Mass for Plasma Photons from Gauge Symmetry Breaking

We derive the effective masses for photons in unmagnetized plasma waves using a quantum field theory with two vector fields (gauge fields). In order to properly define the quantum field degrees of freedom we re-derive the classical wave equations on light-front gauge. This is needed because the usual scalar potential of electromagnetism is, in quantum field theory, not a physical degree of freedom that renders negative energy eigenstates. We also consider a background local fluid metric that allows for a covariant treatment of the problem. The different masses for the longitudinal (plasmon) and transverse photons are in our framework due to the local fluid metric. We apply the mechanism of mass generation by gauge symmetry breaking recently proposed by the authors by giving a non-trivial vacuum-expectation-value to the second vector field (gauge field). The Debye length $\lambda_D$ is interpreted as an effective compactification length and we compute an explicit solution for the large gauge transformations that correspond to the specific mass eigenvalues derived here. Using an usual quantum field theory canonical quantization we obtain the usual results in the literature. Although none of these ingredients are new to physicist, as far as the authors are aware it is the first time that such constructions are applied to Plasma Physics. Also we give a physical interpretation (and realization) for the second vector field in terms of the plasma background in terms of known physical phenomena. Addendum: It is given a short proof that equation (10) is wrong, therefore equations (12-17) are meaningless. The remaining results are correct being generic derivations for nonmagnetized plasmas derived in a covariant QFT framework.Comment: v1: 1+6 pages v2: Several discussions rewritten; Abstract rewritten; References added; v3: includes Addendu

U_e(1)xU_g(1) Actions in 2+1-Dimensions: Full Vectorial Electric and Magnetic Fields

It is considered a dimensional reduction of Ue(1)xUg(1) 3+1-dimensional electromagnetism with a gauge field (photon) and a pseudo-vector gauge field (pseudo-photon) to 2+1-dimensions. In the absence of boundary effects, the quantum structure is maintained, while when boundary effects are considered, as have been previously studied, a cross Chern-Simons term between both gauge fields is present, which accounts for topological effects and changes the quantum structure of the theory. Our construction maintains the dimensional reduced action invariant under parity (P) and time-inversion (T). We show that the theory has two massive degrees of freedom, corresponding to the longitudinal modes of the photon and of the pseudo-photon and briefly discuss the quantization procedures of the theory in the topological limit (wave functional quantization) and perturbative limit (an effective dynamical current theory), pointing out directions to solve the constraints and deal with the negative energy contributions from pseudo-photons. We recall that the physical interpretation of the fields in the planar system is new and is only meaningful in the context of Ue(1)xUg(1) electromagnetism. In this work it is shown that all the six electromagnetic vectorial fields components are present in the dimensional reduced theory and that, independently of the embedding of the planar system, can be described in terms of the two gauge fields only. As far as the author is aware it is the first time that such a construction is fully justified, thus allowing a full vectorial treatment at variational level of electromagnetism in planar systems.Comment: 8 pages, 1 figur

Comparison of clinical rating scales in genetic frontotemporal dementia within the GENFI cohort

BACKGROUND: Therapeutic trials are now underway in genetic forms of frontotemporal dementia (FTD) but clinical outcome measures are limited. The two most commonly used measures, the Clinical Dementia Rating (CDR)+National Alzheimer’s Disease Coordinating Center (NACC) Frontotemporal Lobar Degeneration (FTLD) and the FTD Rating Scale (FRS), have yet to be compared in detail in the genetic forms of FTD. METHODS: The CDR+NACC FTLD and FRS were assessed cross-sectionally in 725 consecutively recruited participants from the Genetic FTD Initiative: 457 mutation carriers (77 microtubule-associated protein tau (MAPT), 187 GRN, 193 C9orf72) and 268 family members without mutations (non-carrier control group). 231 mutation carriers (51 MAPT, 92 GRN, 88 C9orf72) and 145 non-carriers had available longitudinal data at a follow-up time point. RESULTS: Cross-sectionally, the mean FRS score was lower in all genetic groups compared with controls: GRN mutation carriers mean 83.4 (SD 27.0), MAPT mutation carriers 78.2 (28.8), C9orf72 mutation carriers 71.0 (34.0), controls 96.2 (7.7), p<0.001 for all comparisons, while the mean CDR+NACC FTLD Sum of Boxes was significantly higher in all genetic groups: GRN mutation carriers mean 2.6 (5.2), MAPT mutation carriers 3.2 (5.6), C9orf72 mutation carriers 4.2 (6.2), controls 0.2 (0.6), p<0.001 for all comparisons. Mean FRS score decreased and CDR+NACC FTLD Sum of Boxes increased with increasing disease severity within each individual genetic group. FRS and CDR+NACC FTLD Sum of Boxes scores were strongly negatively correlated across all mutation carriers (r_{s} =−0.77, p<0.001) and within each genetic group (r_{s} =−0.67 to −0.81, p<0.001 in each group). Nonetheless, discrepancies in disease staging were seen between the scales, and with each scale and clinician-judged symptomatic status. Longitudinally, annualised change in both FRS and CDR+NACC FTLD Sum of Boxes scores initially increased with disease severity level before decreasing in those with the most severe disease: controls −0.1 (6.0) for FRS, −0.1 (0.4) for CDR+NACC FTLD Sum of Boxes, asymptomatic mutation carriers −0.5 (8.2), 0.2 (0.9), prodromal disease −2.3 (9.9), 0.6 (2.7), mild disease −10.2 (18.6), 3.0 (4.1), moderate disease −9.6 (16.6), 4.4 (4.0), severe disease −2.7 (8.3), 1.7 (3.3). Sample sizes were calculated for a trial of prodromal mutation carriers: over 180 participants per arm would be needed to detect a moderate sized effect (30%) for both outcome measures, with sample sizes lower for the FRS. CONCLUSIONS: Both the FRS and CDR+NACC FTLD measure disease severity in genetic FTD mutation carriers throughout the timeline of their disease, although the FRS may be preferable as an outcome measure. However, neither address a number of key symptoms in the FTD spectrum, for example, motor and neuropsychiatric deficits, which future scales will need to incorporate

Cognitive composites for genetic frontotemporal dementia: GENFI-Cog

Background Clinical endpoints for upcoming therapeutic trials in frontotemporal dementia (FTD) are increasingly urgent. Cognitive composite scores are often used as endpoints but are lacking in genetic FTD. We aimed to create cognitive composite scores for genetic frontotemporal dementia (FTD) as well as recommendations for recruitment and duration in clinical trial design. Methods A standardized neuropsychological test battery covering six cognitive domains was completed by 69 C9orf72, 41 GRN, and 28 MAPT mutation carriers with CDR® plus NACC-FTLD ≥ 0.5 and 275 controls. Logistic regression was used to identify the combination of tests that distinguished best between each mutation carrier group and controls. The composite scores were calculated from the weighted averages of test scores in the models based on the regression coefficients. Sample size estimates were calculated for individual cognitive tests and composites in a theoretical trial aimed at preventing progression from a prodromal stage (CDR® plus NACC-FTLD 0.5) to a fully symptomatic stage (CDR® plus NACC-FTLD ≥ 1). Time-to-event analysis was performed to determine how quickly mutation carriers progressed from CDR® plus NACC-FTLD = 0.5 to ≥ 1 (and therefore how long a trial would need to be). Results The results from the logistic regression analyses resulted in different composite scores for each mutation carrier group (i.e. C9orf72, GRN, and MAPT). The estimated sample size to detect a treatment effect was lower for composite scores than for most individual tests. A Kaplan-Meier curve showed that after 3 years, ~ 50% of individuals had converted from CDR® plus NACC-FTLD 0.5 to ≥ 1, which means that the estimated effect size needs to be halved in sample size calculations as only half of the mutation carriers would be expected to progress from CDR® plus NACC FTLD 0.5 to ≥ 1 without treatment over that time period. Discussion We created gene-specific cognitive composite scores for C9orf72, GRN, and MAPT mutation carriers, which resulted in substantially lower estimated sample sizes to detect a treatment effect than the individual cognitive tests. The GENFI-Cog composites have potential as cognitive endpoints for upcoming clinical trials. The results from this study provide recommendations for estimating sample size and trial duration

Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic frontotemporal dementia

Copyright © 2020 The Authors. Introduction: The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. We investigate this phenomenon in familial frontotemporal dementia (FTD). Methods: We studied 121 presymptomatic FTD mutation carriers and 134 family members without mutations, using multivariate data-driven approach to link cognitive performance with both structural and functional magnetic resonance imaging. Atrophy and brain network connectivity were compared between groups, in relation to the time from expected symptom onset. Results: There were group differences in brain structure and function, in the absence of differences in cognitive performance. Specifically, we identified behaviorally relevant structural and functional network differences. Structure-function relationships were similar in both groups, but coupling between functional connectivity and cognition was stronger for carriers than for non-carriers, and increased with proximity to the expected onset of disease. Discussion: Our findings suggest that the maintenance of functional network connectivity enables carriers to maintain cognitive performance.K.A.T. is supported by the British Academy Postdoctoral Fellowship (PF160048) and the Guarantors of Brain (101149). J.B.R. is supported by the Wellcome Trust (103838), the Medical Research Council (SUAG/051 G101400), and the Cambridge NIHR Biomedical Research Centre. R. S.-V. is supported by the Instituto de Salud Carlos III and the JPND network PreFrontAls (01ED1512/AC14/0013) and the Fundació Marató de TV3 (20143810). M.M and E.F are supported by the UK Medical Research Council, the Italian Ministry of Health, and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, and also a Canadian Institutes of Health Research operating grant (MOP 327387) and funding from the Weston Brain Institute. J.D.R., D.C., and K.M.M. are supported by the NIHR Queen Square Dementia Biomedical Research Unit, the NIHR UCL/H Biomedical Research Centre, and the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility. J.D.R. is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH), the MRC UK GENFI grant (MR/ M023664/1), and The Bluefield Project. F.T. is supported by the Italian Ministry of Health (Grant NET-2011-02346784). L.C.J. and J.V.S. are supported by the Association for Frontotemporal Dementias Research Grant 2009, ZonMw Memorabel project number 733050103 and 733050813, and the Bluefield project. R.G. is supported by Italian Ministry of Health, Ricerca Corrente. J.L. was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145; SyNergy - ID 390857198). The Swedish contributors C.G., L.O., and C.A. were supported by grants from JPND Prefrontals Swedish Research Council (VR) 529-2014-7504, JPND GENFI-PROX Swedish Research Council (VR) 2019-02248, Swedish Research Council (VR) 2015- 02926, Swedish Research Council (VR) 2018-02754, Swedish FTD Initiative-Schorling Foundation, Swedish Brain Foundation, Swedish Alzheimer Foundation, Stockholm County Council ALF, Karolinska Institutet Doctoral Funding, and StratNeuro, Swedish Demensfonden, during the conduct of the study

Hierarchical spectral clustering reveals brain size and shape changes in asymptomatic carriers of C9orf72

Supplementary data: fcac182_Supplementary_Data - https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/braincomms/4/4/10.1093_braincomms_fcac182/1/fcac182_supplementary_data.pdf?Expires=1665138780&Signature=oJFozMlNZiAmxd4~XZaq7YKd7waxislas45NEOp9AiZv-fUYr7X~LhZxFgvYXpCVINyQUQrXe0pgrm9L5kv7xdb0LltVuoEOjwb5uVveMyHMfuqTdCBsEzTVZidx9GuuOB79JsHNYHkUZPsXLiU8-lrosrTb3tasr8Mpv31u7ZVZT~4uGdUf06UsIRu7AEn4bfKf64iwudmFr1QyrLJkXMZm0uJ4e5kh8f7k6Xm~rZGqkaiphsQ~Oat4JHssfuCe5Wibgc4m~rMjQeOmutR3R7KicfH4j3xuab1mzCbf-H~~Ed5Yt8mtlMTsyDB3t-8z3dNVaS2aBrwCABvfa3G2yg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA (pdf file).GENFI consortium authors Sónia Afonso, Maria Rosario Almeida, Sarah Anderl-Straub, Christin Andersson, Anna Antonell, Silvana Archetti, Andrea Arighi, Mircea Balasa, Myriam Barandiaran, Nuria Bargalló, Robart Bartha, Benjamin Bender, Alberto Benussi, Sandra Black, Martina Bocchetta, Sergi Borrego-Ecija, Jose Bras, Marta Canada, Valentina Cantoni, Paola Caroppo, David Cash, Miguel Castelo-Branco, Rhian Convery, Thomas Cope, Giuseppe Di Fede, Alina Díez, Diana Duro, Chiara Fenoglio, Catarina B. Ferreira, Nick Fox, Morris Freedman, Giorgio Fumagalli, Alazne Gabilondo, Roberto Gasparotti, Serge Gauthier, Stefano Gazzina, Giorgio Giaccone, Ana Gorostidi, Caroline Greaves, Rita Guerreiro, Carolin Heller, Tobias Hoegen, Begoña Indakoetxea, Vesna Jelic, Lize Jiskoot, Hans-Otto Karnath, Ron Keren, Tobias Langheinrich, Maria João Leitão, Albert Lladó, Sandra Loosli, Carolina Maruta, Simon Mead, Lieke Meeter, Gabriel Miltenberger, Rick van Minkelen, Sara Mitchell, Katrina Moore, Jennifer Nicholas, Linn Öijerstedt, Jaume Olives, Sebastien Ourselin, Alessandro Padovani, Jessica Panman, Janne M. Papma, Georgia Peakman, Yolande Pijnenburg, Enrico Premi, Sara Prioni, Catharina Prix, Rosa Rademakers, Veronica Redaelli, Tim Rittman, Ekaterina Rogaeva, Pedro Rosa-Neto, Giacomina Rossi, Mar tin Rossor, Beatriz Santiago, Elio Scarpini, Sonja Schönecker, Elisa Semler, Rachelle Shafei, Christen Shoesmith, Miguel Tábuas-Pereira, Mikel Tainta, Ricardo Taipa, David Tang-Wai, David L Thomas, Paul Thompson, Hakan Thonberg, Carolyn Timberlake, Pietro Tiraboschi, Emily Todd, Michele Veldsman, Ana Verdelho, Jorge Villanua, Jason Warren, Carlo Wilke, Ione Woollacott, Elisabeth Wlasich, Henrik Zetterberg, Miren ZulaicaCopyright © The Author(s) 2022. Traditional methods for detecting asymptomatic brain changes in neurodegenerative diseases such as Alzheimer’s disease or frontotemporal degeneration typically evaluate changes in volume at a predefined level of granularity, e.g. voxel-wise or in a priori defined cortical volumes of interest. Here, we apply a method based on hierarchical spectral clustering, a graph-based partitioning technique. Our method uses multiple levels of segmentation for detecting changes in a data-driven, unbiased, comprehensive manner within a standard statistical framework. Furthermore, spectral clustering allows for detection of changes in shape along with changes in size. We performed tensor-based morphometry to detect changes in the Genetic Frontotemporal dementia Initiative asymptomatic and symptomatic frontotemporal degeneration mutation carriers using hierarchical spectral clustering and compared the outcome to that obtained with a more conventional voxel-wise tensor- and voxel-based morphometric analysis. In the symptomatic groups, the hierarchical spectral clustering-based method yielded results that were largely in line with those obtained with the voxel-wise approach. In asymptomatic C9orf72 expansion carriers, spectral clustering detected changes in size in medial temporal cortex that voxel-wise methods could only detect in the symptomatic phase. Furthermore, in the asymptomatic and the symptomatic phases, the spectral clustering approach detected changes in shape in the premotor cortex in C9orf72. In summary, the present study shows the merit of hierarchical spectral clustering for data-driven segmentation and detection of structural changes in the symptomatic and asymptomatic stages of monogenic frontotemporal degeneration.KU Leuven’s ‘Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie’

Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic frontotemporal dementia

Introduction The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. We investigate this phenomenon in familial frontotemporal dementia (FTD). Methods We studied 121 presymptomatic FTD mutation carriers and 134 family members without mutations, using multivariate data-driven approach to link cognitive performance with both structural and functional magnetic resonance imaging. Atrophy and brain network connectivity were compared between groups, in relation to the time from expected symptom onset. Results There were group differences in brain structure and function, in the absence of differences in cognitive performance. Specifically, we identified behaviorally relevant structural and functional network differences. Structure-function relationships were similar in both groups, but coupling between functional connectivity and cognition was stronger for carriers than for non-carriers, and increased with proximity to the expected onset of disease. Discussion Our findings suggest that the maintenance of functional network connectivity enables carriers to maintain cognitive performance