Mirror visual feedback (MVF) is potentially a powerful tool to facilitate recovery of disordered movement and stimulate activation of under-active brain areas due to stroke. The neural mechanisms underlying MVF have therefore been a focus of recent inquiry. Although it is known that sensorimotor areas can be activated via mirror feedback, the network interactions driving this effect remain unknown. The aim of the current study was to fill this gap by using dynamic causal modeling to test the interactions between regions in the frontal and parietal lobes that may be important for modulating the activation of the ipsilesional motor cortex during mirror visual feedback of unaffected hand movement in stroke patients. Our intent was to distinguish between two theoretical neural mechanisms that might mediate ipsilateral activation in response to mirror-feedback: transfer of information between bilateral motor cortices versus recruitment of regions comprising an action observation network which in turn modulate the motor cortex. In an event-related fMRI design, fourteen chronic stroke subjects performed goal-directed finger flexion movements with their unaffected hand while observing real-time visual feedback of the corresponding (veridical) or opposite (mirror) hand in virtual reality. Among 30 plausible network models that were tested, the winning model revealed significant mirror feedback-based modulation of the ipsilesional motor cortex arising from the contralesional parietal cortex, in a region along the rostral extent of the intraparietal sulcus. No winning model was identified for the veridical feedback condition. We discuss our findings in the context of supporting the latter hypothesis, that mirror feedback-based activation of motor cortex may be attributed to engagement of a contralateral (contralesional) action observation network. These findings may have important implications for identifying putative cortical areas, which may be targeted with non-invasive brain stimulation as a means of potentiating the effects of mirror training.

Background: Although biofeedback using electrophysiology has been explored extensively, the approach of using neurofeedback corresponding to hemodynamic response is a relatively young field. Real time functional magnetic resonance imaging-based neurofeedback (rt-fMRI-NF) uses sensory feedback to operantly reinforce patterns of neural response. It can be used, for example, to alter visual perception, increase brain connectivity, and reduce depression symptoms. Within recent years, interest in rt-fMRI-NF in both research and clinical contexts has expanded considerably. As such, building a consensus regarding best practices is of great value. Objective: This systematic review is designed to describe and evaluate the variations in methodology used in previous rt-fMRI-NF studies to provide recommendations for rt-fMRI-NF study designs that are mostly likely to elicit reproducible and consistent effects of neurofeedback. Methods: We conducted a database search for fMRI neurofeedback papers published prior to September 26th, 2019. Of 558 studies identified, 146 met criteria for inclusion. The following information was collected from each study: sample size and type, task used, neurofeedback calculation, regulation procedure, feedback, whether feedback was explicitly related to changing brain activity, feedback timing, control group for active neurofeedback, how many runs and sessions of neurofeedback, if a follow-up was conducted, and the results of neurofeedback training. Results: rt-fMRI-NF is typically upregulation practice based on hemodynamic response from a specific region of the brain presented using a continually updating thermometer display. Most rt-fMRI-NF studies are conducted in healthy samples and half evaluate its effect on immediate changes in behavior or affect. The most popular control group method is to provide sham signal from another region; however, many studies do not compare use a comparison group. Conclusions: We make several suggestions for designs of future rt-fMRI-NF studies. Researchers should use feedback calculation methods that consider neural response across regions (i.e., SVM or connectivity), which should be conveyed as intermittent, Fede et al. Neurofeedback Guide auditory feedback. Participants should be given explicit instructions and should be assessed on individual differences. Future rt-fMRI-NF studies should use clinical samples; effectiveness of rt-fMRI-NF should be evaluated on clinical/behavioral outcomes at follow-up time points in comparison to both a sham and no feedback control group.

Mirror visual feedback (MVF) training is a promising technique to promote activation in the lesioned hemisphere following stroke, and aid recovery. However, current outcomes of MVF training are mixed, in part, due to variability in the task undertaken during MVF. The present study investigated the hypothesis that movements directed toward visual targets may enhance MVF modulation of motor cortex (M1) excitability ipsilateral to the trained hand compared to movements without visual targets. Ten healthy subjects participated in a 2 × 2 factorial design in which feedback (veridical, mirror) and presence of a visual target (target present, target absent) for a right index-finger flexion task were systematically manipulated in a virtual environment. To measure M1 excitability, transcranial magnetic stimulation (TMS) was applied to the hemisphere ipsilateral to the trained hand to elicit motor evoked potentials (MEPs) in the untrained first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles at rest prior to and following each of four 2-min blocks of 30 movements (B1–B4). Targeted movement kinematics without visual feedback was measured before and after training to assess learning and transfer. FDI MEPs were decreased in B1 and B2 when movements were made with veridical feedback and visual targets were absent. FDI MEPs were decreased in B2 and B3 when movements were made with mirror feedback and visual targets were absent. FDI MEPs were increased in B3 when movements were made with mirror feedback and visual targets were present. Significant MEP changes were not present for the uninvolved ADM, suggesting a task-specific effect. Analysis of kinematics revealed learning occurred in visual target-directed conditions, but transfer was not sensitive to mirror feedback. Results are discussed with respect to current theoretical mechanisms underlying MVF-induced changes in ipsilateral excitability.