Novel instructionless eye tracking tasks identify emotion recognition deficits in frontotemporal dementia

BACKGROUND: Current tasks measuring social cognition are usually 'pen and paper' tasks, have ceiling effects and include complicated test instructions that may be difficult to understand for those with cognitive impairment. We therefore aimed to develop a set of simple, instructionless, quantitative, tasks of emotion recognition using the methodology of eye tracking, with the subsequent aim of assessing their utility in individuals with behavioural variant frontotemporal dementia (bvFTD). METHODS: Using the Eyelink 1000 Plus eye tracker, 18 bvFTD and 22 controls completed tasks of simple and complex emotion recognition that involved viewing four images (one target face (simple) or pair of eyes (complex) and the others non-target) followed by a target emotion word and lastly the original four images alongside the emotion word. A dwell time change score was then calculated as the main outcome measure by subtracting the percentage dwell time for the target image before the emotion word appeared away from the percentage dwell time for the target image after the emotion word appeared. All participants also underwent a standard cognitive battery and volumetric T1-weighted magnetic resonance imaging. RESULTS: Analysis using a mixed effects model showed that the average (standard deviation) mean dwell time change score in the target interest area was 35 (27)% for the control group compared with only 4 (18)% for the bvFTD group (p < 0.05) for the simple emotion recognition task, and 15 (26)% for the control group compared with only 2 (18)% for the bvFTD group (p < 0.05) for the complex emotion recognition task. Worse performance in the bvFTD group correlated with atrophy in the right ventromedial prefrontal and orbitofrontal cortices, brain regions previously implicated in social cognition. CONCLUSIONS: In summary, eye tracking is a viable tool for assessing social cognition in individuals with bvFTD, being well-tolerated and able to overcome some of the problems associated with standard psychometric tasks

Early detection of frontotemporal dementia (EDoF): A digital biomarker study

Background: With the commencement of clinical trials in frontotemporal dementia (FTD), robust biomarkers that can detect the earliest signs of the disease and also measure treatment effect, are essential. Pen and paper assessments are laborious, administered infrequently, and can rely on subjective reporting. Using digital devices allows for more frequent, often continuous, assessment from home, whilst producing a wealth of objective data. The Early Detection of Frontotemporal dementia (EDoF) study aims to develop a series of digital measures that may be useful for the diagnosis of FTD and for outcome measures in trials. Method: The EDoF study includes: a computerised cognitive battery, a mobile eye tracking device, a novel app that passively measures cognitive function by monitoring smartphone metadata, speech and language analysis using machine learning algorithms, actigraphy, and gait analysis. These measures are being validated in a large control population before being tested in symptomatic and presymptomatic genetic FTD within the Genetic FTD Initiative (GENFI) study. Result: We are currently recruiting participants to the initial arms of the study, with over 1,300 healthy controls having already completed the computerized cognitive battery. The mobile eye tracking device measures eye movement abnormalities but also uses instructionless eye movement tasks to measure executive function and social cognition. Pilot eye tracking data shows abnormalities of these tasks in symptomatic FTD, and also for antisaccadic eye movements in presymptomatic FTD. Normative data for all of the measures will be generated helping to assess construct validity and retest reliability. Conclusion: EDoF is the first study aiming to use a comprehensive set of digital measures to detect early FTD. It may also prove useful for home monitoring within future therapeutic trials of FTD

Basal forebrain atrophy in frontotemporal dementia

Background: The basal forebrain is a subcortical structure that plays an important role in learning, attention, and memory. Despite the known subcortical involvement in frontotemporal dementia (FTD), there is little research into the role of the basal forebrain in this disease. We aimed to investigate differences in basal forebrain volumes between clinical, genetic, and pathological diagnoses of FTD. / Methods: 356 patients with FTD were recruited from the UCL Dementia Research Centre and matched on age and gender with 83 cognitively normal controls. All subjects had a T1-weighted MR scan suitable for analysis. Basal forebrain volumes were calculated using the Geodesic Information Flow (GIF) parcellation method and were compared between clinical (148 bvFTD, 82 svPPA, 103 nfvPPA, 14 PPA-NOS, 9 FTD-MND), genetic (24 MAPT, 15 GRN, 26 C9orf72) and pathological groups (28 tau, 3 FUS, 35 TDP-43) and controls. A subanalysis was also performed comparing pathological subgroups of tau (11 Pick's disease, 6 FTDP-17, 7 CBD, 4 PSP) and TDP-43 (12 type A, 2 type B, 21 type C). / Results: All clinical subtypes of FTD showed significantly smaller volumes than controls (p≤ 0.010, ANCOVA), with svPPA (10% volumetric difference) and bvFTD (9%) displaying the smallest volumes. Reduced basal forebrain volumes were also seen in MAPT mutations (18%, p<0.0005) and in individuals with pathologically confirmed FTDP-17 (17%), Pick's disease (12%), and TDP-43 type C (8%) (p<0.001). / Conclusion: Involvement of the basal forebrain is a common feature in FTD, although the extent of volume reduction differs between clinical, genetic, and pathological diagnoses. Tauopathies, particularly those with MAPT mutations, had the smallest volumes. However, atrophy was also seen in those with TDP-43 type C pathology (most of whom have svPPA clinically). This suggests that the basal forebrain is vulnerable to multiple types of FTD-associated protein inclusions

Eye movements in frontotemporal dementia: Abnormalities of fixation, saccades and anti-saccades

Copyright © 2021 The Authors. Introduction: Oculomotor function has not been systematically studied in frontotemporal dementia (FTD) and yet may offer a simple target to monitor disease activity. Methods: We assessed fixation stability, smooth pursuit, pro-saccades, and anti-saccades using the Eyelink 1000-plus eye-tracker in 19 individuals with behavioral variant FTD (bvFTD) and 22 controls. Neuroanatomical correlates were assessed using a region of interest magnetic resonance imaging (MRI) analysis. Results: Measures of fixation stability were impaired in the bvFTD group compared with controls. However, performance did not differ from controls in the pro-saccade tasks except in the vertical overlap condition. The bvFTD group performed worse in the anti-saccade task, which correlated strongly with executive function. Neural correlates included the orbitofrontal and ventromedial prefrontal cortices and striatum for fixation stability, and the dorsolateral prefrontal and parietal cortices and striatum for anti-saccades. Discussion: Overall, oculomotor function is abnormal in bvFTD, with performance likely related to impairment of inhibitory control and executive dysfunction.The Dementia Research Centre is supported by Alzheimer's Research UK, Alzheimer's Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society, and Alzheimer's Research UK. JDR 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). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Bluefield Project, and the JPND GENFI-PROX grant (2019-02248). MB is supported by a Fellowship award from the Alzheimer's Society, UK (AS-JF-19a-004-517). MB's work is also supported by the UK Dementia Research Institute, which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society, and Alzheimer's Research UK. RC/CG are supported by a Frontotemporal Dementia Research Studentships in Memory of David Blechner funded through The National Brain Appeal (RCN 290173). JDW is supported by the Alzheimer's Society, Alzheimer's Research UK, and the UCLH/UCL NIHR Biomedical Research Centre. The GIF template database includes volumetric MRI scans from the University College London Genetic FTD Initiative (GENFI) study (www.genfi.org.uk), which is funded by the Medical Research Council UK GENFI grant (MR/M023664/1)

Search for time-dependent B0s - B0s-bar oscillations using a vertex charge dipole technique

We report a search for B0s - B0s-bar oscillations using a sample of 400,000 hadronic Z0 decays collected by the SLD experiment. The analysis takes advantage of the electron beam polarization as well as information from the hemisphere opposite that of the reconstructed B decay to tag the B production flavor. The excellent resolution provided by the pixel CCD vertex detector is exploited to cleanly reconstruct both B and cascade D decay vertices, and tag the B decay flavor from the charge difference between them. We exclude the following values of the B0s - B0s-bar oscillation frequency: Delta m_s < 4.9 ps-1 and 7.9 < Delta m_s < 10.3 ps-1 at the 95% confidence level.Comment: 18 pages, 3 figures, replaced by version accepted for publication in Phys.Rev.D; results differ slightly from first versio

Calibration of the charge and energy loss per unit length of the MicroBooNE liquid argon time projection chamber using muons and protons

We describe a method used to calibrate the position- and time-dependent response of the MicroBooNE liquid argon time projection chamber anode wires to ionization particle energy loss. The method makes use of crossing cosmic-ray muons to partially correct anode wire signals for multiple effects as a function of time and position, including cross-connected TPC wires, space charge effects, electron attachment to impurities, diffusion, and recombination. The overall energy scale is then determined using fully-contained beam-induced muons originating and stopping in the active region of the detector. Using this method, we obtain an absolute energy scale uncertainty of 2% in data. We use stopping protons to further refine the relation between the measured charge and the energy loss for highly-ionizing particles. This data-driven detector calibration improves both the measurement of total deposited energy and particle identification based on energy loss per unit length as a function of residual range. As an example, the proton selection efficiency is increased by 2% after detector calibration

Reconstruction and measurement of (100) MeV energy electromagnetic activity from π0 arrow γγ decays in the MicroBooNE LArTPC

We present results on the reconstruction of electromagnetic (EM) activity from photons produced in charged current νμ interactions with final state π0s. We employ a fully-automated reconstruction chain capable of identifying EM showers of (100) MeV energy, relying on a combination of traditional reconstruction techniques together with novel machine-learning approaches. These studies demonstrate good energy resolution, and good agreement between data and simulation, relying on the reconstructed invariant π0 mass and other photon distributions for validation. The reconstruction techniques developed are applied to a selection of νμ + Ar → μ + π0 + X candidate events to demonstrate the potential for calorimetric separation of photons from electrons and reconstruction of π0 kinematics

The CBI-R detects early behavioural impairment in genetic frontotemporal dementia

Introduction: Behavioural dysfunction is a key feature of genetic frontotemporal dementia (FTD) but validated clinical scales measuring behaviour are lacking at present. Methods: We assessed behaviour using the revised version of the Cambridge Behavioural Inventory (CBI-R) in 733 participants from the Genetic FTD Initiative study: 466 mutation carriers (195 C9orf72, 76 MAPT, 195 GRN) and 267 non-mutation carriers (controls). All mutation carriers were stratified according to their global CDR plus NACC FTLD score into three groups: asymptomatic (CDR = 0), prodromal (CDR = 0.5) and symptomatic (CDR = 1+). Mixed-effects models adjusted for age, education, sex and family clustering were used to compare between the groups. Neuroanatomical correlates of the individual domains were assessed within each genetic group. Results: CBI-R total scores were significantly higher in all CDR 1+ mutation carrier groups compared with controls [C9orf72 mean 70.5 (standard deviation 27.8), GRN 56.2 (33.5), MAPT 62.1 (36.9)] as well as their respective CDR 0.5 groups [C9orf72 13.5 (14.4), GRN 13.3 (13.5), MAPT 9.4 (10.4)] and CDR 0 groups [C9orf72 6.0 (7.9), GRN 3.6 (6.0), MAPT 8.5 (13.3)]. The C9orf72 and GRN 0.5 groups scored significantly higher than the controls. The greatest impairment was seen in the Motivation domain for the C9orf72 and GRN symptomatic groups, whilst in the symptomatic MAPTgroup, the highest-scoring domains were Stereotypic and Motor Behaviours and Memory and Orientation. Neural correlates of each CBI-R domain largely overlapped across the different mutation carrier groups. Conclusions: The CBI-R detects early behavioural change in genetic FTD, suggesting that it could be a useful measure within future clinical trials

Augmentation of osteochondral repair with hyperbaric oxygenation: a rabbit study

<p>Abstract</p> <p>Background</p> <p>Current treatments for osteochondral injuries often result in suboptimal healing. We hypothesized that the combination of hyperbaric oxygen (HBO) and fibrin would be superior to either method alone in treating full-thickness osteochondral defects.</p> <p>Methods</p> <p>Osteochondral repair was evaluated in 4 treatment groups (control, fibrin, HBO, and HBO+fibrin groups) at 2-12 weeks after surgical injury. Forty adult male New Zealand white rabbits underwent arthrotomy and osteochondral surgery on both knees. Two osteochondral defects were created in each femoral condyle, one in a weight-bearing area and the other in a non-weight-bearing area. An exogenous fibrin clot was placed in each defect in the right knee. Left knee defects were left empty. Half of the rabbits then underwent hyperbaric oxygen therapy. The defects in the 4 treatment groups were then examined histologically at 2, 4, 6, 8, and 12 weeks after surgery.</p> <p>Results</p> <p>The HBO+fibrin group showed more rapid and more uniform repair than the control and fibrin only groups, but was not significantly different from the group receiving HBO alone. In the 2 HBO groups, organized repair and good integration with adjacent cartilage were seen at 8 weeks; complete regeneration was observed at 12 weeks.</p> <p>Conclusions</p> <p>HBO significantly accelerated the repair of osteochondral defects in this rabbit model; however, the addition of fibrin produced no further improvement.</p