Common and unique responses to dopamine agonist therapy and deep brain stimulation in Parkinson's disease: an H(2)(15)O PET study

Abstract

Background: Dopamine agonist therapy and deep brain stimulation (DBS) of the subthalamic nucleus (STN) are antiparkinsonian treatments that act on a different part of the basal ganglia-thalamocortical motor circuitry, yet produce similar symptomatic improvements.

Objective/hypothesis: The purpose of this study was to identify common and unique brain network features of these standard treatments.

Methods: We analyzed images produced by H(2)(15)O positron emission tomography (PET) of patients with Parkinson's disease (PD) at rest. Nine patients were scanned before and after injection of apomorphine, and 11 patients were scanned while bilateral stimulators were off and while they were on.

Results: Both treatments produced common deactivations of the neocortical sensorimotor areas, including the supplementary motor area, precentral gyrus, and postcentral gyrus, and in subcortical structures, including the putamen and cerebellum. We observed concomitant activations of the superior parietal lobule and the midbrain in the region of the substantia nigra/STN. We also detected unique, treatment-specific changes with possible motor-related consequences in the basal ganglia, thalamus, neocortical sensorimotor cortex, and posterolateral cerebellum. Unique changes in nonmotor regions may reflect treatment-specific effects on verbal fluency and limbic functions.

Conclusions: Many of the common effects of these treatments are consistent with the standard pathophysiologic model of PD. However, the common effects in the cerebellum are not readily explained by the model. Consistent deactivation of the cerebellum is interesting in light of recent reports of synaptic pathways directly connecting the cerebellum and basal ganglia, and may warrant further consideration for incorporation into the model.

Figure 1

Standard model of connections between basal ganglia, thalamus, and cortex. Excitatory connections are orange, and inhibitory connections are blue with the width of the connections representing their strengths (SNc = substantia nigra pars compacta, GPi = globus pallidus interna, GPe = globus pallidus externa, STN = subthalamic nucleus). a Normal state of circuitry. b State of circuitry during Parkinson’s disease. The target sites of dopamine agonists and STN DBS are shown to be the striatum and STN respectively.

Figure 2

Common effects of STN DBS and apomorphine injection. Axial slices in neurological convention are overlaid with images of z-scores that represent activations (red = 1 to white = 4) and deactivations (blue = −1 to green = −4). Both DBS and apomorphine deactivated the SMA, PrG, PoG, putamen, and cerebellum and activated the SPL and the region of the SN/STN.

Figure 3

Unique effects of STN DBS and apomorphine injection. Axial slices in neurological convention are overlaid with images of z-scores that represent activations (red = 1 to white = 4) and deactivations (blue = −1 to green = −4). a DBS uniquely activated the posterolateral cerebellum (Crus II), inferior frontal gyrus, GP, amygdala, hippocampus, and ventrolateral thalamus and deactivated the posterolateral cerebellum (Lobule VI), cerebellar vermis, PrG, SMA, PoG, and putamen. b Apomorphine uniquely activated the PrG, pre-SMA, PoG, and hippocampus and deactivated the posterolateral cerebellum (Crus II), inferior frontal gyrus, putamen, and ventrolateral thalamus.