Are pathological lesions in neurodegenerative disorders the cause or the effect of the degeneration?

Pathological lesions in the form of extracellular protein deposits, intracellular inclusions and changes in cell morphology occur in the brain in the majority of neurodegenerative disorders. Studies of the presence, distribution, and molecular determinants of these lesions are often used to define individual disorders and to establish the mechanisms of lesion pathogenesis. In most disorders, however, the relationship between the appearance of a lesion and the underlying disease process is unclear. Two hypotheses are proposed which could explain this relationship: (i) lesions are the direct cause of the observed neurodegeneration ('causal' hypothesis); and (ii) lesions are a reaction to neurodegeneration ('reaction' hypothesis). These hypotheses are considered in relation to studies of the morphology and molecular determinants of lesions, the effects of gene mutations, degeneration induced by head injury, the effects of experimentally induced brain lesions, transgenic studies and the degeneration of anatomical pathways. The balance of evidence suggests that in many disorders, the appearance of the pathological lesions is a reaction to degenerative processes rather than being their cause. Such a conclusion has implications both for the classification of neurodegenerative disorders and for studies of disease pathogenesis.

Language against the odds, or rather not:the weak central coherence hypothesis and language

EV is a child with a talent for learning language combined with Asperger syndrome. EV’s talent is evident in the unusual circumstances of her acquisition of both her first (Bulgarian) and second (German) languages and the unique patterns of both receptive and expressive language (in both the L1 and L2), in which she shows subtle dissociations in competence and performance consistent with an uneven cognitive profile of skills and abilities. We argue that this case provides support for theories of language learning and usage that require more general underlying cognitive mechanisms and skills. One such account, the Weak Central Coherence (WCC) hypothesis of autism, provides a plausible framework for the interpretation of the simultaneous co-occurrence of EV’s particular pattern of cognitive strengths and weaknesses. Furthermore, we show that specific features of the uneven cognitive profile of Asperger syndrome can help explain the observed language talent displayed by EV. Thus, rather than demonstrating a case where language learning takes place despite the presence of deficits, EV’s case illustrates how a pattern of strengths within this profile can specifically promote language learning.

Does the neurodegeneration of Alzheimer’s disease spread between visual cortical regions B17 and B18 via the feedforward or feedback short cortico-cortical projections?

The laminar distribution of senile plaques (SP) and neurofibrillary tangles (NFT) was studied in areas B17 and B18 of the visual cortex in 18 cases of Alzheimer’s disease which varied in disease onset and duration. The objective was to test the hypothesis that SP and NFT could spread via either the feedforward or feedback short cortico-cortical projections. In area B17, the mean density of SP and NFT reached a maximum in lamina III and in laminae II and III respectively. In B18, mean SP density was maximal in laminae III and IV and NFT density in laminae II and III. No significant correlations were observed in any cortical lamina between the density of SP and patient age. However, the density of NFT in laminae III, IV and VI in B18 was negatively correlated with patient age. In addition, in B18, the density of SP in lamina II and lamina V was negatively correlated with disease duration and disease onset respectively. Although these results suggest that SP and NFT might spread between B17 and B18 via the feedforward short cortico-cortical projections, it is also possible that the longer cortico-cortical and cortico-subcortical connections may be involved.

'Compliance or contradiction'? Teaching 'History' in the 'New' Ukraine. A view from Ukraine's Eastern borderlands

Whilst much academic rigour has been devoted to analysing the ‘contents’ of historical textbooks in Ukraine, this article examines the teacher's role in the ‘transfer’ of the state's message to schoolchildren. This article demonstrates that in Ukraine's eastern borderlands teachers are highly active in negotiating the new historical narrative. Teachers are found to subtly change the accent or focus away from the ‘nationalist’ stance towards Russia, as found in the school history textbooks, to a more tolerant stance which aims to promote rather than negate Ukraine's historical interactions with Russia. Thus, this simultaneously reinforces a particular ‘regional’ understanding of historical events.

On the 'classification' of neurodegenerative disorders:discrete entities, overlap or continuum?

The traditional method of classifying neurodegenerative diseases is based on the original clinico-pathological concept supported by 'consensus' criteria and data from molecular pathological studies. This review discusses first, current problems in classification resulting from the coexistence of different classificatory schemes, the presence of disease heterogeneity and multiple pathologies, the use of 'signature' brain lesions in diagnosis, and the existence of pathological processes common to different diseases. Second, three models of neurodegenerative disease are proposed: (1) that distinct diseases exist ('discrete' model), (2) that relatively distinct diseases exist but exhibit overlapping features ('overlap' model), and (3) that distinct diseases do not exist and neurodegenerative disease is a 'continuum' in which there is continuous variation in clinical/pathological features from one case to another ('continuum' model). Third, to distinguish between models, the distribution of the most important molecular 'signature' lesions across the different diseases is reviewed. Such lesions often have poor 'fidelity', i.e., they are not unique to individual disorders but are distributed across many diseases consistent with the overlap or continuum models. Fourth, the question of whether the current classificatory system should be rejected is considered and three alternatives are proposed, viz., objective classification, classification for convenience (a 'dissection'), or analysis as a continuum.

Statistical guidelines for the analysis of data obtained from one or both eyes

Purpose - Measurements obtained from the right and left eye of a subject are often correlated whereas many statistical tests assume observations in a sample are independent. Hence, data collected from both eyes cannot be combined without taking this correlation into account. Current practice is reviewed with reference to articles published in three optometry journals, viz., Ophthalmic and Physiological Optics (OPO), Optometry and Vision Science (OVS), Clinical and Experimental Optometry (CEO) during the period 2009–2012. Recent findings - Of the 230 articles reviewed, 148/230 (64%) obtained data from one eye and 82/230 (36%) from both eyes. Of the 148 one-eye articles, the right eye, left eye, a randomly selected eye, the better eye, the worse or diseased eye, or the dominant eye were all used as selection criteria. Of the 82 two-eye articles, the analysis utilized data from: (1) one eye only rejecting data from the adjacent eye, (2) both eyes separately, (3) both eyes taking into account the correlation between eyes, or (4) both eyes using one eye as a treated or diseased eye, the other acting as a control. In a proportion of studies, data were combined from both eyes without correction. Summary - It is suggested that: (1) investigators should consider whether it is advantageous to collect data from both eyes, (2) if one eye is studied and both are eligible, then it should be chosen at random, and (3) two-eye data can be analysed incorporating eyes as a ‘within subjects’ factor.

Build-up of auditory stream segregation induced by tone sequences of constant or alternating frequency and the resetting effects of single deviants

A sequence of constant-frequency tones can promote streaming in a subsequent sequence of alternating-frequency tones, but why this effect occurs is not fully understood and its time course has not been investigated. Experiment 1 used a 2.0-s-long constant-frequency inducer (10 repetitions of a low-frequency pure tone) to promote segregation in a subsequent, 1.2-s test sequence of alternating low- and high-frequency tones. Replacing the final inducer tone with silence substantially reduced reported test-sequence segregation. This reduction did not occur when either the 4th or 7th inducer was replaced with silence. This suggests that a change at the induction/test-sequence boundary actively resets build-up, rather than less segregation occurring simply because fewer inducer tones were presented. Furthermore, Experiment 2 found that a constant-frequency inducer produced its maximum segregation-promoting effect after only three tones—this contrasts with the more gradual build-up typically observed for alternating-frequency sequences. Experiment 3 required listeners to judge continuously the grouping of 20-s test sequences. Constant-frequency inducers were considerably more effective at promoting segregation than alternating ones; this difference persisted for ~10 s. In addition, resetting arising from a single deviant (longer tone) was associated only with constant-frequency inducers. Overall, the results suggest that constant-frequency inducers promote segregation by capturing one subset of test-sequence tones into an ongoing, preestablished stream, and that a deviant tone may reduce segregation by disrupting this capture. These findings offer new insight into the dynamics of stream segregation, and have implications for the neural basis of streaming and the role of attention in stream formation. (PsycINFO Database Record (c) 2013 APA, all rights reserved)

The United Kingdom between Mars and Venus:bridge or Bermuda triangle?

The concept of the United Kingdom acting as a bridge between Europe and the United States has been a key element in British foreign policy for six decades. Under the second Blair Premiership it reached both its apogee and its nadir. This paper analyses these developments focusing both on the transatlantic and European ends. Particular attention is paid to the failure of the Blair government either to establish a secure place for Britain as a co-leader or to make the British people more comfortable in their European skins. This failure occurred at a period when the EU is characterised by leadership transition and confusion. New leaderships will emerge in the EU over the next two years but it seems unlikely that Britain, characterised by a continuing disconnect between a Euro-sceptic public discourse and deep involvement at a governmental level will develop a European policy narrative that is regarded as convincing at either the EU or domestic level. This weakness is compounded by a failure to develop new thinking about the rise of new powers such as China and India.

Build-up of auditory stream segregation induced by tone sequences of constant or alternating frequency and the resetting effects of single deviants

A sequence of constant-frequency tones can promote streaming in a subsequent sequence of alternating-frequency tones, but why this effect occurs is not fully understood and its time course has not been investigated. Experiment 1 used a 2.0-s-long constant-frequency inducer (10 repetitions of a low-frequency pure tone) to promote segregation in a subsequent, 1.2-s test sequence of alternating low- and high-frequency tones. Replacing the final inducer tone with silence substantially reduced reported test-sequence segregation. This reduction did not occur when either the 4th or 7th inducer was replaced with silence. This suggests that a change at the induction/test-sequence boundary actively resets build-up, rather than less segregation occurring simply because fewer inducer tones were presented. Furthermore, Experiment 2 found that a constant-frequency inducer produced its maximum segregation-promoting effect after only three tones—this contrasts with the more gradual build-up typically observed for alternating-frequency sequences. Experiment 3 required listeners to judge continuously the grouping of 20-s test sequences. Constant-frequency inducers were considerably more effective at promoting segregation than alternating ones; this difference persisted for ~10 s. In addition, resetting arising from a single deviant (longer tone) was associated only with constant-frequency inducers. Overall, the results suggest that constant-frequency inducers promote segregation by capturing one subset of test-sequence tones into an ongoing, preestablished stream, and that a deviant tone may reduce segregation by disrupting this capture. These findings offer new insight into the dynamics of stream segregation, and have implications for the neural basis of streaming and the role of attention in stream formation. (PsycINFO Database Record (c) 2013 APA, all rights reserved)

Build-up of auditory stream segregation induced by tone sequences of constant or alternating frequency and the resetting effects of single deviants

Three experiments investigated the dynamics of auditory stream segregation. Experiment 1 used a 2.0-s constant-frequency inducer (10 repetitions of a low-frequency pure tone) to promote segregation in a subsequent, 1.2-s test sequence of alternating low- and high-frequency tones. Replacing the final inducer tone with silence reduced reported test-sequence segregation substantially. This reduction did not occur when either the 4th or 7th inducer was replaced with silence. This suggests that a change at the induction/test-sequence boundary actively resets buildup, rather than less segregation occurring simply because fewer inducer tones were presented. Furthermore, Experiment 2 found that a constant-frequency inducer produced its maximum segregation-promoting effect after only 3 tone cycles - this contrasts with the more gradual build-up typically observed for alternating sequences. Experiment 3 required listeners to judge continuously the grouping of 20-s test sequences. Constant-frequency inducers were considerably more effective at promoting segregation than alternating ones; this difference persisted for ∼10 s. In addition, resetting arising from a single deviant (longer tone) was associated only with constant-frequency inducers. Overall, the results suggest that constant-frequency inducers promote segregation by capturing one subset of test-sequence tones into an on-going, pre-established stream and that a deviant tone may reduce segregation by disrupting this capture. © 2013 Acoustical Society of America.