Prefrontal cortico-thalamic regulation of pain by mindfulness meditation

Mindfulness meditation reliably reduces pain. We have repeatedly found that mindfulness-based analgesia is associated with thalamic deactivation and prefrontal-cortical (PFC) activation. Our working theoretical model proposes that mindfulness-induced shifts in executive attention facilitate pain-relief by PFC-driven thalamic inhibition to reduce the elaboration of nociception throughout the cortex. Yet, there are no studies that have identified neuro-functional connections supporting mindfulness meditation-based pain relief. The proposed study tested if mindfulness-based analgesia is associated with stronger a) PFC-thalamic connectivity and b) thalamic decoupling with lower-level nociceptive targets in somatosensory cortices. Forty healthy, pain-free volunteers were randomized to a 4-session (20-minutes each) mindfulness training or book-listening control group (n=20/group). After their respective interventions, four total “heat” series (ten, 10-second plateaus of 49°C) were administered to the right calf during functional MRI (fMRI) acquisition (2-rest vs. 2-meditation). Pain intensity and unpleasantness ratings (11-point visual analog scale) were collected after each series. Seed based connectivity analyses (pre-registered: NCT03414138) were carried out with a contralateral thalamic seed corresponding to peak deactivation correlates of meditation-related analgesia derived from our previous study. For each participant, mean time course values corresponding to the seed per heat fMRI-series were entered as regressors to identify significant seed-to-whole brain voxel correlations and covariation with pain reports. Mindfulness produced (p<.001) greater pain intensity (-32%) and unpleasantness (-33%) reductions when compared to rest and the controls (intensity = +20%; unpleasantness = +23%). When compared to rest, meditation produced stronger connectivity between the contralateral thalamus and ventrolateral PFC (vlPFC), right anterior insula, and greater decoupling with the bilateral thalamus. Mindfulness-based analgesia was also associated with stronger contralateral thalamic 1) decoupling with the contralateral posterior insula and periaqueductal gray matter (PAG) and 2) connectivity with the vlPFC. We provide novel evidence that mindfulness engages a unique PFC-thalamocortical mediated pain modulatory mechanism that bypasses PAG-driven descending inhibition. This work was supported by the National Center for Complementary and Integrative Health (K99/R00-AT008238; R01-AT009693; R21-AT010352).