Effects of intensive sensorimotor rehabilitation in resting state functional connectivity in a rodent model of Cerebral Palsy

ABSTRACT Background Sensorimotor stimulation has been shown to protect against brain damage and function impairments following experimental Cerebral Palsy (CP). Functional ultrasound (fUS) gives valuable information about brain connectivity at unprecedented spatial and time resolutions with high translational potential. We tested brain function and connectivity using fUS following experimental CP and the effects of early sensorimotor rehabilitation in the model. Methods Pregnant Wistar rats were exposed to maternal immune challenge at E18-19. Pups received perinatal anoxia at postnatal day 0 (P0) and restriction of the hindlimbs from P2 to P21. Rehabilitation (EETT) used environmental enrichment (EE) and Treadmill Training (TT) from P21 to P28. At P29, fUS was performed to access brain connectivity and graph theoretic analysis was used to distinguish patterns of brain connectivity. Results CP increased intrinsic brain functional connectivity compared to Controls and EETT animals. Connectivity was increased in CP animals in cortical areas related to sensorimotor function and subcortical myelinated structures. EETT animals showed levels of brain connectivity similar to Controls. Conclusions Sensorimotor stimulation changed brain hyperconnectivity profile induced by CP. Brain connectivity pattern alterations can be detected using fUS with high accuracy, suggesting great potential to be used as earlier biomarker for neurodevelopmentalal disorders such as CP.