Towards a new neurological model of language that explains outcome after stroke.

Lead Research Organisation: University College London
Department Name: Institute of Neurology

Abstract

Every five minutes one person in the UK has a stroke. More than a third of these patients will develop aphasia, which can impair the ability to speak, understand speech, read and/or write. Aphasia is the most feared outcome after stroke because it severely impairs quality of life and makes stroke patients prone to social isolation, dependence and depression. One of the most demoralizing outcomes for aphasic patients is the lack of any information on their likely prognosis for recovery. This is a consequence of there being no established way to predict when, how or whether language skills will recover, which in turn makes it difficult to decide which course of therapy is best suited to an individual patient. Our research aims to Predict Language Outcome and Recovery After Stroke (PLORAS, http://www.ucl.ac.uk/ploras). In pursuit of this goal, we generating a database that records as many details as possible about hundreds of different stroke patients.

Our initial investigations show that we can make confident predictions for language outcome for many patients. For example, we have identified 2 brain areas where the presence or absence of damage (caused by the stroke) very reliably predicts whether or not a patient will have "persistent" difficulty producing speech (i.e. years after stroke). These findings are important to share with new patients and their carers as they help to provide realistic expectations of likely recovery. Prognoses of good outcome are valuable because they substantially reduce anxiety about the future. Prognoses of poor outcome are more challenging for patients and their carers to deal with in the short term, but they can ease future frustration and depression associated with a failure to meet unrealistic targets.

The aim of the proposed research is to provide a scientific explanation of how the predictions are working. This comes in the form of what we refer to as a "neurological model" of language that predicts speech and language outcome after stroke by identifying which brain regions are critical to language, the functions they support (e.g. speech comprehension or reading) and how the regions connect to one another.

The current neurological model of language, illustrated in medical textbooks today, is based on crude post mortem data from less than a handful of aphasic patients tested at the end of the 19th Century by Paul Broca (1861) and Karl Wernicke (1874). Despite its enduring popularity, this model has not stood the test of time because it does not reliably predict outcome in new patients. Thus, although the classic neurological model is conceptually appealing, it does not make predictions that are accurate enough to be clinically useful. Conversely, our data-led analyses are starting to make very accurate predictions but we do not understand their scientific basis.

Our proposal aims to provide a new neurological model that can be used to explain and ultimately improve the predictions we make. The new neurological model will illustrate the set of brain regions that support different language abilities (e.g. the ability to speak or understand speech). These brain regions will correspond to the parts of the brain that are typically damaged in patients who have selective difficulty with one particular language skill. In order to find these areas, and demonstrate how consistently they affect other patients, we have developed a completely new method for analysing the exact location and extent of brain damage. Our studies also place great importance on how much time, since the stroke, the patient has had to recover. We also aim to investigate the influence of many other factors on a patient's recovery, including the amount of speech therapy they have been given.

Technical Summary

We will investigate the combinations of brain areas that are critical to core language functions. In Step 1, for each function of interest, we select patients who each have difficulty performing all the tasks that are assumed to tap that function. For example, when the function of interest is speech production, we select patients who have difficulties with all speech production tasks (object naming, reading and fluency) but not on tasks that don't (picture-word-matching etc). The lesion site in each of the selected patients is defined in high-definition 3-dimensional space and becomes a region of interest (ROI) with the assumption that the ROI must include brain areas that contribute to all the neural pathways that have the potential to support the tasks and functions that the patient has difficulty with. Further analyses are then required to determine which parts of the ROI are critical or not, and whether the different parts contribute to the same neural pathway or a separate pathway (if there are different ways that the same task can be performed).

In Step 2, we select other patients who either have damage that includes all or a part of an ROI. The language abilities of each of these patients determine which parts of the ROI are critical and how the lesion-deficit relationship varies (i) across patients and (ii) with time post stroke. If different parts are from the same neural pathway, we expect that damage to each part will impair task performance. If different parts contribute to different neural pathways (for the same task) then we expect task performance to be worst when damage includes all relevant pathways than when it includes just one or a subset of pathways. Each result will be validated in new cohorts of patients who are closely matched for lesion site and followed up longitudinally. All results will be integrated in a new neurological model of language that can predict both initial symptom severity and the likelihood of recovery in new patients.

Planned Impact

Our proposal fits with the NHS and the UK government's goals to improve quality of life and reduce unnecessary costs for people with long term impairments caused by diseases such as stroke. Our target is to provide (A) an extensive database of brain scans and language measures from stroke survivors tested at many different time points during the course of their recovery; (B) predictions of how a lesion will affect language and (C) a neurological model that explains the predictions. This will allow clinicians, new patients, and their carers, to find out whether, how and when they are likely to be affected and recover. Below, we emphasize the social and economic benefits that souch a resource could provide to stroke survivors, healthcare professions, NHS resources and the general public.

Stroke survivors: Patients want to know whether, when and how they can recover their language skills after stroke. The neurological model we are creating aims to address these questions confidently and precisely for as many patients as possible. In the short term, our predictions will only indicate how likely it is that a patient's language skills will return to normal or not in the first year or two after their stroke. This "likelihood" could range from confident (more than 95% likely) to unknown (50% likely). If we are able to provide confident prognoses of recovery, patients will be relieved to know that they should be able to return to normal life. If our predictions are confident that recovery will be limited, patients may initially become demoralised. However, realistic long term expectations can greatly reduce the emotional and economic burden on the patient and their family. For example, realistic expectations can reduce the frustration of wasting time, money and hope on treatments and therapies that are unlikely to work, while guiding patients to other therapeutic assistance that maximises their wellbeing through the most appropriate support. Most patients and their families therefore tell us that they want to know their likely outcome whatever the scenario. Having some information is better than not knowing. Therefore, patients for whom we are unable to make confident predictions (good or poor), will motivate further research.

Healthcare professionals: Physicians, speech and language therapists, neuro-radiologists and neurosurgeons will ultimately benefit from our research. Clinicians need to know what to advise patients and their families who are asking for details on their prognosis. Speech and language therapists need to select therapies that are best suited to the brain structures that are available to support recovery. Currently, therapies are selected according to the patients' symptoms, not the integrity of recovery pathways we are identifying. Nevertheless, it is clearly recognised that the success of a therapy varies greatly from patient to patient. The predictions we generate by considering brain structure should provide (a) testable hypotheses to indicate which therapies are most likely to work for an individual patient; (b) a means of stratifying patients when testing the efficacy of a new treatment and (c) baseline predictions from which to quantify how much a therapy has accelerated recovery relative to that expected regardless of any intervention.

NHS economic efficiency: Healthcare provisions need to maximise treatment and support for aphasic patients while minimizing costs. Selecting appropriately tailored therapies will facilitate recovery and reduce the inevitable cost of selecting the wrong treatment.

Public: Provision of quality medical information on the web empowers the general public to find answers to frequently asked questions. Our research has a growing online presence and, through the project website and social media, is raising awareness of the potential to predict language recovery after stroke.
 
Title fMRI overlap maps. 
Description The method provides a simple way of visualising whole-brain consistency and variability in brain responses across patients using threshold-weighted voxel-based overlap maps. The output quantifies the proportion of patients activating a particular voxel or region over a wide range of statistical thresholds. This will be particularly useful when it comes to explaining typical (or atypical) compensatory mechanisms used by patients following brain damage. 
Type Of Material Model of mechanisms or symptoms - human 
Provided To Others? No  
Impact The paper has only just been published but the method will be incorporated into a toolbox called "SPM: Statistical Parametric Mapping". This is used for analyzing brain images by an estimated 3000 researchers worldwide (calculated by the number of times the software has been downloaded). 
URL http://www.ncbi.nlm.nih.gov/pubmed/26846561
 
Title PLORAS 
Description The PLORAS Database is a relational repository of anatomical and functional imaging data that has primarily been acquired from stroke survivors, along with standardized scores on a wide range of sensory, motor and cognitive abilities, demographic details and medical history. As of January 2017, we have data from 1050 patients with an expected accrual rate of 200 patients per year. Expansion will accelerate as we extend our collaborations. The main aim of the database is to Predict Language Outcome and Recovery After Stroke (PLORAS) on the basis of a single structural (anatomical) brain scan that indexes the stereotactic location and extent of brain damage. Predictions are made for individual patients by indicating how other patients with the most similar brain damage, cognitive abilities and demographic details recovered their language skills over time. Predictions are validated by longitudinal follow-ups of patients who initially presented with speech and language difficulties. The PLORAS Database can also be used to predict recovery of other cognitive abilities on the basis of anatomical brain scans. The functional imaging data can be used to understand the neural mechanisms that support recovery from brain damage; and all the data can be used to understand the main sources of inter-subject variability in structure-function mappings in the human brain. Data will be made available for sharing, subject to: funding, ethical approval and patient consent. 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact Many forthcoming publications. 
URL http://www.ncbi.nlm.nih.gov/pubmed/25882753
 
Description Collaboration of Aphasia Trialists 
Organisation University of Glasgow
Department NMAHP Research Unit,
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution The Collaboration of Aphasia Trialists (CATs)research into communication problems after stroke. We aim to establish a network of leading European multidisciplinary aphasia investigators in rehabilitation, social science, linguistics and language research. This network enhances knowledge, skills and methodology relating to aphasia research. Consensus activities facilitate international agreement in aphasia assessment & diagnosis. Data sharing activities contribute to enhanced prognosis and rehabilitation of aphasia. This Action facilitates the development of high quality aphasia research to address the needs of people with aphasia, their families, health and social care providers and voluntary groups.
Collaborator Contribution We are sharing data with other researchers. We are also collaborating on grant applications for aphasia therapy trials. Research Activities: 1. Data acquisition: Our PLORAS database records the following information from all volunteer stroke survivors: (i) a high resolution anatomical brain scan; (ii) a full language assessment and cognitive screening; (iii) a questionnaire to document the patient's history of aphasic symptoms and severity, time course of recovery and type and duration of intervention; (iv) demographic details; and (v) medical information. 2. Data analysis: Lesion location is identified automatically with high spatial definition (Seghier et al., 2008). Similarity measures match lesion sites and detect lesion features that are consistently associated with a particular symptom. The influence of many factors on aphasia recovery is investigated. 3. Implementation: A consistent association between lesion features, behavioural symptoms and the dependence of this relationship on other factors (e.g. handedness) becomes a lesion rule which is routinely tested (i.e. cross validated) in all subsequent patients. The clinical tool checks for all lesion rules and outputs the range of scores for all other patients who meet the same rule, plotted against time since stroke. Outcomes: Our ongoing work will: (i) improve the range, accuracy and precision of our predictive tool; (ii) increase theoretical understanding of aphasia; (iii) guide the selection of the best therapeutic intervention; and (iv) offer a way to stratify patients when assessing the success of experimental interventions.
Impact No outputs or outcomes so far
Start Year 2015
 
Description Andrew Marr TV programme 2016 
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 Public/other audiences
Results and Impact I have been involved a TV programme being made by Andrew Marr called My Brain and Me in 2017.
Year(s) Of Engagement Activity 2016
 
Description Barts Health NHS Trust Stroke Research Team - London October 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Rachel Bruce from my PLORAS group gave a lecture at the Barts Health NHS Trust Stroke Research Team meeting on 24 October.
Year(s) Of Engagement Activity 2016
 
Description Bloomsbury Festival 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact In October 2016, the PLORAS research team were involved in the Bloomsbury Festival. Events, inspired by the theme of language, invited the public to explore and experience the concept of language. Around 3000 people are thought to have attended. The PLORAS team organised a village fete style language game, based on Taboo. The game is designed to give members of the public a glimpse of what it feels like to lose their language. The public were also given information about the PLORAS study and introduced to one of our research participants with aphasia. Our goal was to raise awareness of aphasia.
Year(s) Of Engagement Activity 2016
URL http://bloomsburyfestival.org.uk/events/beyond-words/
 
Description CRN: Eastern Stroke Education Meeting November 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Rachel Bruce gave a lecture at the CRN Eastern Stroke Education Meeting in Newmarket on 17 November 2016.
Year(s) Of Engagement Activity 2016
 
Description CRN: Wessex Spring Stroke Meeting 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Rachel Bruce from my research group held an exhibition stand on PLORAS.
Year(s) Of Engagement Activity 2016
 
Description CRN:South London Stroke Training Meeting 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact I gave a talk at the CRN: South London Stroke Training Meeting and Niamh Devane from the PLORAS group gave Aphasia Training.

These activities helped improve knowledge in this research area.
Year(s) Of Engagement Activity 2015
 
Description Cardiff Masterclass Stroke Meeting 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The main purpose of the event was to learn about the hidden effects of stroke from leading experts in stroke care. The Masterclass was aimed at professionals working in stroke care enabling them to gain valuable CPD.
Year(s) Of Engagement Activity 2016
 
Description Foundations of Neurology 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Rachel Bruce and Zula Haigh from my group presented an overview of PLORAS and the latest results to Adult Speech and Language Therapists at the 'Foundations of Neurology' course for Adult Speech and Language Therapists - at the The National Hospital for Neurology and Neurosurgery, Queen Square, London.
Year(s) Of Engagement Activity 2016
URL https://www.uclhcharitycourses.com/sites/default/files/course-pdfs/Foundations%20of%20Neurology%20-%...
 
Description Hidden Effects of Stroke, Cardiff Stroke Masterclass 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact I gave a lecture on "Predicting language outcomes" at the Hidden Effects of Stroke, Cardiff Stroke Masterclass meeting in February 2016.
Year(s) Of Engagement Activity 2016
 
Description Invited Lecture given at University of Zurich in 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact My talk increased the knowledge regarding the PLORAS work.

Several questions were asked about my research from the audience.
Year(s) Of Engagement Activity 2015
 
Description Lewisham and Greenwich NHS Trust 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Sophie Roberts from my group gave an overview of PLORAS and practical information on getting involved to the Lewsiham and Greenwich NHS Trust SLT Team CPD meeting in October 2016.
Year(s) Of Engagement Activity 2016
 
Description UCL/ARNI Stroke Rehab Workshop February 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Sophie Roberts from my group gave aphasia training at the UCL/ARNI Stroke Rehabilitation Workshop in February 2016.
Year(s) Of Engagement Activity 2016
 
Description UCL/ARNI Stroke Rehabilitation Workshop October 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Stroke rehabilitation workshop designed for therapists and professional physical exercise instructors, to increase knowledge and skills concerning rehabilitation from stroke.
Year(s) Of Engagement Activity 2016
URL http://arni.uk.com/wp-content/uploads/2016/08/ARNI-UCL-programme-28th-October-2016.pdf
 
Description UK Stroke Forum Conference 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact PLORAS group members Rachel Bruce gave a presentation and Hayley Tolfrey gave aphasia training at the UK Stroke Forum Conference in Liverpool at a Study Update Meeting at this conference in December 2015. They also held an exhibition stand.

The purpose was to give:
1. Further information and training for current and potential Clinical Research Networks sites/health professionals about the study, and set up procedures.
2. Training on aphasia and equipping audience with basic skills to facilitate communication, to empower audience to communicate with people with aphasia and facilitate their participation in research.


Talk and training increased understanding of this field of work.
Year(s) Of Engagement Activity 2015