Publications
618 results found
Kirby P, Lai H, Horrocks S, et al., 2024, Patient and public involvement in technology-related dementia research: a scoping review, JMIR Aging, Vol: 7, ISSN: 2561-7605
Background:Technology-related research for people with dementia and their carers often aims to enable people to remain living at home for longer and to prevent unnecessary hospital admissions. To develop research that is person-centred, effective and ethical, patient and public involvement (PPI) is necessary, though may be perceived as more difficult with this cohort. With recent and rapid expansions in health and care related technology, this review explores how, and with what impact, collaborations between researchers and stakeholders such as people with dementia have taken place.Objective:To describe approaches to PPI used to date in technology-related dementia research, along with the barriers and facilitators and impact of PPI in this area.Methods:A scoping review of literature relating to dementia, technology and patient and public involvement was conducted using Medline, PsycINFO, EMBASE and CINAHL. Papers were screened for inclusion by two authors. Data was then extracted using a pre-designed data extraction table by the same two authors; a third author supported resolution of any conflicts at each stage. Barriers and facilitators of undertaking PPI were then examined and themed.Results:Thirty-one papers were included for analysis. The majority (21/31) did not make clear distinctions between activities undertaken as PPI and activities undertaken by research participants, and as such their involvement did not fit easily into the NIHR definition of PPI. Most of this mixed involvement focused on the reviewing or evaluating of technology prototypes. A range of approaches was described, most typically using focus groups or co-design workshops. Nine studies described involvement at multiple stages through the research cycle, sometimes with evidence of sharing of decision-making power. Some studies commented on barriers or facilitators to effective PPI. Challenges identified were often around issues of working with people with significant cognitive impairments, and
Graham N, Zimmerman K, Heslegrave A, et al., 2024, Alzheimer’s disease marker phospho-tau181 is not elevated in the first year after moderate-severe TBI, Journal of Neurology, Neurosurgery and Psychiatry, Vol: 95, Pages: 356-359, ISSN: 0022-3050
Background: Traumatic brain injury (TBI) is associated with the tauopathies Alzheimer’s disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheimer’s disease marker that could potentially seed progressive neurodegeneration. We tested whether post-traumatic p-tau181 concentrations are elevated and relate to progressive brain atrophy.Methods: Plasma p-tau181 and other post-traumatic biomarkers, including total-tau (t-tau), neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), were assessed after moderate-to-severe TBI in the BIO-AX-TBI cohort (first sample mean 2.7 days, second sample within 10 days, then 6 weeks, 6 months and 12 months, n=42). Brain atrophy rates were assessed in aligned serial MRI (n=40). Concentrations were compared patients with and without Alzheimer’s disease, with healthy controls.Results: Plasma p-tau181 concentrations were significantly raised in patients with Alzheimer’s disease but not after TBI, where concentrations were non-elevated, and remained stable over one year. P-tau181 after TBI was not predictive of brain atrophy rates in either grey or white matter. In contrast, substantial trauma-associated elevations in t-tau, NfL, GFAP and UCH-L1 were seen, with concentrations of NfL and t-tau predictive of brain atrophy rates.Conclusions: Plasma p-tau181 is not significantly elevated during the first year after moderate-to-severe TBI and levels do not relate to neuroimaging measures of neurodegeneration.
Guymon GG, Sharp D, Cohen TA, et al., 2024, Electrohydrodynamic Printing-Based Heterointegration of Quantum Dots on Suspended Nanophotonic Cavities, Advanced Materials Technologies
Nanophotonic structures are a foundation for the growing field of light-based quantum networks and devices enabled by their ability to couple with and manipulate photons. Colloidal quantum dots (QDs) are uniquely suited to complement this range of devices due to their solution-processability, broad tuneability, and near-unity photoluminescence quantum yields in some cases. To bridge the gap between them, electrohydrodynamic inkjet (EHDIJ) printing serves as a highly precise and scalable nanomanufacturing method for deterministic positioning and deposition of attoliter-scale QD droplets. This includes heterointegration in devices that are challenging to create by conventional subtractive semiconductor processing, such as QDs emitters coupled to substrate-decoupled nanoscale resonant structures. In this work, the first successful application of EHDIJ printing for the integration of these colloidal QDs into suspended nanophotonic cavities is demonstrated, achieving selective single-cavity deposition for cavity pairs as close as 100 nm apart. These results motivate the development of future suspended hetero-integrated devices that utilize EHDIJ printing as a sustainable, additive, and scalable method for quantum photonics nanomanufacturing.
Vinao-Carl M, Gal-Shohet Y, Rhodes E, et al., 2024, Just a phase? Causal probing reveals spurious phasic dependence of sustained attention, NeuroImage, Vol: 285, ISSN: 1053-8119
For over a decade, electrophysiological studies have reported correlations between attention / perception and the phase of spontaneous brain oscillations. To date, these findings have been interpreted as evidence that the brain uses neural oscillations to sample and predict upcoming stimuli. Yet, evidence from simulations have shown that analysis artefacts could also lead to spurious pre-stimulus oscillations that appear to predict future brain responses. To address this discrepancy, we conducted an experiment in which visual stimuli were presented in time to specific phases of spontaneous alpha and theta oscillations. This allowed us to causally probe the role of ongoing neural activity in visual processing independent of the stimulus-evoked dynamics. Our findings did not support a causal link between spontaneous alpha / theta rhythms and behaviour. However, spurious correlations between theta phase and behaviour emerged offline using gold-standard time-frequency analyses. These findings are a reminder that care should be taken when inferring causal relationships between neural activity and behaviour using acausal analysis methods.
Molero Y, Sharp DJ, D'Onofrio BM, et al., 2024, Medication utilization in traumatic brain injury patients-insights from a population-based matched cohort study., Front Neurol, Vol: 15, ISSN: 1664-2295
INTRODUCTION: Traumatic brain injury (TBI) is associated with health problems across multiple domains and TBI patients are reported to have high rates of medication use. However, prior evidence is thin due to methodological limitations. Our aim was thus to examine the use of a wide spectrum of medications prescribed to address pain and somatic conditions in a population-based cohort of TBI patients, and to compare this to a sex- and age-matched cohort. We also examined how patient factors such as sex, age, and TBI severity were associated with medication use. METHODS: We assessed Swedish nationwide registers to include all individuals treated for TBI in hospitals or specialist outpatient care between 2006 and 2012. We examined dispensed prescriptions for eight different non-psychotropic medication classes for the 12 months before, and 12 months after, the TBI. We applied a fixed-effects model to compare TBI patients with the matched population cohort. We also stratified TBI patients by sex, age, TBI severity and carried out comparisons using a generalized linear model. RESULTS: We identified 239,425 individuals with an incident TBI and 239,425 matched individuals. TBI patients were more likely to use any medication [Odds ratio (OR) = 2.03, 95% Confidence Interval (CI) = 2.00-2.05], to present with polypharmacy (OR = 1.96, 95% CI = 1.90-2.02), and to use each of the eight medication classes before their TBI, as compared to the matched population cohort. Following the TBI, TBI patients were more likely to use any medication (OR = 1.83, 95% CI = 1.80-1.86), to present with polypharmacy (OR = 1.74, 95% CI = 1.67-1.80), and to use all medication classes, although differences were attenuated. However, differences increased for antibiotics/antivirals (OR = 2.02, 95% CI = 1.99-2.05) and NSAIDs/antirheumatics (OR =&t
Cohen Z, Steinbrenner M, Piper RJ, et al., 2024, Transcranial electrical stimulation during functional magnetic resonance imaging in patients with genetic generalized epilepsy: a pilot and feasibility study., Front Neurosci, Vol: 18, ISSN: 1662-4548
OBJECTIVE: A third of patients with epilepsy continue to have seizures despite receiving adequate antiseizure medication. Transcranial direct current stimulation (tDCS) might be a viable adjunct treatment option, having been shown to reduce epileptic seizures in patients with focal epilepsy. Evidence for the use of tDCS in genetic generalized epilepsy (GGE) is scarce. We aimed to establish the feasibility of applying tDCS during fMRI in patients with GGE to study the acute neuromodulatory effects of tDCS, particularly on sensorimotor network activity. METHODS: Seven healthy controls and three patients with GGE received tDCS with simultaneous fMRI acquisition while watching a movie. Three tDCS conditions were applied: anodal, cathodal and sham. Periods of 60 s without stimulation were applied between each stimulation condition. Changes in sensorimotor cortex connectivity were evaluated by calculating the mean degree centrality across eight nodes of the sensorimotor cortex defined by the Automated Anatomical Labeling atlas (primary motor cortex (precentral left and right), supplementary motor area (left and right), mid-cingulum (left and right), postcentral gyrus (left and right)), across each of the conditions, for each participant. RESULTS: Simultaneous tDCS-fMRI was well tolerated in both healthy controls and patients without adverse effects. Anodal and cathodal stimulation reduced mean degree centrality of the sensorimotor network (Friedman's ANOVA with Dunn's multiple comparisons test; adjusted p = 0.02 and p = 0.03 respectively). Mean degree connectivity of the sensorimotor network during the sham condition was not different to the rest condition (adjusted p = 0.94). CONCLUSION: Applying tDCS during fMRI was shown to be feasible and safe in a small group of patients with GGE. Anodal and cathodal stimulation caused a significant reduction in network connectivity of the sensorimotor cortex across participants. This
Parker TD, Zimmerman KA, Laverse E, et al., 2023, Active elite rugby participation is associated with altered precentral cortical thickness, Brain Communications, Vol: 5, ISSN: 2632-1297
There is growing concern that elite rugby participation may negatively influence brain health, but the underlying mechanisms are unclear. Cortical thickness is a widely applied biomarker of grey matter structure, but there is limited research into how it may be altered in active professional rugby players. Cross-sectional MRI data from 44 active elite rugby players, including 21 assessed within 1 week of head injury, and 47 healthy controls were analysed. We investigated how active elite rugby participation with and without sub-acute traumatic brain injury influenced grey matter structure using whole cortex and region of interest cortical thickness analyses. Relationships between cortical thickness and biomarkers of traumatic brain injury, including fractional anisotropy, plasma neurofilament light and glial fibrillary acidic protein, were also examined. In whole-cortex analyses, precentral cortical thickness in the right hemisphere was lower in rugby players compared with controls, which was due to reductions in non-injured players. Post hoc region of interest analyses showed non-injured rugby players had reduced cortical thickness in the inferior precentral sulcal thickness bilaterally (P = 0.005) and the left central sulcus (P = 0.037) relative to controls. In contrast, players in the sub-acute phase of mild traumatic brain injury had higher inferior precentral sulcal cortical thickness in the right hemisphere (P = 0.015). Plasma glial fibrillary acidic protein, a marker of astrocyte activation, was positively associated with right inferior precentral sulcal cortical thickness in injured rugby players (P = 0.0012). Elite rugby participation is associated with localized alterations in cortical thickness, specifically in sulcal motor regions. Sub-acute changes after mild traumatic brain injury are associated with evidence of astrocytic activation. The combination of cortical thickness and glial fibrillary acidic protein may be useful in understanding the pathophysi
Graham NS, Sharp DJ, 2023, Dementia after traumatic brain injury, BMJ: British Medical Journal, Vol: 383, Pages: 2065-2065, ISSN: 1759-2151
Sharp DJ, Graham NSN, 2023, Clinical outcomes evolve years after traumatic brain injury, Nature Reviews Neurology, Vol: 19, Pages: 579-580, ISSN: 1759-4766
Parkinson M, Doherty R, Curtis F, et al., 2023, Using home monitoring technology to study the effects of traumatic brain injury in older multimorbid adults, Annals of Clinical and Translational Neurology, Vol: 10, Pages: 1688-1694, ISSN: 2328-9503
Internet of things (IOT) based in-home monitoring systems can passively collect high temporal resolution data in the community, offering valuable insight into the impact of health conditions on patients' day-to-day lives. We used this technology to monitor activity and sleep patterns in older adults recently discharged after traumatic brain injury (TBI). The demographics of TBI are changing, and it is now a leading cause of hospitalisation in older adults. However, research in this population is minimal. We present three cases, showcasing the potential of in-home monitoring systems in understanding and managing early recovery in older adults following TBI.
Fan X-R, Wang Y-S, Chang D, et al., 2023, A longitudinal resource for population neuroscience of school-age children and adolescents in China, SCIENTIFIC DATA, Vol: 10
Munley C, Manna A, Sharp D, et al., 2023, Visible Wavelength Flatband in a Gallium Phosphide Metasurface, ACS Photonics, Vol: 10, Pages: 2456-2460
Engineering the dispersion of light in a metasurface allows for controlling the light-matter interaction strength between light confined in the metasurface and materials placed within its near-field. Specifically, engineering a flatband dispersion increases the photonic density of states, thereby enhancing the light-matter interaction. Here, we experimentally demonstrate a metasurface with a flat dispersion at visible wavelengths. We designed and fabricated a suspended one-dimensional gallium phosphide metasurface and measured the photonic band structure via energy-momentum spectroscopy, observing a photonic band that is flat over 10° of half angle at ∼590 nm. We integrated cadmium selenide nanoplatelets with the metasurface and measured coupled photoluminescence into the flatband. Our demonstration of a photonic flatband enables the possibility of integrating emerging quantum emitters to the metasurface with possible applications in nonlinear image processing and topological photonics.
Crook-Rumsey M, Daniels S, Abulikemu S, et al., 2023, Multicohort cross-sectional study of cognitive and behavioural digital biomarkers in neurodegeneration: the Living Lab study protocol, BMJ Open, Vol: 13, Pages: 1-9, ISSN: 2044-6055
Introduction and aimsDigital biomarkers can provide a cost-effective, objective, and robust measure forneurological disease progression, changes in care needs, and the effect of interventions.Motor function, physiology and behaviour can provide informative measures of neurologicalconditions and neurodegenerative decline. New digital technologies present an opportunityto provide remote, high-frequency monitoring of patients from within their homes. Thepurpose of the Living Lab study is to develop novel digital biomarkers of functionalimpairment in those living with neurodegenerative disease (NDD) and neurologicalconditions.Methods and analysisThe Living Lab Study is a cross-sectional observational study of cognition and behaviour inpeople living with NDDs and other, non-degenerative neurological conditions. Patients (n≥25for each patient group) with Dementia, Parkinson’s disease, Amyotrophic Lateral Sclerosis, Mild Cognitive Impairment, Traumatic Brain Injury, and Stroke along with controls (n≥60) willbe pragmatically recruited. Patients will carry out activities of daily living and functionalassessments within the living lab. The living lab is an apartment-laboratory containing afunctional kitchen, bathroom, bed and living area to provide a controlled environment todevelop novel digital biomarkers. The living lab provides an important intermediary stagebetween the conventional laboratory and the home. Multiple passive environmental sensors,internet-enabled medical devices, wearables, and EEG will be used to characterise functionalimpairments of NDDs and non-NDD conditions. We will also relate these digital technologymeasures to clinical and cognitive outcomes.Ethics and disseminationEthical approvals have been granted by the Imperial College Research Ethics Committee(reference number: 21IC6992). Results from the study will be disseminated at conferencesand within peer-reviewed journals.
Graham NSN, Cole JH, Bourke NJ, et al., 2023, Distinct patterns of neurodegeneration after TBI and in Alzheimer's disease, Alzheimer's and Dementia, Vol: 19, Pages: 3065-3077, ISSN: 1552-5260
IntroductionTraumatic brain injury (TBI) is a dementia risk factor, with Alzheimer's disease (AD) more common following injury. Patterns of neurodegeneration produced by TBI can be compared to AD and aging using volumetric MRI.MethodsA total of 55 patients after moderate to severe TBI (median age 40), 45 with AD (median age 69), and 61 healthy volunteers underwent magnetic resonance imaging over 2 years. Atrophy patterns were compared.ResultsAD patients had markedly lower baseline volumes. TBI was associated with increased white matter (WM) atrophy, particularly involving corticospinal tracts and callosum, whereas AD rates were increased across white and gray matter (GM). Subcortical WM loss was shared in AD/TBI, but deep WM atrophy was TBI-specific and cortical atrophy AD-specific. Post-TBI atrophy patterns were distinct from aging, which resembled AD.DiscussionPost-traumatic neurodegeneration 1.9–4.0 years (median) following moderate-severe TBI is distinct from aging/AD, predominantly involving central WM. This likely reflects distributions of axonal injury, a neurodegeneration trigger.HighlightsWe compared patterns of brain atrophy longitudinally after moderate to severe TBI in late-onset AD and healthy aging.Patients after TBI had abnormal brain atrophy involving the corpus callosum and other WM tracts, including corticospinal tracts, in a pattern that was specific and distinct from AD and aging.This pattern is reminiscent of axonal injury following TBI, and atrophy rates were predicted by the extent of axonal injury on diffusion tensor imaging, supporting a relationship between early axonal damage and chronic neurodegeneration.
Rakshasa-Loots AM, Bakewell NJ, Sharp DJ, et al., 2023, Biomarkers of central and peripheral inflammation mediate the association between HIV and depressive symptoms, TRANSLATIONAL PSYCHIATRY, Vol: 13, ISSN: 2158-3188
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Li L, Heselgrave A, Soreq E, et al., 2023, Investigating the characteristics and correlates of systemic inflammation after traumatic brain injury: the TBI-BraINFLAMM study, BMJ Open, Vol: 13, ISSN: 2044-6055
Introduction: A significant environmental risk factor for neurodegenerative disease is traumatic brain injury (TBI). However, it is not clear how TBI results in ongoing chronic neurodegeneration. Animal studies show that systemic inflammation is signalled to the brain. This can result in sustained and aggressive microglial activation, which in turn is associated with widespread neurodegeneration. We aim to evaluate systemic inflammation as a mediator of ongoing neurodegeneration after TBI.Methods and analysis: TBI-braINFLAMM will combine data already collected from two large prospective TBI studies. The CREACTIVE study, a broad consortium which enrolled >8000 patients with TBI to have CT scans and blood samples in the hyperacute period, has data available from 854 patients. The BIO-AX-TBI study recruited 311 patients to have acute CT scans, longitudinal blood samples and longitudinal MRI brain scans. The BIO-AX-TBI study also has data from 102 healthy and 24 non-TBI trauma controls, comprising blood samples (both control groups) and MRI scans (healthy controls only). All blood samples from BIO-AX-TBI and CREACTIVE have already been tested for neuronal injury markers (GFAP, tau and NfL), and CREACTIVE blood samples have been tested for inflammatory cytokines. We will additionally test inflammatory cytokine levels from the already collected longitudinal blood samples in the BIO-AX-TBI study, as well as matched microdialysate and blood samples taken during the acute period from a subgroup of patients with TBI (n=18).We will use this unique dataset to characterise post-TBI systemic inflammation, and its relationships with injury severity and ongoing neurodegeneration.Ethics and dissemination: Ethical approval for this study has been granted by the London—Camberwell St Giles Research Ethics Committee (17/LO/2066). Results will be submitted for publication in peer-review journals, presented at conferences and inform the design of larger observational and experime
Parkinson M, Dani M, Fertleman M, et al., 2023, Using home monitoring technology to study the effects of traumatic brain Injury in older multimorbid adults: protocol for a feasibility study, BMJ Open, Vol: 13, ISSN: 2044-6055
Introduction:The prevalence of Traumatic Brain Injury (TBI) among older adults is increasing exponentially. The sequelae can be severe in older adults and interacts with age-related conditions such a multimorbidity. Despite this, TBI research in older adults, is sparse. Minder, an in-home monitoring system using developed by the UK DRI Centre for Care Research and Technology, uses infra-red sensors and a bed mat to passively collect sleep and activity data. Similar systems have been used to monitor the health of older adults living with dementia. We will assess the feasibility of using this system to study changes in the health status of older adults in the early period post TBI.Methods and analysis:The study will recruit 15 inpatients (>60 years) with a moderate-severe TBI, who will have their daily activity and sleep patterns monitored using passive and wearable sensors over 6 months. Participants will report on their health during weekly calls, which will be used to validate sensor data. Physical, functional, and cognitive assessments will be conducted across the duration of the study. Activity levels and sleep patterns derived from sensor data will be calculated and visualised using activity maps. Within participant analysis will be performed to determine if participants are deviating from their own routines. We will apply machine learning approaches to activity and sleep data to assess whether these changes in these data can predict clinical events. Qualitative analysis of interviews conducted with participants, carers, and clinical staff will assess acceptability and utility of the system.Ethics and dissemination:Ethical approval for this study has been granted by the London - Camberwell St Giles Research Ethics Committee (REC number: 17/LO/2066). Results will be submitted for publication in peer review journals, presented at conferences and inform the design of a larger trial assessing recovery after TBI.
Del Giovane M, Trender WR, Bălăeţ M, et al., 2023, Computerised cognitive assessment in patients with traumatic brain injury: an observational study of feasibility and sensitivity relative to established clinical scales, EClinicalMedicine, Vol: 59, ISSN: 2589-5370
Background:Online technology could potentially revolutionise how patients are cognitively assessed and monitored. However, it remains unclear whether assessments conducted remotely can match established pen-and-paper neuropsychological tests in terms of sensitivity and specificity.Methods:This observational study aimed to optimise an online cognitive assessment for use in traumatic brain injury (TBI) clinics. The tertiary referral clinic in which this tool has been clinically implemented typically sees patients a minimum of 6 months post-injury in the chronic phase. Between March and August 2019, we conducted a cross-group, cross-device and factor analyses at the St. Mary’s Hospital TBI clinic and major trauma wards at Imperial College NHS trust and St. George’s Hospital in London (UK), to identify a battery of tasks that assess aspects of cognition affected by TBI. Between September 2019 and February 2020, we evaluated the online battery against standard face-to-face neuropsychological tests at the Imperial College London research centre. Canonical Correlation Analysis (CCA) determined the shared variance between the online battery and standard neuropsychological tests. Finally, between October 2020 and December 2021, the tests were integrated into a framework that automatically generates a results report where patients’ performance is compared to a large normative dataset. We piloted this as a practical tool to be used under supervised and unsupervised conditions at the St. Mary’s Hospital TBI clinic in London (UK).Findings:The online assessment discriminated processing-speed, visual-attention, working-memory, and executive-function deficits in TBI. CCA identified two significant modes indicating shared variance with standard neuropsychological tests (r = 0.86, p < 0.001 and r = 0.81, p = 0.02). Sensitivity to cognitive deficits after TBI was evident in the TBI clinic setting under supervised and unsupervised conditions (F (15,555) = 3.9
Bourke N, Trender W, Hampshire A, et al., 2023, Assessing prospective and retrospective metacognitive accuracy following traumatic brain injury remotely across cognitive domains, Neuropsychological Rehabilitation, Vol: 33, Pages: 574-591, ISSN: 0960-2011
The ability to monitor one's behaviour is frequently impaired following TBI, impacting on patients’ rehabilitation. Inaccuracies in judgement or self-reflection of one’s performance provides a useful marker of metacognition. However, metacognition is rarely measured during routine neuropsychology assessments and how it varies across cognitive domains is unclear. A cohort of participants consisting of 111 TBI patients [mean age = 45.32(14.15), female = 29] and 84 controls [mean age = 31.51(12.27), female = 43] was studied. Participants completed cognitive assessments via a bespoke digital platform on their smartphones. Included in the assessment were a prospective evaluation of memory and attention, and retrospective confidence judgements of task performance. Metacognitive accuracy was calculated from the difference between confidence judgement of task performance and actual performance. Prospective judgment of attention and memory was correlated with task performance in these domains for controls but not patients. TBI patients had lower task performance in processing speed, executive functioning and working memory compared to controls, maintaining high confidence, resulting in overestimation of cognitive performance compared to controls. Additional judgments of task performance complement neuropsychological assessments with little additional time–cost. These results have important theoretical and practical implications for evaluation of metacognitive impairment in TBI patients and neurorehabilitation.
Graham NSN, Blissitt G, Zimmerman K, et al., 2023, ADVANCE-TBI study protocol: traumatic brain injury outcomes in UK military personnel serving in Afghanistan between 2003 and 2014 - a longitudinal cohort study, BMJ Open, Vol: 13, ISSN: 2044-6055
INTRODUCTION: Outcomes of traumatic brain injury (TBI) are highly variable, with cognitive and psychiatric problems often present in survivors, including an increased dementia risk in the long term. Military personnel are at an increased occupational risk of TBI, with high rates of complex polytrauma including TBI characterising the UK campaign in Afghanistan. The ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE)-TBI substudy will describe the patterns, associations and long-term outcomes of TBI in the established ADVANCE cohort. METHODS AND ANALYSIS: The ADVANCE cohort comprises 579 military personnel exposed to major battlefield trauma requiring medical evacuation, and 566 matched military personnel without major trauma. TBI exposure has been captured at baseline using a standardised interview and registry data, and will be refined at first follow-up visit with the Ohio State Method TBI interview (a National Institute of Neurological Disorders and Stroke TBI common data element). Participants will undergo blood sampling, MRI and detailed neuropsychological assessment longitudinally as part of their follow-up visits every 3-5 years over a 20-year period. Biomarkers of injury, neuroinflammation and degeneration will be quantified in blood, and polygenic risk scores calculated for neurodegeneration. Age-matched healthy volunteers will be recruited as controls for MRI analyses. We will describe TBI exposure across the cohort, and consider any relationship with advanced biomarkers of injury and clinical outcomes including cognitive performance, neuropsychiatric symptom burden and function. The influence of genotype will be assessed. This research will explore the relationship between military head injury exposure and long-term outcomes, providing insights into underlying disease mechanisms and informing prevention interventions. ETHICS AND DISSEMINATION: The ADVANCE-TBI substudy has received a favourable opinion from the Ministry of Defence Research Eth
David MCB, Kolanko M, Del Giovane M, et al., 2023, Remote monitoring of physiology in people living with dementia: an observational cohort study, JMIR Aging, Vol: 6, Pages: 1-14, ISSN: 2561-7605
BACKGROUND: Internet of Things (IoT) technology enables physiological measurements to be recorded at home from people living with dementia and monitored remotely. However, measurements from people with dementia in this context have not been previously studied. We report on the distribution of physiological measurements from 82 people with dementia over approximately 2 years. OBJECTIVE: Our objective was to characterize the physiology of people with dementia when measured in the context of their own homes. We also wanted to explore the possible use of an alerts-based system for detecting health deterioration and discuss the potential applications and limitations of this kind of system. METHODS: We performed a longitudinal community-based cohort study of people with dementia using "Minder," our IoT remote monitoring platform. All people with dementia received a blood pressure machine for systolic and diastolic blood pressure, a pulse oximeter measuring oxygen saturation and heart rate, body weight scales, and a thermometer, and were asked to use each device once a day at any time. Timings, distributions, and abnormalities in measurements were examined, including the rate of significant abnormalities ("alerts") defined by various standardized criteria. We used our own study criteria for alerts and compared them with the National Early Warning Score 2 criteria. RESULTS: A total of 82 people with dementia, with a mean age of 80.4 (SD 7.8) years, recorded 147,203 measurements over 958,000 participant-hours. The median percentage of days when any participant took any measurements (ie, any device) was 56.2% (IQR 33.2%-83.7%, range 2.3%-100%). Reassuringly, engagement of people with dementia with the system did not wane with time, reflected in there being no change in the weekly number of measurements with respect to time (1-sample t-test on slopes of linear fit, P=.45). A total of 45% of people with dementia met criteria for hypertension. People with dem
Bernini A, Magnoni S, Miroz J-P, et al., 2023, Cerebral metabolic dysfunction at the acute phase of traumatic brain injury correlates with long-term tissue loss, Journal of Neurotrauma, Vol: 40, Pages: 472-481, ISSN: 0897-7151
Following traumatic brain injury (TBI), cerebral metabolic dysfunction, characterized by an elevated cerebral microdialysis (CMD) lactate/pyruvate (LP) ratio, is associated with poor outcome. However, the exact pathophysiological mechanisms underlying this association are not entirely established. In this pre-planned analysis of the BIOmarkers of AXonal injury after Traumatic Brain Injury (BIO-AX-TBI) prospective study, we investigated any associations of LP ratio with brain structure volume change rates at 1 year. Fourteen subjects underwent acute-phase (0–96 h post-TBI) CMD monitoring and had longitudinal magnetic resonance imaging (MRI) quantification of brain volume loss between the subacute phase (14 days to 6 weeks) and 1 year after TBI, recalculated as an annual rate. On average, CMD showed an elevated (>25) LP ratio (31 [interquartile range (IQR) 24–34]), indicating acute cerebral metabolic dysfunction. Annualized whole brain and total gray matter (GM) volume change rates were abnormally reduced (−3.2% [−9.3 to −2.2] and −1.9% [−4.4 to 1.7], respectively). Reduced annualized total GM volume correlated significantly with elevated CMD LP ratio (Spearman's ρ = −0.68, p-value = 0.01) and low CMD glucose (ρ = 0.66, p-value = 0.01). After adjusting for age, admission Glasgow Coma Scale (GCS) score and CT Marshall score, CMD LP ratio remained strongly associated with 1-year total GM volume change rate (p < 0.001; multi-variable analysis). No relationship was found between WM volume changes and CMD metabolites. We demonstrate a strong association between acute post-traumatic cerebral metabolic dysfunction and 1-year gray matter atrophy, reinforcing the role of CMD LP ratio as an early biomarker of poor long-term recovery after TBI.
Ibitoye R, Mallas E-J, Bourke N, et al., 2023, The human vestibular cortex: functional anatomy of OP2, its connectivity and the effect of vestibular disease, Cerebral Cortex, Vol: 33, Pages: 567-582, ISSN: 1047-3211
Area OP2 in the posterior peri-sylvian cortex has been proposed to be the core human vestibular cortex. We investigated the functional anatomy of OP2 and adjacent areas (OP2+) using spatially constrained independent component analysis of functional MRI data from the Human ConnectomeProject. Ten ICA-derived subregions were identified. OP2+ responses to vestibular and visual-motion were analysed in 17 controls and 17 right-sided vestibular neuritis patients who had previously undergone caloric and optokinetic stimulation during functional MRI. In controls, a posterior part of right OP2+ showed: (a) direction-selective responses to visual motion; and (b) activation during caloric stimulation that correlated positively with perceived self-motion, and negatively with visual dependence and peak slow phase nystagmus velocity. Patients showed abnormal OP2+ activity, with an absence of visual or caloric activation of the healthy ear and no correlations with vertigo or visual dependence – despite normal slow-phase nystagmus responses to caloric stimulation. Activity in a lateral part of right OP2+ correlated with chronic visually-induced dizziness in patients. In summary, distinct functional subregions of right OP2+ show strong connectivity to other vestibular areas and a profile of caloric and visual responses suggesting a central role for vestibular function in health and disease.
Nguyen HA, Sharp D, Fröch JE, et al., 2023, Deterministic Quantum Light Arrays from Giant Silica-Shelled Quantum Dots., ACS Appl Mater Interfaces, Vol: 15, Pages: 4294-4302
Colloidal quantum dots (QDs) are promising candidates for single-photon sources with applications in photonic quantum information technologies. Developing practical photonic quantum devices with colloidal materials, however, requires scalable deterministic placement of stable single QD emitters. In this work, we describe a method to exploit QD size to facilitate deterministic positioning of single QDs into large arrays while maintaining their photostability and single-photon emission properties. CdSe/CdS core/shell QDs were encapsulated in silica to both increase their physical size without perturbing their quantum-confined emission and enhance their photostability. These giant QDs were then precisely positioned into ordered arrays using template-assisted self-assembly with a 75% yield for single QDs. We show that the QDs before and after assembly exhibit antibunching behavior at room temperature and their optical properties are retained after an extended period of time. Together, this bottom-up synthetic approach via silica shelling and the robust template-assisted self-assembly offer a unique strategy to produce scalable quantum photonics platforms using colloidal QDs as single-photon emitters.
Curtis F, Li L, Kolanko M, et al., 2023, 1362 Anticholinergic prescribing habits and its associations in a community population of people living with dementia, British Geriatrics Society Autumn Meeting 2022, Publisher: Oxford University Press, ISSN: 0002-0729
Parkinson M, Doherty R, Curtis F, et al., 2023, 1415 Novel approaches to post discharge care.remote healthcare monitoring systems following traumatic brain injury in older adults, British Geriatrics Society Autumn Meeting 2022, Publisher: Oxford University Press, ISSN: 0002-0729
Zimmerman K, 2022, The biomechanical signature of loss of consciousness: computational modelling of elite athlete head injuries, Brain: a journal of neurology, ISSN: 0006-8950
Azor AM, Sharp DJ, Jolly AE, et al., 2022, Automation and standardization of subject-specific region-of-interest segmentation for investigation of diffusion imaging in clinical populations, PLOS ONE, Vol: 17, ISSN: 1932-6203
Mallas E-J, Gorgoraptis N, Dautricourt S, et al., 2022, Pathological slow-wave activity and impaired working memory binding in post-traumatic amnesia, The Journal of Neuroscience, Vol: 42, Pages: 9193-9210, ISSN: 0270-6474
Associative binding is key to normal memory function and is transiently disrupted during periods of post-traumatic amnesia (PTA) following traumatic brain injury (TBI). Electrophysiological abnormalities including low-frequency activity are common following TBI. Here, we investigate associative memory binding during PTA and test the hypothesis that misbinding is caused by pathological slowing of brain activity disrupting cortical communication. Thirty acute moderate-severe TBI patients (25 males; 5 females) and 26 healthy controls (20 males; 6 females) were tested with a precision working memory paradigm requiring the association of object and location information. Electrophysiological effects of TBI were assessed using resting-state EEG in a subsample of 17 patients and 21 controls. PTA patients showed abnormalities in working memory function and made significantly more misbinding errors than patients who were not in PTA and controls. The distribution of localisation responses was abnormally biased by the locations of non-target items for patients in PTA suggesting a specific impairment of object and location binding. Slow wave activity was increased following TBI. Increases in the delta-alpha ratio indicative of an increase in low-frequency power specifically correlated with binding impairment in working memory. Connectivity changes in TBI did not correlate with binding impairment. Working memory and electrophysiological abnormalities normalised at six-month follow-up. These results show that patients in PTA show high rates of misbinding that are associated with a pathological shift towards lower frequency oscillations.
Lima MR, Wairagkar M, Gupta M, et al., 2022, Conversational affective social robots for ageing and dementia support, IEEE Transactions on Cognitive and Developmental Systems, Vol: 14, Pages: 1378-1397, ISSN: 2379-8920
Socially assistive robots (SAR) hold significant potential to assist older adults and people with dementia in human engagement and clinical contexts by supporting mental health and independence at home. While SAR research has recently experienced prolific growth, long-term trust, clinical translation and patient benefit remain immature. Affective human-robot interactions are unresolved and the deployment of robots with conversational abilities is fundamental for robustness and humanrobot engagement. In this paper, we review the state of the art within the past two decades, design trends, and current applications of conversational affective SAR for ageing and dementia support. A horizon scanning of AI voice technology for healthcare, including ubiquitous smart speakers, is further introduced to address current gaps inhibiting home use. We discuss the role of user-centred approaches in the design of voice systems, including the capacity to handle communication breakdowns for effective use by target populations. We summarise the state of development in interactions using speech and natural language processing, which forms a baseline for longitudinal health monitoring and cognitive assessment. Drawing from this foundation, we identify open challenges and propose future directions to advance conversational affective social robots for: 1) user engagement, 2) deployment in real-world settings, and 3) clinical translation.
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