Brain mechanisms underlying reading improvement in post-stroke central alexia

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.

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.

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.