1,721,037 research outputs found
Why musical memory can be preserved in advanced Alzheimer's disease
Get PDFMusical memory is relatively preserved in Alzheimer's disease and other dementias. In a 7 Tesla functional MRI study employing multi-voxel pattern analysis, Jacobsen et al. identify brain regions encoding long-term musical memory in young healthy controls, and show that these same regions display relatively little atrophy and hypometabolism in patients with Alzheimer's disease.See Clark and Warren (doi:10.1093/brain/awv148) for a scientific commentary on this article.
Musical memory is relatively preserved in Alzheimer's disease and other dementias. In a 7 Tesla functional MRI study employing multi-voxel pattern analysis, Jacobsen et al. identify brain regions encoding long-term musical memory in young healthy controls, and show that these same regions display relatively little atrophy and hypometabolism in patients with Alzheimer's disease.See Clark and Warren (doi:10.1093/awv148) for a scientific commentary on this article
Crowdsourcing reproducible seizure forecasting in human and canine epilepsy
Get PDFAccurate forecasting of epileptic seizures has the potential to transform clinical epilepsy care. However, progress toward reliable seizure forecasting has been hampered by lack of open access to long duration recordings with an adequate number of seizures for investigators to rigorously compare algorithms and results. A seizure forecasting competition was conducted on kaggle.com using open access chronic ambulatory intracranial electroencephalography from five canines with naturally occurring epilepsy and two humans undergoing prolonged wide bandwidth intracranial electroencephalographic monitoring. Data were provided to participants as 10-min interictal and preictal clips, with approximately half of the 60 GB data bundle labelled (interictal/preictal) for algorithm training and half unlabelled for evaluation. The contestants developed custom algorithms and uploaded their classifications (interictal/preictal) for the unknown testing data, and a randomly selected 40% of data segments were scored and results broadcasted on a public leader board. The contest ran from August to November 2014, and 654 participants submitted 17 856 classifications of the unlabelled test data. The top performing entry scored 0.84 area under the classification curve. Following the contest, additional held-out unlabelled data clips were provided to the top 10 participants and they submitted classifications for the new unseen data. The resulting area under the classification curves were well above chance forecasting, but did show a mean 6.54 ± 2.45% (min, max: 0.30, 20.2) decline in performance. The kaggle.com model using open access data and algorithms generated reproducible research that advanced seizure forecasting. The overall performance from multiple contestants on unseen data was better than a random predictor, and demonstrates the feasibility of seizure forecasting in canine and human epilepsy
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Genetic and chemogenetic investigation of the circuits underlying schizophrenia-related behaviours in mice
Get PDFMultiple neurotransmitter systems have been implicated in the pathophysiology of schizophrenia. In particular, changes in the GABAergic and glutamatergic system could be upstream to changes in the dopamine system, and also responsible for the cognitive and negative symptoms of the disease.
This thesis has utilised genetic models of glutamatergic dysfunction, both globally in mice lacking the GluA1 AMPAR subunit (Gria1 KO), and in a circuit specific manner in mice lacking the NR1 NMDAR subunit specifically in parvalbumin (PV) positive interneurons (Grin1ΔPV). In addition, the chemogenetic DREADD silencer hM4Di was used to transiently and specifically silence PV positive interneurons in vivo. These genetic and chemogenetic manipulations have been used in combination with behavioural assays that could assess schizophrenia-relevant behaviours in rodents.
Grin1ΔPV animals were found to be largely normal when tested for schizophrenia-relevant behavioural abnormalities. However, when Grin1ΔPV animals were challenged with the NMDAR antagonist MK-801 (commonly used to pharmacologically model glutamatergic dysfunction) there was clear behavioural divergence between Grin1ΔPV and control animals. In contrast to previous reports, Grin1ΔPV mice appeared to be sensitised to the effects of MK-801. This has important implications for the understanding of how NMDAR antagonists can induce schizophrenia-relevant behavioural deficits in rodents.
Hypofunction of PV interneurons, particularly in the hippocampus, is predicted to underlie schizophrenia-relevant behavioural deficits. To directly test this, hM4Di was expressed in PV interneurons in the dorsal or ventral hippocampus, preferentially in area CA1. Despite the fact that hM4Di was capable of reducing the excitability of PV interneurons in vitro, there was no evidence that silencing of PV interneurons in CA1 in vivo could induce the predicted behavioural deficits.
Gria1 KO mice have a well established behavioural phenotype that could be relevant to schizophrenia. A viral-rescue approach was utilised to reintroduce GluA1 preferentially into area CA3 of the hippocampus of Gria1 KO animals. This was sufficient to rescue novelty induced hyperactivity and spatial novelty preference but not spatial working memory in Gria1 KO animals. Recordings of local field potentials (LFP) in the dorsal hippocampus revealed enhanced theta power oscillations in Gria1 KO mice. This elevated theta power was also rescued by GluA1 re-introduction into area CA3 of Gria1 KO mice.
Together these experiments question the hypothesis that NMDAR antagonists preferentially exert their effects through NMDARs on PV interneurons. In addition, with respect to schizophrenia-related behavioural deficits, hypofunction of PV interneurons in area CA1 of the hippocampus might not be be as critical as hypofunction of PV interneurons in other circuits. Finally, area CA3 of the hippocampus is implicated as a brain region in which GluA1 expression appears particularly important for some behaviours relevant to schizophrenia.</p
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Assessing Homeostatic Plasticity in Genetic and Acquired Epilepsies
Get PDFHomeostatic plasticity allows the brain to correct deviations from physiological levels of activity to maintain long term stability. Despite this remarkable level of control, epilepsy is a disease characterized by both cellular and circuit hyperexcitability that homeostatic plasticity seemingly fails to suppress. In this thesis, I demonstrate that during both acquired and genetic epileptogenesis, neurons display numerous changes consistent with homeostatic responses to nascent hyperactivity and that early stages of genetic epileptogenesis are characterized by increased levels of homeostatic response.
In Dravet syndrome, a severe genetic epilepsy of infancy, loss-of-function mutations to the voltage-gated sodium channel NaV1.1 are found in the majority of patients. These mutations generate network hyperactivity due to loss of inhibitory interneuron excitability. Using a mouse model of Dravet, I demonstrate that the first cells to display altered intrinsic properties may in fact be excitatory pyramidal cells. I demonstrate that both diminished intrinsic excitability and increased responsiveness to altered activity levels are seen in pyramidal cells at early stages of Dravet. I then show that the later onset of inhibitory hypofunction generates synaptic excitation/inhibition imbalance and hyperactivity. This hyperactivity appears to drive diminished intrinsic excitability and synaptic downscaling in pyramidal cells, amongst other changes consistent with homeostatic plasticity.
I also demonstrate the viability of a future approach to better assess homeostatic responses to models of acquired epileptogenesis. This approach can contribute to answering the much debated questions about both the pathophysiology of acquired epilepsy and the much understudied mechanisms of homeostatic responses to hyperactivity
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