Feasibility Randomized Controlled Trial of Real-Time fMRI Neurofeedback for Reading Rehabilitation in Aphasia.

Abstract

Reading impairments are common in stroke-induced aphasia and limit participation in functional and leisure activities. Traditional rehabilitation strategies show limited generalization, underscoring the need for novel interventions targeting residual neural networks. This feasibility randomized controlled trial evaluated real-time functional magnetic resonance imaging (fMRI) neurofeedback intervention for poststroke reading deficits. Subacute left-hemisphere stroke survivors and healthy controls completed 3 weekly fMRI neurofeedback and 10 out-of-scanner practice sessions. Stroke participants were randomized to contingent neurofeedback (based on left supramarginal gyrus activity; N=4) or noncontingent neurofeedback (shuffled feedback from another participant; N=3). Healthy controls (N=4) received contingent neurofeedback and served as a normative reference. Primary outcomes were changes from baseline to postintervention (≈3 weeks) in task-based brain activity (motor imagery/word/nonword reading>baseline), resting-state connectivity, and reading aloud. Reading comprehension was a secondary outcome. Group×session effects were tested using repeated-measures analyses and planned contrasts. Task fMRI revealed training-related activation increases in the left supramarginal gyrus (z=4.7; cluster-corrected <i>P</i>=0.05) and broader reading network in the contingent neurofeedback group, particularly during nonword reading. Activation increases in the noncontingent stroke group and healthy controls were more widespread and less reading-specific. Resting-state fMRI revealed greater integration among motor, auditory, and language networks in the contingent groups, with more disorganized patterns in the noncontingent group (permutation <i>P</i>=0.01; Δr=-0.1 to 0.1). No changes were observed in reading aloud. A significant group×session interaction was found for Reading Comprehension Battery for Aphasia, second edition (F[2, 8]=8.00; <i>P</i><0.05; η²=0.67). The contingent neurofeedback stroke group improved more than healthy controls (mean difference in Reading Comprehension Battery for Aphasia, second edition, change=9.75 [95% CI, 1.99-17.51]; t[6]=3.07; <i>P</i><0.05) and noncontingent neurofeedback stroke group (Reading Comprehension Battery for Aphasia, second edition, change=11.42 [95% CI, 1.12-21.71]; t[5]=2.85; <i>P</i><0.05). These findings support the feasibility of targeting the residual reading network during early recovery using fMRI neurofeedback. Confirmation of these preliminary effects awaits completion of the ongoing randomized controlled trial. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04875936.