Objective: To investigate neural circuitry associated with verbal fluency changes after STN-DBS in Parkinson’s disease.

Background: Despite its substantial motor benefits, subtle cognitive changes can occur after STN-DBS for Parkinson’s disease (PD) [1]. A decline in category- and letter-guided verbal fluency following STN lead implantation is well documented [2-3]. While the lesion effect can contribute, stimulation itself can also impact letter-guided verbal fluency (VF) [4]. A network-based mechanism for this effect is not fully understood. We investigated structural connectivity of the volume of tissue activated (VTA) associated with VF decline.

Method: 21 patients with unilateral STN-DBS (12 left, 9 right) were included in our study [figure1]. STN-DBS electrodes of each PD patient were localized based on pre-op MR and post-op CT images [5]. VTAs were produced based on stimulation parameters. Demographically-adjusted letter VF scores (age, sex, education-adjusted T-scores) were compared between baseline preoperative performance and the 2-month postoperative time point. VTAs were seeded in a normative structural connectome to identify connectivity profiles for each patient. These connectivity profiles were correlated with % change in VF to produce R-maps. Additionally, amongst the fibers passing through VTAs, a two-sample t-test was used to assign which fibers were associated with positive or negative VF changes.

Results: A significant decline of VF was observed for left DBS (p = 0.016), but not right DBS (p = 0.87) cohorts. R-maps from structural connectome revealed that VF improvement correlated with greater connectivity to right IFG pars orbitalis (r = 0.56, p=0.007), ventromedial prefrontal cortex (r=0.55, p=0.01), hippocampus (r=0.44, p=0.04), and orbitofrontal cortices [figure2]. Fibers filtered from the right (t-score = 1.99) and left VTAs (t-score = -2.61) were associated with an opposite trend in VF score changes [figure 3].

Conclusion: STN DBS displays strong hemispheric lateralization effects on VF function. Our results suggest that stimulation of the fibers connecting left STN to left prefrontal regions was strongly associated with VF decline, whereas stimulation of right STN fibers was associated with VF improvement. Beyond effects of implant hemisphere, our findings suggest a structural connectivity network for VF that could yield more tailored approaches to DBS programming.

References: [1] Rothlind JC, York MK, Carlson K, et al. Neuropsychological changes following deep brain stimulation surgery for Parkinson’s disease: comparisons of treatment at pallidal and subthalamic targets versus best medical therapy. J Neurol Neurosurg Psychiatry 2014.
[2] Parsons TD, Rogers SA, Braaten AJ, Woods SP, Troster AI. Cognitive sequelae of subthalamic nucleus deep brain stimulation in Parkinson’s disease: a meta-analysis. Lancet neurology 2006;5:578-588.
[3] Del Bene VA, Martin RC, Brinkerhoff SA, et al. Differential cognitive effects of unilateral left and right subthalamic nucleus deep brain stimulation for Parkinson disease. medRxiv 2023:2023.2002.2027.23286478.
[4] Tröster AI, Jankovic J, Tagliati M, Peichel D, Okun MS. Neuropsychological outcomes from constant current deep brain stimulation for Parkinson’s disease. Mov Disord 2017;32:433-440. PMC5363377
[5] Horn A, Kühn AA. Lead-DBS: a toolbox for deep brain stimulation electrode localizations and visualizations. Neuroimage 2015;107:127-135.

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/verbal-fluency-changes-after-unilateral-stn-deep-brain-stimulation-in-parkinsons-disease-a-connectomics-based-approach/