Closed-Loop Infraslow Brain–Computer Interface can Modulate Cortical Activity and Connectivity in Individuals With Chronic Painful Knee Osteoarthritis: A Secondary Analysis of a Randomized Placebo-Controlled Clinical Trial

Introduction. Chronic pain is a percept due to an imbalance in the activity between sensory-discriminative, motivational-affective, and descending pain-inhibitory brain regions. Evidence suggests that electroencephalography (EEG) infraslow fluctuation neurofeedback (ISF-NF) training can improve clinical outcomes. It is unknown whether such training can induce EEG activity and functional connectivity (FC) changes. A secondary data analysis of a feasibility clinical trial was conducted to determine whether EEG ISF-NF training can significantly alter EEG activity and FC between the targeted cortical regions in people with chronic painful knee osteoarthritis (OA). Methods. A parallel, two-arm, double-blind, randomized, sham-controlled clinical trial was conducted. People with chronic knee pain associated with OA were randomized to receive sham NF training or source-localized ratio ISF-NF training protocol to down-train ISF bands at the somatosensory (SSC), dorsal anterior cingulate (dACC), and uptrain pregenual anterior cingulate cortices (pgACC). Resting state EEG was recorded at baseline and immediate post-training. Results. The source localization mapping demonstrated a reduction ( P = .04) in the ISF band activity at the left dorsolateral prefrontal cortex (LdlPFC) in the active NF group. Region of interest analysis yielded significant differences for ISF ( P = .008), slow ( P = .007), beta ( P = .043), and gamma ( P = .012) band activities at LdlPFC, dACC, and bilateral SSC. The FC between pgACC and left SSC in the delta band was negatively correlated with pain bothersomeness in the ISF-NF group. Conclusion. The EEG ISF-NF training can modulate EEG activity and connectivity in individuals with chronic painful knee osteoarthritis, and the observed EEG changes correlate with clinical pain measures.