Machine learning predicts spinal cord stimulation surgery outcomes and reveals novel neural markers for chronic pain

Spinal cord stimulation (SCS) is a well-accepted therapy for refractory chronic pain. However, predicting responders remain a challenge due to a lack of objective pain biomarkers. The present study applies machine learning to predict which patients will respond to SCS based on intraoperative electroencephalogram (EEG) data and recognized outcome measures. The study included 20 chronic pain patients who were undergoing SCS surgery. During intraoperative monitoring, EEG signals were recorded under SCS OFF (baseline) and ON conditions, including tonic and high density (HD) stimulation. Once spectral EEG features were extracted during offline analysis, principal component analysis (PCA) and a recursive feature elimination approach were used for feature selection. A subset of EEG features, clinical characteristics of the patients and preoperative patient reported outcome measures (PROMs) were used to build a predictive model. Responders and nonresponders were grouped based on 50% reduction in 3-month postoperative Numeric Rating Scale (NRS) scores. The two groups had no statistically significant differences with respect to demographics (including age, diagnosis, and pain location) or PROMs, except for the postoperative NRS (worst pain: p = 0.028; average pain: p < 0.001) and Oswestry Disability Index scores (ODI, p = 0.030). Alpha-theta peak power ratio differed significantly between CP3-CP4 and T3-T4 (p = 0.019), with the lowest activity in CP3-CP4 during tonic stimulation. The decision tree model performed best, achieving 88.2% accuracy, an F1 score of 0.857, and an area under the curve (AUC) of the receiver operating characteristic (ROC)  of 0.879. Our findings suggest that combination of subjective self-reports, intraoperatively obtained EEGs, and well-designed machine learning algorithms might be potentially used to distinguish responders and nonresponders. Machine and deep learning hold enormous potential to predict patient responses to SCS therapy resulting in refined patient selection and improved patient outcomes.