ABSTRACTThe existence of abnormal connectivity patterns between resting state networks in neuropsychiatric disorders, including Autism Spectrum Disorder (ASD), has been well established. Traditional treatment methods in ASD are limited, and do not address the aberrant network structure. Using real-time fMRI neurofeedback, we directly trained 3 brain nodes in participants with ASD, in which the aberrant connectivity has been shown to correlate with symptom severity. 17 ASD participants and 10 control participants were scanned over multiple sessions (123 sessions in total). Desired network connectivity patterns were reinforced in real-time, without participants’ awareness of the training taking place. This training regimen produced large, significant long-term changes in correlations at the network level, and whole brain analysis revealed that the greatest changes were focused on the areas being trained. These changes were not found in the control group. Moreover, changes in ASD resting state connectivity following the training were correlated to changes in behavior, suggesting that neurofeedback can be used to directly alter complex, clinically relevant network connectivity patterns.Significance StatementMany disorders are characterized by underlying abnormalities in network connectivity. These abnormalities are difficult to address with explicit training procedures (which are unlikely to target the specific abnormalities). Covert neurofeedback however, can directly target these networks, positively reinforcing the desired connections. We have developed a method for reinforcing correlations in real-time, and show that such training is effective, inducing significant, long-lasting changes in connectivity between aberrant networks in Autism Spectrum Disorder. This provides a potential mechanism for modulating aberrant correlation structures in other clinical groups as well.