Found 18624 matches for
Attentional networks are sensitive to sleep deprivation. However, variation in attentional performance as a function of normal sleep parameters is understudied. We examined whether attentional performance is influenced by (a) individual differences in sleep duration, (b) sleep duration variability, and/or (c) their interaction. A total of 57 healthy participants (61.4% female, Mage = 32.37 years, SD = 8.68) completed questionnaires, wore wrist actigraphy for 1 week, and subsequently completed the attention network test. Sleep duration and sleep duration variability did not predict orienting score, executive control score, or error rates. Sleep duration variability appeared to moderate the association between sleep duration with overall reaction time (β = -.34, t = -2.13, p = .04) and alerting scores (β = .43, t = 2.94, p = .01), though further inspection of the data suggested that these were spurious findings. Time of testing was a significant predictor of alerting score (β = .35, t = 2.96, p = .01), chronotype of orienting (β = .31, t = 2.28, p = .03), and age of overall reaction time (β = .35, t = 2.70, p = .01). Our results highlight the importance of examining the associations between variations in sleep-wake patterns and attentional networks in samples with greater variation in sleep, as well as the importance of rigorously teasing apart mechanisms of the sleep homeostat from those related to the circadian rhythm in studies examining cognition.
OBJECTIVE: To determine whether brain imaging markers of tissue microstructure can detect the effect of disease progression across the preclinical stages of Huntington's disease. METHODS: Longitudinal microstructural changes in diffusion imaging metrics (mean diffusivity and fractional anisotropy) were investigated in participants with presymptomatic Huntington's disease (N = 35) stratified into three preclinical subgroups according to their estimated time until onset of symptoms, compared with age- and gender-matched healthy controls (N = 19) over a 1y period. RESULTS: Significant differences were found over the four groups in change of mean diffusivity in the posterior basal ganglia and the splenium of the corpus callosum. This overall effect was driven by significant differences between the group far-from-onset (FAR) of symptoms and the groups midway- (MID) and near-the-onset (NEAR) of symptoms. In particular, an initial decrease of mean diffusivity in the FAR group was followed by a subsequent increase in groups closer to onset of symptoms. The seemingly counter-intuitive decrease of mean diffusivity in the group furthest from onset of symptoms might be an early indicator of neuroinflammatory process preceding the neurodegenerative phase. In contrast, the only clinical measure that was able to capture a difference in 1y changes between the preclinical stages was the UHDRS confidence in motor score. CONCLUSIONS: With sensitivity to longitudinal changes in brain microstructure within and between preclinical stages, and potential differential response to distinct pathophysiological mechanisms, diffusion imaging is a promising state marker for monitoring treatment response and identifying the optimal therapeutic window of opportunity in preclinical Huntington's disease.
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare central nervous system inflammatory disorder primarily affecting the brainstem and cerebellum. We report a case of CLIPPERS in a 45-year-old man presenting with left facial numbness and dizziness. Imaging studies were conducted repeatedly over an 8-year follow-up period. Given diagnostic uncertainty in the early stages of the disease, three serial biopsies were obtained, which together with the clinical and radiological findings, led to the diagnosis. This case highlights the diagnostic challenges regarding the rare entity of CLIPPERS and discusses the main differential diagnoses that are necessary to consider. Additionally, some of the atypical features of this case, including the presenting finding of a large, solidly enhancing lesion on radiological imaging and prominent plasma cells on pathology, contribute to expanding the spectrum of appearances for CLIPPERS.
Pooling magnetic resonance imaging (MRI) data across research studies, or utilizing shared data from imaging repositories, presents exceptional opportunities to advance and enhance reproducibility of neuroscience research. However, scanner confounds hinder pooling data collected on different scanners or across software and hardware upgrades on the same scanner, even when all acquisition protocols are harmonized. These confounds reduce power and can lead to spurious findings. Unfortunately, methods to address this problem are scant. In this study, we propose a novel denoising approach that implements a data-driven linked independent component analysis (LICA) to identify scanner-related effects for removal from multimodal MRI to denoise scanner effects. We utilized multi-study data to test our proposed method that were collected on a single 3T scanner, pre- and post-software and major hardware upgrades and using different acquisition parameters. Our proposed denoising method shows a greater reduction of scanner-related variance compared with standard GLM confound regression or ICA-based single-modality denoising. Although we did not test it here, for combining data across different scanners, LICA should prove even better at identifying scanner effects as between-scanner variability is generally much larger than within-scanner variability. Our method has great promise for denoising scanner effects in multi-study and in large-scale multi-site studies that may be confounded by scanner differences.
Tensor Image Registration Library: Automated Non-Linear Registration of Sparsely Sampled Histological Specimens to Post-Mortem MRI of the Whole Human Brain
<jats:title>Abstract</jats:title><jats:p>There is a need to understand the histopathological basis of MRI signal characteristics in complex biological matter. Microstructural imaging holds promise for sensitive and specific indicators of the early stages of human neurodegeneration but requires validation against traditional histological markers before it can be reliably applied in the clinical setting. Validation relies on a precise and preferably automatic method to align MRI and histological images of the same tissue, which poses unique challenges compared to more conventional MRI-to-MRI registration.</jats:p><jats:p>A customisable open-source platform, Tensor Image Registration Library (TIRL) is presented. Based on TIRL, a fully automated pipeline was implemented to align small stained histological images with dissection photographs of corresponding tissue blocks and coronal brain slices, and further with high-resolution (0.5 mm) whole-brain post-mortem MRI data. The pipeline performed three separate deformable registrations to achieve accurate mapping between whole-brain MRI and small-slide histology coordinates. The robustness and accuracy of the individual registration steps were evaluated using both simulated data and real-life images from 6 different anatomical locations of one post-mortem human brain.</jats:p><jats:p>The automated registration method demonstrated sub-millimetre accuracy in all steps, robustness against tissue damage, and good reproducibility between experiments. The method also outperformed manual landmark-based slice-to-volume registration, also correcting for curvatures in the slicing plane. Due to the customisability of TIRL, the pipeline can be conveniently adapted for other research needs and is therefore suitable for the large-scale comparison of routinely collected histology and MRI data.</jats:p><jats:sec><jats:title>Highlights</jats:title><jats:p><jats:list list-type="bullet"><jats:list-item><jats:p>TIRL: new framework for prototyping bespoke image registration pipelines</jats:p></jats:list-item><jats:list-item><jats:p>Pipeline for automated registration of small-slide histology to whole-brain MRI</jats:p></jats:list-item><jats:list-item><jats:p>Slice-to-volume registration accounting for through-plane deformations</jats:p></jats:list-item><jats:list-item><jats:p>No need for serial histological sampling</jats:p></jats:list-item></jats:list></jats:p></jats:sec>
Protocol for a prospective, controlled, cross-sectional, diagnostic accuracy study to evaluate the specificity and sensitivity of ambulatory monitoring systems in the prompt detection of hypoxia and during movement
<jats:sec><jats:title>Introduction</jats:title><jats:p>Automated continuous ambulatory monitoring may provide an alternative to intermittent manual vital signs monitoring. This has the potential to improve frequency of measurements, timely escalation of care and patient safety. However, a major barrier to the implementation of these wearable devices in the ward environment is their uncertain reliability, efficiency and data fidelity. The purpose of this study is to test performance of selected devices in a simulated clinical setting including during movement and low levels of peripheral oxygen saturation.</jats:p></jats:sec><jats:sec><jats:title>Methods and analysis</jats:title><jats:p>This is a single centre, prospective, controlled, cross-sectional, diagnostic accuracy study to determine the specificity and sensitivity of currently available ambulatory vital signs monitoring equipment in the detection of hypoxia and the effect of movement on data acquisition. We will recruit up to 45 healthy volunteers who will attend a single study visit; starting with a movement phase and followed by the hypoxia exposure phase where we will gradually decrease saturation levels down to 80%. We will simultaneously test one chest patch, one wrist worn only and three wrist worn with finger probe devices against ‘clinical standard ‘and ‘gold standard’ references. We will measure peripheral oxygen saturations, pulse rate, heart rate and respiratory rate continuously and arterial blood gases intermittently throughout the study.</jats:p></jats:sec><jats:sec><jats:title>Ethics and dissemination</jats:title><jats:p>This study has received ethical approval by the East of Scotland Research Ethics Service REC 2 (19/ES/0008). The results will be broadly distributed through conference presentations and peer-reviewed publications.</jats:p></jats:sec><jats:sec><jats:title>Trial registration number</jats:title><jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="ISRCTN61535692">ISRCTN61535692</jats:ext-link> registered on 10/06/2019.</jats:p></jats:sec>
Inclusion of PF68 Surfactant Improves Stability of rAAV Titer when Passed through a Surgical Device Used in Retinal Gene Therapy.
Recent advances in recombinant adeno-associated virus (rAAV) gene therapy for choroideremia show gene replacement to be a promising approach. It is, however, well known that contact of vector solution with plastic materials in the surgical device may result in non-specific adsorption with resulting loss of physical titer and/or level of protein expression and activity. Here we assessed the biocompatibility and stability of rAAV2-REP1 (Rab Escort Protein-1) before and following passage through the injection device over a period of time to mimic the clinical scenario. Three identical devices were screened using two concentrations of vector: high (1E+12 DNase-resistant particles [DRP]/mL) and low (1E+11 DRP/mL), to mimic high- and low-dose administrations of vector product. The low dose was prepared using either formulation buffer that contained 0.001% of a non-ionic surfactant (PF68) or balanced salt solution (BSS). We observed significant losses in the genomic titer of samples diluted with BSS for all time points. The addition of 0.001% PF68 did not, however, affect rAAV physical titer, or REP1 protein expression and biological activity. Hence we observed that neither the genomic titer nor the biological activity of a rAAV2-REP1-containing solution was affected following passage through the surgical device when PF68 was present as a surfactant and this was maintained over a period up to 10 h.
© 2015 American Academy of Neurology. Objective: To assess the clinical relevance of the differential binding of antibodies against the 2 main aquaporin-4 (AQP4) isoforms in neuromyelitis optica (NMO) patient sera using stably transfected human embryonic kidney cells. Methods: Flow cytometry of human embryonic kidney cells stably transfected with either M23 or M1 AQP4 was used to measure antibody endpoint titers in 52 remission samples and 26 relapse samples from 34 patients with clinically well-characterized AQP4 antibody-positive NMO/NMO spectrum disorder. Results: The AQP4 M23 (40-61,440) and AQP4 M1 (,20-20,480) titers varied widely between patients, asdid the M23:M1 antibody ratio (1-192). In 76 of 78 samples, binding to M23 was higher than binding to M1, including during relapses and remissions (p, 0.0001), and the M23:M1 ratio was relatively constant within an individual patient. Titers usually fell after immunosuppression, but the titers at which relapses occurred varied markedly; no threshold level for relapses could be identified, and relapses could occur without a rise in titers. Relapse severity did not correlate with M23 or M1 antibody titers, although there was a correlation between the earliest M23 titers and annualized relapse rates. The M23:M1 ratio and absolute M23 and M1 titers did not relateto age at disease onset, ethnicity, disease severity, phenotype, or relapses at different anatomical sites. Conclusion: Relative AQP4 antibody binding to M23 and M1 isoforms differs between patients but there is no consistent association between these differences and clinical characteristics of disease. Nevertheless, the M23 isoform provided a slightly more sensitive substrate for AQP4-antibody assays, particularly for follow-up studies.
INTRODUCTION: Bursts of beta frequency band activity in the basal ganglia of patients with Parkinson's disease (PD) are associated with impaired motor performance. Here we test in human adults if small variations in the timing of movement relative to beta bursts have a critical effect on movement velocity and if the cumulative effects of multiple beta bursts, both locally and across networks, matter. METHODS: We recorded local field potentials from the subthalamic nucleus (STN) in 15 PD patients of both genders OFF-medication, during temporary lead externalization after deep brain stimulation surgery. Beta bursts were defined as periods exceeding the 75th percentile amplitude threshold. Subjects performed a visual cued joystick reaching task, with the visual cue being triggered in real time with different temporal relationships to bursts of STN beta activity. RESULTS: The velocity of actions made in response to cues prospectively triggered by STN beta bursts was slower than when responses were not time-locked to recent beta bursts. Importantly, slow movements were those that followed multiple bursts close to each other within a trial. In contrast, small differences in the delay between the last burst and movement onset had no significant impact on velocity. Moreover, when the overlap of bursts between the two STN was high, slowing was more pronounced. CONCLUSION: Our findings suggest that the cumulative, but recent, history of beta bursting, both locally and across basal ganglia networks, may impact on motor performance.Significance Statement: Bursts of beta frequency band activity in the basal ganglia are associated with slowing of voluntary movement in patients with Parkinson's disease. We show that slow movements are those that follow multiple bursts close to each other and bursts that are coupled across regions. These results suggest that the cumulative, but recent, history of beta bursting, both locally and across basal ganglia networks, impacts on motor performance in this condition. The manipulation of burst dynamics may be a means of selectively improving motor impairment.
Understanding and reducing variability of response to transcranial direct current stimulation (tDCS) requires measuring what factors predetermine sensitivity to tDCS and tracking individual response to tDCS. Human trials, animal models, and computational models suggest structural traits and functional states of neural systems are the major sources of this variance. There are 118 published tDCS studies (up to October 1, 2018) that used fMRI as a proxy measure of neural activation to answer mechanistic, predictive, and localization questions about how brain activity is modulated by tDCS. FMRI can potentially contribute as: a measure of cognitive state-level variance in baseline brain activation before tDCS; inform the design of stimulation montages that aim to target functional networks during specific tasks; and act as an outcome measure of functional response to tDCS. In this systematic review, we explore methodological parameter space of tDCS integration with fMRI spanning: (a) fMRI timing relative to tDCS (pre, post, concurrent); (b) study design (parallel, crossover); (c) control condition (sham, active control); (d) number of tDCS sessions; (e) number of follow up scans; (f) stimulation dose and combination with task; (g) functional imaging sequence (BOLD, ASL, resting); and (h) additional behavioral (cognitive, clinical) or quantitative (neurophysiological, biomarker) measurements. Existing tDCS-fMRI literature shows little replication across these permutations; few studies used comparable study designs. Here, we use a representative sample study with both task and resting state fMRI before and after tDCS in a crossover design to discuss methodological confounds. We further outline how computational models of current flow should be combined with imaging data to understand sources of variability. Through the representative sample study, we demonstrate how modeling and imaging methodology can be integrated for individualized analysis. Finally, we discuss the importance of conducting tDCS-fMRI with stimulation equipment certified as safe to use inside the MR scanner, and of correcting for image artifacts caused by tDCS. tDCS-fMRI can address important questions on the functional mechanisms of tDCS action (e.g., target engagement) and has the potential to support enhancement of behavioral interventions, provided studies are designed rationally.
Rational performance metrics for operating theatres, principles of efficiency, and how to achieve it.
BACKGROUND: Several performance metrics are commonly used by National Health Service (NHS) organizations to measure the efficiency and productivity of operating lists. These include: start time, utilization, cancellations, number of operations and gap time between operations. The authors describe reasons why these metrics are flawed, and use clinical evidence and mathematics to define a rational, balanced efficiency metric. METHODS: A narrative review of literature on the efficiency and productivity of elective NHS operating lists was undertaken. The aim was to rationalize how best to define and measure the efficiency of an operating list, and describe strategies to achieve it. RESULTS: There is now a wealth of literature on how optimally to measure the performance of elective surgical lists. Efficiency may be defined as the completion of all scheduled operations within the allocated time with no over- or under-runs. CONCLUSION: Achieving efficiency requires appropriate scheduling using specific procedure mean (or median) times and their associated variance (standard deviation or interquartile range) to calculate the probability they can be completed on time. The case mix may be adjusted to yield better time management. This review outlines common misconceptions applied to managing scheduled operating theatre lists and the challenges of measuring unscheduled operations in emergency settings.
Rational planning of operating lists: a prospective comparison of 'booking to the mean' vs. 'probabilistic case scheduling' in urology.
The efficient use of operating theatres requires accurate case scheduling. One common method is 'booking to the mean'. Here, the mean times for individual operations are summed to approximate the time allocated to the list. An alternative approach is 'probabilistic scheduling'. Here, the means and standard deviation of the individual case times are combined to estimate the probability that the planned list will finish on time. This study assessed how probabilistic booking would have changed list utilisation, over-running and case cancellations in 60 urology lists during eight months that had been 'booked to the mean'. Booking to the mean resulted in 53/60 (88%) lists over-running and correctly predicted the finish times in just 13% of lists. Out of 264 patients, 36 (14%) were cancelled on the day due to over-runs in 24/60 (40%) lists. In contrast, probabilistic scheduling correctly predicted an over-run or under-run in 77% of lists, which would have allowed the case mix to be adjusted to prevent cancellation and optimise utilisation.
Neoadjuvant intravitreal ranibizumab treatment in high-risk ocular melanoma patients: a two-stage single-centre phase II single-arm study.
Despite an established history of intraocular antivascular endothelial growth factor (anti-VEGF) agents therapy in a variety of ocular pathologies as well as other cancer forms, use in the primary treatment of uveal melanoma has not been well assessed. This was a two-stage therapeutic and exploratory phase II, non-randomised, single centre trial involving intraocular treatment with 0.5 mg in 0.05 ml of ranibizumab via six intravitreous injections over 6 months in patients with primary ocular melanoma that otherwise required radical surgery because of tumour size. Seven patients were recruited with a median age of 66 years. At baseline, the longest basal diameter was 15.1 mm (mean, range 10-20.4 mm) with a height measured by ultrasonography of 9.2 mm (mean, range 6.6-12.7 mm). No patients achieved complete or partial response at any visit. All required enucleation. Histopathological analysis revealed mixed cell melanoma in 5/7 (71%) and spindle cell morphology in 2/7 (29%) with ciliary body involvement in 4/7 (57%) and the presence of closed loops also in 4/7 (57%). Genetic analysis demonstrated loss of chromosome 3 in 5/7 (71%) but abnormalities in chromosome 1,6 or 8 in all cases. Our study was terminated early as alternative treatments were clearly superior for local tumour control. There continues to be a role of intravitreal anti-VEGF for the treatment of the sequelae of local radiotherapy in the form of radiation retinopathy and so these agents may be used as adjuncts in the treatment of uveal melanoma rather than as a primary treatment.
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Cortical slow oscillations (SOs) and thalamo-cortical sleep spindles hallmark slow wave sleep and facilitate sleep-dependent memory consolidation. Experiments utilising auditory closed-loop stimulation to enhance these oscillations have shown great potential in young and older subjects. However, the magnitude of responses has yet to be compared between these age groups.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>We examined the possibility of enhancing SOs and performance on different memory tasks in a healthy older population using auditory closed-loop stimulation and contrast effects to a young adult cohort.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In a within-subject design, subjects (n = 17, 55.7 ± 1.0 years, 9 female) received auditory click stimulation in synchrony with SO up-states, which was compared to a no-stimulation sham condition. Overnight memory consolidation was assessed for declarative word-pairs and procedural finger-tapping skill. Post-sleep encoding capabilities were tested with a picture recognition task. Electrophysiological effects of stimulation were compared to those reported previously in a younger cohort (n = 11, 24.2 ± 0.9 years, 8 female).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Overnight retention and post-sleep encoding performance of the older cohort revealed no beneficial effect of stimulation, which contrasts with the enhancing effect the same stimulation protocol had in our younger cohort. Auditory stimulation prolonged endogenous SO trains and induced sleep spindles phase-locked to SO up-states in the older population. However, responses were markedly reduced compared to younger subjects. Additionally, the temporal dynamics of stimulation effects on SOs and spindles differed between age groups.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our findings suggest that the susceptibility to auditory stimulation during sleep drastically changes with age and reveal the difficulties of translating a functional protocol from younger to older populations.</jats:p></jats:sec><jats:sec><jats:title>Highlights</jats:title><jats:p><jats:list list-type="bullet"><jats:list-item><jats:p>Auditory closed-loop stimulation induced SOs and sleep spindles in older subjects</jats:p></jats:list-item><jats:list-item><jats:p>Stimulation effects were reduced and overall susceptibility diminished with age</jats:p></jats:list-item><jats:list-item><jats:p>Slow oscillation and sleep spindle dynamics deviated from those in younger subjects</jats:p></jats:list-item><jats:list-item><jats:p>Stimulation shows no evidence for memory effect in older subjects</jats:p></jats:list-item></jats:list></jats:p></jats:sec>