Brain activation profiles obtained using magnetoencephalography were compared between middle-school students experiencing reading difficulties and non-reading-impaired students during performance of a continuous printed word recognition task. Struggling readers underwent small–group remedial instruction, and students who showed significant gains in word reading efficiency at a one-year follow-up assessment were classified as Adequate Responders whereas those not demonstrating such gains as Inadequate Responders. At baseline, compared to Inadequate Responders, the activation profiles of Adequate Responders featured increased activity in the left middle, superior temporal, and ventral occipitotemporal regions, as well as in the right mesial temporal cortex. The degree of activity in these regions was a significant predictor of improvement in word reading efficiency beyond the prediction afforded by baseline reading accuracy or fluency measures. The engagement of brain areas that typically serve as key components of the brain circuit for reading may be an important factor in predicting response to intervention in older students who experience reading difficulties.