Title : Ultrashort wave modulates brain functional connectivity and behavioral recovery in mTBI rats: A longitudinal 11.7T rs-fMRI study
Abstract:
Background: Mild traumatic brain injury (mTBI) is common, with subtle symptoms and long-term consequences, but the brain network remodeling and its link to behavioral disorders remain unclear. Ultrashort wave (USW) therapy, a potential non-invasive treatment, has not been systematically studied for its role in regulating this process and aiding recovery.
Methods: Male Sprague-Dawley (SD) rats were randomly assigned to three groups: mTBI model group (mTBI), ultrashort wave intervention group (USW), and control group (Ctrl). An mTBI model was established via a single explosive shock, and the USW group received intervention post-injury. Serum biomarkers (Tau, S100B, NEFL), resting-state functional Magnetic Resonance Imaging (rs-fMRI) at 11.7T, and behavioral assessments (open field test, elevated plus maze test) were conducted on days 4, 14, and 30 post-injury. Functional connectivity (FC) between regions of interest (ROIs) in the whole brain was analyzed using the SIGMA standard brain atlas. Longitudinal changes in FC were modeled using a Linear Mixed-Effects Model (LMM), and FC × group interaction analysis was performed to investigate whether ultrashort wave intervention altered the relationship between FC and behavioral outcomes in mTBI rats.
Results: Compared to the Ctrl group, the mTBI group exhibited early post-injury motor deficits and anxiety-like behaviors, accompanied by elevated serum levels of Tau, S100B, and NEFL. ultrashort wave intervention significantly improved motor and exploratory behaviors in the mTBI rats, alleviated anxiety-like symptoms, and accelerated the recovery of serum S100B and NEFL levels to control levels. Longitudinal comparisons based on the LMM revealed that, compared to the mTBI group, the USW group exhibited a reversal in the time slope of FC changes, approaching that of the Ctrl group. Further FC × Group interaction analysis suggested that the behavioral improvements induced by ultrashort wave intervention were likely associated with the remodeling of specific neural circuits. Notably, the strength of connectivity between the Left Dentate Gyrus - Left Secondary Auditory Cortex Ventral Part showed a significant positive interaction with Slow Movement Time (β = 26.258, p = 0.0046), and a significant negative interaction with Immobility Time (β = -59.574, p = 0.0195). Additionally, the strength of connectivity between the Left Basal Forebrain Region -- Left Granule Cell Level of the Cerebellum showed a negative interaction with Center Zone Distance (β = -333.396, p = 0.0444). These results suggest that USW may regulate the relationship between specific functional connections and behavioral outcomes, thus facilitating neurobehavioral recovery following mTBI.
Conclusions: USW intervention may promote neurobehavioral recovery following mTBI by modulating the remodeling of brain network connectivity. This study provides experimental evidence supporting ultrashort wave as a potential non-invasive therapeutic strategy for mTBI, with implications from whole-brain network alterations to behavioral improvements.
