Understanding the dopaminergic deficits in Parkinson’s disease: Insights into disease heterogeneity

Parkinson’s disease is a common condition with a broad clinical diversity suggesting the existence of distinct subgroups of patients. This paper describes how dopaminergic disruption within basal ganglia circuitry accounts for some of the major features of the disease and examines how the limited repertoire of the output nuclei within these pathways could allow for an element of “cross-talk” between competing inputs. It is proposed that such conditions could lead to an excessive inhibition of the thalamus and pedunculopontine nucleus and account for many of the familiar patterns of clinical phenotype. It is further postulated that this phenomenon may be acting via increased synchronization within the basal ganglia circuitry.