Resting-state brain functional connectivity in patients with chronic intractable pain who respond to spinal cord stimulation therapy

Abstract

Background: Spinal cord stimulation (SCS) is widely accepted as a useful treatment for patients with intractable chronic pain. However, its effectiveness varies between individuals. Therefore, a tool for evaluating its effectiveness in advance is eagerly awaited. We examined whether resting-state functional magnetic resonance imaging as a diagnostic and prognostic tool can predict responsiveness to SCS.

Methods: Twenty-nine patients with intractable chronic pain participated in this study. Participants were divided into responder and non-responder groups based on a pain relief rate after SCS trials. All participants underwent resting-state functional magnetic resonance imaging scans before the SCS trials. We searched for functional connectivity that differed significantly in strength between the two groups and was correlated with pain relief rate. We conducted receiver operating characteristic (ROC) analysis and a one-sample proportion test to determine the cut-off value and evaluate the predictive power of the functional connectivity-based prediction model.

Results: In total, 14 and 15 participants were assigned to the responder and non-responder groups, respectively. Functional connectivity between the middle anterior cingulate cortex and precuneus/posterior cingulate cortex showed significant between-group differences and a significant negative correlation with the pain relief rate. Moreover, this functional connectivity could accurately predict SCS responsiveness greater than chance (sensitivity: 71%; specificity: 87%; area under the curve: 0.814; P<0.001).

Conclusions: For patients with intractable chronic pain, functional connectivity between the middle anterior cingulate cortex and precuneus/posterior cingulate cortex is a promising candidate biomarker to estimate responsiveness to spinal cord stimulation before treatment.

Keywords: anterior cingulate cortex; chronic intractable pain; default mode network; functional MRI; functional connectivity; precuneus; spinal cord stimulation.