Publications
38 results found
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.
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.
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
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
Rosnati M, Soreq E, Monteiro M, et al., 2022, Automatic lesion analysis for increased efficiency in outcome prediction of traumatic brain injury, 5th International Workshop, MLCN 2022, Publisher: Springer Nature Switzerland, Pages: 135-146, ISSN: 0302-9743
The accurate prognosis for traumatic brain injury (TBI) patients is difficult yet essential to inform therapy, patient management, and long-term after-care. Patient characteristics such as age, motor and pupil responsiveness, hypoxia and hypotension, and radiological findings on computed tomography (CT), have been identified as important variables for TBI outcome prediction. CT is the acute imaging modality of choice in clinical practice because of its acquisition speed and widespread availability. However, this modality is mainly used for qualitative and semi-quantitative assessment, such as the Marshall scoring system, which is prone to subjectivity and human errors. This work explores the predictive power of imaging biomarkers extracted from routinely-acquired hospital admission CT scans using a state-of-the-art, deep learning TBI lesion segmentation method. We use lesion volumes and corresponding lesion statistics as inputs for an extended TBI outcome prediction model. We compare the predictive power of our proposed features to the Marshall score, independently and when paired with classic TBI biomarkers. We find that automatically extracted quantitative CT features perform similarly or better than the Marshall score in predicting unfavourable TBI outcomes. Leveraging automatic atlas alignment, we also identify frontal extra-axial lesions as important indicators of poor outcome. Our work may contribute to a better understanding of TBI, and provides new insights into how automated neuroimaging analysis can be used to improve prognostication after TBI.
Li LM, Dilley MD, Carson A, et al., 2022, Response to: Management of traumatic brain injury: practical development of a recent proposal, CLINICAL MEDICINE, Vol: 22, Pages: 358-359, ISSN: 1470-2118
Li L, Vichayanrat E, Del Giovane M, et al., 2022, Autonomic dysfunction after moderate-to-severe traumatic brain injury: symptom spectrum and clinical testing outcomes, BMJ Open Neurology, Vol: 4, ISSN: 2632-6140
Background: Survivors of moderate-to-severe traumatic brain injury (msTBI) frequently experience troublesome unexplained somatic symptoms. Autonomic dysfunction may contribute to these symptoms. However, there is no previous study of clinical subjective and objective autonomic dysfunction in msTBI.Methods: We present results from two groups of patients with msTBI. The first, a case–control comparative study, comprises prospectively recruited msTBI outpatients, in whom we measured burden of autonomic symptoms using the Composite Autonomic Symptom Score (COMPASS31) questionnaire. The second, a descriptive case series, comprises retrospectively identified msTBI outpatients who had formal clinical autonomic function testing at a national referral autonomics unit.Results: Group 1 comprises 39 patients with msTBI (10F:20M, median age 40 years, range 19–76), median time from injury 19 months (range 6–299) and 44 controls (22F:22M, median age 45, range 25–71). Patients had significantly higher mean weighted total COMPASS-31 score than controls (p<0.001), and higher gastrointestinal, orthostatic and secretomotor subscores (corrected p<0.05). Total COMPASS31 score inversely correlated with subjective rating of general health (p<0.001, rs=−0.84). Group 2 comprises 18 patients with msTBI (7F:11M, median age 44 years, range 21–64), median time from injury 57.5 months (range 2–416). Clinical autonomic function testing revealed a broad spectrum of autonomic dysfunction in 13/18 patients.Conclusions: There is clinically relevant autonomic dysfunction after msTBI, even at the chronic stage. We advocate for routine enquiry about potential autonomic symptoms, and demonstrate the utility of formal autonomic testing in providing diagnoses. Larger prospective studies are warranted, which should explore the causes and clinical correlates of post-TBI autonomic dysfunction.
Parkinson M, Doherty R, Curtis C, et al., 2022, Exploring interactions between traumatic brain injury, Association of British Neurologists
Ekhtiari H, Ghobadi-Azbari P, Thielscher A, et al., 2022, A checklist for assessing the methodological quality of concurrent tES-fMRI studies (ContES checklist): a consensus study and statement, NATURE PROTOCOLS, Vol: 17, Pages: 596-+, ISSN: 1754-2189
- Author Web Link
- Cite
- Citations: 8
Kurtin DL, Violante IR, Zimmerman K, et al., 2021, Investigating the interaction between white matter and brain state on tDCS-induced changes in brain network activity, Brain Stimulation, Vol: 14, Pages: 1261-1270, ISSN: 1876-4754
BACKGROUND: Transcranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation whose potential as a cognitive therapy is hindered by our limited understanding of how participant and experimental factors influence its effects. Using functional MRI to study brain networks, we have previously shown in healthy controls that the physiological effects of tDCS are strongly influenced by brain state. We have additionally shown, in both healthy and traumatic brain injury (TBI) populations, that the behavioral effects of tDCS are positively correlated with white matter (WM) structure. OBJECTIVES: In this study we investigate how these two factors, WM structure and brain state, interact to shape the effect of tDCS on brain network activity. METHODS: We applied anodal, cathodal and sham tDCS to the right inferior frontal gyrus (rIFG) of healthy (n = 22) and TBI participants (n = 34). We used the Choice Reaction Task (CRT) performance to manipulate brain state during tDCS. We acquired simultaneous fMRI to assess activity of cognitive brain networks and used Fractional Anisotropy (FA) as a measure of WM structure. RESULTS: We find that the effects of tDCS on brain network activity in TBI participants are highly dependent on brain state, replicating findings from our previous healthy control study in a separate, patient cohort. We then show that WM structure further modulates the brain-state dependent effects of tDCS on brain network activity. These effects are not unidirectional - in the absence of task with anodal and cathodal tDCS, FA is positively correlated with brain activity in several regions of the default mode network. Conversely, with cathodal tDCS during CRT performance, FA is negatively correlated with brain activity in a salience network region. CONCLUSIONS: Our results show that experimental and participant factors interact to have unexpected effects on brain network activity, and that these effects are not fully predictable by studying the fa
Li LM, Bourke NJ, Lai HHL, et al., 2021, Conferences in the time of COVID: notes on organizing and delivering the first Brain Conference, Brain Communications, Vol: 3, ISSN: 2632-1297
To further fulfil their missions of promoting teaching, education and research in neurology and related clinical-academic disciplines, the Guarantors of Brain and the Brain journal family invited delegates to the first Brain Conference in Spring of this year. This event aimed to deliver excellent teaching and scientific presentations across a broad spectrum of neuroscience fields, with the key aim of making the content as accessible as possible. We hoped to capitalize on the benefits of an online format, whilst trying to capture a little of the joy of the in-person meeting. This article reports on the approach and practical choices made to achieve these goals, and we hope this will provide some guidance and advice to others organizing their own online conference.
Olsen A, Babikian T, Bigler ED, et al., 2021, Toward a global and reproducible science for brain imaging in neurotrauma: the ENIGMA adult moderate/severe traumatic brain injury working group, BRAIN IMAGING AND BEHAVIOR, Vol: 15, Pages: 526-554, ISSN: 1931-7557
- Author Web Link
- Cite
- Citations: 11
Li LM, Dilley MD, Carson A, et al., 2021, Management of traumatic brain injury (TBI): a clinical neuroscience-led pathway for the NHS., Clinical medicine (London, England), Vol: 21, Pages: e198-e205, ISSN: 1470-2118
Following hyperacute management after traumatic brain injury (TBI), most patients receive treatment which is inadequate or inappropriate, and delayed. This results in suboptimal rehabilitation outcome and avoidable detrimental chronic effects on patients' recovery. This worsens long-term disability, and magnifies costs to the individual and society. We believe that accurate diagnosis (at the level of pathology, impairment and function) of the causes of disability is a prerequisite for appropriate care and for accessing effective rehabilitation. An expert-led, integrated care pathway is needed to deliver accurate and timely diagnosis and optimal treatment at all stages during a TBI patient's care.We propose the introduction of a specialist interdisciplinary traumatic brain injury team, led by a neurosciences-trained brain injury consultant. This team would engage acutely and for a longer term after TBI to provide accurate diagnoses, which guides subsequent management and rehabilitation. This approach would also encourage more efficient collaboration between research and the clinic. We propose that the current major trauma network is leveraged to introduce and evaluate this proposal. Improvements to patient outcomes through this approach would lead to reduced personal, societal and economic impact of TBI.
Mallas E-J, De Simoni S, Scott G, et al., 2021, Abnormal dorsal attention network activation in memory impairment after traumatic brain injury, Brain: a journal of neurology, Vol: 144, Pages: 114-127, ISSN: 0006-8950
Memory impairment is a common, disabling effect of traumatic brain injury. In healthy individuals, successful memory encoding is associated with activation of the dorsal attention network as well as suppression of the default mode network. Here, in traumatic brain injurypatients we examined whether: i) impairments in memory encoding are associated with abnormal brain activation in these networks; ii) whether changes in this brain activity predict subsequent memory retrieval; and iii) whether abnormal white matter integrity underpinningfunctional networks is associated with impaired subsequent memory. 35 patients with moderate-severetraumatic brain injury aged 23-65 years (74% males) in the post-acute/chronic phase after injury and 16 healthy controls underwent functional MRI during performance of an abstract image memory encoding task. Diffusion tensor imaging was used to assess structural abnormalities across patient groups compared to 28 age-matched healthy controls. Successful memory encoding across all participants was associated with activation of the dorsal attention network, the ventral visual stream and medial temporal lobes. Decreased activation was seen in the default mode network. Patients with preserved episodic memory demonstrated increased activation in areas of the dorsal attention network.Patients with impaired memory showed increased left anterior prefrontal activity. White matter microstructure underpinning connectivity between core nodes of the encoding networks was significantly reduced in patients with memory impairment. Our results show for the first time that patients with impaired episodic memory show abnormal activation of key nodes within the dorsal attention network and regions regulating default mode network activity during encoding. Successful encoding was associated with an opposite direction of signal
Varatharaj A, Thomas N, Ellul MA, et al., 2020, Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study., Lancet Psychiatry, Vol: 7, Pages: 875-882
BACKGROUND: Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series. Larger studies have been limited by both geography and specialty. Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies. The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain. METHODS: During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care. Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations). Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available. Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies. FINDINGS: The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020
Deb S, Crawford M, Sharp D, et al., 2020, Risperidone versus placebo for aggression following traumatic brain injury: a feasibility randomised controlled trial, BMJ Open, Vol: 10, ISSN: 2044-6055
Objectives: To conduct a feasibility randomised controlled trial of risperidone for the treatment of aggression in adults with traumatic brain injury (TBI).Design: Multi-centre, parallel design, placebo controlled (1:1 ratio) double-blind feasibility trial with an embedded process evaluation. No statistical comparison was performed between the two study groups.Setting Four neuropsychiatric and neurology outpatient clinics in London and Kent, UK. Participants Our aim was to recruit 50 TBI patients over 18 months. Follow up participants at 12 weeks using a battery of assessment scales to measure changes in aggressive behaviour (MOAS-primary outcome, IRQ) as well as global functioning (GOS-E, CGI) and quality of life (EQ-5D-5L, SF-12), mental health (HADS) and medication adverse effects (UKU).Results: Six participants were randomised to the active arm of the trial and eight to the placebo arm over a 10-month period (28% of our target). Two participants withdrew because of adverse events. Twelve out of 14 (85.7%) patients completed a follow up assessment at 12 weeks. At follow up, the scores of all outcome measures improved in both groups. Placebo group showed numerically better score change according to the primary outcome MOAS. No severe adverse events were reported. The overall rate of adverse events remained low. Data from the process evaluation suggest that existence of specialised TBI Follow-up clinics, availability of a dedicated database of TBI patients’ clinical details, simple study procedures and regular support to participants would enhance recruitment and retention in the trial. Feedback from participants showed that once in the study, they did not find the trial procedure onerous.Conclusions: It was not feasible to conduct a successful randomised trial of risperidone versus placebo for post-TBI aggression using the methods we deployed in this study. It is not possible to draw any definitive conclusion about risperidone’s efficacy from such a s
Li L, Violante I, Zimmerman K, et al., 2019, Traumatic axonal injury influences the cognitive effect of non-invasive brain stimulation, Brain, Vol: 142, Pages: 3280-3293, ISSN: 1460-2156
Non-invasive brain stimulation has been widely investigated for as a potentialtreatment for a range of neurological and psychiatric conditions, including braininjury. However, the behavioural effects of brain stimulation are very variable, forreasons that are poorly understood. This is a particular challenge for traumatic braininjury, where patterns of damage and their clinical effects are heterogenous. Here wetest the hypothesis that the response to transcranial direct current stimulationfollowing traumatic brain injury is dependent on white matter damage within thestimulated network. We used a novel simultaneous stimulation-MRI protocolapplying anodal, cathodal and sham stimulation to 24 healthy and 35 moderate/severetraumatic brain injury patients. Stimulation was applied to the right inferior frontalgyrus/anterior insula node of the Salience Network, which was targeted because ourprevious work had shown its importance to executive function. Stimulation wasapplied during performance of the Stop Signal Task, which assesses responseinhibition, a key component of executive function. Structural MRI was used to assessthe extent of brain injury, including diffusion MRI assessment of post-traumaticaxonal injury. Functional MRI, which was simultaneously acquired to delivery ofstimulation, assessed the effects of stimulation on cognitive network function. Anodalstimulation improved response inhibition in control participants, an effect that was notobserved in the patient group. The extent of traumatic axonal injury within theSalience Network strongly influenced the behavioural response to stimulation.Increasing damage to the tract connecting the stimulated right inferior frontalgyrus/anterior insula to the rest of the SN was associated with reduced beneficialeffects of stimulation. In addition, anodal stimulation normalised Default ModeNetwork activation in patients with poor response inhibition, suggesting thatstimulation modulates communication between the networks invo
Gorgoraptis N, Li LM, Whittington A, et al., 2019, In vivo detection of cerebral tau pathology in long-term survivors of traumatic brain injury, Science Translational Medicine, Vol: 11, Pages: 1-14, ISSN: 1946-6234
Traumatic brain injury (TBI) can trigger progressive neurodegeneration, with tau pathology seen years after a single moderate-severe TBI. Identifying this type of posttraumatic pathology in vivo might help to understand the role of tau pathology in TBI pathophysiology. We used flortaucipir positron emission tomography (PET) to investigate whether tau pathology is present many years after a single TBI in humans. We examined PET data in relation to markers of neurodegeneration in the cerebrospinal fluid (CSF), structural magnetic resonance imaging measures, and cognitive performance. Cerebral flortaucipir binding was variable, with many participants with TBI showing increases in cortical and white matter regions. At the group level, flortaucipir binding was increased in the right occipital cortex in TBI when compared to healthy controls. Flortaucipir binding was associated with increased total tau, phosphorylated tau, and ubiquitin carboxyl-terminal hydrolase L1 CSF concentrations, as well as with reduced fractional anisotropy and white matter tissue density in TBI. Apolipoprotein E (APOE) ε4 genotype affected the relationship between flortaucipir binding and time since injury, CSF β amyloid 1–42 (Aβ42) concentration, white matter tissue density, and longitudinal Mini-Mental State Examination scores in TBI. The results demonstrate that tau PET is a promising approach to investigating progressive neurodegeneration associated with tauopathy after TBI.
Li L, Ribeiro Violante I, Leech R, et al., 2019, Brain state and polarity dependent modulation of brain networks by transcranial direct current stimulation, Human Brain Mapping, Vol: 40, Pages: 904-915, ISSN: 1065-9471
Despite its widespread use in cognitive studies, there is still limited understanding of whether and how transcranial direct current stimulation (tDCS) modulates brain network function. To clarify its physiological effects, we assessed brain network function using functional magnetic resonance imaging (fMRI) simultaneously acquired during tDCS stimulation. Cognitive state was manipulated by having subjects perform a Choice Reaction Task or being at “rest.” A novel factorial design was used to assess the effects of brain state and polarity. Anodal and cathodal tDCS were applied to the right inferior frontal gyrus (rIFG), a region involved in controlling activity large‐scale intrinsic connectivity networks during switches of cognitive state. tDCS produced widespread modulation of brain activity in a polarity and brain state dependent manner. In the absence of task, the main effect of tDCS was to accentuate default mode network (DMN) activation and salience network (SN) deactivation. In contrast, during task performance, tDCS increased SN activation. In the absence of task, the main effect of anodal tDCS was more pronounced, whereas cathodal tDCS had a greater effect during task performance. Cathodal tDCS also accentuated the within‐DMN connectivity associated with task performance. There were minimal main effects of stimulation on network connectivity. These results demonstrate that rIFG tDCS can modulate the activity and functional connectivity of large‐scale brain networks involved in cognitive function, in a brain state and polarity dependent manner. This study provides an important insight into mechanisms by which tDCS may modulate cognitive function, and also has implications for the design of future stimulation studies.
Li L, Ribeiro Violante I, Leech R, et al., 2019, Cognitive enhancement with Salience Network electrical stimulation is influenced by network structural connectivity, NeuroImage, Vol: 185, Pages: 425-433, ISSN: 1053-8119
The Salience Network (SN) and its interactions are important for cognitive control. We have previously shown that structural damage to the SN is associated with abnormal functional connectivity between the SN and Default Mode Network (DMN), abnormal DMN deactivation, and impaired response inhibition, which is an important aspect of cognitive control. This suggests that stimulating the SN might enhance cognitive control. Here, we tested whether non-invasive transcranial direct current stimulation (TDCS) could be used to modulate activity within the SN and enhance cognitive control. TDCS was applied to the right inferior frontal gyrus/anterior insula cortex during performance of the Stop Signal Task (SST) and concurrent functional (f)MRI. Anodal TDCS improved response inhibition. Furthermore, stratification of participants based on SN structural connectivity showed that it was an important influence on both behavioural and physiological responses to anodal TDCS. Participants with high fractional anisotropy within the SN showed improved SST performance and increased activation of the SN with anodal TDCS, whilst those with low fractional anisotropy within the SN did not. Cathodal stimulation of the SN produced activation of the right caudate, an effect which was not modulated by SN structural connectivity. Our results show that stimulation targeted to the SN can improve response inhibition, supporting the causal influence of this network on cognitive control and confirming it as a target to produce cognitive enhancement. Our results also highlight the importance of structural connectivity as a modulator of network to TDCS, which should guide the design and interpretation of future stimulation studies.
Deb S, Leeson V, Aimola L, et al., 2018, Aggression following traumatic brain injury: effectiveness of Risperidone (AFTER): study protocol for a feasibility randomised controlled trial, Trials, Vol: 19, ISSN: 1745-6215
BackgroundTraumatic brain injury (TBI) is a major public health concern and many people develop long-lasting physical and neuropsychiatric consequences following a TBI. Despite the emphasis on physical rehabilitation, it is the emotional and behavioural consequences that have greater impact on people with TBI and their families. One such problem behaviour is aggression which can be directed towards others, towards property or towards the self. Aggression is reported to be common after TBI (37–71%) and causes major stress for patients and their families. Both drug and non-drug interventions are used to manage this challenging behaviour, but the evidence-base for these interventions is poor and no drugs are currently licensed for the treatment of aggression following TBI. The most commonly used drugs for this purpose are antipsychotics, particularly second-generation drugs such as risperidone. Despite this widespread use, randomised controlled trials (RCTs) of antipsychotic drugs, including risperidone, have not been conducted. We have, therefore, set out to test the feasibility of conducting an RCT of this drug for people who have aggressive behaviour following TBI.Methods/designWe will examine the feasibility of conducting a placebo-controlled, double-blind RCT of risperidone for the management of aggression in adults with TBI and also assess participants’ views about their experience of taking part in the study.We will randomise 50 TBI patients from secondary care services in four centres in London and Kent to up to 4 mg of risperidone orally or an inert placebo and follow them up 12 weeks later. Participants will be randomised to active or control treatment in a 1:1 ratio via an external and remote web-based randomisation service. Participants will be assessed at baseline and 12-week follow-up using a battery of assessment scales to measure changes in aggressive behaviour (MOAS, IRQ) as well as global functioning (GOS-E, CGI), quality of life (EQ-5D-5L
Feeney C, Sharp DJ, Hellyer PJ, et al., 2017, Serum IGF-I levels are associated with improved white matter recovery after TBI., Annals of Neurology, Vol: 82, Pages: 30-43, ISSN: 0364-5134
OBJECTIVE: Traumatic brain injury (TBI) is a common disabling condition with limited treatment options. Diffusion tensor imaging (DTI) measures recovery of axonal injury in white matter (WM) tracts after TBI. Growth hormone deficiency (GHD) after TBI may impair axonal and neuropsychological recovery, and serum IGF-I may mediate this effect. We conducted a longitudinal study to determine the effects of baseline serum IGF-I concentrations on WM tract and neuropsychological recovery after TBI. METHODS: Thirty-nine adults after TBI (84.6% male; age median 30.5y; 87.2% moderate-severe; time since TBI median 16.3 months, n=4 with GHD) were scanned twice, 13.3 months (12.1-14.9) apart, and 35 healthy controls scanned once. Symptom and quality of life questionnaires and cognitive assessments were completed at both visits (n=33). Our main outcome measure was fractional anisotropy (FA), a measure of WM tract integrity, in a priori regions of interest: splenium of corpus callosum (SPCC), and posterior limb of internal capsule (PLIC). RESULTS: At baseline, FA was reduced in many WM tracts including SPCC and PLIC following TBI compared to controls, indicating axonal injury, with longitudinal increases indicating axonal recovery. There was a significantly greater increase in SPCC FA over time in patients with serum IGF-I above vs. below the median-for-age. Only the higher IGF-I group had significant improvements in immediate verbal memory recall over time. INTERPRETATION: WM recovery and memory improvements after TBI were greater in patients with higher serum IGF-I at baseline. These findings suggest that GH/IGF-I system may be a potential therapeutic target following TBI. This article is protected by copyright. All rights reserved.
Violante IR, Li LM, Carmichael DW, et al., 2017, Externally induced frontoparietal synchronization modulates network dynamics and enhances working memory performance, ELIFE, Vol: 6, ISSN: 2050-084X
Cognitive functions such as working memory (WM) are emergent properties of large-scale network interactions. Synchronisation of oscillatory activity might contribute to WM by enabling the coordination of long-range processes. However, causal evidence for the way oscillatory activity shapes network dynamics and behavior in humans is limited. Here we applied transcranial alternating current stimulation (tACS) to exogenously modulate oscillatory activity in a right frontoparietal network that supports WM. Externally induced synchronization improved performance when cognitive demands were high. Simultaneously collected fMRI data reveals tACS effects dependent on the relative phase of the stimulation and the internal cognitive processing state. Specifically, synchronous tACS during the verbal WM task increased parietal activity, which correlated with behavioral performance. Furthermore, functional connectivity results indicate that the relative phase of frontoparietal stimulation influences information flow within the WM network. Overall, our findings demonstrate a link between behavioral performance in a demanding WM task and large-scale brain synchronization.
Jamall O, Feeney C, Zaw-Linn J, et al., 2016, Prevalence and correlates of vitamin D deficiency in adults after traumatic brain injury, Clinical Endocrinology, Vol: 85, Pages: 636-644, ISSN: 1365-2265
Objectives: Traumatic brain injury (TBI) is a major cause of long-term disability with variable recovery. Preclinicalstudies suggest that vitamin D status influences recovery after TBI. However, there is no publishedclinical data on links between vitamin D status and TBI outcomes. To determine the: (i) prevalence ofvitamin D deficiency/insufficiency, and associations of vitamin D status with (ii) demographic factors andTBI severity, and with (iii) cognitive function, symptoms and quality of life, in adults after TBI.Design: Retrospective audit of patients seen between July 2009 and March 2015. Serum vitamin D (25-hydroxy-cholecalciferol) was categorised as deficient (<40nmol/L), insufficient (40-70nmol/L) or replete(>70nmol/L).Patients: 353 adults seen in tertiary hospital clinic (75.4% lighter-skinned, 74.8% male, age median 35.1y,range 26.6-48.3y), 0.3-56.5 months after TBI (74.5% moderate-severe).Measurements: Serum vitamin D concentrations; Addenbrooke’s Cognitive Examination (ACE-R), BeckDepression Inventory II (BDI-II), SF-36 Quality of Life, Pittsburgh Sleep Quality Index.Results: 46.5% of patients after TBI had vitamin D deficiency and 80.2% insufficiency/deficiency. Patientswith vitamin D deficiency had lower ACE-R scores than those vitamin D replete (mean effect size ± SEM 4.5± 2.1, P=0.034), and higher BDI-II scores than those vitamin D insufficient (4.5 ± 1.6, P=0.003), correcting forage, gender, time since TBI, TBI severity. There was no association between vitamin D status and markers ofTBI severity, sleep or quality of life.Conclusion: Vitamin D deficiency is common in patients after TBI and associated with impaired cognitivefunction and more severe depressive symptoms.
Li LM, Leech R, Scott GT, et al., 2015, The effect of oppositional parietal transcranial direct current stimulation on lateralized brain functions, European Journal of Neuroscience, Vol: 42, Pages: 2904-2914, ISSN: 1460-9568
Cognitive functions such as numerical processing and spatial attention show varying degrees of lateralization. Transcranial direct current stimulation (tDCS) can be used to investigate how modulating cortical excitability affects performance of these tasks. This study investigated the effect of bi-parietal tDCS on numerical processing, spatial and sustained attention. It was hypothesized that tDCS would have distinct effects on these tasks because of varying lateralization (numerical processing left, spatial attention right) and that these effects are partly mediated by modulation of sustained attention. A single-blinded, crossover, sham-controlled study was performed. Eighteen healthy right-handed participants performed cognitive tasks during three sessions of oppositional parietal tDCS stimulation: sham; right anodal with left cathodal (RA/LC); and right cathodal with left anodal (RC/LA). Participants performed a number comparison task, a modified Posner task, a choice reaction task (CRT) and the rapid visual processing task (RVP). RA/LC tDCS impaired number comparison performance compared with sham, with slower responses to numerically close numbers pairs. RA/LC and RC/LA tDCS had distinct effects on CRT performance, specifically affecting vigilance level during the final block of the task. No effect of stimulation on the Posner task or RVP was found. It was demonstrated that oppositional parietal tDCS affected both numerical performance and vigilance level in a polarity-dependent manner. The effect of tDCS on numerical processing may partly be due to attentional effects. The behavioural effects of tDCS were specifically observed under high task demands, demonstrating the consequences of an interaction between stimulation type and cognitive load.
Li LM, Uehara K, Hanakawa T, 2015, The contribution of interindividual factors to variability of response in transcranial direct current stimulation studies, Frontiers in Cellular Neuroscience, Vol: 9, ISSN: 1662-5102
There has been an explosion of research using transcranial direct current stimulation (tDCS) for investigating and modulating human cognitive and motor function in healthy populations. It has also been used in many studies seeking to improve deficits in disease populations. With the slew of studies reporting “promising results” for everything from motor recovery after stroke to boosting memory function, one could be easily seduced by the idea of tDCS being the next panacea for all neurological ills. However, huge variability exists in the reported effects of tDCS, with great variability in the effect sizes and even contradictory results reported. In this review, we consider the interindividual factors that may contribute to this variability. In particular, we discuss the importance of baseline neuronal state and features, anatomy, age and the inherent variability in the injured brain. We additionally consider how interindividual variability affects the results of motor-evoked potential (MEP) testing with transcranial magnetic stimulation (TMS), which, in turn, can lead to apparent variability in response to tDCS in motor studies.
Rokicki J, Li L, Imabayashi E, et al., 2015, Daily Carnosine and Anserine Supplementation Alters Verbal Episodic Memory and Resting State Network Connectivity in Healthy Elderly Adults., Front Aging Neurosci, Vol: 7, ISSN: 1663-4365
Carnosine and anserine are strong antioxidants, previously demonstrated to reduce cognitive decline in animal studies. We aimed to investigate their cognitive and neurophysiological effects, using functional MRI, on humans. Thirty-one healthy participants (age 40-78, 10 male/21 female) were recruited to a double-blind placebo-controlled study. Participants were assigned to twice-daily doses of imidazole dipeptide formula (n = 14), containing 500 mg (carnosine/anserine, ratio 1/3) or an identical placebo (n = 17). Functional MRI and neuropsychological assessments were carried out at baseline and after 3 months of supplementation. We analyzed resting state functional connectivity with the FSL fMRI analysis package. There were no differences in neuropsychological scores between the groups at baseline. After 3 months of supplementation, the carnosine/anserine group had better verbal episodic memory performance and decreased connectivity in the default mode network, the posterior cingulate cortex and the right fronto parietal network, as compared with the placebo group. Furthermore, there was a correlation between the extents of cognitive and neuroimaging changes. These results suggest that daily carnosine/anserine supplementation can impact cognitive function and that network connectivity changes are associated with its effects.
Li LM, Menon DK, Janowitz T, 2014, Cross-Sectional Analysis of Data from the U.S. Clinical Trials Database Reveals Poor Translational Clinical Trial Effort for Traumatic Brain Injury, Compared with Stroke, PLoS ONE, Vol: 9, Pages: e84336-e84336
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.