Feasibility and utility of amygdala neurofeedback.

Amygdala NeuroFeedback (NF) have the potential of being a valuable non-invasive intervention tool in many psychiatric disporders. However, the feasibility and best practices of this method have not been systematically examined. The current article presents a review of amygdala-NF studies, an analytic summary of study design parameters, and examination of brain mechanisms related to successful amygdala-NF performance. A meta-analysis of 33 publications showed that real amygdala-NF facilitates learned modulation compared to control conditions. In addition, while variability in study dsign parameters is high, these design choices are implicitly organized by the targeted valence domain (positive or negative). However, in most cases the neuro-behavioral effects of targeting such domains were not directly assessed. Lastly, re-analyzing six data sets of amygdala-fMRI-NF revealed that successful amygdala down-modulation is coupled with deactivation of the posterior insula and nodes in the Default-Mode-Network. Our findings suggest that amygdala self-modulation can be acquired using NF. Yet, additional controlled studies, relevant behavioral tasks before and after NF intervention, and neural 'target engagement' measures are critically needed to establish efficacy and specificity. In addition, the fMRI analysis presented here suggest that common accounts regarding the brain network involved in amygdala NF might reflect unsuccessful modulation attempts rather than successful modulation.

Neurofeedback through the lens of reinforcement learning.

Despite decades of experimental and clinical practice, the neuropsychological mechanisms underlying neurofeedback (NF) training remain obscure. NF is a unique form of reinforcement learning (RL) task, during which participants are provided with rewarding feedback regarding desired changes in neural patterns. However, key RL considerations - including choices during practice, prediction errors, credit-assignment problems, or the exploration-exploitation tradeoff - have infrequently been considered in the context of NF. We offer an RL-based framework for NF, describing different internal states, actions, and rewards in common NF protocols, thus fashioning new proposals for characterizing, predicting, and hastening the course of learning. In this way we hope to advance current understanding of neural regulation via NF, and ultimately to promote its effectiveness, personalization, and clinical utility.

An Investigation of Awareness and Metacognition in Neurofeedback with the Amygdala Electrical Fingerprint.

Awareness theory posits that individuals connected to a brain-computer interface can learn to estimate and discriminate their brain states. We used the amygdala Electrical Fingerprint (amyg-EFP) - a functional Magnetic Resonance Imaging-inspired Electroencephalogram surrogate of deep brain activation - to investigate whether participants could accurately estimate their own brain activation. Ten participants completed up to 20 neurofeedback runs and estimated their amygdala-EFP activation (depicted as a thermometer) and confidence in this rating during each trial. We analysed data using multilevel models, predicting the real thermometer position with participant rated position and adjusted for activation during the previous trial. Hypotheses on learning regulation and improvement of estimation were not confirmed. However, participant ratings were significantly associated with the amyg-EFP signal. Higher rating accuracy also predicted higher subjective confidence in the rating. This proof-of-concept study introduces an approach to study awareness with fMRI-informed neurofeedback and provides initial evidence for metacognition in neurofeedback.

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.

Improved emotion regulation after neurofeedback: A single-arm trial in patients with borderline personality disorder.

Real-time functional magnetic resonance imaging (fMRI) neurofeedback training of amygdala hemodynamic activity directly targets a neurobiological mechanism, which contributes to emotion regulation problems in borderline personality disorder (BPD). However, it remains unknown which outcome measures can assess changes in emotion regulation and affective instability, associated with amygdala downregulation in a clinical trial. The current study directly addresses this question. Twenty-four female patients with a DSM-IV BPD diagnosis underwent four runs of amygdala neurofeedback. Before and after the training, as well as at a six-weeks follow-up assessment, participants completed measures of emotion dysregulation and affective instability at diverse levels of analysis (verbal report, clinical interview, ecological momentary assessment, emotion-modulated startle, heart rate variability, and fMRI). Participants were able to downregulate their amygdala blood oxygen-dependent (BOLD) response with neurofeedback. There was a decrease of BPD symptoms as assessed with the Zanarini rating scale for BPD (ZAN-BPD) and a decrease in emotion-modulated startle to negative pictures after training. Further explorative analyses suggest that patients indicated less affective instability, as seen by lower hour-to-hour variability in negative affect and inner tension in daily life. If replicated by an independent study, our results imply changes in emotion regulation and affective instability for several systems levels, including behavior and verbal report. Conclusions are limited due to the lack of a control group. A randomized controlled trial (RCT) will be needed to confirm effectiveness of the training.

Neurofeedback and neuroplasticity of visual self-processing in depressed and healthy adolescents: A preliminary study.

Adolescence is a neuroplastic period for self-processing and emotion regulation transformations, that if derailed, are linked to persistent depression. Neural mechanisms of adolescent self-processing and emotion regulation ought to be targeted via new treatments, given moderate effectiveness of current interventions. Thus, we implemented a novel neurofeedback protocol in adolescents to test the engagement of circuits sub-serving self-processing and emotion regulation. METHODS: Depressed (n = 34) and healthy (n = 19) adolescents underwent neurofeedback training using a novel task. They saw their happy face as a cue to recall positive memories and increased displayed amygdala and hippocampus activity. The control condition was counting-backwards while viewing another happy face. A self vs. other face recognition task was administered before and after neurofeedback training. RESULTS: Adolescents showed higher frontotemporal activity during neurofeedback and higher amygdala and hippocampus and hippocampi activity in time series and region of interest analyses respectively. Before neurofeedback there was higher saliency network engagement for self-face recognition, but that network engagement was lower after neurofeedback. Depressed youth exhibited higher fusiform, inferior parietal lobule and cuneus activity during neurofeedback, but controls appeared to increase amygdala and hippocampus activity faster compared to depressed adolescents. CONCLUSIONS: Neurofeedback recruited frontotemporal cortices that support social cognition and emotion regulation. Amygdala and hippocampus engagement via neurofeedback appears to change limbic-frontotemporal networks during self-face recognition. A placebo group or condition and contrasting amygdala and hippocampus, hippocampi or right amygdala versus frontal loci of neurofeedback, e.g. dorsal anterior cingulate cortex, with longer duration of neurofeedback training will elucidate dosage and loci of neurofeedback in adolescents.

Current progress in real-time functional magnetic resonance-based neurofeedback: Methodological challenges and achievements.

Neurofeedback (NF) is a research and clinical technique, characterized by live demonstration of brain activation to the subject. The technique has become increasingly popular as a tool for the training of brain self-regulation, fueled by the superiority in spatial resolution and fidelity brought along with real-time analysis of fMRI (functional magnetic resonance imaging) data, compared to the more traditional EEG (electroencephalography) approach. NF learning is a complex phenomenon and a controversial discussion on its feasibility and mechanisms has arisen in the literature. Critical aspects of the design of fMRI-NF studies include the localization of neural targets, cognitive and operant aspects of the training procedure, personalization of training, and the definition of training success, both through neural effects and (for studies with therapeutic aims) through clinical effects. In this paper, we argue that a developmental perspective should inform neural target selection particularly for pediatric populations, and different success metrics may allow in-depth analysis of NF learning. The relevance of the functional neuroanatomy of NF learning for brain target selection is discussed. Furthermore, we address controversial topics such as the role of strategy instructions, sometimes given to subjects in order to facilitate learning, and the timing of feedback. Discussion of these topics opens sight on problems that require further conceptual and empirical work, in order to improve the impact that fMRI-NF could have on basic and applied research in future.

The orbitofrontal cortex processes neurofeedback failure signals.

Receiving feedback from neural activity, dubbed neurofeedback, can reinforce brain self-regulation. In a real-time functional magnetic resonance imaging (fMRI) experiment, healthy participants received amygdala neurofeedback via a visual brain-computer interface. The brain response to signals of reward and failure was modeled. In contrast to previous analyses, we take into account feedback that immediately preceded these signals. That means we tested whether responses were modulated while participants observed sequent reward and failure signals. The orbitofrontal cortex (OFC) showed a negative Blood Oxygenation Level Dependent (BOLD) response to failure signals, when they were preceded by more failure signals. When failure signals were preceded by reward, in contrast, the response was less pronounced. The results suggest weighted processing of neurofeedback value in the OFC. Learning to self-regulate the brain with neurofeedback may involve similar neural networks as the learning of goal-directed action.

Process-based framework for precise neuromodulation.

Functional MRI neurofeedback (NF) allows humans to self-modulate neural patterns in specific brain areas. This technique is regarded as a promising tool to translate neuroscientific knowledge into brain-guided psychiatric interventions. However, its clinical implementation is restricted by unstandardized methodological practices, by clinical definitions that are poorly grounded in neurobiology, and by lack of a unifying framework that dictates experimental choices. Here we put forward a new framework, termed 'process-based NF', which endorses a process-oriented characterization of mental dysfunctions to form precise and effective psychiatric treatments. This framework relies on targeting specific dysfunctional mental processes by modifying their underlying neural mechanisms and on applying process-specific contextual feedback interfaces. Finally, process-based NF offers designs and a control condition that address the methodological shortcomings of current approaches, thus paving the way for a precise and personalized neuromodulation.

fMRI neurofeedback in emotion regulation: A literature review.

OBJECTIVES: Emotion regulation is one of the most prevalent objectives for real-time fMRI neurofeedback (rt-fMRI-NF) studies. The existing studies differ in a number of methodological parameters. This study provides a literature review of the main parameters and results of studies using rt-fMRI-NF for emotion regulation enhancement. METHOD: A search of the Web of Science database up through November 8, 2018, identified 144 articles written in English, 89 of which were excluded as irrelevant for this study. The remaining 51 original studies and four secondary analyses of previously published original studies were included in the literature review. The selection of target brain areas, target populations, emotion regulation protocols, NF presentation, control group types, and emotion regulation instructions were examined in relation to achieved brain regulation and changes in cognitive or clinical outcomes. Study results were evaluated in terms of their statistical robustness. RESULTS: The results show that healthy people are able to regulate their brain activity in the presence of rt-fMRI-NF from various brain regions related to emotion regulation, including the amygdala, anterior insula, and anterior cingulate cortex. The regulation of brain activity using rt-fMRI-NF from prefrontal-limbic connectivity or from individually navigated brain areas is feasible as well. Most studies that used a control group show that rt-fMRI-NF actually induces some effects on brain regulation, cognitive variables, and clinical variables. Generally, the success of ROI regulation during NF training is related to the combination of target brain region, the type of emotion regulation task, and the population undergoing the training. In terms of patient groups, the strongest support for the beneficial effects of rt-fMRI-NF has been shown in increased positive emotion experiencing in patients with depression and in decreased anxiety in patients with anxiety disorders. Symptom reduction following NF training has been also reported in patients with PTSD, BPD, and schizophrenia, but direct comparisons with control groups in these studies makes it impossible to evaluate the added value of NF. Studies often do not report all the relevant analyses for evaluating NF success and many studies lack statistical robustness. CONCLUSIONS: Overall, rt-fMRI-NF seems a promising tool for emotion regulation enhancement with the potential to induce long-term symptom reduction in patients with various mental disorders. Preplanning of statistical analyses, careful interpretations of the results, and evaluations of the NF effect on symptom reduction in patient groups is recommended.