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Article ; Online: Psychiatric sequelae of traumatic brain injury - future directions in research.

Li, Lucia M / Carson, Alan / Dams-O'Connor, Kristen

2023 Volume 19, Issue 9, Page(s) 556–571

Abstract: Despite growing appreciation that traumatic brain injury (TBI) is an important public health burden, our understanding of the psychiatric and behavioural consequences of TBI remains limited. These changes are particularly detrimental to a person's sense ... ...

Abstract	Despite growing appreciation that traumatic brain injury (TBI) is an important public health burden, our understanding of the psychiatric and behavioural consequences of TBI remains limited. These changes are particularly detrimental to a person's sense of self, their relationships and their participation in the wider community, and they continue to have devastating individual and cumulative effects long after TBI. This Review relates specifically to TBIs that confer objective clinical or biomarker evidence of structural brain injury; symptomatic head injuries without such evidence are outside the scope of this article. Common psychiatric, affective and behavioural sequelae of TBI and their proposed underlying mechanisms are outlined, along with a brief overview of current treatments. Suggestions for how scientists and clinicians can work together in the future to address the chasms in clinical care and knowledge are discussed in depth.
MeSH term(s)	Humans ; Brain Injuries, Traumatic/complications ; Brain Injuries ; Disease Progression ; Public Health
Language	English
Publishing date	2023-08-17
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2491514-2
ISSN	1759-4766 ; 1759-4758
ISSN (online)	1759-4766
ISSN	1759-4758
DOI	10.1038/s41582-023-00853-8
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Article ; Online: Autonomic dysfunction after moderate-to-severe traumatic brain injury: symptom spectrum and clinical testing outcomes.

Li, Lucia M / Vichayanrat, Ekawat / Del Giovane, Martina / Lai, Helen Hoi Lun / Iodice, Valeria

BMJ neurology open

2022 Volume 4, Issue 1, Page(s) e000308

Abstract: 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 ...

Abstract	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, r 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.
Language	English
Publishing date	2022-04-24
Publishing country	England
Document type	Journal Article
ISSN	2632-6140
ISSN (online)	2632-6140
DOI	10.1136/bmjno-2022-000308
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Article ; Online: Using home monitoring technology to study the effects of traumatic brain injury on older multimorbid adults: protocol for a feasibility study.

Parkinson, Megan E / Dani, Melanie / Fertleman, Michael / Soreq, Eyal / Barnaghi, Payam / Sharp, David J / Li, Lucia M

BMJ open

2023 Volume 13, Issue 5, Page(s) e068756

Abstract: Introduction: The prevalence of traumatic brain injury (TBI) among older adults is increasing exponentially. The sequelae can be severe in older adults and interact with age-related conditions such as multimorbidity. Despite this, TBI research in older ... ...

Abstract	Introduction: The prevalence of traumatic brain injury (TBI) among older adults is increasing exponentially. The sequelae can be severe in older adults and interact with age-related conditions such as multimorbidity. Despite this, TBI research in older adults is sparse. Minder, an in-home monitoring system developed by the UK Dementia Research Institute Centre for Care Research and Technology, uses infrared 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 the 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) (REC number: 17/LO/2066). Results will be submitted for publication in peer-reviewed journals, presented at conferences and inform the design of a larger trial assessing recovery after TBI.
MeSH term(s)	Humans ; Aged ; Feasibility Studies ; Multimorbidity ; Brain Injuries, Traumatic ; Caregivers ; Dementia
Language	English
Publishing date	2023-05-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2022-068756
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Article ; Online: Targeted non-invasive brain stimulation boosts attention and modulates contralesional brain networks following right hemisphere stroke.

Olgiati, Elena / Violante, Ines R / Xu, Shuler / Sinclair, Toby G / Li, Lucia M / Crow, Jennifer N / Kapsetaki, Marianna E / Calvo, Roberta / Li, Korina / Nayar, Meenakshi / Grossman, Nir / Patel, Maneesh C / Wise, Richard J S / Malhotra, Paresh A

NeuroImage. Clinical

2024 Volume 42, Page(s) 103599

Abstract: Right hemisphere stroke patients frequently present with a combination of lateralised and non-lateralised attentional deficits characteristic of the neglect syndrome. Attentional deficits are associated with poor functional outcome and are challenging to ...

Abstract	Right hemisphere stroke patients frequently present with a combination of lateralised and non-lateralised attentional deficits characteristic of the neglect syndrome. Attentional deficits are associated with poor functional outcome and are challenging to treat, with non-lateralised deficits often persisting into the chronic stage and representing a common complaint among patients and families. In this study, we investigated the effects of non-invasive brain stimulation on non-lateralised attentional deficits in right-hemispheric stroke. In a randomised double-blind sham-controlled crossover study, twenty-two patients received real and sham transcranial Direct Current Stimulation (tDCS) whilst performing a non-lateralised attentional task. A high definition tDCS montage guided by stimulation modelling was employed to maximise current delivery over the right dorsolateral prefrontal cortex, a key node in the vigilance network. In a parallel study, we examined brain network response to this tDCS montage by carrying out concurrent fMRI during stimulation in healthy participants and patients. At the group level, stimulation improved target detection in patients, reducing overall error rate when compared with sham stimulation. TDCS boosted performance throughout the duration of the task, with its effects briefly outlasting stimulation cessation. Exploratory lesion analysis indicated that response to stimulation was related to lesion location rather than volume. In particular, reduced stimulation response was associated with damage to the thalamus and postcentral gyrus. Concurrent stimulation-fMRI revealed that tDCS did not affect local connectivity but influenced functional connectivity within large-scale networks in the contralesional hemisphere. This combined behavioural and functional imaging approach shows that brain stimulation targeted to surviving tissue in the ipsilesional hemisphere improves non-lateralised attentional deficits following stroke. This effect may be exerted via contralesional network effects.
Language	English
Publishing date	2024-03-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2701571-3
ISSN	2213-1582 ; 2213-1582
ISSN (online)	2213-1582
ISSN	2213-1582
DOI	10.1016/j.nicl.2024.103599
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Article ; Online: Using home monitoring technology to study the effects of traumatic brain injury in older multimorbid adults.

Parkinson, Megan E / Doherty, Rebecca / Curtis, Francesca / Soreq, Eyal / Lai, Helen H L / Serban, Alina-Irina / Dani, Melanie / Fertleman, Michael / Barnaghi, Payam / Sharp, David J / Li, Lucia M

Annals of clinical and translational neurology

2023 Volume 10, Issue 9, Page(s) 1688–1694

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Aged ; Brain Injuries, Traumatic ; Hospitalization ; Monitoring, Physiologic ; Patient Discharge
Language	English
Publishing date	2023-08-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2740696-9
ISSN	2328-9503 ; 2328-9503
ISSN (online)	2328-9503
ISSN	2328-9503
DOI	10.1002/acn3.51849
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Article ; Online: Population incidence and associated mortality of urinary tract infection in people living with dementia.

The Journal of infection

2024 Volume 88, Issue 6, Page(s) 106167

Abstract: Objectives: Urinary tract infections (UTIs) frequently cause hospitalisation and death in people living with dementia (PLWD). We examine UTI incidence and associated mortality among PLWD relative to matched controls and people with diabetes and ... ...

Abstract	Objectives: Urinary tract infections (UTIs) frequently cause hospitalisation and death in people living with dementia (PLWD). We examine UTI incidence and associated mortality among PLWD relative to matched controls and people with diabetes and investigate whether delayed or withheld treatment further impacts mortality. Methods: Data were extracted for n = 2,449,814 people aged ≥ 50 in Wales from 2000-2021, with groups matched by age, sex, and multimorbidity. Poisson regression was used to estimate incidences of UTI and mortality. Cox regression was used to study the effects of treatment timing. Results: UTIs in dementia (HR=2.18, 95 %CI [1.88-2.53], p < .0) and diabetes (1.21[1.01-1.45], p = .035) were associated with high mortality, with the highest risk in individuals with diabetes and dementia (both) (2.83[2.40-3.34], p < .0) compared to matched individuals with neither dementia nor diabetes. 5.4 % of untreated PLWD died within 60 days of GP diagnosis-increasing to 5.9 % in PLWD with diabetes. Conclusions: Incidences of UTI and associated mortality are high in PLWD, especially in those with diabetes and dementia. Delayed treatment for UTI is further associated with high mortality.
MeSH term(s)	Humans ; Dementia/epidemiology ; Dementia/complications ; Dementia/mortality ; Urinary Tract Infections/epidemiology ; Urinary Tract Infections/mortality ; Urinary Tract Infections/complications ; Male ; Female ; Aged ; Incidence ; Middle Aged ; Aged, 80 and over ; Wales/epidemiology ; Risk Factors ; Diabetes Mellitus/epidemiology
Language	English
Publishing date	2024-04-26
Publishing country	England
Document type	Journal Article
ZDB-ID	424417-5
ISSN	1532-2742 ; 0163-4453
ISSN (online)	1532-2742
ISSN	0163-4453
DOI	10.1016/j.jinf.2024.106167
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Article ; Online: Remote Monitoring of Physiology in People Living With Dementia: An Observational Cohort Study.

David, Michael C B / Kolanko, Magdalena / Del Giovane, Martina / Lai, Helen / True, Jessica / Beal, Emily / Li, Lucia M / Nilforooshan, Ramin / Barnaghi, Payam / Malhotra, Paresh A / Rostill, Helen / Wingfield, David / Wilson, Danielle / Daniels, Sarah / Sharp, David J / Scott, Gregory

JMIR aging

2023 Volume 6, Page(s) e43777

Abstract: 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 ... ...

Abstract	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 dementia with α-synuclein-related dementia had lower systolic blood pressure; 30% had clinically significant weight loss. Depending on the criteria used, 3.03%-9.46% of measurements generated alerts, at 0.066-0.233 per day per person with dementia. We also report 4 case studies, highlighting the potential benefits and challenges of remote physiological monitoring in people with dementia. These include case studies of people with dementia developing acute infections and one of a person with dementia developing symptomatic bradycardia while taking donepezil. Conclusions: We present findings from a study of the physiology of people with dementia recorded remotely on a large scale. People with dementia and their carers showed acceptable compliance throughout, supporting the feasibility of the system. Our findings inform the development of technologies, care pathways, and policies for IoT-based remote monitoring. We show how IoT-based monitoring could improve the management of acute and chronic comorbidities in this clinically vulnerable group. Future randomized trials are required to establish if a system like this has measurable long-term benefits on health and quality of life outcomes.
Language	English
Publishing date	2023-03-09
Publishing country	Canada
Document type	Journal Article
ISSN	2561-7605
ISSN (online)	2561-7605
DOI	10.2196/43777
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Article ; Online: Investigating the characteristics and correlates of systemic inflammation after traumatic brain injury: the TBI-BraINFLAMM study.

Li, Lucia M / Heslegrave, Amanda / Soreq, Eyal / Nattino, Giovanni / Rosnati, Margherita / Garbero, Elena / Zimmerman, Karl A / Graham, Neil S N / Moro, Federico / Novelli, Deborah / Gradisek, Primoz / Magnoni, Sandra / Glocker, Ben / Zetterberg, Henrik / Bertolini, Guido / Sharp, David J

BMJ open

2023 Volume 13, Issue 5, Page(s) e069594

Abstract: 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 ... ...

Abstract	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 experimental medicine studies assessing the role and management of post-TBI systemic inflammation.
MeSH term(s)	Animals ; Neurodegenerative Diseases ; Prospective Studies ; Brain Injuries, Traumatic ; Brain ; Cytokines ; Inflammation
Chemical Substances	Cytokines
Language	English
Publishing date	2023-05-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2022-069594
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Article ; Online: Multicohort cross-sectional study of cognitive and behavioural digital biomarkers in neurodegeneration: the Living Lab Study protocol.

Crook-Rumsey, Mark / Daniels, Sarah J C / Abulikemu, Subati / Lai, Helen / Rapeaux, Adrien / Hadjipanayi, Charalambos / Soreq, Eyal / Li, Lucia M / Bashford, James / Jeyasingh-Jacob, Julian / Gruia, Dragos C / Lambert, Damion / Weil, Rimona / Hampshire, Adam / Sharp, David J / Haar, Shlomi

BMJ open

2023 Volume 13, Issue 8, Page(s) e072094

Abstract: Introduction and aims: Digital biomarkers can provide a cost-effective, objective and robust measure for neurological disease progression, changes in care needs and the effect of interventions. Motor function, physiology and behaviour can provide ... ...

Abstract	Introduction and aims: Digital biomarkers can provide a cost-effective, objective and robust measure for neurological disease progression, changes in care needs and the effect of interventions. Motor function, physiology and behaviour can provide informative measures of neurological conditions and neurodegenerative decline. New digital technologies present an opportunity to provide remote, high-frequency monitoring of patients from within their homes. The purpose of the living lab study is to develop novel digital biomarkers of functional impairment in those living with neurodegenerative disease (NDD) and neurological conditions. Methods and analysis: The Living Lab study is a cross-sectional observational study of cognition and behaviour in people living with NDDs and other, non-degenerative neurological conditions. Patients (n≥25 for each patient group) with dementia, Parkinson's disease, amyotrophic lateral sclerosis, mild cognitive impairment, traumatic brain injury and stroke along with controls (n≥60) will be pragmatically recruited. Patients will carry out activities of daily living and functional assessments within the Living Lab. The Living Lab is an apartment-laboratory containing a functional kitchen, bathroom, bed and living area to provide a controlled environment to develop novel digital biomarkers. The Living Lab provides an important intermediary stage between the conventional laboratory and the home. Multiple passive environmental sensors, internet-enabled medical devices, wearables and electroencephalography (EEG) will be used to characterise functional impairments of NDDs and non-NDD conditions. We will also relate these digital technology measures to clinical and cognitive outcomes. Ethics and dissemination: Ethical approvals have been granted by the Imperial College Research Ethics Committee (reference number: 21IC6992). Results from the study will be disseminated at conferences and within peer-reviewed journals.
MeSH term(s)	Humans ; Cross-Sectional Studies ; Activities of Daily Living ; Neurodegenerative Diseases/diagnosis ; Cognitive Dysfunction/psychology ; Cognition ; Biomarkers ; Observational Studies as Topic
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-08-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2023-072094
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Article: The contribution of interindividual factors to variability of response in transcranial direct current stimulation studies.

Li, Lucia M / Uehara, Kazumasa / Hanakawa, Takashi

Frontiers in cellular neuroscience

2015 Volume 9, Page(s) 181

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2015-05-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2015.00181
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