A P300 Based Cognitive Assessment Battery for Severely Motor-impaired and Overtly Non-responsive Patients

Diagnosing disorders of consciousness (DOC) is notoriously difficult, with estimates of misdiagnosis rates as high as 40%. Moreover, recent studies have demonstrated that patients who do not show signs of volitional motor responses can exhibit preserved command following detected by functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Although these patients clearly retain some cognitive abilities, lack of consistent motor responses makes administration of standard neuropsychological tests impossible. Consequently, the extent of their cognitive function is unknown. In the current study, we developed and validated a P300b event related potential (ERP) neuropsychological battery in healthy participants to assess components of executive function without requiring motor output. First, participants were instructed to attend to a target auditory stimulus. P300b responses to attended relative to unattended stimuli were used as a neural proxy for detecting command following. To assess working memory capacity we adapted a digit span test to use a similar P300b response mechanism. Finally, reasoning was assessed by adapting a verbal reasoning task in the same manner. At the group level, and in a large majority of participants at the single-participant level, accurate performance could be detected using the P300b ERP, validating the potential utility of the battery. Additionally, the normalized magnitude of the P300b predicted individual differences in performance, but only when a suitable level of variability between participants was present. A post hoc Monte Carlo analysis was conducted to examine the necessary time required to conduct the battery as well as the interaction between time and performance in determining statistically significant performance. At 100% accuracy, a mean time of five minutes was required to achieve a significant result, with time increasing as a function of decreasing performance. These results demonstrate that covert control of attention, as measured by the P300b ERP, can be used to assess command following, working memory and reasoning abilities with a high degree of reliabilit

GrassPlot v. 2.00 – first update on the database of multi-scale plant diversity in Palaearctic grasslands

Abstract: GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). Following a previous Long Database Report (Dengler et al. 2018, Phyto- coenologia 48, 331–347), we provide here the first update on content and functionality of GrassPlot. The current version (GrassPlot v. 2.00) contains a total of 190,673 plots of different grain sizes across 28,171 independent plots, with 4,654 nested-plot series including at least four grain sizes. The database has improved its content as well as its functionality, including addition and harmonization of header data (land use, information on nestedness, structure and ecology) and preparation of species composition data. Currently, GrassPlot data are intensively used for broad-scale analyses of different aspects of alpha and beta diversity in grassland ecosystems

The Evolution of Combinatorial Gene Regulation in Fungi

It is widely suspected that gene regulatory networks are highly plastic. The rapid turnover of transcription factor binding sites has been predicted on theoretical grounds and has been experimentally demonstrated in closely related species. We combined experimental approaches with comparative genomics to focus on the role of combinatorial control in the evolution of a large transcriptional circuit in the fungal lineage. Our study centers on Mcm1, a transcriptional regulator that, in combination with five cofactors, binds roughly 4% of the genes in Saccharomyces cerevisiae and regulates processes ranging from the cell-cycle to mating. In Kluyveromyces lactis and Candida albicans, two other hemiascomycetes, we find that the Mcm1 combinatorial circuits are substantially different. This massive rewiring of the Mcm1 circuitry has involved both substantial gain and loss of targets in ancient combinatorial circuits as well as the formation of new combinatorial interactions. We have dissected the gains and losses on the global level into subsets of functionally and temporally related changes. One particularly dramatic change is the acquisition of Mcm1 binding sites in close proximity to Rap1 binding sites at 70 ribosomal protein genes in the K. lactis lineage. Another intriguing and very recent gain occurs in the C. albicans lineage, where Mcm1 is found to bind in combination with the regulator Wor1 at many genes that function in processes associated with adaptation to the human host, including the white-opaque epigenetic switch. The large turnover of Mcm1 binding sites and the evolution of new Mcm1–cofactor interactions illuminate in sharp detail the rapid evolution of combinatorial transcription networks

Prion-like domain mutations in hnRNPs cause multisystem proteinopathy and ALS

Summary Algorithms designed to identify canonical yeast prions predict that ~250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbor a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood. Here, we define pathogenic mutations in PrLDs of hnRNPA2/B1 and hnRNPA1 in families with inherited degeneration affecting muscle, brain, motor neuron and bone, and a case of familial ALS. Wild-type hnRNPA2 and hnRNPA1 display an intrinsic tendency to assemble into self-seeding fibrils, which is exacerbated by the disease mutations. Indeed, the pathogenic mutations strengthen a ‘steric zipper’ motif in the PrLD, which accelerates formation of self-seeding fibrils that cross-seed polymerization of wild-type hnRNP. Importantly, the disease mutations promote excess incorporation of hnRNPA2 and hnRNPA1 into stress granules and drive the formation of cytoplasmic inclusions in animal models that recapitulate the human pathology. Thus, dysregulated polymerization caused by a potent mutant ‘steric zipper’ motif in a PrLD can initiate degenerative disease. Related proteins with PrLDs must be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone

Stochastic Resonance Modulates Neural Synchronization within and between Cortical Sources

Neural synchronization is a mechanism whereby functionally specific brain regions establish transient networks for perception, cognition, and action. Direct addition of weak noise (fast random fluctuations) to various neural systems enhances synchronization through the mechanism of stochastic resonance (SR). Moreover, SR also occurs in human perception, cognition, and action. Perception, cognition, and action are closely correlated with, and may depend upon, synchronized oscillations within specialized brain networks. We tested the hypothesis that SR-mediated neural synchronization occurs within and between functionally relevant brain areas and thus could be responsible for behavioral SR. We measured the 40-Hz transient response of the human auditory cortex to brief pure tones. This response arises when the ongoing, random-phase, 40-Hz activity of a group of tuned neurons in the auditory cortex becomes synchronized in response to the onset of an above-threshold sound at its “preferred” frequency. We presented a stream of near-threshold standard sounds in various levels of added broadband noise and measured subjects' 40-Hz response to the standards in a deviant-detection paradigm using high-density EEG. We used independent component analysis and dipole fitting to locate neural sources of the 40-Hz response in bilateral auditory cortex, left posterior cingulate cortex and left superior frontal gyrus. We found that added noise enhanced the 40-Hz response in all these areas. Moreover, added noise also increased the synchronization between these regions in alpha and gamma frequency bands both during and after the 40-Hz response. Our results demonstrate neural SR in several functionally specific brain regions, including areas not traditionally thought to contribute to the auditory 40-Hz transient response. In addition, we demonstrated SR in the synchronization between these brain regions. Thus, both intra- and inter-regional synchronization of neural activity are facilitated by the addition of moderate amounts of random noise. Because the noise levels in the brain fluctuate with arousal system activity, particularly across sleep-wake cycles, optimal neural noise levels, and thus SR, could be involved in optimizing the formation of task-relevant brain networks at several scales under normal conditions

HTLV-1 infection: a dynamic struggle between viral persistence and host immunity

Human T-lymphotropic virus type I (HTLV-I) causes chronic infection for which there is no cure or neutralising vaccine. HTLV-I has been clinically linked to the development of adult T-cell leukaemia/lymphoma (ATL), an aggressive blood cancer, and HAM/TSP, a progressive neurological and inflammatory disease. Infected individuals typically mount a large, persistently activated CD8+ cytotoxic T-lymphocyte (CTL) response against HTLV-I-infected cells, but ultimately fail to effectively eliminate the virus. Moreover, the identification of determinants to disease manifestation has thus far been elusive.\ud \ud A key issue in current HTLV-I research is to better understand the dynamic interaction between persistent infection by HTLV-I and virus-specific host immunity. Recent experimental hypotheses for the persistence of HTLV-I in vivo have led to the development of mathematical models illuminating the balance between proviral latency and activation in the target cell population. We investigate the role of a constantly changing anti-viral immune environment acting in response to the effects of infected T-cell activation and subsequent viral expression. The resulting model is a four-dimensional, non-linear system of ordinary differential equations that describes the dynamic interactions among viral expression, infected target cell activation, and the HTLV-I-specific CTL response. The global dynamics of the model is established through the construction of appropriate Lyapunov functions. Examining the particular roles of viral expression and host immunity during the chronic phase of HTLV-I infection offers important insights regarding the evolution of viral persistence and proposes a hypothesis for pathogenesis

Two ballet scenes for The Masque of the Red Death

Thesis (M.M.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at [email protected]. Thank you.This project is part of an adaptation of Edgar Alan Poe's short story "The Masque of the Red Death" into a ballet. The music is scored for a chamber orchestra with single winds and brass, piano, two percussionists, and string quintet. The two scenes presented herein are the opening two of the ballet. The first scene ("The Red Death Had Long Devastated the Country") depicts the eponymous disease consuming the population. In the second scene ("The Prince Prospero & the March to the Walled Abbey") Prospero attempts to ignore the plague and retire to his walled abbey. While his message is beautiful on its own, it is in constant disharmony with the world in which he now lives. The music reflects tlus, with the Prince often in the wrong key. The scene concludes with the Prince and his knaves marching to the abbey

Subversiver Messianismus : interdisziplinäre Agamben-Lektüren

Dieselbe Welt – und doch alles anders. Dies könnte eine knappe Formel für das sein, was der italienische Philosoph Giorgio Agamben in seinen Studien freizulegen sucht: Kategorien eines neuen Denkens, eines anderen Gebrauchs und einer Lebens-Form, in denen das natürliche Leben nicht vom sozialen Leben getrennt werden kann und in denen die Logik des Ausschlusses und die Gewalt der Herrschaft außer Kraft gesetzt sind, die unsere Welt in Bann halten. Ausgehend vom letzten Band des Homo-Sacer-Projekts zeichnen die Studien dieses Bandes Agambens Suche nach einer „destituierenden Kraft“ nach, die einen Ausweg aus dem Ausnahmezustand öffnet, in dem wir leben. Ein solcher „subversiver Messianismus“ bewegt sich zwischen Politik und Theologie, Ontologie und Poesie; er arbeitet sich archäologisch durch die griechischen und römischen, jüdischen und christlichen Wurzeln westlicher Kultur, um sie in überraschenden Konstellationen einem neuen Gebrauch zuzuführen

Exclusive electroproduction of vector mesons in lepton nucleon scattering at the HERMES experiment

Exclusive electroproduction of vector mesons has been measured on hydrogen and deuterium targets at HERMES using the 27.6 GeV electron/positron beam of HERA. From this process, information can be obtained about generalized parton distributions (GPDs), which provide a unified description of the structure of hadrons embedding longitudinal-momentum distributions (ordinary PDFs) and transverse-position information (form factors). The study of the azimuthal distribution of the decay products via spin-density matrix elements provide constraints on helicity-amplitudes used to describe exclusive vector-meson production. Recent results from the HERMES experiment on the production of ρ0, ω and ϕ vector mesons will be presented