Clustering and periodicity of neurofibrillary tangles in the upper and lower cortical laminae in Alzheimer's disease

In Alzheimer's disease (AD), neurofibrillary tangles (NFT) occur within neurons in both the upper and lower cortical laminae. Using a statistical method that estimates the size and spacing of NFT clusters along the cortex parallel to the pia mater, two hypotheses were tested: 1) that the cluster size and distribution of the NFT in gyri of the temporal lobe reflect degeneration of the feedforward (FF) and feedback (FB) cortico-cortical pathways, and 2) that there is a spatial relationship between the clusters of NFT in the upper and lower laminae. In 16 temporal lobe gyri from 10 cases of sporadic AD, NFT were present in both the upper and lower laminae in 11/16 (69%) gyri and in either the upper or lower laminae in 5/16 (31%) gyri. Clustering of the NFT was observed in all gyri. A significant peak-to-peak distance was observed in the upper laminae in 13/15 (87%) gyri and in the lower laminae in 8/ 12 (67%) gyri, suggesting a regularly repeating pattern of NFT clusters along the cortex. The regularly distributed clusters of NFT were between 500 and 800 μm in size, the estimated size of the cells of origin of the FF and FB cortico-cortical projections, in the upper laminae of 6/13 (46%) gyri and in the lower laminae of 2/8 (25%) gyri. Clusters of NFT in the upper laminae were spatially correlated (in phase) with those in the lower laminae in 5/16 (31%) gyri. The clustering patterns of the NFT are consistent with their formation in relation to the FF and FB cortico-cortical pathways. In most gyri, NFT clusters appeared to develop independently in the upper and lower laminae.

Stochasticity, periodicity and localized light structures in partially mode-locked fibre lasers

Physical systems with co-existence and interplay of processes featuring distinct spatio-temporal scales are found in various research areas ranging from studies of brain activity to astrophysics. The complexity of such systems makes their theoretical and experimental analysis technically and conceptually challenging. Here, we discovered that while radiation of partially mode-locked fibre lasers is stochastic and intermittent on a short time scale, it exhibits non-trivial periodicity and long-scale correlations over slow evolution from one round-trip to another. A new technique for evolution mapping of intensity autocorrelation function has enabled us to reveal a variety of localized spatio-temporal structures and to experimentally study their symbiotic co-existence with stochastic radiation. Real-time characterization of dynamical spatio-temporal regimes of laser operation is set to bring new insights into rich underlying nonlinear physics of practical active- and passive-cavity photonic systems.

The role of oscillatory brain activity in object processing and figure-ground segmentation in human vision

The perception of an object as a single entity within a visual scene requires that its features are bound together and segregated from the background and/or other objects. Here, we used magnetoencephalography (MEG) to assess the hypothesis that coherent percepts may arise from the synchronized high frequency (gamma) activity between neurons that code features of the same object. We also assessed the role of low frequency (alpha, beta) activity in object processing. The target stimulus (i.e. object) was a small patch of a concentric grating of 3c/°, viewed eccentrically. The background stimulus was either a blank field or a concentric grating of 3c/° periodicity, viewed centrally. With patterned backgrounds, the target stimulus emerged--through rotation about its own centre--as a circular subsection of the background. Data were acquired using a 275-channel whole-head MEG system and analyzed using Synthetic Aperture Magnetometry (SAM), which allows one to generate images of task-related cortical oscillatory power changes within specific frequency bands. Significant oscillatory activity across a broad range of frequencies was evident at the V1/V2 border, and subsequent analyses were based on a virtual electrode at this location. When the target was presented in isolation, we observed that: (i) contralateral stimulation yielded a sustained power increase in gamma activity; and (ii) both contra- and ipsilateral stimulation yielded near identical transient power changes in alpha (and beta) activity. When the target was presented against a patterned background, we observed that: (i) contralateral stimulation yielded an increase in high-gamma (>55 Hz) power together with a decrease in low-gamma (40-55 Hz) power; and (ii) both contra- and ipsilateral stimulation yielded a transient decrease in alpha (and beta) activity, though the reduction tended to be greatest for contralateral stimulation. The opposing power changes across different regions of the gamma spectrum with 'figure/ground' stimulation suggest a possible dual role for gamma rhythms in visual object coding, and provide general support of the binding-by-synchronization hypothesis. As the power changes in alpha and beta activity were largely independent of the spatial location of the target, however, we conclude that their role in object processing may relate principally to changes in visual attention.

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.

Grouping and the pitch of a mistuned fundamental component:effects of applying simultaneous multiple mistunings to the other harmonics

Mistuning a harmonic produces an exaggerated change in its pitch. This occurs because the component becomes inconsistent with the regular pattern that causes the other harmonics (constituting the spectral frame) to integrate perceptually. These pitch shifts were measured when the fundamental (F0) component of a complex tone (nominal F0 frequency = 200 Hz) was mistuned by +8% and -8%. The pitch-shift gradient was defined as the difference between these values and its magnitude was used as a measure of frame integration. An independent and random perturbation (spectral jitter) was applied simultaneously to most or all of the frame components. The gradient magnitude declined gradually as the degree of jitter increased from 0% to ±40% of F0. The component adjacent to the mistuned target made the largest contribution to the gradient, but more distant components also contributed. The stimuli were passed through an auditory model, and the exponential height of the F0-period peak in the averaged summary autocorrelation function correlated well with the gradient magnitude. The fit improved when the weighting on more distant channels was attenuated by a factor of three per octave. The results are consistent with a grouping mechanism that computes a weighted average of periodicity strength across several components. © 2006 Elsevier B.V. All rights reserved.

Dark solitons in optical communication systems

This thesis presents experimental and theoretical work on the use of dark optical solitons as data carriers in communications systems. The background chapters provide an introduction to nonlinear optics, and to dark solitons, described as intensity dips in a bright background, with an asymmetrical phase profile. The motivation for the work is explained, considering both the superior stability of dark solitons and the need for a soliton solution suitable for the normal, rather than the anomalous (bright soliton) dispersion regime. The first chapters present two generation techniques, producing packets of dark solitons via bright pulse interaction, and generating continuous trains of dark pulses using a fibre laser. The latter were not dark solitons, but were suitable for imposition of the required phase shift by virtue of their extreme stability. The later chapters focus on the propagation and control of dark solitons. Their response to periodic loss and gain is shown to result in the exponential growth of spectral sidebands. This may be suppressed by reducing the periodicity of the loss/gain cycle or using periodic filtering. A general study of the response of dark solitons to spectral filtering is undertaken, showing dramatic differences in the behaviour of black and 99.9% grey solitons. The importance of this result is highlighted by simulations of propagation in noisy systems, where the timing jitter resulting from random noise is actually enhanced by filtering. The results of using sinusoidal phase modulation to control pulse position are presented, showing that the control is at the expense of serious modulation of the bright background. It is concluded that in almost every case, dark and bright solitons have very different properties, and to continue to make comparisons would not be so productive as to develop a deeper understanding of the interactions between the dark soliton and its bright background.

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.

Clustering of cerebral cortical lesions in patients with corticobasal degeneration

Clustering of ballooned neurons (BN) and tau positive neurons with inclusion bodies (tau+ neurons) was studied in the upper and lower laminae of the frontal, parietal and temporal cortex in 12 patients with corticobasal degeneration (CBD). In a significant proportion of brain areas examined, BN and tau+ neurons exhibited clustering with a regular distribution of clusters parallel to the pia mater. A regular pattern of clustering of BN and tau+ neurons was observed equally frequently in all cortical areas examined and in the upper and lower laminae. No significant correlations were observed between the cluster sizes of BN or tau+ neurons in the upper compared with the lower cortex or between the cluster sizes of BN and tau+ neurons. The results suggest that BN and tau+ neurons in CBD exhibit the same type of spatial pattern as lesions in Alzheimer's disease, Lewy body dementia and Pick's disease. The regular periodicity of the cerebral cortical lesions is consistent with the degeneration of the cortico-cortical projections in CBD.

Spatial distribution of diffuse, primitive, and classic amyloid-beta deposits and blood vessels in the upper laminae of the frontal cortex in Alzheimer disease

The spatial distribution of the diffuse, primitive, and classic amyloid-beta deposits was studied in the upper laminae of the superior frontal gyrus in cases of sporadic Alzheimer disease (AD). Amyloid-beta-stained tissue was counterstained with collagen IV to determine whether the spatial distribution of the amyloid-beta deposits along the cortex was related to blood vessels. In all patients, amyloid-beta deposits and blood vessels were aggregated into distinct clusters and in many patients, the clusters were distributed with a regular periodicity along the cortex. The clusters of diffuse and primitive deposits did not coincide with the clusters of blood vessels in most patients. However, the clusters of classic amyloid-beta deposits coincided with those of the large diameter (>10 microm) blood vessels in all patients and with clusters of small-diameter (< 10 microm) blood vessels in four patients. The data suggest that, of the amyloid-beta subtypes, the clusters of classic amyloid-beta deposits appear to be the most closely related to blood vessels and especially to the larger-diameter, vertically penetrating arterioles in the upper cortical laminae.

Clustering of Pick bodies in patients with Pick's disease

Clustering of Pick bodies (PB) was studied in the frontal and temporal lobe in 10 cases of Pick's disease (PD). Pick bodies exhibited clustering in 47/50 (94%) brain areas analysed. In 20/50 (40%) brain areas, PB were present in a single large cluster ≤ 6400 μm in diameter, in 27/50 (54%) PB occurred in smaller clusters (200-3200 μm in diameter) which exhibited a regular periodicity relative to the tissue boundary, in 1/50 (2%) there was a regular distribution of individual PB and in 2/50 (4%), PB were randomly distributed. Mean cluster size of the PB was greater in the dentate gyrus compared with the inferior temporal gyrus and lateral occipitotemporal gyrus. Mean cluster size of PB in a brain region was positively correlated with the mean density of PB. Hence, PB exhibit essentially the same spatial patterns as senile plaques and neurofibrillary tangles in Alzheimer's disease (AD) and Lewy bodies in Dementia with Lewy bodies (DLB).

The spatial patterns of Lewy bodies, senile plaques, and neurofibrillary tangles in dementia with Lewy bodies

The spatial patterns of Lewy bodies (LB), senile plaques (SP), and neurofibrillary tangles (NFT) were studied in ubiquitin-stained sections of the temporal lobe in cases of dementia with Lewy bodies (DLB), which varied in the degree of associated Alzheimer's disease (AD) pathology. In all patients, LB, SP, and NFT developed in clusters and in a significant proportion of brain areas, the clusters exhibited a regular periodicity parallel to the tissue boundary. In the lateral occipitotemporal gyrus (LOT) and parahippocampal gyrus (PHG), the clusters of LB were larger than those of the SP and NFT but in the hippocampus, clusters of the three lesions were of similar size. Mean cluster size of the LB, SP, and NFT was similar in cases of DLB with and without significant associated AD pathology. LB density was positively correlated with SP and NFT density in 42 and 17% of brain areas analyzed, respectively, while SP and NFT densities were positively correlated in 7% of brain areas. The data suggest that LB in DLB exhibit similar spatial patterns to SP and NFT in AD and that SP and NFT exhibit similar spatial patterns in DLB and AD. In addition, in some instances, clusters of LB appeared to be more closely related spatially to the clusters of SP than to NFT.

Dementia with Lewy bodies:Clustering of Lewy bodies in human patients

Clustering of Lewy bodies (LB) was studied in four regions of the medial temporal lobe in 12 cases of dementia with LB (DLB). LB exhibited clustering in 67/70 (96%) brain areas analysed. In 34/70 (49%) analyses, LB were present in a single large cluster ≤6400 μm in diameter, in 33/70 (47%) LB occurred in smaller clusters 200-3200 μm in diameter which exhibited a regular periodicity relative to the tissue boundary and in 3/70 (4%), LB were randomly distributed. A regular pattern of LB clusters was observed equally frequently in the cortex and hippocampus, in upper and lower cortical laminae and in 'pure' cases of DLB with negligible Alzheimer's disease (AD) pathology compared with cases of AD with DLB. In cortical regions, there was no significant correlation between LB cluster size in the upper and lower cortical laminae. The regular periodicity of LB clusters suggests that LB develop in relation to the cells of origin of specific cortico-cortical and cortico-hippocampal projections.

The spatial pattern of discrete beta-amyloid deposits in Alzheimer's disease reflects synaptic disconnection

The spatial pattern of discrete beta-amyloid (A beta) deposits was studied in the superficial laminae of cortical fields of different types and in the hippocampus in 6 cases of Alzheimer's disease (AD). In 41/42 tissues examined, discrete A beta deposits were aggregated into clusters and in 34/41 tissues (25/34 of the cortical tissues), there was evidence for a regular periodicity of the A beta deposit clusters parallel to the tissue boundary. The dimensions of the clusters varied from 400 to > 12,800 microns in different tissues. Although the A beta deposit clusters were larger than predicted, the regular periodicity suggests that they develop in relation to groups of cells associated with specific projections. This would be consistent with the hypothesis that the distribution of discrete A beta deposits in AD could reflect progressive synaptic disconnection along interconnected neuronal pathways. This implies that amyloid deposition could be a response to, rather than a cause of, synaptic disconnection in AD.

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 β-amyloid (Aβ) deposits in the frontal cortex of Alzheimer patients determined by blood vessels?

The clustering pattern of diffuse, primitive and classic β-amyloid (Aβ) deposits was studied in the upper laminae of the frontal cortex of 9 patients with sporadic Alzheimer's disease (AD). Aβ stained tissue was counterstained with collagen type IV antiserum to determine whether the clusters of Aβ deposits were related to blood vessels. In all patients, Aβ deposits and blood vessels were clustered, with in many patients, a regular periodicity of clusters along the cortex parallel to the pia. The classic Aβ deposit clusters coincided with those of the larger blood vessels in all patients and with clusters of smaller blood vessels in 4 patients. Diffuse deposit clusters were related to blood vessels in 3 patients. Primitive deposit clusters were either unrelated to or negatively correlated with the blood vessels in six patients. Hence, Aβ deposit subtypes differ in their relationship to blood vessels. The data suggest a direct and specific role for the larger blood vessels in the formation of amyloid cores in AD. © 1995.