Validation of real-time fMRI neurofeedback procedure for cognitive training using counterbalanced active-sham study design.

Investigation of neural mechanisms of real-time functional MRI neurofeedback (rtfMRI-nf) training requires an efficient study control approach. A common rtfMRI-nf study design involves an experimental group, receiving active rtfMRI-nf, and a control group, provided with sham rtfMRI-nf. We report the first study in which rtfMRI-nf procedure is controlled through counterbalancing training runs with active and sham rtfMRI-nf for each participant. Healthy volunteers (n = 18) used rtfMRI-nf to upregulate fMRI activity of an individually defined target region in the left dorsolateral prefrontal cortex (DLPFC) while performing tasks that involved mental generation of a random numerical sequence and serial summation of numbers in the sequence. Sham rtfMRI-nf was provided based on fMRI activity of a different brain region, not involved in these tasks. The experimental procedure included two training runs with the active rtfMRI-nf and two runs with the sham rtfMRI-nf, in a randomized order. The participants achieved significantly higher fMRI activation of the left DLPFC target region during the active rtfMRI-nf conditions compared to the sham rtfMRI-nf conditions. fMRI functional connectivity of the left DLPFC target region with the nodes of the central executive network was significantly enhanced during the active rtfMRI-nf conditions relative to the sham conditions. fMRI connectivity of the target region with the nodes of the default mode network was similarly enhanced. fMRI connectivity changes between the active and sham conditions exhibited meaningful associations with individual performance measures on the Working Memory Multimodal Attention Task, the Approach-Avoidance Task, and the Trail Making Test. Our results demonstrate that the counterbalanced active-sham study design can be efficiently used to investigate mechanisms of active rtfMRI-nf in direct comparison to those of sham rtfMRI-nf. Further studies with larger group sizes are needed to confirm the reported findings and evaluate clinical utility of this study control approach.