Neurofeedback: A Comprehensive Review on System Design, Methodology and Clinical Applications

Inputs from GABAergic and glutamatergic neurons are suspected to play an important role in regulating the activity of the gonadotropin-releasing hormone (GnRH) neurons. The GnRH neurons exhibit marked plasticity to control the ovarian cycle with circulating estradiol concentrations having profound “feedback” effects on their activity. This includes “negative feedback” responsible for suppressing GnRH neuron activity and “positive feedback” that occurs at mid-cycle to activate the GnRH neurons to generate the preovulatory luteinizing hormone surge. In the present study, we employed brain slice electrophysiology to question whether synaptic ionotropic GABA and glutamate receptor signaling at the GnRH neuron changed at times of negative and positive feedback. We used a well characterized estradiol (E)–treated ovariectomized (OVX) mouse model to replicate negative and positive feedback. Miniature and spontaneous postsynaptic currents (mPSCs and sPSCs) attributable to GABAA and glutamatergic receptor signaling were recorded from GnRH neurons obtained from intact diestrous, OVX, OVX + E (negative feedback), and OVX + E+E (positive feedback) female mice. Approximately 90% of GnRH neurons exhibited spontaneous GABAA-mPSCs in all groups but no significant differences in the frequency or kinetics of mPSCs were found at the times of negative or positive feedback. Approximately 50% of GnRH neurons exhibited spontaneous glutamate mPSCs but again no differences were detected. The same was true for spontaneous PSCs in all cases. These observations indicate that the kinetics of ionotropic GABA and glutamate receptor synaptic transmission to GnRH neurons remain stable across the different estrogen feedback states.

Neurofeedback therapy is a fast-growing field of tinnitus treatment, which is a new type of biofeedback therapy. In the past, the "muscle tone" and "blood flow" were used as feedback signals in biofeedback therapy to treat tinnitus, however there was no long-term follow-up report. Instead, neurofeedback therapy utilizes EEG (electroencephalogram) as the feedback signal, which is also called EEG biofeedback therapy. At present, most treatments of tinnitus only record subjective measures of patients as evaluation indicators, whereas neurofeedback therapy is more convincing for using comprehensive evaluation including changes of brain wave as objective indicators and subjective measures of patients. A significant number of tinnitus patients have varying degree of hearing loss. As neurofeedback therapy takes advantage of EEG as feedback signal that is delivered to the patients through visual information, it has unique advantages of being not affected by the degree of hearing loss compared to the sound masking or other sound treatment. Long-term follow-up results showed that the efficacy of neurofeedback therapy was stable after half a year of short-term treatment. This paper summarizes the progress of the various types of biofeedback therapy in the treatment of tinnitus, and focuses on the neurofeedback therapy for the mechanism, indication, process, efficacy evaluation, defect and prospect of neurofeedback therapy in tinnitus treatment in order to help promote the development of domestic clinical neurofeedback therapy in tinnitus.

Performance feedback signals to people where they stand in their goal progress. Positive feedback suggests that one is on a good track to achieve a goal. Negative feedback indicates that another strategy or greater effort is required. However, not everyone reacts equally to such feedback. Through four studies using a variety of methods, we examined how individuals’ experience of power affects motivation and performance depending on whether they receive negative or positive performance feedback. While results were not completely uniform, a general pattern could be observed. Specifically, a meta‐analysis across all studies showed that negative feedback had an overall detrimental effect on motivation and performance of low‐power individuals but not of high‐power individuals. Positive feedback neither impacted low‐ nor high‐power individuals' motivation but increased low‐power individuals’ performance relative to their high‐power counterparts. Our findings imply that performance feedback needs to be tailored to the recipient's experience of power.

How children learn from positive and negative performance feedback lies at the foundation of successful learning and is therefore of great importance for educational practice. In this study, we used functional magnetic resonance imaging (fMRI) to examine the neural developmental changes related to feedback-based learning when performing a rule search and application task. Behavioral results from three age groups (8-9, 11-13, and 18-25 years of age) demonstrated that, compared with adults, 8- to 9-year-old children performed disproportionally more inaccurately after receiving negative feedback relative to positive feedback. Additionally, imaging data pointed toward a qualitative difference in how children and adults use performance feedback. That is, dorsolateral prefrontal cortex and superior parietal cortex were more active after negative feedback for adults, but after positive feedback for children (8-9 years of age). For 11- to 13-year-olds, these regions did not show differential feedback sensitivity, suggesting that the transition occurs around this age. Pre-supplementary motor area/anterior cingulate cortex, in contrast, was more active after negative feedback in both 11- to 13-year-olds and adults, but not 8- to 9-year-olds. Together, the current data show that cognitive control areas are differentially engaged during feedback-based learning across development. Adults engage these regions after signals of response adjustment (i.e., negative feedback). Young children engage these regions after signals of response continuation (i.e., positive feedback). The neural activation patterns found in 11- to 13-year-olds indicate a transition around this age toward an increased influence of negative feedback on performance adjustment. This is the first developmental fMRI study to compare qualitative changes in brain activation during feedback learning across distinct stages of development.

One barrier to interpreting past studies of cognition and major depressive disorder (MDD) has been the failure in many studies to adequately dissociate the effects of MDD from the potential cognitive side effects of selective serotonin reuptake inhibitors (SSRIs) use. To better understand how remediation of depressive symptoms affects cognitive function in MDD, we evaluated three groups of subjects: medication-naïve patients with MDD, medicated patients with MDD receiving the SSRI paroxetine, and healthy control (HC) subjects. All were administered a category-learning task that allows for dissociation between learning from positive feedback (reward) vs. learning from negative feedback (punishment). Healthy subjects learned significantly better from positive feedback than medication-naïve and medicated MDD groups, whose learning accuracy did not differ significantly. In contrast, medicated patients with MDD learned significantly less from negative feedback than medication-naïve patients with MDD and healthy subjects, whose learning accuracy was comparable. A comparison of subject’s relative sensitivity to positive vs. negative feedback showed that both the medicated MDD and HC groups conform to Kahneman and Tversky’s (1979) Prospect Theory, which expects losses (negative feedback) to loom psychologically slightly larger than gains (positive feedback). However, medicated MDD and HC profiles are not similar, which indicates that the state of medicated MDD is not “normal” when compared to HC, but rather balanced with less learning from both positive and negative feedback. On the other hand, medication-naïve patients with MDD violate Prospect Theory by having significantly exaggerated learning from negative feedback. This suggests that SSRI antidepressants impair learning from negative feedback, while having negligible effect on learning from positive feedback. Overall, these findings shed light on the importance of dissociating the cognitive consequences of MDD from those of SSRI treatment, and from cognitive evaluation of MDD subjects in a medication-naïve state before the administration of antidepressants. Future research is needed to correlate the mood-elevating effects and the cognitive balance between reward- and punishment-based learning related to SSRIs.

It is well known that noise is inevitable in gene regulatory networks due to the low-copy numbers of molecules and local environmental fluctuations. The prediction of noise effects is a key issue in ensuring reliable transmission of information. Interlinked positive and negative feedback loops are essential signal transduction motifs in biological networks. Positive feedback loops are generally believed to induce a switch-like behavior, whereas negative feedback loops are thought to suppress noise effects. Here, by using the signal sensitivity (susceptibility) and noise amplification to quantify noise propagation, we analyze an abstract model of the Myc/E2F/MiR-17-92 network that is composed of a coupling between the E2F/Myc positive feedback loop and the E2F/Myc/miR-17-92 negative feedback loop. The role of the feedback loop on noise effects is found to depend on the dynamic properties of the system. When the system is in monostability or bistability with high protein concentrations, noise is consistently suppressed. However, the negative feedback loop reduces this suppression ability (or improves the noise propagation) and enhances signal sensitivity. In the case of excitability, bistability, or monostability, noise is enhanced at low protein concentrations. The negative feedback loop reduces this noise enhancement as well as the signal sensitivity. In all cases, the positive feedback loop acts contrary to the negative feedback loop. We also found that increasing the time scale of the protein module or decreasing the noise autocorrelation time can enhance noise suppression; however, the systems sensitivity remains unchanged. Taken together, our results suggest that the negative/positive feedback mechanisms in coupled feedback loop dynamically buffer noise effects rather than only suppressing or amplifying the noise.

687: The relationship of type of feedback to learning during simulation: a randomized clinical trial

A wide range of cellular processes require molecular regulatory pathways to convert a graded signal into a discrete response. One prevalent switching mechanism relies on the coexistence of two stable states (bistability) caused by positive feedback regulations. Intriguingly, positive feedback is often supplemented with negative feedback, raising the question of whether and how these two types of feedback can cooperate to control discrete cellular responses. To address this issue, we formulate a canonical model of a protein–protein interaction network and analyze the dynamics of a prototypical two-component circuit. The appropriate combination of negative and positive feedback loops can bring a bistable circuit close to the oscillatory regime. Notably, sharply activated negative feedback can give rise to a bistable regime wherein two stable fixed points coexist and may collide pairwise with two saddle points. This specific type of bistability is found to allow for separate and flexible control of switch-on and switch-off events, for example (i) to combine fast and reversible transitions, (ii) to enable transient switching responses and (iii) to display tunable noise-induced transition rates. Finally, we discuss the relevance of such bistable switching behavior, and the circuit topologies considered, to specific biological processes such as adaptive metabolic responses, stochastic fate decisions and cell-cycle transitions. Taken together, our results suggest an efficient mechanism by which positive and negative feedback loops cooperate to drive the flexible and multifaceted switching behaviors arising in biological systems.

Feedback modules, which appear ubiquitously in biological regulations, are often subject to disturbances from the input, leading to fluctuations in the output. Thus, the question becomes how a feedback system can produce a faithful response with a noisy input. We employed multiple time scale analysis, Fluctuation Dissipation Theorem, linear stability, and numerical simulations to investigate a module with one positive feedback loop driven by an external stimulus, and we obtained a critical quantity in noise attenuation, termed as “signed activation time”. We then studied the signed activation time for a system of two positive feedback loops, a system of one positive feedback loop and one negative feedback loop, and six other existing biological models consisting of multiple components along with positive and negative feedback loops. An inverse relationship is found between the noise amplification rate and the signed activation time, defined as the difference between the deactivation and activation time scales of the noise-free system, normalized by the frequency of noises presented in the input. Thus, the combination of fast activation and slow deactivation provides the best noise attenuation, and it can be attained in a single positive feedback loop system. An additional positive feedback loop often leads to a marked decrease in activation time, decrease or slight increase of deactivation time and allows larger kinetic rate variations for slow deactivation and fast activation. On the other hand, a negative feedback loop may increase the activation and deactivation times. The negative relationship between the noise amplification rate and the signed activation time also holds for the six other biological models with multiple components and feedback loops. This principle may be applicable to other feedback systems.

Previous studies have suggested that negative feedback is more effective in driving learning than positive feedback. We investigated the effect on learning of providing varying amounts of negative and positive feedback while listeners attempted to discriminate between three identical tones; an impossible task that nevertheless produces robust learning. Four feedback conditions were compared during training: 90% positive feedback or 10% negative feedback informed the participants that they were doing equally well, while 10% positive or 90% negative feedback informed them they were doing equally badly. In all conditions the feedback was random in relation to the listeners’ responses (because the task was to discriminate three identical tones), yet both the valence (negative vs. positive) and the probability of feedback (10% vs. 90%) affected learning. Feedback that informed listeners they were doing badly resulted in better post-training performance than feedback that informed them they were doing well, independent of valence. In addition, positive feedback during training resulted in better post-training performance than negative feedback, but only positive feedback indicating listeners were doing badly on the task resulted in learning. As we have previously speculated, feedback that better reflected the difficulty of the task was more effective in driving learning than feedback that suggested performance was better than it should have been given perceived task difficulty. But contrary to expectations, positive feedback was more effective than negative feedback in driving learning. Feedback thus had two separable effects on learning: feedback valence affected motivation on a subjectively difficult task, and learning occurred only when feedback probability reflected the subjective difficulty. To optimize learning, training programs need to take into consideration both feedback valence and probability.

Abstract. Using the National Center for Atmospheric Research (NCAR) general circulation model (CCM2), a suite of alternative cloud radiation parameterizations has been tested. Our methodology relies on perpetual July integrations driven by ±2 K sea surface temperature forcing. The tested parameterizations include relative humidity based clouds and versions of schemes involving a prognostic cloud water budget. We are especially interested in testing the effect of cloud optical thickness feedbacks on global climate sensitivity. All schemes exhibit negative cloud radiation feedbacks, i.e., cloud moderates the global warming. However, these negative net cloud radiation feedbacks consist of quite different shortwave and longwave components between a scheme with interactive cloud radiative properties and several schemes with specified cloud water paths. An increase in cloud water content in the warmer climate leads to optically thicker middle- and low-level clouds and in turn negative shortwave feedbacks for the interactive radiative scheme, while a decrease in cloud amount leads to a positive shortwave feedback for the other schemes. For the longwave feedbacks, a decrease in high effective cloudiness for the schemes without interactive radiative properties leads to a negative feedback, while no distinct changes in effective high cloudiness and the resulting feedback are exhibited for the scheme with interactive radiative properties. The resulting magnitude of negative net cloud radiation feed-back is largest for the scheme with interactive radiative properties. Even though the simulated values of cloud radiative forcing for the present climate using this method differ most from the observational data, the approach shows great promise for the future.

The direct effects of climate change are increasing the frequency of high-intensity fire events in many ecosystems across the globe, including wet Eucalypt forests of south-eastern (SE) Australia. Recurrent high-intensity fire can alter vegetation structure and composition, and the resultant alternative vegetation states may be more likely (positive feedback) or less likely (negative feedback) to burn again than the vegetation community replaced. These indirect effects of climate change have been reported for a range of different ecosystems across the globe. However, a common limitation to many empirical studies is the narrow temporal range of observations, often limited to a single fire season. In turn, this limits our understanding of the potential for vegetation-mediated indirect effects of climate change to generate positive or negative fire feedbacks across the range of climate conditions common to the region. In wet Eucalypt forests of SE Australia, dead fuel moisture content (FMC) is a key determinant of fire activity, and therefore a useful metric on which to quantify the potential for feedbacks across alternative forest states. To quantify potential for indirect effects of climate change to alter future fire activity, FMC was modelled in the open and at seven alternative forest states to wet Eucalypt forest using a process-based FMC model. The model was run using a long-term climate dataset spanning 1973 – 2020, which were transferred from macro- to microclimate values using forest structural properties derived from lidar. Hourly FMC outputs were summarised to fuel availability (FMC < 16% for one hour each day) to understand the potential for positive, negative of no feedbacks on potential fire activity. Mean annual FMC was significantly different between each alternative forest state across each of the 48 years of climate data – which act as a replicate for different climate conditions in our experimental design. By quantifying these differences using the metric of fuel availability, we have demonstrated that statistically significant differences in FMC translate into meaningful differences in the context of potential fire activity. Overall, the results show strong positive and negative feedbacks across the alternative forest states compared to the mature wet Eucalypt forest that they replaced, which were greater than age-related differences within the wet Eucalypt forest sites. Overall, our results support the hypothesis that indirect effects of climate change, acting through vegetation conversion to alternative forest states, have a substantial impact on the potential for future fire activity, with important implications for land and fire managers in this region.

Failure to retreat: Blunted sensitivity to negative feedback supports risky behavior in adolescents

. Positive feedback is one of the core strategies used to make educational environment and students’ learning outcomes better. This review aims at revealing the role of positive feedback in improving students’ psychological and physical learning outcomes. Meanwhile, it questions the efficiency of combining positive and negative feedbacks in order to provide better educational experience for students. The findings of the analysis reveal that there is positive relationship between positive feedback and students’ physical and psychological learning outcomes. More specifically, positive feedback is advantageous in increasing students’ motivation, confidence, self-efficacy and academic skills. Furthermore, the study also confirms the benefits of combining positive and negative feedbacks in order to improve students’ learning outcomes and advance their academic skills.

Cone photoreceptors and horizontal cells (HCs) have a reciprocal synapse thatunderlies lateral inhibition and establishes the antagonistic center-surroundorganization of the visual system. Cones transmit to HCs through an excitatorysynapse and HCs feed back to cones through an inhibitory synapse. Here we reportthat HCs also transmit to cone terminals a positive feedback signal thatelevates intracellular Ca2+ and accelerates neurotransmitterrelease. Positive and negative feedback are both initiated by AMPA receptors onHCs, but positive feedback appears to be mediated by a change in HCCa2+, whereas negative feedback is mediated by a change inHC membrane potential. Local uncaging of AMPA receptor agonists suggests thatpositive feedback is spatially constrained to active HC-cone synapses, whereasthe negative feedback signal spreads through HCs to affect release fromsurrounding cones. By locally offsetting the effects of negative feedback,positive feedback may amplify photoreceptor synaptic release without sacrificingHC-mediated contrast enhancement.