Converging into a unified model of Parkinson’s disease pathophysiology

ZOLD CL; BELLUSCIO MA; KASANETZ F; POMATA PE; RIQUELME LA; GONON F; MURER MG

Cortico-subcortical dynamics in Parkinson’s disease”.

Humana Press & Springer Editors

Lugar: New York; Año: 2009; p. 143 - 156

Early models of basal ganglia functional organization pointed at changes in spontaneous activity as the underlying basis of akinesia, the main clinical manifestation of Parkinson’s disease. The “classical” model posits that an imbalance between the direct and indirect pathways results in an increase in the average firing rate of basal ganglia output neurons, tonic inhibition of motor thalamo-cortical circuits, and reduced motor output (1, 2). However, after nearly 20 years most researchers in the field would probably agree in that there is little evidence to support this hypothesis (3, 4). Nowadays, there is another kind of model which posits that dopamine depletion impedes movement by promoting excessive oscillatory synchronization of basal ganglia neurons. According to this model, spontaneous oscillation and synchronization could induce resonance at certain frequencies, precluding the encoding of other frequencies more relevant to movement (5) and/or spatial segregation of information flow (6). Nevertheless, the mechanism underlying abnormal oscillatory synchronization is a matter of debate. Current models point at intrinsic oscillations in the GP-STN network (7, 8) or at changes in the gain of pathways conveying and reinforcing cortical oscillations (9, 10).