title: Pathophysiology of Parkinson's disease behavior--a view from the network.
abstract: Advancements in neuroscience have uncovered an amazing complexity of connectivity between nuclei sites and circuits within the brain. Moreover, clinical and neuropathological study has revealed diffuse involvement of the nervous system in Parkinson's disease associated with early and/or significant clinical symptoms. Behavior manifestations in Parkinson's disease include cognitive decline and unwanted positive behaviors such as hallucinations and impulse-control disorders. The pathophysiology of Parkinson's disease can be conceptualized at multiple levels that include: (1) Molecular pathogenesis, (2) Cellular/Tissue abnormalities, (3) Neurochemical changes, (4) Site and circuit dysfunction, and (5) Network dysfunction. Currently, there is only a vague correlation with genetic abnormalities that manifest worse Parkinson's disease behavior problems, but abnormalities in misfolded proteins such as α-synuclein and Aβ peptide that are increased in cortical and subcortical areas do correlate with worse behavior signs and symptoms. Both Lewy-type synucleinopathy and Alzheimer's disease pathologies, along with loss of synaptic integrity, seem to correlate with Parkinson's disease cognitive decline. Neurochemical changes of dopamine, acetylcholine, and other monoamines are associated. The frontostriate circuit is most commonly implicated in Parkinson's disease behavior. However, there is now beginning to be evidence that diffuse global network dysfunction is possibly the unifying pathophysiology from all of these level abnormalities.
authors.affiliation: Mayo Clinic School of Medicine, Mayo Clinic Movement Disorders Division, Scottsdale, AZ, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Caviness
mesh_terms: D001526:Behavioral Symptoms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009415:Nerve Net / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D010300:Parkinson Disease / Q000150:complications* / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents
keywords: Behavior; Dementia; Network; Parkinson's disease; Pathophysiology