Investigating working memory deficits following traumatic brain injury (TBI)

Lead Research Organisation: Imperial College London
Department Name: Dept of Medicine

Abstract

Project Title: Investigating working memory deficits following traumatic brain injury (TBI)

Background:
Traumatic brain injury (TBI) is the leading cause of death and disability in under 40s (1). Despite improved survival rates, cognitive impairment following TBI remains a significant and often difficult symptom to treat. Deficits in working memory (WM) among patients are common and can persist long after injury (2). These can lead to difficulties in returning to work and impact upon quality of life (3)

Working memory is an integral part of everyday functioning and is employed in a range of cognitive processes such as decision making, problem solving and performing actions (4). It can be defined as the ability to manipulate, retain and update information over a short period of time (5).

Numerous neuroimaging studies have implicated the frontal and parietal cortices as important in the function of working memory. These areas are prone to damage following TBI and disruption to white matter connections between these cortices may contribute to working memory deficits in TBI (6).

Evidence of plasticity, the brains ability to reorganize, following WM cognitive training has provided some promising results for use in TBI rehabilitation (7). However, there is limited evidence to suggest plasticity and improvements in cognitive training tasks have transferable and long-term benefits, particularly in the context of TBI (8).

Understanding the neurophysiological processes that underpin WM and the effects TBI has on these will help to inform the development and testing of cognitive training packages.

Aims:
My research will aim to:
1) Investigate the neural correlates of TBI related working memory impairment
2) Assess the efficacy of computerized training on improving working memory deficits
3) Identify if cognitive training in working memory provides global cognitive improvements.

Hypothesis:
(1) Disruption to structural and functional connectivity in the brain following TBI will correlate with WM impairment.
(2) Longitudinal cognitive training in WM will improve WM deficits, which will lead to improved global cognitive functioning and correlate with increased connectivity in the brain.

Research outcomes:
My research will investigate the neural mechanisms underlying working memory impairments following traumatic brain injury to help further our understanding of TBI related cognitive impairment. By employing structural and functional imaging as well as cognitive and quality of life measures we can begin to identify how working memory is impaired and the potential targets for interventional treatment to improve patients outcomes. This research will also provide empirical evidence of the effects of computerized working memory training within a TBI population, which has the potential to inform future research in cognitive re-training following TBI.
 
Description Training of research postgraduates for use of novel neuroimaging techniques in traumatic brain injury research
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
 
Title Cogntitrack-Longitudinal cognitive assessments of working memory and cognitive impairments after traumatic brain injury 
Description This is an app and internet platform with tasks that have been specifically tailored for use in patients with traumatic brain injury using contributions from my previous research and data collected in our outpatients traumatic brain injury clinic. These tools were developed as part of a team and have the potential to be rolled out accross the country for assessment. Importantly, we developed these cognitive tools in collaboration with patients, their caregivers and clinicians in order to provide a feasible tool to assess cognitive abilities very early on as well as long after a patients injury. 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2018 
Provided To Others? Yes  
Impact This tool has now been rolled out into our outpatient clinic and on the major trauma wards we are collaborating with to assess patients remotely and quickly in order to indentify any working memory or other cognitive impairments. This is a proof of principal study that has demonstrated that the tool is an effective assessment tool that could be used at the bedside or remotely prior to a clinical appointment to help guide treatments and interventions. 
 
Title Development of a diffusion tensor imaging diagnostic tool to identify axonal injury 
Description During my PhD i have developed a novel tool designed to identify traumatic axonal injury in individuals using diffusion tensor imaging and a large healthy control population. This tool has been used to help diagnose patients with often normal looking clinical MRI scans with axonal injury which is not visible to the naked eye in the absence of microbleeds. This tool has demonstrated that a proportion of patients with long-term cognitive impairments such as working memory difficulties do have strucutral damage to the brain that is often overlooked without the use of individualised tools and advanced sequences that i use. This has the potential to reovulitionise how we diagnose patients with axonal injury and treat them in clinical settings. I have worked with neurologists and lawyers in developing this tool for clinical and private use. 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2018 
Provided To Others? Yes  
Impact This tool has been used in a number of clinical cases to determine evidence of an organic injury and has helped contribute towards a patients clinical care. This tool has also begun to be adopted in medicolegal cases where non-advanced imaging has been unable to determine whether axonal injury is present or not. 
 
Title Clinical outcomes after TBI database 
Description This database contains blood biomarkers, MRI imaging, clinical records and cognitive testing of moderate-severe TBI patients at the acute (within the first few days of injury) to chronic points in their injury. This is an extremely novel and rich dataset which will help to influence and advance our understanding of the types of impairments that arise and has the potential to help us improve prognosis and interventions in a hard to treat population. 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? No  
Impact This database has begun to provide large amoounts of data that include potential blood biomarkers that provide evidence of brain injury. Importantly, this database provides longtudinal observational data that allows for us to begin modelling and predicting outcomes. 
 
Title Individualised assessment of axonal injury 
Description This is a diagnostic tool designed to be used at an individual level to help determine a patients brain injury and influence their treatments. 
Type Of Material Data analysis technique 
Year Produced 2018 
Provided To Others? Yes  
Impact This model has helped to diagnose patients with axonal injury that would otherwise be treated as psychological rather than biological origins. This is particularly important as this has now been adopted in a number of clinical psychologists practice in order to determine axonal injury and make recommendations for treatment. 
 
Title Strucutral connectome changes to identify working memory and reasoning impairment 
Description Here we have developed and demonstrated unique features of strucutral disconnectivity after traumatic brain injury that provide a better understanding towards the development of working memory and reasoning impairments after axonal injury. 
Type Of Material Data analysis technique 
Year Produced 2019 
Provided To Others? No  
Impact This work has the potential to be used as a prognostic marker for working memory and reasoning impairments in TBI in the acute stages of injury which we are currently testing. Importantly, this provides potential areas for tailored intervention and targeted treatments. 
 
Description Clinical outcomes after Traumatic Brain Injury 
Organisation Mario Negri Institute for Pharmacological Research
Country Italy 
Sector Academic/University 
PI Contribution This is a multi-center study to observe the clinical outcomes of patients with moderate-severe traumatic brain injury in a longitudinal manner. I was solely in charge of securing the ethical approval and contracts accross the multiple NHS college sites to begin this study. I collect cognitive, clinical and MRI data on TBI patients along with my team and work with other major trauma centers in London to recruit patients. We are also part of a largerEeuropean study called CREACTIVE whereby we share neuroimaging and clinical data to help identify prognostic markers and cognitive features of traumatic brain injury from the acute to chronic phases of injury.
Collaborator Contribution Our partners accross English sites and as part of the large European CREACTIVE study have provided us with patients for recruitment, collected blood and clinical data as well as colelcting data from patients in intensive care units in Italy that we would otherwise not have access to.
Impact This is multi-disciplinary in the fact that we work with Neurologists, Neurosurgeons, Clinical Psychologists, Cognitive Neuroscientists and molecular biologists.
Start Year 2017
 
Description Clinical outcomes after Traumatic Brain Injury 
Organisation St George's Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution This is a multi-center study to observe the clinical outcomes of patients with moderate-severe traumatic brain injury in a longitudinal manner. I was solely in charge of securing the ethical approval and contracts accross the multiple NHS college sites to begin this study. I collect cognitive, clinical and MRI data on TBI patients along with my team and work with other major trauma centers in London to recruit patients. We are also part of a largerEeuropean study called CREACTIVE whereby we share neuroimaging and clinical data to help identify prognostic markers and cognitive features of traumatic brain injury from the acute to chronic phases of injury.
Collaborator Contribution Our partners accross English sites and as part of the large European CREACTIVE study have provided us with patients for recruitment, collected blood and clinical data as well as colelcting data from patients in intensive care units in Italy that we would otherwise not have access to.
Impact This is multi-disciplinary in the fact that we work with Neurologists, Neurosurgeons, Clinical Psychologists, Cognitive Neuroscientists and molecular biologists.
Start Year 2017
 
Description Clinical outcomes after Traumatic Brain Injury 
Organisation St Mary's Hospital, London
Country United Kingdom 
Sector Hospitals 
PI Contribution This is a multi-center study to observe the clinical outcomes of patients with moderate-severe traumatic brain injury in a longitudinal manner. I was solely in charge of securing the ethical approval and contracts accross the multiple NHS college sites to begin this study. I collect cognitive, clinical and MRI data on TBI patients along with my team and work with other major trauma centers in London to recruit patients. We are also part of a largerEeuropean study called CREACTIVE whereby we share neuroimaging and clinical data to help identify prognostic markers and cognitive features of traumatic brain injury from the acute to chronic phases of injury.
Collaborator Contribution Our partners accross English sites and as part of the large European CREACTIVE study have provided us with patients for recruitment, collected blood and clinical data as well as colelcting data from patients in intensive care units in Italy that we would otherwise not have access to.
Impact This is multi-disciplinary in the fact that we work with Neurologists, Neurosurgeons, Clinical Psychologists, Cognitive Neuroscientists and molecular biologists.
Start Year 2017
 
Description Clinical outcomes after Traumatic Brain Injury 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution This is a multi-center study to observe the clinical outcomes of patients with moderate-severe traumatic brain injury in a longitudinal manner. I was solely in charge of securing the ethical approval and contracts accross the multiple NHS college sites to begin this study. I collect cognitive, clinical and MRI data on TBI patients along with my team and work with other major trauma centers in London to recruit patients. We are also part of a largerEeuropean study called CREACTIVE whereby we share neuroimaging and clinical data to help identify prognostic markers and cognitive features of traumatic brain injury from the acute to chronic phases of injury.
Collaborator Contribution Our partners accross English sites and as part of the large European CREACTIVE study have provided us with patients for recruitment, collected blood and clinical data as well as colelcting data from patients in intensive care units in Italy that we would otherwise not have access to.
Impact This is multi-disciplinary in the fact that we work with Neurologists, Neurosurgeons, Clinical Psychologists, Cognitive Neuroscientists and molecular biologists.
Start Year 2017
 
Title Diagnostic tools for axonal injury 
Description This is a clinical diagnostic tool for identifying axonal injury. This tool examines diffusion tensor imaging in individuals and compares to a large healthy control cohort to determine if axonal injury is present and whether a patient can therefore be diagnosed with this to help guide future treatments and support. 
Type Diagnostic Tool - Imaging
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2019
Development Status Under active development/distribution
Impact This tool is now used in private medicolegal cases to help determine if there is evidence of axonal injury and is also used in our outpatient traumatic brain injury clinic to determine whether patients have evidence of axonal injury to help with their clinical care. 
 
Title Cognitrack and cogniclinic software for patients with traumatic brain inury 
Description Cogniclinic provides a one-off clinical assessment of cognitive abilities of patients with a traumatic brain injury at the bedside or in outpatient clinics. Cognitrack provides a longitudinal tool to track the development of cognitive impairments over time in this population and can be used as an app on patients phones. This provides a mapping of cognition in patients that has until now been impossible to collect due to limited resources for neuropsychological testing. 
Type Of Technology Webtool/Application 
Year Produced 2018 
Open Source License? Yes  
Impact This product will help provide assessments to patients that might otherwise have to wait months for formal neuropsychological testing. This also provides longitudinal data so that clinicians will be able to see the development of particular cognitive impairments if a patient has to wait months prior to any medical input after discharge from hospital. This has the potential to ensure clinicians tailor their treatment strategies based on the data collected from these apps. 
 
Description Britains most intelligent family 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact I along with members of my research group were science advisors to the BBC's new television programme titled Britains most intelligent family. This was a TV series hosted by Dara O'Briain in which families completed the computerised cognitive tasks we have developed in the lab to test cognitive abilities. This programme has helped our online cognitive testing platform to be presented to thousands of people of the general public and will hopefully encourage them to complete some tests online to provide us with large healthy individuals performance so that we are able to accurately understand the impact of traumatic brain injury on cognition such as working memory.
Year(s) Of Engagement Activity 2019
 
Description Host of two students from the In2Science scheme 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact In2Science is a scheme designed for school students from underprivileged backgrounds to spend two weeks at an institution so that they can gain skills, ask questions and learn about topics they are interested in to help encourage them to reach their potential and attend university. These are often high performing AS-leve students who may go on to become first generation university students. This is a STEM outreach programme that has has significant impacts on the students who take part.
Year(s) Of Engagement Activity 2019
URL https://in2scienceuk.org/
 
Description Meet the Scientist-Imperial College London 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact These are our annual meet the scientist events in which we invite members of the public as well as patients and their caregivers to come to our research facilities and learn about the work we do. For these events, i helped organise the days and presented some of my PhD work to help people understand research and engage members of the public. This year i gave a talk on the history of cognitive neuroscience and demonstrated some of the cognitive tests we have developed as part of my PhD project.
Year(s) Of Engagement Activity 2017,2018,2019
 
Description Meeting of the Minds 2020 workshop leader 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact The meeting of the minds is a conference put on by the Imperial College London neuroscience society. I was asked to hold several workshops throughout the day discussing the research we do at my lab and providing practical talks to teach a broad audience about neuroscience and imaging.
Year(s) Of Engagement Activity 2020
URL https://allevents.in/london/imperial-college-meeting-of-the-minds-2020/200018473164836
 
Description Pint of Science UK 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact I was an event organiser for the Beautiful mind theme in 2018 and then became the Imperial College London Co-ordinator for the Pint of Science UK festival. I managed 10 teams to deliver three nights each covering a broad range of topic around science featuring speakers from the University. This is a grassroots organisation designed to engage the public in science and encourage good science communication. This is an international annual event with much media coverage and we were one of many London based universities to host the events.
Year(s) Of Engagement Activity 2017,2018,2019
URL https://pintofscience.co.uk/about/