy). However, in the context of receptor "signal noise," the signal based on adaptation yields predictions in better qualitative agreement with the experimental orientation data of Zigmond. From this cell orientation model we can estimate the effective time-averaging period required for noise diminution to a level allowing orientation predictions to match observed levels. This time-averaging period presumably reflects the time constant for receptor signal transduction and locomotory response.

Animals↗

Correlations among bone mineral density, broadband ultrasound attenuation, mechanical indentation testing, and bone orientation in bovine femoral neck samples.

Broadband ultrasound attenuation (BUA) of the calcaneus has been found to correlate with bone mineral density (BMD) of the femoral neck. The purpose of this study was to determine if a correlation exists among femoral neck BUA, femoral neck BMD, and incremental indent depth, a qualitative indicator of local mechanical bone strength, in bovine samples, and if this correlation is dependent upon orientation. For 12 of the bovine samples obtained, BUA was measured at the femoral neck and was followed by a BMD determination of the same area. A 19 mm diameter bicortical core containing the center of the area of interest was removed, transversely cut into 7 mm, thick disks, and tested for hardness by indent depth. For these tests, BMD was well correlated with BUA (R2 = 0.85, P < 0.001). An inversely proportional relationship with a modest correlation was found between indent depth and BMD (R2 = 0.59, P = 0.026), and indent depth and BUA (R2 = 0.57, P = 0.031). In a second set of tests involving 15 different bovine samples, a bicortical core was removed from the femoral neck. A trabecular bone cube measuring 1.5 cm on a side was removed from the center of the core. BUA and BMD measurements were made along the anterior-posterior (AP), medial-lateral (ML), and cephalic-caudal (CC) aspects of the cube. The cubes were randomly separated into three groups, cut in half perpendicular to the axis of interest, and tested for hardness by indent depth. In these tests, no significant difference was found in BMD among the three orientations of the cubes scanned (P = 0.77). In contrast, the BUA along the ML orientation of the cube was significantly greater than that along the AP orientation (P < 0.05). No significant difference was found in the incremental indent depth measurements among cube orientations (P = 0.41). In the test involving only trabecular bone, a much higher correlation between BMD and incremental indent depth was found regardless of cube orientation (R2 = 0.64, P < 0.001). The data indicate that BUA, but not BMD, is affected by trabecular orientation, and that BMD is negatively correlated with incremental indent depth.

Animals↗

Canonical correlations between masticatory muscle orientation and dentoskeletal morphology in children.

In order to identify associations between the orientation of the superficial masseter and temporalis muscles and dentoskeletal morphology in a sample of fifty-five children with various malocclusions, eight muscle-orientation variables (relative to the occlusal plane) and twenty-three dentoskeletal variables were evaluated from lateral head films. The thirty-one measurements were reduced to six muscle-orientation and sixteen dentoskeletal variables by a principal component analysis. Three canonical correlations were identified between the muscle orientation and dentoskeletal variable groups at the 0.05 level of significance and canonical loadings were determined for each set of variables. The first canonical correlation (r1 = 0.931) represents a growth-related correlation factor between the masticatory muscle insertion positions relative to the occlusal plane and the dimensional and positional changes of craniofacial structures during growth. The second canonical correlation (r2 = 0.846) may account for an operational artifact in the geometric measurement process, and the third canonical correlation (r3 = 0.813) suggests an association between superficial masseter muscle orientation relative to the occlusal plane and mandibular form. This report confirms the usefulness of multivariate statistical methods to extract latent associations between muscle orientation and craniofacial morphology; the results obtained suggest a contribution from the geometric orientation of the masticatory muscles to the development and maintenance of the dentoskeletal system.

Adolescent↗

Inner cell allocation in the mouse morula: the role of oriented division during fourth cleavage.

Two populations of blastomeres become positionally distinct during fourth cleavage in the mouse embryo; the inner cells become enclosed within the embryo and the outer cells form the enclosing layer. The segregation of these two cell populations is important for later development, because it represents the initial step in the divergence of placental and fetal lineages. The mechanism by which the inner cells become allocated has been thought to involve the oriented division of polarized 8-cell blastomeres, but this has never been examined in the intact embryo. By using the technique of time-lapse cinemicrography, we have been able for the first time to directly examine the division planes of 8-cell blastomeres during fourth cleavage, and find that there are three, rather than two, major division plane orientations; anticlinal (perpendicular to the outer surface of the blastomere), periclinal (parallel to the outer surface of the blastomere), and oblique (at an angle between the other two). The observed frequencies of each type of division plane orientation provide evidence that the inner cells of the morula must derive from oriented division of 8-cell blastomeres, in accordance with the polarization hypothesis. Analysis of fourth cleavage division plane orientation with respect to either lineage or division order reveals that it is not associated with lineage from either the 2- or the 4-cell stage, but has a slight statistical association with fourth cleavage division order. The lack of association between division plane orientation and lineage supports the prediction that packing patterns and intercellular interactions within the 8-cell embryo during compaction play a role in determining fourth cleavage division plane orientation and thus, the positional fate of the daughter 16-cell blastomeres.

Animals↗

Myosin crossbridge orientation in demembranated muscle fibres studied by birefringence and X-ray diffraction measurements.

Muscle contraction is generally thought to involve changes in the orientation of myosin crossbridges during their ATP-driven cyclical interaction with actin. We have investigated crossbridge orientation in equilibrium states of the crossbridge cycle in demembranated fibres of frog and rabbit muscle, using a novel combination of techniques: birefringence and X-ray diffraction. Muscle birefringence is sensitive to both crossbridge orientation and the transverse spacing of the contractile filament lattice. The latter was determined from the equatorial X-ray diffraction pattern, allowing accurate characterization of the orientation component of birefringence changes. We found that this component decreased when relaxed muscle fibres were put into rigor at rest length, and when either the ionic strength or temperature of relaxed fibres was lowered. In each case the birefringence decrease was accompanied by an increase in the intensity of the (1,1) equatorial X-ray reflection relative to that of the (1,0) reflection. When fibres that had been stretched largely to eliminate overlap between actin- and myosin-containing filaments were put into rigor, there was no change in the orientation component of the birefringence. When isolated myosin subfragment-1 was bound to these rigor fibres, the orientation component of the birefringence increased. The birefringence changes at rest length are likely to be due to changes in the orientation of myosin crossbridges, and in particular of the globular head region of the myosin molecules. In relaxed fibres from rabbit muscle, at 100 mM ionic strength, 15 degrees C, the long axis of the heads appears to be relatively well aligned with the filament axis. When fibres are put into rigor, or the temperature or ionic strength is lowered, the degree of alignment decreases and there is a transfer of crossbridge mass towards the actin-containing filaments.

Adenosine Triphosphate↗

Human orientation discrimination tested with long stimuli.

Human orientation discrimination was measured for single long lines presented sequentially. Orientation sensitivity is better for a narrow range of orientations around the principal meridians. Both the orientation sensitivity and its meridional variation increase with stimulus length. Control experiments show that the "oblique effect" can be obtained as well with a signal detection method as with the method of constant stimuli and that the subjects used a visual orientation cue in their judgments. Comparison of these findings with properties of visual cortical cells suggest that cells similar to S cells of cat and monkey striate cortex, carry the neuronal representation used in the decision process. And indeed the meridional variation in orientation sensitivity can be predicted from the number of monkey S cells preferring different orientations.

Adult↗

The influence of contextual stimuli on the orientation selectivity of cells in primary visual cortex of the cat.

Perception of a visual attribute, such as orientation, is strongly dependent on the context within which a feature is presented, such as that seen in the tilt illusion. The possibility that the neurophysiological basis for this phenomenon may be manifest at the level of cells in striate cortex is suggested by anatomical and physiological observations of orientation dependent long range horizontal connections which relate disparate points in the visual field. This study explores the dependency of the functional properties of single cells on visual context. We observed several influences of the visual field area surrounding cells' receptive field on the properties of the receptive field center: inhibition or facilitation dependent on the orientation of the surround, shifts in orientation preference and changes in the bandwidth of orientation tuning. To relate these changes to perceptual changes in orientation we modeled a neuronal ensemble encoding orientation. Our results show that the filter characteristics of striate cortical cells are not necessarily fixed, but can be dynamic, changing according to context.

Animals↗

Simultaneous orientation contrast for lines in the human fovea.

When it is surrounded by lines of a differing orientation, a test line changes its apparent orientation in a direction away from that of the surround lines. Using a nulling technique to arrive at numerical values, the properties of this simultaneous orientation contrast have been analyzed: it diminishes with distance of the surround lines; rises and then falls off as a function of surround line orientation; decreases with exposure duration; is sharply tuned (+/- 100 msec) for synchrony of test and surround line presentation; is robust to differences between test and surround line disparity but not intensity; and is reduced with dichoptic presentation of test and surround lines. Orientation contrast can be induced in a variety of oriented features, including illusory contours, an ellipse, a moving dot and a row of dots or lines, but two dots alone don't suffice. The results are taken as evidence that orientation is a domain sui generis, in which simultaneous contrast is exhibited in the same manner as in the domains of color, brightness and disparity.

Contrast Sensitivity↗

Dissociation of orientation discrimination from form detection for motion-defined bars and luminance-defined bars: effects of dot lifetime and presentation duration.

A stationary bar-shaped area that was perfectly camouflaged within a dot pattern was rendered visible by moving the dots inside and outside the bar at equal and opposite speeds. Orientation discrimination for this motion-defined (MD) bar was compared with orientation discrimination for a luminance-defined (LD) bar created by switching off all dots outside the bar. The best values of orientation discrimination threshold were similar for MD and LD bars at long presentation durations and long dot lifetimes. But, as presentation duration or dot lifetime was reduced below 1.0 sec, orientation discrimination threshold for MD bars increased at an accelerating rate, while discrimination for LD bars was comparatively unaffected. However, these effects of presentation duration and dot lifetime were largely due to changes in bar visibility. When bar visibility was normalised relative to the relevant bar detection threshold, the effect of presentation duration upon orientation discrimination was abolished for both MD and LD bars, and the effect of dot lifetime was abolished or even reversed. These observations dissociate detection and discrimination for MD and LD form. We suggest that orientation discrimination for MD and LD bars is determined by opponent-orientation mechanisms whose performance is not directly affected by presentation duration, nor degraded by reducing dot lifetime.

Adolescent↗

Processing of linear elements in stereopsis: effects of positional and orientational distinctiveness.

The stereoscopic processing of small linear elements is probed through the comparative analysis of stereograms containing needles or crosses, differing in the local spatial arrangement and orientation of the elements, and the presence or absence of slant. Depending upon the details of the textural design, depth analysis may proceed faster with crosses than with needles, or the reverse. It proceeds faster with vertical than with horizontal needles, except in the case of unslanted regularly-spaced needles. On the whole the data suggest that the elements to be matched in a stereogram are first processed along a common pathway, in which positional regularity has a detrimental effect. In the presence of small linear elements, orientation-tuned neurons would be recruited and their participation would lead either to an inhibition effect when the elements are all similarly oriented, or to a facilitation effect when there is sufficient orientational diversity among the elements. Here, slant plays an indirect role, by widening the orientation spectrum in otherwise regularly oriented textures. Positional irregularity is useful to suppress false matches, while orientational diversity helps to stabilize the perceived surfaces.

Depth Perception↗

Detection of orientationally multimodal textures.

Oriented textures were produced with the use of probability density functions modulated sinusoidally over orientation. Orientational contrast sensitivity functions (OCSFs) for a task involving the discrimination of these patterns from orientationally-random textures were found for several human observers. An inverse Fourier transform of this OCSF yielded a weighting function, or filter, defined over orientation. The weighting function is broad, with a half-height full-width of 34 deg. This orientational filter was able to predict human performance in further discrimination tasks employing a variety of probability density functions over orientation.

Contrast Sensitivity↗