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Rapid adaptation to auditory-visual spatial disparity.

The so-called ventriloquism aftereffect is a remarkable example of rapid adaptative changes in spatial localization caused by visual stimuli. After exposure to a consistent spatial disparity of auditory and visual stimuli, localization of sound sources is systematically shifted to correct for the deviation of the sound from visual positions during the previous adaptation period. In the present study, this aftereffect was induced by presenting, within 17 min, 1800 repetitive noise or pure-tone bursts in combination with synchronized, and 20 degrees disparate flashing light spots, in total darkness. Post-adaptive sound localization, measured by a method of manual pointing, was significantly shifted 2.4 degrees (noise), 3.1 degrees (1 kHz tones), or 5.8 degrees (4 kHz tones) compared with the pre-adaptation condition. There was no transfer across frequencies; that is, shifts in localization were insignificant when the frequencies used for adaptation and the post-adaptation localization test were different. It is hypothesized that these aftereffects may rely on shifts in neural representations of auditory space with respect to those of visual space, induced by intersensory spatial disparity, and may thus reflect a phenomenon of neural short-term plasticity.

Acoustic Stimulation↗

A weighted average likelihood ratio test for spatial clustering of disease.

We consider methods proposed for detecting localized spatial clustering. We propose a new test statistic, the weighted average likelihood ratio test, as an alternative to the spatial scan (maximum likelihood ratio) test statistic. Two different types of weights are considered. We propose an unbiased cluster selection criterion and evaluate the bias of the tests through simulation. We also examine the power of the tests through simulations and apply the methods to the well-known New York leukaemia data.

Cluster Analysis↗

Roughness coding in the somatosensory system.

Roughness perception is coded in the somatosensory system by neurons in the type I slowly adapting (SAI) system. When the fingers scan a surface, an isomorphic representation of the surface is encoded in the discharge patterns of SAI afferents. Central neurons in area 3b of primary somatosensory (SI) cortex spatially filter the peripheral image to compute local spatial variation. The outputs from these neurons converge onto neurons in area 1 and onto neurons in secondary somatosensory (SII) cortex which we believe is the critical processing pathway underlying roughness perception.

Afferent Pathways↗

Direction specific masking and the analysis of motion in two dimensions.

We measured the effects of moving two-component cosine grating masks on the detectability of a moving spatially localized test pattern with a 1.0 octave spatial frequency bandwidth. Masking was used to distinguish between two-component patterns with fluid motion (blobs) and those with rigid motion (plaids). The two gratings which made up the two-dimensional masking patterns were always of the same spatial frequency and contrast, but moved in different directions. We find that plaid masks consistently produced threshold elevations that are 2.0-4.0 times greater than are produced by a single component mask at twice the contrast. Furthermore, this effect is nearly independent of the angle between the two mask components. For fluid motion, however, masking is determined by the mask component whose direction of motion is closest to that of the test. The results obtained with moving two-dimensional patterns demonstrate that, for blobs, the motion of the pattern as a whole has no effect on the degree of masking, whereas, for plaids, the signals arising from the two components interact in a nonlinear manner, thus producing a substantial enhancement of masking, which is clearly related to the coherent motion of the entire pattern. These data shed light on the properties of higher order motion units (possibly in MT cortex) that respond to the direction of two-dimensional pattern motion, suggesting that they combine, in a nonlinear manner, the outputs of units which respond independently to the direction of each mask component.

Form Perception↗

What do developmental mapping rules optimize?

Convergence ratios between pre- and postsynaptic cells in the visual system vary widely between cell classes, areas of the visual field, between individuals and between species. Proper stabilization of the convergence and divergence of single visual neurons is critical for visual integration generally, and for specific functions such as those of rod and cone pathways, or the center and peripheral regions of the visual field. In early development, retinal ganglion cells, target cells and all their processes are produced in excess and stabilize at certain mature values. The intent of the investigations described here is to determine what features of cell connectivity are stabilized over normal variability by these developmental processes and how such stabilization is accomplished, using the developing mammalian retinotectal system as an example. Orderly compression of the retinotopic map into a half tectum was induced by a partial tectal ablation at birth in hamsters, increasing the ratio of retinal ganglion cells to superior colliculus target cells. The convergence problem is solved in this case by undersampling the spatial array with respect to normal, preserving local spatial resolution, but potentially reducing sensitivity or introducing aliasing artifacts. Receptive field sizes of single neurons are indistinguishable from normal, and reduction of branching of presynaptic axon arbors is the mechanism of the remapping. Behaviorally, though the entire visual field is still represented in the remaining colliculus, the solution has a cost in decreased probability and increased latency to orient to visual stimuli, particularly in the peripheral visual field. The generality of this solution for retinal and other central convergence regulation problems is evaluated.

Animals↗

Segmentation of MRS signals using ASPECT (analysis of SPectra using Eigenvector Decomposition of Targets).

Efforts to minimize the effects of partial volume contamination (PVC) in in vivo magnetic resonance spectroscopy (MRS) have focused upon improving the sensitivity and efficiency of spatially localized MRS measurements. Such improvements may improve spatial resolution and reduce the time required to acquire multiple spectra, however, PVC can affect in vivo spectra at any resolution. In this paper, a model for segmenting in vivo MRS signals compromised by PVC in selected applications is introduced. The segmentation algorithm used is linear and is based on filters originally developed for image processing applications. The model is developed from first principles and evaluated using computer simulations. It is suited for segmenting multivoxel or chemical shift imaging data, and can be used with spectra acquired at any spatial resolution. It is used to estimate the size of the partial volumes contributing to a voxel compromised by PVC and the spatially selective signal components that would be expected to arise from these partial volumes if they could be measured directly. Several spectral perturbants present in in vivo MRS measurements violate the linearity assumptions underlying the model and produce systematic errors that must be accounted for. A number of perturbants are discussed, and the potential in vivo applications of the model are illustrated using solvent-suppressed 1H-CSI spectra from the normal human brain.

Brain↗

In situ polymerase chain reaction-based localization studies support role of human herpesvirus-8 as the cause of two AIDS-related neoplasms: Kaposi's sarcoma and body cavity lymphoma.

Several lines of investigation point to a new herpesvirus, human herpesvirus-8 (HHV-8), as the cause of two different neoplasms seen in AIDS patients-Kaposi's sarcoma (KS) and body cavity B cell lymphoma. If this virus is the etiological agent, rather than another opportunistic infectious agent, it should be present in the earliest detectable clinical lesions on a temporal basis, and localize to specific target cells in a spatial pattern consistent with tumorigenic pathways. In this study, we take advantage of the clinical accessibility to biopsy early (patch stage) skin lesions of KS to address the temporal issue, combined with in situ PCR and dual immunostaining using a marker identifying malignant cells, to address the spatial localization issue. 21 different tissue samples were subjected to PCR analysis and in situ PCR with and without simultaneous immunostaining. In normal skin from healthy individuals, no HHV-8 DNA was detected by PCR or in situ PCR. However, in all PCR-positive tissues, distinct and specific in situ PCR staining was observed. In four different patch stage KS lesions, in situ PCR staining localized to nuclei of endothelial cells and perivascular spindle-shaped tumor cells. Later stage KS lesions (plaques and nodules) revealed additional positive cells, including epidermal keratinocytes (four of five), and eccrine epithelia (two of four). These patterns were nonrestricted to skin, as pulmonary KS also revealed HHV-8-specific infection of endothelial cells and KS tumor cells, as well as epithelioid pneumocytes (two of two). In body cavity B cell lymphoma by dual staining, HHV-8 was present in malignant tumor cells (EMA immunostained positive) and not in reactive lymphocytes. These results reveal an early temporal onset and nonrandom tissue and cellular distribution pattern for HHV-8 infection that is consistent with a causal link between this DNA virus and two AIDS-related neoplasms.

DNA, Viral↗

Caudate nucleus and memory for egocentric localization.

A large body of evidence suggests that the caudate nucleus (CN) plays a critical role in the processing of spatial localization information. Furthermore, evidence has begun to accumulate that the CN is involved in the processing of a very specific class of spatial cues, namely, egocentric cues (localization with reference to the organism). This is in contrast to allocentric localization, where an organism localizes on the basis of cues external to the organism. One would then predict that lesions to the CN should disrupt performance on any tasks that depend chiefly on egocentric spatial cues, while leaving performance on allocentric tasks intact. To test this prediction, two groups of rats were trained on two different egocentric memory tasks and two different allocentric memory tasks. Specifically, one group of rats was trained on an adjacent-arm (egocentric) and an 8-arm radial maze task (allocentric). A second group of rats was trained on a right-left discrimination (egocentric) and a place-learning task (allocentric). After training, both groups received bilateral lesions of the CN. Results showed that CN-lesioned animals were profoundly impaired on retention of the egocentric tasks. In sharp contrast to this, the same animals were not or were only transiently impaired or transiently affected on allocentric tasks. Sham-operated controls were either unimpaired or transiently affected on all tasks. These findings further support the idea that the CN plays a critical modulatory role in the processing of egocentric spatial and not allocentric spatial cues.

Animals↗

Spatial processing in the primate auditory cortex.

Spatial localization of auditory stimuli is dependent on the cerebral cortex, yet it remains unclear how cortical activity gives rise to spatial percepts. It has recently been proposed that spatial information is processed serially within the primate auditory cortex, initially in the primary auditory cortex (AI) through the auditory areas caudal to AI, particularly the caudomedial (CM) and caudolateral fields, and onward to the parietal lobe. The activity of single neurons in AI and CM supports this hypothesis, where a greater percentage of CM neurons are sensitive to the spatial location of acoustic stimuli than AI neurons, and the spatial sensitivity of CM neurons extends across a broader range of the stimulus spectrum compared to AI neurons. Further, populations of CM neurons are better able to predict sound localization ability than are populations of AI neurons. We have recently explored the effects of stimulus intensity on both sound localization performance and the spatial sensitivity of auditory cortical neurons. The preliminary results of these experiments again indicate that spatial information is serially processed between AI and the caudal fields. The effects of visual stimulation on auditory localization have also been investigated. Under the appropriate circumstances, visual stimuli can "capture" the spatial location of auditory stimuli in both humans and monkeys. This perceptual illusion suggests that there is a plastic shift in auditory spatial perception. Where the representation of this shift resides is unknown, although two likely candidates are the multimodal regions of the parietal lobe and the superior temporal sulcus.

Acoustic Stimulation↗

Traveling wave fronts and localized traveling wave convection in binary fluid mixtures.

Nonlinear fronts between spatially extended traveling wave (TW) convection and quiescent fluid and spatially localized traveling waves (LTWs) are investigated in quantitative detail in the bistable regime of binary fluid mixtures heated from below. A finite-difference method is used to solve the full hydrodynamic field equations in a vertical cross section of the layer perpendicular to the convection roll axes. Results are presented for ethanol-water parameters with several strongly negative separation ratios where TW solutions bifurcate subcritically. Fronts and LTWs are compared with each other and similarities and differences are elucidated. Phase propagation out of the quiescent fluid into the convective structure entails a unique selection of the latter while fronts and interfaces where the phase moves into the quiescent state behave differently. Interpretations of various experimental observations are suggested.

Journal Article↗

Speckle activity images based on the spatial variance of the phase.

We propose the display of the local spatial variance of the temporal variations of the phase as an activity descriptor in dynamic speckle images. The spatial autocorrelation of the speckle intensity is calculated in sliding windows, and an estimation of the variance of the phase variations in each region of the sample is determined. The activity images obtained in this way depict some interesting features and in some cases they could be related to physical magnitudes in the samples. A simulation is presented, and examples corresponding to usual study cases are also shown, namely, fruit bruising and paint drying.

Journal Article↗

Spatial Transcriptomics Identifies Characteristic Immunological Niches in Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) is primarily driven by a Type 2 immune response, with T helper (TH2) cells producing IL-4 and IL-13, thereby promoting inflammation, itch, and a compromised skin barrier. Yet, the spatial organization of pathogenic immune cells and their interactions with stromal and epithelial compartments in human AD skin remain incompletely understood. METHODS: We performed 10× Genomics Visium spatial transcriptomics on FFPE skin biopsies from patients with AD (n = 6), psoriasis (n = 2), and healthy controls (n = 5). Data were integrated with AD single-cell RNA sequencing (scRNA-seq) datasets and complemented by imaging mass cytometry (IMC) and multiplex immunofluorescence (IF) to validate the spatial localization of immune cells. Cell-cell communication analysis revealed putative signaling interactions within immune niches. RESULTS: Spatial clustering resolved tissue compartments and demonstrated transcriptional dysregulation in keratinocytes in AD and psoriasis. AD lesions showed a conserved spatial organization of immune aggregates within the superficial dermis. Integration of scRNA-seq signatures revealed spatially organized co-localization of T cells and mature migratory dendritic cells (mmDCs). We developed a ring-based neighborhood analysis to characterize the cellular organization of the immune-stromal niches, revealing T cell-enriched regions surrounded by inflammatory fibroblasts and activated keratinocytes. Intercellular communication analysis further identified putative signaling within mmDC-T cell niches that may promote pathogenic T cell recruitment and activation. Application of tertiary lymphoid structure (TLS) signatures indicated the presence of TLS-like regions. IMC and IF validated the close spatial proximity between activated TH2 cells and mmDCs. CONCLUSION: AD lesions contain spatially organized TLS-like immune niches at the dermal-epidermal junction, characterized by the close association of T cells and mmDCs and coordinated interactions with surrounding stromal and epithelial compartments. These mmDC-T cell niches may represent potential targets for future therapeutic strategies aimed at disrupting persistent local inflammatory pathways and improving long-term disease control.

atopic dermatitis↗

Iterative random aggregation of small units using regional measures of spatial autocorrelation for cluster localization.

A method for localization of spatial disease clusters which uses a regional measure of spatial autocorrelation (RSAC) was recently developed by Munasinghe and Morris. They found this method to be an effective tool for the identification of regional disease clusters. In order to reduce the spurious variability of the estimated relative risks, the smallest geographic units were aggregated into analytic areas, consisting of a predefined minimum number of persons at risk (PAR). We found RSAC to be a valuable method and will propose some improvements. The present study illustrates that RSAC is quite sensitive both to the choice of PAR and the aggregation algorithm. Moreover, it does not utilize all the geographic details provided by the data sets, for instance the disease rates of the geographic units within the analytic areas. In order to overcome, at least to some extent, these problems, a modified version of the RSAC, called IRARSAC, is proposed. This method uses information, provided by the RSAC, from many different levels of aggregation. The performance of IRARSAC was shown to be more stable as compared to the RSAC, and it also seems to localize a greater proportion of the true clustering areas.

Central Nervous System Neoplasms↗

Detection of temporal structure depends on spatial structure.

Observers can more easily detect correlated patterns of temporal contrast modulation within hybrid visual images composed of two components when those components are drawn from the same original picture (Blake, R., & Yang, Y. (1997). Proceedings of the National Academy of Science, 94, 7115-7119). To learn whether spatial phase is a mediating variable, we measured thresholds for detection of contrast modulation over time among component gratings while manipulating spatial phase among those components. In Experiment 1, observers more easily detected correlated contrast modulation when two component gratings were aligned in peaks-subtract phase. Experiment 2 showed that this phase-dependent detectability of synchronized contrast modulation is mediated by the phase-dependent, non-linear interaction among spatial frequency channels. The rigorous evaluation of several a priori reasonable hypotheses indicates that the phase-dependent detectability is not based on local spatial features such as local luminance, contrast or luminance gradient. Taken together, our results indicate that the spatial phase relationship and the temporal correlation of contrast modulation of two component gratings are both important for triggering facilitatory interaction between neural analyzers tuned to those gratings.

Contrast Sensitivity↗

Effects of fetal hippocampal field grafts on ischaemic-induced deficits in spatial navigation in the water maze.

Transitory global cerebral ischaemia induced in rats by four vessel occlusion for 15 min produced substantial loss of CA1 cells in dorsal hippocampus, and minimal damage in other intra- and extrahippocampal forebrain regions examined. Ischaemic rats showed long-lasting deficits in spatial navigation in the water-maze, consisting of impaired learning to locate a hidden platform in a novel pool, a substantial increase in time spent searching close to the platform without finding it, and moderate deficits in matching to position in a working memory task. Groups of ischaemic rats were implanted with fetal tissue dissected from hippocampal CA1 field, containing glutamatergic CA1 pyramidal cells, from dentate gyrus, containing glutamatergic dentate granule cells, and from basal forebrain, containing cholinergic cells, with grafts sited in the alveus above the damaged CA1 region, for comparison with non-grafted ischaemic and non-ischaemic control groups, over a series of tests from four to 20 weeks after grafting. All ischaemic groups showed comparable acquisition deficits prior to transplantation, and similar loss of CA1 cells on post mortem examination. When tested in a familiar pool in retention and reversal learning of the original platform position, and a working memory task, all ischaemic rats performed better than in initial acquisition. However, rats receiving CA1 grafts showed the most consistent improvement relative to ischaemic controls. When tested in a second (i.e. novel) pool, ischaemic rats again showed marked impairment, whereas rats with CA1 grafts were significantly superior, and learned as rapidly as non-ischaemic controls. The performance of groups with dentate granule and basal forebrain grafts was similar to that of the non-grafted ischaemic control group throughout testing. These results suggest that ischaemic rats are impaired in the adaptive use of spatial information, as shown by acquisition and working memory deficits, but not in long- or short-term memory storage processes, and are also impaired in precise spatial localization. The effects of CA1 grafts in restoring spatial abilities, shown most clearly when rats were tested in a novel environment, suggest that these grafts may have assisted with repair to the damaged host circuit, rather than acted through the release of an appropriate neurotransmitter, since the glutamatergic dentate granule grafts were ineffective. However, CA1 grafts showed better survival and growth than the other types of transplant, so that functional recovery may have been related to graft viability rather than to the specific type of graft.

Animals↗

Subcellular localization and signaling properties of dishevelled in developing vertebrate embryos.

The Dishevelled protein mediates several diverse biological processes. Intriguingly, within the same tissues where Xenopus Dishevelled (Xdsh) controls cell fate via canonical Wnt signaling, it also controls cell polarity via the vertebrate planar cell polarity (PCP) cascade [1, 2, 3, 4, 5, 6, 7, 8 and 9]. The relationship between subcellular localization of Dishevelled and its signaling activities remains unclear; conflicting results have been reported depending upon the organism and cell types examined [8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20]. We have approached this issue by developing new reagents to sequester wild-type Dishevelled protein either at the cell membrane or away from the cell membrane. Removal of Dishevelled from the cell membrane disrupts convergent extension by preventing Rho/Rac activation and mediolateral cell polarization. By manipulating the subcellular localization of K-->M (dsh1), we show that this mutation inhibits Dishevelled activation of Rac, regardless of its subcellular localization. These data demonstrate that membrane localization of Dishevelled is a prerequisite for vertebrate PCP signaling. However, both membrane-targeted and cytoplasm-targeted Dishevelled can potently activate canonical Wnt signaling, suggesting that local concentration of Dishevelled protein, but not its spatial localization, is central to canonical Wnt signaling. These results suggest that in vertebrate embryos, subcellular localization is insufficient to account for the pathway specificity of Dishevelled in the canonical Wnt versus PCP signaling cascades.

Adaptor Proteins, Signal Transducing↗

Isolation rearing affects sequential organization of motor behavior in post-pubertal but not pre-pubertal Lister and Sprague-Dawley rats.

OBJECTIVE: Dopaminergic and serotonergic modulation potently influences the sequential organization of rat movements in a simple unconditioned motor paradigm. Rats reared in social isolation post-weaning differ profoundly from their socially reared litter mates on behavioral, neurochemical, and neuroanatomical measures. This investigation examined (1) whether social isolation significantly affects the sequential organization of rat movements, (2) whether these changes occur at different ages, and (3) whether these changes differ across strains. METHOD: male Lister and Sprague Dawley rats reared in isolation post-weaning and socially reared controls were tested at 2 and 8 weeks post-weaning, in the Behavioral Pattern Monitor for 30-min sessions. The amount of activity and the spatial patterns of movements as measured by both the spatial scaling exponent and the fluctuation spectrum of local spatial scaling exponents were assessed in 10-min intervals. RESULTS: Habituation of locomotor activity was significantly attenuated in isolation reared rats during the 30-min sessions irrespective of strain. Spatial patterns of movements were significantly affected by isolation rearing in movements in post-pubertal but not pre-pubertal Lister and Sprague-Dawley rats. The spatial scaling exponent and the fluctuation spectrum analysis revealed a shift towards straight, distance-covering, and repetitive movements rather than a complex re-organization of the behavioral repertoire. CONCLUSIONS: Isolation rearing profoundly affects the sequential organization of movements in post-pubertal rats, suggesting that emerging behavioral dysfunctions parallel developmentally those found in patients with schizophrenia.

Animals↗

Patterns of flow and conduction during early ventricular arrhythmias following coronary arterial occlusion in the dog.

The early ventricular arrhythmias of acute myocardial ischaemia arise against a background of rapid alterations in regional myocardial blood flow and electrophysiological properties. The relation between patterns of flow and epicardial activation has been examined in eight open chest anaesthetised dogs at time of onset of these arrhythmias following a proximal occlusion of the left anterior descending coronary artery. Data were derived from 80 epicardial and endocardial sites within a 4 X 5 cm area of left ventricular free wall and processed utilising a three-dimensional computer plotting program. Mean flow within the ischaemic zone was reduced to 0.27 and 0.24 cm3 x g-1 x min-1 in epicardium and endocardium respectively. Marked epicardial activation delays and fragmentation of conduction were observed confined to areas of flow less than 0.3 cm3 x g-1 x min-1. 74% of endocardial and 71% of epicardial tissue samples within the ischaemic zone derived from this area and analysis of flow distribution between adjacent samples demonstrated spatial heterogeneity of flow. It is suggested that local spatial variability in flow within the central ischaemic region may be a prerequisite for abnormal fractionation of conduction leading to re-entrant excitation at the time of onset of early ventricular arrhythmias.

Animals↗