Structures outside the basal ganglia may compensate for dopamine loss in the presymptomatic stages of Parkinson's disease

Abstract

We used the 2‐DG metabolic mapping technique to demonstrate the changes in neural activity that occur in a monkey model of Parkinson's disease, which recapitulates the progressive nature of the disease observed in humans. In this way, we could identify the changes in neuronal activity that occur before and after the appearance of parkinsonian motor abnormalities. Our data demonstrate that the changes in metabolic activity within the basal ganglia are responsible for generating symptoms are actually established before symptoms appear. However, abnormalities in supplementary motor cortex activity accompany the appearance of symptoms. These findings demonstrate that compensation for striatal dopamine depletion can occur outside the basal ganglia and that marked changes in neuronal activity of within basal ganglia circuitry are tolerated up to a critical threshold. Defining the nonbasal ganglia mechanisms that compensate for increasing dopaminergic loss in Parkinson's disease will have implications for the treatment and presymptomatic diagnosis of this important neurodegenerative condition.