A brief real-time fNIRS-informed neurofeedback training of the prefrontal cortex changes brain activity and connectivity during subsequent working memory challenge

Working memory (WM) represents a building-block of higher cognitive functions and a wide range of mental disorders are associated with WM impairments. Initial studies have shown that several sessions of functional nearinfrared spectroscopy (fNIRS) informed real-time neurofeedback (NF) allow healthy individuals to volitionally increase activity in the dorsolateral prefrontal cortex (DLPFC), a region critically involved in WM. For the translation to therapeutic or neuroenhancement applications, however, it is critical to assess whether fNIRS-NF success transfers into neural and behavioral WM enhancement in the absence of feedback. We therefore combined single-session fNIRS-NF of the left DLPFC with a randomized sham-controlled design (N = 62 participants) and a subsequent WM challenge with concomitant functional MRI. Over four runs of fNIRS-NF, the left DLPFC NF training group demonstrated enhanced neural activity in this region, reflecting successful acquisition of neural selfregulation. During the subsequent WM challenge, we observed no evidence for performance differences between the training and the sham group. Importantly, however, examination of the fMRI data revealed that - compared to the sham group - the training group exhibited significantly increased regional activity in the bilateral DLPFC and decreased left DLPFC - left anterior insula functional connectivity during the WM challenge. Exploratory analyses revealed a negative association between DLPFC activity and WM reaction times in the NF group. Together, these findings indicate that healthy individuals can learn to volitionally increase left DLPFC activity in a single training session and that the training success translates into WM-related neural activation and connectivity changes in the absence of feedback. This renders fNIRS-NF as a promising and scalable WM intervention approach that could be applied to various mental disorders.