Project Summary A growing body of research indicates that music may be used effectively for improving a variety of symptoms, including pain. However, little is known about the mechanisms that underlie the beneficial effects of music- based treatments. The primary objective of this R21 exploratory study is to evaluate the feasibility of performing a full R01 study in a sample of individuals with moderate to severe chronic low back pain to address knowledge gaps regarding the mechanisms of music-based treatments. To address the primary aims of this study, we propose a 3-arm trial in which individuals with chronic low back pain will be randomly assigned to one of three conditions: (1) live music played by a board-certified music therapist (Music Therapy), (2) audio recorded music (Music Medicine), or (3) a no sound control condition (n = 20 subjects per condition). We will also enroll 20 individuals without chronic pain and assign them to the Music Medicine condition. An EEG assessment measuring brain oscillation spectral power will be conducted before and during a session of each experimental condition. Measures of pain intensity will be administered before and after the sessions. Low back pain was selected because it is among the most common, costly, and disabling chronic pain problems; including a non-pain sample will also allow us to determine if having chronic pain or not influences the effects of music on the primary mechanism variables. We will compute effect sizes for (1) the effects of the treatments on frontal midline theta power and (2) the mediation effects of changes in frontal midline theta power on the pre- to post-session effects of the music conditions, relative to the control condition. We will also evaluate the differences between the two music conditions, compare the effects of Music Medicine on the mechanism variables as a function of having or not having chronic pain, and explore the extent to which the experimental conditions have lingering effects on pain intensity and secondary outcomes (depression, anxiety, pain interference, and sleep quality) during the 24 hours after the experimental sessions. We will perform interviews and qualitative data analyses to identify additional unanticipated effects of the experimental conditions that would be worth examining more closely in a full R01 study. The findings from this study will be used to determine if a full R01 study to evaluate the mechanisms of music-based treatments is warranted, and to inform the design of such as study. This program of research will provide important foundational knowledge regarding the mechanisms of music-based interventions. Transferred to clinical care, this knowledge could help in patient-treatment matching which would enhance the overall effectiveness for music-based treatments and other non-pharmacological treatments that may operate via their effects on brain states, as measured by EEG.