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In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. However, persistent non-motor symptoms, such as excessive daytime sleepiness, remain a significant challenge and necessitate further investigation. In this study, we conducted repeated measurements of daytime sleepiness using a modified multiple sleep latency test in a healthy monkey macaca fascicularis , which was later rendered parkinsonian through MPTP administration.
Deep brain stimulation targeting the lateral hypothalamic area revealed frequency-dependent modulation of both sleepiness level and core body temperature. High-frequency stimulation 80 Hz increased sleepiness in the healthy state, while low-frequency stimulation 20 Hz promoted wakefulness in the parkinsonian state. Excessive daytime sleepiness EDS poses a significant clinical challenge, characterized by an increase need for sleep and intrusive sleep episodes, severely impacting daily functioning and overall well-being 1 , 2 , 3 , 4.
However, evidence for effective treatment options remains limited, deserving further investigation. Given the challenges of targeting the pedunculopontine nucleusβprimarily due to its deep location, small size, and proximity to critical brainstem regionsβ we shifted our focus to a more accessible yet equally important structure involved in the regulation of sleep and wakefulness, the lateral hypothalamic area LHA.
In particular, the orexin Ox , alternatively called hypocretin Hcrt , neurons within the LHA play a pivotal role in arousal stabilization 9 , 10 and core body temperature regulation 11 , The parkinsonian state was established through the chronic administration of 1-methylphenyl-1,2,3,6-tetrahydropyridine MPTP , which led to stable onset of motor symptoms parkinsonian score: Dopaminergic depletion was confirmed through postmortem immunohistology, which revealed markedly decreased tyrosine hydroxylase expression in the striatum and substantia nigra Fig.
