vidence suggests that mindfulness meditation-induced pain relief is associated with the engagement of unique corticothalamo-cortical nociceptive filtering mechanisms. However, the functional neural connections supporting mindfulness meditation-based analgesia remain unknown. This mechanistically focused clinical trial combined functional magnetic resonance imaging with psychophysical pain testing [49°C stimulation & pain visual analog scales (VAS)] to identify the neural connectivity supporting the direct modulation of pain-related behavioral and neural responses by mindfulness meditation. We hypothesized that mindfulness meditation-based would be reflected by greater decoupling between brain mechanisms supporting appraisal (prefrontal) and nociceptive processing (thalamus). After baseline pain testing, 40 participants were randomized to a well-validated, four-session mindfulness meditation or book-listening regimen. Functional-MRI and noxious heat (49°C; right calf) were combined during meditation to test study…