Brain mechanisms underlying reading improvement in post-stroke central alexia
Lead Research Organisation:
University College London
Department Name: Institute of Cognitive Neuroscience
Abstract
Central alexia is a common reading disorder caused by stroke and other forms of brain injury. Patients with central alexia are slow to read and make errors when they do so. They also have other problems with their language, most commonly speaking. Reading is important to most people so patients with central alexia have trouble returning to work, communicating by email or text, or simply reading for pleasure.
The present research has four aims, described in detail below.
1. Investigating the neural networks that support reading in patients with stroke
Despite being a relatively common syndrome, there have been no functional brain imaging studies of central alexia. The primary aim of this research project is to use functional imaging to understand how preserved parts of the reading network can be encouraged by therapy to support reading again. This will be done with a state-of-the-art technique of network connectivity analysis using magnetoencephalography (MEG). MEG detects changes in brain activity with a highly precise time resolution at the millisecond range, which makes it ideal for investigating reading (words can be recognized at exposures of less than 20ms). Our previous research using MEG has identified brain areas that form the 'normal' reading network, and the proposed study will test how this model is affected in patients with central alexia.
2. Developing a new treatment for central alexia
There are currently no easy-to-access therapies for central alexia, and only two previous group-level studies of reading training have been conducted in this patient group. We plan to develop a computer-based reading training system to improve word reading speed in patients with central alexia. The research team has developed training software called 'iReadMore', which uses an intensive cross-modal approach (visual written words paired with auditory spoken words) to train word reading. This therapy has been shown to be effective in a group of patients with a similar form of reading disorder called pure alexia. The iReadMore software will be adapted to address the reading deficit in central alexia, and the research will test whether it leads to significant improvements in reading speed that makes a difference to patients' lives.
3. Using brain stimulation to enhance behavioural training
Transcranial direct current stimulation (tDCS) is a relatively new brain stimulation technique that has been shown to improve language performance in healthy controls and stroke patients. It has not yet been applied to the treatment of acquired reading disorders. The present study will test whether tDCS, delivered simultaneously with the 'iReadMore' reading training, significantly enhances the improvement in reading speed. To do this, the patients participating in the study will be split into two groups. One group will receive a 4-week block of training plus real tDCS first; and the other half will receive the same training but with 'sham' tDCS that is indistinguishable to the real brain stimulation. The two groups will then swap over in the second 4-week block, so that both groups ultimately get the same amount of treatment. Comparing the reading improvement over the real and sham tDCS blocks will demonstrate whether tDCS enhances the behavioural improvements in reading speed.
4. Developing web-based therapy for central alexia
There are currently no web-based therapy aids for patients with central alexia to access for themselves. . If 'iReadMore' proves effective and acceptable to patients then we plan to make it available via a web browser for suitable patients to use. We have a proven track record in this area and have already produced two high-quality, therapy "web-apps", www.readright.ucl.ac.uk and www.eyesearch.ucl.ac.uk, for patients with visual impairment after stroke.
The present research has four aims, described in detail below.
1. Investigating the neural networks that support reading in patients with stroke
Despite being a relatively common syndrome, there have been no functional brain imaging studies of central alexia. The primary aim of this research project is to use functional imaging to understand how preserved parts of the reading network can be encouraged by therapy to support reading again. This will be done with a state-of-the-art technique of network connectivity analysis using magnetoencephalography (MEG). MEG detects changes in brain activity with a highly precise time resolution at the millisecond range, which makes it ideal for investigating reading (words can be recognized at exposures of less than 20ms). Our previous research using MEG has identified brain areas that form the 'normal' reading network, and the proposed study will test how this model is affected in patients with central alexia.
2. Developing a new treatment for central alexia
There are currently no easy-to-access therapies for central alexia, and only two previous group-level studies of reading training have been conducted in this patient group. We plan to develop a computer-based reading training system to improve word reading speed in patients with central alexia. The research team has developed training software called 'iReadMore', which uses an intensive cross-modal approach (visual written words paired with auditory spoken words) to train word reading. This therapy has been shown to be effective in a group of patients with a similar form of reading disorder called pure alexia. The iReadMore software will be adapted to address the reading deficit in central alexia, and the research will test whether it leads to significant improvements in reading speed that makes a difference to patients' lives.
3. Using brain stimulation to enhance behavioural training
Transcranial direct current stimulation (tDCS) is a relatively new brain stimulation technique that has been shown to improve language performance in healthy controls and stroke patients. It has not yet been applied to the treatment of acquired reading disorders. The present study will test whether tDCS, delivered simultaneously with the 'iReadMore' reading training, significantly enhances the improvement in reading speed. To do this, the patients participating in the study will be split into two groups. One group will receive a 4-week block of training plus real tDCS first; and the other half will receive the same training but with 'sham' tDCS that is indistinguishable to the real brain stimulation. The two groups will then swap over in the second 4-week block, so that both groups ultimately get the same amount of treatment. Comparing the reading improvement over the real and sham tDCS blocks will demonstrate whether tDCS enhances the behavioural improvements in reading speed.
4. Developing web-based therapy for central alexia
There are currently no web-based therapy aids for patients with central alexia to access for themselves. . If 'iReadMore' proves effective and acceptable to patients then we plan to make it available via a web browser for suitable patients to use. We have a proven track record in this area and have already produced two high-quality, therapy "web-apps", www.readright.ucl.ac.uk and www.eyesearch.ucl.ac.uk, for patients with visual impairment after stroke.
Technical Summary
We will examine therapy-induced changes in the brain networks supporting reading in patients being treated for central alexia. Our current network model of reading in controls and patients with pure alexia, will be developed to account for central alexia using data acquired from magnetoencephalography (MEG). We will test how well the effects of behavioural therapy, on performance and neural mechanisms, are influenced by tDCS, using a randomized, double-blind, crossover design. Therapeutic intervention will involve an adaptation of a computer-based, cross-modal reading program 'iReadMore' that has already been shown to improve reading speeds in patients with pure alexia. There are theoretical and practical reasons to support the use of this therapy in the larger population of patients with central alexia. If 'iReadMore' proves effective, we will make it available for use via a "web app", meeting an important, widespread, unmet clinical need.
Planned Impact
This research will have an impact upon five groups of beneficiaries:
1. Those in the neuroscience community interested in developing network models of reading.
Investigation of the impact of damage to the reading system is important for treating acquired reading disorders, but also for understanding the function of the intact neural network for reading. This research will contribute to that effort, particularly by providing data on the associations between the location of brain damage and the effect on behavioural speech and language functions.
2. Stroke patients with central alexia.
One of the aims of the proposed study is to develop more effective treatments for improving the reading ability of patients with central alexia. In the short term, this may be a direct result of the iReadMore reading training combined with a-tDCS brain stimulation. In the long term, there may be further benefits from using the results of the MEG and MRI functional imaging to better understand the functional locus of the reading deficit in central alexia, and to identify targets for future therapy studies. In either case, the benefits of developing computer-based therapies that improve reading ability in central alexia would be substantial, potentially including an increased quality of life, an increased likelihood of being able to return to work, and a decreased burden on existing NHS Speech and Language Therapy services.
3. Those in the neuroscience community with an interest in investigating the efficacy of transcranial direct current stimulation as a method for enhancing cognitive therapies.
The proposed research will demonstrate whether tDCS is a useful tool in the field of reading rehabilitation, and will have more general implications for the efficacy of tDCS in cognitive therapy. This will be of benefit in directing future studies using tDCS.
4. Neuropsychologists and speech and language therapists involved in developing or applying new methods for the rehabilitation of acquired reading disorders.
The proposed research will demonstrate whether cross-modal training is an effective theraputic approach, which will be beneficial for updating models of functional reorganisation after stroke and directing future research into reading rehabilitation.
5. Research staff employed on the project.
The proposed research presents considerable opportunities for professional development of the research staff. The project Researcher (Zoe Woodhead) and Research Assistant will receive training in the use of a range of neuroscientific techniques (tDCS, MEG and MRI) as well as in delivering behavioural assessments of speech and language. Acquisition of these skills will be of considerable benefit to them in pursuing research careers in this area.
1. Those in the neuroscience community interested in developing network models of reading.
Investigation of the impact of damage to the reading system is important for treating acquired reading disorders, but also for understanding the function of the intact neural network for reading. This research will contribute to that effort, particularly by providing data on the associations between the location of brain damage and the effect on behavioural speech and language functions.
2. Stroke patients with central alexia.
One of the aims of the proposed study is to develop more effective treatments for improving the reading ability of patients with central alexia. In the short term, this may be a direct result of the iReadMore reading training combined with a-tDCS brain stimulation. In the long term, there may be further benefits from using the results of the MEG and MRI functional imaging to better understand the functional locus of the reading deficit in central alexia, and to identify targets for future therapy studies. In either case, the benefits of developing computer-based therapies that improve reading ability in central alexia would be substantial, potentially including an increased quality of life, an increased likelihood of being able to return to work, and a decreased burden on existing NHS Speech and Language Therapy services.
3. Those in the neuroscience community with an interest in investigating the efficacy of transcranial direct current stimulation as a method for enhancing cognitive therapies.
The proposed research will demonstrate whether tDCS is a useful tool in the field of reading rehabilitation, and will have more general implications for the efficacy of tDCS in cognitive therapy. This will be of benefit in directing future studies using tDCS.
4. Neuropsychologists and speech and language therapists involved in developing or applying new methods for the rehabilitation of acquired reading disorders.
The proposed research will demonstrate whether cross-modal training is an effective theraputic approach, which will be beneficial for updating models of functional reorganisation after stroke and directing future research into reading rehabilitation.
5. Research staff employed on the project.
The proposed research presents considerable opportunities for professional development of the research staff. The project Researcher (Zoe Woodhead) and Research Assistant will receive training in the use of a range of neuroscientific techniques (tDCS, MEG and MRI) as well as in delivering behavioural assessments of speech and language. Acquisition of these skills will be of considerable benefit to them in pursuing research careers in this area.
Organisations
Publications
Yong KX
(2015)
Facilitating text reading in posterior cortical atrophy.
in Neurology
Woodhead ZVJ
(2018)
Randomized trial of iReadMore word reading training and brain stimulation in central alexia.
in Brain : a journal of neurology
Woodhead ZV
(2014)
Reading front to back: MEG evidence for early feedback effects during word recognition.
in Cerebral cortex (New York, N.Y. : 1991)
Woodhead ZV
(2013)
Reading therapy strengthens top-down connectivity in patients with pure alexia.
in Brain : a journal of neurology
Woodhead Z
(2015)
Web-based therapy for hemianopic alexia is syndrome-specific
in BMJ Innovations
Woodhead Z
(2017)
Auditory training changes temporal lobe connectivity in 'Wernicke's aphasia': a randomised trial
in Journal of Neurology, Neurosurgery & Psychiatry
Starrfelt R
(2013)
Word-superiority in pure alexia.
in Behavioural neurology
Robotham R
(2021)
Behavioural test battery for the Back of the Brain project
Leff A
(2014)
Alexia - Diagnosis, Treatment and Theory
Kerry SJ
(2019)
How Does iReadMore Therapy Change the Reading Network of Patients with Central Alexia?
in The Journal of neuroscience : the official journal of the Society for Neuroscience
Hope TMH
(2019)
Recovery after stroke: not so proportional after all?
in Brain : a journal of neurology
Hope TMH
(2018)
Predicting language outcomes after stroke: Is structural disconnection a useful predictor?
in NeuroImage. Clinical
Hope T
(2018)
Recovery after stroke: not so proportional after all?
Crinion JT
(2015)
Using functional imaging to understand therapeutic effects in poststroke aphasia.
in Current opinion in neurology
Aguilar O
(2018)
Dorsal and ventral visual stream contributions to preserved reading ability in patients with central alexia
in Cortex
Aguilar O
(2018)
Lesion-site-dependent responses to therapy after aphasic stroke
in Journal of Neurology, Neurosurgery & Psychiatry
Description | MRC Industrial CASE studentship (UCL-Birkbeck MRC Doctoral Training Partnership) |
Amount | £70,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 05/2018 |
End | 05/2021 |
Description | iReadMore commercial release and sustainability project |
Amount | £29,097 (GBP) |
Organisation | Higher Education Innovation Funding (HEIF) |
Sector | Public |
Country | United Kingdom |
Start | 01/2020 |
End | 03/2021 |
Title | iReadMore |
Description | The phase II clinical trial closed in July 2016 and the full data set has been analysed, written up and submitted for publication. The therapy (iReadMore) was clinically effective in treating patients with central alexia with an average (unstandardized) effect size of 9% across the group of 21 patients (standardized effect size: Cohen's d = 1.2). tDCS (transcranial direct current) effects were about 1/3 of the size but were also significant. |
Type | Therapeutic Intervention - Psychological/Behavioural |
Current Stage Of Development | Late clinical evaluation |
Year Development Stage Completed | 2014 |
Development Status | Closed |
Clinical Trial? | Yes |
Impact | Still ongoing. |
URL | https://clinicaltrials.gov/show/NCT02062619 |
Title | iReadMore |
Description | It is a therapy app for patients with acquired alexia (both pure alexia and central alexia). It has now received a CE mark as a class I medical device by the MHRA and is available for download from the Google Play Store (https://play.google.com/store/apps/details?id=ac.uk.ucl.iReadMore). It has been made available in a sustainability model, where users pay a monthly subscription following free, full access for 7 days. This app was produced in partnership with Passio Ltd [https://passio.co.uk/ previously Neurodiversity]. |
Type Of Technology | Webtool/Application |
Year Produced | 2020 |
Impact | This is one of very few evidence-based therapy apps for acquired reading disorders that is available for public download, and as such it has the potential to provide benefits to a large audience of users. We have plans to develop this app further, building in functionality that will make it more user-friendly. |
URL | https://www.ucl.ac.uk/icn/research/research-groups/neurotherapeutics/therapy-apps/ireadmore-app |
Title | iReadMore |
Description | It is a therapy app for patients with acquired alexia 9both pure alexia and central alexia). It has yet to be released (July 2019) but we have had it CE marked as a class I medical device by the MHRA (confirmation on 13th Feb 2019). This is an important step as now we can release with a plan to charge for its use (monthly subscription following free, full access for 7 days) on a sustainability model. Our SME partner for this is called Passio [https://passio.co.uk/ previously Neurodiversity] and they are finalizing the app with a release date planned for July 2019. |
Type Of Technology | Webtool/Application |
Year Produced | 2019 |
Impact | None yet, but will have on release. |
URL | https://www.ucl.ac.uk/aphasialab/apps/ireadmore.html |
Title | iReadMore |
Description | This is a practice-based, adaptive, reading therapy for patients with acquired brain injury (usually stroke) that has caused a certain type of reading disorder: 1) central alexia (reading disorder in the context of a generalized language disorder = aphasia); 2) pure alexia, an isolated reading disorder (other language functions OK) affecting visual word-form recognition. |
Type Of Technology | Webtool/Application |
Year Produced | 2014 |
Impact | The therapy has been put to the test in a phase II, baseline controlled, cross-over trial and the results were positive (submitted for publication but not accepted yet). Update 2018: paper about to be accepted (probably later this week). Have contacted MHRA regarding CE marking for roll-out release which will be on a social enterprise/sustainability model. Aim to roll-out by the end of 2018. |
URL | http://www.ucl.ac.uk/aphasialab/apps/ireadmore.html |
Title | iReadMore |
Description | This is an adaptive, mass-practice, single-word reading therapy for patients with post-stroke alexia (central or pure) and patients with dementia and reading problems (PPA). The second version of the software is now being released as we were able to add more functionality with the HEIF grant. We employed a software developer to upgrade and add more tests and improve the therapy. |
Type Of Technology | Webtool/Application |
Year Produced | 2021 |
Impact | It is due for release this week. |
URL | https://www.ucl.ac.uk/icn/research/research-groups/neurotherapeutics/therapy-apps/ireadmore-app |
Description | Neurobiology of Language conference 2014 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Poster session, well attended. Also demonstrated the reading therapy (iRead More) on a tablet device. Interesting discussion with other people in the field of reading rehabilitation. |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.neurolang.org/?page=poster_detail&show=authors&sort=board_a&go=&session=Friday,+August+29... |