Physiology and pathophysiology of Parkinson's disease

The behavior of neurons in the basal ganglia is severely disrupted in Parkinson's disease (PD). In nonhuman parkinsonian primate models, the disturbance in neurons in basal ganglia output structures include increased firing, bursting, an augmented synchrony, correlated activity, and a tendency towards loss of specificity in their receptive fields. This abnormal neuronal behavior, transmitted to the thalamus, cortex and brainstem, is thought to disrupt the functioning of the motor system and underlie the major motor manifestations of PD-tremor, rigidity, akinesia, gait, and postural disturbances. The mainstay of treatment has been to replace the missing dopamine with medication. With time and disease progression, however, dopamine replacement becomes less efficacious and new adverse effects, including the development of motor fluctuations and drug-induced involuntary movements or dyskinesias, emerge. When the patients reach this stage, surgical therapy becomes an option. Most surgical interventions are performed at the level of the thalamus, globus pallidus, and subthalamic nucleus, aiming at the disruption of the pathological activity that accompanies the Parkinson's deficiency state. With this abnormal neuronal activity neutralized, normal movements can in many cases be restored.