Effect of "Mind-Body Co-Regulation" Rehabilitation Training on Regional Homogeneity of Brain in Mice with Cognitive Frailty

<bold>Objective</bold>To explore the mechanism by which “Mind-Body Co-regulation” rehabilitation training improves motor and cognitive functions in mice with cognitive frailty.<bold>Methods</bold>Six-month-old C57BL/6 mice served as the adult control group. Sixteen-month-old male C57BL/6 mice were randomly assigned to four groups (<italic>n</italic>=10 per group): cognitive frailty group, physical-tuning group, spirit-tuning group, and mind-body group. The physical-tuning group underwent treadmill training (passive motion at 12 m/min, 1 hour/session, once daily). The spirit-tuning group was housed in a Shen-Nourishing Chamber (2 hours/session, once daily). The mind-body group received the same treadmill training as the physical-tuning group followed by Shen-Nourishing Chamber housing. The adult control group and cognitive frailty group were housed in standard cages without additional intervention. After 6 weeks of intervention, muscle strength was assessed using the grip strength test; balance ability was evaluated with the rotarod test. Hematoxylin and eosin (HE) staining and Masson's trichrome staining were employed to measure the cross-sectional area percentage of muscle fibers and collagen fiber deposition, respectively. Cognitive function was evaluated using the novel object recognition test and Morris water maze test. Subsequently, Bold-fMRI scanning was performed to analyze changes in regional homogeneity.<bold>Results</bold>Compared with the adult control group, the muscle strength of the cognitive frailty group was significantly reduced (<italic>P</italic>&lt;0.05); compared with the cognitive frailty group, the muscle strength of the physical-tuning group and the mind-body group was enhanced (<italic>P</italic>&lt;0.05); compared with the spirit-tuning group, both the physical-tuning group and the mind-body group showed increased muscle strength (<italic>P</italic>&lt;0.05). Compared with the adult control group, the cognitive frailty group showed a reduction in the rotating rod dwell time (<italic>P</italic>&lt;0.05); compared with the cognitive frailty group, the physical-tuning group, the spirit-tuning group, and the mind-body group showed an increase in the rotating rod dwell time (<italic>P</italic>&lt;0.05); compared with the spirit-tuning group, the physical-tuning group and the mind-body group had a longer rotating rod dwell time (<italic>P</italic>&lt;0.05); compared with the physical-tuning group, the mind-body group showed an increase in the rotating rod dwell time (<italic>P</italic>&lt;0.05). Compared with the adult control group, the proportion of muscle fiber cross-sectional area decreased (<italic>P</italic>&lt;0.05) and collagen fiber deposition increased (<italic>P</italic>&lt;0.05) in the cognitive frailty group; compared with the cognitive frailty group, the proportion of muscle fiber cross-sectional area increased (<italic>P</italic>&lt;0.05) and collagen fiber deposition decreased (<italic>P</italic>&lt;0.05) in the physical-tuning group and the mind-body group; compared with the spirit-tuning group, the proportion of muscle fiber cross-sectional area increased (<italic>P</italic>&lt;0.05) and collagen fiber deposition decreased (<italic>P</italic>&lt;0.05) in the physical-tuning group and the mind-body group. Compared with the adult control group, the object recognition index of the cognitive frailty group decreased (<italic>P</italic>&lt;0.05); compared with the cognitive frailty group, the object recognition index increased in the physical-tuning group, spirit-tuning group, and mind-body group (<italic>P</italic>&lt;0.05); compared with the physical-tuning group and the spirit-tuning group, the object recognition index of the mind-body group increased (<italic>P</italic>&lt;0.05). Compared with the adult control group, the escape latency of the cognitive frailty group was prolonged from day 1 to day 4 (<italic>P</italic>&lt;0.05); compared with the cognitive frailty group, the escape latency of the physical-tuning group decreased on day 3 and day 4 (<italic>P</italic>&lt;0.05), and the escape latency of the mind-body group decreased from day 1 to day 4 (<italic>P</italic>&lt;0.05); compared with the physical-tuning group, the escape latency of the mind-body group decreased on the third day (<italic>P</italic>&lt;0.05). Compared with the adult control group, the cognitive frailty group showed a significant decrease in the number of platform crossings and the shorter duration in the target quadrant (<italic>P</italic>&lt;0.05); compared with the cognitive frailty group, the physical-tuning group, the spirit-tuning group, and the mind-body group all showed an increased number of platform crossings and prolonged duration of stay in the target quadrant (<italic>P</italic>&lt;0.05); compared with the physical-tuning and spirit-tuning groups, the mind-body group showed an increase in the number of platform crossings and longer duration of stay in the target quadrant (<italic>P</italic>&lt;0.05). The ReHo analysis results showed that compared with the adult control group, the ReHo value in the right cortical amygdala area of the cognitive frailty group significantly increased (<italic>P</italic>&lt;0.05); compared with the cognitive frailty group, the ReHo value in the right cortical amygdala region significantly decreased in the physical-tuning group, spirit-tuning group, and mind-body group (<italic>P</italic>&lt;0.05).<bold>Conclusion</bold>The mind-body co-regulation rehabilitation training directly or indirectly changes the functional activity of the amygdala through physical-tuning and spirit-tuning training, promoting the recovery of motor and cognitive abilities in mice with cognitive frailty.