The spatial patterns of beta-amyloid deposits and neurofibrillary tangles in the cerebral cortex in Alzheimer's disease

In Alzheimer's disease (AD) brain, beta-amyloid (Abeta) deposits and neurofibrillary tangles (NFT) are not randomly distributed but exhibit a spatial pattern, i.e., a departure from randomness towards regularity or clustering. Studies of the spatial pattern of a lesion may contribute to an understanding of its pathogenesis and therefore, of AD itself. This article describes the statistical methods most commonly used to detect the spatial patterns of brain lesions and the types of spatial patterns exhibited by ß-amyloid deposits and NFT in the cerebral cortex in AD. These studies suggest that within the cerebral cortex, Abeta deposits and NFT exhibit a similar spatial pattern, i.e., an aggregation of individual lesions into clusters which are regularly distributed parallel to the pia mater. The location, size and distribution of these clusters supports the hypothesis that AD is a 'disconnection syndrome' in which degeneration of specific cortical pathways results in the formation of clusters of NFT and Abeta deposits. In addition, a model to explain the development of the pathology within the cerebral cortex is proposed.

Anisotropy for spatial summation of elongated patches of grating:A tale of two tails

Studies of spatial summation often use sinusoidal gratings with blurred edges. When the envelope is elongated (i) along the grating stripes and (ii) at right angles to the grating stripes, we refer to the stimuli as skunk-tails and tiger-tails respectively. Previous work [Polat & Tyler, 1999; Vision Research, 39, 887-895.] has found that sensitivity to skunk-tails is greater than for tiger-tails, but there have been several failures to replicate this result within a subset of the conditions. To address this we measured detection thresholds for skunk-tails, tiger-tails and squares of grating with sides matched to the lengths of the tails. For foveal viewing, we found a contrast sensitivity advantage in the order of 2 dB for skunk-tails over tiger-tails, but only for horizontal gratings. For vertical gratings, sensitivity was very similar for both tail-types. When the stimuli were presented parafoveally (upper right visual field), a small advantage was found for skunk-tails over tiger-tails at both orientations, and spatial summation slopes were close to that of the ideal observer. We did not replicate the findings of Polat & Tyler, but our results are consistent with (i) those of Foley et al. [Foley, J. M., Varadharajan, S., Koh, C. C., & Farias, C. Q. (2007) Vision Research, 47, 85-107.] who used only vertical gratings and (ii) those from modelfest, where only horizontal gratings were used. The small effect of tail-type here suggests an anisotropy in the underlying physiology. © 2007 Elsevier Ltd. All rights reserved.

The spatial patterns of β/A4 deposit subtypes in Down's syndrome

The spatial patterns of diffuse, primitive and classic β/A4 deposits were studied in coronal sections of the hippocampus and adjacent gyri in 11 cases of Down's syndrome (DS) varying in age from 38 to 67 years. The objectives of the study were first, to compare the spatial patterns of β/A4 deposits revealed in DS with those reported in cases of Alzheimer's disease (AD) and second, to study how the spatial patterns of β/A4 deposits may develop in the tissue. The spatial patterns revealed in DS exhibited a number of similarities with those reported in AD: (1) the range and frequency of the different types of spatial pattern revealed were similar, (2) β/A4 deposits occurred in clusters and in many cortical tissues, the clusters were distributed in a regular pattern parallel to the pia, (3) the clusters of diffuse and primitive β/A4 deposits occurred in an alternating pattern along the cortex, and (4) the clusters of classic β/A4 deposits were not correlated with the clusters of the diffuse and primitive deposits. Primitive deposits may develop from the diffuse deposits in regions of the cortex where extracellular paired helical filaments were formed. However, clusters of the classic β/A4 deposits, which are formed in older cases, appear to develop independently of the diffuse and primitive deposits. © 1994 Springer-Verlag.

Chronic administration of an aluminium-enriched diet impairs spatial orientation in a sub-group of C57BL6 female mice

Disturbances of spatial orientation are an early clinical component of senile dementia of the Alzheimer type (SDAT). since it has been suggested that an elevated aluminium intake associated with chronic nutritional deficiencies of calcium and magnesium may play an important role in the aetiology of SDAT, we have investigated the effect of such a dietary regime on the spatial orientation abilities of female C57BL6 mice using the Morris swimming pool test. Statistical analysis of the performances of control and experimental groups indicate that the ability to orientate towards a submerged and thus invisible platform is conistently and markedly impaired in the experimental group. The ability to orientate towards a visible platform is also significantly impaired although to a lesser extent. Analysis of the performances of individual animals demonstrate that this impairment of orientation in the experimental group only occurs in a sub-group of animals: the remainder display normal orientational ability.

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.

Excitation of higher spatial harmonics by a moving light pattern in sillenites

We investigate numerically the dependence of higher harmonics of the space-charge field on the detuning frequency between the pump waves, which form a running interference pattern. Bistability and hysteresis of harmonics are predicted for a contrast of the interference pattern m =(0.25-0.3). For contrasts m˜1 and small detuning frequencies we show the existence of a narrow resonance, connected with the nonlinear excitation of a slowly decreasing sequence of spatial harmonics. For experiments we use a BSO crystal in the optical configuration which avoids nonlinear optical distortions. The experimental data show good qualitative agreement with theory.

Spatial patterns of FUS-immunoreactive neuronal cytoplasmic inclusions (NCI) in neuronal intermediate filament inclusion disease (NIFID)

Neuronal intermediate filament inclusion disease (NIFID), a rare form of frontotemporal lobar degeneration (FTLD), is characterized neuropathologically by focal atrophy of the frontal and temporal lobes, neuronal loss, gliosis, and neuronal cytoplasmic inclusions (NCI) containing epitopes of ubiquitin and neuronal intermediate filament (IF) proteins. Recently, the 'fused in sarcoma' (FUS) protein (encoded by the FUS gene) has been shown to be a component of the inclusions of NIFID. To further characterize FUS proteinopathy in NIFID, we studied the spatial patterns of the FUS-immunoreactive NCI in frontal and temporal cortex of 10 cases. In the cerebral cortex, sectors CA1/2 of the hippocampus, and the dentate gyrus (DG), the FUS-immunoreactive NCI were frequently clustered and the clusters were regularly distributed parallel to the tissue boundary. In a proportion of cortical gyri, cluster size of the NCI approximated to those of the columns of cells was associated with the cortico-cortical projections. There were no significant differences in the frequency of different types of spatial patterns with disease duration or disease stage. Clusters of NCI in the upper and lower cortex were significantly larger using FUS compared with phosphorylated, neurofilament heavy polypeptide (NEFH) or a-internexin (INA) immunohistochemistry (IHC). We concluded: (1) FUS-immunoreactive NCI exhibit similar spatial patterns to analogous inclusions in the tauopathies and synucleinopathies, (2) clusters of FUS-immunoreactive NCI are larger than those revealed by NEFH or ???, and (3) the spatial patterns of the FUS-immunoreactive NCI suggest the degeneration of the cortico-cortical projections in NIFID.

Spatial tuning studies of the pattern evoked electroretinogram

The locus of origin of the pattern evoked electroretinogram, (PERG), has been the subject of considerable discussion. A novel approach was adopted in this study to further elaborate the nature of the PERG evoked by pattern onset/offset presentation. The PERG was found to be linearly related to stimulus contrast and in particular was linearly related to the temporal contrast of the retinal image, when elicited by patterns of low spatial frequency. At high spatial frequencies the retinal image contrast is significantly reduced because of optical degradation. This is described by the eye's modulation transfer function (MTF). The retinal contrast of square wave grating and chequerboard patterns of increasing spatial frequency were found by filtering their Fourier transforms by the MTF. The filtered pattern harmonics were then resynthesised to constitute a profile of retinal image illuminance from which the temporal and spatial contrast of the image could be calculated. If the PERG is a pure illuminance response it should be spatially insensitive and dependent upon the temporal contrast of stimulation. The calculated loss of temporal contrast for finer patterns was expressed as a space-averaged temporal contrast attentuation factor. This factor, applied to PERGs evoked by low spatial frequency patterns, was used to predict the retinal illuminance response elicited by a finer pattern. The predicted response was subtracted from the recorded signal and residual waveform was proposed to represent specific activity. An additional correction for the attenuation of spatial contrast was applied to the extracted pattern specific response. Pattern specific responses computed for different spatial frequency patterns in this way are the predicted result of iso-contrast pattern stimulation. The pattern specific responses demonstrate a striking bandpass spatial selectivity which peaks at higher spatial frequencies in the more central retina. The variation of spatial sensitivity with eccentricity corresponds closely with estimated ganglion receptive field centre separation and psychophysical data. The variation of retinal structure with eccentricity, in the form of the volumes of the nuclear layers, was compared with the amplitudes of the computed retinal illuminance and pattern specific responses. The retinal illuminance response corresponds more closely to the outer and inner nuclear layers whilst the pattern specific response appears more closely related to the ganglion cell layer. In general the negative response transients correspond to the more proximal retinal layers. This thesis therefore supports the proposed contribution of proximal retinal cell activity to the PERG and describes techniques which may be further elaborated for more detailed studies of retinal receptive field dimensions.

The carbon dioxide emissions of firms:a spatial analysis

In order to gain a greater understanding of firms' 'environmental behaviour' this paper explores the factors that influence firms' emissions intensities and provides the first analysis of the determinants of firm level carbon dioxide (CO2) emissions. Focussing on Japan, the paper also examines whether firms' CO2 emissions are influenced by the emissions of neighbouring firms and other possible sources of spatial correlation. Results suggest that size, the capital-labour ratio, R&D expenditure, the extent of exports and concern for public profile are the key determinants of CO2 emissions. Local lobbying pressure, as captured by regional community characteristics, does not appear to play a role, however emissions are found to be spatially correlated. This raises implications for the manner in which the environmental performance of firms is modelled in future. © 2013 Elsevier Inc.

The spatial distribution of self-employment in India:evidence from semi-parametric geoadditive models

The spatial distribution of self-employment in India: evidence from semiparametric geoadditive models, Regional Studies. The entrepreneurship literature has rarely considered spatial location as a micro-determinant of occupational choice. It has also ignored self-employment in developing countries. Using Bayesian semiparametric geoadditive techniques, this paper models spatial location as a micro-determinant of self-employment choice in India. The empirical results suggest the presence of spatial occupational neighbourhoods and a clear north–south divide in self-employment when the entire sample is considered; however, spatial variation in the non-agriculture sector disappears to a large extent when individual factors that influence self-employment choice are explicitly controlled. The results further suggest non-linear effects of age, education and wealth on self-employment.

Implicit leadership and followership theories 'in the wild':taking stock of information-processing approaches to leadership and followership in organizational settings

For over 30. years information-processing approaches to leadership and more specifically Implicit Leadership Theories (ILTs) research has contributed a significant body of knowledge on leadership processes in applied settings. A new line of research on Implicit Followership Theories (IFTs) has re-ignited interest in information-processing and socio-cognitive approaches to leadership and followership. In this review, we focus on organizational research on ILTs and IFTs and highlight their practical utility for the exercise of leadership and followership in applied settings. We clarify common misperceptions regarding the implicit nature of ILTs and IFTs, review both direct and indirect measures, synthesize current and ongoing research on ILTs and IFTs in organizational settings, address issues related to different levels of analysis in the context of leadership and follower schemas and, finally, propose future avenues for organizational research. © 2013 Elsevier Inc.

The two forms of visuo-spatial perspective taking are differently embodied and subserve different spatial prepositions

We set out to distinguish level 1 (VPT-1) and level 2 (VPT-2) perspective taking with respect to the embodied nature of the underlying processes as well as to investigate their dependence or independence of response modality (motor vs. verbal). While VPT-1 reflects understanding of what lies within someone else’s line of sight, VPT-2 involves mentally adopting someone else’s spatial point of view. Perspective taking is a high-level conscious and deliberate mental transformation that is crucially placed at the convergence of perception, mental imagery, communication, and even theory of mind in the case of VPT-2. The differences between VPT-1 and VPT-2 mark a qualitative boundary between humans and apes, with the latter being capable of VPT-1 but not of VPT-2. However, our recent data showed that VPT-2 is best conceptualized as the deliberate simulation or emulation of a movement, thus underpinning its embodied origins. In the work presented here we compared VPT-2 to VPT-1 and found that VPT-1 is not at all, or very differently embodied. In a second experiment we replicated the qualitatively different patterns for VPT-1 and VPT-2 with verbal responses that employed spatial prepositions. We conclude that VPT-1 is the cognitive process that subserves verbal localizations using “in front” and “behind,” while VPT-2 subserves “left” and “right” from a perspective other than the egocentric. We further conclude that both processes are grounded and situated, but only VPT-2 is embodied in the form of a deliberate movement simulation that increases in mental effort with distance and incongruent proprioception. The differences in cognitive effort predict differences in the use of the associated prepositions. Our findings, therefore, shed light on the situated, grounded and embodied basis of spatial localizations and on the psychology of their use.

Excitation of higher spatial harmonics by a moving light pattern in sillenites

We investigate numerically the dependence of higher harmonics of the space-charge field on the detuning frequency between the pump waves, which form a running interference pattern. Bistability and hysteresis of harmonics are predicted for a contrast of the interference pattern m =(0.25-0.3). For contrasts m˜1 and small detuning frequencies we show the existence of a narrow resonance, connected with the nonlinear excitation of a slowly decreasing sequence of spatial harmonics. For experiments we use a BSO crystal in the optical configuration which avoids nonlinear optical distortions. The experimental data show good qualitative agreement with theory.

Measuring the spatial extent of texture pooling using reverse correlation

The local image representation produced by early stages of visual analysis is uninformative regarding spatially extensive textures and surfaces. We know little about the cortical algorithm used to combine local information over space, and still less about the area over which it can operate. But such operations are vital to support perception of real-world objects and scenes. Here, we deploy a novel reverse-correlation technique to measure the extent of spatial pooling for target regions of different areas placed either in the central visual field, or more peripherally. Stimuli were large arrays of micropatterns, with their contrasts perturbed individually on an interval-by-interval basis. By comparing trial-by-trial observer responses with the predictions of computational models, we show that substantial regions (up to 13 carrier cycles) of a stimulus can be monitored in parallel by summing contrast over area. This summing strategy is very different from the more widely assumed signal selection strategy (a MAX operation), and suggests that neural mechanisms representing extensive visual textures can be recruited by attention. We also demonstrate that template resolution is much less precise in the parafovea than in the fovea, consistent with recent accounts of crowding. © 2014 The Authors.

The impact of university research on corporate patenting

This paper analyses the association between the number of patenting manufacturing firms and the quantity and quality of relevant university research across UK postcode areas. We show that different measures of research `power' and `excellence' positively affect the patenting of small firms within the same postcode area. Patenting by large firms, in contrast, is unaffected by research undertaken in nearby universities. This confirms the commonly held view that location matters more for small firms than large firms. We also investigate specific channels of technology transfer, finding that university-industry knowledge transfer occurs through both formal and informal channels. From a methodological point of view, we contribute to the existing literature by accounting for potential simultaneity between university research and patenting of local firms by adopting an instrumental variable approach. Moreover, we also allow for the effects of the presence of universities in neighbouring postcode areas to influence firms' patenting activity by incorporating spatial neighborhood effects.