https://doi.org/10.1140/epjs/s11734-025-01829-z
Regular Article
Computational modeling of prefrontal cortex-basal ganglia-thalamus loops associated with Parkinson’s disease dementia
School of Mathematics and Statistics, Shaanxi Normal University, 710062, Xi’an, People’s Republic of China
Received:
23
May
2025
Accepted:
21
July
2025
Published online:
30
July
2025
Parkinson’s disease dementia (PDD) is a neurodegenerative disease secondary to Parkinson’s disease (PD), featuring severe cognitive impairments in addition to the same motor symptoms as PD. PDD is characterized pathologically by the degeneration of dopaminergic neurons and clinically by electroencephalography (EEG) slowing. To explore the behavior of EEG slowing and its underlying dynamic mechanisms from neurocomputational perspective, first, we develop a mean-field computational model of the prefrontal cortex-basal ganglia-thalamus loop modulated by dopamine from ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Second, VTA dopamine depletion is simulated by decreasing the value of connection strengths between pyramidal neurons and increasing the value of strengths between interneurons in the prefrontal cortex (PFC), while SNc dopamine depletion is simulated by increasing the value of strengths from D1 neurons to globus pallidus internus/substantia nigra pars reticulata and decreasing the value of strengths from D2 neurons to globus pallidus externus. Then, the numerical results demonstrate that VTA dopamine depletion leads to a significant decrease in the power ratio of PFC, which aligns well with clinical studies of PDD patients showing reduced power ratios alongside declines in simple mental state examination scores. Furthermore, based on dynamical analysis, we reveal that the underlying dynamical mechanism of EEG slowing may be attributed to diminished oscillatory activity in PFC. Specifically, the oscillation amplitude of PFC pyramidal neurons is significantly reduced, with a progressive transition from a limit cycle to an attractor state. Finally, analogous studies on dopamine depletion in SNc demonstrate that dopamine depletion in this region induces only a minor reduction in the power ratio and does not significantly alter the oscillation dynamics. These findings highlight that dopamine depletion in VTA has a far more pronounced impact on EEG slowing in PDD than dopamine depletion in SNc. Moreover, the results underscore the robust association between dopamine depletion and EEG slowing, offering novel mechanistic insights into cognitive impairment in PDD.
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Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
