Acute central metabolic effects of otolithic vestibular stimulation in a non-human primate model of Parkinsonism: proof-of-concept neuroimaging and functional study
8 affiliations
- 1Department of Otorhinolaryngology, Complejo Hospitalario Universitario Insular Materno-Infantil
- 2Department of Nuclear Medicine, Clínica Universidad de Navarra
- 3Translational Molecular Imaging Unit (UNIMTRA), Department of Nuclear Medicine, Clínica Universidad de Navarra
- 4IdiSNA, Instituto de Investigación Sanitaria de Navarra, Universidad de Navarra, CIMA
- 5Cochlear Technology Centre Belgium
- 6Department of Otorhinolaryngology, Clínica Universidad de Navarra
- 7CNS Gene Therapy Program, Center for Applied Medical Research (Cima), University of Navarre
- 8Center for Biomedical Network Research on Neurodegenerative Diseases (CIBERNED-ISCIII)
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.
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BibTeX
@article{lorentepiera2026acute,
title = {{Acute central metabolic effects of otolithic vestibular stimulation in a non-human primate model of Parkinsonism: proof-of-concept neuroimaging and functional study}},
author = {Joan Lorente-Piera and María Collantes and Ángel Ramos de Miguel and Manuel Manrique and Ángel Ramos-Macías and Sebastián Picciafuoco and Ricardo Bugallo Delgado and Irene Marcilla García and Gloria González Aseguinolaza and Purificación Ripalda-Cemboráin and José Luis Lanciego and Raquel Manrique-Huarte},
journal = {Frontiers in Neurology},
year = {2026},
month = oct,
doi = {10.3389/fneur.2026.1981761},
url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1981761/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Acute central metabolic effects of otolithic vestibular stimulation in a non-human primate model of Parkinsonism: proof-of-concept neuroimaging and functional study
AU - Joan Lorente-Piera
AU - María Collantes
AU - Ángel Ramos de Miguel
AU - Manuel Manrique
AU - Ángel Ramos-Macías
AU - Sebastián Picciafuoco
AU - Ricardo Bugallo Delgado
AU - Irene Marcilla García
AU - Gloria González Aseguinolaza
AU - Purificación Ripalda-Cemboráin
AU - José Luis Lanciego
AU - Raquel Manrique-Huarte
PY - 2026
DA - 2026/10/28
JO - Frontiers in Neurology
DO - 10.3389/fneur.2026.1981761
UR - https://www.frontiersin.org/articles/10.3389/fneur.2026.1981761/full
AB - 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.
SN - 1664-2295
ER -