Neurofeedback for Depression

Previous studies in neurophysiology have found a higher beta activity of electroencephalography (EEG) at the posterior cortex among patients with comorbid major depressive disorder and anxiety symptoms. Thus, this present study aimed to examine the effect of alpha-symmetry neurofeedback (ALAY) and high-beta down-training (beta) neurofeedback in symptoms of depression and anxiety. Eighty-seven patients with comorbid MDD and anxiety symptoms were allocated to the ALAY, Beta, or control groups. Both neurofeedback groups received ten-sessions of neurofeedback and all three groups partook in various psychological tests. The results showcased that both neurofeedback groups displayed decreased symptoms of depression and anxiety. The Beta group specifically was more effective in decreasing high-beta power at the parietal cortex compared to other groups. This study concludes that the non-invasive psychological intervention of neurofeedback can be used to aid patients with comorbid MDD and anxiety symptoms.

Real-time neurofeedback techniques allow one to map the controllability of sensory, cognitive and affective centres in the brain. The subgenual anterior cingulate cortex (sACC) is thought to be involved in the generation of affective states. In this study, researchers examined whether individuals could use real-time fMRI neurofeedback to modulate sACC activity. An experimental group of eight women partook in the study. Initially a localizer task was used to identify an sACC region of interest, followed by four scans: (1) a pretraining scan in which they were asked to decrease activity in the sACC without neurofeedback; (2) two training scans in which sACC neurofeedback was presented along with instruction to decrease sACC activity; and (3) a neurofeedback-free post-training scan. In addition to this a control group was made so as to compare results across the board. Post-training results showcased significantly reduced activity in the sACC during neurofeedback training in the experimental group, but not in the control group. The findings that individuals can down-modulate sACC activity shows that neurofeedback training can aid in controlling a primary emotion centre in which functional abnormalities have a strong implication in affective disorders.

Real-time fMRI neurofeedback (rtfMRI-nf) is an emerging novel approach to the treatment of major depressive disorder (MDD). EEG performed simultaneously with an rtfMRI-nf procedure allows an independent evaluation of rtfMRI-nf brain modulation effects. Frontal EEG asymmetry in the alpha band is a widely used measure of emotion and motivation that shows profound changes in depression. In this study MDD patients in the experimental group learned to upregulate BOLD activity of the left amygdala using an rtfMRI-nf during a happy emotion induction task. Conversely MDD patients in the control group were provided with a sham rtfMRI-nf. Throughout the sessions correlations between frontal EEG asymmetry in the upper alpha band and BOLD activity across the brain were examined. The average asymmetry changes significantly correlated with the amygdala BOLD laterality. Temporal correlations between frontal EEG asymmetry and BOLD activity were significantly enhanced, during the rtfMRI-nf task, for the amygdala and many regions associated with emotion regulation. This study demonstrates an important link between amygdala BOLD activity and frontal EEG asymmetry during emotion regulation. The results suggest that rtfMRI-nf training targeting the amygdala is beneficial to MDD patients. A combination of EEG-nf based on frontal EEG asymmetry in the alpha band and amygdala-based rtfMRI-nf, could enhance emotion regulation training and benefit MDD patients.

Stress is a normal response to situational pressures and demands. This study aims to investigate the effects of employing brainwave neurofeedback training on life stress and depression in female college students. Twenty-six subjects were chosen and randomly assorted into the experimental group and the control group. The neurofeedback sessions ran for a total of 8 weeks, after which post-training results were taken. The results showed a statistically significant difference between both the experimental group and the control group for life stress and depression. In both cases, the experimental group showed significantly decreased life stress and depression levels than the control group. The results observed from this study allow researchers to conclude that neurofeedback training for the decrease of life stress and depression, has a positive effect.

At least 30% of patients with major depressive disorder (MDD) do not respond to standard pharmacological and/or psychological treatments, and a considerable number of those who do respond to standard treatment go on to develop a chronic remission cycle. Through this study researchers explore the feasibility of a brain self-regulation technique that utilizes neurofeedback with functional magnetic resonance imaging (fMRI). Eight patients with depression learned to upregulate brain areas involved in the generation of positive emotions. This was done over the span of four neurofeedback sessions. Their clinical symptoms were assessed using the 17-item Hamilton Rating Scale for Depression (HDRS), and showed significant improvement. This study supports the notion that neurofeedback may in fact be a useful adjunct to current therapies for depression.

In this report, the author details the biological component associated with anxiety, depression and obsessive compulsive disorder, noting the findings from a robust body of research, including EEG studies. In addition to documenting biological predispositions that exist for anxiety, depression, and obsessive compulsive disorders, new research has also shown that medication is only mildly effective in the treatment of these problems when compared to a placebo. This report offers a detailed review of available research of uncontrolled studies that investigate the efficacy of neurofeedback treatment. Although the findings from these uncontrolled studies are promising, the author notes that there is a need for controlled research due to the fact that the current pool of research only represents uncontrolled studies. The author concludes by providing his own impressions from incorporating neurofeedback into private practise, noting the significant and enduring improvements seen in clients who have the same kind of alpha frontal symmetry that reflects a biological predisposition to depression.

This article engages with existing research on functional brain abnormalities associated with depression, anxiety, and obsessive-compulsive disorder. The authors describe, in detail, the neurophysiological basis for various symptoms and differentiate these factors from biological predisposition. It is argued that despite psychiatry’s strong reliance on the use of medication for the treatment of depression and anxiety; current evidence seems to suggest that pharmacologic treatment may not be as effective as was previously believed. The authors provide a brief overview of the research done to determine the efficacy of more traditional treatment models and stress the point that an increasing number of patients seem interested in less invasive treatment than medication. Neurofeedback is introduced as an alternative treatment option for modifying dysfunctional, biologic brain patterns that are associated with various psychiatric conditions and the advantages are discussed.

33% of patients taking medication for major depressive disorder fail to achieve remission. This study investigates the impact of neurofeedback on working memory performance in 60 patients with major depressive disorder. Participants were not randomly assigned a group; rather they were purposely allocated to the neurofeedback group or control group. Neurofeedback protocol aimed to increase individual upper alpha power in the parieto-occipital area of the scalp. Results suggest that the stronger effect of neurofeedback training is specifically found in working memory performance and processing speed, whereas the improvement in episodic memory, executive functions and verbal fluency was marginal and likely explained by an enhancement of cognitive processing as a whole. Furthermore, participants in the neurofeedback group showed pre-post enhancement in the upper alpha power of the training, better visible in task-related activity as compared to resting state.

This study examines whether neurofeedback training designed to increase the relative activity of the right frontal alpha band would have an impact on the symptoms of depressive subjects suffering from emotional, behavioural and cognitive problems. Research proposes that frontal asymmetric activation is the underlying mechanism for depression; therefore enhancement of a relative right frontal alpha activity by asymmetry neurofeedback training leads to improvement in depressive symptoms. To test this, the authors’ randomly assigned 24 participants who meet the DSM-IV criteria for depressive disorders into 2 groups. One group underwent neurofeedback training twice a week for 5 weeks for a total of 10 sessions. The other group did not receive neurofeedback; instead they underwent psychotherapy placebo training for 5 weeks. The results of this study indicate that asymmetry neurofeedback training increased the relative right frontal alpha power, and it remained effective even after the end of treatment. The authors’ preliminary conclusion is that asymmetry training is important for controlling and regulating emotion and it may facilitate the left frontal lobe functions.

This report is the first of its kind to observe the impact of concurrent neurofeedback (NFB) and heart rate variability (HRV) training as a viable intervention strategy for symptoms of anxiety and depression. 183 children and adults with anxiety and/or depression symptoms underwent treatment consisting of concurrent NFB and HRV training for a total of 30 sessions within a time period of 6 to 24 weeks. Results showed that symptoms of anxiety and depression reduced in both adults and children. Both questionnaire assessment and changes in EEG, breathing rate and HRV were of clinical significance. The authors concluded that NFB and HRV training is an effective, non-pharmaceutical option for intervention to reduce symptoms of anxiety and depression. It was also concluded that NFB and HRV may improve EEG, blood pressure, resting breathing rate and HRV.

In this study, Health university students were randomly assigned to the experimental group, sham group or control group. Participants in the experimental group trained to enhance beta waves at F4 and P4. Attentional performance and MRI data were recorded one week before training and one week after training. Higher scores on auditory and visual sustained attention were present in experiment group. Gray matter volume increases were detected in cerebral structures involved in this type of attention. This study constitutes the first empirical demonstration that neurofeedback training leads to microstructural changes in white and gray matter.

Previously, using fMRI, the authors of this study demonstrated lower connectivity between right anterior superior temporal (ATL) and anterior subgenual cingulate (SCC) regions while patients with major depressive disorder (MDD) experience guilt. This neural signature was detected despite symptomatic remission which suggested a putative role in vulnerability. This randomised controlled double-blind parallel group clinical trial investigated whether patients with MDD are able to voluntarily modulate this neural signature. To this end, they developed a fMRI neurofeedback software (FRIEND), which measures ATL-SCC coupling and displays its levels in real time. Twenty-eight patients with remitted MDD were randomised to two groups, each receiving one session of fMRI neurofeedback whilst retrieving guilt and indignation/anger-related autobiographical memories. They were instructed to feel the emotion whilst trying to increase the level of a thermometer-like display on a screen. Active intervention group: The thermometer levels increased with increasing levels of ATL-SCC correlations in the guilt condition. Control intervention group: The thermometer levels decreased when correlation levels deviated from the previous baseline level in the guilt condition, thus reinforcing stable correlations. Both groups also received feedback during the indignation condition reinforcing stable correlations. It confirmed our predictions that patients in the active intervention group were indeed able to increase levels of ATL-SCC correlations for guilt vs. indignation and their self-esteem after training compared to before training and that this differed significantly from the control intervention group. The data provides proof-of-concept for a novel treatment target for MDD patients and are in keeping with the hypothesis that ATL-SCC connectivity plays a key role in self-worth.

According to the World Health Organization, 322 million people in the world were depressed in 2015. This study aimed to develop an effective training intervention for minimizing the depressive symptoms in persons with depression disorder. Neurofeedback Training (NT) was tested in a control-group experimental design: immediately after the NT and one week later. Participants were 32 Chinese college students (22 female students; mean age = 22.18). The experimental study found positive effects of the training intervention on alpha band and depressive symptoms. Overall, NT can protect persons with depression disorder from an increase in depressive symptoms at the stage of depression.

Functional magnetic resonance imaging neurofeedback (fMRI-NF) training of areas involved in emotion processing can reduce depressive symptoms by over 40% on the Hamilton Depression Rating Scale (HDRS). However, it remains unclear if this efficacy is specific to feedback from emotion-regulating regions. This was tested in a single-blind, randomized, controlled trial if upregulation of emotion areas (NFE) yields superior efficacy compared to upregulation of a control region activated by visual scenes (NFS). Forty-three moderately to severely depressed medicated patients were randomly assigned to five sessions augmentation treatment of either NFE or NFS training. At primary outcome (week 12) no significant group mean HDRS difference was found (B = −0.415 [95% CI −4.847 to 4.016], p = 0.848) for the 32 completers (16 per group). However, across groups depressive symptoms decreased by 43%, and 38% of patients remitted. These improvements lasted until follow-up (week 18). Both groups upregulated target regions to a similar extent. Further, clinical improvement was correlated with an increase in self-efficacy scores. However, the interpretation of clinical improvements remains limited due to lack of a sham-control group. Thus, the effects reported for accepted augmentation therapies in depression were surveyed. Data indicated that the findings exceed expected regression to the mean and placebo effects that have been reported for drug trials and other sham-controlled high-technology interventions. Taken together, the study suggests that the experience of successful self-regulation during fMRI-NF training may be therapeutic. To conclude if fMRI-NF is effective for depression, self-regulation training of higher visual areas may provide an effective alternative.

In major depressive disorder (MDD) amygdala hemodynamic responses to positive stimuli are reduced. This study looked at using real-time fMRi neurofeedback (NFB) to modulate this activity by enhancing amygdala responses to positive autobiographical memories (AM) and seeing whether this can alter the severity of symptoms in depressed patients. 21 unmedicated MDD subjects were divided into an experimental and control group. The experimental group of 14 participants received NFB from the left amygdala and the control group of 7 participants received NFB from the intraparietal sulcus. Both groups were instructed to think about happy autobiographical memories in order to raise the level of a bar that represented the hemodynamic signal from the target region to a target level. The results of the study showed that subjects in the experimental group upregulated their amygdala responses during positive autobiographical memory recall. There were also significant decreases in anxiety ratings and increases in happiness ratings in the experimental group compared to the control group. This study suggests that NFB training with positive AM recall holds potential as a novel therapeutic approach in the treatment of depression.

Typical adolescents have increased limbic engagement unchecked by regulatory medial prefrontal cortex (PFC) activity as well as heightened self-focus. The resulting emotion dysregulation and self-focused rumination make adolescents more susceptible to depression and suicide attempts. Heightened self-focus converges with mental illness among depressed adolescents, who deploy exaggerated attention to negative self-relevant stimuli and neglect positive ones as part of depression’s phenomenology. This results in rigid negative self-representations during an identity formative period with potential lifetime repercussions. Current empirically supported treatments fail to allay recurrent depression. Evidence-based interventions for illnesses linked to suicide ideation and attempts (e.g., depression) underperform across the lifespan. This could be because current treatments are not successful in altering pervasive negative self-representations and affect dysregulation, which is known to be a risk factor of chronic depression. This study departs from the premise that increasing positive self-processing might be protective against chronic depression particularly during adolescence. The present research is a novel investigation of neurofeedback as a potential treatment alternative for adolescent depression. To enhance positive self-processing, the researchers used the happy self-face as a cue to initiate neurofeedback from the bilateral amygdala and hippocampus and adolescents attempted to upregulate that limbic activity through the recall of positive autobiographical memories. They identified limbic functional circuitry engaged during neurofeedback and links to short-term symptoms’ change in depression and rumination. They found that depressed youth showed greater right amygdala to right frontocortical connectivity and lower left amygdala to right frontocortical connectivity compared to healthy controls during neurofeedback vs. control conditions. Depressed youth also showed significant symptom reduction. Connectivity between the right amygdala and frontocortical regions was positively correlated with rumination and depression change, but connectivity between frontocortical regions and the left amygdala was negatively correlated with depression change. The results suggest that depressed youth might engage implicit emotion regulation circuitry while healthy youth recruit explicit emotion regulation circuits during neurofeedback. The findings support a compensatory approach (i.e., target the right amygdala) during future neurofeedback interventions in depressed youth. Future work ought to include a placebo condition or group.

Neural models of major depressive disorder (MDD) posit that over-response of components of the brain's salience network (SN) to negative stimuli plays a crucial role in the pathophysiology of MDD. In the present proof-of-concept study, the authors tested this formulation directly by examining the affective consequences of training depressed persons to down-regulate response of SN nodes to negative material. Ten participants in the real neurofeedback group saw, and attempted to learn to down-regulate, activity from an empirically identified node of the SN. Ten other participants engaged in an equivalent procedure with the exception that they saw SN-node neurofeedback indices from participants in the real neurofeedback group. Before and after scanning, all participants completed tasks assessing emotional responses to negative scenes and to negative and positive self-descriptive adjectives. Compared to participants in the sham-neurofeedback group, from pre- to post-training, participants in the real-neurofeedback group showed a greater decrease in SN-node response to negative stimuli, a greater decrease in self-reported emotional response to negative scenes, and a greater decrease in self-reported emotional response to negative self-descriptive adjectives. The findings provide support for a neural formulation in which the SN plays a primary role in contributing to negative cognitive biases in MDD.

Depression is a common illness worldwide, with Approximately 280 million people in the world having depression.The aim of this study was to evaluate the effectiveness of neurofeedback on working memory, cognitive flexibility in patients with mild depression. This quasi-experimental study was performed on 30 patients with mild depression in Rasht in 2021 who were purposefully selected. Neurofeedback intervention program and Goldberg Depression Inventory, Dennis and Vanderwall Cognitive Flexibility and Danman & Carpenter Working Memory Questionnaire were used. Data was analyzed by analysis of covariance. The results showed that neurofeedback training was effective in increasing working memory (P <0.038),and cognitive flexibility (P <0.001) in patients with mild depression. Neurofeedback training can change brain activity using a simple reward system. Therefore, neurofeedback training is suggested as a potential complementary therapy for patients with depression.

The purpose of this experimental study was to determine if neurofeedback has an effect on depressive symptoms in alcoholic individuals. The participants received biofeedback pretraining, and then they completed 20 40-minute sessions of alpha-theta brainwave neurofeedback as part of the experiment. After neurofeedback, the participants with depressive syndrome showed a significant decrease in self-assessed depression. After a 21 month follow-up, the improvements remained and there was a sustained prevention of relapse in alcoholics who completed the neurofeedback training.

Rumination is a maladaptive emotional-regulation strategy in which there is a tendency to fixate on certain thoughts or thought patterns, and it has been found to be strongly associated with depression. Impairments in executive functioning can make it difficult to reduce rumination, thus increasing depressive symptoms. This study used an EEG neurofeedback protocol that enhances peak alpha frequency (PAF) in the prefrontal region, to determine if it is helpful in reducing rumination and depression. 30 participants with depressive symptoms were randomly assigned to either the neurofeedback training group or the control group and their depression, rumination, and executive functioning were examined at pre and post training. The results of the study indicate that the neurofeedback protocol used can enhance an individual’s target PAF. After undergoing 20 neurofeedback training sessions, the participants displayed significant improvements in executive functioning. Furthermore, the participants in the training group experienced significantly fewer depressive symptoms and significantly reduced rumination compared to the participants in the control group. The results indicate target PAF and executive functioning to be negatively correlated with depression and rumination; as target PAF and executive functioning improve, depression and rumination decline. Therefore, this neurofeedback protocol has gained evidence of being effective in reducing rumination and depression by enhancing executive functioning. 

Adolescence is a period of self-processing and transformations in emotion regulation and can be linked to chronic depression if derailed. This study used neurofeedback (NFB) training to assess the engagement of circuits involved in self-processing and emotion regulation in adolescents. 34 depressed and 19 healthy individuals underwent neurofeedback training using a novel task where they were cued to recall positive memories when presented with a happy face which would increased amygdala and hippocampus activity. The control condition group was instructed to count backwards while viewing another happy face. The results of the study revealed higher frontotemporal activity during neurofeedback and higher amygdala and hippocampus and hippocampi activity in the experimental group. They also found there was a lower saliency network engagement for self-face recognition after NFB training. Furthermore, depressed youth displayed higher fusiform, inferior parietal lobule and cuneus activity during NFB however controls appeared to increase amygdala and hippocampus activity faster than depressed adolescents. This study has shown that neurofeedback can recruit frontotemporal cortices that support social cognition and emotion regulation as well as change limbic-frontotemporal networks during self-face recognition through amygdala and hippocampus engagement. Their results suggest that having a longer duration of neurofeedback training targeting the amygdala, hippocampus and/or dorsal anterior cingulate cortex might be effective in adolescents.

Previous research found that remitted patients with major depressive disorder (MDD) were able to modulate connectivity between brain regions associated with self-blame using fMRI neurofeedback training (NFT) thereby increasing their self-esteem. This study wanted to evaluate the potential of using this approach in symptomatic MDD patients. 43 individuals with insufficiently recovered MDD completed three weekly self-guided sessions with additional fMRI neurofeedback and 35 individuals completed the same self-guided sessions without additional NFT. The results of the study indicated that participants who received additional NFT, had reduced connectivity in brain regions associated with self-blame vs other-blame. There was also a 46% reduction on the Beck Depression Inventory-II for all participants. The researchers also found group differences such that individuals with non-anxious MDD exhibited a superior response to NFT compared with the psychological intervention and the opposite pattern was found in individuals with anxious MDD. Overall this study suggests that self-blame-rebalance neurofeedback may benefit individuals with non-anxious MDD more compared to solely providing psychological intervention. 

The literature on brain activity in individuals with depression finds that they have higher alpha and theta activity compared to normal controls. There is also extensive literature on the effectiveness of using neurofeedback (NF) to reduce symptoms of depression. Therefore, this study further examined the effectiveness of neurofeedback in reducing depressive symptoms by administering NF to  three individuals with diagnosed but unmedicated depression. After 20 training sessions, all the individuals underwent remission of their depressive symptoms, and a significant decrease in theta activity over frontal and central areas was observed in all patients, under all testing conditions.  

Individuals with depression show and attentional bias toward negatively valenced stimuli and thoughts. In this proof-of-concept study, a novel closed-loop neurofeedback procedure intended to remediate the bias was presented. Internal attentional states were detected in real time by applying machine learning techniques to functional magnetic resonance imaging data on a cloud server; these attentional states were externalized using a visual stimulus that the participant could learn to control. 15 participants with major depressive disorder were trained along with 12 healthy control participants over the course of 3 functional magnetic resonance imaging sessions. Exploratory analysis showed that participants with major depressive disorder were initially more likely than healthy control participants to get stuck in negative attentional states, but this diminished with neurofeedback training relative to the control group. Depression severity also decreased from pre- to posttraining. These results demonstrate that their method is sensitive to the negative attentional bias in major depressive disorder and showcases the potential of this novel technique as a treatment that can be evaluated in future clinical trials.

Depressive disorders contribute heavily to global disease burden; This is possibly because patients are often treated homogeneously, despite having heterogeneous symptoms with differing underlying neural mechanisms. A novel treatment that can directly influence the neural circuit relevant to an individual patient’s subset of symptoms might more precisely and thus effectively aid in the alleviation of their specific symptoms. This hypothesis was tested in a proof-of-concept study using fMRI functional connectivity neurofeedback. The connectivity was tested between the left dorsolateral prefrontal cortex/middle frontal gyrus and the left precuneus/posterior cingulate cortex, because this connection has been well-established as relating to a specific subset of depressive symptoms. Specifically, this connectivity has been shown in a data-driven manner to be less anticorrelated in patients with melancholic depression than in healthy controls. Furthermore, a posterior cingulate dominant state—which results in a loss of this anticorrelation—is expected to specifically relate to an increase in rumination symptoms such as brooding. In line with predictions, it was found that, with neurofeedback training, the more a participant normalized this connectivity (restored the anticorrelation), the more related (depressive and brooding symptoms), but not unrelated (trait anxiety), symptoms were reduced. Through these results preliminary evidence is provided for a correlation between the normalization of a neural network and a reduction in related symptoms. Showing their reproducibility, these results were found in two experiments that took place several years apart by different experimenters. Indicative of its potential clinical utility, effects of this treatment remained one-two months later.

Real-time functional magnetic resonance imaging (fMRI) can be used to train patients in the self regulation of neural circuits relevant to emotion, motivation, and depression, and thus complement existing neurofeedback technologies based on electroencephalography (EEG). EEG neurofeedback for depression has mainly been based on models of altered hemispheric asymmetry. fMRI-based neurofeedback (fMRI-NF) can utilize functional localizer scans that allow the dynamic adjustment of the target areas or networks for self-regulation training to individual patterns of emotion processing. An initial application of fMRI-NF in depression has produced promising clinical results, and further clinical trials are underway. Challenges lie in the design of appropriate control conditions for rigorous clinical trials, and in the transfer of neurofeedback protocols from the laboratory to mobile devices to enhance the sustainability of any clinical benefits.

Neurofeedback training has been suggested as a potential additional treatment option for MDD patients not reaching remission from standard care (i.e., psychopharmacology and psychotherapy). This study systematically reviewed neurofeedback studies employing EEG, or fMRI-based protocols in depressive patients. 24 studies were included in this review article (N = 480 MDD patients and N = 194 controls. Clinical efficacy was evaluated across studies. In most studies, MDD patients showed symptom improvement superior to the control group(s). However, most articles did not comply with the most stringent study quality and reporting practices. The authors concluded with recommendations on best practices for experimental designs and reporting standards for neurofeedback training.

Earlier studies have shown that the reduction of asymmetry of alpha-activity between left and right prefrontal areas with neurofeedback has been effective at treating depressive symptoms. Unfortunately, methodological shortcomings limit conclusions that can be drawn from these studies. This pilot-study investigated the effectiveness of reduction of asymmetry of alpha-activity with neurofeedback in depressed participants with the use of a stringent methodological approach. Nine participants meeting DSM-IV criteria for major depressive disorder were treated with a maximum of 30 neurofeedback-sessions, aimed at reducing asymmetry of alpha-activity, over a 10-week period. No changes in the use of antidepressants were allowed 6 weeks before and during the intervention. Changes in depressive symptomatology were assessed with the Quick Inventory of Depressive Symptoms, self-report version. A response in 1 and remission in 4 out of a total of 9 participants was observed. The effectiveness appeared largest in female participants. The mean asymmetry of alpha-activity decreased significantly over sessions in a quadratic fashion. This decrease was associated with clinical response. This pilot study suggests that neurofeedback aimed at a reduction of frontal asymmetry of alpha-activity may be effective as a treatment for depression. However, randomized controlled trials will have to establish the efficacy of neurofeedback for depression.

Abnormal characteristics of resting-state EEG power and functional connectivity are considered trait markers of depressive symptoms in major depression. However, the relationship between EEG spectral features and functional connectivity in late-life depression (LLD) remains unknown. In this study, 44 patients with LLD and 41 participants without depression underwent an eyes-closed resting-state EEG. EEG power spectra, alpha asymmetry, and functional connectivity were calculated and analyzed. Although alpha frontal asymmetry and cortical functional connectivity between the two groups showed no significant differences, the LLD group exhibited abnormal neural oscillation patterns of higher beta frequency activity in the parietal, central, and occipital lobes while alpha activity was increased in the parietal central electrodes. These abnormal patterns may be associated with a disturbed balance of cortical excitation, inhibition, and hyperactivity. In the future, a neurofeedback protocol based on the findings of neural oscillation patterns in certain types of LLD should be explored.

This study evaluated the effects of neurofeedback as an augmentation treatment on depressive symptoms and functional recovery in patients with treatment-resistant depression (TRD). 24 adult patients with TRD and 12 healthy adults were included in the study. 24 TRD patients were assigned to the neurofeedback augmentation group (n = 12) and the medication-only group (n = 12). The neurofeedback augmentation group underwent combined therapy comprising medication and 12-24 sessions of neurofeedback training for 12 weeks. To assess the serum levels of brain-derived neurotrophic factor (BDNF) in both groups, pre- and post-treatment blood samples were obtained. Patients were evaluated using the Hamilton Depression Rating Scale (HAM-D), Beck Depression Inventory (BDI), Clinical Global Impression-Severity (CGI-S), 5-level version of European Quality of Life Questionnaire 5-Dimensional Classification (EQ-5D-5L), and Sheehan Disability Scale (SDS) at baseline, and at the 1-, 4-, and 12-week. From baseline to week 12, neurofeedback training reduced mean scores on HAM-D, BDI-II, CGI-S, and SDS, and increased mean EQ-5D-5L tariff score. In the neurofeedback augmentation group, the response and remission rates were 58.3% and 50.0%, respectively, at week 12. Changes in HAM-D, EQ-5D-5L tariff score, and SDS were significantly larger in the neurofeedback group than in the medication-only (TAU) group. No significant difference in BDNF level was found pre- vs. post-treatment in any of the groups. Despite the small sample size, these results suggest that neurofeedback treatment may be effective as an augmentation treatment, not only for depressive symptoms, but also for functional recovery, in patients with TRD.

This study evaluated the effect of neurofeedback on depressive symptoms in patients with major depressive disorder. Twenty participants underwent left prefrontal beta with alpha/theta training two or three times a week for 8 weeks. Every visit, patients received beta training at F3 for 30 min, and then alpha/theta training at Pz for 30 min. Baseline, 4 and 8 week scores of the Hamilton rating scale for Depression (HAM-D), the Hamilton rating scale for Anxiety (HAM-A), the Beck Depression Inventory (BDI)-II, the Beck Anxiety Inventory (BAI), Clinical global impression-severity (CGI-S), and pre- and post-treatment resting state EEGs were compared. Interhemispheric alpha power asymmetry (A score) was computed for homologous sites F3-F4. Pre- and post-training clinical assessments revealed significant improvements in HAM-D, HAM-A, BDI, and CGI-S scores. Cumulative response rates by HAM-D were 35.0 and 75.0 % at 4 and 8 weeks, respectively, corresponding cumulative remission rates by HAM-D were 15.0 and 55.0 %, respectively. No significant differences were found between pre- and post-treatment A score. In conclusion, neurofeedback treatment could improve depressive symptoms significantly.

This study performed a meta-analysis on the effectiveness of biofeedback and neurofeedback in the treatment of depression.  Two different strings were considered for each of the two objectives of the study: A first group comprising studies of patients with major depressive disorder (MDD) and a second group including studies targeting depressive symptomatology reduction in other mental or medical conditions. In the first group of studies including patients with MDD, the within-group analyses yielded an effect size of Hedges' g = 0.717, while the between-group analysis had an effect size of Hedges' g = 1.050. Moderator analyses indicated that treatment efficacy is only significant when accounting for experimental design, in favor of randomized controlled trials (RCTs) in comparison to non RCTs, whereas the type of neurofeedback, trial design, year of publication, number of sessions, age, sex and quality of study did not influence treatment efficacy. In the second group of studies, a small but significant effect between groups was found (Hedges' g = 0.303) in favor of bio- and neurofeedback against control groups. Moderator analyses revealed that treatment efficacy was not moderated by any of the sociodemographic and clinical variables. Heart rate variability (HRV) biofeedback and neurofeedback are associated with a reduction in self-reported depression. Despite the fact that the field still has a large room for improvement in terms of research quality, the results presented in this study suggest that both modalities may become relevant complementary strategies for the treatment of MDD and depressive symptomatology in the coming years.

This study evaluated a neurofeedback protocol that targets emotional regulation and self-processing in adolescents. 34 depressed and 19 healthy adolescents completed a neurofeedback task that involved viewing their own happy face and simultaneously recalling a positive autobiographical memory. Additionally, a self- vs. other-face recognition task with happy, neutral and sad expressions was completed before and after the training session. Reduced depression scores in the depressed youth was associated with increased activity in self-referential and visual areas during training, particularly the cuneus, precuneus and parietal lobe. Further, during a self-recognition task, reduced depression was associated with increased activation of emotional regulation and cross-modal areas including the cerebellum, middle temporal gyrus, superior temporal gyrus, and supramarginal gyrus. Decreased rumination however was associated with decreased precuneus, angular and temporal gyri activity during neurofeedback training. This suggests that neurofeedback may induce short-term neurobiological changes in the self-referential and emotional regulation networks associated with reduced symptom severity among depressed adolescents. 

This study used exact low resolution brain electromagnetic tomography (eLORETA) to investigate EEG source activities during a fMRI-EEG neurofeedback procedure in major depressive disorder (MDD) patients. The exploratory analyses revealed significant changes in hemispheric lateralities of upper alpha and high-beta current source densities in the prefrontal regions. Similar laterality changes were observed for current source densities in the amygdala. Prefrontal upper alpha current density changes showed significant negative correlations with anhedonia severity. Changes in prefrontal high-beta current density are consistent with reduction in comorbid anxiety. Comparisons with results of previous LORETA studies suggest that fMRI-EEG-nf training is beneficial to MDD patients, and may have the ability to correct functional deficiencies associated with anhedonia and comorbid anxiety in MDD.

The objective of this study was to compare real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback with cognitive behavioral therapy. 20 adults with mild or moderate depression were assigned to either 8 half-hour sessions of neurofeedback targeting the left medial prefrontal cortex or 16 sessions of cognitive behavioral therapy. The Montgomery-Asberg Depression Rating Scale was completed at baseline, mid- and post-intervention. It was found that both interventions improved mild and moderate depression, though neurofeedback was not superior to cognitive behavioral therapy. Though greater improvement was observed in the cognitive behavioral therapy group, neurofeedback training was associated with continuous improvement in the self-regulation skill without plateau. This study is however limited by its small sample size, and non-random participant assignment, which can lead to insufficient power and selection bias, respectively.

It has been hypothesized that the left ventrolateral prefrontal cortex (vlPFC) may insufficiently regulate emotion processing in the amygdala for example, which can contribute to various affective disorders. This double-blind cross-over study investigated neurofeedback-supported cognitive reappraisal training in patients with major depression and age and gender matched controls. On two separate days, participants were trained to upregulate either the left or the right vlPFC during cognitive reprisal of negative images. It was found that vlPFC activity increase was stronger after neurofeedback training from the left- than the right-hemispheric ROI. This regional specific effect was present across patients with depression and controls, and supports the role of the left vlPFC for cognitive reappraisal. Further, activity in the left target region was associated with increased use of cognitive reappraisal strategies. Lastly, at the 4-week follow-up 75% of patients with depression reported being able to successfully apply learned strategies to everyday life and 55% a clinically significant improvement in symptoms. 

This study aimed to assess the use of real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback as a method to guide patients with depression in achieving a healthy brain state. First, researchers trained a brain classifier using neural information of happy autobiographical imagery and motor imagery blocks received from a healthy female participant during an MRI session. Then, 7 right-handed female patients with mild or moderate depressive symptoms were trained to match their own neural activity to “happiness emotional brain state” of the healthy participant. These participants underwent 4 neurofeedback training sessions over 2 weeks. The study found that patients showed clinical improvement in their depressive symptoms both right after the training period as well as 10 days after the intervention. The results suggest that rt-fMRI neurofeedback could be a novel, noninvasive option for neural modulation and symptom alleviation in depression. 

The objective of this study was to determine the effectiveness of neurofeedback in treating depression and fatigue in patients with multiple sclerosis (MS). twenty-four MS patients with primary fatigue and depression were randomly assigned to either the neurofeedback training group (16 sessions of neurofeedback) or treatment as usual. Participants were evaluated at three different timepoints (baseline, end of treatment and at a 2-month follow up) using the Fatigue Severity Scale and Depression subscale of the Hospital Anxiety and Depression Scale as outcome measures. It was found that neurofeedback significantly decreased depressive and fatigue symptoms in MS patients compared to treatment as usual, and that these effects were maintained at the 2-month follow up. 

It has been found that individuals with comorbid major depressive disorder (MDD) and anxiety symptoms have increased beta activity. Therefore, the present study sought to examine the effectiveness of a high beta down-training neurofeedback protocol which could presumably decrease high beta activity and therefore negative emotions. 23 patients with comorbid MDD and anxiety symptoms underwent 5 weeks of high beta down-training. They were trained twice a week to reduce their beta amplitude at EEG sites P3 and P4. The trainability, independence, and interpretability were examined by comparing pre and post-training EEGs. The trainability index revealed the learning curves of reduced high beta activity at P3 and P4, confirming training effects across and within sessions. The independence index revealed only beta band activity decreased. Lastly, the interpretability index showed that decreased high beta was positively correlated with decreased depression severity, especially for cognitive depression. Overall, this study supports the use of a high beta down-training neurofeedback protocol to decrease beta activity and depressive symptoms in patients with comorbid depression and anxiety symptoms. 

Typically, patients with depression demonstrate a blunted amygdala hemodynamic activity to positive stimuli, including autobiographical memories. The objective of this study was to examine the efficacy of real-time fMRI neurofeedback (rtfMRI-nf) at increasing the amygdala’s hemodynamic response to positive memories in patients with depression. In a double-blind, placebo-controlled, randomized clinical trial, unmedicated adults with depression with randomly assigned to receive either two sessions of rtfMRI-nf either from the amygdala or from a parietal control region not involved in emotional processing. It was found that amongst the experimental group participants,hemodynamic response in the amygdala increased relative to their respective baselines and the control group. Twelve participants in the amygdala rtfMRI-nf group, compared with only two in the control group had a >50% decrease on the Montgomery Asberg Depression Rating Scale (MADRS). Six participants in the experimental group, compared with one in the control group met criteria for remission at the end of the study. Lastly, amongst the experimental group participants, the percent of positive specific memories recalled increased relative to their respective baselines and to the control group. 

This review aims to detail the level of evidence supporting the use of biofeedback and neurofeedback to treat depression. It was found that Heart rate variability (HRV) biofeedback was found to be a moderately supportable treatment option for Major depressive disorder (MDD). In addition, Electroencephalographic (EEG) neurofeedback protocols, such as alpha-theta, alpha, and sensorimotor rhythm upregulation, were ranked as “possibily efficacious”. Other forms of neurofeedback training including real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback targeting the amygdala and frontal cortices were found to demonstrate some effectiveness. In all, the author concludes that neurofeedback specifically targeting depression is moderately supported by existing studies. 

This study was a double-blind randomized sham-controlled, proof-of-concept study that utilized real-time functional magnetic resonance imaging neurofeedback to reduce repetitive negative thinking in major depression. Individuals that reported symptoms of major depression disorder were assigned to either active neurofeedback or sham feedback. Repetitive negative thinking was assessed by the Ruminative Response Scale-brooding subscale (RRS-B) before and 1 week after intervention. The authors found that individuals in the active, but not the sham group, showed a significant reduction in repetitive negative thinking. They also saw that a greater reduction in the retrosplenial cortex (RSC)-right temporoparietal junction (rTPJ) connectivity correlated with a more pronounced reduction in RRS-B scores in the activity group. Overall, these results suggest that real time functional magnetic resonance imaging neurofeedback could be effective in improving depressive symptoms such as repetitive negative thinking.