Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. The symptoms of PD are accompanied by non-motor symptoms such as sleep disturbance, mental function and sensory abnormality as well as movement disorders, which greatly reduces the quality of life. Recently, transcranial direct current stimulation (tDCS) has been used as an adjuvant therapy to improve motor and non-motor function of PD patients. Although the tDCS treatment has showed great clinical improvement, it remains unclear how this treatment works for PD patients at the level of metabolites.

In this study, a non-targeted metabolomics approach was introduced to observe metabolite changes in cerebrospinal fluid (CSF) samples taken before and after tDCS treatment from PD patients. Metabolite extracts from the CSF samples were analyzed using a high-resolution Q-TOF mass spectrometer equipped with a UHPLC system. Multivariate statistical techniques, such as principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were applied based on the molecular features extracted from the MS/MS datasets. The PLS-DA plots showed distinct segregation of CSF samples before and after tDCS treatment, and we found several metabolites that tDCS treatment caused changes in PD patients. These observations would enable us to interpret the mechanisms of action of tDCS treatment in PD patients, and broaden our insights into developing therapies for various neurodegenerative disorders.