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bioRxiv · 10.64898/2026.05.15.725133

Dopamine Depletion Drives Whole-Brain Oscillatory Disruptions via Cortico-Subcortical Resonance: A Multiscale Model of Parkinson's Disease in Mice

Gambosi, B.·Perdikis, D.·Meier, J.·Geminiani, A.·Antonietti, A.·Mazzoni, A.·Ferrigno, G.·Ritter, P.·Pedrocchi, A.
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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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Gambosi, B., Perdikis, D., Meier, J., Geminiani, A., Antonietti, A., Mazzoni, A., Ferrigno, G., Ritter, P., Pedrocchi, A.. 2026-05-18. Dopamine Depletion Drives Whole-Brain Oscillatory Disruptions via Cortico-Subcortical Resonance: A Multiscale Model of Parkinson's Disease in Mice. https://doi.org/10.64898/2026.05.15.725133

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