Subthalamic nucleus deep brain stimulation connectivity related to apathy outcomes in Parkinson's disease

BackgroundSubthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD); however, apathy is a commonly reported side-effect that counteracts quality of life improvements offered by DBS. To date, the structural connectivity of postoperative apathy is largely unknown.ObjectiveThis study aimed to identify streamlines associated with worsening apathy following STN-DBS in PD.MethodsPatients with PD who received bilateral STN-DBS (n = 53) were pseudorandomized into "training" (n = 38) and "holdout" (n = 15) groups. In the training group, a normative structural connectivity analysis was conducted using pre- and postoperative apathy outcomes [Frontal Systems Behavior Scale (FrSBe) apathy subscale]. The resulting model was cross-validated and then tested in the holdout group.ResultsAn asymmetric profile emerged that was associated with worsening apathy. Right hemisphere streamlines were consistent with the dentatorubrothalamic pathway, connecting to the supplementary motor area. In the left hemisphere, the model included streamlines spanning the anteromedial STN to the anterior cingulate and orbitofrontal areas. The validity of the connectivity model was evaluated using cross-validation paradigms (leave-one-patient-out: R = 0.38, p = 0.023; 5-fold: R = 0.46, p = 0.004; 10-fold: R = 0.33, p = 0.048). The model was used to assess its association with apathy changes in the holdout group (R = 0.71, p = 0.005).ConclusionResults suggest that worsening of apathy following STN-DBS in PD involves the stimulation of circuits associated with a range of emotional and motivational processes, potentially disrupting auto-activation and emotional-affective processes in some patients.Plain Language TitleUnderstanding Apathy in Parkinson's Disease After Deep Brain Stimulation.