Acute central metabolic effects of otolithic vestibular stimulation in a non-human primate model of Parkinsonism: proof-of-concept neuroimaging and functional study

Source abstract

Background Vestibular dysfunction has increasingly been recognized in the pathophysiology of Parkinson’s disease (PD), particularly in relation to postural instability, gait impairment, and altered sensorimotor integration. However, the central metabolic effects associated with acute targeted otolithic vestibular stimulation remain poorly understood. Objectives To explore the acute metabolic correlates associated with otolithic vestibular stimulation using 18 F-FDG PET in a non-human primate model of PD following vestibular implantation. Methods A unilateral otolithic vestibular implant was placed in a macaque ( Macaca fascicularis ) with MPTP-induced Parkinsonism. Parkinsonian severity and persistence of motor impairment were descriptively assessed using repeated blinded Kurlan motor scale evaluations and standardized fine motor performance tasks. Longitudinal 18 F-FDG PET imaging was performed during four experimental stages: basal pre-MPTP condition, MPTP-induced parkinsonian state before implantation, and one- and two-month post-implantation evaluations. Post-implantation PET acquisitions were obtained under OFF and ON stimulation conditions. Voxel-wise subtraction analyses were performed to characterize relative metabolic differences across experimental stages and stimulation conditions. Results MPTP administration induced a persistent parkinsonian phenotype characterized by marked deterioration in fine motor performance relative to baseline, together with persistently elevated Kurlan motor scores throughout follow-up. Metabolically, the MPTP-induced condition was associated with relative hypermetabolism involving especially audiovestibular cortical areas, accompanied by relative hypometabolism in frontal executive, paralimbic, and visual associative regions. Acute vestibular stimulation (ON vs. OFF) demonstrated state-dependent metabolic differences across post-implantation evaluations. During stimulation, increased metabolism predominantly involved vestibulo–thalamo–striatal, sensorimotor, and limbic–paralimbic networks. In contrast, OFF conditions showed relatively greater involvement in visual associative cortices and cerebellar vermis. Conclusion Acute otolithic vestibular stimulation was associated with metabolic modulation of vestibulo–thalamo–striatal and sensorimotor-related networks in a parkinsonian non-human primate model. These findings provide proof-of-concept evidence supporting the capacity of vestibular neurostimulation to engage distributed central motor integration circuits.