Tai Chi Improves Brain Functional Connectivity and Plasma Lysophosphatidylcholines in Postmenopausal Women With Knee Osteoarthritis: An Exploratory Pilot Study Author: Chwan-Li Shen1,2,3, Bruce A Watkins4, Chanaka Kahathuduwa2,3,5,6, Ming-Chien Chyu2,7, Masoud Zabet-Moghaddam8, Moamen M Elmassry9, Hui-Ying Luk2,3,10, Jean-Michel Brismée2,11, Ami Knox12, Jaehoon Lee2,13, Mimi Zumwalt2,14, Rui Wang1, Tor D Wager15, Volker Neugebauer2,3,16,17 Affiliation: <sup>1</sup> Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX, United States. <sup>2</sup> Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX, United States. <sup>3</sup> Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX, United States. <sup>4</sup> Department of Nutrition, University of California, Davis, Davis, CA, United States. <sup>5</sup> Department of Laboratory Sciences and Primary Care, Texas Tech University Health Sciences Center, Lubbock, TX, United States. <sup>6</sup> Department of Psychiatry, Texas Tech University Health Sciences Center, Lubbock, TX, United States. <sup>7</sup> Department of Medical Engineering, Texas Tech University, Lubbock, TX, United States. <sup>8</sup> Center for Biotechnology and Genomics, Texas Tech University, Lubbock, TX, United States. <sup>9</sup> Department of Biological Sciences, Texas Tech University, Lubbock, TX, United States. <sup>10</sup> Department of Kinesiology and Sport Management, Texas Tech University, Lubbock, TX, United States. <sup>11</sup> Department of Rehabilitation Sciences, Texas Tech University Health Sciences Center, Lubbock, TX, United States. <sup>12</sup> Clinical Research Institute, Texas Tech University Health Sciences Center, Lubbock, TX, United States. <sup>13</sup> Department of Educational Psychology and Leadership, Texas Tech University, Lubbock, TX, United States. <sup>14</sup> Department of Orthopedic Surgery, Texas Tech University Health Sciences Center, Lubbock, TX, United States. <sup>15</sup> Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, United States. <sup>16</sup> Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, United States. <sup>17</sup> Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States. Conference/Journal: Front Med (Lausanne) Date published: 2022 Jan 3 Other: Volume ID: 8 , Pages: 775344 , Special Notes: doi: 10.3389/fmed.2021.775344. , Word Count: 428 Objective: A pre/post pilot study was designed to investigate neurobiological mechanisms and plasma metabolites in an 8-week Tai-Chi (TC) group intervention in subjects with knee osteoarthritis. Methods: Twelve postmenopausal women underwent Tai-Chi group exercise for 8 weeks (60 min/session, three times/week). Outcomes were measured before and after Tai Chi intervention including pain intensity (VAS), Brief Pain Inventory (BPI), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), plasma metabolites (amino acids and lipids), as well as resting-state functional magnetic resonance imaging (rs-fMRI, 10 min, eyes open), diffusion tensor imaging (DTI, 12 min), and structural MRI (4.5 min) in a subgroup. Clinical data was analyzed using paired t-tests; plasma metabolites were analyzed using Wilcoxon signed-rank tests; and rs-fMRI data were analyzed using seed-based correlations of the left and right amygdala in a two-level mixed-effects model (FSL software). Correlations between amygdala-medial prefrontal cortex (mPFC) connectivity and corresponding changes in clinical outcomes were examined. DTI connectivity of each amygdala was modeled using a Bayesian approach and probabilistic tractography. The associations between neurobiological effects and pain/physical function were examined. Results: Significant pre/post changes were observed with reduced knee pain (VAS with most pain: p = 0.018; WOMAC-pain: p = 0.021; BPI with worst level: p = 0.018) and stiffness (WOMAC-stiffness, p = 0.020), that likely contributed to improved physical function (WOMAC-physical function: p = 0.018) with TC. Moderate to large effect sizes pre/post increase in rs-fMRI connectivity were observed between bilateral mPFC and the amygdala seed regions (i.e., left: d = 0.988, p = 0.355; right: d = 0.600, p = 0.282). Increased DTI connectivity was observed between bilateral mPFC and left amygdala (d = 0.720, p = 0.156). There were moderate-high correlations (r = 0.28-0.60) between TC-associated pre-post changes in amygdala-mPFC functional connectivity and pain/physical function improvement. Significantly higher levels of lysophosphatidylcholines were observed after TC but lower levels of some essential amino acids. Amino acid levels (alanine, lysine, and methionine) were lower after 8 weeks of TC and many of the lipid metabolites were higher after TC. Further, plasma non-HDL cholesterol levels were lower after TC. Conclusion: This pilot study showed moderate to large effect sizes, suggesting an important role that cortico-amygdala interactions related to TC have on pain and physical function in subjects with knee osteoarthritis pain. Metabolite analyses revealed a metabolic shift of higher lyso-lipids and lower amino acids that might suggest greater fatty acid catabolism, protein turnover and changes in lipid redistribution in response to TC exercise. The results also support therapeutic strategies aimed at strengthening functional and structural connectivity between the mPFC and the amygdala. Controlled clinical trials are warranted to confirm these observed preliminary effects. Keywords: WOMAC; metabolomics; mind-body exercise; neuroimaging; pain. PMID: 35047525 PMCID: PMC8761802 DOI: 10.3389/fmed.2021.775344