Spatial correlations between beta-amyloid (Abeta) deposits and blood vessels in early-onset Alzheimer's disease

In cases of late-onset Alzheimer’s disease (AD), there is a spatial correlation between the classsic ‘cored’ type of Beta-amyloid (Abeta) deposit and the large vertically penetrating arterioles in the cerebral cortex suggesting that blood vessels are involved in the pathogenesis of the classic deposits. In this chapter, the spatial correlations between the diffuse, primitive, and classic Abeta deposits and blood vessels were studied in 10 cases of early-onset AD in the age range 40 – 65 years. Sections of frontal cortex were immunostained with antibodies against Abeta?and with collagen IV to reveal the Abeta deposits and blood vessel profiles. In the early-onset cases as a whole, all types of Abeta? deposit and blood vessel profiles were distributed in clusters. There was a positive spatial correlation between the clusters of the diffuse Abeta deposits and the larger (>10µm) and smaller diameter (<10?m) blood vessel profiles in one and three cases respectively. The primitive and classic Abeta deposits were spatially correlated with larger and smaller blood vessels both in three and four cases respectively. Spatial correlations between the Abeta deposits and blood vessels may be more prevalent in cases expressing amyloid precursor protein (APP) than presenilin 1 (PSEN1) mutations. Apolipoprotein E (Apo E) genotype of the patient did not appear to influence the spatial correlation with blood vessel profiles. The data suggest that the larger diameter blood vessels are less important in the pathogenesis of the classic Abeta deposits in early-onset compared with late-onset AD.

The spatial patterns of beta-amyloid (Abeta) deposits and neurofibrillary tangles (NFT) in late-onset sporadic Alzheimer's disease

The spatial patterns of beta-amyloid (Abeta) deposits and neurofibrillary tangles (NFT) were studied in areas of the cerebral cortex in 16 patients with the late-onset, sporadic form of Alzheimer’s disease (AD). Diffuse, primitive, and classic Abeta deposits and NFT were aggregated into clusters; the clusters being regularly distributed parallel to the pia mater in many areas. In a significant proportion of regions, the sizes of the regularly distributed clusters approximated to those of the cells of origin of the cortico-cortical projections. The diffuse and primitive Abeta deposits exhibited a similar range of spatial patterns but the classic Abeta deposits occurred less frequently in large clusters >6400microm. In addition, the NFT often occurred in larger regularly distributed clusters than the Abeta deposits. The location, size, and distribution of the clusters of Abeta deposits and NFT supports the hypothesis that AD is a 'disconnection syndrome' in which degeneration of specific cortico-cortical and cortico-hippocampal pathways results in synaptic disconnection and the formation of clusters of NFT and Abeta deposits.

Wideband inhibition modulates the effect of onset asynchrony as a grouping cue

Onset asynchrony is arguably the most powerful grouping cue for the separation of temporally overlapping sounds (see Bregman 1990). A component that begins only 30–50 ms before the others makes a greatly reduced contribution to the timbre of a complex tone, or to the phonetic quality of a vowel (e.g. Darwin 1984). This effect of onset asynchrony does not necessarily imply a cognitive grouping process; instead it may result from peripheral adaptation in the response to the leading component in the few tens of milliseconds before the other components begin (e.g., Westerman and Smith 1984). However, two findings suggest that the effect of onset asynchrony cannot be explained entirely by peripheral adaptation. First, though the effect is smaller, the contribution of a component to the phonetic quality of a short-duration vowel is reduced when it ends after the other components (Darwin and Sutherland 1984; Roberts and Moore 1991).

Contralateral influences of wideband inhibition on the effect of onset asynchrony as a cue for auditory grouping

Onset asynchrony is an important cue for segregating sound mixtures. A harmonic of a vowel that begins before the other components contributes less to vowel quality. This asynchrony effect can be partly reversed by accompanying the leading portion of the harmonic with an octave-higher captor tone. The original interpretation was that the captor and leading portion formed a perceptual group, but it has recently been shown that the captor effect depends on neither a common onset time nor harmonic relations with the leading portion. Instead, it has been proposed that the captor effect depends on wideband inhibition in the central auditory system. Physiological evidence suggests that such inhibition occurs both within and across ears. Experiment 1 compared the efficacy of a pure-tone captor presented in the same or opposite ear to the vowel and leading harmonic. Contralateral presentation was at least as effective as ipsilateral presentation. Experiment 2 used multicomponent captors in a more comprehensive evaluation of harmonic influences on captor efficacy. Three captors with different fundamental frequencies were used, one of which formed a consecutive harmonic series with the leading harmonic. All captors were equally effective, irrespective of the harmonic relationship. These findings support and refine the inhibitory account. © 2007 Acoustical Society of America.

Cognition, ocular accommodation, and cardiovascular function in emmetropes and late-onset myopes

PURPOSE. To investigate objectively and noninvasively the role of cognitive demand on autonomic control of systemic cardiovascular and ocular accommodative responses in emmetropes and myopes of late-onset. METHODS. Sixteen subjects (10 men, 6 women) aged between 18 and 34 years (mean ± SD: 22.6 ± 4.4 years), eight emmetropes (EMMs; mean spherical equivalent [MSE] refractive error ± SD: 0.05 ± 0.24 D) and eight with late-onset myopia (LOMs; MSE ± SD: -3.66 ± 2.31 D) participated in the study. Subjects viewed stationary numerical digits monocularly within a Badal optical system (at both 0.0 and -3.0 D) while performing a two-alternative, forced-choice paradigm that matched cognitive loading across subjects. Five individually matched cognitive levels of increasing difficulty were used in random order for each subject. Five 20-second, continuous-objective recordings of the accommodative response measured with an open-view infrared autorefractor were obtained for each cognitive level, whereas simultaneous measurement of heart rate was continuously recorded with a finger-mounted piezoelectric pulse transducer for 5 minutes. Fast Fourier transformation of cardiovascular function allowed the relative power of the autonomic components to be assessed in the frequency domain, whereas heart period gave an indication of the time-domain response. RESULTS. Increasing the cognitive demand led to a significant reduction in the accommodative response in all subjects (0.0 D: by -0.35 ± 0.33 D; -3.0 D: by -0.31 ± 0.40 D, P < 0.001). The greater lag of LOMs compared with EMMs was not significant (P = 0.07) at both distance (0.38 ± 0.35 D) and near (0.14 ± 0.42 D). Mean heart period reduced with increasing levels of workload (P < 0.0005). LOMs exhibited a relative elevation in sympathetic system activity compared to EMMs. Within refractive groups, however, accommodative shifts with increasing cognition correlated with parasympathetic activity (r = 0.99, P < 0.001), more than with sympathetic activity (r = 0.62, P > 0.05). CONCLUSIONS. In an equivalent workload paradigm, increasing cognitive demand caused a reduction in accommodative response that was attributable principally to a concurrent reduction in the relative power of the parasympathetic component of the autonomic nervous system (ANS). The disparity in accommodative response between EMMs and LOMs, however, appears to be augmented by changes in the sympathetic nervous component of the systemic ANS. Copyright © Association for Research in Vision and Ophthalmology.

Chronotopographical analysis of the pattern onset visual evoked magnetic response (VEMR):Implications for waveform peak identification

The topography of the visual evoked magnetic response (VEMR) to a pattern onset stimulus was studied in five normal subjects using a single channel BTi magnetometer. Topographic distributions were analysed at regular intervals following stimulus onset (chronotopograpby). Two distinct field distributions were observed with half field stimulation: (1) activity corresponding to the C11 m which remains stable for an average of 34 msec and (2) activity corresponding to the C111 m which remains stable for about 50 msec. However, the full field topography of the largest peak within the first 130 msec does not have a predictable latency or topography in different subjects. The data suggest that the appearance of this peak is dependent on the amplitude, latency and duration of the half field C11 m peaks and the efficiency of half field summation. Hence, topographic mapping is essential to correctly identify the C11 m peak in a full field response as waveform morphology, peak latency and polarity are not reliable indicators. © 1993.

Topographic mapping and source localization of the pattern onset visual evoked magnetic response

The topography of the visual evoked magnetic response (VEMR) to a pattern onset stimulus was investigated using 4 check sizes and 3 contrast levels. The pattern onset response consists of three early components within the first 200ms, CIm, CIIm and CIIIm. The CIIm is usually of high amplitude and is very consistent in latency within a subject. Half field (HF) stimuli produce their strongest response over the contralateral hemisphere; the RHF stimulus exhibiting a lower positivity (outgoing field) and an upper negativity (ingoing field), rotated towards the midline. LHF stimulation produced the opposite response, a lower negative and an upper positive. Larger check sizes produce a single area of ingoing and outgoing field while smaller checks produce on area of ingoing and outgoing field over each hemisphere. Latency did not appear to vary with change in contrast but amplitudes increased with increasing contrast. A more detailed topographic study incorporating source localisation procedures suggested a source for CIIm - 4cm below the scalp, close to the midline with current flowing towards the lateral surface. Similar depth and position estimates but with opposite polarity were obtained for the pattern shift P100m previously. Hence, the P100m and the CIIm may originate in similar areas of visual cortex but reveal different aspects of visual processing. © 1992 Human Sciences Press, Inc.

A comparison of βamyloid (aβ deposition in the medial temporal lobe in late-onset sporadic Alzheimer's disease, and down's syndrome

The density of diffuse, primitive, classic and compact βamyloid (Aβ deposits was estimated in regions of the medial temporal lobe (MTL) in 15 cases of late-onset sporadic Alzheimer's disease (AD) and 12 cases of Down's syndrome (DS). A similar pattern of Aβ deposition was observed in the MTL in the AD and DS cases with a reduced density of deposits in the hippocampus compared with the adjacent cortical regions. Total Aβ deposit density was greater in DS than in AD in all brain regions examined. This could be attributable to overexpression of the amyloid precursor protein gene. The ratio of the primitive to the diffuse Aβ deposits was greater in DS than in AD which suggests that the formation of mature amyloid deposits is enhanced in DS. The diffuse deposits exhibited a parabolic and the primitive deposits an inverted parabolic response with age in the DS cases. This suggests either that the diffuse and primitive deposits are sequentially related or that there are alternate pathways of Aβ deposition. © 1995 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

The visual evoked magnetic response to a pattern onset stimulus

The topography of the visual evoked magnetic response to a pattern onset stimulus was studied in four normal subjects. The topography of th CIIm component was consistent when measured on the same subject nine months apart. Full field responses were more variable than half field responses. With decreasing check size, the field pattern changes from a simple distribution with one outgoing and one ingoing area of field to a more complex pattern with in and outgoing fields over each hemisphere of the brain. The source may originate at the pole or from within the calcarine fissure.

The influence of adaptation and inhibition on the effects of onset asynchrony on auditory grouping

Onset asynchrony is an important cue for auditory scene analysis. For example, a harmonic of a vowel that begins before the other components contributes less to the perceived phonetic quality. This effect was thought primarily to involve high-level grouping processes, because the contribution can be partly restored by accompanying the leading portion of the harmonic (precursor) with a synchronous captor tone an octave higher, and hence too remote to influence adaptation of the auditory-nerve response to that harmonic. However, recent work suggests that this restoration effect arises instead from inhibitory interactions relatively early in central auditory processing. The experiments reported here have reevaluated the role of adaptation in grouping by onset asynchrony and explored further the inhibitory account of the restoration effect. Varying the frequency of the precursor in the range ± 10% relative to the vowel harmonic (Experiment 1), or introducing a silent interval from 0 to 320 ms between the precursor and the vowel (Experiment 2), both produce effects on vowel quality consistent with those predicted from peripheral adaptation or recovery from it. However, there were some listeners for whom even the smallest gap largely eliminated the effect of the precursor. Consistent with the inhibitory account of the restoration effect, a contralateral pure tone whose frequency is close to that of the precursor is highly effective at restoring the contribution of the asynchronous harmonic (Experiment 3). When the frequencies match, lateralization cues arising from binaural fusion of the precursor and contralateral tone may also contribute to this restoration. (PsycINFO Database Record (c) 2012 APA, all rights reserved)

Topography of visual evoked magnetic responses to pattern shift, pattern onset and flash stimuli

Different visual stimuli may activate separate channels in the visual system and produce magnetic responses from the human bran which originate from distinct regions of the visual cortex. To test this hypothesis, we have investigated the distribution of visual evoked magnetic responses to three distinct visual stimuli over the occipital region of the scalp with a DC-SQUID second-order gradiometer in an ubshielded environment. Patterned stimuli were presented full field and to the right half field, while a flash stimulus was presented full field only, in five normal subjects. Magnetic responses were recorded from 20 to 42 positions over the occipital scalp. Topographic maps were prepared of the major positive component within the first 150ms to the three stimuli, i.e., the P100m (pattern shift), C11m (pattern onset) and P2m (flash). For the pattern shift stimulus the data suggested the source of the P100m was close to the midline with the current directed towards the medial surface. The data for the pattern onset C11m suggested a source at a similar depth but with the current directed away from the midline towards the lateral surface. The flash P2m appeared to originate closer to the surface of the occipital pole than both the patterned stimuli. Hence the pattern shift (which may represent movement), and the pattern onset C11m (representing contrast and contour) appear to originate in similar areas of brain but to represent different asepcts of cortical processing. By contrast, the flash P2m (representing luminance change) appears to originate in a distinct area of visual cortex closer to the occipital pole.

Distributed source analysis of the pattern onset visual evoked magnetic response

Distributed source analyses of half-field pattern onset visual evoked magnetic responses (VEMR) were carried out by the authors with a view to locating the source of the largest of the components, the CIIm. The analyses were performed using a series of realistic source spaces taking into account the anatomy of the visual cortex. Accuracy was enhanced by constraining the source distributions to lie within the visual cortex only. Further constraints on the source space yielded reliable, but possibly less meaningful, solutions.

Hemispherical differences in the pattern onset visual evoked magnetic response

Recently, hemispherical asymmetries have been demonstrated for primary visual processing suggesting that basic spatiotemporal features of the stimulus may play a role in the lateralisation effects that have been observed in the human brain. However, to our knowledge no studies have reported hemispheric differences using magnetoencephalography (MEG). Hence, the objective of this study was to determine whether MEG could detect hemispherical asymmetry to the onset of a checkerboard pattern.