Computational modelling of acetylcholine deficiency-mediated dysfunction in the basal ganglia-thalamocortical network related to Parkinson’s disease dementia
- 1School of Mathematics and Computer Engineering, Ordos Institute of Technology, Ordos, China
Abstract
Parkinson’s disease dementia (PDD) is a significant form of dementia. Its pathophysiology involves not only the dopaminergic system impairment but also the degeneration of cholinergic neurons in the pedunculopontine nucleus (PPN), which is considered a potential contributor to the cognitive decline in PDD. Therefore, this study develops a computational model of the PPN-modulated basal ganglia-thalamic-cortical network to investigate how acetylcholine deficiency affects cortical oscillations. Based on anatomical evidence, acetylcholine deficiency is modeled by modulating synaptic connections from the PPN to the thalamus and basal ganglia output nuclei. Power spectrum analysis shows that acetylcholine deficiency, whether in the PPN-thalamic nucleus pathway or in the PPN-basal ganglia output nucleus pathway, leads to a decrease in cortical power ratio between the high-frequency band and low-frequency band. These results qualitatively reproduce the characteristics of electrophysiological measurements recorded in PDD. Further dynamical analysis suggests that this reduction may be associated with weakened oscillatory activity, reflected by a shift in neuronal firing patterns from limit cycle to point attractor. Moreover, simulations of combined acetylcholine and dopamine deficiencies reveal that both neurotransmitters can reduce the cortical power ratio, with a synergistic interaction rather than a simple additive effect. These findings provide a systems-level perspective on how ACh deficiency may contribute to cortical dysfunction in PDD and may offer a potential direction for future therapeutic research.
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BibTeX
@article{yang2026computational,
title = {{Computational modelling of acetylcholine deficiency-mediated dysfunction in the basal ganglia-thalamocortical network related to Parkinson’s disease dementia}},
author = {Hao Yang},
journal = {PLOS One},
year = {2026},
month = nov,
doi = {10.1371/journal.pone.0361725},
url = {https://doi.org/10.1371/journal.pone.0361725},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Computational modelling of acetylcholine deficiency-mediated dysfunction in the basal ganglia-thalamocortical network related to Parkinson’s disease dementia
AU - Hao Yang
PY - 2026
DA - 2026/11/04
JO - PLOS One
DO - 10.1371/journal.pone.0361725
UR - https://doi.org/10.1371/journal.pone.0361725
AB - Parkinson’s disease dementia (PDD) is a significant form of dementia. Its pathophysiology involves not only the dopaminergic system impairment but also the degeneration of cholinergic neurons in the pedunculopontine nucleus (PPN), which is considered a potential contributor to the cognitive decline in PDD. Therefore, this study develops a computational model of the PPN-modulated basal ganglia-thalamic-cortical network to investigate how acetylcholine deficiency affects cortical oscillations. Based on anatomical evidence, acetylcholine deficiency is modeled by modulating synaptic connections from the PPN to the thalamus and basal ganglia output nuclei. Power spectrum analysis shows that acetylcholine deficiency, whether in the PPN-thalamic nucleus pathway or in the PPN-basal ganglia output nucleus pathway, leads to a decrease in cortical power ratio between the high-frequency band and low-frequency band. These results qualitatively reproduce the characteristics of electrophysiological measurements recorded in PDD. Further dynamical analysis suggests that this reduction may be associated with weakened oscillatory activity, reflected by a shift in neuronal firing patterns from limit cycle to point attractor. Moreover, simulations of combined acetylcholine and dopamine deficiencies reveal that both neurotransmitters can reduce the cortical power ratio, with a synergistic interaction rather than a simple additive effect. These findings provide a systems-level perspective on how ACh deficiency may contribute to cortical dysfunction in PDD and may offer a potential direction for future therapeutic research.
SN - 1932-6203
ER -