gms | German Medical Science

Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to modulate autonomic nervous system activity. Harnessing this effect could have clinical benefits for subjects with symptoms of autonomic dysfunction, however, the mechanism responsible for autonomic changes with STN DBS remains unclear. The aim of this study was to use whole-brain tractography to identify elements of the connectivity ‘fingerprint’ of the DBS electrodes that are associated with post-operative changes in autonomic symptoms.

Methods: Eight subjects with Parkinson’s disease were recruited. All subjects completed the COMPASS-31 autonomic symptom questionnaire before surgery and nine months after implantation of STN DBS (range 5-24 months). Diffusion-weighted and T1-weighted pre-operative MRI scans were obtained for each patient, and pre- and post-operative stereotactic CT scans were also performed. We used a previously described analytic pipeline (Fernandes et al 2015) to model the volume of activated tissue (VAT) for each electrode, parcellate the brain into 116 cortical, subcortical and cerebellar areas (‘network nodes’) based on the automated anatomical labeling (AAL) template, and apply probabilistic tractography to the VAT on a voxel-by-voxel basis. Permutation-based paired t-tests were then used to identify significant differences in connectivity profile between the groups with ‘positive’ and ‘negative’ autonomic outcomes. We also identified nodes that survived a 5% threshold in all subjects within either the ‘positive’ or the ‘negative’ outcome group.

Results: The ‘positive autonomic outcome’ group had stronger connectivity between the stimulated areas and the left rolandic operculum, right post-central gyrus, right supramarginal gyrus, and right cerebellar vermis than the ‘negative autonomic outcome’ group, but that ‘negative outcome’ group displayed stronger connections with the right cerebellum (AAL cerebellar area 9) (p < 0.05). Using the second method of comparison, connections to the thalamus bilaterally and the left caudate survived thresholding in all subjects with positive autonomic outcomes, but not in all subjects with negative autonomic outcomes.

Conclusions: There are clear differences between connectivity fingerprints of the ‘positive’ and ‘negative’ autonomic outcome groups. The use of pre-operative tractography to predict electrode locations and stimulation settings that generate ‘positive autonomic outcome’ connectivity profiles could facilitate improved consistency in achieving a good autonomic outcome following STN DBS and should be the subject of future study.