Are neuritic plaques in Alzheimer’s disease related to neurofibrillary tangles?

The density and spatial patterns of neuritic plaques (NP) and cellular neurofibrillary tangles (cNFT) were studied in various brain regions in cases of Alzheimer’s disease. The objective was to test the hypothesis that NP develop from cNFT. cNFT were most abundant in the cornu Ammonis (CA) region of the hippocampus while NP were most abundant in gyri adjacent to the hippocampus. The density of NP in a brain region was positively correlated with the density of cNFT. In 83% of brain regions examined, NP occurred in clusters and in 51% the clusters exhibited a regular periodicity parallel to the tissue boundary. cNFT were clustered in 97% of brain regions, 61% exhibiting a regular periodicity. Mean cluster size of NP in a brain region was not significantly correlated with the cluster size of the cNFT. In most cortical regions, clusters of NP and cNFT were spatially unrelated to each other. However, coincident clusters of NP and cNFT were observed in the CA region of the hippocampus in 4/5 patients. It was concluded that the spatial patterns of the NP and cNFT clusters were not consistent with the hypothesis that the majority of NP evolved from cNFT.

DNA Mutation of the progranulin (GRN) gene in familial frontotemporal lobar degeneration (FTLD):a study of the pathology of nine cases

Frontotemporal lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43kDa (TDP-43) proteinopathy (FTLD-TDP) is a neurodegenerative disease characterized by variable neocortical and allocortical atrophy principally affecting the frontal and temporal lobes. Histologically, there is neuronal loss, microvacuolation in the superficial cortical laminae, and a reactive astrocytosis. A variety of TDP-43 immunoreactive changes are present in FTLD-TDP including neuronal cytoplasmic inclusions (NCI), neuronal intranuclear inclusions (NII), dystrophic neurites (DN) and, oligodendroglial inclusions (GI). Many cases of familial FTLD-TDP are caused by DNA mutations of the progranulin (GRN) gene. Hence, the density, spatial patterns, and laminar distribution of the pathological changes were studied in nine cases of FLTD-TDP with GRN mutation. The densities of NCI and DN were greater in cases caused by GRN mutation compared with sporadic cases. In cortical regions, the commonest spatial pattern exhibited by the TDP-43 immunoreactive lesions was the presence of clusters of inclusions regularly distributed parallel to the pia mater. In approximately 50% of cortical gyri, the NCI exhibited a peak of density in the upper cortical laminae while the GI were commonly distributed across all laminae. The distribution of the NII and DN was variable, the most common pattern being a peak of NII density in the lower cortical laminae and DN in the upper cortical laminae. These results suggest in FTLD-TDP caused by GRN mutation: 1) there are greater densities of NCI and DN than in sporadic cases of the disease, 2) there is degeneration of the cortico-cortical and cortico-hippocampal pathways, and 3) cortical degeneration occurs across the cortical laminae, the various TDP-43 immunoreactive inclusions often being distributed in different cortical laminae.

Effects of pixel noise and stimulus structure on visual detection performance

This thesis consisted of two major parts, one determining the masking characteristics of pixel noise and the other investigating the properties of the detection filter employed by the visual system. The theoretical cut-off frequency of white pixel noise can be defined from the size of the noise pixel. The empirical cut-off frequency, i.e. the largest size of noise pixels that mimics the effect of white noise in detection, was determined by measuring contrast energy thresholds for grating stimuli in the presence of spatial noise consisting of noise pixels of various sizes and shapes. The critical i.e. minimum number of noise pixels per grating cycle needed to mimic the effect of white noise in detection was found to decrease with the bandwidth of the stimulus. The shape of the noise pixels did not have any effect on the whiteness of pixel noise as long as there was at least the minimum number of noise pixels in all spatial dimensions. Furthermore, the masking power of white pixel noise is best described when the spectral density is calculated by taking into account all the dimensions of noise pixels, i.e. width, height, and duration, even when there is random luminance only in one of these dimensions. The properties of the detection mechanism employed by the visual system were studied by measuring contrast energy thresholds for complex spatial patterns as a function of area in the presence of white pixel noise. Human detection efficiency was obtained by comparing human performance with an ideal detector. The stimuli consisted of band-pass filtered symbols, uniform and patched gratings, and point stimuli with randomised phase spectra. In agreement with the existing literature, the detection performance was found to decline with the increasing amount of detail and contour in the stimulus. A measure of image complexity was developed and successfully applied to the data. The accuracy of the detection mechanism seems to depend on the spatial structure of the stimulus and the spatial spread of contrast energy.

White matter pathology in progressive supranuclear palsy (PSP):a quantitative study of 8 cases

Aims: To quantify white matterpathology in progressive supranuclear palsy (PSP). Material: Histological sections of white matter of 8 PSP and 8 control cases \Method: Densities and spatial patterns of vacuolation, glial cell nuclei, and glial inclusions (GI) were measured in 8cortical and subcortical fiber tracts. Results: No GI wereobserved in control fiber tracts. Densities of vacuoles and glial cell nuclei were greater in PSP than in controls. In PSP, density of vacuoles was greatest in the alveus, frontopontine fibers (FPF), and central tegmental tract (CTT), and densities of glial cell nuclei were greater in cortical than subcortical regions.The highest densities of GI were observed in the basal ganglia, FPF, cerebellum, andsuperior frontal gyrus (SFG). Vacuoles, glialcells and GI were distributed randomly, uniformly,in regularly distributed clusters, or in large clusters across fiber tracts. GI wermore frequently distributed in regular clusters than the vacuoles and glial cell nuclei.Vacuoles, glial cell nuclei, and GI were not spatially correlated. Conclusions: The data suggest significant degeneration of white matter in PSP, vacuolation being related to neuronal loss in adjacent gray matterregions,GI the result of abnormal tau released from damaged axons, and gliosis a responseto these changes. © 2013.

Planning the neighbourhood economy:land-use plans and the economic potential of urban residential neighbourhoods in the Netherlands

This article investigates the relationship between zoning by-laws, as put forward in governmental land-use plans and the viability of urban residential neighbourhood economies. The Dutch planning tradition has long been characterized by strict separation of functions and top-down planning. We argue that profound changes in social and economic structures make land-use planning practices less suitable for the current policy formula of "mixed urban milieus". Although the residential neighbourhood might not be the location of large firms, it definitely attracts small ones, and facilitates starting businesses whose presence (and potential growth) can be beneficial to the city as a whole. We present a typology of spatial patterns of neighbourhood economies based on land-use plans and describe whether these are related to the distinctive economic development of the neighbourhood over the period 1999-2007. © 2013 Taylor & Francis.

Measuring the spatial arrangement patterns of pathological lesions in histological sections of brain tissue

The development of abnormal protein aggregates in the form of extracellular plaques and intracellular inclusions is a characteristic feature of many neurodegenerative diseases such as Alzheimer's disease (AD), Creutzfeldt-Jakob disease (CJD) and the fronto-temporal dementias (FTD). An important aspect of a pathological protein aggregate is its spatial topography in the tissue. Lesions may not be randomly distributed within a histological section but exhibit spatial pattern, a departure from randomness either towards regularity or clustering. Information on the spatial pattern of a lesion may be useful in elucidating its pathogenesis and in studying the relationships between different lesions. This article reviews the methods that have been used to study the spatial topography of lesions. These include simple tests of whether the distribution of a lesion departs significantly from random using randomized points or sample fields, and more complex methods that employ grids or transects of contiguous fields and which can detect the intensity of aggregation and the sizes, distribution and spacing of the clusters. The usefulness of these methods in elucidating the pathogenesis of protein aggregates in neurodegenerative disease is discussed.

The spatial distribution and temporal dynamics of brain regions activated during the perception of object and non-object patterns

Both animal and human studies suggest that the efficiency with which we are able to grasp objects is attributable to a repertoire of motor signals derived directly from vision. This is in general agreement with the long-held belief that the automatic generation of motor signals by the perception of objects is based on the actions they afford. In this study, we used magnetoencephalography (MEG) to determine the spatial distribution and temporal dynamics of brain regions activated during passive viewing of object and non-object targets that varied in the extent to which they afforded a grasping action. Synthetic Aperture Magnetometry (SAM) was used to localize task-related oscillatory power changes within specific frequency bands, and the time course of activity within given regions-of-interest was determined by calculating time-frequency plots using a Morlet wavelet transform. Both single subject and group-averaged data on the spatial distribution of brain activity are presented. We show that: (i) significant reductions in 10-25 Hz activity within extrastriate cortex, occipito-temporal cortex, sensori-motor cortex and cerebellum were evident with passive viewing of both objects and non-objects; and (ii) reductions in oscillatory activity within the posterior part of the superior parietal cortex (area Ba7) were only evident with the perception of objects. Assuming that focal reductions in low-frequency oscillations (< 30 Hz) reflect areas of heightened neural activity, we conclude that: (i) activity within a network of brain areas, including the sensori-motor cortex, is not critically dependent on stimulus type and may reflect general changes in visual attention; and (ii) the posterior part of the superior parietal cortex, area Ba7, is activated preferentially by objects and may play a role in computations related to grasping. © 2006 Elsevier Inc. All rights reserved.

The spatial arrangement patterns of senile plaques in senile dementia of the Alzheimer type (SDAT)

The spatial arrangement patterns of senile plaques have been studied in 10 micron cresyl violet stained sections cut from embedded portions of 20 brain regions from SDAT brains. Two studies are reported: an initial study using the Poisson distribution and a subsequent study using pattern analysis. The initial study indicated that plaques are arranged in discrete clumps in all brain regions when examined at x100 and x400 – suggesting that both small and larger scale clumping may be present. The pattern analysis study was applied to 8 cortical regions. This technique allows a more detailed study of pattern to be made. In all regions the technique revealed that the basic pattern of plaque arrangement is the regularly spaced discrete clump – which may be present on both large and small scales.

Spatial arrangement patterns of senile plaques in post-mortem senile dementia of the Alzheimer type brains

We have studied the spatial distribution of plaques in coronal and tangential sections of the parahippocampal gyrus (PHG), the hippocampus, the frontal lobe and the temporal lobe of five SDAT patients. Sections were stained with cresyl violet and examined at two magnifications (x100 and x400). in all cases (and at both magnifications) statistical analysis using the Poisson distribution showed that the plaques were arranged in clumps (x100: V/M = 1.48 - 4.49; x400 V/M = 1.17 - 1.95). this indicates that both large scale and small scale clumping occurs. Application of the statistical techniques of pattern analysis to coronal sections of frontal and temporal cortex and PHG showed. furthermore, that both large (3200-6400 micron) and small scale (100 - 400 micron) clumps were arranged with a high degree of regularity in the tissue. This suggests that the clumps of plaques reflect underlying neural structure.

A penny for your thoughts! Patterns of fMRI activity reveal the content and the spatial topography of visual mental images

Visual mental imagery is a complex process that may be influenced by the content of mental images. Neuropsychological evidence from patients with hemineglect suggests that in the imagery domain environments and objects may be represented separately and may be selectively affected by brain lesions. In the present study, we used functional magnetic resonance imaging (fMRI) to assess the possibility of neural segregation among mental images depicting parts of an object, of an environment (imagined from a first-person perspective), and of a geographical map, using both a mass univariate and a multivariate approach. Data show that different brain areas are involved in different types of mental images. Imagining an environment relies mainly on regions known to be involved in navigational skills, such as the retrosplenial complex and parahippocampal gyrus, whereas imagining a geographical map mainly requires activation of the left angular gyrus, known to be involved in the representation of categorical relations. Imagining a familiar object mainly requires activation of parietal areas involved in visual space analysis in both the imagery and the perceptual domain. We also found that the pattern of activity in most of these areas specifically codes for the spatial arrangement of the parts of the mental image. Our results clearly demonstrate a functional neural segregation for different contents of mental images and suggest that visuospatial information is coded by different patterns of activity in brain areas involved in visual mental imagery. Hum Brain Mapp 36:945-958, 2015.

Correlations between the clustering patterns of the pathological changes in sporadic Creutzfeldt-Jakob disease

Correlations between the clustering patterns of the vacuolation ('spongiform change'), prion protein (PrP) deposits, and surviving neurons were studied in the cerebral cortex, hippocampus, and cerebellum in 11 cases of sporadic Creutzfeldt-Jakob disease (sCJD). Differences in the sizes of the clusters of vacuoles were observed between brain regions and in the cerebral cortex, between the upper and lower laminae. With the exception of the parietal cortex, mean cluster size of the vacuoles was similar to that of the PrP deposits in each brain area. Clusters of the vacuoles were spatially correlated with the density of surviving neurons and with the clusters of PrP deposits in 47% and 53% of cortical areas analysed respectively but there were few spatial correlation between the PrP deposits and the density of surviving neurons. The data suggest that the pathology of sCJD may spread through the brain via specific anatomical pathways. Development of the clusters of vacuoles is spatially related to surviving neurons while the appearance of clusters of PrP deposits is related to the development of the vacuolation.

Humans assume a mixture of diffuse and point-source lighting when viewing sinusoidal shading patterns

Observers perceive sinusoidal shading patterns as being due to sinusoidally corrugated surfaces, and perceive surface peaks to be offset from luminance maxima by between zero and 1/4 wavelength. This offset varies with grating orientation. Physically, the shading profile of a sinusoidal surface will be approximately sinusoidal, with the same spatial frequency as the surface, only when: (A) it is lit suitably obliquely by a point source, or (B) the light source is diffuse and hemispherical--the 'dark is deep' rule applies. For A, surface peaks will be offset by 1/4 wavelength from the luminance maxima; for B, this offset will be zero. As the sum of two same-frequency sinusoids with different phases is a sinusoid of intermediate phase, our results suggest that observers assume a mixture of two light sources whose relative strength varies with grating orientation. The perceived surface offsets imply that gratings close to horizontal are taken to be lit by a point source; those close to vertical by a diffuse source. [Supported by EPSRC grants to AJS and MAG].

Higher-order co-occurrences for exploratory point pattern analysis and decision tree clustering on spatial data

Analyzing geographical patterns by collocating events, objects or their attributes has a long history in surveillance and monitoring, and is particularly applied in environmental contexts, such as ecology or epidemiology. The identification of patterns or structures at some scales can be addressed using spatial statistics, particularly marked point processes methodologies. Classification and regression trees are also related to this goal of finding "patterns" by deducing the hierarchy of influence of variables on a dependent outcome. Such variable selection methods have been applied to spatial data, but, often without explicitly acknowledging the spatial dependence. Many methods routinely used in exploratory point pattern analysis are2nd-order statistics, used in a univariate context, though there is also a wide literature on modelling methods for multivariate point pattern processes. This paper proposes an exploratory approach for multivariate spatial data using higher-order statistics built from co-occurrences of events or marks given by the point processes. A spatial entropy measure, derived from these multinomial distributions of co-occurrences at a given order, constitutes the basis of the proposed exploratory methods. © 2010 Elsevier Ltd.

Changes in the clustering patterns of beta-amyloid (Abeta) with age in Down's syndrome

The spatial distribution patterns of the diffuse, primitive, and classic beta-amyloid (Abeta) deposits were studied in areas of the medial temporal lobe in 12 cases of Down's Syndrome (DS) 35 to 67 years of age. Large clusters of diffuse deposits were present in the youngest patients; cluster size then declined with patient age but increased again in the oldest patients. By contrast, the cluster sizes of the primitive and classic deposits increased with age to a maximum in patients 45 to 55 and 60 years of age respectively and declined in size in the oldest patients. In the parahippocampal gyrus (PHG), the clusters of the primitive deposits were most highly clustered in cases of intermediate age. The data suggest a developmental sequence in DS in which Abeta is deposited initially in the form of large clusters of diffuse deposits that are then gradually replaced by clusters of primitive and classic deposits. The oldest patients were an exception to this sequence in that the pattern of clustering resembled that of the youngest patients.

The relationship between the spatial pattern of senile plaques and neurofibrillary tangles in Alzheimer's disease

The topographic pattern of senile plaques (SP) and neurofibrillary tangles (NFT) was studied in silver stained coronal sections of neocortex and hippocampus in ten cases of Alzheimer's disease (AD). Both lesions showed evidence of clustering in the tissue with many of the clusters being regularly spaced. The patterns of SP and NFT were compared 1) in the same cortical zone, 2) between upper and lower zones of the cortex and 3) in regions connected by either association fibres or the perforant path. Correlations between the lesions in the same cortical zone were found in 20% of the layers examined while correlations between upper and lower zones occurred in 64% of cortical regions examined. There was evidence that NFT in upper and lower cortex may be in register in some tissues. In addition, positive correlations were found between upper NFT and lower SP and negative correlations between upper SP and lower NFT in some tissues. Regular clustering of lesions was also observed in brain regions connected to one another suggesting that they develop on functinally related sets of neurons.