Sarah Prinsloo

Background Chemotherapy‐induced peripheral neuropathy (CIPN) includes negative sensations that remain a major chronic problem for cancer survivors. Previous research demonstrated that neurofeedback (a closed‐loop brain–computer interface [BCI]) was effective at treating CIPN versus a waitlist control (WLC). The authors' a priori hypothesis was that BCI would be superior to placebo feedback (placebo control [PLC]) and to WLC in alleviating CIPN and that changes in brain activity would predict symptom report. Methods Randomization to one of three conditions occurred between November 2014 and November 2018. Breast cancer survivors no longer in treatment were assessed at baseline, at the end of 20 treatment sessions, and 1 month later. Auditory and visual rewards were given over 20 sessions based on each patient's ability to modify their own electroencephalographic signals. The Pain Quality Assessment Scale (PQAS) at the end of treatment was the primary outcome, and changes in electroencephalographic signals and 1‐month data also were examined. Results The BCI and PLC groups reported significant symptom reduction. The BCI group demonstrated larger effect size differences from the WLC group than the PLC group (mean change score: BCI vs. WLC, −2.60 vs. 0.38; 95% confidence interval, −3.67, −1.46 [ p = .000; effect size, 1.07]; PLC, −2.26; 95% confidence interval, −3.33, −1.19 [ p = .001 vs. WLC; effect size, 0.9]). At 1 month, symptoms continued to improve only for the BCI group. Targeted brain changes at the end of treatment predicted symptoms at 1 month for the BCI group only. Conclusions BCI is a promising treatment for CIPN and may have a longer lasting effect than placebo (nonspecific BCI), which is an important consideration for long‐term symptom relief. Although scientifically interesting, the ability to separate real from placebo treatment may not be as important as understanding the placebo effects differently from effects of the intervention. Plain Language Summary Chemotherapy‐induced nerve pain (neuropathy) can be disabling for cancer survivors; however, the way symptoms are felt depends on how the brain interprets the signals from nerves in the body. We determined that the perception of neuropathy can be changed by working directly with the brain. Survivors in our trial played 20 sessions of a type of video game that was designed to change the way the brain processed sensation and movement. In this, our second trial, we again observed significant improvement in symptoms that lasted after the treatment was complete.