Purpose of review: The on-going quest for potentially disease-modifying therapies in Parkinson's disease has prompted the development of methods that can differentiate direct disease effects from compensatory processes.
Recent findings: PET studies have suggested a number of changes at the synaptic level to maintain integrity of dopaminergic systems. Functional MRI studies support the long-held belief that relatively intact cerebellar circuits may compensate for impaired basal ganglia function. Altered connectivity and increased spatial extent of activation also appear to be mechanisms through which motor and cognitive performance can be maintained.
Summary: Ascertaining which changes in brain activation in Parkinson's disease are, in fact, compensatory represents a serious challenge. Compensatory mechanisms have been demonstrated from the microscopic, synaptic level to the macroscopic, system level. Augmentation of compensatory mechanisms, in addition to ameliorating the loss of dopaminergic neurons, may represent a joint strategy for overall minimization of disability.