Modeling the Varied Expression of the Triad of Motor Symptoms in Parkinson's Disease

Parkinson's disease (PD) is a progressive neurological disorder caused by the gradual death of neurons throughout the body. This neuron death particularly affects several key neurotransmitter-producing neurons, including dopaminergic, serotonergic, noradrenergic, and cholinergic neurons located in the substantia nigra pars compacta, raphe nuclei, locus coeruleus, and nucleus basalis, respectively. Dopaminergic neurons are most associated with PD, with the decrease in dopamine believed to be the primary driver behind the "triad" of parkinsonian motor symptoms: bradykinesia, rigidity, and tremor. However, theories for how dopamine depletion modifies human motor control do not yet link all three symptoms to this single dysfunction. This proposed model expands upon a tremor model based on unstable feedback to capture all three symptoms. Furthermore, the model implements high-level control parameters that capture the potential effects of other neurotransmitters on symptom expression. This new type of model captures the existence of PD subtypes based on the relative levels of neuron death in different brain regions. This knowledge could provide insight into how differing disease progression across brain regions may produce the varying symptoms experienced across PD patients.