Brain Mechanisms Supporting Mindfulness Meditation-Induced Pain and Stress Relief - Project Summary Stress and chronic pain disorders are comorbid conditions wherein stress exacerbates pain. Mindfulness meditation, a non-opioidergic and self-regulatory technique that trains non-reactive awareness to arising sensory and affective events, reduces clinical and experimentally induced pain and stress. Our recently completed psychophysical and functional magnetic resonance imaging (fMRI) study found that four, 20-minute sessions of mindfulness training in healthy participants reduced stress ( 39%, p = .023) and pain intensity ( 32%, p < .001) in response to noxious heat (49°C). Stress reductions also predicted lower pain intensity (p = .013). The perigenual anterior cingulate cortex (pgACC), a cognitive-affective brain area involved in reappraisal, and the amygdala, a key brain area involved in sensory and emotional processing, are associated with modulating pain and stress and share extensive anatomical connections. Our laboratory has demonstrated that increased pgACC activity underlies mindfulness-induced reductions in pain and anxiety in healthy individuals, while mindfulness-induced deactivation of the amygdala has been shown to correlate with pain and stress relief across separate studies. Despite these findings, no study has determined whether mindfulness meditation promotes stress relief and analgesia by modulating the pgACC and corresponding neural activity in and connectivity between nociceptive and negative affect-specific brain regions. To this end, we will analyze the blood-oxygen-level-dependent fMRI data corresponding to our behavioral findings to test the following hypotheses. We will first determine if higher pgACC (HYP1a) and lower amygdala (HYP1b) activity during mindfulness is associated with higher pain/stress relief. We will next determine if increased pgACC-amygdalar functional connectivity correlates with mindfulness-induced pain (HYP1c) and stress relief (HYP1d). Our preliminary analyses found that mindfulness-induced analgesia correlates with reductions in machine-learned, multivariate fMRI signatures sensitive and specific to nociception (neurologic pain signature; NPS, p = .03) and stimulus-induced negative affect (p = .01). We will similarly determine if reductions in negative affect brain responses correspond to stress relief (HYP2a). Finally, we will confirm if increased NPS- (HYP2b) and negative affect signature- (HYP2c) pgACC connectivity is associated with pain and/or stress relief. The proposed research and training will be accomplished under the mentorship of my Sponsor, Co- sponsors, and Co-Mentor, who are experts in fMRI clinical trials on pain, meditation, and/or stress. Activities include a) training in pain-evoking procedures and statistical and computational techniques, programming, and neuroanatomy for analysis of behavioral and fMRI data b) ethical interactions with individuals with chronic pain and stress, c) scientifically validated mindfulness training, and d) fostering career development strategies. The knowledge and skills gained will prepare me to successfully navigate a career as an independent cognitive neuroscientist identifying the brain mechanisms of novel treatments for pain and comorbid health ailments.
