Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults

© 2014, The Author(s).Prefrontal dopamine levels are relatively increased in adolescence compared to adulthood. Genetic variation of COMT (COMT Val158Met) results in lower enzymatic activity and higher dopamine availability in Met carriers. Given the dramatic changes of synaptic dopamine during adolescence, it has been suggested that effects of COMT Val158Met genotypes might have oppositional effects in adolescents and adults. The present study aims to identify such oppositional COMT Val158Met effects in adolescents and adults in prefrontal brain networks at rest. Resting state functional connectivity data were collected from cross-sectional and multicenter study sites involving 106 healthy young adults (mean age 24 ± 2.6 years), gender matched to 106 randomly chosen 14-year-olds. We selected the anterior medial prefrontal cortex (amPFC) as seed due to its important role as nexus of the executive control and default mode network. We observed a significant age-dependent reversal of COMT Val158Met effects on resting state functional connectivity between amPFC and ventrolateral as well as dorsolateral prefrontal cortex, and parahippocampal gyrus. Val homozygous adults exhibited increased and adolescents decreased connectivity compared to Met homozygotes for all reported regions. Network analyses underscored the importance of the parahippocampal gyrus as mediator of observed effects. Results of this study demonstrate that adolescent and adult resting state networks are dose-dependently and diametrically affected by COMT genotypes following a hypothetical model of dopamine function that follows an inverted U-shaped curve. This study might provide cues for the understanding of disease onset or dopaminergic treatment mechanisms in major neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder

Geppetto: a reusable modular open platform for exploring neuroscience data and models

Geppetto is an open-source platform that provides generic middleware infrastructure for building both online and desktop tools for visualizing neuroscience models and data and managing simulations. Geppetto underpins a number of neuroscience applications, including Open Source Brain (OSB), Virtual Fly Brain (VFB), NEURON-UI and NetPyNE-UI. OSB is used by researchers to create and visualize computational neuroscience models described in NeuroML and simulate them through the browser. VFB is the reference hub for Drosophila melanogaster neural anatomy and imaging data including neuropil, segmented neurons, microscopy stacks and gene expression pattern data. Geppetto is also being used to build a new user interface for NEURON, a widely used neuronal simulation environment, and for NetPyNE, a Python package for network modelling using NEURON. Geppetto defines domain agnostic abstractions used by all these applications to represent their models and data and offers a set of modules and components to integrate, visualize and control simulations in a highly accessible way. The platform comprises a backend which can connect to external data sources, model repositories and simulators together with a highly customizable frontend.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'

Altered hippocampal morphology in unmedicated patients with major depressive illness

Despite converging evidence that major depressive illness is associated with both memory impairment and hippocampal pathology, findings vary widely across studies and it is not known whether these changes are regionally specific. In the present study we acquired brain MRIs (magnetic resonance images) from 31 unmedicated patients with MDD (major depressive disorder; mean age 39.2±11.9 years; 77% female) and 31 demographically comparable controls. Three-dimensional parametric mesh models were created to examine localized alterations of hippocampal morphology. Although global volumes did not differ between groups, statistical mapping results revealed that in MDD patients, more severe depressive symptoms were associated with greater left hippocampal atrophy, particularly in CA1 (cornu ammonis 1) subfields and the subiculum. However, previous treatment with atypical antipsychotics was associated with a trend towards larger left hippocampal volume. Our findings suggest effects of illness severity on hippocampal size, as well as a possible effect of past history of atypical antipsychotic treatment, which may reflect prolonged neuroprotective effects. This possibility awaits confirmation in longitudinal studies

Emotional aspects of mental time travel

We consider three possible reasons why humans might accord a privileged status to emotional information when mentally traveling backward or forward in time. First, mental simulation of emotional situations helps one to make adaptive decisions. Second, it can serve an emotion regulation function. Third, it helps people to construct and maintain a positive view of the sel

Methodology for Evaluating a Domain-Specific Model Transformation Language

Sobald ein System durch mehrere Modelle beschrieben wird, können sich diese verschiedenen Beschreibungen auch gegenseitig widersprechen. Modelltransformationen sind ein geeignetes Mittel, um das selbst dann zu vermeiden, wenn die Modelle von mehreren Parteien parallel bearbeitet werden. Es gibt mittlerweile reichhaltige Forschungsergebnisse dazu, Änderungen zwischen zwei Modellen zu transformieren. Allerdings ist die Herausforderung, Modelltransformationen zwischen mehr als zwei Modellen zu entwickeln, bislang unzureichend gelöst. Die Gemeinsamkeiten-Sprache ist eine deklarative, domänenspezifische Programmiersprache, mit der multidirektionale Modelltransformationen programmiert werden können, indem bidirektionale Abbildungsspezifikationen kombiniert werden. Da sie bis jetzt jedoch nicht empirisch validiert wurde, stellt es eine offene Frage dar, ob die Sprache dazu geeignet ist, realistische Modelltransformationen zu entwickeln, und welche Vorteile die Sprache gegenüber einer alternativen Programmiersprache für Modelltransformationen bietet. In dieser Abschlussarbeit entwerfe ich eine Fallstudie, mit der die Gemeinsamkeiten-Sprache evaluiert wird. Ich bespreche die Methodik und die Validität dieser Fallstudie. Weiterhin präsentiere ich Kongruenz, eine neue Eigenschaft für bidirektionale Modelltransformationen. Sie stellt sicher, dass die beiden Richtungen einer Transformation zueinander kompatibel sind. Ich leite aus praktischen Beispielen ab, warum wir erwarten können, dass Transformationen normalerweise kongruent sein werden. Daraufhin diskutiere ich die Entwurfsentscheidungen hinter einer Teststrategie, mit der zwei Modelltransformations- Implementierungen, die beide dieselbe Konsistenzspezifikation umsetzen, getestet werden können. Die Teststrategie beinhaltet auch einen praktischen Einsatzzweck von Kongruenz. Zuletzt stelle ich Verbesserungen der Gemeinsamkeiten-Sprache vor. Die Beiträge dieser Abschlussarbeit ermöglichen gemeinsam, eine Fallstudie zu Programmiersprachen für Modelltransformationen umzusetzen. Damit kann ein besseres Verständnis der Vorteile dieser Sprachen erzielt werden. Kongruenz kann die Benutzerfreundlichkeit beliebiger Modelltransformationen verbessern und könnte sich als nützlich herausstellen, um Modelltransformations-Netzwerke zu konstruieren. Die Teststrategie kann auf beliebige Akzeptanztests für Modelltransformationen angewendet werden

Neural Computations Mediating One-Shot Learning in the Human Brain

Incremental learning, in which new knowledge is acquired gradually through trial and error, can be distinguished from one-shot learning, in which the brain learns rapidly from only a single pairing of a stimulus and a consequence. Very little is known about how the brain transitions between these two fundamentally different forms of learning. Here we test a computational hypothesis that uncertainty about the causal relationship between a stimulus and an outcome induces rapid changes in the rate of learning, which in turn mediates the transition between incremental and one-shot learning. By using a novel behavioral task in combination with functional magnetic resonance imaging (fMRI) data from human volunteers, we found evidence implicating the ventrolateral prefrontal cortex and hippocampus in this process. The hippocampus was selectively “switched” on when one-shot learning was predicted to occur, while the ventrolateral prefrontal cortex was found to encode uncertainty about the causal association, exhibiting increased coupling with the hippocampus for high-learning rates, suggesting this region may act as a “switch,” turning on and off one-shot learning as required

Altering speech synthesis prosody through real time natural gestural control

A significant amount of research has been and continues to be undertaken into generating expressive prosody within speech synthesis. Separately, recent developments in HMM-based synthesis (specifically pHTS, developed at University of Mons) provide a platform for reactive speech synthesis, able to react in real time to surroundings or user interaction. Considering both of these elements, this project explores whether it is possible to generate superior prosody in a speech synthesis system, using natural gestural controls, in real time. Building on a previous piece of work undertaken at The University of Edinburgh, a system is constructed in which a user may apply a variety of prosodic effects in real time through natural gestures, recognised by a Microsoft Kinect sensor. Gestures are recognised and prosodic adjustments made through a series of hand-crafted rules (based on data gathered from preliminary experiments), though machine learning techniques are also considered within this project and recommended for future iterations of the work. Two sets of formal experiments are implemented, both of which suggest that - under further development - the system developed may work successfully in a real world environment. Firstly, user tests show that subjects can learn to control the device successfully, adding prosodic effects to the intended words in the majority of cases with practice. Results are likely to improve further as buffering issues are resolved. Secondly, listening tests show that the prosodic effects currently implemented significantly increase perceived naturalness, and in some cases are able to alter the semantic perception of a sentence in an intended way. Alongside this paper, a demonstration video of the project may be found on the accompanying CD, or online at http://tinyurl.com/msc-synthesis. The reader is advised to view this demonstration, as a way of understanding how the system functions and sounds in action

Serial Recall Order and Semantic Features of Category Fluency Words to Study Semantic Memory in Normal Ageing

Copyright © 2021 De Marco, Blackburn and Venneri. Background: Category Fluency Test (CFT) is a common measure of semantic memory (SM). Test performance, however, is also influenced by other cognitive functions. We here propose a scoring procedure that quantifies the correlation between the serial recall order (SRO) of words retrieved during the CFT and a number of linguistic features, to obtain purer SM measures. To put this methodology to the test, we addressed a proof-of-concept hypothesis whereby, in alignment with the literature, older adults would show better SM. Methods: Ninety participants (45 aged 18–21 years; 45 aged 70–81 years) with normal neurological and cognitive functioning completed a 1-min CFT. SRO was scored as an ordinal variable incrementing by one unit for each valid entry. Each word was also scored for 16 additional linguistic features. Participant-specific normalised correlation coefficients were calculated between SRO and each feature and were analysed with group comparisons and graph theory. Results: Younger adults showed more negative correlations between SRO and “valence” (a feature of words pleasantness). This was driven by the first five words generated. When analysed with graph theory, SRO had significantly higher degree and lower betweenness centrality among older adults. Conclusion: In older adults, SM relies significantly less on pleasantness of entries typically retrieved without semantic control. Moreover, graph-theory metrics indicated better optimised links between SRO and linguistic features in this group. These findings are aligned with the principle whereby SM processes tend to solidify with ageing. Although additional work is needed in support of an SRO-based item-level scoring procedure of CFT performance, these initial findings suggest that this methodology could be of help in characterising SM in a purer form.Neurocare (United Kingdom), Grant agreement No. 181924 to MDM and AV; Alzheimer’s Research United Kingdom, Pump Priming Grant scheme to MDM

Topics in Programming Languages, a Philosophical Analysis through the case of Prolog

[EN]Programming languages seldom find proper anchorage in philosophy of logic, language and science. is more, philosophy of language seems to be restricted to natural languages and linguistics, and even philosophy of logic is rarely framed into programming languages topics. The logic programming paradigm and Prolog are, thus, the most adequate paradigm and programming language to work on this subject, combining natural language processing and linguistics, logic programming and constriction methodology on both algorithms and procedures, on an overall philosophizing declarative status. Not only this, but the dimension of the Fifth Generation Computer system related to strong Al wherein Prolog took a major role. and its historical frame in the very crucial dialectic between procedural and declarative paradigms, structuralist and empiricist biases, serves, in exemplar form, to treat straight ahead philosophy of logic, language and science in the contemporaneous age as well. In recounting Prolog's philosophical, mechanical and algorithmic harbingers, the opportunity is open to various routes. We herein shall exemplify some: - the mechanical-computational background explored by Pascal, Leibniz, Boole, Jacquard, Babbage, Konrad Zuse, until reaching to the ACE (Alan Turing) and EDVAC (von Neumann), offering the backbone in computer architecture, and the work of Turing, Church, Gödel, Kleene, von Neumann, Shannon, and others on computability, in parallel lines, throughly studied in detail, permit us to interpret ahead the evolving realm of programming languages. The proper line from lambda-calculus, to the Algol-family, the declarative and procedural split with the C language and Prolog, and the ensuing branching and programming languages explosion and further delimitation, are thereupon inspected as to relate them with the proper syntax, semantics and philosophical élan of logic programming and Prolog