Lobe interactions within the thallus margin and the maintenance of symmetry in the lichen Parmelia conspersa (Ehrh. ex Ach.)Ach.

This study determined whether the radial growth of lobes of the foliose lichen Parmelia conspersa (Ehrh. ex Ach.)Ach. was influenced by the radial growth and morphology of their closest neighbours and whether such interactions influence thallus symmetry. The radial growth and morphology of a sample of adjacent lobes from six thalli was measured. Positive correlations were observed between radial growth and lobe width in three thalli and with the degree of bifurcation of the lobe in two thalli. Negative correlations between the radial growth of adjacent lobes were observed in four thalli suggesting that faster growing lobes may inhibit the growth of their neighbours.Lobes glued next to individual lobes had no signifiacnt effect on the radial growth of wide or narrow lobes. Lobes glued 1-2 mm in front of their neighbours exhibited an intital phase of increased radial growth and then a phase of slower growth. Radial growth decreased when the lobes were glued 2 mm behind their neighbours and these lobes were essentially eliminated by the growth of the adjacent lobes. The data suggest that lobe interactions may incresae lobe growth variation within a thallus. However, the decrease in radial growth of lobes which protrude from the margin and the elimination of slower growing lobes may help to maintain thallus symmetry.

Clustering and spatial correlations of the neuronal cytoplasmic inclusions, astrocytic plaques and ballooned neurons in corticobasal degeneration

This study tested three hypotheses: (1) that there is clustering of the neuronal cytoplasmic inclusions (NCI), astrocytic plaques (AP) and ballooned neurons (BN) in corticobasal degeneration (CBD), (2) that the clusters of NCI and BN are not spatially correlated, and (3) that the lesions are correlated with disease ‘stage’. In 50% of the regions, clusters of lesions were 400–800 µm in diameter and regularly distributed parallel to the tissue boundary. Clusters of NCI and BN were larger in laminae II/III and V/VI, respectively. In a third of regions, the clusters of BN and NCI were negatively spatially correlated. Cluster size of the BN in the parahippocampal gyrus (PHG) was positively correlated with disease ‘stage’. The data suggest the following: (1) degeneration of the cortico-cortical pathways in CBD, (2) clusters of NCI and BN may affect different anatomical pathways and (3) BN may develop after the NCI in the PHG.

The spatial patterns of prion protein deposits in cases of variant Creutzfeldt-Jakob disease

The spatial patterns of the prion protein (PrP) deposits were studied in immunostained sections of areas of the cerebral cortex, hippocampus, dentate gyrus, and the molecular layer of the cerebellum in 11 cases of variant Creutzfeldt-Jakob disease (vCJD). Clustering of PrP deposits, with a regular distribution of the clusters parallel to the tissue boundary, was the most common spatial pattern observed. Two morphological types of PrP deposit were recognised, those consisting of a condensed core (florid deposits) and those deposits lacking a condensed core (non-florid deposits). The florid and non-florid PrP deposits exhibited a different profile of spatial patterns. First, the florid deposits exhibited a regularly distributed pattern of clusters more frequently than the non-florid deposits. Second, the florid deposits formed larger clusters (greater than1,600 µm in diameter) less frequently than the non-florid deposits. In the areas of the cerebral cortex that exhibited a regular distribution of PrP deposit clusters, the cluster size of the deposits approximated that of the groups of cells of the cortico-cortical pathway origin in only 12% of analyses. No significant differences in the frequency of the different types of spatial pattern were observed in different brain regions, or in the cerebral cortex between the upper and lower laminae. It was concluded that the spatial patterns of the PrP deposits in the cerebral cortex in vCJD are unlikely to reflect the degeneration of the cortico-cortical pathways as has been reported in sporadic CJD (sCJD). In addition, different factors could be involved in the development of the deposits with and without a condensed core.

Spatial patterns of the vacuolation in subcortical white matter in sporadic Creutzfeldt-Jakob disease (sCJD)

OBJECTIVE: To study the spatial patterns of the vacuolation ("spongiform change") in the subcortical white matter in the "classical" form of sporadic Creutzfeldt-Jakob disease (sCJD). MATERIAL: Frontal, parietal, occipital and temporal lobes of 11 cases of sCJD. METHOD: Spatial patterns were studied across the white matter at the base of the gyri using spatial pattern analysis. RESULTS: In the white matter of all gyri studied, vacuoles were aggregated into clusters, 50 to > 800 microm in diameter and in 22/37 (59%) of gyri, the clusters of vacuoles exhibited a regular distribution across the base of the gyri. In the remaining gyri, the vacuoles were aggregated into large clusters, at least 400 microm or 800 microm in diameter, but without evidence of a regular distribution. In a significant proportion of gyri, the spatial patterns of the vacuolation were similar to those reported previously for spongiform change and prion protein (PrP) deposits in the corresponding grey matter. CONCLUSIONS: Degeneration of the white matter and the formation of clusters of vacuoles may occur before the degeneration of the grey matter or could be a consequence of pathology affecting the cortico-cortical pathways.

Spatial pattern of prion protein deposits in patients with sporadic Creutzfeldt–Jakob disease

The spatial pattern of the prion protein (PrP) deposits was studied in the cerebral cortex and cerebellum in 10 patients with sporadic Creutzfeldt–Jakob disease (CJD). In all patients the PrP deposits were aggregated into clusters and, in 90% of cortical areas and in 50% of cerebellar sections, the clusters exhibited a regular periodicity parallel to the tissue boundary; a spatial pattern also exhibited by ß-amyloid (Aß) deposits in Alzheimer's disease (AD). In the cerebral cortex, the incidence of regular clustering of the PrP deposits was similar in the upper and lower cortical laminae. The sizes of the PrP clusters in the upper and lower cortex were uncorrelated. No significant differences in mean cluster size of the PrP deposits were observed between brain regions. The size, location and distribution of the PrP deposit clusters suggest that PrP deposition occurs in relation to specific anatomical pathways and supports the hypothesis that prion pathology spreads through the brain via such pathways. In addition, the data suggest that there are similarities in the pathogenesis of extracellular protein deposits in prion disease and in AD.

Diffuse beta-amyloid (A beta) deposits and neurons: in situ secretion or diffusion of A beta?

The association between diffuse-type beta -amyloid (AP) deposits and neuronal cell bodies in Alzheimer's disease (AD) and Down's syndrome (DS) could result from the secretion of AP from clusters of neurons in situ or the diffusion of A beta from cell processes, glial cells or blood vessels. To decide between these hypotheses, spatial pattern analysis was used to study the relationship between the degree of clustering of neuronal cell bodies and the presence of diffuse deposits in the temporal lobe of patients with DS. Significant clustering of neuronal cell bodies was present in 17/24 (71%) of brain areas studied. in addition, in 23/24 (96%) of brain areas, there was a positive correlation between the presence of diffuse deposits and the density of neurons. Hence, the data support the hypothesis that diffuse deposits develop in situ mainly as a result of the secretion of A beta by local clusters of neurons rather than by significant diffusion. Furthermore, the size of a diffuse deposit is likely to be determined by the number of neurons within a cluster which secrete A beta. The number and density of neurons could also be a factor determining the evolution of a diffuse into a mature amyloid deposit.

The spatial pattern of the vacuolation in patients with sporadic Creutzfeldt-Jakob disease

The spatial pattern of the vacuolation ('spongiform change') was studied in the upper and lower laminae of the cerebral cortex, the CA1/CA2 sectors of the hippocampus and the molecular layer of the cerebellum in 11 cases of sporadic Creutzfeldt-Jakob disease (CJD). Individual vacuoles were grouped into clusters, 50 to >1600 μm in diameter and, in the majority of tissue sections, the vacuole clusters were distributed with regular periodicity parallel to the tissue boundary. The size of the vacuole clusters was positively correlated with patient age in the lower laminae of the occipital cortex and the inferior temporal gyrus (ITG) and negatively correlated with age in the hippocampus. In addition, the size of the vacuole clusters was positively correlated with disease duration in the upper laminae of the ITG. The size and distribution of the vacuole clusters suggests that the vacuolation in CJD reflects the degeneration of specific brain pathways and supports the hypothesis that prion pathology may spread through the brain along well defined anatomical pathways. (C) 2000 Elsevier Science Ireland Ltd.

Spatial pattern analysis of beta-amyloid (A beta) deposits in Alzheimer disease by linear regression

The spatial patterns of discrete beta-amyloid (Abeta) deposits in brain tissue from patients with Alzheimer disease (AD) were studied using a statistical method based on linear regression, the results being compared with the more conventional variance/mean (V/M) method. Both methods suggested that Abeta deposits occurred in clusters (400 to <12,800 mu m in diameter) in all but 1 of the 42 tissues examined. In many tissues, a regular periodicity of the Abeta deposit clusters parallel to the tissue boundary was observed. In 23 of 42 (55%) tissues, the two methods revealed essentially the same spatial patterns of Abeta deposits; in 15 of 42 (36%), the regression method indicated the presence of clusters at a scale not revealed by the V/M method; and in 4 of 42 (9%), there was no agreement between the two methods. Perceived advantages of the regression method are that there is a greater probability of detecting clustering at multiple scales, the dimension of larger Abeta clusters can be estimated more accurately, and the spacing between the clusters may be estimated. However, both methods may be useful, with the regression method providing greater resolution and the V/M method providing greater simplicity and ease of interpretation. Estimates of the distance between regularly spaced Abeta clusters were in the range 2,200-11,800 mu m, depending on tissue and cluster size. The regular periodicity of Abeta deposit clusters in many tissues would be consistent with their development in relation to clusters of neurons that give rise to specific neuronal projections.

Is the clustering of neurofibrillary tangles in Alzheimer's patients related to the cells of origin of specific cortico-cortical projections?

The spatial pattern of cellular neurofibrillary tangles (NFT) was studied in the supra- and infragranular layers of various cortical regions in cases of Alzheimer's disease (AD). The objective was to test the hypothesis that NFT formation was associated with the cells of origin of specific cortico-cortical projections. The novel feature of the study was that pattern analysis enabled the dimension and spacing of NFT clusters along the cortical ribbon to be estimated. In the majority of brain regions studied, NFT occurred in clusters of neurons which were regularly spaced along the cortical strip. This pattern is consistent with the predicted distribution of the cells of origin of specific cortico-cortico projections. Mean NFT cluster size varied from 250 to > 12800 microns in different cortical tissues suggesting either variation in the size of the cell clusters or a dynamic process in the development of NFT in relation to these cell clusters. The formation of NFT in cell clusters which may give rise to the feed-forward and feed-back cortico-cortical projections suggests a possible route of spread of NFT pathology in AD between cortical regions and from the cortex to subcortical areas.

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.

Clustering patterns of neurofibrillary tangles in Alzheimer’s disease

Clustering of cellular neurofibrillary tangles (NFT) was studied in the cerebral cortex and hippocampus in cases of Alzheimer’s disease (AD) using a regression method. The objective of the study was to test the hypothesis that clustering of NFTs reflects the degeneration of the cortico-cortical pathways. In 25/38 (66%) of analyses of individual brain areas, a significant peak to trough and peak to peak distance was obtained suggesting that the clusters of NFTs were regularly distributed in bands parallel to the tissue boundary. In analyses of cortical tissues with regularly distributed clusters, peak to peak distance was between 1000 and 1600 microns in 13/24 (54%) of analyses, >1600 microns in 10/24 (42%) and <1000 microns in 1/24 (4%) of analyses. A regular distribution of NFT clusters was less evident in the CA sectors of the hippocampus than in the cortex. Hence, in a significant proportion of brain areas, the spacing of NFT clusters along the cerebral cortex was consistent with the predicted distribution of the cells of origin of specific cortico-cortical projections. However, in many brain regions, the sizes of the NFT clusters were larger than predicted which may be attributable to the spread of NFTs to adjacent groups of cells as the disease progresses.

The spatial patterns of Pick bodies, Pick cells and Alzheimer’s disease pathology in Pick’s disease

The spatial patterns of Pick bodies (PB), Pick cells (PC), senile plaques (SP) and neurofibrillary tangles (NFT) were studied in the frontal and temporal lobe in nine cases of Pick’s disease (PD). Pick bodies exhibited clustering in 41/44 (93%) of analyses and clusters of PB were regularly distributed parallel to the tissue boundary in 24/41 (58%) of analyses. Pick cells exhibited clustering with regular periodicity of clusters in 14/16 (88%) analyses, SP in three out of four (75%) analyses and NFT in 21/27 (78%) analyses. The largest clusters of PB were observed in the dentate gyrus and PC in the frontal cortex. In 10/17 (59%) brain areas studied, a positive or negative correlation was observed between the densities of PB and PC. The densities of PB and NFT were not significantly correlated in the majority of brain areas but a negative correlation was observed in 7/29 (24%) brain areas. The data suggest that PB and PC in patients with PD exhibit essentially the same spatial patterns as SP and NFT in Alzheimer’s disease (AD) and Lewy bodies (LB) in dementia with Lewy bodies (DLB). In addition, there was a spatial correlation between the clusters of PB and PC, suggesting a pathogenic relationship between the two lesions. However, in the majority of tissues examined there was no spatial correlation between the clusters of PB and NFT, suggesting that the two lesions develop in association with different populations of neurons.

The spatial patterns of beta-amyloid (Abeta) deposits in elderly non-demented patients and patients with Alzheimer’s disease

The spatial patterns of diffuse, primitive, classic and compact beta-amyloid (Abeta) deposits were studied in the medial temporal lobe in 14 elderly, non-demented patients (ND) and in nine patients with Alzheimer’s disease (AD). In both patient groups, Abeta deposits were clustered and in a number of tissues, a regular periodicity of Abeta deposit clusters was observed parallel to the tissue boundary. The primitive deposit clusters were significantly larger in the AD cases but there were no differences in the sizes of the diffuse and classic deposit clusters between patient groups. In AD, the relationship between Abeta deposit cluster size and density in the tissue was non-linear. This suggested that cluster size increased with increasing Abeta deposit density in some tissues while in others, Abeta deposit density was high but contained within smaller clusters. It was concluded that the formation of large clusters of primitive deposits could be a factor in the development of AD.

The perceptual organization of sine-wave speech under competitive conditions

Speech comprises dynamic and heterogeneous acoustic elements, yet it is heard as a single perceptual stream even when accompanied by other sounds. The relative contributions of grouping “primitives” and of speech-specific grouping factors to the perceptual coherence of speech are unclear, and the acoustical correlates of the latter remain unspecified. The parametric manipulations possible with simplified speech signals, such as sine-wave analogues, make them attractive stimuli to explore these issues. Given that the factors governing perceptual organization are generally revealed only where competition operates, the second-formant competitor (F2C) paradigm was used, in which the listener must resist competition to optimize recognition [Remez et al., Psychol. Rev. 101, 129-156 (1994)]. Three-formant (F1+F2+F3) sine-wave analogues were derived from natural sentences and presented dichotically (one ear = F1+F2C+F3; opposite ear = F2). Different versions of F2C were derived from F2 using separate manipulations of its amplitude and frequency contours. F2Cs with time-varying frequency contours were highly effective competitors, regardless of their amplitude characteristics. In contrast, F2Cs with constant frequency contours were completely ineffective. Competitor efficacy was not due to energetic masking of F3 by F2C. These findings indicate that modulation of the frequency, but not the amplitude, contour is critical for across-formant grouping.

The spatial patterns of the tau immunopositive neuronal cytoplasmic inclusions (NCI) in the tauopathies

Tau positive neuronal cytoplasmic inclusions (NCI) are the ‘hallmark’ pathological feature of several neurodegenerative diseases collectively known as the tauopathies. This study compared the spatial patterns of various types of NCI in selected tauopathies including the neurofibrillary tangles (NFT) in Alzheimer's disease (AD) and progressive supranuclear palsy (PSP), Pick bodies (PB) in Pick’s disease (PiD), and the tau positive (tau+) neurons in corticobasal degeneration (CBD). In the cerebral cortex of these disorders, the tau+ NCI were distributed in clusters and in a significant proportion of analyses, the clusters were distributed with a regular periodicity parallel to the pia mater. The inclusions in AD, PiD and CBD exhibited a similar range of spatial patterns but in PSP were less frequently clustered and more frequently randomly distributed. In gyri where the NCI were clustered, there was a significant difference in mean cluster size between disorders. Hence, clusters of NFT in AD were larger than those in PSP and the tau+ neurons in CBD and clusters of PB in PiD were larger than the tau+ neurons in CBD and the NFT in PSP. The cluster size of the tau+ neurons in CBD was similar to the NFT in PSP. The data suggest that the formation of clusters of NCI, regularly distributed parallel to the pia mater, is a common feature of the tauopathies indicating similar patterns of cortical degeneration and pathogenic mechanisms across different diseases. Furthermore, the data suggest that cortical degeneration affecting the short and long cortico-cortical pathways may be a characteristic of the tauopathies.