show Abstracthide AbstractParkinson's disease is the second most prevalent neurodegenerative disorder, characterized by the degeneration of dopaminergic neurons. Significant improvements in gait balance, particularly step length and velocity, were revealed by less-invasive wireless cortical stimulation. Transcriptome sequencing was performed to demonstrate the cellular mechanism, specifically targeting the primary motor cortex where the stimulation was applied. Our findings indicated that the differentially expressed genes (DEGs), initially down-regulated following Parkinson's disease induction, were subsequently restored to normal levels after cortical stimulation. We propose these DEGs as a potential target for motor disorder treatment in Parkinson's disease. These genes are implicated in crucial processes such as astrocyte-mediated blood vessel development and microglia-mediated phagocytosis of damaged motor neurons, suggesting their significant roles in improvement of behavior disorder. Moreover, these biomarkers not only facilitate rapid and accurate diagnosis of Parkinson's disease but also assist precision medicine approaches. Overall design: This study evaluated the efficacy of cortical stimulation using a cutting-edge graphene-based electrode array and wireless technology to mitigate the symptoms in a rat model of PD induced by 6-OHDA. Specifically, the graphene array was surgically placed in the primary motor cortex of the rats, followed by daily wireless stimulation at 130 Hz for one hour, over two weeks. The participants were divided into three groups: control (Ctrl), PD, and Stimulation (Stim). This study aimed to explore the biological mechanisms that facilitate the observed behavioral improvements in patients with PD following stimulation through comprehensive transcriptome analysis using NGS techniques.