Neural and molecular changes during a mind-body reconceptualization, meditation, and open label placebo healing intervention

Abstract Mind-body interventions offer promising avenues for improving physical and mental health, yet the comprehensive biological effects of increasingly popular mind-body retreat interventions remain poorly understood. The neural and molecular effects of a 7-day retreat intervention combining meditation, reconceptualization, and open-label placebo healing rituals are investigated in an observational study on 20 healthy human participants randomly selected from 561 retreat participants. BOLD fMRI functional connectivity during rest and meditation and whole plasma proteomics, metabolomics, exosome-specific miRNA transcriptomics, and neurite growth and real-time metabolism cellular assays are compared pre- and post-intervention. Meditation decreases functional integration in the default mode ( p = 0.00009) and salience networks ( p = 0.000003) and decreases whole-brain modularity ( p = 0.001). Compared to pre-intervention plasma, post plasma increases in vitro neurite outgrowth ( p = 0.01), enhances glycolytic metabolism ( p = 0.008), induces upregulation of BDNF ( p = 0.001), inflammatory ( p = 0.0001), anti-inflammatory ( p = 0.03), and endogenous opioid ( p = 0.03) pathways, and modulates tryptophan metabolism ( p FDR = 0.03) and neurotransmission-associated exosome miRNA transcripts. This intensive non-pharmacological mind-body intervention produces broad short-term neural and plasma-based molecular changes associated with enhanced neuroplasticity, metabolic reprogramming, and modulation of functional cell signaling pathways, highlighting the potential of mind-body techniques to modulate neural circuits and pathways important to health and well-being.