Abstract.SignificanceSpatial working memory (SWM) is essential for daily life and deficits in this domain represent a common impairment across aging and several mental disorders. Impaired SWM has been closely linked to dysregulations in dorsolateral prefrontal cortex (DLPFC) activation.AimThe present study evaluates the feasibility and maintenance of functional near-infrared spectroscopy neurofeedback (fNIRS-NF) training of the DLPFC to enhance SWM in healthy individuals using a real-time fNIRS-NF platform developed by the authors.ApproachWe used a randomized sham-controlled between-subject fNIRS-NF design with 60 healthy subjects as a sample. Training-induced changes in the DLPFC, SWM, and attention performance served as primary outcomes.ResultsFeedback from the target channel significantly increased regional-specific DLPFC activation over the fNIRS-NF training compared to sham NF. A significant group difference in NF-induced frontoparietal connectivity was observed. Compared to the control group, the experimental group demonstrated significantly improved SWM and attention performance that were maintained for 1 week. Furthermore, a mediation analysis demonstrated that increased DLPFC activation mediated the effects of fNIRS-NF treatment on better SWM performance.ConclusionsThe present results demonstrated that successful self-regulation of DLPFC activation may represent a long-lasting intervention to improve human SWM and has the potential for further applications.