Objective: To describe the structural connectivity profile associated with apathy following subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson’s disease (PD).

Background: While STN-DBS is an established treatment for PD, postoperative apathy is common and associated with decreased quality of life. At present, the structural connectivity of apathy in STN-DBS is largely unexplored.

Method: Normative structural connectivity analysis was performed in PD patients who received bilateral STN-DBS (n=53) and were evaluated before and after surgery using the Frontal Systems Behavior Scale (FrSBe) apathy subscale with standardized norm-referenced T scores (mean=50, SD=10). Mean±SD disease duration of the cohort (75% male) was 8.0±4.7 years, age at surgery was 64.5±8.6 years, and follow-up duration after surgery was 8.5±1.8 months. A fiber filtering analysis using a DBS tractography atlas [1] was used to identify an apathy fiber tract model, seeding from active contacts. The model was developed and cross-validated in a training group (n=38) and then used to estimate apathy score variance in a holdout group (n=15).

Results: While the mean FrSBe apathy change score after DBS was 3.2±14.2 (i.e., 0.32±1.42 SD), scores were highly variable, ranging from 27-point improvement to 37-point worsening (i.e., -2.7 to +3.7 SD). The connectivity profile associated with increased apathy following STN-DBS was asymmetric, and only tracts associated with worse apathy were identified. The left hemisphere included fibers spanning from the anteromedial STN to the medial orbitofrontal cortex and subgenual anterior cingulate cortex, via the nucleus accumbens. The right hemisphere included fibers from the decussating pathway of the dentatorubrothalamic tract projecting to the supplementary motor area (SMA). In the training group, validity of the fiber tract model was assessed with leave-one-patient-out (R=0.38, p=0.02), 5-fold (R=0.46, p=0.004), and 10-fold (R=0.33, p=0.048) cross-validation paradigms. Robustness of the model was demonstrated in the holdout group (R=0.71, p=0.005).

Conclusion: Increased apathy after STN-DBS in PD was associated with stimulating tracts connecting to left orbitofrontal areas and the right SMA, suggesting involvement of networks known to regulate behavioral inhibition and initiation. More work is needed to understand the connectivity associated with apathy following STN-DBS.

References: [1] Middlebrooks et al., 2020; 10.3174/ajnr.A6693

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MDS Abstracts - https://www.mdsabstracts.org/abstract/connectivity-profile-for-increased-apathy-following-subthalamic-nucleus-deep-brain-stimulation-in-parkinsons-disease/