Overview

The purpose of this study is to evaluate the safety and efficacy of accelerated intermittent theta burst stimulation (aiTBS) targeting personalized nodes within the somato-cognitive action network (SCAN) and action motor network (AMN) for the treatment of chronic pain. The study will employ Thompson Sampling, a Bayesian reinforcement learning algorithm, to optimize stimulation site selection based on individual response patterns. This approach has the potential to revolutionize pain management by improving treatment accessibility through shortened timelines, addressing individual variations in pain networks through precision targeting, and potentially achieving more robust pain relief through accelerated neuroplasticity.

The specific aims of the study are:

1. To establish the relationship between SCAN and AMN connectivity and cognitive- affective pain symptoms.
2. To evaluate the efficacy of Thompson Sampling-optimized aiTBS across SCAN and AMN on affective and sensorimotor pain dimensions.
3. To identify fMRI connectivity biomarkers predictive of treatment response and remission.

Eligibility

Inclusion Criteria:

• Ages 18 years or older
• Ability to provide written informed consent
• Ability to read and to communicate verbally and in writing in English
• Chronic pain persisting for at least 12 months
• Pain refractory to oral pain medication (defined as failing at least two different medication classes)
• Average pain intensity of ≥5 on the Numerical Rating Scale (NRS) over the past two weeks
• Stable pain medication regimen for at least 4 weeks prior to enrollment
• Willing and able to attend all study visits and comply with study procedures

Exclusion Criteria:

• Current substance use disorder (except for nicotine or cannabis) as determined by DSM-5 criteria
• Active suicidal ideation with intent or plan as determined by the Columbia-Suicide Severity Rating Scale (C-SSRS)
• Lifetime history of bipolar disorder, schizophrenia, or other psychotic disorder as determined by medical history
• Self-reported unstable medical conditions that would pose increased risks for TMS or MRI
• Pregnancy (as determined by urine pregnancy test) or planned pregnancy during the study period
• Contraindications to TMS, including:
• History of seizure or epilepsy
• Metallic implants in the head (excluding dental fillings)
• Cardiac pacemaker or other implanted medical devices
• History of significant head trauma
• History of intracranial surgery
• Medication that significantly lowers seizure threshold that cannot be safely held
• Contraindications to MRI, including:
• Claustrophobia
• Metallic implants or devices
• Inability to lie flat for the duration of the scan
• Current use of high-dose opioids (\>90 morphine milligram equivalents daily)
• Participation in another clinical trial of an investigational medication or device within 30 days prior to enrollment
• Any condition that, in the investigator\'s opinion, would make it unsafe or difficult for the participant to complete the study