Source localized infraslow neurofeedback training in people with chronic painful knee osteoarthritis: A randomized, double-blind, sham-controlled feasibility clinical trial

Abstract

Persistent pain is a key symptom in people living with knee osteoarthritis (KOA). Infra-slow Neurofeedback (ISF-NF) training is a recent development focusing on modulating cortical slow-wave activity to improve pain outcomes. A parallel, two-armed double-blinded, randomized sham-controlled, feasibility clinical trial aimed to determine the feasibility and safety of a novel electroencephalography-based infraslow fluctuation neurofeedback (EEG ISF-NF) training in people with KOA and determine the variability of clinical outcomes and EEG changes following NF training. Eligible participants attended nine 30-min ISF-NF training sessions involving three cortical regions linked to pain. Feasibility measures were monitored during the trial period. Pain and functional outcomes were measured at baseline, post-intervention, and follow-up after 2 weeks. Resting-state EEG was recorded at baseline and immediate post-intervention. Participants were middle-aged (61.7 ± 7.6 years), New Zealand European (90.5%), and mostly females (62%) with an average knee pain duration of 4 ± 3.4 years. The study achieved a retention rate of 91%, with 20/22 participants completing all the sessions. Participants rated high levels of acceptance and “moderate to high levels of perceived effectiveness of the training.” No serious adverse events were reported during the trial. Mean difference (95% CI) for clinical pain and function measures are as follows for pain severity [active: 0.89 ± 1.7 (−0.27 to 2.0); sham: 0.98 ± 1.1 (0.22–1.7)], pain interference [active: 0.75 ± 2.3 (−0.82 to 2.3); Sham: 0.89 ± 2.1 (−0.60 to 2.4)], pain unpleasantness [active: 2.6 ± 3.7 (0.17–5.1); sham: 2.8 ± 3 (0.62–5.0)] and physical function [active: 6.2 ± 13 (−2.6 to 15); sham: 1.6 ± 12 (−6.8 to 10)]. EEG sources demonstrated frequency-specific neuronal activity, functional connectivity, and ISF ratio changes following NF training. The findings of the study indicated that the ISF-NF training is a feasible, safe, and acceptable intervention for pain management in people with KOA, with high levels of perceived effectiveness. The study also reports the variability in clinical, brain activity, and connectivity changes following training.

Infraslow Neurofeedback Training Alters Effective Connectivity in Individuals with Chronic Low Back Pain: A Secondary Analysis of a Pilot Randomized Placebo-Controlled Study

“…Previous EEG-NF studies, however, have used conventional neurofeedback techniques, reinforcing alpha (~8–12 Hz) or sensorimotor (~12–15 Hz) rhythms and suppressing a combination of theta (~4–8 Hz) and/or beta (~13–30 Hz) rhythms, at one to two specific electrode levels [ 9 , 10 , 11 ]. However, only one study evaluated source-localized EEG-NF training of the ISF (<0.01 Hz) at three cortical regions simultaneously for the treatment of chronic pain [ 68 ]. The source-localized EEG-NF permits training specific and multiple brain regions simultaneously, potentially changing the activity in the trained area and connectivity to/from the trained area [ 69 , 70 ].…”

Exploring electroencephalographic infraslow neurofeedback treatment for chronic low back pain: a double-blinded safety and feasibility randomized placebo-controlled trial

“…Therefore, we hypothesise that the source localised EEG-NF specifically targeting the ISF bands in pain processing brain regions (pgACC, dACC, and SSC) could be more effective than targeting higher frequency bands at specific electrode levels and can potentially promote greater pain relief. To date, EEG ISF-NF training has been explored and demonstrated positive results by a few pilot studies as a potential treatment option for food addiction 26 , internalizing disorders 27 , 28 , and osteoarthritic pain 29 . However, none of the studies has explored EEG ISF-NF training as a potential treatment option for treatment of CLBP and is warranted given the high burden of CLBP.…”

Self-regulation training for people with knee osteoarthritis: a protocol for a feasibility randomised control trial (MiNT trial)

“…NF also improves anxiety, emotional regulation, brain activity, and autonomic modulation, potentially mediating mechanisms of pain reduction (56-63). Pilot EEG-NF training targeting infraslow frequency bands demonstrated encouraging patterns for pain outcomes in people with chronic musculoskeletal pain (64,65).…”

“…However, evidence of the effectiveness of these two self-regulation training methods is lacking in people with knee OA, a common chronic secondary musculoskeletal pain condition. Although both interventions appear to rely on self-regulatory principles, the physiological and psychological mechanisms through which these two interventions improve pain outcomes may be different (63)(64)(65)(66)(67)(68)(69). Therefore, identifying the mechanisms for how these self-regulatory interventions improve outcomes can assist in further optimising protocols to enhance outcomes.…”

“…However, prior to conducting this full RCT, we propose conducting a feasibility trial to address the factors that could influence the design of the full clinical trial (64). The feasibility issues/questions that require understanding prior to conducting a full-powered RCT are as follows: Are mindfulness meditation and neurofeedback training feasible, safe, and acceptable interventions for people with knee OA?…”