Dopamine Depletion Drives Whole-Brain Oscillatory Disruptions via Cortico-Subcortical Resonance: A Multiscale Model of Parkinson's Disease in Mice
- 1Politecnico di Milano
Abstract
Parkinson's disease is defined by dopaminergic neuron loss in the substantia nigra, yet its hallmark, exaggerated beta-band synchrony, pervades motor cortex, thalamus, and cerebellum, implicating network dynamics far beyond any single circuit. How focal subcortical dopamine depletion translates into brain-wide oscillatory pathology remains unresolved. We use a connectome-constrained multiscale model of the mouse brain, embedding biophysically detailed spiking networks of basal ganglia and cerebellum within whole-brain corticothalamic dynamics grounded in the Allen Mouse Brain Connectivity Atlas. We show that confining dopamine depletion exclusively to subcortical circuits is sufficient to produce widespread beta hypersynchrony (10-30 Hz), accompanied by heterogeneous theta and gamma dysregulation. Virtual loop ablations reveal that cortical and cerebellar beta amplification strictly requires intact cortico-basal ganglia-thalamic feedback; severing this loop confines beta to subcortical generators. These results support resonance within closed large-scale loops, rather than local rhythmogenesis, as the mechanism underlying distributed Parkinsonian beta pathology.
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BibTeX
@misc{gambosi2026dopamine,
title = {{Dopamine Depletion Drives Whole-Brain Oscillatory Disruptions via Cortico-Subcortical Resonance: A Multiscale Model of Parkinson's Disease in Mice}},
author = {B. Gambosi and D. Perdikis and J. Meier and A. Geminiani and A. Antonietti and A. Mazzoni and G. Ferrigno and P. Ritter and A. Pedrocchi},
howpublished = {bioRxiv},
year = {2026},
month = may,
doi = {10.64898/2026.05.15.725133},
url = {https://www.biorxiv.org/content/10.64898/2026.05.15.725133v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - Dopamine Depletion Drives Whole-Brain Oscillatory Disruptions via Cortico-Subcortical Resonance: A Multiscale Model of Parkinson's Disease in Mice
AU - B. Gambosi
AU - D. Perdikis
AU - J. Meier
AU - A. Geminiani
AU - A. Antonietti
AU - A. Mazzoni
AU - G. Ferrigno
AU - P. Ritter
AU - A. Pedrocchi
PY - 2026
DA - 2026/05/15
PB - bioRxiv
DO - 10.64898/2026.05.15.725133
UR - https://www.biorxiv.org/content/10.64898/2026.05.15.725133v2
AB - Parkinson's disease is defined by dopaminergic neuron loss in the substantia nigra, yet its hallmark, exaggerated beta-band synchrony, pervades motor cortex, thalamus, and cerebellum, implicating network dynamics far beyond any single circuit. How focal subcortical dopamine depletion translates into brain-wide oscillatory pathology remains unresolved. We use a connectome-constrained multiscale model of the mouse brain, embedding biophysically detailed spiking networks of basal ganglia and cerebellum within whole-brain corticothalamic dynamics grounded in the Allen Mouse Brain Connectivity Atlas. We show that confining dopamine depletion exclusively to subcortical circuits is sufficient to produce widespread beta hypersynchrony (10-30 Hz), accompanied by heterogeneous theta and gamma dysregulation. Virtual loop ablations reveal that cortical and cerebellar beta amplification strictly requires intact cortico-basal ganglia-thalamic feedback; severing this loop confines beta to subcortical generators. These results support resonance within closed large-scale loops, rather than local rhythmogenesis, as the mechanism underlying distributed Parkinsonian beta pathology.
ER -