Lifespan dynamics of STN-based functional connectivity and network properties: Implications for motor dysfunction and circuit-based neuromodulation

Functional connectivity (FC) is crucial for the execution of functional activities and the progression of diseases. From a functional perspective, changes in subthalamic nucleus (STN)-based FC and network properties across lifespan and their effectiveness in predicting age require further investigation. The STN-based atlas was constructed using neuroimaging data from 1060 healthy participants. Based on this atlas, the FC and brain network properties were quantified subsequently. Both linear and non-linear changes in FC and network properties with aging, and relationships across brain regions were analyzed with generalized additive model (GAM). Connectome-based predictive modeling (CPM) was used to evaluate the performance of FC in predicting age, while computational lesion analysis was utilized to identify the FC with significant contributions to model performance. The STN-based atlas mainly involved bilateral sensory, motor, and sensory-motor integration cortices, subcortical nuclei, and cerebellar crus I and II. Global network properties were declined with aging (all P ​< ​0.05). Significant non-linear age-related changes were identified in regional network properties of bilateral M1 and right STN (all P ​< ​0.05). There were non-linear negative relationships between bilateral M1, and between right M1 and right STN (all P ​< ​0.05). The FC within motor cortex, and between limbic areas and subcortical nuclei, significantly contributed to the performance of CPM. Therefore, from a functional perspective, dynamic changes in FC and network properties across the lifespan were highlighted, particularly within motor-related circuits. This provides valuable insights into neural mechanisms underlying motor dysfunction during aging and informs circuit-based neuromodulation strategies.