UC San Diego

The human brain is an organ of prediction. It does not passively receive sensory information but actively constructs perception, action, and the felt sense of the body by issuing precision-weighted predictions and updating them against ascending prediction error. Under this hierarchical predictive architecture, suffering and well-being are not only outcomes of peripheral physiology but configurations of the brain's generative model: how rigidly its priors are held, where its attention is allocated, and how its high-level beliefs are coupled to interoceptive and exteroceptive signals. This dissertation investigates whether, and how, mind-body techniques transiently reorganize the predictive hierarchy, and what neural, molecular, and computational signatures accompany that reorganization.Three complementary studies are presented. Chapter 1 reports a randomized controlled trial demonstrating that four days of mindfulness meditation training produces a 33% reduction in experimentally induced pain that is predicted, within meditators, by a meditation-induced rise in the Shannon entropy of cortical functional connectivity networks, consistent with a flattening of the prediction-driven attractor landscape that ordinarily sustains pain. Chapter 2 reports a multi-omics, fMRI, and behavioral characterization of a seven-day retreat combining meditation, cognitive reconceptualization, and open-label placebo healing rituals, showing that the intervention disengages the default mode and salience networks, increases circulating BDNF and endogenous opioid pathway proteins, enhances glycolytic metabolism, and modulates exosomal neurotransmission-related microRNAs. This coordinated brain-body reorganization is interpreted as the joint relaxation of high-level priors, the recalibration of embodied first priors, and the reopening of the predictive system to new beliefs. Finally, Chapter 3 develops a unifying theoretical framework arguing that serotonergic psychedelics, contemplative practice, and caloric restriction converge on a single computational endpoint, a transient near-critical regime of relaxed priors and expanded degrees of freedom in the generative model, and that the depth of the resulting mystical-like experience is the primary therapeutic agent. Together, these studies advance an empirically grounded, computationally explicit account of how transformative brain-body states are produced, how they heal, and how the science of such states may be pursued with greater precision.