Brain circuitry, behavior, and cognition: A randomized placebo-controlled trial of donepezil in fragile X syndrome.

Reduced functional brain activation for the active group may represent less arousal in response to direct eye gaze, relative to the placebo group. Change in functional magnetic resonance imaging activation patterns may serve as a more sensitive metric and predictor of response to treatment when compared to cognitive and behavioral assessments. Our results suggest that donepezil may have an impact on brain functioning, but longer term follow-up and concomitant behavioral intervention may be required to demonstrate improvement in cognition and behavior.