Chapter 7 - Parkinson’s Disease and the Cerebral Cortex

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease that is an age-related disorder, typically affecting middle-aged and elderly individuals. It is commonly associated with movement disorders such as tremor, rigidity, akinesia (poverty of movement), bradykinesia (slowness and impaired scaling of voluntary movement), and difficulty in walking and gait. The motor symptoms of PD are primarily caused by the loss of dopaminergic neurons in the substantia nigra, pars compacta in the midbrain, although the cerebral cortex is intimately involved in all of the pathways associated with the dopamine input to the basal ganglia. However, there are additional behavioral symptoms that can occur in later stages of the disease. These can include various characteristics of dementia, depression, sleep and sensory disruption, and emotional issues. Animal models of PD have been particularly effective in delineating the mechanisms of this condition and have been particularly useful for understanding the role of cortical circuits in both motor and nonmotor dysfunction. There are three symptoms of PD for which the cerebral cortex has been implicated. These include the tremors associated with PD, other motor disturbances such as akinesia, and some of the cognitive disturbances, including dementia. Although each of these symptoms has been examined clinically in PD, the details of the mechanisms have been elaborated in animal models, including nonhuman primates, rats, and mice. There are metabolic changes observed in motor and nonmotor cortical regions, and these changes occur in regions of the cortex that also have neurotransmitter changes including levels of dopamine and serotonin. This implication of the cerebral cortex in most of the complications of PD provides an opportunity to explore in more detail the critical mechanisms and molecules contributing to this progressive debilitating disease and suggests new approaches for therapeutic targets.