Combined STN-DBS and acupuncture modulate cortico striatal oscillations and glymphatic function in anxious Parkinsonian rats

STN-DBS improves motor symptoms in Parkinson's disease (PD), but its effects on anxiety are variable. We tested whether manual acupuncture complements STN-DBS in A53T α-synuclein rats with anxiety-like behavior and examined paired scalp EEG in five DBS-treated patients with PD and anxiety. In rats, STN-DBS preferentially improved locomotion and modulated dorsomedial striatum-primary motor cortex coupling, whereas acupuncture preferentially reduced anxiety-like behavior and modulated dorsomedial striatum-medial prefrontal cortex coupling. Combined intervention improved both behavioral domains and shifted regional power, coherence and theta-gamma phase-amplitude coupling toward control profiles. Multi-omic and validation experiments implicated AQP4-associated glymphatic dysfunction: combined intervention improved cerebrospinal fluid influx, reduced striatal tracer retention, restored perivascular AQP4 polarization and reduced α-synuclein burden. TGN-020 partially attenuated behavioral benefit, supporting a contributory role for AQP4-associated clearance. Exploratory patient EEG showed additional prefrontal modulation during acupuncture with active STN-DBS. These findings support complementary circuit and clearance-related effects of combined intervention.