Preliminary findings on long-term effects of fMRI neurofeedback training on functional networks involved in sustained attention.

INTRODUCTION: Neurofeedback based on functional magnetic resonance imaging allows for learning voluntary control over one's own brain activity, aiming to enhance cognition and clinical symptoms. We previously reported improved sustained attention temporarily by training healthy participants to up-regulate the differential activity of the sustained attention network minus the default mode network (DMN). However, the long-term brain and behavioral effects of this training have not yet been studied. In general, despite their relevance, long-term learning effects of neurofeedback training remain under-explored. METHODS: Here, we complement our previously reported results by evaluating the neurofeedback training effects on functional networks involved in sustained attention and by assessing behavioral and brain measures before, after, and 2 months after training. The behavioral measures include task as well as questionnaire scores, and the brain measures include activity and connectivity during self-regulation runs without feedback (i.e., transfer runs) and during resting-state runs from 15 healthy individuals. RESULTS: Neurally, we found that participants maintained their ability to control the differential activity during follow-up sessions. Further, exploratory analyses showed that the training increased the functional connectivity between the DMN and the occipital gyrus, which was maintained during follow-up transfer runs but not during follow-up resting-state runs. Behaviorally, we found that enhanced sustained attention right after training returned to baseline level during follow-up. CONCLUSION: The discrepancy between lasting regulation-related brain changes but transient behavioral and resting-state effects raises the question of how neural changes induced by neurofeedback training translate to potential behavioral improvements. Since neurofeedback directly targets brain measures to indirectly improve behavior in the long term, a better understanding of the brain-behavior associations during and after neurofeedback training is needed to develop its full potential as a promising scientific and clinical tool.

Facing emotions: real-time fMRI-based neurofeedback using dynamic emotional faces to modulate amygdala activity.

Introduction: Maladaptive functioning of the amygdala has been associated with impaired emotion regulation in affective disorders. Recent advances in real-time fMRI neurofeedback have successfully demonstrated the modulation of amygdala activity in healthy and psychiatric populations. In contrast to an abstract feedback representation applied in standard neurofeedback designs, we proposed a novel neurofeedback paradigm using naturalistic stimuli like human emotional faces as the feedback display where change in the facial expression intensity (from neutral to happy or from fearful to neutral) was coupled with the participant's ongoing bilateral amygdala activity. Methods: The feasibility of this experimental approach was tested on 64 healthy participants who completed a single training session with four neurofeedback runs. Participants were assigned to one of the four experimental groups (n = 16 per group), i.e., happy-up, happy-down, fear-up, fear-down. Depending on the group assignment, they were either instructed to "try to make the face happier" by upregulating (happy-up) or downregulating (happy-down) the amygdala or to "try to make the face less fearful" by upregulating (fear-up) or downregulating (fear-down) the amygdala feedback signal. Results: Linear mixed effect analyses revealed significant amygdala activity changes in the fear condition, specifically in the fear-down group with significant amygdala downregulation in the last two neurofeedback runs as compared to the first run. The happy-up and happy-down groups did not show significant amygdala activity changes over four runs. We did not observe significant improvement in the questionnaire scores and subsequent behavior. Furthermore, task-dependent effective connectivity changes between the amygdala, fusiform face area (FFA), and the medial orbitofrontal cortex (mOFC) were examined using dynamic causal modeling. The effective connectivity between FFA and the amygdala was significantly increased in the happy-up group (facilitatory effect) and decreased in the fear-down group. Notably, the amygdala was downregulated through an inhibitory mechanism mediated by mOFC during the first training run. Discussion: In this feasibility study, we intended to address key neurofeedback processes like naturalistic facial stimuli, participant engagement in the task, bidirectional regulation, task congruence, and their influence on learning success. It demonstrated that such a versatile emotional face feedback paradigm can be tailored to target biased emotion processing in affective disorders.

Real-time and Recursive Estimators for Functional MRI Quality Assessment.

Real-time quality assessment (rtQA) of functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) signal changes is critical for neuroimaging research and clinical applications. The losses of BOLD sensitivity because of different types of technical and physiological noise remain major sources of fMRI artifacts. Due to difficulty of subjective visual perception of image distortions during data acquisitions, a comprehensive automatic rtQA is needed. To facilitate rapid rtQA of fMRI data, we applied real-time and recursive quality assessment methods to whole-brain fMRI volumes, as well as time-series of target brain areas and resting-state networks. We estimated recursive temporal signal-to-noise ratio (rtSNR) and contrast-to-noise ratio (rtCNR), and real-time head motion parameters by a framewise rigid-body transformation (translations and rotations) using the conventional current to template volume registration. In addition, we derived real-time framewise (FD) and micro (MD) displacements based on head motion parameters and evaluated the temporal derivative of root mean squared variance over voxels (DVARS). For monitoring time-series of target regions and networks, we estimated the number of spikes and amount of filtered noise by means of a modified Kalman filter. Finally, we applied the incremental general linear modeling (GLM) to evaluate real-time contributions of nuisance regressors (linear trend and head motion). Proposed rtQA was demonstrated in real-time fMRI neurofeedback runs without and with excessive head motion and real-time simulations of neurofeedback and resting-state fMRI data. The rtQA was implemented as an extension of the open-source OpenNFT software written in Python, MATLAB and C++ for neurofeedback, task-based, and resting-state paradigms. We also developed a general Python library to unify real-time fMRI data processing and neurofeedback applications. Flexible estimation and visualization of rtQA facilitates efficient rtQA of fMRI data and helps the robustness of fMRI acquisitions by means of substantiating decisions about the necessity of the interruption and re-start of the experiment and increasing the confidence in neural estimates.

Human brain functional MRS reveals interplay of metabolites implicated in neurotransmission and neuroenergetics.

While functional MRI (fMRI) localizes brain activation and deactivation, functional MRS (fMRS) provides insights into the underlying metabolic conditions. There is much interest in measuring task-induced and resting levels of metabolites implicated in neuroenergetics (e.g., lactate, glucose, or ß-hydroxybutyrate (BHB)) and neurotransmission (e.g., γ-aminobutyric acid (GABA) or pooled glutamate and glutamine (Glx)). Ultra-high magnetic field (e.g., 7T) has boosted the fMRS quantification precision, reliability, and stability of spectroscopic observations using short echo-time (TE) 1H-MRS techniques. While short TE 1H-MRS lacks sensitivity and specificity for fMRS at lower magnetic fields (e.g., 3T or 4T), most of these metabolites can also be detected by J-difference editing (JDE) 1H-MRS with longer TE to filter overlapping resonances. The 1H-MRS studies show that JDE can detect GABA, Glx, lactate, and BHB at 3T, 4T and 7T. Most recently, it has also been demonstrated that JDE 1H-MRS is capable of reliable detection of metabolic changes in different brain areas at various magnetic fields. Combining fMRS measurements with fMRI is important for understanding normal brain function, but also clinically relevant for mechanisms and/or biomarkers of neurological and neuropsychiatric disorders. We provide an up-to-date overview of fMRS research in the last three decades, both in terms of applications and technological advances. Overall the emerging fMRS techniques can be expected to contribute substantially to our understanding of metabolism for brain function and dysfunction.

Brain Network Dysfunction in Poststroke Delirium and Spatial Neglect: An fMRI Study.

BACKGROUND AND PURPOSE: Delirium, an acute reduction in cognitive functioning, hinders stroke recovery and contributes to cognitive decline. Right-hemisphere stroke is linked with higher delirium incidence, likely, due to the prevalence of spatial neglect (SN), a right-brain disorder of spatial processing. This study tested if symptoms of delirium and SN after right-hemisphere stroke are associated with abnormal function of the right-dominant neural networks specialized for maintaining attention, orientation, and arousal. METHODS: Twenty-nine participants with right-hemisphere ischemic stroke undergoing acute rehabilitation completed delirium and SN assessments and functional neuroimaging scans. Whole-brain functional connectivity of 4 right-hemisphere seed regions in the cortical-subcortical arousal and attention networks was assessed for its relationship to validated SN and delirium severity measures. RESULTS: Of 29 patients, 6 (21%) met the diagnostic criteria for delirium and 16 (55%) for SN. Decreased connectivity of the right basal forebrain to brain stem and basal ganglia predicted more severe SN. Increased connectivity of the arousal and attention network regions with the parietal, frontal, and temporal structures in the unaffected hemisphere was also found in more severe delirium and SN. CONCLUSIONS: Delirium and SN are associated with decreased arousal network activity and an imbalance of cortico-subcortical hemispheric connectivity. Better understanding of neural correlates of poststroke delirium and SN will lead to improved neuroscience-based treatment development for these disorders. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03349411.

Progressive modulation of resting-state brain activity during neurofeedback of positive-social emotion regulation networks.

Neurofeedback allows for the self-regulation of brain circuits implicated in specific maladaptive behaviors, leading to persistent changes in brain activity and connectivity. Positive-social emotion regulation neurofeedback enhances emotion regulation capabilities, which is critical for reducing the severity of various psychiatric disorders. Training dorsomedial prefrontal cortex (dmPFC) to exert a top-down influence on bilateral amygdala during positive-social emotion regulation progressively (linearly) modulates connectivity within the trained network and induces positive mood. However, the processes during rest that interleave the neurofeedback training remain poorly understood. We hypothesized that short resting periods at the end of training sessions of positive-social emotion regulation neurofeedback would show alterations within emotion regulation and neurofeedback learning networks. We used complementary model-based and data-driven approaches to assess how resting-state connectivity relates to neurofeedback changes at the end of training sessions. In the experimental group, we found lower progressive dmPFC self-inhibition and an increase of connectivity in networks engaged in emotion regulation, neurofeedback learning, visuospatial processing, and memory. Our findings highlight a large-scale synergy between neurofeedback and resting-state brain activity and connectivity changes within the target network and beyond. This work contributes to our understanding of concomitant learning mechanisms post training and facilitates development of efficient neurofeedback training.

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.

Metabolic underpinnings of activated and deactivated cortical areas in human brain.

Neuroimaging with functional MRI (fMRI) identifies activated and deactivated brain regions in task-based paradigms. These patterns of (de)activation are altered in diseases, motivating research to understand their underlying biochemical/biophysical mechanisms. Essentially, it remains unknown how aerobic metabolism of glucose to lactate (aerobic glycolysis) and excitatory-inhibitory balance of glutamatergic and GABAergic neuronal activities vary in these areas. In healthy volunteers, we investigated metabolic distinctions of activating visual cortex (VC, a task-positive area) using a visual task and deactivating posterior cingulate cortex (PCC, a task-negative area) using a cognitive task. We used fMRI-guided J-edited functional MRS (fMRS) to measure lactate, glutamate plus glutamine (Glx) and γ-aminobutyric acid (GABA), as indicators of aerobic glycolysis and excitatory-inhibitory balance, respectively. Both lactate and Glx increased upon activating VC, but did not change upon deactivating PCC. Basal GABA was negatively correlated with BOLD responses in both brain areas, but during functional tasks GABA decreased in VC upon activation and GABA increased in PCC upon deactivation, suggesting BOLD responses in relation to baseline are impacted oppositely by task-induced inhibition. In summary, opposite relations between BOLD response and GABAergic inhibition, and increases in aerobic glycolysis and glutamatergic activity distinguish the BOLD response in (de)activated areas.

Can we predict real-time fMRI neurofeedback learning success from pretraining brain activity?

Neurofeedback training has been shown to influence behavior in healthy participants as well as to alleviate clinical symptoms in neurological, psychosomatic, and psychiatric patient populations. However, many real-time fMRI neurofeedback studies report large inter-individual differences in learning success. The factors that cause this vast variability between participants remain unknown and their identification could enhance treatment success. Thus, here we employed a meta-analytic approach including data from 24 different neurofeedback studies with a total of 401 participants, including 140 patients, to determine whether levels of activity in target brain regions during pretraining functional localizer or no-feedback runs (i.e., self-regulation in the absence of neurofeedback) could predict neurofeedback learning success. We observed a slightly positive correlation between pretraining activity levels during a functional localizer run and neurofeedback learning success, but we were not able to identify common brain-based success predictors across our diverse cohort of studies. Therefore, advances need to be made in finding robust models and measures of general neurofeedback learning, and in increasing the current study database to allow for investigating further factors that might influence neurofeedback learning.

Network-based fMRI-neurofeedback training of sustained attention.

The brain regions supporting sustained attention (sustained attention network; SAN) and mind-wandering (default-mode network; DMN) have been extensively studied. Nevertheless, this knowledge has not yet been translated into advanced brain-based attention training protocols. Here, we used network-based real-time functional magnetic resonance imaging (fMRI) to provide healthy individuals with information about current activity levels in SAN and DMN. Specifically, 15 participants trained to control the difference between SAN and DMN hemodynamic activity and completed behavioral attention tests before and after neurofeedback training. Through training, participants improved controlling the differential SAN-DMN feedback signal, which was accomplished mainly through deactivating DMN. After training, participants were able to apply learned self-regulation of the differential feedback signal even when feedback was no longer available (i.e., during transfer runs). The neurofeedback group improved in sustained attention after training, although this improvement was temporally limited and rarely exceeded mere practice effects that were controlled by a test-retest behavioral control group. The learned self-regulation and the behavioral outcomes suggest that neurofeedback training of differential SAN and DMN activity has the potential to become a non-invasive and non-pharmacological tool to enhance attention and mitigate specific attention deficits.

The role of the subgenual anterior cingulate cortex in dorsomedial prefrontal-amygdala neural circuitry during positive-social emotion regulation.

Positive-social emotions mediate one's cognitive performance, mood, well-being, and social bonds, and represent a critical variable within therapeutic settings. It has been shown that the upregulation of positive emotions in social situations is associated with increased top-down signals that stem from the prefrontal cortices (PFC) which modulate bottom-up emotional responses in the amygdala. However, it remains unclear if positive-social emotion upregulation of the amygdala occurs directly through the dorsomedial PFC (dmPFC) or indirectly linking the bilateral amygdala with the dmPFC via the subgenual anterior cingulate cortex (sgACC), an area which typically serves as a gatekeeper between cognitive and emotion networks. We performed functional MRI (fMRI) experiments with and without effortful positive-social emotion upregulation to demonstrate the functional architecture of a network involving the amygdala, the dmPFC, and the sgACC. We found that effortful positive-social emotion upregulation was associated with an increase in top-down connectivity from the dmPFC on the amygdala via both direct and indirect connections with the sgACC. Conversely, we found that emotion processes without effortful regulation increased network modulation by the sgACC and amygdala. We also found that more anxious individuals with a greater tendency to suppress emotions and intrusive thoughts, were likely to display decreased amygdala, dmPFC, and sgACC activity and stronger connectivity strength from the sgACC onto the left amygdala during effortful emotion upregulation. Analyzed brain network suggests a more general role of the sgACC in cognitive control and sheds light on neurobiological informed treatment interventions.

Consensus on the reporting and experimental design of clinical and cognitive-behavioural neurofeedback studies (CRED-nf checklist).

Neurofeedback has begun to attract the attention and scrutiny of the scientific and medical mainstream. Here, neurofeedback researchers present a consensus-derived checklist that aims to improve the reporting and experimental design standards in the field.

Earliest amyloid and tau deposition modulate the influence of limbic networks during closed-loop hippocampal downregulation.

Research into hippocampal self-regulation abilities may help determine the clinical significance of hippocampal hyperactivity throughout the pathophysiological continuum of Alzheimer's disease. In this study, we aimed to identify the effects of amyloid-ß peptide 42 (amyloid-ß42) and phosphorylated tau on the patterns of functional connectomics involved in hippocampal downregulation. We identified 48 cognitively unimpaired participants (22 with elevated CSF amyloid-ß peptide 42 levels, 15 with elevated CSF phosphorylated tau levels, mean age of 62.705 ± 4.628 years), from the population-based 'Alzheimer's and Families' study, with baseline MRI, CSF biomarkers, APOE genotyping and neuropsychological evaluation. We developed a closed-loop, real-time functional MRI neurofeedback task with virtual reality and tailored it for training downregulation of hippocampal subfield cornu ammonis 1 (CA1). Neurofeedback performance score, cognitive reserve score, hippocampal volume, number of apolipoprotein ε4 alleles and sex were controlled for as confounds in all cross-sectional analyses. First, using voxel-wise multiple regression analysis and controlling for CSF biomarkers, we identified the effect of healthy ageing on eigenvector centrality, a measure of each voxel's overall influence based on iterative whole-brain connectomics, during hippocampal CA1 downregulation. Then, controlling for age, we identified the effects of abnormal CSF amyloid-ß42 and phosphorylated tau levels on eigenvector centrality during hippocampal CA1 downregulation. Across subjects, our main findings during hippocampal downregulation were: (i) in the absence of abnormal biomarkers, age correlated with eigenvector centrality negatively in the insula and midcingulate cortex, and positively in the inferior temporal gyrus; (ii) abnormal CSF amyloid-ß42 (<1098) correlated negatively with eigenvector centrality in the anterior cingulate cortex and primary motor cortex; and (iii) abnormal CSF phosphorylated tau levels (>19.2) correlated with eigenvector centrality positively in the ventral striatum, anterior cingulate and somatosensory cortex, and negatively in the precuneus and orbitofrontal cortex. During resting state functional MRI, similar eigenvector centrality patterns in the cingulate had previously been associated to CSF biomarkers in mild cognitive impairment and dementia patients. Using the developed closed-loop paradigm, we observed such patterns, which are characteristic of advanced disease stages, during a much earlier presymptomatic phase. In the absence of CSF biomarkers, our non-invasive, interactive, adaptive and gamified neuroimaging procedure may provide important information for clinical prognosis and monitoring of therapeutic efficacy. We have released the developed paradigm and analysis pipeline as open-source software to facilitate replication studies.

Data-driven tensor independent component analysis for model-based connectivity neurofeedback.

Neurofeedback based on real-time functional MRI is an emerging technique to train voluntary control over brain activity in healthy and disease states. Recent developments even allow for training of brain networks using connectivity feedback based on dynamic causal modeling (DCM). DCM is an influential hypothesis-driven approach that requires prior knowledge about the target brain network dynamics and the modulatory influences. Data-driven approaches, such as tensor independent component analysis (ICA), can reveal spatiotemporal patterns of brain activity without prior assumptions. Tensor ICA allows flexible data decomposition and extraction of components consisting of spatial maps, time-series, and session/subject-specific weights, which can be used to characterize individual neurofeedback regulation per regulation trial, run, or session. In this study, we aimed to better understand the spatiotemporal brain patterns involved and affected by model-based feedback regulation using data-driven tensor ICA. We found that task-specific spatiotemporal brain patterns obtained using tensor ICA were highly consistent with model-based feedback estimates. However, we found that the DCM approach captured specific network interdependencies that went beyond what could be detected with either general linear model (GLM) or ICA approaches. We also found that neurofeedback-guided regulation resulted in activity changes that were characteristic of the mental strategies used to control the feedback signal, and that these activity changes were not limited to periods of active self-regulation, but were also evident in distinct gradual recovery processes during subsequent rest periods. Complementary data-driven and model-based approaches could aid in interpretation of the neurofeedback data when applied post-hoc, and in the definition of the target brain area/pattern/network/model prior to the neurofeedback training study when applied to the pilot data. Systematically investigating the triad of mental effort, spatiotemporal brain network changes, and activity and recovery processes might lead to a better understanding of how learning with neurofeedback is accomplished, and how such learning can cause plastic brain changes along with specific behavioral effects.

Functional MRS with J-edited lactate in human motor cortex at 4 T.

While functional MRI (fMRI) localizes regions of brain activation, functional MRS (fMRS) provides insights into metabolic underpinnings. Previous fMRS studies detected task-induced lactate increase using short echo-time non-edited 1H-MRS protocols, where lactate changes depended on accurate exclusion of overlapping lactate and lipid/macromolecule signals. Because long echo-time J-difference 1H-MRS detection of lactate is less susceptible to this shortcoming, we posited if J-edited fMRS protocol could reliably detect metabolic changes in the human motor cortex during a finger-tapping paradigm in relation to a reliable measure of basal lactate. Our J-edited fMRS protocol at 4T was guided by an fMRI pre-scan to determine the 1H-MRS voxel placement in the motor cortex. Because lactate and ß-hydroxybutyrate (BHB) follow similar J-evolution profiles we observed both metabolites in all spectra, but only lactate showed reproducible task-induced modulation by 0.07 mM from a basal value of 0.82 mM. These J-edited fMRS results demonstrate good sensitivity and specificity for task-induced lactate modulation, suggesting that J-edited fMRS studies can be used to investigate the metabolic underpinning of human cognition by measuring lactate dynamics associated with activation and deactivation fMRI paradigms across brain regions at magnetic field lower than 7T.

Volitional modulation of higher-order visual cortex alters human perception.

Can we change our perception by controlling our brain activation? Awareness during binocular rivalry is shaped by the alternating perception of different stimuli presented separately to each monocular view. We tested the possibility of causally influencing the likelihood of a stimulus entering awareness. To do this, participants were trained with neurofeedback, using realtime functional magnetic resonance imaging (rt-fMRI), to differentially modulate activation in stimulus-selective visual cortex representing each of the monocular images. Neurofeedback training led to altered bistable perception associated with activity changes in the trained regions. The degree to which training influenced perception predicted changes in grey and white matter volumes of these regions. Short-term intensive neurofeedback training therefore sculpted the dynamics of visual awareness, with associated plasticity in the human brain.

Brain networks for engaging oneself in positive-social emotion regulation.

Positive emotions facilitate cognitive performance, and their absence is associated with burdening psychiatric disorders. However, the brain networks regulating positive emotions are not well understood, especially with regard to engaging oneself in positive-social situations. Here we report convergent evidence from a multimodal approach that includes functional magnetic resonance imaging (fMRI) brain activations, meta-analytic functional characterization, Bayesian model-driven analysis of effective brain connectivity, and personality questionnaires to identify the brain networks mediating the cognitive up-regulation of positive-social emotions. Our comprehensive approach revealed that engaging in positive-social emotion regulation with a self-referential first-person perspective is characterized by dynamic interactions between functionally specialized prefrontal cortex (PFC) areas, the temporoparietal junction (TPJ) and the amygdala. Increased top-down connectivity from the superior frontal gyrus (SFG) controls affective valuation in the ventromedial and dorsomedial PFC, self-referential processes in the TPJ, and modulate emotional responses in the amygdala via the ventromedial PFC. Understanding the brain networks engaged in the regulation of positive-social emotions that involve a first-person perspective is important as they are known to constitute an effective strategy in therapeutic settings.

Real-time fMRI data for testing OpenNFT functionality.

Here, we briefly describe the real-time fMRI data that is provided for testing the functionality of the open-source Python/Matlab framework for neurofeedback, termed Open NeuroFeedback Training (OpenNFT, Koush et al. [1]). The data set contains real-time fMRI runs from three anonymized participants (i.e., one neurofeedback run per participant), their structural scans and pre-selected ROIs/masks/weights. The data allows for simulating the neurofeedback experiment without an MR scanner, exploring the software functionality, and measuring data processing times on the local hardware. In accordance with the descriptions in our main article, we provide data of (1) periodically displayed (intermittent) activation-based feedback; (2) intermittent effective connectivity feedback, based on dynamic causal modeling (DCM) estimations; and (3) continuous classification-based feedback based on support-vector-machine (SVM) estimations. The data is available on our public GitHub repository: https://github.com/OpenNFT/OpenNFT_Demo/releases.

OpenNFT: An open-source Python/Matlab framework for real-time fMRI neurofeedback training based on activity, connectivity and multivariate pattern analysis.

Neurofeedback based on real-time functional magnetic resonance imaging (rt-fMRI) is a novel and rapidly developing research field. It allows for training of voluntary control over localized brain activity and connectivity and has demonstrated promising clinical applications. Because of the rapid technical developments of MRI techniques and the availability of high-performance computing, new methodological advances in rt-fMRI neurofeedback become possible. Here we outline the core components of a novel open-source neurofeedback framework, termed Open NeuroFeedback Training (OpenNFT), which efficiently integrates these new developments. This framework is implemented using Python and Matlab source code to allow for diverse functionality, high modularity, and rapid extendibility of the software depending on the user's needs. In addition, it provides an easy interface to the functionality of Statistical Parametric Mapping (SPM) that is also open-source and one of the most widely used fMRI data analysis software. We demonstrate the functionality of our new framework by describing case studies that include neurofeedback protocols based on brain activity levels, effective connectivity models, and pattern classification approaches. This open-source initiative provides a suitable framework to actively engage in the development of novel neurofeedback approaches, so that local methodological developments can be easily made accessible to a wider range of users.

Maintenance of Voluntary Self-regulation Learned through Real-Time fMRI Neurofeedback.

Neurofeedback based on real-time functional magnetic resonance imaging (fMRI) is an emerging technique that allows for learning voluntary control over brain activity. Such brain training has been shown to cause specific behavioral or cognitive enhancements, and even therapeutic effects in neurological and psychiatric patient populations. However, for clinical applications it is important to know if learned self-regulation can be maintained over longer periods of time and whether it transfers to situations without neurofeedback. Here, we present preliminary results from five healthy participants who successfully learned to control their visual cortex activity and who we re-scanned 6 and 14 months after the initial neurofeedback training to perform learned self-regulation. We found that participants achieved levels of self-regulation that were similar to those achieved at the end of the successful initial training, and this without further neurofeedback information. Our results demonstrate that learned self-regulation can be maintained over longer periods of time and causes lasting transfer effects. They thus support the notion that neurofeedback is a promising therapeutic approach whose effects can last far beyond the actual training period.