Brain Training: Neurofeedback
Training protocols, frequency bands, and evidence-based neurofeedback approaches.
This collection focuses on neurofeedback training protocols, methodology, efficacy studies, and best practices. Research covers different training approaches, frequency-specific protocols, and evidence for various clinical applications.
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We've curated 366 research papers for this use case.
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Research Citations (100 of 366)
Individual brain regulation as learned via neurofeedback is related to affective changes in adolescents with autism spectrum disorder
Abstract Background Emotions often play a role in neurofeedback (NF) regulation strategies. However, investigations of the relationship between the induced neuronal changes and improvements in affective domains are scarce in electroencephalography-based studies. Thus, we extended the findings of the first study on slow cortical potential (SCP) NF in autism spectrum disorder (ASD) by linking affective changes to whole-brain activity during rest and regulation. Methods Forty-one male adolescents with ASD were scanned twice at rest using functional magnetic resonance imaging. Between scans, half underwent NF training, whereas the other half received treatment as usual. Furthermore, parents reported on their child’s affective characteristics at each measurement. The NF group had to alternatingly produce negative and positive SCP shifts during training and was additionally scanned using functional magnetic resonance imaging while applying their developed regulation strategies. Results No significant treatment group-by-time interactions in affective or resting-state measures were found. However, we found increases of resting activity in the anterior cingulate cortex and right inferior temporal gyrus as well as improvements in affective characteristics over both groups. Activation corresponding to SCP differentiation in these regions correlated with the affective improvements. A further correlation was found for Rolandic operculum activation corresponding to positive SCP shifts. There were no significant correlations with the respective achieved SCP regulation during NF training. Conclusion SCP NF in ASD did not lead to superior improvements in neuronal or affective functioning compared to treatment as usual. However, the affective changes might be related to the individual strategies and their corresponding activation patterns as indicated by significant correlations on the whole-brain level. Trial registration This clinical trial was registered at drks.de (DRKS00012339) on 20th April, 2017.
Higher prefrontal activity based on short-term neurofeedback training can prevent working memory decline in acute stroke
This study aimed to clarify whether short-term neurofeedback training during the acute stroke phase led to prefrontal activity self-regulation, providing positive efficacy to working memory. A total of 30 patients with acute stroke performed functional near-infrared spectroscopy-based neurofeedback training for a day to increase their prefrontal activity. A randomized, Sham-controlled, double-blind study protocol was used comparing working memory ability before and after neurofeedback training. Working memory was evaluated using a target-searching task requiring spatial information retention. A decline in spatial working memory performance post-intervention was prevented in patients who displayed a higher task-related right prefrontal activity during neurofeedback training compared with the baseline. Neurofeedback training efficacy was not associated with the patient’s clinical background such as Fugl–Meyer Assessment score and time since stroke. These findings demonstrated that even short-term neurofeedback training can strengthen prefrontal activity and help maintain cognitive ability in acute stroke patients, at least immediately after training. However, further studies investigating the influence of individual patient clinical background, especially cognitive impairment, on neurofeedback training is needed. Current findings provide an encouraging option for clinicians to design neurorehabilitation programs, including neurofeedback protocols, for acute stroke patients.
Functional disorders - new proposals for definition, psychosomatics, somatization
Functional Disorders are common medical problems both in primary and in secondary health care. The mechanisms that cause symptoms such as primary pain, fatigue, dizziness are still unknown. Various classifications, including ICD-10 or DSM-5, describe these conditions differently, and new proposals are being developed e.g. in ICD-11, RDoC. Many controversies are evoked by lack of unequivocal explanatory theory. The early psychoanalytical concept has been modified by other explanations, such as immunological abnormalities, dysfunction of vegetative system and HPA axis, central sensitization, diverted processes of perception or predictive processes within cognitive homeostasis dysregulation. Insufficient scientific evidence makes therapies unsuccessful and justifies further study. Psychotherapy, pharmacology and complementary medicine are supplemented by new experimental methods of treatment connected with progress in neuroscience. The recently developed non-invasive Transcranial Direct Current Stimulation (tDCS), Transcranial Magnetic Stimulation (TMS) and - neurofeedback (EEG-NF), based on EEG registration, are undergoing tests. Applying complex mathematical algorithms to localized bioelectrical signal sources makes it possible to modulate and reshape connections of neuronal networks within specific cortex areas. This article presents the current state of knowledge concerning functional disorders, highlighting the ways in which different definitions of FD have an impact on approaches to treatment.
View Full Paper →Mental imagery content is associated with disease severity and specific brain functional connectivity changes in patients with Parkinson's disease
Mental imagery is the mental re-creation of perceptual experiences, events and scenarios, and motor acts. In our previous study, we assessed whether motor imagery (MI) training combined with functional magnetic resonance imaging-based neurofeedback could improve the motor function of nondemented subjects with mild Parkinson's disease (PD) (N = 22). We used visual imagery (VI) (e.g., of scenes or events, but not of self-movements) training without neurofeedback for the control group (N = 22). Notably, both groups showed significant and comparable improvement in motor function after four weeks of daily imagery practice. In this study, we further examined the neural correlates of the motor enhancement as a result of the VI training by analyzing the self-reported VI content during daily practice and relating its quality to the functional connectivity characteristics of the same subjects. We demonstrated that the VI practice encompassed multisensory, spatial, affective, and executive processes all of which are also important for motor function in real life. Subjects with worse global disease severity also showed poorer quality of the VI content. Finally, the quality of the VI content showed significant positive correlations with the functional connectivity changes during the VI tasks in brain areas supporting visuospatial and sensorimotor processes. Our findings suggest that mental imagery training combining VI and MI may enhance motor function in patients with mild PD, and more broadly, underline the importance of incorporating self-reports of thoughts and experiences in neuroimaging studies that examine the brain mechanisms of complex cognitive processes especially in neuropsychiatric patient populations.
View Full Paper →Would frontal midline theta indicate cognitive changes induced by non-invasive brain stimulation? A mini review
To the best of our knowledge, neurophysiological markers indicating changes induced by non-invasive brain stimulation (NIBS) on cognitive performance, especially one of the most investigated under these procedures, working memory (WM), are little known. Here, we will briefly introduce frontal midline theta (FM-theta) oscillation (4–8 Hz) as a possible indicator for NIBS effects on WM processing. Electrophysiological recordings of FM-theta oscillation seem to originate in the medial frontal cortex and the anterior cingulate cortex, but they may be driven more subcortically. FM-theta has been acknowledged to occur during memory and emotion processing, and it has been related to WM and sustained attention. It mainly occurs in the frontal region during a delay period, in which specific information previously shown is no longer perceived and must be manipulated to allow a later (delayed) response and observed in posterior regions during information maintenance. Most NIBS studies investigating effects on cognitive performance have used n-back tasks that mix manipulation and maintenance processes. Thus, if considering FM-theta as a potential neurophysiological indicator for NIBS effects on different WM components, adequate cognitive tasks should be considered to better address the complexity of WM processing. Future research should also evaluate the potential use of FM-theta as an index of the therapeutic effects of NIBS intervention on neuropsychiatric disorders, especially those involving the ventral medial prefrontal cortex and cognitive dysfunctions.
Cognitive training based on functional near-infrared spectroscopy neurofeedback for the elderly with mild cognitive impairment: a preliminary study
Introduction Mild cognitive impairment (MCI) is often described as an intermediate stage of the normal cognitive decline associated with aging and dementia. There is a growing interest in various non-pharmacological interventions for MCI to delay the onset and inhibit the progressive deterioration of daily life functions. Previous studies suggest that cognitive training (CT) contributes to the restoration of working memory and that the brain-computer-interface technique can be applied to elicit a more effective treatment response. However, these techniques have certain limitations. Thus, in this preliminary study, we applied the neurofeedback paradigm during CT to increase the working memory function of patients with MCI. Methods Near-infrared spectroscopy (NIRS) was used to provide neurofeedback by measuring the changes in oxygenated hemoglobin in the prefrontal cortex. Thirteen elderly MCI patients who received CT-neurofeedback sessions four times on the left dorsolateral prefrontal cortex (dlPFC) once a week were recruited as participants. Results Compared with pre-intervention, the activity of the targeted brain region increased when the participants first engaged in the training; after 4 weeks of training, oxygen saturation was significantly decreased in the left dlPFC. The participants demonstrated significantly improved working memory compared with pre-intervention and decreased activity significantly correlated with improved cognitive performance. Conclusion Our results suggest that the applications for evaluating brain-computer interfaces can aid in elucidation of the subjective mental workload that may create additional or decreased task workloads due to CT.
Magnetoencephalographic neurofeedback training decreasesβ-low-γphase-amplitude coupling of the motor cortex of healthy adults: a double-blinded randomized crossover feasibility study
Objective.The coupling between the beta (13-30 Hz) phase and low gamma (50-100 Hz) amplitude in the motor cortex is thought to regulate motor performance. Abnormal phase-amplitude coupling (PAC) of beta-low gamma (β-low-γPAC) is associated with motor symptoms of Parkinson's disease. However, the causal relationship betweenβ-low-γPAC and motor performance in healthy subjects is unknown. We hypothesized that healthy subjects could change the strength of theβ-low-γPAC in the resting state by neurofeedback training (NFT) to control theβ-low-γPAC, such that the motor performance changes in accordance with the changes inβ-low-γPAC in the resting state.Approach.We developed an NFT to control the strength of theβ-low-γPAC in the motor cortex, which was evaluated by magnetoencephalography (MEG) using a current source estimation technique. Twenty subjects were enrolled in a double-blind randomized crossover trial to test the feasibility of the MEG NFT. In the NFT for 2 d, the subjects were instructed to reduce the size of a black circle whose radius was proportional (down-training) or inversely proportional (up-training) to the strength of theβ-low-γPAC. The reaction times (RTs) to press a button according to some cues were evaluated before and after training. This study was registered at ClinicalTrials.gov (NCT03837548) and UMIN-CTR (UMIN000032937).Main results.Theβ-low-γPAC during the resting state was significantly decreased after down-training, although not significantly after up-training. RTs tended to decrease after both trainings, however the differences were not statistically significant. There was no significant correlation between the changes inβ-low-γPAC during rest and RTs.Significance.The proposed MEG NFT was demonstrated to change theβ-low-γPAC of the motor cortex in healthy subjects. However, a relationship between PAC and RT has not yet been demonstrated.
View Full Paper →Frontoparietal Dysconnection in Covert Bipedal Activity for Enhancing the Performance of the Motor Preparation-Based Brain-Computer Interface
Motor-based brain-computer interfaces (BCIs) were developed from the brain signals during motor imagery (MI), motor preparation (MP), and motor execution (ME). Motor-based BCIs provide an active rehabilitation scheme for post-stroke patients. However, BCI based solely on MP was rarely investigated. Since MP is the precedence phase before MI or ME, MP-BCI could potentially detect brain commands at an earlier state. This study proposes a bipedal MP-BCI system, which is actuated by the reduction in frontoparietal connectivity strength. Three substudies, including bipedal classification, neurofeedback, and post-stroke analysis, were performed to validate the performance of our proposed model. In bipedal classification, functional connectivity was extracted by Pearson's correlation model from electroencephalogram (EEG) signals recorded while the subjects were performing MP and MI. The binary classification of MP achieved short-lived peak accuracy of 73.73(±7.99)% around 200-400 ms post-cue. The peak accuracy was found synchronized to the MP-related potential and the decrement in frontoparietal connection strength. The connection strengths of the right frontal and left parietal lobes in the alpha range were found negatively correlated to the classification accuracy. In the subjective neurofeedback study, the majority of subjects reported that motor preparation instead of the motor imagery activated the frontoparietal dysconnection. Post-stroke study also showed that patients exhibit lower frontoparietal connections compared to healthy subjects during both MP and ME phases. These findings suggest that MP reduced alpha band functional frontoparietal connectivity and the EEG signatures of left and right foot MP could be discriminated more effectively during this phase. A neurofeedback paradigm based on the frontoparietal network could also be utilized to evaluate post-stroke rehabilitation training.
View Full Paper →Neurocircuit models of obsessive-compulsive disorder: limitations and future directions for research
Obsessive-compulsive disorder (OCD) is a common psychiatric condition classically characterized by obsessions (recurrent, intrusive and unwanted thoughts) and compulsions (excessive, repetitive and ritualistic behaviors or mental acts). OCD is heterogeneous in its clinical presentation and not all patients respond to first-line treatments. Several neurocircuit models of OCD have been proposed with the aim of providing a better understanding of the neural and cognitive mechanisms involved in the disorder. These models use advances in neuroscience and findings from neuropsychological and neuroimaging studies to suggest links between clinical profiles that reflect the symptoms and experiences of patients and dysfunctions in specific neurocircuits. Several models propose that treatments for OCD could be improved if directed to specific neurocircuit dysfunctions, thereby restoring efficient neurocognitive function and ameliorating the symptomatology of each associated clinical profile. Yet, there are several important limitations to neurocircuit models of OCD. The purpose of the current review is to highlight some of these limitations, including issues related to the complexity of brain and cognitive function, the clinical presentation and course of OCD, etiological factors, and treatment methods proposed by the models. We also provide suggestions for future research to advance neurocircuit models of OCD and facilitate translation to clinical application.
View Full Paper →Possible Mechanisms Underlying Neurological Post-COVID Symptoms and Neurofeedback as a Potential Therapy
Theoretical considerations related to neurological post-COVID complications have become a serious issue in the COVID pandemic. We propose 3 theoretical hypotheses related to neurological post-COVID complications. First, pathophysiological processes responsible for long-term neurological complications caused by COVID-19 might have 2 phases: (1) Phase of acute Sars-CoV-2 infection linked with the pathogenesis responsible for the onset of COVID-19-related neurological complications and (2) the phase of post-acute Sars-CoV-2 infection linked with the pathogenesis responsible for long-lasting persistence of post-COVID neurological problems and/or exacerbation of another neurological pathologies. Second, post-COVID symptoms can be described and investigated from the perspective of dynamical system theory exploiting its fundamental concepts such as system parameters, attractors and criticality. Thirdly, neurofeedback may represent a promising therapy for neurological post-COVID complications. Based on the current knowledge related to neurofeedback and what is already known about neurological complications linked to acute COVID-19 and post-acute COVID-19 conditions, we propose that neurofeedback modalities, such as functional magnetic resonance-based neurofeedback, quantitative EEG-based neurofeedback, Othmer’s method of rewarding individual optimal EEG frequency and heart rate variability-based biofeedback, represent a potential therapy for improvement of post-COVID symptoms.
View Full Paper →Volitional Control of Brain Motor Activity and Its Therapeutic Potential
BACKGROUND: Neurofeedback training is a closed-loop neuromodulatory technique in which real-time feedback of brain activity and connectivity is provided to the participant for the purpose of volitional neural control. Through practice and reinforcement, such learning has been shown to facilitate measurable changes in brain function and behavior. OBJECTIVES: In this review, we examine how neurofeedback, coupled with motor imagery training, has the potential to improve or normalize motor function in neurological diseases such as Parkinson disease and chronic stroke. We will also explore neurofeedback in the context of brain-machine interfaces (BMIs), discussing both noninvasive and invasive methods which have been used to power external devices (eg, robot hand orthosis or exoskeleton) in the context of motor neurorehabilitation. CONCLUSIONS: The published literature provides mounting high-quality evidence that neurofeedback and BMI control may lead to clinically relevant changes in brain function and behavior.
View Full Paper →Self-regulation of the posterior cingulate cortex with real-time fMRI neurofeedback augmented mindfulness training in healthy adolescents: A nonrandomized feasibility study
Mindfulness training (MT) promotes the development of one's ability to observe and attend to internal and external experiences with objectivity and nonjudgment with evidence to improve psychological well-being. Real-time functional MRI neurofeedback (rtfMRI-nf) is a noninvasive method of modulating activity of a brain region or circuit. The posterior cingulate cortex (PCC) has been hypothesized to be an important hub instantiating a mindful state. This nonrandomized, single-arm study examined the feasibility and tolerability of training typically developing adolescents to self-regulate the posterior cingulate cortex (PCC) using rtfMRI-nf during MT. Thirty-four adolescents (mean age: 15 years; 14 females) completed the neurofeedback augmented mindfulness training task, including Focus-on-Breath (MT), Describe (self-referential thinking), and Rest conditions, across three neurofeedback and two non-neurofeedback runs (Observe, Transfer). Self-report assessments demonstrated the feasibility and tolerability of the task. Neurofeedback runs differed significantly from non-neurofeedback runs for the Focus-on-Breath versus Describe contrast, characterized by decreased activity in the PCC during the Focus-on-Breath condition (z = -2.38 to -6.27). MT neurofeedback neural representation further involved the medial prefrontal cortex, anterior cingulate cortex, dorsolateral prefrontal cortex, posterior insula, hippocampus, and amygdala. State awareness of physical sensations increased following rtfMRI-nf and was maintained at 1-week follow-up (Cohens' d = 0.69). Findings demonstrate feasibility and tolerability of rtfMRI-nf in healthy adolescents, replicates the role of PCC in MT, and demonstrate a potential neuromodulatory mechanism to leverage and streamline the learning of mindfulness practice. ( ClinicalTrials.gov identifier #NCT04053582; August 12, 2019).
View Full Paper →Efficacy of bio- and neurofeedback for depression: a meta-analysis
BACKGROUND: For many years, biofeedback and neurofeedback have been implemented in the treatment of depression. However, the effectiveness of these techniques on depressive symptomatology is still controversial. Hence, we conducted a meta-analysis of studies extracted from PubMed, Scopus, Web of Science and Embase. METHODS: Two different strings were considered for each of the two objectives of the study: A first group comprising studies patients with major depressive disorder (MDD) and a second group including studies targeting depressive symptomatology reduction in other mental or medical conditions. RESULTS: 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 an effect size of Hedges' g = 1.050. Moderator analyses indicate 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. CONCLUSIONS: Heart rate variability (HRV) biofeedback and neurofeedback are associated with a reduction in self-reported depression. Despite the fact that the field has still a large room for improvement in terms of research quality, the results presented in this study suggests that both modalities may become relevant complementary strategies for the treatment of MDD and depressive symptomatology in the coming years.
View Full Paper →EEG-heart rate connectivity changes after sensorimotor rhythm neurofeedback training: Ancillary study
OBJECTIVES: Neurofeedback can induce long-term changes in brain functional connectivity, but its influence on the connectivity between different physiological systems is unknown. The present paper is an ancillary study of a previous paper that confirmed the effect of neurofeedback on brain connectivity associated with chronic pain. We analysed the influence of neurofeedback on the connectivity between the electroencephalograph (EEG) and heart rate (HR). METHODS: Seventeen patients diagnosed with fibromyalgia were divided into three groups: good sensorimotor rhythm (SMR) training responders (n = 4), bad SMR responders (n = 5) and fake training (SHAM, n = 8). Training consisted of six sessions in which participants learned to synchronize and desynchronize SMR power. Before the first training (pre-resting state) and sixth training (post-resting state) session, open-eye resting-state EEG and electrocardiograph signals were recorded. RESULTS: Good responders reduced pain ratings after SMR neurofeedback training. This improvement in fibromyalgia symptoms was associated with a reduction of the connectivity between the central area and HR, between central and frontal areas, within the central area itself, and between central and occipital areas. The sham group and poor responders experienced no changes in their fibromyalgia symptoms. CONCLUSIONS: Our results provide new evidence that neurofeedback is a promising tool that can be used to treat of chronic pain syndromes and to obtain a better understanding of the interactions between physiological networks. These findings are preliminary, but they may pave the way for future studies that are more methodologically robust. In addition, new research questions are raised: what is the role of the central-peripheral network in chronic pain and what is the effect of neurofeedback on this network.
View Full Paper →Brain training with neurofeedback in patients with mild cognitive impairment: a review study
Objective: The study aimed to establish the differences in the levels of adaptation, social support, and perceived family functionality according to sex, age, and school grade of a sample of 160 children and adolescents affected by floods in the Mojana sub-region of the Department of Sucre, Colombia.
View Full Paper →Neurological Mechanisms of Diagnosis and Therapy in School Children with ADHD in Poland
The paper aims to present a holistic view of attention deficit hyperactivity disorder (ADHD) in pedagogical, psychological, legal, and social dimensions in Polish schools. The authors present the benefits of neurofeedback therapy for elementary school pupils. In order to verify the validity, the paper compares the concordance of a medical diagnosis confirming ADHD syndrome with the occurrence of abnormal electrical brain function recording and abnormalities therein as well as the effectiveness of the neurofeedback therapy. The study confirms that the reported problems faced by pupils and affecting their emotional functioning are reflected in their EEG records. Conclusions from the study lead to the proposal that the neurofeedback assessment should be performed at schools, which should result in the implementation of effective therapy. Moreover, the neurofeedback method should be promoted in Polish schools as an alternative to pharmacological therapy, which, as the research proves, is not always effective. Neurofeedback therapy, similarly to behavioral therapy, is very much needed and useful because it provides optimal conditions for the child's development and shapes their relations with the environment effectively and harmlessly.
View Full Paper →Effectivity of ILF Neurofeedback on Autism Spectrum Disorder—A Case Study
Autism spectrum disorder (ASD) is a neural and mental developmental disorder that impacts brain connectivity and information processing. Although application of the infra-low frequency (ILF) neurofeedback procedure has been shown to lead to significant changes in functional connectivity in multiple areas and neuronal networks of the brain, rather limited data are available in the literature for the efficacy of this technique in a therapeutic context to treat ASD. Here we present the case study of a 5-year-old boy with ASD, who received a treatment of 26 sessions of ILF neurofeedback over a 6-month period. A systematic and quantitative tracking of core ASD symptoms in several categories was used to document behavioral changes over time. The ILF neurofeedback intervention decreased the average symptom severity of every category to a remarkable degree, with the strongest effect (80 and 77% mean severity reduction) for physical and sleep symptoms and the lowest influence on behavioral symptoms (15% mean severity reduction). This case study is representative of clinical experience, and thus shows that ILF neurofeedback is a practical and effective therapeutic instrument to treat ASD in children.
View Full Paper →The efficacy of neurofeedback for alcohol use disorders - a systematic review
Background: Alcoholism is a serious social, economic and public health problem. Alcoholism can affect the gastrointestinal, neurological, cardiovascular and respiratory systems, and it can be fatal, costing the healthcare system huge amounts of money. Despite the availability of cognitive-behavioural and psychosocial therapies, alcoholism has a high recurrence rate and a dismal prognosis, with a wide inter-individual variation. As a result, better or adjuvant therapies that improve or facilitate alcoholism therapy are required. We conducted a systematic review to look into the published studies that reported the effectiveness of non-pharmacological neurofeedback (NF) interventions in patients with alcohol use disorders (AUDs). Methods: PubMed, Google Scholar, The Cochrane Library, Science Direct and Clinicaltrial.gov were searched until 4 April 2022. Original articles of any design reporting on the use of NF approaches in the treatment of AUDs were included. Information related to study design, participants, control group, neuromodulation therapy, number of sessions and key findings of the study were extracted. The Joanna Briggs Institute’s (JBI) Critical Appraisal Checklist for Studies was used to assess the quality of studies. Results: A total of 20 research articles (including 618 participants) were retrieved and included for qualitative analysis. The sample size ranged from 1 (case report) to 80, with years of publication ranging from 1977 to 2022. Nine of the 20 articles included in the study were conducted in the United States, followed by Germany, the United Kingdom, India, the Netherlands and South Korea. Out of the 20 studies included, 8 (40%) had a moderate risk of bias, while the other, i.e. 60% had a low risk of bias. The effectiveness of various neurological treatments in the treatment of AUDs was established in these 20 studies. There have been 11 studies on EEG NF training, three studies on real-time FMRI NF, two studies each on transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), and one study each on deep brain stimulation (DBS) and theta burst stimulation (TBS). These alternative neurological therapies have been demonstrated to lower alcohol cravings and consumption temporarily, reduce anxiety and depression scores, reduce relapse rates and increase control of brain activity. Conclusions: The use of various neuromodulation approaches to the treatment of AUD shows promise. However, more research with larger sample size is required.
Double-Blind, Sham-Controlled Randomized Trial Testing the Efficacy of fMRI Neurofeedback on Clinical and Cognitive Measures in Children With ADHD
OBJECTIVE: Functional MRI neurofeedback (fMRI-NF) could potentially be a novel, safe nonpharmacological treatment for attention deficit hyperactivity disorder (ADHD). A proof-of-concept randomized controlled trial of fMRI-NF of the right inferior frontal cortex (rIFC), compared to an active control condition, showed promising improvement of ADHD symptoms (albeit in both groups) and in brain function. However, comparison with a placebo condition in a larger trial is required to test efficacy. METHODS: This double-blind, sham-controlled randomized controlled trial tested the effectiveness and efficacy of fMRI-NF of the rIFC on symptoms and executive functions in 88 boys with ADHD (44 each in the active and sham arms). To investigate treatment-related changes, groups were compared at the posttreatment and 6-month follow-up assessments, controlling for baseline scores, age, and medication status. The primary outcome measure was posttreatment score on the ADHD Rating Scale (ADHD-RS). RESULTS: No significant group differences were found on the ADHD-RS. Both groups showed similar decreases in other clinical and cognitive measures, except for a significantly greater decrease in irritability and improvement in motor inhibition in sham relative to active fMRI-NF at the posttreatment assessment, covarying for baseline. There were no significant side effects or adverse events. The active relative to the sham fMRI-NF group showed enhanced activation in rIFC and other frontal and temporo-occipital-cerebellar self-regulation areas. However, there was no progressive rIFC upregulation, correlation with ADHD-RS scores, or transfer of learning. CONCLUSIONS: Contrary to the hypothesis, the study findings do not suggest that fMRI-NF of the rIFC is effective in improving clinical symptoms or cognition in boys with ADHD.
Infralow neurofeedback in the treatment of substance use disorders: a randomized controlled trial
Background: Infralow neurofeedback (ILF-NF) was recently developed as a subtype of traditional, frequency-based neurofeedback that targets cerebral rhythmic activity below 0.5 Hz and improves brain self-regulation. The efficacy of ILF-NF in the treatment of substance use disorder has not yet been evaluated, but clinical evidence suggests that it may prevent relapse by improving functioning in various life domains. The current study aimed to fill this research gap and extend empirical evidence related to this issue. Methods: Ninety-three patients with substance use disorders at an outpatient unit in Norway were randomized to receive 20 sessions (30 minutes each) of ILF-NF training combined with treatment as usual (TAU), or TAU alone. The primary outcome was quality of life post-treatment as an overall measure of functioning. We analyzed between-group differences using Student t tests. Results: We found no significant differences in quality of life between groups. We found similar nonsignificant results for most of the secondary outcome measures, including drug use, sleep, anxiety and depression. Compared to TAU, the ILF-NF + TAU group reported significantly lower restlessness scores post-treatment (mean difference −1.8, 95% confidence interval –3.1 to –0.5; p = 0.006). Limitations: This study was limited by broad inclusion criteria and a lack of placebo control (sham neurofeedback treatment). Conclusion: ILF-NF offered limited additional benefit when combined with TAU, except in the area of restlessness. Future studies could further investigate the relationship between ILF-NF, restlessness and substance use in targeted subpopulations to illuminate relapse mechanisms. Clinical trial registration: ClinicalTrials.gov: NCT03356210.
View Full Paper →Real-time fMRI neurofeedback as a new treatment for psychiatric disorders: A meta-analysis
Neurofeedback using real-time functional MRI (RT-fMRI-NF) is an innovative technique that allows to voluntarily modulate a targeted brain response and its associated behavior. Despite promising results in the current literature, its effectiveness on symptoms management in psychiatric disorders is not yet clearly demonstrated. Here, we provide 1) a state-of-art qualitative review of RT-fMRI-NF studies aiming at alleviating clinical symptoms in a psychiatric population; 2) a quantitative evaluation (meta-analysis) of RT-fMRI-NF effectiveness on various psychiatric disorders and 3) methodological suggestions for future studies. Thirty-one clinical trials focusing on psychiatric disorders were included and categorized according to standard diagnostic categories. Among the 31 identified studies, 22 consisted of controlled trials, of which only eight showed significant clinical improvement in the experimental vs. control group after the training. Nine studies found an effect at follow-up on ADHD symptoms, emotion dysregulation, facial emotion processing, depressive symptoms, hallucinations, psychotic symptoms, and specific phobia. Within-group meta-analysis revealed large effects of the NF training on depressive symptoms right after the training (g = 0.81, p < 0.01) and at follow-up (g = 1.19, p < 0.01), as well as medium effects on anxiety (g = 0.44, p = 0.01) and emotion regulation (g = 0.48, p < 0.01). Between-group meta-analysis showed a medium effect on depressive symptoms (g = 0.49, p < 0.01) and a large effect on anxiety (g = 0.77, p = 0.01). However, the between-studies heterogeneity is very high. The use of RT-fMRI-NF as a treatment for psychiatric symptoms is promising, however, further double-blind, multicentric, randomized-controlled trials are warranted.
View Full Paper →Effects of an intensive slow cortical potentials neurofeedback training in female and male adolescents with autism spectrum disorder : Are there sex differences?
BACKGROUND: This study aims to compare the effects of neurofeedback training on male and female adolescents with autism spectrum disorder (ASD). Furthermore, it examines sex differences regarding improvements in co-occurring psychopathological symptoms, cognitive flexibility and emotion recognition abilities. The study might provide first hints whether there is an influence of sex on treatment outcomes. METHODS: Six female and six male adolescents with ASD were matched according to age, IQ and symptom severity. All participants received 24 sessions of electroencephalography-based neurofeedback training. Before and after the intervention, psychological data for measuring co-occurring psychopathological symptoms as well as behavioral data for measuring cognitive flexibility and emotion recognition abilities were recorded. RESULTS: Caregivers rated statistically significant higher psychopathological problems in female than in male adolescents with ASD at baseline. Apart from that, no statistically significant sex-related differences were revealed in this sample; however, male adolescents tended to report greater improvements of externalizing, internalizing and total symptoms, whereas females experienced smaller improvements of externalizing and total problems, but no improvements of internalizing problems. Regarding caregivers' assessments, more improvement of total problems was reported for females. For males, only improvements of internalizing and total problems were described. CONCLUSION: This study reveals preliminary results that sex-related differences might play a role when evaluating treatment outcomes after neurofeedback training regarding comorbid psychopathological symptoms. Adolescents' self-report and parental assessments, especially concerning psychopathological symptoms, should be combined and considered in future studies to help prevent sex bias in adolescents with ASD.
Effect of neurofeedback therapy on neurological post-COVID-19 complications (A pilot study)
OBJECTIVE: Anxiety, fatigue and depression are common neurological manifestations after COVID-19. So far, post-COVID complications were treated by rehabilitation, oxygen therapy and immunotherapy. Effects of neurofeedback on post-COVID complications and their potential interrelatedness have not been studied yet. In this pilot study, we investigated the effectiveness of neurofeedback (Othmer method) for treatment of fatigue, anxiety, and depression after COVID-19. METHODS: 10 participants met inclusion criteria for having positive anamnesis of at least one of the following complications following COVID-19: fatigue, anxiety, and depression which were measured by questionnaires. ANOVA was used for calculating differences in questionnaire score before and after neurofeedback. Pearson's correlation coefficient was used to calculate correlations between anxiety, depression and fatigue. RESULTS: After five neurofeedback sessions, there came to significant reduction of severity of post-COVID anxiety and depression persisting for at least one month. Effect of neurofeedback on fatigue was insignificant. Severity of anxiety, fatigue and depression as well as reductions in depression and fatigue were positively correlated with each other. CONCLUSION: These findings showed effectiveness neurofeedback for reducing anxiety and depression after COVID-19 and for studying correlations between neurological complications after COVID-19. However, since our pilot clinical trial was open-label, it is hard to differentiate between neurofeedback-specific and unspecific effects on our participants. Future randomized controlled trials with more robust sample are necessary to investigate feasibility of neurofeedback for post-COVID neurological complications. The study has identification number trial ID ISRCTN49037874 in ISRCTN register of clinical trials (Retrospectively registered).
View Full Paper →Impulsivity Moderates the Effect of Neurofeedback Training on the Contingent Negative Variation in Autism Spectrum Disorder
Background The contingent negative variation (CNV) is a well-studied indicator of attention- and expectancy-related processes in the human brain. An abnormal CNV amplitude has been found in diverse neurodevelopmental psychiatric disorders. However, its role as a potential biomarker of successful clinical interventions in autism spectrum disorder (ASD) remains unclear. Methods In this randomized controlled trial, we investigated how the CNV changes following an intensive neurofeedback training. Therefore, twenty-one adolescents with ASD underwent 24 sessions of slow cortical potential (SCP) neurofeedback training. Twenty additional adolescents with ASD formed a control group and received treatment as usual. CNV waveforms were obtained from a continuous performance test (CPT), which all adolescents performed before and after the corresponding 3-month long training period. In order to utilize all available neural time series, trial-based area under the curve values for all four electroencephalogram (EEG) channels were analyzed with a hierarchical Bayesian model. In addition, the model included impulsivity, inattention, and hyperactivity as potential moderators of change in CNV. Results Our model implies that impulsivity moderates the effects of neurofeedback training on CNV depending on group. In the control group, the average CNV amplitude decreased or did not change after treatment as usual. In the experimental group, the CNV changed depending on the severity of comorbid impulsivity symptoms. The average CNV amplitude of participants with low impulsivity scores decreased markedly, whereas the average CNV amplitude of participants with high impulsivity increased. Conclusion The degree of impulsivity seems to play a crucial role in the changeability of the CNV following an intensive neurofeedback training. Therefore, comorbid symptomatology should be recorded and analyzed in future EEG-based brain training interventions. Clinical Trial Registration https://www.drks.de , identifier DRKS00012339.
Improving cognitive control: Is theta neurofeedback training associated with proactive rather than reactive control enhancement?
Frontal-midline (FM) theta activity (4-8 Hz) is proposed to reflect a mechanism for cognitive control that is needed for working memory retention, manipulation, and interference resolution. Modulation of FM theta activity via neurofeedback training (NFT) demonstrated transfer to some but not all types of cognitive control. Therefore, the present study investigated whether FM theta NFT enhances performance and modulates underlying EEG characteristics in a delayed match to sample (DMTS) task requiring mainly proactive control and a color Stroop task requiring mainly reactive control. Moreover, temporal characteristics of transfer were explored over two posttests. Across seven 30-min NFT sessions, an FM theta training group exhibited a larger FM theta increase compared to an active control group who upregulated randomly chosen frequency bands. In a posttest performed 13 days after the last training session, the training group showed better retention performance in the DMTS task. Furthermore, manipulation performance was associated with NFT theta increase for the training but not the control group. Contrarily, behavioral group differences and their relation to FM theta change were not significant in the Stroop task, suggesting that NFT is associated with proactive but not reactive control enhancement. Transfer to both tasks at a posttest one day after training was not significant. Behavioral improvements were not accompanied by changes in FM theta activity, indicating no training-induced modulation of EEG characteristics. Together, these findings suggest that NFT supports transfer to cognitive control that manifests late after training but that other training-unspecific factors may also contribute to performance enhancement.
View Full Paper →Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review
Top‐tier evidence on the safety/tolerability of 80 medications in children/adolescents with mental disorders has recently been reviewed in this journal. To guide clinical practice, such data must be combined with evidence on efficacy and acceptability. Besides medications, psychosocial interventions and brain stimulation techniques are treatment options for children/adolescents with mental disorders. For this umbrella review, we systematically searched network meta‐analyses (NMAs) and meta‐analyses (MAs) of randomized controlled trials (RCTs) evaluating 48 medications, 20 psychosocial interventions, and four brain stimulation techniques in children/adolescents with 52 different mental disorders or groups of mental disorders, reporting on 20 different efficacy/acceptability outcomes. Co‐primary outcomes were disease‐specific symptom reduction and all‐cause discontinuation (“acceptability”). We included 14 NMAs and 90 MAs, reporting on 15 mental disorders or groups of mental disorders. Overall, 21 medications outperformed placebo regarding the co‐primary outcomes, and three psychosocial interventions did so (while seven outperformed waiting list/no treatment). Based on the meta‐analytic evidence, the most convincing efficacy profile emerged for amphetamines, methylphenidate and, to a smaller extent, behavioral therapy in attention‐deficit/hyperactivity disorder; aripiprazole, risperidone and several psychosocial interventions in autism; risperidone and behavioral interventions in disruptive behavior disorders; several antipsychotics in schizophrenia spectrum disorders; fluoxetine, the combination of fluoxetine and cognitive behavioral therapy (CBT), and interpersonal therapy in depression; aripiprazole in mania; fluoxetine and group CBT in anxiety disorders; fluoxetine/selective serotonin reuptake inhibitors, CBT, and behavioral therapy with exposure and response prevention in obsessive‐compulsive disorder; CBT in post‐traumatic stress disorder; imipramine and alarm behavioral intervention in enuresis; behavioral therapy in encopresis; and family therapy in anorexia nervosa. Results from this umbrella review of interventions for mental disorders in children/adolescents provide evidence‐based information for clinical decision making.
View Full Paper →Deep brain electrical neurofeedback allows Parkinson patients to control pathological oscillations and quicken movements
Parkinsonian motor symptoms are linked to pathologically increased beta-oscillations in the basal ganglia. While pharmacological treatment and deep brain stimulation (DBS) reduce these pathological oscillations concomitantly with improving motor performance, we set out to explore neurofeedback as an endogenous modulatory method. We implemented real-time processing of pathological subthalamic beta oscillations through implanted DBS electrodes to provide deep brain electrical neurofeedback. Patients volitionally controlled ongoing beta-oscillatory activity by visual neurofeedback within minutes of training. During a single one-hour training session, the reduction of beta-oscillatory activity became gradually stronger and we observed improved motor performance. Lastly, endogenous control over deep brain activity was possible even after removing visual neurofeedback, suggesting that neurofeedback-acquired strategies were retained in the short-term. Moreover, we observed motor improvement when the learnt mental strategies were applied 2 days later without neurofeedback. Further training of deep brain neurofeedback might provide therapeutic benefits for Parkinson patients by improving symptom control using strategies optimized through neurofeedback.
View Full Paper →Double-Blind Placebo-Controlled Randomized Clinical Trial of Neurofeedback for Attention-Deficit/Hyperactivity Disorder With 13-Month Follow-up
OBJECTIVE: To determine whether theta/beta-ratio (TBR) electroencephalographic biofeedback (neurofeedback [NF]) has a specific effect on attention-deficit/hyperactivity disorder (ADHD) beyond nonspecific benefit. METHOD: In a 2-site double-blind randomized clinical trial, 144 children aged 7 to 10 years with rigorously diagnosed moderate/severe ADHD and theta/beta-ratio (TBR) ≥4.5 were randomized 3:2 to deliberate TBR downtraining versus a control of equal duration, intensity, and appearance. Two early dropouts left 142 children for modified intent-to-treat analysis. The control used prerecorded electroencephalograms with the participant's artifacts superimposed. Treatment was programmed via Internet by an off-site statistician-guided co-investigator. Fidelity was 98.7% by trainers/therapists and 93.2% by NF expert monitor. The primary outcome was parent- and teacher-rated inattention; analysis was mixed-effects regression. Because the expense and effort of NF can be justified only by enduring benefit, follow-ups were integrated. RESULTS: Blinding was excellent. Although both groups showed significant improvement (p < .001, d = 1.5) in parent/teacher-rated inattention from baseline to treatment end and 13-month follow-up, NF was not significantly superior to the control condition at either time point on this primary outcome (d = 0.01, p = .965 at treatment end; d = 0.23, p = .412 at 13-month follow-up). Responders (Clinical Global Impression-Improvement [CGI-I] = 1-2) were 61% of NF and 54% of controls (p = .36). Adverse events were distributed proportionally between treatments. The 13-month follow-up found nonsignificant improvement from treatment end for NF (d = 0.1), with mild deterioration for controls (d = -0.07). NF required significantly less medication at follow-up (p = .012). CONCLUSION: This study does not support a specific effect of deliberate TBR NF at either treatment end or 13-month follow-up. Participants will be reassessed at 25-month follow-up. CLINICAL TRIAL REGISTRATION INFORMATION: Double-Blind 2-Site Randomized Clinical Trial of Neurofeedback for ADHD; https://clinicaltrials.gov/; NCT02251743.
View Full Paper →The impact of real-time fMRI denoising on online evaluation of brain activity and functional connectivity
Objective. Comprehensive denoising is imperative in functional magnetic resonance imaging (fMRI) analysis to reliably evaluate neural activity from the blood oxygenation level dependent signal. In real-time fMRI, however, only a minimal denoising process has been applied and the impact of insufficient denoising on online brain activity estimation has not been assessed comprehensively. This study evaluated the noise reduction performance of online fMRI processes in a real-time estimation of regional brain activity and functional connectivity.Approach.We performed a series of real-time processing simulations of online fMRI processing, including slice-timing correction, motion correction, spatial smoothing, signal scaling, and noise regression with high-pass filtering, motion parameters, motion derivatives, global signal, white matter/ventricle average signals, and physiological noise models with image-based retrospective correction of physiological motion effects (RETROICOR) and respiration volume per time (RVT).Main results.All the processing was completed in less than 400 ms for whole-brain voxels. Most processing had a benefit for noise reduction except for RVT that did not work due to the limitation of the online peak detection. The global signal regression, white matter/ventricle signal regression, and RETROICOR had a distinctive noise reduction effect, depending on the target signal, and could not substitute for each other. Global signal regression could eliminate the noise-associated bias in the mean dynamic functional connectivity across time.Significance.The results indicate that extensive real-time denoising is possible and highly recommended for real-time fMRI applications.
View Full Paper →Visual perceptual learning of a primitive feature in human V1/V2 as a result of unconscious processing, revealed by decoded functional MRI neurofeedback (DecNef)
Although numerous studies have shown that visual perceptual learning (VPL) occurs as a result of exposure to a visual feature in a task-irrelevant manner, the underlying neural mechanism is poorly understood. In a previous psychophysical study (Watanabe et al., 2002), subjects were repeatedly exposed to a task-irrelevant Sekuler motion display that induced the perception of not only the local motions, but also a global motionmoving in the direction of the spatiotemporal average of the local motion vectors. As a result of this exposure, subjects enhanced their sensitivity only to the local moving directions, suggesting that early visual areas (V1/V2) that process local motions are involved in task-irrelevant VPL. However, this hypothesis has never been tested directly using neuronal recordings. Here, we employed a decoded neurofeedback technique (DecNef) using functional magnetic resonance imaging in human subjects to examine the involvement of early visual areas (V1/V2) in task-irrelevant VPL of local motion within a Sekuler motion display. During the DecNef training, subjects were trained to induce the activity patterns in V1/V2 that were similar to those evoked by the actual presentation of the Sekuler motion display. The DecNef training was conducted with neither the actual presentation of the display nor the subjects' awareness of the purpose of the experiment. After the experiment, subjects reported that they neither perceived nor imagined the trained motion during the DecNef training. As a result of DecNef training, subjects increased their sensitivity to the local motion directions, but not specifically to the global motion direction. Neuronal changes related to DecNef training were confined to V1/V2. These results suggest that V1/V2 are involved in exposure-based task-irrelevant VPL of local motion.
View Full Paper →Predictors of real-time fMRI neurofeedback performance and improvement - A machine learning mega-analysis
Real-time fMRI neurofeedback is an increasingly popular neuroimaging technique that allows an individual to gain control over his/her own brain signals, which can lead to improvements in behavior in healthy participants as well as to improvements of clinical symptoms in patient populations. However, a considerably large ratio of participants undergoing neurofeedback training do not learn to control their own brain signals and, consequently, do not benefit from neurofeedback interventions, which limits clinical efficacy of neurofeedback interventions. As neurofeedback success varies between studies and participants, it is important to identify factors that might influence neurofeedback success. Here, for the first time, we employed a big data machine learning approach to investigate the influence of 20 different design-specific (e.g. activity vs. connectivity feedback), region of interest-specific (e.g. cortical vs. subcortical) and subject-specific factors (e.g. age) on neurofeedback performance and improvement in 608 participants from 28 independent experiments. With a classification accuracy of 60% (considerably different from chance level), we identified two factors that significantly influenced neurofeedback performance: Both the inclusion of a pre-training no-feedback run before neurofeedback training and neurofeedback training of patients as compared to healthy participants were associated with better neurofeedback performance. The positive effect of pre-training no-feedback runs on neurofeedback performance might be due to the familiarization of participants with the neurofeedback setup and the mental imagery task before neurofeedback training runs. Better performance of patients as compared to healthy participants might be driven by higher motivation of patients, higher ranges for the regulation of dysfunctional brain signals, or a more extensive piloting of clinical experimental paradigms. Due to the large heterogeneity of our dataset, these findings likely generalize across neurofeedback studies, thus providing guidance for designing more efficient neurofeedback studies specifically for improving clinical neurofeedback-based interventions. To facilitate the development of data-driven recommendations for specific design details and subpopulations the field would benefit from stronger engagement in open science research practices and data sharing.
View Full Paper →Matched neurofeedback during fMRI differentially activates reward-related circuits in active and sham groups
BACKGROUND AND PURPOSE: Functional MRI neurofeedback (fMRI-nf) leverages the brain's ability to self-regulate its own activity. However, self-regulation processes engaged during fMRI-nf are incompletely understood. Here, we used matched feedback in an fMRI-nf experimental protocol to investigate whether brain processes recognize true neurofeedback signals. METHODS: We implemented an existing fMRI-nf protocol to train lateralized motor activity using a finger-tap task in conjunction with real-time feedback. Twelve healthy, right-handed, adult participants were assigned into age- and sex-matched active and sham study groups. Matched participant pairs received the same visual feedback, based on brain activity of the participant from the active group. We compared group-averaged activation maps before, during, and after neurofeedback, and analyzed changes in lateralized motor activity due to neurofeedback. RESULTS: Active and sham groups demonstrated different brain activation to the same feedback during neurofeedback. In particular, there was higher activation in visual cortex, secondary somatosensory cortex, and right inferior frontal gyrus in the active group compared to the sham group. Conversely, sham participants demonstrated higher activation in anterior cingulate cortex, left frontal pole, and posterior superior temporal gyrus. Despite differing brain activations during neurofeedback, neither group demonstrated significant improvement in lateralized motor activity from pre to postfeedback scan in the same session. We also observed no significant difference between pre and postfeedback activation maps, suggesting that no significant finger-tap related functional reorganization had occurred. CONCLUSIONS: These findings suggest that fMRI neurofeedback paradigms that monitor or incorporate activity from regions reported here would provide enhanced efficacy for research investigation and clinical intervention.
View Full Paper →Interacting brains coming in sync through their minds: an interbrain neurofeedback study
Neurophysiological evidence shows that interpersonal action coordination is accompanied by interbrain synchronization (IBS). However, the functional significance of this association remains unclear. Using two experimental designs, we explored whether IBS is amenable to neurofeedback (NFB). Feedback was provided either as two balls approaching each other (so-called ball design), or as two pendula, each reflecting the oscillatory activity of one of the two participants (so-called pendulum design). The NFB was provided at delta (i.e., 2.5 Hz) and theta (i.e., 5 Hz) electroencephalography frequencies, and manipulated by enhanced and inverse feedback. We showed that the participants were able to increase IBS by using NFB, especially when it was fed back at the theta frequency. Apart from intra- and interbrain coupling, other oscillatory activities (e.g., power spectral density, peak amplitude, and peak frequency) also changed during the task compared with the rest. Moreover, all the measures showed specific correlations with the subjective postsurvey item scores, reflecting subjective feeling and appraisal. We conclude that the use of IBS for NFB might help in specifying the contribution of IBS to interpersonal action coordination and in providing important information about the neural mechanisms of social interaction and the causal dimension of IBS.
View Full Paper →Neurofeedback therapy for the management of multiple sclerosis symptoms: current knowledge and future perspectives
Fatigue is a frequent and debilitating symptom in patients with multiple sclerosis (MS). Affective manifestations are also of high prevalence in this population and can drastically impact the patients' functioning. A considerable proportion of patients with MS suffer from cognitive deficits affecting general and social cognitive domains. In addition, pain in MS is commonly observed in neurology wards, could be of different types, and may result from or be exacerbated by other MS comorbidities. These complaints tend to cluster together in some patients and seem to have a complex pathophysiology and a challenging management. Exploring the effects of new interventions could improve these outcomes and ameliorate the patients' quality of life. Neurofeedback (NFB) might have its place in this context by enhancing or reducing the activity of some regions in specific electroencephalographic bands (i.e., theta, alpha, beta, sensorimotor rhythm). This work briefly revisits the principles of NFB and its application. The published data are scarce and heterogeneous yet suggest preliminary evidence on the potential utility of NFB in patients with MS (i.e., depression, fatigue, cognitive deficits and pain). NFB is simple to adapt and easy to coach, and its place in the management of MS symptoms merits further investigations. Comparing different NFB protocols (i.e., cortical target, specific rhythm, session duration and number) and performing a comprehensive evaluation could help developing and optimizing interventions targeting specific symptoms. These aspects could also open the way for the association of this technique with other approaches (i.e., brain stimulation, cognitive rehabilitation, exercise training, psychotherapies) that have proved their worth in some MS domains.
View Full Paper →Can neurophysiological markers of anticipation and attention predict ADHD severity and neurofeedback outcomes?
Neurophysiological measures of preparation and attention are often atypical in ADHD. Still, replicated findings that these measures predict which patients improve after Neurofeedback (NF), reveal neurophysiological specificity, and reflect ADHD-severity are limited. METHODS: We analyzed children's preparatory (CNV) and attentional (Cue-P3) brain activity and behavioral performance during a cued Continuous Performance Task (CPT) before and after slow cortical potential (SCP)-NF or semi-active control treatment (electromyogram biofeedback). Mixed-effects models were performed with 103 participants at baseline and 77 were assessed for pre-post comparisons focusing on clinical outcome prediction, specific neurophysiological effects of NF, and associations with ADHD-severity. RESULTS: Attentional and preparatory brain activity and performance were non-specifically reduced after treatment. Preparatory activity in the SCP-NF group increased with clinical improvement. Several performance and brain activity measures predicted non-specific treatment outcome. CONCLUSION: Specific neurophysiological effects after SCP-NF were limited to increased neural preparation associated with improvement on ADHD-subscales, but several performance and neurophysiological measures of attention predicted treatment outcome and reflected symptom severity in ADHD. The results may help to optimize treatment.
Neurofeedback Training Based on Motor Imagery Strategies Increases EEG Complexity in Elderly Population
Neurofeedback training (NFT) has shown promising results in recent years as a tool to address the effects of age-related cognitive decline in the elderly. Since previous studies have linked reduced complexity of electroencephalography (EEG) signal to the process of cognitive decline, we propose the use of non-linear methods to characterise changes in EEG complexity induced by NFT. In this study, we analyse the pre- and post-training EEG from 11 elderly subjects who performed an NFT based on motor imagery (MI–NFT). Spectral changes were studied using relative power (RP) from classical frequency bands (delta, theta, alpha, and beta), whilst multiscale entropy (MSE) was applied to assess EEG-induced complexity changes. Furthermore, we analysed the subject’s scores from Luria tests performed before and after MI–NFT. We found that MI–NFT induced a power shift towards rapid frequencies, as well as an increase of EEG complexity in all channels, except for C3. These improvements were most evident in frontal channels. Moreover, results from cognitive tests showed significant enhancement in intellectual and memory functions. Therefore, our findings suggest the usefulness of MI–NFT to improve cognitive functions in the elderly and encourage future studies to use MSE as a metric to characterise EEG changes induced by MI–NFT.
Improving Clinical, Cognitive, and Psychosocial Dysfunctions in Patients with Schizophrenia: A Neurofeedback Randomized Control Trial
OBJECTIVES: The aim of this study was to use neurofeedback (NF) training as the add-on therapy in patients with schizophrenia to improve their clinical, cognitive, and psychosocial condition. The study, thanks to the monitoring of various conditions, quantitative electroencephalogram (QEEG) and brain-derived neurotrophic factor (BDNF), was supposed to give an insight into mechanisms underlying NF training results. METHODS: Forty-four male patients with schizophrenia, currently in a stable, incomplete remission, were recruited into two, 3-month rehabilitation programs, with standard rehabilitation as a control group (R) or with add-on NF training (NF). Pre- and posttherapy primary outcomes were compared: clinical (Positive and Negative Syndrome Scale (PANSS)), cognitive (Color Trails Test (CTT), d2 test), psychosocial functioning (General Self-Efficacy Scale (GSES), Beck Cognitive Insight Scale (BCIS), and Acceptance of Illness Scale (AIS)), quantitative electroencephalogram (QEEG), auditory event-related potentials (ERPs), and serum level of BDNF. Results. Both groups R and NF improved significantly in clinical ratings (Positive and Negative Syndrome Scale (PANSS)). In-between analyses unveiled some advantages of add-on NF therapy over standard rehabilitation. GSES scores improved significantly, giving the NF group of patients greater ability to cope with stressful or difficult social demands. Also, the serum-level BDNF increased significantly more in the NF group. Post hoc analyses indicated the possibility of creating a separate PANSS subsyndrome, specifically related to cognitive, psychosocial, and BDNF effects of NF therapy. CONCLUSIONS: Neurofeedback can be effectively used as the add-on therapy in schizophrenia rehabilitation programs. The method requires further research regarding its clinical specificity and understanding mechanisms of action.
View Full Paper →Effect of BCI-Controlled Pedaling Training System With Multiple Modalities of Feedback on Motor and Cognitive Function Rehabilitation of Early Subacute Stroke Patients
Brain-computer interfaces (BCIs) are currently integrated into traditional rehabilitation interventions after stroke. Although BCIs bring many benefits to the rehabilitation process, their effects are limited since many patients cannot concentrate during training. Despite this outcome post-stroke motor-attention dual-task training using BCIs has remained mostly unexplored. This study was a randomized placebo-controlled blinded-endpoint clinical trial to investigate the effects of a BCI-controlled pedaling training system (BCI-PT) on the motor and cognitive function of stroke patients during rehabilitation. A total of 30 early subacute ischemic stroke patients with hemiplegia and cognitive impairment were randomly assigned to the BCI-PT or traditional pedaling training. We used single-channel Fp1 to collect electroencephalography data and analyze the attention index. The BCI-PT system timely provided visual, auditory, and somatosensory feedback to enhance the patient's participation to pedaling based on the real-time attention index. After 24 training sessions, the attention index of the experimental group was significantly higher than that of the control group. The lower limbs motor function (FMA-L) increased by an average of 4.5 points in the BCI-PT group and 2.1 points in the control group (P = 0.022) after treatments. The difference was still significant after adjusting for the baseline indicators ( β = 2.41 , 95%CI: 0.48-4.34, P = 0.024). We found that BCI-PT significantly improved the patient's lower limb motor function by increasing the patient's participation. (clinicaltrials.gov: NCT04612426).
View Full Paper →Volitional modification of brain activity in adolescents with Autism Spectrum Disorder: A Bayesian analysis of Slow Cortical Potential neurofeedback
Autism spectrum disorder is (ASD) characterized by a persisting triad of impairments of social interaction, language as well as inflexible, stereotyped and ritualistic behaviors. Increasingly, scientific evidence suggests a neurobiological basis of these emotional, social and cognitive deficits in individuals with ASD. The aim of this randomized controlled brain self-regulation intervention study was to investigate whether the core symptomatology of ASD could be reduced via an electroencephalography (EEG) based brain self-regulation training of Slow Cortical Potentials (SCP). 41 male adolescents with ASD were recruited and allocated to a) an experimental group undergoing 24 sessions of EEG-based brain training (n1 = 21), or to b) an active control group undergoing conventional treatment (n2 = 20), that is, clinical counseling during a 3-months intervention period. We employed real-time neurofeedback training recorded from a fronto-central electrode intended to enable participants to volitionally regulate their brain activity. Core autistic symptomatology was measured at six time points during the intervention and analyzed with Bayesian multilevel approach to characterize changes in core symptomatology. Additional Bayesian models were formulated to describe the neural dynamics of the training process as indexed by SCP (time-domain) and power density (PSD, frequency-domain) measures. The analysis revealed a substantial improvement in the core symptomatology of ASD in the experimental group (reduction of 21.38 points on the Social Responsiveness Scale, SD = 5.29), which was slightly superior to that observed in the control group (evidence Ratio = 5.79). Changes in SCP manifested themselves as different trajectories depending on the different feedback conditions and tasks. Further, the model of PSD revealed a continuous decrease in delta power, parallel to an increase in alpha power. Most notably, a non-linear (quadratic) model turned out to be better at predicting the data than a linear model across all analyses. Taken together, our analyses suggest that behavioral and neural processes of change related to neurofeedback training are complex and non-linear. Moreover, they have implications for the design of future trials and training protocols.
View Full Paper →Toward Personalizing Alzheimer’s Disease Therapy Using an Intelligent Cognitive Control System
Subjective cognitive decline is an early state of Alzheimer’s Disease which affects almost 10 million people every year. It results from negative emotions such as frustration which are more present than healthy adults. For this reason, our work focuses on relaxing subjective cognitive decline patients using virtual reality environments to improve their memory performance. We proposed in our previous work a neurofeedback approach which adapts the virtual environment to each patient according to their emotions using a Neural Agent. We found that the Neural Agent can adapt the environment to each participant but have limitations. This work is a continuation of our approach in which we propose a Limbic Agent able to monitor the interactions between the Neural Agent and patients’ emotional reactions, learn from these interactions, and modify the Neural Agent in order to enhance the adaptation to each patient with an Intelligent Cognitive Control System. Our goal is to create a system able to support the Limbic System which is the main area in charge of controlling emotions and creating memory in the human brain. We used data collected form our previous work to train the Limbic Agent and results showed that the agent is capable of modifying the weight of existing rules, generating new intervention rules, and predicting if they will work or not.
Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder
An important challenge in mental health research is to translate findings from cognitive neuroscience and neuroimaging research into effective treatments that target the neurobiological alterations involved in psychiatric symptoms. To address this challenge, in this review we propose a heuristic neurocircuit-based taxonomy to guide the treatment of obsessive-compulsive disorder (OCD). We do this by integrating information from several sources. First, we provide case vignettes in which patients with OCD describe their symptoms and discuss different clinical profiles in the phenotypic expression of the condition. Second, we link variations in these clinical profiles to underlying neurocircuit dysfunctions, drawing on findings from neuropsychological and neuroimaging studies in OCD. Third, we consider behavioral, pharmacological, and neuromodulatory treatments that could target those specific neurocircuit dysfunctions. Finally, we suggest methods of testing this neurocircuit-based taxonomy as well as important limitations to this approach that should be considered in future research.
View Full Paper →Towards semantic fMRI neurofeedback: navigating among mental states using real-time representational similarity analysis
Objective. Real-time functional magnetic resonance imaging neurofeedback (rt-fMRI-NF) is a non-invasive MRI procedure allowing examined participants to learn to self-regulate brain activity by performing mental tasks. A novel two-step rt-fMRI-NF procedure is proposed whereby the feedback display is updated in real-time based on high-level representations of experimental stimuli (e.g. objects to imagine) via real-time representational similarity analysis of multi-voxel patterns of brain activity.Approach. In a localizer session, the stimuli become associated with anchored points on a two-dimensional representational space where distances approximate between-pattern (dis)similarities. In the NF session, participants modulate their brain response, displayed as a movable point, to engage in a specific neural representation. The developed method pipeline is verified in a proof-of-concept rt-fMRI-NF study at 7 T involving a single healthy participant imagining concrete objects. Based on this data and artificial data sets with similar (simulated) spatio-temporal structure and variable (injected) signal and noise, the dependence on noise is systematically assessed.Main results. The participant in the proof-of-concept study exhibited robust activation patterns in the localizer session and managed to control the neural representation of a stimulus towards the selected target in the NF session. The offline analyses validated the rt-fMRI-NF results, showing that the rapid convergence to the target representation is noise-dependent.Significance. Our proof-of-concept study introduces a new NF method allowing the participant to navigate among different mental states. Compared to traditional NF designs (e.g. using a thermometer display to set the level of the neural signal), the proposed approach provides content-specific feedback to the participant and extra degrees of freedom to the experimenter enabling real-time control of the neural activity towards a target brain state without suggesting a specific mental strategy to the subject.
View Full Paper →Neurofeedback for cognitive enhancement and intervention and brain plasticity
In recent years, neurofeedback has been used as a cognitive training tool to improve brain functions for clinical or recreational purposes. It is based on providing participants with feedback about their brain activity and training them to control it, initiating directional changes. The overarching hypothesis behind this method is that this control results in an enhancement of the cognitive abilities associated with this brain activity, and triggers specific structural and functional changes in the brain, promoted by learning and neuronal plasticity effects. Here, we review the general methodological principles behind neurofeedback and we describe its behavioural benefits in clinical and experimental contexts. We review the non-specific effects of neurofeedback on the reinforcement learning striato-frontal networks as well as the more specific changes in the cortical networks on which the neurofeedback control is exerted. Last, we analyse the current challenges faces by neurofeedback studies, including the quantification of the temporal dynamics of neurofeedback effects, the generalisation of its behavioural outcomes to everyday life situations, the design of appropriate controls to disambiguate placebo from true neurofeedback effects and the development of more advanced cortical signal processing to achieve a finer-grained real-time modelling of cognitive functions.
View Full Paper →Recent findings on neurofeedback training for auditory hallucinations in schizophrenia
PURPOSE OF REVIEW: To provide recent evidence on real-time neurofeedback (NFB) training for auditory verbal hallucinations (AVH) in schizophrenia patients. RECENT FINDINGS: NFB is a promising technique that allows patients to gain control over their AVH by modulating their own speech-related/language-related networks including superior temporal gyrus (STG) and anterior cingulate cortex (ACC) using fMRI, fNIRS and EEG/MEG. A recent limited number of studies showed that while an EEG-based NFB study failed to regulate auditory-evoked potentials and reduce AVH, downregulation of STG hyperactivity and upregulation of ACC activity with fMRI-based NFB appear to alleviate treatment-resistant AVH in schizophrenia patients. A deeper understanding of AVH and development of more effective methodologies are still needed. SUMMARY: Despite recent innovations in antipsychotics, many schizophrenia patients continue to suffer from treatment-resistant AVH and social dysfunctions. Recent studies suggested that real-time NFB shows promise in enabling patients to gain control over AVH by regulating their own speech-related/language-related networks. Although fMRI-NFB is suitable for regulating localized activity, EEG/MEG-NFB are ideal for regulating the ever-changing AVH. Although there are still many challenges including logistic complexity and burden on patients, we hope that such innovative real-time NFB trainings will help patients to alleviate severe symptoms and improve social functioning.
View Full Paper →Neurotherapeutics for Attention Deficit/Hyperactivity Disorder (ADHD): A Review
This review focuses on the evidence for neurotherapeutics for attention deficit/hyperactivity disorder (ADHD). EEG-neurofeedback has been tested for about 45 years, with the latest meta-analyses of randomised controlled trials (RCT) showing small/medium effects compared to non-active controls only. Three small studies piloted neurofeedback of frontal activations in ADHD using functional magnetic resonance imaging or near-infrared spectroscopy, finding no superior effects over control conditions. Brain stimulation has been applied to ADHD using mostly repetitive transcranial magnetic and direct current stimulation (rTMS/tDCS). rTMS has shown mostly negative findings on improving cognition or symptoms. Meta-analyses of tDCS studies targeting mostly the dorsolateral prefrontal cortex show small effects on cognitive improvements with only two out of three studies showing clinical improvements. Trigeminal nerve stimulation has been shown to improve ADHD symptoms with medium effect in one RCT. Modern neurotherapeutics are attractive due to their relative safety and potential neuroplastic effects. However, they need to be thoroughly tested for clinical and cognitive efficacy across settings and beyond core symptoms and for their potential for individualised treatment.
Neurofeedback of Alpha Activity on Memory in Healthy Participants: A Systematic Review and Meta-Analysis
Background: Neurofeedback training (NFT) has recently been proposed as a valuable technique for cognitive enhancement and psychiatric amelioration. However, effect of NFT of alpha activity on memory is controversial. The current study analyzed previous works in terms of randomized and blinded analyses, training paradigms, and participant characteristics to validate the efficacy of alpha NFT on memory in a healthy population. Objectives: A systematic meta-analysis of studies with randomized controlled trials was performed to explore the effect of alpha NFT on working memory (WM) and episodic memory (EM) in a healthy population. Methods: We searched PubMed, Embase, and Cochrane Library from January 1, 1999, to November 30, 2019. Previous studies were evaluated with the Cochrane risk of bias (RoB). A meta-analysis calculating absolute weighted standardized mean difference (SMD) using random-effects models was employed. Heterogeneity was estimated using I 2 statistics. Funnel plots and Egger's test were performed to evaluate the quality of evidence. Results: Sixteen studies with 217 healthy participants in the control group and 210 participants in the alpha group met the eligibility criteria. Alpha NFT studies with WM measures presented little publication bias ( P = 0.116), and 5 of 7 domains in the Cochrane RoB exhibited a low risk of bias. The overall effect size from 14 WM studies was 0.56 (95% CI 0.31–0.81, P < 0.0001; I 2 = 28%). Six EM studies exhibited an effect size of 0.77 (95% CI 0.06–1.49, P = 0.03; I 2 = 77%). Conclusion: Meta-analysis results suggest that alpha NFT seems to have a positive effect on the WM and EM of healthy participants. Future efforts should focus on the neurophysiological mechanisms of alpha NFT in memory.
View Full Paper →Balancing the brain of offenders with psychopathy? Resting state EEG and electrodermal activity after a pilot study of brain self-regulation training
Although investigation of the brains of criminals began quite early in the history of psychophysiological research, little is known about brain plasticity of offenders with psychopathy. Building on our preliminary study reporting successful brain self-regulation using slow cortical potential (SCP) neurofeedback in offenders with psychopathy, we investigated the central nervous and autonomic peripheral changes occurring after brain self-regulation in a group of severe male offenders with psychopathy. Regarding the central nervous system, an overall suppression of the psychopathic overrepresentation of slow frequency bands was found, such as delta and theta band activity, after EEG neurofeedback. In addition, an increase in alpha band activity could be observed after the SCP self-regulation training. Electrodermal activity adaptively changed according to the regulation task, and this flexibility improved over training time. The results of this study point towards a constructive learning process and plasticity in neural and peripheral measures of offenders with psychopathy.
View Full Paper →Enhancing learning in a perceptual-cognitive training paradigm using EEG-neurofeedback
This paper provides the framework and supporting evidence for a highly efficient closed-loop paradigm that modifies a classic learning scenario using real-time brain activity in order to improve learning performance in a perceptual-cognitive training paradigm known as 3-dimensional multiple object tracking, or 3D-MOT. Results demonstrate that, over 10 sessions, when manipulating this novel task by using real-time brain signals, speed and degree of learning can be substantially improved compared with a classic learning system or an active sham-control group. Superior performance persists even once the feedback signal is removed, which suggests that the effects of enhanced training are consolidated and do not rely on continued feedback. This type of learning paradigm could contribute to overcoming one of the fundamental limitations of neurofeedback and other cognitive enhancement techniques, a lack of observable transfer effects, by utilizing a method that can be directly integrated into the context in which improved performance is sought.
View Full Paper →Mobile Neurofeedback for Pain Management in Veterans with TBI and PTSD
OBJECTIVE: Chronic pain is common in military veterans with traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Neurofeedback, or electroencephalograph (EEG) biofeedback, has been associated with lower pain but requires frequent travel to a clinic. The current study examined feasibility and explored effectiveness of neurofeedback delivered with a portable EEG headset linked to an application on a mobile device. DESIGN: Open-label, single-arm clinical trial. SETTING: Home, outside of clinic. SUBJECTS: N = 41 veterans with chronic pain, TBI, and PTSD. METHOD: Veterans were instructed to perform "mobile neurofeedback" on their own for three months. Clinical research staff conducted two home visits and two phone calls to provide technical assistance and troubleshoot difficulties. RESULTS: N = 36 veterans returned for follow-up at three months (88% retention). During this time, subjects completed a mean of 33.09 neurofeedback sessions (10 minutes each). Analyses revealed that veterans reported lower pain intensity, pain interference, depression, PTSD symptoms, anger, sleep disturbance, and suicidal ideation after the three-month intervention compared with baseline. Comparing pain ratings before and after individual neurofeedback sessions, veterans reported reduced pain intensity 67% of the time immediately following mobile neurofeedback. There were no serious adverse events reported. CONCLUSIONS: This preliminary study found that veterans with chronic pain, TBI, and PTSD were able to use neurofeedback with mobile devices independently after modest training and support. While a double-blind randomized controlled trial is needed for confirmation, the results show promise of a portable, technology-based neuromodulatory approach for pain management with minimal side effects.
View Full Paper →Training negative connectivity patterns between the dorsolateral prefrontal cortex and amygdala through fMRI-based neurofeedback to target adolescent socially-avoidant behaviour
Social anxiety is prevalent in adolescence. Given its role in maintaining fears, reducing social avoidance through cognitive reappraisal may help attenuate social anxiety. We used fMRI-based neurofeedback (NF) to increase 'adaptive' patterns of negative connectivity between the dorsolateral prefrontal cortex (DLPFC) and the amygdala to change reappraisal ability, and alter social avoidance and approach behaviours in adolescents. Twenty-seven female participants aged 13-17 years with varying social anxiety levels completed a fMRI-based NF training task where they practiced cognitive reappraisal strategies, whilst receiving real-time feedback of DLPFC-amygdala connectivity. All participants completed measures of cognitive reappraisal and social approach-avoidance behaviour before and after NF training. Avoidance of happy faces was associated with greater social anxiety pre-training. Participants who were unable to acquire a more negative pattern of connectivity through NF training displayed significantly greater avoidance of happy faces at post-training compared to pre-training. These 'maladaptive' participants also reported significant decreases in re-appraisal ability from pre to post-training. In contrast, those who were able to acquire a more 'adaptive' connectivity pattern did not show these changes in social avoidance and re-appraisal. Future research could consider using strategies to improve the capacity of NF training to boost youth social-approach behaviour.
View Full Paper →Linking alpha oscillations, attention and inhibitory control in adult ADHD with EEG neurofeedback
Abnormal patterns of electrical oscillatory activity have been repeatedly described in adult ADHD. In particular, the alpha rhythm (8-12 Hz), known to be modulated during attention, has previously been considered as candidate biomarker for ADHD. In the present study, we asked adult ADHD patients to self-regulate their own alpha rhythm using neurofeedback (NFB), in order to examine the modulation of alpha oscillations on attentional performance and brain plasticity. Twenty-five adult ADHD patients and 22 healthy controls underwent a 64-channel EEG-recording at resting-state and during a Go/NoGo task, before and after a 30 min-NFB session designed to reduce (desynchronize) the power of the alpha rhythm. Alpha power was compared across conditions and groups, and the effects of NFB were statistically assessed by comparing behavioral and EEG measures pre-to-post NFB. Firstly, we found that relative alpha power was attenuated in our ADHD cohort compared to control subjects at baseline and across experimental conditions, suggesting a signature of cortical hyper-activation. Both groups demonstrated a significant and targeted reduction of alpha power during NFB. Interestingly, we observed a post-NFB increase in resting-state alpha (i.e. rebound) in the ADHD group, which restored alpha power towards levels of the normal population. Importantly, the degree of post-NFB alpha normalization during the Go/NoGo task correlated with individual improvements in motor inhibition (i.e. reduced commission errors) only in the ADHD group. Overall, our findings offer novel supporting evidence implicating alpha oscillations in inhibitory control, as well as their potential role in the homeostatic regulation of cortical excitatory/inhibitory balance.
View Full Paper →Emotion self-regulation training in major depressive disorder using simultaneous real-time fMRI and EEG neurofeedback
Simultaneous real-time fMRI and EEG neurofeedback (rtfMRI-EEG-nf) is an emerging neuromodulation approach, that enables simultaneous volitional regulation of both hemodynamic (BOLD fMRI) and electrophysiological (EEG) brain activities. Here we report the first application of rtfMRI-EEG-nf for emotion self-regulation training in patients with major depressive disorder (MDD). In this proof-of-concept study, MDD patients in the experimental group (n = 16) used rtfMRI-EEG-nf during a happy emotion induction task to simultaneously upregulate two fMRI and two EEG activity measures relevant to MDD. The target measures included BOLD activities of the left amygdala (LA) and left rostral anterior cingulate cortex (rACC), and frontal EEG asymmetries in the alpha band (FAA, [7.5-12.5] Hz) and high-beta band (FBA, [21-30] Hz). MDD patients in the control group (n = 8) were provided with sham feedback signals. An advanced procedure for improved real-time EEG-fMRI artifact correction was implemented. The experimental group participants demonstrated significant upregulation of the LA BOLD activity, FAA, and FBA during the rtfMRI-EEG-nf task, as well as significant enhancement in fMRI connectivity between the LA and left rACC. Average individual FAA changes during the rtfMRI-EEG-nf task positively correlated with depression and anhedonia severities, and negatively correlated with after-vs-before changes in depressed mood ratings. Temporal correlations between the FAA and FBA time courses and the LA BOLD activity were significantly enhanced during the rtfMRI-EEG-nf task. The experimental group participants reported significant mood improvements after the training. Our results suggest that the rtfMRI-EEG-nf may have potential for treatment of MDD.
View Full Paper →Pain Control by Co-adaptive Learning in a Brain-Machine Interface
Innovation in the field of brain-machine interfacing offers a new approach to managing human pain. In principle, it should be possible to use brain activity to directly control a therapeutic intervention in an interactive, closed-loop manner. But this raises the question as to whether the brain activity changes as a function of this interaction. Here, we used real-time decoded functional MRI responses from the insula cortex as input into a closed-loop control system aimed at reducing pain and looked for co-adaptive neural and behavioral changes. As subjects engaged in active cognitive strategies orientated toward the control system, such as trying to enhance their brain activity, pain encoding in the insula was paradoxically degraded. From a mechanistic perspective, we found that cognitive engagement was accompanied by activation of the endogenous pain modulation system, manifested by the attentional modulation of pain ratings and enhanced pain responses in pregenual anterior cingulate cortex and periaqueductal gray. Further behavioral evidence of endogenous modulation was confirmed in a second experiment using an EEG-based closed-loop system. Overall, the results show that implementing brain-machine control systems for pain induces a parallel set of co-adaptive changes in the brain, and this can interfere with the brain signals and behavior under control. More generally, this illustrates a fundamental challenge of brain decoding applications-that the brain inherently adapts to being decoded, especially as a result of cognitive processes related to learning and cooperation. Understanding the nature of these co-adaptive processes informs strategies to mitigate or exploit them.
View Full Paper →Using connectivity-based real-time fMRI neurofeedback to modulate attentional and resting state networks in people with high trait anxiety
High levels of trait anxiety are associated with impaired attentional control, changes in brain activity during attentional control tasks and altered network resting state functional connectivity (RSFC). Specifically, dorsolateral prefrontal cortex to anterior cingulate cortex (DLPFC - ACC) functional connectivity, thought to be crucial for effective and efficient attentional control, is reduced in high trait anxious individuals. The current study examined the potential of connectivity-based real-time functional magnetic imaging neurofeedback (rt-fMRI-nf) for enhancing DLPFC - ACC functional connectivity in trait anxious individuals. We specifically tested if changes in DLPFC - ACC connectivity were associated with reduced anxiety levels and improved attentional control. Thirty-two high trait anxious participants were assigned to either an experimental group (EG), undergoing veridical rt-fMRI-nf, or a control group (CG) that received sham (yoked) feedback. RSFC (using resting state fMRI), anxiety levels and Stroop task performance were assessed pre- and post-rt-fMRI-nf training. Post-rt-fMRI-nf training, relative to the CG, the EG showed reduced anxiety levels and increased DLPFC-ACC functional connectivity as well as increased RSFC in the posterior default mode network. Moreover, in the EG, changes in DLPFC - ACC functional connectivity during rt-fMRI-nf training were associated with reduced anxiety levels. However, there were no group differences in Stroop task performance. We conclude that rt-fMRI-nf targeting DLPFC - ACC functional connectivity can alter network connectivity and interactions and is a feasible method for reducing trait anxiety.
View Full Paper →Connectome-wide search for functional connectivity locus associated with pathological rumination as a target for real-time fMRI neurofeedback intervention
Real-time fMRI neurofeedback (rtfMRI-nf) enables noninvasive targeted intervention in brain activation with high spatial specificity. To achieve this promise of rtfMRI-nf, we introduced and demonstrated a data-driven framework to design a rtfMRI-nf intervention through the discovery of precise target location associated with clinical symptoms and neurofeedback signal optimization. Specifically, we identified the functional connectivity locus associated with rumination symptoms, utilizing a connectome-wide search in resting-state fMRI data from a large cohort of mood and anxiety disorder individuals (N = 223) and healthy controls (N = 45). Then, we performed a rtfMRI simulation analysis to optimize the online functional connectivity neurofeedback signal for the identified functional connectivity. The connectome-wide search was performed in the medial prefrontal cortex and the posterior cingulate cortex/precuneus brain regions to identify the precise location of the functional connectivity associated with rumination severity as measured by the ruminative response style (RRS) scale. The analysis found that the functional connectivity between the loci in the precuneus (-6, −54, 48 mm in MNI) and the right temporo-parietal junction (RTPJ; 49, −49, 23 mm) was positively correlated with RRS scores (depressive, p < 0.001; brooding, p < 0.001; reflective, p = 0.002) in the mood and anxiety disorder group. We then performed a rtfMRI processing simulation to optimize the online computation of the precuneus-RTPJ connectivity. We determined that the two-point method without a control region was appropriate as a functional connectivity neurofeedback signal with less dependence on signal history and its accommodation of head motion. The present study offers a discovery framework for the precise location of functional connectivity targets for rtfMRI-nf intervention, which could help directly translate neuroimaging findings into clinical rtfMRI-nf interventions.
View Full Paper →Neural mechanisms of persistent avoidance in OCD: A novel avoidance devaluation study
Obsessive-Compulsive Disorder (OCD) is characterized by repetitive avoidance behavior which is distressing and associated with marked impairment of everyday life. Recently, paradigms have been designed to explore the hypothesis that avoidance behavior in OCD is consistent with a formal conception of habit. Such studies have involved a devaluation paradigm, in which the value of a previously rewarded cue is altered so that avoidance is no longer necessary. We employed a rule-based avoidance task which included a devaluation, examining behavioral performance on the task and their neural correlates using functional MRI in groups of participants with OCD (n = 44) and healthy control participants (n = 46). Neuroimaging data were analyzed using a general linear model (GLM), modelling valued, devalued and control cues, as well as feedback events. First, while no overall effect of OCD was seen on devaluation performance, patients with longer illness duration showed poorer devaluation performance (χ2 = 13.84, p < 0.001). Reduced devaluation was related to impaired learning on the overtraining phase of the task, and to enhanced feedback activation in the caudate and parietal lobe during within-scanner retraining (T = 5.52, p_FWE = 0.003), across all participants. Second, a significant interaction effect was observed in the premotor cortex (F = 29.03, p_FWE = 0.007) coupled to the devalued cue. Activations were divergent in participants with OCD (lower activation) and healthy controls (higher activation) who did not change responding to the devalued cue following devaluation, and intermediate in participants who did change responding (T = 5.39, p_FWE = 0.003). Finally, consistent with previous work, medial orbitofrontal cortex activation coupled to valued cues was reduced in OCD compared to controls (T = 3.49, p_FWE = 0.009). The findings are discussed in terms of a prediction error-based model of goal-directed and habitual control: specifically, how goal-directed control might be diminished in OCD in favor of habits. They suggest that illness duration might be significant determinant of variation in impaired goal-directed learning in OCD, and be a factor relevant for understanding discrepancies across studies. Overall, the study shows the potential of conceptual replication attempts to provide complementary insights into compulsive behavior and its associated neural circuitry in OCD.
View Full Paper →Practical considerations for the evaluation and management of Attention Deficit Hyperactivity Disorder (ADHD) in adults
Attention deficit with or without hyperactivity disorder (ADHD) is one of the most frequent neuropsychiatric disorders, and affects 2-4% of adults. In contrast with many European countries, the identification and management of adult ADHD remains underdeveloped in France, and a subject of controversy. This review provides a practical update on current knowledge about ADHD in adults for French-speaking professionals who have to detect or manage adult patients with ADHD. ADHD is classified as a neurodevelopmental disorder in the recent update of the international diagnostic classification. While symptoms and impairment due to ADHD are frequently severe during childhood, they often evolve as children grow older, with frequent persistent disabilities in adulthood. In adulthood, the clinical presentation, as in childhood, involves the symptom triad of inattention, hyperactivity and impulsivity. However, differences are noted: hyperactivity is more often internalized, symptoms of inattention may be masked by anxiety symptoms or obsessive-like compensation strategies. ADHD is often diagnosed during childhood, but it is not rare for the diagnosis to be made later. Failure to recognise symptoms resulting in misdiagnosis, or alternatively well-developed compensation factors could be two underlying reasons for the long delay until diagnosis. Other symptoms, such as emotional deregulation or executive function-related symptoms are also usually observed in adults. In addition, in adults, ADHD is often associated with other psychiatric disorders (in 80% of cases); this makes the diagnosis even more difficult. These disorders encompass a broad spectrum, from mood disorders (unipolar or bipolar), to anxiety disorders, and other neurodevelopmental disorders and personality disorders, especially borderline and antisocial personality disorder. Substance-use disorders are very common, either as a consequence of impulsivity and emotional dysregulation or as an attempt at self-treatment. Sleep disorders, especially restless leg syndrome and hypersomnolence, could share common pathophysiological mechanisms with ADHD. ADHD and comorbidity-related symptoms are responsible for serious functional impairment, in various domains, leading to academic, social, vocational, and familial consequences. The impact on other psychiatric disorders as an aggravating factor should also be considered. The considerable disability and the poorer quality of life among adults with ADHD warrant optimal evaluation and management. The diagnostic procedure for ADHD among adults should be systematic. Once the positive diagnosis is made, the evaluation enables characterisation of the levels of severity and impairment at individual level. A full examination should also assess medical conditions associated with ADHD, to provide personalized care. In recent years, a growing number of assessment tools have been translated and validated in French providing a wide range of structured interviews and standardized self-report questionnaires for the evaluation of core and associated ADHD symptoms, comorbidities and functional impairment. The treatment of ADHD in adults is multimodal, and aims to relieve the symptoms, limit the burden of the disease, and manage comorbidities. The most relevant and validated psychological approaches are psycho-education, cognitive-behavioural therapy and "third wave therapies" with a specific focus on emotional regulation. Cognitive remediation and neurofeedback are promising strategies still under evaluation. Medications, especially psychostimulants, are effective for alleviating ADHD symptoms with a large effect size. Their safety and tolerance are satisfactory, although their long-term clinical benefit is still under discussion. In France, methylphenidate is the only stimulant available for the treatment of ADHD. Unfortunately, there is no authorization for its use among adults except in continuation after adolescence. Hence the prescription, which is subject to the regulations on narcotics, is off-label in France. This article aims to provide practical considerations for the management of ADHD and associated disorders in adults, in this particular French context.
View Full Paper →Train Your Brain? Can We Really Selectively Train Specific EEG Frequencies With Neurofeedback Training
Neurofeedback (NFB) is an operant conditioning procedure whereby an individual learns to self-regulate the electrical activity of his/her brain. Initially developed as a treatment intervention for pathologies with underlying EEG dysfunctions, NFB is also used as a training tool to enhance specific cognitive states required in high-performance situations. The original idea behind the NFB training effect is that the changes should only be circumscribed to the trained EEG frequencies. The EEG frequencies which are not used as feedback frequencies should be independent and not affected by the neurofeedback training. Despite the success of sensorimotor rhythm NFB training in cognitive performance enhancement, it remains unclear whether all participants can intentionally modify the power densities of specifically selected electroencephalographic (EEG) frequencies. In the present study, participants were randomly assigned to either a control heart rate variability (HRV) biofeedback (HRV) training group or a combination of HRV biofeedback and neurofeedback (HRV/NFB) training group. This randomized mixed design experiment consisted of two introductory theoretical lessons and a training period of 6 weeks. We investigated the evolution of the different EEG frequency bands of our two experimental groups across and within session. All the participants exhibited EEG changes across and within session. However, within the HRV/NFB training group, untrained EEG frequencies have been significantly modified, unlike some of the trained frequencies. Moreover, EEG activity was modified in both the HRV group and the HRV/NFB groups. Hence, the EEG changes were not only circumscribed to the trained frequency bands or to the training modality.
View Full Paper →A systematic review of fMRI neurofeedback reporting and effects in clinical populations
Real-time fMRI-based neurofeedback is a relatively young field with a potential to impact the currently available treatments of various disorders. In order to evaluate the evidence of clinical benefits and investigate how consistently studies report their methods and results, an exhaustive search of fMRI neurofeedback studies in clinical populations was performed. Reporting was evaluated using a limited number of Consensus on the reporting and experimental design of clinical and cognitive-behavioral neurofeedback studies (CRED-NF checklist) items, which was, together with a statistical power and sensitivity calculation, used to also evaluate the existing evidence of the neurofeedback benefits on clinical measures. The 62 found studies investigated regulation abilities and/or clinical benefits in a wide range of disorders, but with small sample sizes and were therefore unable to detect small effects. Most points from the CRED-NF checklist were adequately reported by the majority of the studies, but some improvements are suggested for the reporting of group comparisons and relations between regulation success and clinical benefits. To establish fMRI neurofeedback as a clinical tool, more emphasis should be placed in the future on using larger sample sizes determined through a priori power calculations and standardization of procedures and reporting.
View Full Paper →Non-Pharmacological Management of Painful Peripheral Neuropathies: A Systematic Review
INTRODUCTION: Peripheral neuropathic pain (PNP) is defined as the neuropathic pain that arises either acutely or in the chronic phase of a lesion or disease affecting the peripheral nervous system. PNP is associated with a remarkable disease burden, and there is an increasing demand for new therapies to be used in isolation or combination with currently available treatments. The aim of this systematic review was to evaluate the current evidence, derived from randomized controlled trials (RCTs) that assess non-pharmacological interventions for the treatment of PNP. METHODS: After a systematic Medline search, we identified 18 papers eligible to be included. RESULTS: The currently best available evidence (level II of evidence) exist for painful diabetic peripheral neuropathy. In particular, spinal cord stimulation as adjuvant to conventional medical treatment can be effectively used for the management of patients with refractory pain. Similarly, adjuvant repetitive transcranial magnetic stimulation of the motor cortex is effective in reducing the overall pain intensity, whereas adjuvant static magnetic field therapy can lead to a significant decrease in exercise-induced pain. Weaker evidence (level III of evidence) exists for the use of acupuncture as a monotherapy and neurofeedback, either as an add-on or a monotherapy approach, for treatment of painful chemotherapy-induced peripheral neuropathy CONCLUSIONS: Future RCTs should be conducted to shed more light in the use of non-pharmacological approaches in patients with PNP.
View Full Paper →Effects of neurofeedback in the management of chronic pain: A systematic review and meta-analysis of clinical trials
BACKGROUND AND OBJECTIVE: Neurofeedback (NFB) provides real-time feedback about neurophysiological signals to patients, thereby encouraging modulation of pain-associated brain activity. This review aims to evaluate the effectiveness and safety of NFB in alleviating pain and pain-associated symptoms in chronic pain patients. METHODS: MEDLINE, PUBMED, Web of Science and PsycINFO databases were searched using the strategy: ("Neurofeedback" OR "EEG Biofeedback" OR "fMRI Biofeedback") AND ("Pain" or "Chronic Pain"). Clinical trials reporting changes in pain following electroencephalogram (EEG) or functional magnetic resonance imaging (fMRI) NFB in chronic pain patients were included. Only Randomized-controlled trials (RCT), non-randomized controlled trials (NRCT) and case series were included. Effect size was pooled for all RCTs in a meta-analysis. RESULTS: Twenty-one studies were included. Reduction in pain following NFB was reported by one high-quality RCT, five of six low-quality RCT or NRCT and 13 of 14 case-series. Pain reduction reported by studies ranged from 6% to 82%, with 10 studies reporting a clinically significant reduction in pain of >30%. The overall effect size was medium (cohen's d -0.76, 95% confidence interval -1.31 to -0.20). Studies were highly heterogeneous (Q [df = 5] = 18.46, p = .002, I2 = 73%). Improvements in depression, anxiety, fatigue and sleep were also seen in some studies. Common side-effects included headache, nausea and drowsiness. These generally did not lead to withdrawal of therapy except in one study. CONCLUSIONS: Neurofeedback is a safe and effective therapy with promising but largely low-quality evidence supporting its use in chronic pain. Further high-quality trials comparing different protocols is warranted to determine the most efficacious way to deliver NFB. SIGNIFICANCE: Neurofeedback is a novel neuromodulatory approach which can be used to reduce the severity of pain and pain-associated symptoms such as sleep disturbances, mood disturbances, fatigue and anxiety in a number of chronic pain conditions. It has a potential to provide integrative non-pharmacological management for chronic pain patients with pain refractory to pharmacological agents with high side-effect profiles. Further high-quality double-blinded randomized sham-controlled trials are needed in order to fully explore the potential of this therapy.
View Full Paper →Just a very expensive breathing training? Risk of respiratory artefacts in functional connectivity-based real-time fMRI neurofeedback
Real-time functional magnetic resonance imaging neurofeedback (rtfMRI NFB) is a promising method for targeted regulation of pathological brain processes in mental disorders. But most NFB approaches so far have used relatively restricted regional activation as a target, which might not address the complexity of the underlying network changes. Aiming towards advancing novel treatment tools for disorders like schizophrenia, we developed a large-scale network functional connectivity-based rtfMRI NFB approach targeting dorsolateral prefrontal cortex and anterior cingulate cortex connectivity with the striatum. In a double-blind randomized yoke-controlled single-session feasibility study with N = 38 healthy controls, we identified strong associations between our connectivity estimates and physiological parameters reflecting the rate and regularity of breathing. These undesired artefacts are especially detrimental in rtfMRI NFB, where the same data serves as an online feedback signal and offline analysis target. To evaluate ways to control for the identified respiratory artefacts, we compared model-based physiological nuisance regression and global signal regression (GSR) and found that GSR was the most effective method in our data. Our results strongly emphasize the need to control for physiological artefacts in connectivity-based rtfMRI NFB approaches and suggest that GSR might be a useful method for online data correction for respiratory artefacts.
View Full Paper →Randomized, Sham-Controlled Trial of Real-Time Functional Magnetic Resonance Imaging Neurofeedback for Tics in Adolescents With Tourette Syndrome
BACKGROUND: Activity in the supplementary motor area (SMA) has been associated with tics in Tourette syndrome (TS). The aim of this study was to test a novel intervention-real-time functional magnetic resonance imaging neurofeedback from the SMA-for reduction of tics in adolescents with TS. METHODS: Twenty-one adolescents with TS were enrolled in a double-blind, randomized, sham-controlled, crossover study involving two sessions of neurofeedback from their SMA. The primary outcome measure of tic severity was the Yale Global Tic Severity Scale administered by an independent evaluator before and after each arm. The secondary outcome was control over the SMA assessed in neuroimaging scans, in which subjects were cued to increase/decrease activity in SMA without receiving feedback. RESULTS: All 21 subjects completed both arms of the study and all assessments. Participants had significantly greater reduction of tics on the Yale Global Tic Severity Scale after real neurofeedback as compared with the sham control (p < .05). Mean Yale Global Tic Severity Scale Total Tic score decreased from 25.2 ± 4.6 at baseline to 19.9 ± 5.7 at end point in the neurofeedback condition and from 24.8 ± 8.1 to 23.3 ± 8.5 in the sham control condition. The 3.8-point difference is clinically meaningful and corresponds to an effect size of 0.59. However, there were no differences in changes on the secondary measure of control over the SMA. CONCLUSIONS: This first randomized controlled trial of real-time functional magnetic resonance imaging neurofeedback in adolescents with TS suggests that this neurofeedback intervention may be helpful for improving tic symptoms. However, no effects were found in terms of change in control over the SMA, the hypothesized mechanism of action.
View Full Paper →Real-Time Functional Magnetic Resonance Imaging Neurofeedback for the Relief of Distressing Auditory-Verbal Hallucinations: Methodological and Empirical Advances
Auditory-verbal hallucinations (AVH) are often associated with high levels of distress and disability in individuals with schizophrenia-spectrum disorders. In around 30% of individuals with distressing AVH and diagnosed with schizophrenia, traditional antipsychotic drugs have little or no effect. Thus, it is important to develop mechanistic models of AVH to inform new treatments. Recently a small number of studies have begun to explore the use of real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) for the treatment of AVH in individuals with schizophrenia. rtfMRI-NF protocols have been developed to provide feedback about brain activation in real time to enable participants to progressively achieve voluntary control over their brain activity. We offer a conceptual review of the background and general features of neurofeedback procedures before summarizing and evaluating existing mechanistic models of AVH to identify feasible neural targets for the application of rtfMRI-NF as a potential treatment. We consider methodological issues, including the choice of localizers and practicalities in logistics when setting up neurofeedback procedures in a clinical setting. We discuss clinical considerations relating to the use of rtfMRI-NF for AVH in individuals distressed by their experiences and put forward a number of questions and recommendations about best practice. Lastly, we conclude by offering suggestions for new avenues for neurofeedback methodology and mechanistic targets in relation to the research and treatment of AVH.
View Full Paper →Subthalamic beta-targeted neurofeedback speeds up movement initiation but increases tremor in Parkinsonian patients
Previous studies have explored neurofeedback training for Parkinsonian patients to suppress beta oscillations in the subthalamic nucleus (STN). However, its impacts on movements and Parkinsonian tremor are unclear. We developed a neurofeedback paradigm targeting STN beta bursts and investigated whether neurofeedback training could improve motor initiation in Parkinson's disease compared to passive observation. Our task additionally allowed us to test which endogenous changes in oscillatory STN activities are associated with trial-to-trial motor performance. Neurofeedback training reduced beta synchrony and increased gamma activity within the STN, and reduced beta band coupling between the STN and motor cortex. These changes were accompanied by reduced reaction times in subsequently cued movements. However, in Parkinsonian patients with pre-existing symptoms of tremor, successful volitional beta suppression was associated with an amplification of tremor which correlated with theta band activity in STN local field potentials, suggesting an additional cross-frequency interaction between STN beta and theta activities.
View Full Paper →Real-time fMRI neurofeedback reduces auditory hallucinations and modulates resting state connectivity of involved brain regions: Part 2: Default mode network -preliminary evidence
Auditory hallucinations (AHs) are one of the most distressing symptoms of schizophrenia (SZ) and are often resistant to medication. Imaging studies of individuals with SZ show hyperactivation of the default mode network (DMN) and the superior temporal gyrus (STG). Studies in SZ show DMN hyperconnectivity and reduced anticorrelation between DMN and the central executive network (CEN). DMN hyperconnectivity has been associated with positive symptoms such as AHs while reduced DMN anticorrelations with cognitive impairment. Using real-time fMRI neurofeedback (rt-fMRI-NFB) we trained SZ patients to modulate DMN and CEN networks. Meditation is effective in reducing AHs in SZ and to modulate brain network integration and increase DMN anticorrelations. Consequently, patients were provided with meditation strategies to enhance their abilities to modulate DMN/CEN. Results show a reduction of DMN hyperconnectivity and increase in DMNCEN anticorrelation. Furthermore, the change in individual DMN connectivity significantly correlated with reductions in AHs. This is the first time that meditation enhanced through rt-fMRI-NFB is used to reduce AHs in SZ. Moreover, it provides the first empirical evidence for a direct causal relation between meditation enhanced rt-fMRI-NFB modulation of DMNCEN activity and post-intervention modulation of resting state networks ensuing in reductions in frequency and severity of AHs.
View Full Paper →Improving episodic memory: Frontal-midline theta neurofeedback training increases source memory performance
Cognitive and neurofeedback training (NFT) studies have demonstrated that training-induced alterations of frontal-midline (FM) theta activity (4-8 Hz) transfer to cognitive control processes. Given that FM theta oscillations are assumed to provide top-down control for episodic memory retrieval, especially for source retrieval, that is, accurate recollection of contextual details of prior episodes, the present study investigated whether FM theta NFT transfers to memory control processes. It was assessed (1) whether FM theta NFT improves source retrieval and modulates its underlying EEG characteristics and (2) whether this transfer extends over two posttests. Over seven NFT sessions, the training group who trained individual FM theta activity showed greater FM theta increase than an active control group who trained randomly chosen frequency bands. The training group showed better source retrieval in a posttraining session performed 13 days after NFT and their performance increases from pre- to both posttraining sessions were predicted by NFT theta increases. Thus, training-induced enhancement of memory control processes seems to protect newly formed memories from proactive interference of previously learned information. EEG analyses revealed that during pretest both groups showed source memory specific theta activity at frontal and parietal sites. Surprisingly, training-induced improvements in source retrieval tended to be accompanied by less prestimulus FM theta activity, which was predicted by NFT theta change for the training but not the control group, suggesting a more efficient use of memory control processes after training. The present findings provide unique evidence for the enhancement of memory control processes by FM theta NFT.
View Full Paper →Modulatory effects of dynamic fMRI-based neurofeedback on emotion regulation networks in adolescent females
Research has shown that difficulties with emotion regulation abilities in childhood and adolescence increase the risk for developing symptoms of mental disorders, e.g anxiety. We investigated whether functional magnetic resonance imaging (fMRI)-based neurofeedback (NF) can modulate brain networks supporting emotion regulation abilities in adolescent females. We performed three experiments (Experiment 1: N = 18; Experiment 2: N = 30; Experiment 3: N = 20). We first compared different NF implementations regarding their effectiveness of modulating prefrontal cortex (PFC)-amygdala functional connectivity (fc). Further we assessed the effects of fc-NF on neural measures, emotional/metacognitive measures and their associations. Finally, we probed the mechanism underlying fc-NF by examining concentrations of inhibitory and excitatory neurotransmitters. Results showed that NF implementations differentially modulate PFC-amygdala fc. Using the most effective NF implementation we observed important relationships between neural and emotional/metacognitive measures, such as practice-related change in fc was related with change in thought control ability. Further, we found that the relationship between state anxiety prior to the MRI session and the effect of fc-NF was moderated by GABA concentrations in the PFC and anterior cingulate cortex. To conclude, we were able to show that fc-NF can be used in adolescent females to shape neural and emotional/metacognitive measures underlying emotion regulation. We further show that neurotransmitter concentrations moderate fc-NF-effects.
View Full Paper →Neurofeedback Training for Social Cognitive Deficits: A Systematic Review
<p><strong>Orndorff and his colleagues [1]</strong> suggested that if a neural activity is considered a treatment variable instead of outcome, it widens the scope of research and has a specific implication for social neuroscience. Given this, the empirical evidence is collected and analyzed where neural activity as self-manipulation design through neurofeedback training specifically for social cognition deficit is done. The objective of the present article is to provide a systematic review of 1) how NFT is utilized to treat social cognitive deficits, 2) how NFT is utilized to target Social Cognition Deficit in ASD, 3) examining the directions, strengths, and quality of evidence to support the use of NFT for ASD. The databases for studies were searched in PubMed, MEDLINE, EMBASE, Springer, Science Direct, Psychinfo, and Google Scholar, using combinations of the following keywords: ‘Neurofeedback,’ ‘Autism Spectrum Disorder,’ ‘Mu Rhythm’ and ‘Social Cognition.’ Studies were eligible for inclusion if they were specific to 1) autistic and typically developed population, 2) intervention study, 3) Delivered by NFT, 4) participants showed social cognitive deficit and/or improvement. Total one eighty-seven studies were found of key interest; out of which 17 studies were eligible for inclusion in this review. All studies reported the improvement in different domains of social cognition and were moderately methodologically sound. Eleven out of seventeen studies satisfied the trainability and interpretability criteria suggested by <strong>Zoefel and his colleagues [2].</strong> The conclusion from the present review is in line with comments of <strong>Marzbani and colleagues [3]</strong> that, ‘current research does not provide sufficient conclusive results about its efficacy.’ The patterns and directions concluded from studies related to protocol, methodology and results are discussed in detail in the present review.</p>
View Full Paper →Neurofeedback-Linked Suppression of Cortical β Bursts Speeds Up Movement Initiation in Healthy Motor Control: A Double-Blind Sham-Controlled Study
Abnormally increased β bursts in cortical-basal ganglia-thalamic circuits are associated with rigidity and bradykinesia in patients with Parkinson's disease. Increased β bursts detected in the motor cortex have also been associated with longer reaction times (RTs) in healthy participants. Here we further hypothesize that suppressing β bursts through neurofeedback training can improve motor performance in healthy subjects. We conducted a double-blind sham-controlled study on 20 human volunteers (10 females) using a sequential neurofeedback-behavior task with the neurofeedback reflecting the occurrence of β bursts over sensorimotor cortex quantified in real time. The results show that neurofeedback training helps healthy participants learn to volitionally suppress β bursts in the sensorimotor cortex, with training being accompanied by reduced RT in subsequent cued movements. These changes were only significant in the real feedback group but not in the sham group, confirming the effect of neurofeedback training over simple motor imagery. In addition, RTs correlated with the rate and accumulated duration of β bursts in the contralateral motor cortex before the go-cue, but not with averaged β power. The reduced RTs induced by neurofeedback training positively correlated with reduced β bursts across all tested hemispheres. These results strengthen the link between the occurrence of β bursts in the sensorimotor cortex before the go-cue and slowed movement initiation in healthy motor control. The results also highlight the potential benefit of neurofeedback training in facilitating voluntary suppression of β bursts to speed up movement initiation.SIGNIFICANCE STATEMENT This double-blind sham-controlled study suggested that neurofeedback training can facilitate volitional suppression of β bursts in sensorimotor cortex in healthy motor control better than sham feedback. The training was accompanied by reduced reaction time (RT) in subsequent cued movements, and the reduced RT positively correlated with the level of reduction in cortical β bursts before the go-cue, but not with average β power. These results provide further evidence of a causal link between sensorimotor β bursts and movement initiation and suggest that neurofeedback training could potentially be used to train participants to speed up movement initiation.
View Full Paper →An Integrative Model for the Effectiveness of Biofeedback Interventions for Anxiety Regulation: Viewpoint
Biofeedback has shown to be a promising tool for the treatment of anxiety; however, several theoretical as well as practical limitations have prevented widespread adaptation until now. With current technological advances and the increasing interest in the use of self-monitoring technology to improve mental health, we argue that this is an ideal time to launch a new wave of biofeedback training. In this viewpoint paper, we reflect on the current state of biofeedback training, including the more traditional techniques and mechanisms that have been thought to explain the effectiveness of biofeedback such as the integration of operant learning and meditation techniques, and the changes in interoceptive awareness and physiology. Subsequently, we propose an integrative model that includes a set of cognitive appraisals as potential determinants of adaptive trajectories within biofeedback training such as growth mindset, self-efficacy, locus of control, and threat-challenge appraisals. Finally, we present a set of detailed guidelines based on the integration of our model with the mechanics and mechanisms offered by emerging interactive technology to encourage a new phase of research and implementation using biofeedback. There is a great deal of promise for future biofeedback interventions that harness the power of wearables and video games, and that adopt a user-centered approach to help people regulate their anxiety in a way that feels engaging, personal, and meaningful.
View Full Paper →The NeMo real-time fMRI neurofeedback study: protocol of a randomised controlled clinical intervention trial in the neural foundations of mother-infant bonding
INTRODUCTION: Most mothers feel an immediate, strong emotional bond with their newborn. On a neurobiological level, this is accompanied with the activation of the brain reward systems, including the striatum. However, approximately 10% of all mothers report difficulties to bond emotionally with their infant and display impaired reward responses to the interaction with their infant which might have long-term negative effects for the child's development. As previous studies suggest that activation of the striatal reward system can be regulated through functional MRI (fMRI)-based neurofeedback (NFB), we have designed and investigate fMRI-NFB training to treat maternal bonding difficulties. METHODS AND ANALYSIS: In the planned trial, mothers will be presented pictures of their infant and real-time fMRI (rtfMRI), peripheral measures, neural, endocrine, psychophysiological and behavioural measures will be assessed. Mothers with bonding difficulties (n=68) will be randomised to one of two double-blind intervention groups at 4-6 months postpartum. They will participate in three repeated NFB training sessions with rtfMRI-NFB training to increase activation of (a) the ventral striatum or (b) the anterior cingulate. Interview data and real-time mother-infant interaction behaviour pre-intervention, post-intervention and at follow-up will serve as clinical outcome measures. ETHICS AND DISSEMINATION: Study procedures are in line with the recommendations of the World Medical Association (revised Declaration of Helsinki) and were approved by the Ethics Committee of the Medical Faculty, s-450/2017, Heidelberg University. All participants will provide written informed consent after receiving a detailed oral and written explanation of all procedures and can withdraw their consent at any time without negative consequence. Results will be internationally published and disseminated, to further the discussion on non-pharmacological treatment options in complex mental disorders. TRIAL REGISTRATION NUMBER: DRKS00014570; Pre-results.
View Full Paper →Functional connectivity changes associated with fMRI neurofeedback of right inferior frontal cortex in adolescents with ADHD
Attention Deficit Hyperactivity Disorder (ADHD) is associated with poor self-control, underpinned by inferior fronto-striatal deficits. We showed previously that 18 ADHD adolescents over 11 runs of 8.5 min of real-time functional magnetic resonance neurofeedback of the right inferior frontal cortex (rIFC) progressively increased activation in 2 regions of the rIFC which was associated with clinical symptom improvement. In this study, we used functional connectivity analyses to investigate whether fMRI-Neurofeedback of rIFC resulted in dynamic functional connectivity changes in underlying neural networks. Whole-brain seed-based functional connectivity analyses were conducted using the two clusters showing progressively increased activation in rIFC as seed regions to test for changes in functional connectivity before and after 11 fMRI-Neurofeedback runs. Furthermore, we tested whether the resulting functional connectivity changes were associated with clinical symptom improvements and whether they were specific to fMRI-Neurofeedback of rIFC when compared to a control group who had to self-regulate another region. rIFC showed increased positive functional connectivity after relative to before fMRI-Neurofeedback with dorsal caudate and anterior cingulate and increased negative functional connectivity with regions of the default mode network (DMN) such as posterior cingulate and precuneus. Furthermore, the functional connectivity changes were correlated with clinical improvements and the functional connectivity and correlation findings were specific to the rIFC-Neurofeedback group. The findings show for the first time that fMRI-Neurofeedback of a typically dysfunctional frontal region in ADHD adolescents leads to strengthening within fronto-cingulo-striatal networks and to weakening of functional connectivity with posterior DMN regions and that this may be underlying clinical improvement.
View Full Paper →Neurofeedback Treatment of Negative Symptoms in Schizophrenia: Two Case Reports
Negative symptoms of schizophrenia, like diminished emotional expression and a dearth of self-initiated behavior do not respond reliably to anti-psychotic medication or to conventional psychotherapeutic approaches. Starting from evidence on the probable neural basis of such symptoms and on the effectiveness of neurofeedback with other psychological disorders, the present case study applied 20 sessions of EEG neurofeedback to a 45-year-old female and a 30-year-old male, both diagnosed with severe negative symptoms of schizophrenia. In both cases GAF scores were improved significantly and at the end of treatment, both patients did not meet the diagnostic criteria of negative symptomatology any longer. Symptom reduction went along with an obvious improvement of social, interpersonal, and cognitive abilities according to the clinical impression. Detailed data analysis revealed that these improvements went along with corresponding changes of EEG parameters and with distinct patterns and strategies of change in each of the two individuals. The results suggest that EEG neurofeedback should be examined on a larger scale as it offers a promising alternative to existing treatment approaches for negative symptoms in schizophrenia.
View Full Paper →Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety
BACKGROUND: Deficient emotion regulation and exaggerated anxiety represent a major transdiagnostic psychopathological marker. On the neural level these deficits have been closely linked to impaired, yet treatment-sensitive, prefrontal regulatory control over the amygdala. Gaining direct control over these pathways could therefore provide an innovative and promising intervention to regulate exaggerated anxiety. To this end the current proof-of-concept study evaluated the feasibility, functional relevance and maintenance of a novel connectivity-informed real-time fMRI neurofeedback training. METHODS: In a randomized crossover sham-controlled design, 26 healthy subjects with high anxiety underwent real-time fMRI-guided neurofeedback training to enhance connectivity between the ventrolateral prefrontal cortex (vlPFC) and the amygdala (target pathway) during threat exposure. Maintenance of regulatory control was assessed after 3 days and in the absence of feedback. Training-induced changes in functional connectivity of the target pathway and anxiety ratings served as primary outcomes. RESULTS: Training of the target, yet not the sham control, pathway significantly increased amygdala-vlPFC connectivity and decreased levels of anxiety. Stronger connectivity increases were significantly associated with higher anxiety reduction on the group level. At the follow-up, volitional control over the target pathway was maintained in the absence of feedback. CONCLUSIONS: The present results demonstrate for the first time that successful self-regulation of amygdala-prefrontal top-down regulatory circuits may represent a novel intervention to control anxiety. As such, the present findings underscore both the critical contribution of amygdala-prefrontal circuits to emotion regulation and the therapeutic potential of connectivity-informed real-time neurofeedback.
View Full Paper →The BOLD response in primary motor cortex and supplementary motor area during kinesthetic motor imagery based graded fMRI neurofeedback
There is increasing interest in exploring the use of functional MRI neurofeedback (fMRI-NF) as a therapeutic technique for a range of neurological conditions such as stroke and Parkinson's disease (PD). One main therapeutic potential of fMRI-NF is to enhance volitional control of damaged or dysfunctional neural nodes and networks via a closed-loop feedback model using mental imagery as the catalyst of self-regulation. The choice of target node/network and direction of regulation (increase or decrease activity) are central design considerations in fMRI-NF studies. Whilst it remains unclear whether the primary motor cortex (M1) can be activated during motor imagery, the supplementary motor area (SMA) has been robustly activated during motor imagery. Such differences in the regulation potential between primary and supplementary motor cortex are important because these areas can be differentially affected by a stroke or PD, and the choice of fMRI-NF target and grade of self-regulation of activity likely have substantial influence on the clinical effects and cost effectiveness of NF-based interventions. In this study we therefore investigated firstly whether healthy subjects would be able to achieve self-regulation of the hand-representation areas of M1 and the SMA using fMRI-NF training. There was a significant decrease in M1 neural activity during fMRI-NF, whereas SMA neural activity was increased, albeit not with the predicated graded effect. This study has important implications for fMRI-NF protocols that employ motor imagery to modulate activity in specific target regions of the brain and to determine how they may be tailored for neurorehabilitation.
View Full Paper →Clinical and Experimental Factors Influencing the Efficacy of Neurofeedback in ADHD: A Meta-Analysis
Meta-analyses have been extensively used to evaluate the efficacy of neurofeedback (NFB) treatment for Attention Deficit/Hyperactivity Disorder (ADHD) in children and adolescents. However, each meta-analysis published in the past decade has contradicted the methods and results from the previous one, thus making it difficult to determine a consensus of opinion on the effectiveness of NFB. This works brings continuity to the field by extending and discussing the last and much controversial meta-analysis by Cortese et al. (1). The extension comprises an update of that work including the latest control trials, which have since been published and, most importantly, offers a novel methodology. Specifically, NFB literature is characterized by a high technical and methodological heterogeneity, which partly explains the current lack of consensus on the efficacy of NFB. This work takes advantage of this by performing a Systematic Analysis of Biases (SAOB) in studies included in the previous meta-analysis. Our extended meta-analysis (k = 16 studies) confirmed the previously obtained results of effect sizes in favor of NFB efficacy as being significant when clinical scales of ADHD are rated by parents (non-blind, p-value = 0.0014), but not when they are rated by teachers (probably blind, p-value = 0.27). The effect size is significant according to both raters for the subset of studies meeting the definition of “standard NFB protocols” (parents' pvalue = 0.0054; teachers' p-value = 0.043, k = 4). Following this, the SAOB performed on k = 33 trials identified three main factors that have an impact on NFB efficacy: first, a more intensive treatment, but not treatment duration, is associated with higher efficacy; second, teachers report a lower improvement compared to parents; third, using high-quality EEG equipment improves the effectiveness of the NFB treatment. The identification of biases relating to an appropriate technical implementation of NFB certainly supports the efficacy of NFB as an intervention. The data presented also suggest that the probably blind assessment of teachers may not be considered a good proxy for blind assessments, therefore stressing the need for studies with placebo-controlled intervention as well as carefully reported neuromarker changes in relation to clinical response
View Full Paper →Volitional limbic neuromodulation exerts a beneficial clinical effect on Fibromyalgia
Volitional neural modulation using neurofeedback has been indicated as a potential treatment for chronic conditions that involve peripheral and central neural dysregulation. Here we utilized neurofeedback in patients suffering from Fibromyalgia - a chronic pain syndrome that involves sleep disturbance and emotion dysregulation. These ancillary symptoms, which have an amplificating effect on pain, are known to be mediated by heightened limbic activity. In order to reliably probe limbic activity in a scalable manner fit for EEG-neurofeedback training, we utilized an Electrical Finger Print (EFP) model of amygdala-BOLD signal (termed Amyg-EFP), that has been successfully validated in our lab in the context of volitional neuromodulation. We anticipated that Amyg-EFP-neurofeedback training aimed at limbic down modulation would improve chronic pain in patients suffering from Fibromyalgia, by reducing sleep disorder improving emotion regulation. We further expected that improved clinical status would correspond with successful training as indicated by improved down modulation of the Amygdala-EFP signal. Thirty-Four Fibromyalgia patients (31F; age 35.6 ± 11.82) participated in a randomized placebo-controlled trial with biweekly Amyg-EFP-neurofeedback sessions or sham neurofeedback (n = 9) for a total duration of five consecutive weeks. Following training, participants in the real-neurofeedback group were divided into good (n = 13) or poor (n = 12) modulators according to their success in the neurofeedback training. Before and after treatment, self-reports on pain, depression, anxiety, fatigue and sleep quality were obtained, as well as objective sleep indices. Long-term clinical follow-up was made available, within up to three years of the neurofeedback training completion. REM latency and objective sleep quality index were robustly improved following the treatment course only in the real-neurofeedback group (time × group p < 0.05) and to a greater extent among good modulators (time × sub-group p < 0.05). In contrast, self-report measures did not reveal a treatment-specific response at the end of the neurofeedback training. However, the follow-up assessment revealed a delayed improvement in chronic pain and subjective sleep experience, evident only in the real-neurofeedback group (time × group p < 0.05). Moderation analysis showed that the enduring clinical effects on pain evident in the follow-up assessment were predicted by the immediate improvements following training in objective sleep and subjective affect measures. Our findings suggest that Amyg-EFP-neurofeedback that specifically targets limbic activity down modulation offers a successful principled approach for volitional EEG based neuromodulation treatment in Fibromyalgia patients. Importantly, it seems that via its immediate sleep improving effect, the neurofeedback training induced a delayed reduction in the target subjective symptom of chronic pain, far and beyond the immediate placebo effect. This indirect approach to chronic pain management reflects the substantial link between somatic and affective dysregulation that can be successfully targeted using neurofeedback.
View Full Paper →The efficacy of biofeedback approaches for obsessive-compulsive and related disorders: A systematic review and meta-analysis
Biofeedback is applied to target excessive and/or deficient physiological signals to help patients identifying and self-managing their symptoms. Biofeedback has been employed in psychiatric disorders, including obsessive-compulsive disorder (OCD), mainly by using neural signals - neurofeedback. Recently, OCD has been integrated into the obsessive-compulsive and related disorders (OCD&RD) category (body dysmorphic, hoarding, trichotillomania/hair-pulling, and excoriation/skin-picking disorders). The efficacy of biofeedback for OCD&RD is still unknown. Our work provides a complete overview of publications assessing the therapeutic efficacy of biofeedback in OCD&RD with a systematic review and meta-analysis. We found ten studies involving 102 OCD participants (three randomized controlled trials) mostly applying neurofeedback (one publication used thermal biofeedback). Five neurofeedback studies were selected for meta-analysis (89 patients; two randomized controlled trials). The overall effect size within the treatment group varied between medium to large, but high heterogeneity and inconsistency values were found. The methodological quality was low indicating a high risk of bias. In conclusion, a beneficial effect of neurofeedback for OCD patients was found but also critical limitations on methodology, high heterogeneity among studies, and a putative reporting bias. Future research following high-quality guidelines should be conducted to address the efficacy of biofeedback approaches for OCD&RD.
Neuromodulation for tinnitus treatment: an overview of invasive and non-invasive techniques
Tinnitus is defined as a perception of sound without any external sound source. Chronic tinnitus is a frequent condition that can affect the quality of life. So far, no causal cure for tinnitus has been documented, and most pharmacologic and psychosomatic treatment modalities aim to diminish tinnitus' impact on the quality of life. Neuromodulation, a novel therapeutic modality, which aims at alternating nerve activity through a targeted delivery of a stimulus, has emerged as a potential option in tinnitus treatment. This review provides a brief overview of the current neuromodulation techniques as tinnitus treatment options. The main intention is to provide updated knowledge especially for medical professionals counselling tinnitus patients in this emerging field of medicine. Non-invasive methods such as repetitive transcranial magnetic stimulation, transcranial electrical stimulation, neurofeedback, and transcutaneous vagus nerve stimulation were included, as well as invasive methods such as implanted vagus nerve stimulation and invasive brain stimulation. Some of these neuromodulation techniques revealed promising results; nevertheless, further research is needed, especially regarding the pathophysiological principle as to how these neuromodulation techniques work and what neuronal change they induce. Various studies suggest that individually different brain states and networks are involved in the generation and perception of tinnitus. Therefore, in the future, individually tailored neuromodulation strategies could be a promising approach in tinnitus treatment for achieving a more substantial and longer lasting improvement of complaints.
View Full Paper →Involvement of the Red Nucleus in the Compensation of Parkinsonism may Explain why Primates can develop Stable Parkinson's Disease
Neurological compensatory mechanisms help our brain to adjust to neurodegeneration as in Parkinson's disease. It is suggested that the compensation of the damaged striato-thalamo-cortical circuit is focused on the intact thalamo-rubro-cerebellar pathway as seen during presymptomatic Parkinson, paradoxical movement and sensorimotor rhythm (SMR). Indeed, the size of the red nucleus, connecting the cerebellum with the cerebral cortex, is larger in Parkinson's disease patients suggesting an increased activation of this brain area. Therefore, the red nucleus was examined in MPTP-induced parkinsonian marmoset monkeys during the presymptomatic stage and after SMR activation by neurofeedback training. We found a reverse significant correlation between the early expression of parkinsonian signs and the size of the parvocellular part of the red nucleus, which is predominantly present in human and non-human primates. In quadrupedal animals it consists mainly of the magnocellular part. Furthermore, SMR activation, that mitigated parkinsonian signs, further increased the size of the red nucleus in the marmoset monkey. This plasticity of the brain helps to compensate for dysfunctional movement control and can be a promising target for compensatory treatment with neurofeedback technology, vibrotactile stimulation or DBS in order to improve the quality of life for Parkinson's disease patients.
View Full Paper →Neurofeedback training with a low-priced EEG device leads to faster alpha enhancement but shows no effect on cognitive performance: A single-blind, sham-feedback study
INTRODUCTION: Findings of recent studies indicate that it is possible to enhance cognitive capacities of healthy individuals by means of individual upper alpha neurofeedback training (NFT). Although these results are promising, most of this research was conducted based on high-priced EEG systems developed for clinical and research purposes. This study addresses the question whether such effects can also be shown with an easy to use and comparably low-priced Emotiv Epoc EEG headset available for the average consumer. In addition, critical voices were raised regarding the control group designs of studies addressing the link between neurofeedback training and cognitive performance. Based on an extensive literature review revealing considerable methodological issues in an important part of the existing research, the present study addressed the question whether individual upper alpha neurofeedback has a positive effect on alpha amplitudes (i.e. increases alpha amplitudes) and short-term memory performance focussing on a methodologically sound, single-blinded, sham controlled design. METHOD: Participants (N = 33) took part in four test sessions over four consecutive days of either neurofeedback training (NFT group) or sham feedback (SF group). In the NFT group, five three-minute periods of visual neurofeedback training were administered each day whereas in the SF group (control group), the same amount of sham feedback was presented. Performance on eight digit-span tests as well as participants' affective states were assessed before and after each of the daily training sessions. RESULTS: NFT did not show an effect on individual upper alpha and cognitive performance. While performance increased in both groups over the course of time, this effect could not be explained by changes in individual upper alpha. Additional analyses however revealed that participants in the NFT group showed faster and larger increase in alpha compared to the SF group. Surprisingly, exploratory analyses showed a significant correlation between the initial alpha level and the alpha improvement during the course of the study. This finding suggests that participants with high initial alpha levels benefit more from alpha NFT interventions. In the discussion, the appearance of the alpha enhancement in the SF group and possible reasons for the absence of a connection between NFT and short-term memory are addressed.
View Full Paper →Efficacy of Biofeedback for Medical Conditions: an Evidence Map
BACKGROUND: Biofeedback is increasingly used to treat clinical conditions in a wide range of settings; however, evidence supporting its use remains unclear. The purpose of this evidence map is to illustrate the conditions supported by controlled trials, those that are not, and those in need of more research. METHODS: We searched multiple data sources (MEDLINE, PsycINFO, CINAHL, Epistemonikos, and EBM Reviews through September 2018) for good-quality systematic reviews examining biofeedback for clinical conditions. We included the highest quality, most recent review representing each condition and included only controlled trials from those reviews. We relied on quality ratings reported in included reviews. Outcomes of interest were condition-specific, secondary, and global health outcomes, and harms. For each review, we computed confidence ratings and categorized reported findings as no effect, unclear, or insufficient; evidence of a potential positive effect; or evidence of a positive effect. We present our findings in the form of evidence maps. RESULTS: We included 16 good-quality systematic reviews examining biofeedback alone or as an adjunctive intervention. We found clear, consistent evidence across a large number of trials that biofeedback can reduce headache pain and can provide benefit as adjunctive therapy to men experiencing urinary incontinence after a prostatectomy. Consistent evidence across fewer trials suggests biofeedback may improve fecal incontinence and stroke recovery. There is insufficient evidence to draw conclusions about effects for most conditions including bruxism, labor pain, and Raynaud's. Biofeedback was not beneficial for urinary incontinence in women, nor for hypertension management, but these conclusions are limited by small sample sizes and methodologic limitations of these studies. DISCUSSION: Available evidence suggests that biofeedback is effective for improving urinary incontinence after prostatectomy and headache, and may provide benefit for fecal incontinence and balance and stroke recovery. Further controlled trials across a wide range of conditions are indicated.
View Full Paper →A pilot study of a novel therapeutic approach to obesity: CNS modification by N.I.R. H.E.G. neurofeedback
BACKGROUND & AIMS: Despite the thorough mapping of brain pathways involved in eating behavior, no treatment aimed at modulating eating dysregulation from its neurocognitive root has been established yet. We aimed to evaluate the effect of N.I.R. H.E.G. (Near Infra-Red Hemoencephalography) neurofeedback training on appetite control, weight and food-related brain activity. METHODS: Six healthy male participants with overweight or mild obesity went through 10 N.I.R. H.E.G. neurofeedback sessions designed to practice voluntary activation of the prefrontal cortex. Weight, eating behavior, appetite control and brain activity related to food and self-inhibition based on fMRI were evaluated before and after neurofeedback training. RESULTS: Our study group demonstrated a positive trend of increased self-control and inhibition related to food behavior, reduced weight and increased activation during an fMRI response-inhibition task (Go-No-Go - GNG) in the predefined region of interest (ROI): superior orbitofrontal cortex (sOFC). CONCLUSIONS: N.I.R. H.E.G. holds a promising potential as a feasible neurofeedback platform for modulation of cortical brain circuits involved in self-control and eating behavior and should be further evaluated and developed as a brain modifying device for the treatment and prevention of obesity.
View Full Paper →Self-directed down-regulation of auditory cortex activity mediated by real-time fMRI neurofeedback augments attentional processes, resting cerebral perfusion, and auditory activation
In this work, we investigated the use of real-time functional magnetic resonance imaging (fMRI) with neurofeedback training (NFT) to teach volitional down-regulation of the auditory cortex (AC) using directed attention strategies as there is a growing interest in the application of fMRI-NFT to treat neurologic disorders. Healthy participants were separated into two groups: the experimental group received real feedback regarding activity in the AC; the control group was supplied sham feedback yoked from a random participant in the experimental group and matched for fMRI-NFT experience. Each participant underwent five fMRI-NFT sessions. Each session contained 2 neurofeedback runs where participants completed alternating blocks of "rest" and "lower" conditions while viewing a continuously-updated bar representing AC activation and listening to continuous noise. Average AC deactivation was extracted from each closed-loop neuromodulation run and used to quantify the control over AC (AC control), which was found to significantly increase across training in the experimental group. Additionally, behavioral testing was completed outside of the MRI on sessions 1 and 5 consisting of a subjective questionnaire to assess attentional control and two quantitative tests of attention. No significant changes in behavior were observed; however, there was a significant correlation between changes in AC control and attentional control. Also, in a neural assessment before and after fMRI-NFT, AC activity in response to continuous noise stimulation was found to significantly decrease across training while changes in AC resting perfusion were found to be significantly greater in the experimental group. These results may be useful in formulating effective therapies outside of the MRI, specifically for chronic tinnitus which is often characterized by hyperactivity of the primary auditory cortex and altered attentional processes. Furthermore, the modulation of attention may be useful in developing therapies for other disorders such as chronic pain.
View Full Paper →Amygdala real-time functional magnetic resonance imaging neurofeedback for major depressive disorder: A review
Advances in imaging technologies have allowed for the analysis of functional magnetic resonance imaging data in real-time (rtfMRI), leading to the development of neurofeedback (nf) training. This rtfMRI-nf training utilizes functional magnetic resonance imaging (fMRI) tomographic localization capacity to allow a person to see and regulate the localized hemodynamic signal from his or her own brain. In this review, we summarize the results of several studies that have developed and applied neurofeedback training to healthy and depressed individuals with the amygdala as the neurofeedback target and the goal to increase the hemodynamic response during positive autobiographical memory recall. We review these studies and highlight some of the challenges and advances in developing an rtfMRI-nf paradigm for broader use in psychiatric populations. The work described focuses on our line of research aiming to develop the rtfMRI-nf into an intervention, and includes a discussion of the selection of a region of interest for feedback, selecting a control condition, behavioral and cognitive effects of training, and predicting which participants are most likely to respond well to training. While the results of these studies are encouraging and suggest the clinical potential of amygdala rtfMRI-nf in alleviating symptoms of major depressive disorder, larger studies are warranted to confirm its efficacy.
View Full Paper →Targeting the affective brain-a randomized controlled trial of real-time fMRI neurofeedback in patients with 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. We 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. We thus surveyed effects reported for accepted augmentation therapies in depression. Data indicated that our 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, we suggest that the experience of successful self-regulation during fMRI-NF training may be therapeutic. We conclude that if fMRI-NF is effective for depression, self-regulation training of higher visual areas may provide an effective alternative.
View Full Paper →Hemoencephalography self-regulation training and its impact on cognition: A study with schizophrenia and healthy participants
BACKGROUND: Cognitive impairments in schizophrenia are strongly correlated to functional outcome and recovery rates, with no pharmacological agent approved for its treatment. Neurofeedback has emerged as a non-pharmacological approach to enhance neuroplasticity, which consists in inducing voluntary control of brain responses through operant conditioning. METHOD: The effects of hemoencephalography neurofeedback (HEG-NFBK) in 4 brain sites (F7, Fp1, Fp2 and F8) was studied in 8 patients with schizophrenia (SCH, mean age 36.5±9.98) and 12 health controls (mean age 32.17±5.6). We analyzed groups' performance (10 sessions) and cognitive differences in 3 time points (baseline, after training and follow-up) with generalized estimated equations. For SCH we also evaluate the impact on psychopathology. RESULTS: We found a group∗time interaction for HEG-NFBK performance in the left hemisphere sites (F7 an Fp1) and a near-to-significant in the right frontotemporal region (F8), with no group differences and a significant time effect. Most of cognitive domains improved after intervention, including information processing speed, attention processing, working memory, executive functioning, verbal and visual learning. No group∗time interaction was found. Results suggest that both groups benefit from HEG-NFBK training regardless of cognitive differences at baseline. No significant time effects were found for Calgary and PANSS total scale and subscales (positive, negative neither general). CONCLUSION: To our knowledge, this is the first controlled trial showing effects of NFBK on cognitive performance improvement in schizophrenia. Further research investigating the effects of HEG-NFBK training in schizophrenia should be performed.
View Full Paper →Neurofeedback-Based Enhancement of Single-Trial Auditory Evoked Potentials: Treatment of Auditory Verbal Hallucinations in Schizophrenia
Auditory verbal hallucinations depend on a broad neurobiological network ranging from the auditory system to language as well as memory-related processes. As part of this, the auditory N100 event-related potential (ERP) component is attenuated in patients with schizophrenia, with stronger attenuation occurring during auditory verbal hallucinations. Changes in the N100 component assumingly reflect disturbed responsiveness of the auditory system toward external stimuli in schizophrenia. With this premise, we investigated the therapeutic utility of neurofeedback training to modulate the auditory-evoked N100 component in patients with schizophrenia and associated auditory verbal hallucinations. Ten patients completed electroencephalography neurofeedback training for modulation of N100 (treatment condition) or another unrelated component, P200 (control condition). On a behavioral level, only the control group showed a tendency for symptom improvement in the Positive and Negative Syndrome Scale total score in a pre-/postcomparison ( t(4) = 2.71, P = .054); however, no significant differences were found in specific hallucination related symptoms ( t(7) = -0.53, P = .62). There was no significant overall effect of neurofeedback training on ERP components in our paradigm; however, we were able to identify different learning patterns, and found a correlation between learning and improvement in auditory verbal hallucination symptoms across training sessions ( r = 0.664, n = 9, P = .05). This effect results, with cautious interpretation due to the small sample size, primarily from the treatment group ( r = 0.97, n = 4, P = .03). In particular, a within-session learning parameter showed utility for predicting symptom improvement with neurofeedback training. In conclusion, patients with schizophrenia and associated auditory verbal hallucinations who exhibit a learning pattern more characterized by within-session aptitude may benefit from electroencephalography neurofeedback. Furthermore, independent of the training group, a significant spatial pre-post difference was found in the event-related component P200 ( P = .04).
View Full Paper →Intrinsic connectivity network dynamics in PTSD during amygdala downregulation using real-time fMRI neurofeedback: A preliminary analysis
Posttraumatic stress disorder (PTSD) has been associated with a disturbance in neural intrinsic connectivity networks (ICN), including the central executive network (CEN), default mode network (DMN), and salience network (SN). Here, we conducted a preliminary investigation examining potential changes in ICN recruitment as a function of real-time fMRI neurofeedback (rt-fMRI-NFB) during symptom provocation where we targeted the downregulation of neural response within the amygdala-a key region-of-interest in PTSD neuropathophysiology. Patients with PTSD (n = 14) completed three sessions of rt-fMRI-NFB with the following conditions: (a) regulate: decrease activation in the amygdala while processing personalized trauma words; (b) view: process trauma words while not attempting to regulate the amygdala; and (c) neutral: process neutral words. We found that recruitment of the left CEN increased over neurofeedback runs during the regulate condition, a finding supported by increased dlPFC activation during the regulate as compared to the view condition. In contrast, DMN task-negative recruitment was stable during neurofeedback runs, albeit was the highest during view conditions and increased (normalized) during rest periods. Critically, SN recruitment was high for both the regulate and the view conditions, a finding potentially indicative of CEN modality switching, adaptive learning, and increasing threat/defense processing in PTSD. In conclusion, this study provides provocative, preliminary evidence that downregulation of the amygdala using rt-fMRI-NFB in PTSD is associated with dynamic changes in ICN, an effect similar to those observed using EEG modalities of neurofeedback.
View Full Paper →Emotion Regulation Using Virtual Environments and Real-Time fMRI Neurofeedback
Neurofeedback (NFB) enables the voluntary regulation of brain activity, with promising applications to enhance and recover emotion and cognitive processes, and their underlying neurobiology. It remains unclear whether NFB can be used to aid and sustain complex emotions, with ecological validity implications. We provide a technical proof of concept of a novel real-time functional magnetic resonance imaging (rtfMRI) NFB procedure. Using rtfMRI-NFB, we enabled participants to voluntarily enhance their own neural activity while they experienced complex emotions. The rtfMRI-NFB software (FRIEND Engine) was adapted to provide a virtual environment as brain computer interface (BCI) and musical excerpts to induce two emotions (tenderness and anguish), aided by participants' preferred personalized strategies to maximize the intensity of these emotions. Eight participants from two experimental sites performed rtfMRI-NFB on two consecutive days in a counterbalanced design. On one day, rtfMRI-NFB was delivered to participants using a region of interest (ROI) method, while on the other day using a support vector machine (SVM) classifier. Our multimodal VR/NFB approach was technically feasible and robust as a method for real-time measurement of the neural correlates of complex emotional states and their voluntary modulation. Guided by the color changes of the virtual environment BCI during rtfMRI-NFB, participants successfully increased in real time, the activity of the septo-hypothalamic area and the amygdala during the ROI based rtfMRI-NFB, and successfully evoked distributed patterns of brain activity classified as tenderness and anguish during SVM-based rtfMRI-NFB. Offline fMRI analyses confirmed that during tenderness rtfMRI-NFB conditions, participants recruited the septo-hypothalamic area and other regions ascribed to social affiliative emotions (medial frontal/temporal pole and precuneus). During anguish rtfMRI-NFB conditions, participants recruited the amygdala and other dorsolateral prefrontal and additional regions associated with negative affect. These findings were robust and were demonstrable at the individual subject level, and were reflected in self-reported emotion intensity during rtfMRI-NFB, being observed with both ROI and SVM methods and across the two sites. Our multimodal VR/rtfMRI-NFB protocol provides an engaging tool for brain-based interventions to enhance emotional states in healthy subjects and may find applications in clinical conditions associated with anxiety, stress and impaired empathy among others.
The Treatment of Autism Spectrum Disorder With Auditory Neurofeedback: A Randomized Placebo Controlled Trial Using the Mente Autism Device
Introduction: Children affected by autism spectrum disorder (ASD) often have impairment of social interaction and demonstrate difficulty with emotional communication, display of posture and facial expression, with recognized relationships between postural control mechanisms and cognitive functions. Beside standard biomedical interventions and psychopharmacological treatments, there is increasing interest in the use of alternative non-invasive treatments such as neurofeedback (NFB) that could potentially modulate brain activity resulting in behavioral modification. Methods: Eighty-three ASD subjects were randomized to an Active group receiving NFB using the Mente device and a Control group using a Sham device. Both groups used the device each morning for 45 minutes over a 12 week home based trial without any other clinical interventions. Pre and Post standard ASD questionnaires, qEEG and posturography were used to measure the effectiveness of the treatment. Results: Thirty-four subjects (17 Active and 17 Control) completed the study. Statistically and substantively significant changes were found in several outcome measures for subjects that received the treatment. Similar changes were not detected in the Control group. Conclusions: Our results show that a short 12 week course of NFB using the Mente Autism device can lead to significant changes in brain activity (qEEG), sensorimotor behavior (posturography), and behavior (standardized questionnaires) in ASD children.
View Full Paper →Low Motivational Incongruence Predicts Successful EEG Resting-state Neurofeedback Performance in Healthy Adults
Neurofeedback is becoming increasingly sophisticated and widespread, although predictors of successful performance still remain scarce. Here, we explored the possible predictive value of psychological factors and report the results obtained from a neurofeedback training study designed to enhance the self-regulation of spontaneous EEG microstates of a particular type (microstate class D). Specifically, we were interested in life satisfaction (including motivational incongruence), body awareness, personality and trait anxiety. These variables were quantified with questionnaires before neurofeedback. Individual neurofeedback success was established by means of linear mixed models that accounted for the amount of observed target state (microstate class D contribution) as a function of time and training condition: baseline, training and transfer (results shown in Diaz Hernandez et al.). We found a series of significant negative correlations between motivational incongruence and mean percentage increase of microstate D during the condition transfer, across-sessions (36% of common variance) and mean percentage increase of microstate D during the condition training, within-session (42% of common variance). There were no significant correlations related to other questionnaires, besides a trend in a sub-scale of the Life Satisfaction questionnaire. We conclude that motivational incongruence may be a potential predictor for neurofeedback success, at least in the current protocol. The finding may be explained by the interfering effect on neurofeedback performance produced by incompatible simultaneously active psychological processes, which are indirectly measured by the Motivational Incongruence questionnaire.
View Full Paper →Enhancing health leadership performance using neurotherapy
The discovery of neuroplasticity means the brain can change, functionally, in response to the environment and to learning. While individuals can develop harmful patterns of brain activity in response to stressors, they can also learn to modify or control neurological conditions associated with specific behaviors. Neurotherapy is one way of changing brain functioning to modify troubling conditions which can impair leadership performance, through responding to feedback on their own brain activity, and enhancing optimal leadership functioning through learning to maximize such cognitive strengths as mental efficiency, focus, creativity, perseverance, and executive functioning. The present article outlines the application of the concept of optimal performance training to organizational leadership in a healthcare context, by describing approaches to neurotherapy and illustrating their application through a case study of a health leader learning to overcome the neurological and emotional sequelae of workplace stress and trauma.
View Full Paper →Rapid acquisition of dynamic control over DLPFC using real-time fMRI feedback
It has been postulated that gaining control over activity in the dorsolateral prefrontal cortex (DLPFC), a key region of the working memory brain network, may be beneficial for cognitive performance and treatment of certain psychiatric disorders. Several studies have reported that, with neurofeedback training, subjects can learn to increase DLPFC activity. However, improvement of dynamic control in terms of switching between low and high activity in DLPFC brain states may potentially constitute more effective self-regulation. Here, we report on feasibility of obtaining dynamic control over DLPFC, meaning the ability to both in- and decrease activity at will, within a single functional MRI scan session. Two groups of healthy volunteers (N = 24) were asked to increase and decrease activity in the left DLPFC as often as possible during fMRI scans (at 7 Tesla), while receiving real-time visual feedback. The experimental group practiced with real-time feedback, whereas the control group received sham feedback. The experimental group significantly increased the speed of intentionally alternating DLPFC activity, while performance of the control group did not change. Analysis of the characteristics of the BOLD signal during successful trials revealed that training with neurofeedback predominantly reduced the time for the DLPFC to return to baseline after activation. These results provide a preliminary indication that people may be able to learn to dynamically down-regulate the level of physiological activity in the DLPFC, and may have implications for psychiatric disorders where DLPFC plays a role.
View Full Paper →Time course of clinical change following neurofeedback
Neurofeedback - learning to modulate brain function through real-time monitoring of current brain state - is both a powerful method to perturb and probe brain function and an exciting potential clinical tool. For neurofeedback effects to be useful clinically, they must persist. Here we examine the time course of symptom change following neurofeedback in two clinical populations, combining data from two ongoing neurofeedback studies. This analysis reveals a shared pattern of symptom change, in which symptoms continue to improve for weeks after neurofeedback. This time course has several implications for future neurofeedback studies. Most neurofeedback studies are not designed to test an intervention with this temporal pattern of response. We recommend that new studies incorporate regular follow-up of subjects for weeks or months after the intervention to ensure that the time point of greatest effect is sampled. Furthermore, this time course of continuing clinical change has implications for crossover designs, which may attribute long-term, ongoing effects of real neurofeedback to the control intervention that follows. Finally, interleaving neurofeedback sessions with assessments and examining when clinical improvement peaks may not be an appropriate approach to determine the optimal number of sessions for an application.
View Full Paper →Improving motivation through real-time fMRI-based self-regulation of the nucleus accumbens
OBJECTIVE: Impaired nucleus accumbens (NAcc) activation is associated with amotivation and anhedonia, which are resistant to treatment with antipsychotics and antidepressants in schizophrenia. In this study, healthy participants were trained to self-regulate the activation of their NAcc, a brain region that plays an important role in motivation, using real-time functional magnetic resonance imaging (fMRI) neurofeedback. METHOD: The experimental group (N = 19) received feedback from the NAcc, whereas the control group (N = 5) received "sham" feedback from the posterior parahippocampal gyrus, a control brain region not normally related to motivation. All participants were trained to use mental strategies to regulate their NAcc activations in a 3T MRI scanner. RESULTS: For the learning effect of NAcc regulation, we found that the majority of participants (74%) in the experimental group successfully learned to self-regulate the NAcc. They also showed improved behavioral performance in motivation and decreased functional connectivity between the NAcc and the ventral medial prefrontal cortex and an increase in small-world properties in the reward circuit after training, indicating improved information integration in reward processing. However, improvement in motivation and modification of function connectivity were not observed in the sham control group and the participants who failed to self-regulate the NAcc in the experimental group. Self-regulation was influenced by the baseline motivation. CONCLUSIONS: These findings suggest that the NAcc could be self-regulated using real-time fMRI neurofeedback and can result in improved motivation in cognitive tasks. (PsycINFO Database Record
View Full Paper →Higher-order Brain Areas Associated with Real-time Functional MRI Neurofeedback Training of the Somato-motor Cortex
Neurofeedback (NFB) allows subjects to learn self-regulation of neuronal brain activation based on information about the ongoing activation. The implementation of real-time functional magnetic resonance imaging (rt-fMRI) for NFB training now facilitates the investigation into underlying processes. Our study involved 16 control and 16 training right-handed subjects, the latter performing an extensive rt-fMRI NFB training using motor imagery. A previous analysis focused on the targeted primary somato-motor cortex (SMC). The present study extends the analysis to the supplementary motor area (SMA), the next higher brain area within the hierarchy of the motor system. We also examined transfer-related functional connectivity using a whole-volume psycho-physiological interaction (PPI) analysis to reveal brain areas associated with learning. The ROI analysis of the pre- and post-training fMRI data for motor imagery without NFB (transfer) resulted in a significant training-specific increase in the SMA. It could also be shown that the contralateral SMA exhibited a larger increase than the ipsilateral SMA in the training and the transfer runs, and that the right-hand training elicited a larger increase in the transfer runs than the left-hand training. The PPI analysis revealed a training-specific increase in transfer-related functional connectivity between the left SMA and frontal areas as well as the anterior midcingulate cortex (aMCC) for right- and left-hand trainings. Moreover, the transfer success was related with training-specific increase in functional connectivity between the left SMA and the target area SMC. Our study demonstrates that NFB training increases functional connectivity with non-targeted brain areas. These are associated with the training strategy (i.e., SMA) as well as with learning the NFB skill (i.e., aMCC and frontal areas). This detailed description of both the system to be trained and the areas involved in learning can provide valuable information for further optimization of NFB trainings.
View Full Paper →Current practices in clinical neurofeedback with functional MRI-Analysis of a survey using the TIDieR checklist
BACKGROUND: A core principle of creating a scientific evidence base is that results can be replicated in independent experiments and in health intervention research. The TIDieR (Template for Intervention Description and Replication) checklist has been developed to aid in summarising key items needed when reporting clinical trials and other well designed evaluations of complex interventions in order that findings can be replicated or built on reliably. Neurofeedback (NF) using functional MRI (fMRI) is a multicomponent intervention that should be considered a complex intervention. The TIDieR checklist (with minor modification to increase applicability in this context) was distributed to NF researchers as a survey of current practice in the design and conduct of clinical studies. The aim was to document practice and convergence between research groups, highlighting areas for discussion and providing a basis for recommendations for harmonisation and standardisation. METHODS: The TIDieR checklist was interpreted and expanded (21 questions) to make it applicable to neurofeedback research studies. Using the web-based Bristol Online Survey (BOS) tool, the revised checklist was disseminated to researchers in the BRAINTRAIN European research collaborative network (supported by the European Commission) and others in the fMRI-neurofeedback community. RESULTS: There were 16 responses to the survey. Responses were reported under eight main headings which covered the six domains of the TIDieR checklist: What, Why, When, How, Where and Who. CONCLUSIONS: This piece of work provides encouraging insight into the ability to be able to map neuroimaging interventions to a structured framework for reporting purposes. Regardless of the considerable variability of design components, all studies could be described in standard terms of diagnostic groups, dose/duration, targeted areas/signals, and psychological strategies and learning models. Recommendations are made which include providing detailed rationale of intervention design in study protocols.
View Full Paper →Effects of an Integrated Neurofeedback System with Dry Electrodes: EEG Acquisition and Cognition Assessment
Electroencephalogram (EEG) neurofeedback improves cognitive capacity and behaviors by regulating brain activity, which can lead to cognitive enhancement in healthy people and better rehabilitation in patients. The increased use of EEG neurofeedback highlights the urgent need to reduce the discomfort and preparation time and increase the stability and simplicity of the system's operation. Based on brain-computer interface technology and a multithreading design, we describe a neurofeedback system with an integrated design that incorporates wearable, multichannel, dry electrode EEG acquisition equipment and cognitive function assessment. Then, we evaluated the effectiveness of the system in a single-blind control experiment in healthy people, who increased the alpha frequency band power in a neurofeedback protocol. We found that upregulation of the alpha power density improved working memory following short-term training (only five training sessions in a week), while the attention network regulation may be related to other frequency band activities, such as theta and beta. Our integrated system will be an effective neurofeedback training and cognitive function assessment system for personal and clinical use.
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