Project Summary Chronic inflammation is highly prevalent and has deleterious effects on brain health, including links to brain structural abnormalities1, neural metabolic changes2, psychiatric disorders2, cognitive dysfunction3, and aging- related diseases4,5. Given the increasing prevalence of chronic inflammatory diseases6–9, a better understanding of interventions that may reduce the impacts of inflammation on brain health is imperative10. A growing body of literature demonstrates positive impacts of mindfulness-based interventions (MBIs) on mental and physical health11–15, brain structure and function14,16–19, and chronic inflammation20. Asthma is a chronic inflammatory disease that is uniquely well-suited to examine the protective effects of MBIs across multiple dimensions of health because it is sensitive to changes in stress21–23, highly prevalent and comorbid with depression24,25, and has been associated with compromises in brain structure26–28 and function29,30. The first aim of this proposal is to 1) assess changes in brain health indices in individuals with asthma from pre- to post- 8-week Mindfulness-Based Stress Reduction (MBSR) intervention and at 3-month follow-up (n=46). I will utilize a novel, whole-brain voxel- wise assessment of DWI, modeled using diffusion tensor (DTI) and neurite orientation dispersion and density imaging (NODDI), which provides meaningful, clinically relevant tissue parameters of white and grey matter microstructure and will enable detection of changes at a high spatial resolution. Additionally, I will examine changes in biomarkers of neuroinflammation and neurodegeneration in concert with DTI and NODDI metrics, a novel approach which will strengthen our confidence in the underlying meaning of changes in DWI metrics. The second aim of this proposal is to 2) assess the association of these brain health indices with indices of whole-person health and wellbeing, from pre- to post- 8-week MBSR intervention and at 3-month follow-up (n=46). While previous work has reported structural and functional brain changes related to MBIs, a deeper understanding of how these changes are related to other aspects of whole-person health is needed. High stress and poor sleep are drivers of systemic inflammation31 and brain microstructural deterioration32–35, and their improvement may link MBIs to salubrious outcomes. Sleep quality, life stress, and self-reported wellbeing will serve as indices of a psychological dimension of whole-person health, and asthma severity and airway inflammation will serve as indices of a disease- specific dimension of whole-person health, contributing to our understanding of how changes in brain health after MBI relate to experiential outcomes. The impact of a behavioral intervention on the interrelations of brain- and whole-person health indices in asthma has not previously been investigated and represents a potential for substantial public health impact given the growing evidence of the effects of asthma on the brain and the growing prevalence of asthma. Finally, this training fellowship will facilitate valuable training opportunities in DWI analysis, statistical methods, psychoneuroimmunology and contemplative neuroscience education, experimental design and data collection, writing, public-speaking, mentorship, and ethics.

Project Narrative Asthma is a highly prevalent chronic inflammatory disease of the airways that has been increasingly shown to impact the brain; it is sensitive to changes in stress, often comorbid with anxiety and depression, and has been associated with compromises in brain structure and function. The proposed project seeks to benefit public health by investigating the impact of a Mindfulness Based Stress Reduction intervention on brain health and whole-person health in a population with asthma. We will assess changes in a combination of neuroimaging metrics of brain microstructural integrity, blood-based biomarkers of brain health, asthma symptoms and level of airway inflammation, as well as a host of whole-person health indices such as changes in sleep quality, life stress, and psychological well-being.