EP 36. Could Parkinson’s disease symptoms depend on a cortical malfunction

Abstract

Three pieces of information seem to suggest that the current textbook version of what happens in Parkinson’s disease (PD) might be misleading: The dominant activity in dopamine D2 receptor bearing cells of the indirect pathway might be simplistic. Cures of motor symptoms all reduce the dominant beta oscillations recorded in cortical electroencephalograms. Effective deep brain stimulation (DBS) may be acting on cortex and not basal ganglia. Evidence indicates that stimulating electrodes may be activating antidromically and stochastically cortical layer 5 neurons. But what is going wrong in PD? Maybe by ignoring the basal ganglia output from motor thalamus to cortical layer 1 we have built a blind spot into our interpretation of the basal ganglia anatomy, physiology and pathology. This final output from the basal ganglia may be vital for motor actions. What the DBS sites in globus pallidus and subthalamic nucleus have in common is a close access to corticofugal fibres. It is possible that both sites activate cortical output similarly and disrupt the cortical dominance of the basal ganglia-driven beta waves. We have always thought that the effect of dopamine is on the corticostriatal terminals but the lack of cortical dopamine may very well be another possibility. Recent evidence in animal models of PD suggests both anatomical and physiological changes to cerebral cortical neurons are part and parcel of the consequences of dopamine depletion.