The objectives of this VA Merit application are to demonstrate efficacy of combined intermittent theta burst (iTBS) and yoga (iTBS+yoga) intervention on improving pain, function, analgesic use, self-efficacy, quality of life and well-being among Veterans with chronic low back pain (CLBP). This Merit project will directly benefit Veterans and VA Services by demonstrating efficacy of a new, non-medication treatment for Veterans with CLBP in need of non-opioid treatment options. Neuromodulation including iTBS is now offered at over 50 VA hospitals and yoga is among the complementary and integrative health programs being rolled out as a part of VAs Whole Health implementation efforts. Thus, should iTBS+yoga ultimately prove to be efficacious, VA facilities will be well-poised to offer this treatment. A novel, activity-based, non-medication treatment for Veterans with CLBP is of great need given the high prevalence of CLBP.

Significance to VA: Chronic low back pain (CLBP) is the leading cause of disability worldwide and the most common location of chronic pain among Veterans. Medications are the treatment mainstay for CLBP and yet >50% of chronic pain patients receiving medications are treatment resistant. Lack of pain relief from medications can lead to non-prescription opioid use, opioid use disorder, and Veteran death from opioid overdose, which occurs at a higher rate than US Civilians. This Merit will directly benefit Veterans and VA Services by developing a new, neuromodulatory, non-opioid neurorehabilitation treatment for Veterans with CLBP who do not find existing options to be effective or preferable. Innovation and Impact: Yoga is an activity, and mindfulness-based behavioral intervention and is safe and recommended for CLBP. Given the room for improvement of available treatments and considering the life-threatening opioid epidemic, building an evidence base for novel, precise, non-medication approaches for pain management has high impact for VA Healthcare. The non-invasive treatment transcranial magnetic stimulation (TMS) applied to the motor cortex (M1) reduces pain and has remote effects including neuromodulation of pain pathways. Intermittent theta burst stimulation (iTBS), a type of patterned, excitatory TMS, increases M1 excitability. iTBS can prime the brain to boost the impact of interventions provided during this window of enhanced excitability. By activating the M1 through iTBS prior to participation in an evidence-based yoga program, the investigators theorize that iTBS will boost the effects of yoga resulting in improvements in pain, function and quality of life and these improvements will be sustained. The purpose of this Merit project is to demonstrate efficacy and additive effect of combined iTBS and yoga (iTBS+yoga) and vs. yoga or iTBS alone on improving pain, function, analgesic use, self-efficacy, quality of life (QOL) and well-being among Veterans with CLBP. This Merit is a natural progression of a VA RR&D-funded SPiRE suggesting that iTBS+yoga is safe, feasible, and acceptable among Veterans of all genders with CLBP and provides preliminary evidence of improvements from pre- to post-treatment in pain and QOL. The investigators will build on this evidence and add innovation by testing the additive effects of iTBS+yoga vs. yoga and iTBS each alone. For this Merit, the investigators will complete a randomized controlled trial among 3 groups of Veterans with CLBP receiving (1) active-iTBS+yoga, (2) sham-iTBS+yoga, or (3) active-iTBS alone. Specific Aims: Aim 1 will determine efficacy and sustainability of iTBS+yoga on pain, function, analgesic use, self-efficacy, QOL and well-being among Veterans with CLBP. Aim 2 will determine acceptability of iTBS+yoga for Veterans with CLBP. Exploratory Aim 3 will examine gender and common comorbidity measures as moderators of iTBS+yoga treatment effect. Methodology: The intervention will be provided in small group settings once a week for 6 weeks. Ac-tive- or sham-iTBS will be administered immediately prior to yoga. The investigators will be using an existing, evidence-based, manualized yoga program (LoveYourBrain Yoga). The investigators will collect outcome data related to pain, function, analgesic use, self-efficacy, QOL and well-being, as well as structural MRI data for iTBS neuronavigation. Path to Translation/Implementation: Completion of this Merit project will provide preliminary data for future applications focused on treatment responsiveness and a future larger scale multi-site pragmatic effectiveness study. This Merit project will directly benefit Veterans and VA Services by developing a new, non-pharmacological neurorehabilitation treatment for Veterans with CLBP in need of non-opioid treatment options. TMS is now offered at over 50 VA hospitals nationwide for treatment-resistant depression, and yoga is among the complementary and integrative health programs being rolled out as a part of VAs nation-wide Whole Health implementation efforts. Therefore, should iTBS+yoga ultimately prove to be efficacious and effective, VA facilities will be well-poised to offer this treatment.

Inclusion Criteria:

• 1 mo. stability in pain management strategies.
• 22+ years of age.
• Can read and speak English.
• Able to participate in strengthening, stretching, range of motion exercise via yoga as determined by study physician.
• Chronic Low Back Pain (CLBP): pain in the low back that persists for >6 months and is of moderate to severe intensity with a score of >5 on specific items on the BPI demonstrating disability of at least 20% on the Oswestry Disability Index (ODI).

Exclusion Criteria:

• Contraindications to iTBS/TMS (e.g. epilepsy, psychotic spectrum disorders [i.e. bipolar, schizophrenia], history of anoxic brain injury).
• Moderate to severe heart disease.
• Contraindications to MRI (e.g., claustrophobia, implanted ferromagnetic device such as pacemaker or cardiac defibrillator).
• Pain believed to be associated with cardiac or ischemic conditions.
• Epilepsy, active seizure disorder, personal history of a seizure or individuals with a family history of epilepsy or seizure in a first degree relative.
• Current prescription of psychostimulants (e.g., amphetamines), anticholinergics, tricyclic antidepressants, and antipsychotics or other medications that may increase their risk of having seizures.
• Intracranial lesion.
• History of ischemic or hemorrhagic stroke.
• History of moderate to severe TBI.
• History of or current psychosis not due to an external cause (e.g., due to illicit drug use).
• Other neurological conditions (e.g., neurodegenerative disorders).
• Active suicidal ideation with Columbia Suicide Severity Rating Scale(CSSRS) 3 .
• Are pregnant or nursing.
• Within 12 weeks of a major surgery/operation.

The PI, study statistician, intervention providers, and those collecting study data will be blind to treatment assignment. While participants may be able to discern whether or not they received iTBS alone because there is no yoga component (thus, the single blind), they may not be able to guess if they received active-iTBS+yoga vs. sham-iTBS. Participants will complete a blinding questionnaire after completion of the study intervention. After follow up, the study team will become unblinded to provide participants with the opportunity to complete their preferred intervention types. The study statistician will remained blinded.