Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback can be used to train localized, conscious regulation of blood oxygen level-dependent (BOLD) signals. As a therapeutic technique, rt-fMRI neurofeedback reduces the symptoms of a variety of neurologic disorders. To date, few studies have investigated the use of self-regulation training using rt-fMRI neurofeedback to enhance cognitive performance. This work investigates the utility of rt-fMRI neurofeedback as a tool to enhance human cognition by training healthy individuals to consciously control activity in the left dorsolateral prefrontal cortex (DLPFC). A cohort of 18 healthy participants in the experimental group underwent rt-fMRI neurofeedback from the left DLPFC in five training sessions across two weeks while 7 participants in the control group underwent similar training outside the MRI and without rt-fMRI neurofeedback. Working memory (WM) performance was evaluated on two testing days separated by the five rt-fMRI neurofeedback sessions using two computerized tests. We investigated the ability to control the BOLD signal across training sessions and WM performance across the two testing days. The group with rt-fMRI neurofeedback demonstrated a significant increase in the ability to self-regulate the BOLD signal in the left DLPFC across sessions. WM performance showed differential improvement between testing days one and two across the groups with the highest increases observed in the rt-fMRI neurofeedback group. These results provide evidence that individuals can quickly gain the ability to consciously control the left DLPFC, and this training results in improvements of WM performance beyond that of training alone.

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The use of transcranial electrical stimulation (TES) as a method to augment neural activity has increased in popularity in the last decade and a half. The specific application of TES to the left prefrontal cortex has been shown to produce broad cognitive effects; however, the neural mechanisms underlying these effects remain unknown. In this work, we evaluated the effect of repetitive TES on cerebral perfusion. Stimulation was applied to the left prefrontal cortex on three consecutive days, and resting cerebral perfusion was quantified before and after stimulation using arterial spin labeling. Perfusion was found to decrease significantly more in a matched sham stimulation group than in a group receiving active stimulation across many areas of the brain. These changes were found to originate in the locus coeruleus and were broadly distributed in the neocortex. The changes in the neocortex may be a direct result of the stimulation or an indirect result via the changes in the noradrenergic system produced from the altered activity of the locus coeruleus. These findings indicate that anodal left prefrontal stimulation alters the activity of the locus coeruleus, and this altered activity may excite the noradrenergic system producing the broad behavioral effects that have been reported.

Studies have shown that transcranial direct current stimulation increases neuronal excitability of the targeted region and general connectivity of relevant functional networks. However, relatively little is understood on how the stimulation affects the connectivity relationship of the target with regions across the network structure of the brain. Here, we investigated the effects of transcranial direct current stimulation on the functional connectivity of the targeted region using resting-state fMRI scans of the human brain. Anodal direct current stimulation was applied to the left dorsolateral prefrontal cortex (lDLPFC; cathode on the right bicep), which belongs to the frontoparietal control network (FPCN) and is commonly targeted for neuromodulation of various cognitive functions including short-term memory, long-term memory, and cognitive control. lDLPFC's connectivity characteristics were quantified as graph theory measures, from the resting-state fMRI scans obtained prior to and following the stimulation. Critically, we tested pre- to poststimulation changes of the lDLPFC connectivity metrics following an active versus sham stimulation. We found that the stimulation had two distinct effects on the connectivity of lDLPFC: for Brodmann's area (BA) 9, it increased the functional connectivity between BA 9 and other nodes within the FPCN; for BA 46, net connectivity strength was not altered within FPCN, but connectivity distribution across networks (participation coefficient) was decreased. These findings provide insights that the behavioral changes as the functional consequences of stimulation may come about because of the increased role of lDLPFC in the FPCN.

In traditional fMRI, individuals respond to exogenous stimuli and are naïve to the effects of the stimuli on their neural activity patterns. Changes arising in the fMRI signal are analyzed post-hoc to elucidate the spatial and temporal activation of brain regions associated with the tasks performed. The advent of real-time fMRI has enabled a new method to systematically alter brain activity across space and time using neurofeedback training (NFT), providing a new tool to study internally-driven processes such as neuroplasticity. In this work, we combined n-back practice with fMRI-NFT of the left dorsolateral prefrontal cortex (DLPFC) to better understand the relationship between open-and closed-loop neuromodulation. FMRI data were acquired during both traditional n-back and NFT across five imaging sessions. Region-of-interest (ROI) and voxel-wise 2 × 2 within subjects ANOVAs were carried out to determine the effects of, and interaction between, training session and neuromodulation type. A main effect of training session was identified for only a single, highly focused cluster that shared spatial properties with the fMRI-NFT target region (left DLPFC). This finding indicates that combined open-and closed-loop neuroplastic enhancement techniques result in focal changes that are confined to the target area of NFT, and do not affect up-or down-stream network components that are normally engaged during working memory. Additionally, we identified a main effect of neuromodulation type for 15 clusters with significantly different activation between open-and closed-loop neuromodulation during training, 12 of which demonstrated higher activity during the open-loop neuromodulation. Our results, taken together with previous reports, indicate that fMRI-NFT combined with n-back practice leads to a highly focal volume exhibiting neuroplasticity without additional network effects.