ArticleNPJ Parkinson's disease2026
Behavioral changes preceded by subthalamic nucleus activity alterations in a progressive macaque model of Parkinson's disease.
Article in NPJ Parkinson's disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Parkinson's disease (PD) is diagnosed after motor symptoms appear, although non-motor symptoms emerge years earlier. Following years of pharmacological treatment, high-frequency stimulation (HFS) of the subthalamic nucleus (STN), a key hub in goal-directed behaviors, can be proposed. While HFS-STN reliably improves motor symptoms, it does not specifically address non-motor symptoms. Clarifying how STN dysfunction contributes to these symptoms could improve stimulation strategies. Here, we longitudinally recorded STN local field potentials in two macaques performing a demanding task during chronic low-dose MPTP treatment. This progressive model, evolving from an asymptomatic stage to motivational, cognitive, and motor deficits, enabled detailed characterization of non-motor stages preceding motor impairment. Each stage was associated with distinct electrophysiological alterations, including early loss of reward-related theta activity, followed by disappearance of decision-related theta oscillations and later reduction of movement-related beta rebound. In the stable parkinsonian stage, stimulation of different STN territories produced complementary behavioral effects: dorsal HFS improved motor performance, whereas ventral low-frequency stimulation alleviated motivational deficits. These findings reveal a temporal relationship between STN dysfunction and symptom onset and support site- and frequency-specific stimulation strategies to address motor and non-motor symptoms in PD.
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