How does iReadMore therapy change the reading network of patients with central alexia

Central alexia (CA) is an acquired reading disorder co-occurring with a generalised language deficit (aphasia). The roles of perilesional and ipsilesional tissue in recovery from post-stroke aphasia are unclear. We investigated the impact of reading training (using iReadMore, a therapy app) on the connections within and between the right and left hemisphere of the reading network of patients with CA. In patients with pure alexia, iReadMore increased feedback from left inferior frontal region (IFG) to the left occipital (OCC) region. We aimed to identify if iReadMore therapy was effective through a similar mechanism in CA patients. Participants with chronic post-stroke CA (n=23) completed 35 hours of iReadMore training over four weeks. Reading accuracy for trained and untrained words was assessed before and after therapy. The neural response to reading trained and untrained words in the left and right OCC, ventral occipitotemporal (vOT) and IFG was examined using event-related magnetoencephalography. The training-related modulation in effective connectivity between regions was modelled at the group level with Dynamic Causal Modelling. iReadMore training improved participants9 reading accuracy by an average of 8.4% (range: -2.77 to 31.66) while accuracy for untrained words was stable. Training increased regional sensitivity in bilateral frontal and occipital regions, and strengthened feedforward connections within the left hemisphere. Our data suggests that iReadMore training in these patients modulates lower-order visual representations, as opposed to higher-order, more abstract ones, in order to improve word reading accuracy. SIGNIFICANCE STATEMENT This is the first study to conduct a network-level analyses of therapy effects in participants with post-stroke central alexia. When patients trained with iReadMore (a multimodal, behavioural, mass practice, computer-based therapy), reading accuracy improved by an average 8.4% on trained items. A network analysis of the magnetoencephalography data associated with this improvement revealed an increase in regional sensitivity in bilateral frontal and occipital regions and strengthening of feedforward connections within the left hemisphere. This indicates that in CA patients iReadMore engages lower-order, intact resources within the left hemisphere (posterior to their lesion locations) to improve word reading. This provides a foundation for future research to investigate reading network modulation in different CA subtypes, or for sentence level therapy.