Pedunculopontine-region deep brain stimulation for gait dysfunction in Parkinson's disease: A network-based review of anatomical and circuit determinants of clinical response

Background Axial gait impairment, freezing of gait, postural instability, and falls remain major therapeutic challenges in advanced Parkinson’s disease. Although subthalamic and pallidal deep brain stimulation improve appendicular motor features, gait and balance responses are less predictable. Pedunculopontine-region deep brain stimulation has been investigated for medication-refractory gait dysfunction, but outcomes vary. This review identifies anatomical, circuit-level, stimulation-related, and patient-specific determinants that may explain heterogeneous responses. Methods We conducted a structured narrative review of studies addressing pedunculopontine-region deep brain stimulation, freezing of gait, postural instability, mesencephalic locomotor circuitry, surgical targeting, stimulation parameters, and pathway recruitment in Parkinson’s disease. Evidence was synthesized thematically, with clinical efficacy considered separately from anatomical localization, biological plausibility, and pathway-recruitment evidence. Results Low-frequency pedunculopontine-region stimulation may improve freezing of gait, falls, gait initiation, or balance in selected patients. However, this therapeutic signal remains inconsistent across small cohorts, controlled studies, single-case reports, combined-target studies, and clinical syntheses. Variability appears related to patient phenotype, target terminology, active-contact location, laterality, stimulation frequency and amplitude, medication state, and adjacent pathway recruitment. Anatomical and imaging studies indicate that the pedunculopontine region is not a sharply bounded clinical target, while computational modeling shows that small differences in electrode position and stimulation settings can alter recruited pathways. Conclusions Pedunculopontine-region deep brain stimulation remains promising but unresolved for gait dysfunction in Parkinson’s disease. Current evidence supports a network-based interpretation rather than a uniform single-nucleus efficacy model. Future studies should prioritize precise target terminology, patient-specific imaging, contact-level reporting, standardized outcomes, and computational methods in future trials.