1,720,979 research outputs found
COMT as a drug target for cognitive functions and dysfunctions.
No full textCatechol-O-methyltransferase (COMT) is a promising target for modulation of cognitive functions and dysfunctions. COMT dominates the regulation of dopamine metabolism in the prefrontal cortex. Thus, COMT effects are particularly evident in prefrontal cortex-dependent cognitive functions including executive control, working memory, attentional control and long-term memory. This has been determined by both genetic and pharmacological studies that we will highlight in the present review. In particular, we will discuss how common functional variants of the COMT gene may predict individual variation in selective cognitive abilities and vulnerability to cognitive deficits that characterize several neuropsychiatric disorders. Moreover, COMT genetic variants represent one source of individual differences in the cognitive responses to medications such as those used in psychiatric illnesses. COMT genetic testing may then predict some cognitive dysfunctions often seen in certain psychiatric illnesses even from presymptomatic stages and the efficacy/dosage of drugs used to treat them. The consideration of COMT-dependent differences may be important for the development of more efficient personalized healthcare
The Ultimate Intra-/Extra-dimensional Attentional Set-Shifting Task for Mice.
No full textBACKGROUND:
Alterations in executive control and cognitive flexibility, such as attentional set-shifting abilities, are core features of several neuropsychiatric diseases. The most widely used neuropsychological tests for the evaluation of attentional set shifting in humans are the Wisconsin Card Sorting Test and the Cambridge Neuropsychological Test Automated Battery Intra-/Extra-Dimensional set-shift task (ID/ED). These tasks have proven clinical relevance and have been successfully adapted for monkeys. However, similar tasks currently available for rodents are limited, mainly because of their manual-based testing procedures. The current limitations of rodent attentional set-shifting tasks are hampering translational advances in psychiatric medicine.
METHODS:
To closely mimic the Cambridge Neuropsychological Test Automated Battery ID/ED task in primates, we present the development of a novel operant-based two-chamber ID/ED "Operon" task for mice.
RESULTS:
We show the ability of this novel task to measure attentional set shifting in mice and the effects of genetic and pharmacologic manipulations of dopamine and glutamate. In genetically modified mice with reduced catechol-O-methyltransferase activity there was selective improvement on extradimensional shift abilities and impairment of serial reversal learning. Chronic administration of phencyclidine produced a selective impairment of extradimensional shift while producing a generalized decrease in latency to respond.
CONCLUSIONS:
We demonstrate that this novel ID/ED Operon task may be an effective preclinical tool for drug testing and large genetic screening relevant to the study of executive dysfunctions and cognitive symptoms of psychiatric disorders. These findings may help elucidate the biological validity of similar findings in humans
NMDA and AMPA Receptor Autoantibodies in Brain Disorders: From Molecular Mechanisms to Clinical Features
No full textThe role of autoimmunity in central nervous system (CNS) disorders is rapidly expanding. In the last twenty years, different types of autoantibodies targeting subunits of ionotropic glutamate receptors have been found in a variety of patients affected by brain disorders. Several of these antibodies are directed against NMDA receptors (NMDAR), mostly in autoimmune encephalitis, whereas a growing field of research has identified antibodies against AMPA receptor (AMPAR) subunits in patients with different types of epilepsy or frontotemporal dementia. Several in vitro and in vivo studies performed in the last decade have dramatically improved our understanding of the molecular and functional effects induced by both NMDAR and AMPAR autoantibodies at the excitatory glutamatergic synapse and, consequently, their possible role in the onset of clinical symptoms. In particular, the method by which autoantibodies can modulate the localization at synapses of specific target subunits leading to functional impairments and behavioral alterations has been well addressed in animal studies. Overall, these preclinical studies have opened new avenues for the development of novel pharmacological treatments specifically targeting the synaptic activation of ionotropic glutamate receptors
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe 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
Full text linkWe 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
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