Objective: Understanding the role of distinct basal ganglia pathways in DBS-elicited modulation of bradykinesia across its indications.

Background: Opposing bidirectional effects of selective pathway stimulation and a crucial role of indirect loops in reversing dopamine-deficient hypokinesia were milestone discoveries in the field. In contrast to animal studies, research on DBS in humans demonstrated intrapathway but not interpathway differentiation of DBS effects.

Method: We quantified disturbances of the movement velocity as a normalised sum of MDS-UPDRS III items 4-8 and the stimulation effect as its preoperative to postoperative difference, or STIM OFF to STIM ON, always in MED OFF (BDS–bradykinesia difference score). We employed Lead DBS, FSL randomize and the ARENA toolbox for connectivity analysis.

Results: We retrospectively included 98 PD patients with STN (N=59) and GPi (N=39) DBS and 46 dystonic patients with GPi DBS. We prospectively tested 15 Parkinsonian subjects with STN DBS. The mean BDS in the GPi PD cohort was -0.21±0.74, in the STN PD cohort -0.71±0.77, in the GPi dystonia cohort 0.18±0.56, and in the prospective STN PD cohort -0.56±0.63. The joint fibrefiltering of the retrospective PD data revealed a subpart of the lenticular fasciculus (LF), increasing bradykinesia scores, and a part of the hyperdirect pathway (HF), reducing bradykinesia scores. The leave-one-out cross-validation was significant (R=0.38, p<0.0001). The normative functional connectivity pattern of the induced bradykinesia involved the thalamic nuclei receiving the GPi afference. The PD-derived LF fibres predicted bradykinesia change in the dystonia cohort (R=0.25, p=0.048). The sole stimulation of the fibrefiltering-derived LF fibres induced bradykinesia when tested prospectively (p=0.035). We contrasted the antiparkinsonian and antidystonic effects of pallidal DBS on a single fibre level and found a fascicle of Edinger´s comb, significantly more antiparkinsonian than antidystonic, and some LF fibres and Edinger´s fibres in posterior GPi, vice versa. The antiparkinsonian fascicle of interest was predictive in the subsequent hypothesis-driven analysis (R=0.37, p=0.02).

Conclusion: We attribute induced bradykinesia to pallidothalamic connections and antiparkinsonian effects to the indirect and hyperdirect pathway.

Presented at DBS Expert Summit, 23.02.2026, Wuerzburg, Germany

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MDS Abstracts - https://www.mdsabstracts.org/abstract/basal-ganglia-pathway-recruitment-determines-bidirectional-bradykinesia-modulation-by-dbs-in-humans/