Fibromyalgia is a chronic pain condition contributing to significant disability worldwide. Neuroimaging studies identify abnormal effective connectivity between cortical areas responsible for descending pain modulation (pregenual anterior cingulate cortex, pgACC) and sensory components of pain experience (primary somatosensory cortex, S1). Neurofeedback, a brain-computer interface technique, can normalise dysfunctional brain activity, thereby improving pain and function. This study evaluates the safety, feasibility, and acceptability of a novel electroencephalography-based neurofeedback training, targeting effective alpha-band connectivity from the pgACC to S1 and exploring its effect on pain and function. Participants with fibromyalgia (N = 30; 15 = active, 15 = placebo) received 12 sessions of neurofeedback. Feasibility and outcome measures of pain (Brief Pain Inventory) and function (Revised Fibromyalgia Impact Questionnaire) were collected at baseline and immediately, ten-days, and one-month post-intervention. Descriptive statistics demonstrate effective connectivity neurofeedback training is feasible (recruitment rate: 6 participants per-month, mean adherence: 80.5%, dropout rate: 20%), safe (no adverse events) and highly acceptable (average 8.0/10) treatment approach for fibromyalgia. Active and placebo groups were comparable in their decrease in pain and functional impact. Future fully powered clinical trial is warranted to test the efficacy of the effective connectivity neurofeedback training in people with fibromyalgia with versus without chronic fatigue.

The core resting-state networks (RSNs) have been shown to be dysfunctional in individuals with internalizing disorders (IDs; e.g., anxiety, depression). Source-localised, closed-loop brain training of infraslow (≤ 0.1 Hz) EEG signals may have the potential to reduce symptoms associated with IDs and restore normal core RSN function. We conducted a pilot randomized, double-blind, sham-controlled, parallel-group (3-arm) trial of infraslow neurofeedback (ISF-NFB) in adult females (n = 60) with IDs. Primary endpoints, which included the Hospital Anxiety and Depression Scale (HADS) and resting-state EEG activity and connectivity, were measured at baseline and post 6 sessions. This study found credible evidence of strong nonspecific effects as evidenced by clinically important HADS score improvements (i.e., reductions) across groups. An absence of HADS score change differences between the sham and active groups indicated a lack of specific effects. Although there were credible slow (0.2–1.5 Hz) and delta (2–3.5 Hz) band activity reductions in the 1-region ISF-NFB group relative to sham within the targeted region of interest (i.e., posterior cingulate), differences in activity and connectivity modulation in the targeted frequency band of interest (i.e., ISFs = 0.01–0.1 Hz) were lacking between sham and active groups. Credible positive associations between changes in HADS depression scores and anterior cingulate cortex slow and delta activity also were found. Short-term sham and genuine ISF-NFB resulted in rapid, clinically important improvements that were nonspecific in nature and possibly driven by placebo-related mechanisms. Future ISF-NFB trials should consider implementing design modifications that may better induce differential modulation of ISFs between sham and treatment groups, thereby enhancing the potential for specific clinical effects in ID populations. The trial was prospectively registered with the Australia New Zealand Clinical Trials Registry (ANZCTR; Trial ID: ACTRN12619001428156).

Chronic low back pain (CLBP) is a disabling condition worldwide. In CLBP, neuroimaging studies demonstrate abnormal activities in cortical areas responsible for pain modulation, emotional, and sensory components of pain experience [i.e., pregenual and dorsal anterior cingulate cortex (pgACC, dACC), and somatosensory cortex (SSC), respectively]. This pilot study, conducted in a university setting, evaluated the feasibility, safety, and acceptability of a novel electroencephalography-based infraslow-neurofeedback (EEG ISF-NF) technique for retraining activities in pgACC, dACC and SSC and explored its effects on pain and disability. Participants with CLBP (n = 60), recruited between July’20 to March’21, received 12 sessions of either: ISF-NF targeting pgACC, dACC + SSC, a ratio of pgACC*2/dACC + SSC, or Placebo-NF. Descriptive statistics demonstrated that ISF-NF training is feasible [recruitment rate (7 participants/month), dropouts (25%; 20–27%), and adherence (80%; 73–88%)], safe (no adverse events reported), and was moderate to highly acceptable [Mean ± SD: 7.8 ± 2.0 (pgACC), 7.5 ± 2.7 (dACC + SCC), 8.2 ± 1.9 (Ratio), and 7.7 ± 1.5 (Placebo)]. ISF-NF targeting pgACC demonstrated the most favourable clinical outcomes, with a higher proportion of participants exhibiting a clinically meaningful reduction in pain severity [53%; MD (95% CI): − 1.9 (− 2.7, − 1.0)], interference [80%; MD (95% CI): − 2.3 (− 3.5, − 1.2)], and disability [73%; MD (95% CI): − 4.5 (− 6.1, − 2.9)] at 1-month follow-up. ISF-NF training is a feasible, safe, and an acceptable treatment approach for CLBP.

Abstract Background The core intrinsic connectivity networks (core-ICNs), encompassing the default-mode network (DMN), salience network (SN) and central executive network (CEN), have been shown to be dysfunctional in individuals with internalizing disorders (IDs, e.g. major depressive disorder, MDD; generalized anxiety disorder, GAD; social anxiety disorder, SOC). As such, source-localized, closed-loop brain training of electrophysiological signals, also known as standardized low-resolution electromagnetic tomography (sLORETA) neurofeedback (NFB), targeting key cortical nodes within these networks has the potential to reduce symptoms associated with IDs and restore normal core ICN function. We intend to conduct a randomized, double-blind (participant and assessor), sham-controlled, parallel-group (3-arm) trial of sLORETA infraslow (<0.1 Hz) fluctuation neurofeedback (sLORETA ISF-NFB) 3 times per week over 4 weeks in participants (n=60) with IDs. Our primary objectives will be to examine patient-reported outcomes (PROs) and neurophysiological measures to (1) compare the potential effects of sham ISF-NFB to either genuine 1-region ISF-NFB or genuine 2-region ISF-NFB, and (2) assess for potential associations between changes in PRO scores and modifications of electroencephalographic (EEG) activity/connectivity within/between the trained regions of interest (ROIs). As part of an exploratory analysis, we will investigate the effects of additional training sessions and the potential for the potentiation of the effects over time. Methods We will randomly assign participants who meet the criteria for MDD, GAD, and/or SOC per the MINI (Mini International Neuropsychiatric Interview for DSM-5) to one of three groups: (1) 12 sessions of posterior cingulate cortex (PCC) ISF-NFB up-training (n=15), (2) 12 sessions of concurrent PCC ISF up-training and dorsal anterior cingulate cortex (dACC) ISF-NFB down-training (n=15), or (3) 6 sessions of yoked-sham training followed by 6 sessions genuine ISF-NFB (n=30). Transdiagnostic PROs (Hospital Anxiety and Depression Scale, HADS; Inventory of Depression and Anxiety Symptoms – Second Version, IDAS-II; Multidimensional Emotional Disorder Inventory, MEDI; Intolerance of Uncertainty Scale – Short Form, IUS-12; Repetitive Thinking Questionnaire, RTQ-10) as well as resting-state neurophysiological measures (full-band EEG and ECG) will be collected from all subjects during two baseline sessions (approximately 1 week apart) then at post 6 sessions, post 12 sessions, and follow-up (1 month later). We will employ Bayesian methods in R and advanced source-localisation software (i.e. exact low-resolution brain electromagnetic tomography; eLORETA) in our analysis. Discussion This protocol will outline the rationale and research methodology for a clinical pilot trial of sLORETA ISF-NFB targeting key nodes within the core-ICNs in a female ID population with the primary aims being to assess its potential efficacy via transdiagnostic PROs and relevant neurophysiological measures. Trial registration Our study was prospectively registered with the Australia New Zealand Clinical Trials Registry (ANZCTR; Trial ID: ACTRN12619001428156). Registered on October 15, 2019.

Acute pain is a physiological response that causes an unpleasant sensory and emotional experience in the presence of actual or potential tissue injury. Anatomically and symptomatically, chronic pathological pain can be divided into three distinct but interconnected pathways, a lateral “painfulness” pathway, a medial “suffering” pathway and a descending pain inhibitory circuit. Pain (fullness) can exist without suffering and suffering can exist without pain (fullness). The triple network model is offering a generic unifying framework that may be used to understand a variety of neuropsychiatric illnesses. It claims that brain disorders are caused by aberrant interactions within and between three cardinal brain networks: the self-representational default mode network, the behavioral relevance encoding salience network and the goal oriented central executive network. A painful stimulus usually leads to a negative cognitive, emotional, and autonomic response, phenomenologically expressed as pain related suffering, processed by the medial pathway. This anatomically overlaps with the salience network, which encodes behavioral relevance of the painful stimuli and the central sympathetic control network. When pain lasts longer than the healing time and becomes chronic, the pain- associated somatosensory cortex activity may become functionally connected to the self-representational default mode network, i.e., it becomes an intrinsic part of the self-percept. This is most likely an evolutionary adaptation to save energy, by separating pain from sympathetic energy-consuming action. By interacting with the frontoparietal central executive network, this can eventually lead to functional impairment. In conclusion, the three well-known pain pathways can be combined into the triple network model explaining the whole range of pain related co-morbidities. This paves the path for the creation of new customized and personalized treatment methods.

Background: The core intrinsic connectivity networks (ICNs), encompassing the default-mode network (DMN), salience network (SN) and central executive network (CEN), have been shown to be dysfunctional in individual’s with internalizing disorders (IDs; e.g. major depressive disorder, MDD; generalized anxiety disorder, GAD; social anxiety disorder, SOC). As such, source-localised electroencephalogram neurofeedback (EEG-NFB) therapy targeting key cortical nodes within these networks has the potential to reduce symptoms associated with IDs and restore normal core ICN function. We intend to conduct a transdiagnostic, randomized, double-blind, sham-controlled, dose-response, parallel-group trial of standardized low-resolution electromagnetic tomography electrophysiological infraslow (<0.1 Hz) fluctuation neurofeedback (sLORETA eISF-NFB) 3 times per week over 4 weeks in participants (n=60) with IDs. Our primary aim will be to assess the clinical efficacy of sLORETA eISF-NFB via relevant patient-reported outcomes (PROs). Methods: We will randomly assign participants with a current diagnosis of MDD, GAD, and/or SOC to one of four groups: 1) 12 sessions of posterior cingulate cortex (PCC) up-training (n=15), 2) 6 sessions of yoked-sham training followed by 6 sessions of PCC up-training (n=15), 3) 12 sessions of concurrent mid-cingulate (MCC) down-training and PCC up-training (n=15), or 4) 6 sessions of yoked-sham training followed by 6 sessions of concurrent MCC down-training and PCC up-training. Transdiagnostic PROs, as well as resting-state neuro-physiological measures (EEG; electrocardiography, ECG; electrodermal activity, EDA), will be collected from all subjects at baseline, mid-training, 1 week post-training, and 1 month post-training. We will further compare baseline PROs and neuro-physiological measures to age- and sex-matched non-ID (i.e. no ID diagnosis) controls. Discussion : This protocol will outline the rationale and research methodology for a clinical trial of sLORETA eISF-NFB targeting key nodes within the core ICNs in a population with IDs with the primary aim being to assess its specific (e.g. non-placebo induced) efficacy via PROs. Trial Registration: Our study was prospectively registered with the Australia New Zealand Clinical Trials Registry (ANZCTR; Trial Id: ACTRN12619001428156)

Introduction: Persistent pain is a significant contributor to disability in people living with knee osteoarthritis (KOA). Brain imaging, including electrophysiological studies, confirms altered cortical oscillatory and synchrony patterns in cognitive, affective, and somatosensory areas in individuals with KOA pain. Electroencephalography neurofeedback (EEG-NF) training is a form of neuromodulatory intervention that can help to reduce pain via normalizing dysrhythmic cortical oscillatory patterns that are linked to the pain experience. However, there is a dearth of evidence towards the efficacy of NF in individuals with musculoskeletal pain. Aim: The proposed research is intended to pilot the NF training protocol and assess the feasibility, safety, and acceptability of NF training in individuals with KOA and estimate the variability of experimental and clinical outcome measures following NF training. Design: A parallel, two-armed, double-blind (participant and assessor) pilot randomized sham-controlled clinical trial. Methods: Adults aged 44–75 years with a clinical diagnosis of KOA will be recruited and randomized to either active or sham EEG-NF training. Both groups will receive auditory feedback as a reward for achieving a predetermined activity threshold of the target areas of the brain. Outcome measures include feasibility measures (recruitment, randomization, retention, and dropout rates), acceptability, and adverse events; clinical measures (pain, interference, sleep, mood, and physical activity); and experimental pain outcomes (quantitative sensory testing procedures). Discussion: Outcomes from this study will inform the feasibility and methodology for a future randomized controlled clinical trial.

The posterior cingulate cortex (PCC) is involved in food craving in obese food addicted individuals. This randomised, double-blind, placebo-controlled parallel study explored the potential therapeutic effects of infraslow neurofeedback (ISF-NF) on food craving targeting the PCC in obese women with symptoms of food addiction. Participants received six sessions of either ISF-NF (n = 11) or placebo (n = 10) over a three-week period. There were no reported adverse effects. Electrophysiologically, there were significant increases in infraslow activity (p = 0.0002) and infraslow/beta nesting (p < 0.001) in the PCC in the ISF-NF group (mean r = 0.004 ± 0.002) compared to placebo (mean r = 0.02 ± 0.002) two days after the last intervention. Also, there was a significant decrease in different dimensions of state food craving compared to baseline and to placebo. Findings suggest that source localized IFS-NF results in electrophysiological changes and may be associated with reduced food craving. This trial is registered at www.anzctr.org.au , identifier, ACTRN12617000601336. This study was funded by the Otago Medical Research Grant: CT375.