Limbic self-neuromodulation as a novel treatment option for emotional dysregulation in premenstrual dysphoric disorder (PMDD); a proof-of-concept study.

AIM: To assess the efficacy of a novel neurofeedback (NF) method, targeting limbic activity, to treat emotional dysregulation related to premenstrual dysphoric disorder (PMDD). METHODS: We applied a NF probe targeting limbic activity using a functional magnetic resonance imaging-inspired electroencephalogram model (termed Amyg-EFP-NF) in a double-blind randomized controlled trial. A frontal alpha asymmetry probe (AAS-NF), served as active control. Twenty-seven participants diagnosed with PMDD (mean age = 33.57 years, SD = 5.67) were randomly assigned to Amyg-EFP-NF or AAS-NF interventions with a 2:1 ratio, respectively. The treatment protocol consisted of 11 NF sessions through three menstrual cycles, and a follow-up assessment 3 months thereafter. The primary outcome measure was improvement in the Revised Observer Version of the Premenstrual Tension Syndrome Rating Scale (PMTS-OR). RESULTS: A significant group by time effect was observed for the core symptom subscale of the PMTS-OR, with significant improvement observed at follow-up for the Amyg-EFP group compared with the AAS group [F(1, 15)=4.968, P = 0.042]. This finding was specifically robust for reduction in anger [F(1, 15) = 22.254, P < 0.001]. A significant correlation was found between learning scores and overall improvement in core symptoms (r = 0.514, P = 0.042) suggesting an association between mechanism of change and clinical improvement. CONCLUSION: Our preliminary findings suggest that Amyg-EFP-NF may serve as an affordable and accessible non-invasive treatment option for emotional dysregulation in women suffering from PMDD. Our main limitations were the relatively small number of participants and the lack of a sham-NF placebo arm.

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.

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.

Electrical fingerprint of the amygdala guides neurofeedback training for stress resilience.

Real-time functional magnetic resonance imaging (rt-fMRI) has revived the translational perspective of neurofeedback (NF)1. Particularly for stress management, targeting deeply located limbic areas involved in stress processing2 has paved new paths for brain-guided interventions. However, the high cost and immobility of fMRI constitute a challenging drawback for the scalability (accessibility and cost-effectiveness) of the approach, particularly for clinical purposes3. The current study aimed to overcome the limited applicability of rt-fMRI by using an electroencephalography (EEG) model endowed with improved spatial resolution, derived from simultaneous EEG-fMRI, to target amygdala activity (termed amygdala electrical fingerprint (Amyg-EFP))4-6. Healthy individuals (n = 180) undergoing a stressful military training programme were randomly assigned to six Amyg-EFP-NF sessions or one of two controls (control-EEG-NF or NoNF), taking place at the military training base. The results demonstrated specificity of NF learning to the targeted Amyg-EFP signal, which led to reduced alexithymia and faster emotional Stroop, indicating better stress coping following Amyg-EFP-NF relative to controls. Neural target engagement was demonstrated in a follow-up fMRI-NF, showing greater amygdala blood-oxygen-level-dependent downregulation and amygdala-ventromedial prefrontal cortex functional connectivity following Amyg-EFP-NF relative to NoNF. Together, these results demonstrate limbic specificity and efficacy of Amyg-EFP-NF during a stressful period, pointing to a scalable non-pharmacological yet neuroscience-based training to prevent stress-induced psychopathology.

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.

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 ±â€¯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.