How Does iReadMore Therapy Change the Reading Network of Patients with Central Alexia?

Abstract

Central alexia (CA) is an acquired reading disorder co-occurring with a generalized language deficit (aphasia). The roles of perilesional and ipsilesional tissue in recovery from poststroke 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 gyrus (IFG) region to the left occipital (OCC) region. We aimed to identify whether iReadMore therapy was effective through a similar mechanism in patients with CA. Participants with chronic poststroke CA (n = 23) completed 35 h of iReadMore training over 4 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, and IFG regions was examined using event-related magnetoencephalography. The training-related modulation in effective connectivity between regions was modeled at the group level with dynamic causal modeling. iReadMore training improved participants' 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 suggest that iReadMore training in these patients modulates lower-order visual representations, as opposed to higher-order, more abstract representations, to improve word-reading accuracy.SIGNIFICANCE STATEMENT This is the first study to conduct a network-level analysis of therapy effects in participants with poststroke central alexia. When patients trained with iReadMore (a multimodal, behavioral, 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 patients with CA 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.

Trial registration: ClinicalTrials.gov NCT02062619.

Keywords: DCM; MEG; alexia; aphasia; reading; stroke.

Copyright © 2019 the authors.

Figures

Figure 1.

Study design. The baseline assessment took place over two testing sessions 1–2 weeks apart (T1 and T2). An MEG scan and behavioral assessment was conducted before (T3) and after (T4) a 4 week block of iReadMore training.

Figure 2.

A, Optimal source locations identified using variational Bayesian equivalent current dipole modeling for each subject, plotted on a glass brain in Montreal Neurological Institute (MNI) space. Average dipole location across the group are given for the six sources: occipital (blue), ventral occipital temporal (gray), and inferior frontal gyrus (red). B, Lesion overlay map for the group (n = 23) where hotter colors indicate greater number of patients with lesions affecting that area.

Figure 3.

Stimulus presentation procedure for the MEG scans. Participants were scanned before and after training. At each session, there were 150 trials for each condition of interest (trained and untrained words), 150 trials for false fonts (omitted from this analysis) and 40 catch trials (names).

Figure 4.

A, B, Change over time in mean word-reading accuracy (A; n = 23) and reaction times (B; n = 22) for trained words (blue) and untrained words (red). Error bars indicate 95% confidence intervals. In these pirate plots, each gray point represents a participant, the solid bars show the means and the shaded boxes indicate the 95% confidence intervals.

Figure 5.

Results of the DCM analysis: modulated connection strengths for words trained with iReadMore after training. These are connections that met the following criteria: (1) there was significant modulation in Matrix B1 (Tr_Before vs Tr_After); and (2) the therapy-specific modulation in Matrix B1 was significantly different to the nonspecific change over time in Matrix B2 (Tr_Before vs Un_After). Connections in red became significantly stronger after training, whereas connections in blue became significantly weaker after training.