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BackgroundDespite the evidence of an association between problematic mobile phone use (PMPU) and psychological symptoms, a few studies explore whether physical activity (PA) could moderate the effect of PMPU on psychological symptoms and its neural substrates. The aim of this study was to examine the association between PMPU and psychological symptoms in late adolescents, along with the potential moderating effect of PA and neural basis by brain gray matter volume (GMV).MethodsA total of 251 college students reported on their PMPU, PA, and psychological symptoms and subsequently underwent structural magnetic resonance imaging to explore the neural basis of their PA characteristics. A multiple regression model was performed to detect brain GMV associated with PA by the voxel-based morphometry (VBM) method. Moderating analysis was conducted using PROCESS macro in the SPSS software.ResultsBehavioral results showed that PMPU was correlated to depression, anxiety, and stress, and PA has significantly moderated the association between PMPU with depression, anxiety, and stress. The VBM analysis showed that PA was correlated to GMV of the right fusiform gyrus (FFG), left precuneus (PCUN), left insula (INS), and left triangular part of inferior frontal gyrus (IFGtriang). Moreover, GMV of the left INS moderated the relationship between PMPU and depression.ConclusionThis study has shed light on the neural perspective of PA that moderates the relationship between PMPU and depressive symptom.