Original ArticleCommon and unique responses to dopamine agonist therapy and deep brain stimulation in Parkinson’s disease: An H215O PET study
Section snippets
Patient groups
Two groups of patients with the diagnosis of idiopathic PD were studied. Nine patients (seven males, two females; age 60 ± 11 years (Mean ± SD), age range 43-77 years, duration of disease 16 ± 6 years) without implanted stimulators, but on a waiting list for surgery, were scanned before and after the injection of apomorphine, a mixed D1/D2 agonist. Eleven patients (seven males, four females; age 60 ± 12 years, age range 41-77 years, duration of disease 15 ± 5 years) were studied 2 ± 1 years
Analysis of baseline differences
The three two-sample, two-tailed, t tests between UPDRS measures of tremor, rigidity, and bradykinesia obtained at baseline (off-treatment) in the apomorphine and DBS groups concluded that there were no statistically significant (P > 0.05) differences in disease severity as reflected by these clinical measures. In addition, the t tests for age and disease duration indicated no statistically significant (P > 0.1) group differences.
Common effects of treatments
The conjunction analysis showed that bilateral STN DBS and
Discussion
The standard model of PD pathophysiology attempts to explain the disease as well as the effects of antiparkinsonian treatment in terms of interactions within circumscribed corticobasal gangliathalamocortical circuits (Figure 1).2 DA agonist therapy and STN DBS are present prototypical treatments, each acting at different sites within the network described by this model, resulting in improvement of parkinsonian symptoms.
As with all centrally acting drug and surgical treatments, both of these
Conclusions
We have identified both common and unique effects of two antiparkinsonian therapies, each of which acts at a different node within a network connecting the BG, thalamus, and cortex. Each treatment produced common changes in SMA, PrG, PoG, SPL, BG, and cerebellum. A number of these effects are consistent with the standard model of the pathophysiology of idiopathic PD; others suggest that the model might be modified to integrate regions that are significantly affected by both treatments.
Acknowledgments
We gratefully acknowledge the PET technicians for their assistance with data acquisition and the clinical staff at the University of Kansas Medical Center for their invaluable help with PD patients who participated in this study. We would also like to thank Neal Jeffries for his advice on statistical analyses.
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Cited by (22)
Apomorphine-induced reorganization of striato-frontal connectivity in patients with tremor-dominant Parkinson's disease
2019, Parkinsonism and Related DisordersCitation Excerpt :Previous pharmacological MRI studies in animal and human models demonstrated a robust response to apomorphine administration in several neural hubs extending beyond the classical striato-frontal loop. An H215O PET study revealed that apomorphine induced in idiopathic PD a fast and widespread activation in the BG, thalamus, sensorimotor cortex, and cerebellum [24]. Animal studies have provided a deeper understanding of apomorphine effects on the neural oscillation of the globus pallidus and subthalamic nuclei.
High-frequency stimulation of the subthalamic nucleus selectively decreases central variance of rhythmic finger tapping in Parkinson's disease
2012, NeuropsychologiaCitation Excerpt :However, dopaminergic therapy is not selective to the basal ganglia and is known to influence many motor areas (Buhmann et al., 2003), thus making it difficult to generate causal claims about these observed changes. Stimulation of the STN also induces a widespread pattern of activation in the brain (Limousin et al., 1997), however it increases activity in basal ganglia i.e., globus pallidus, and associated nuclei such as the ventrolateral thalamus more effectively than dopamine (Bradberry et al., 2011). Here, by stimulating the STN we provide evidence that manipulation of the basal ganglia has a direct, relatively immediate and reversible influence on rhythmic movement performance.
This study was financially supported by the Division of Intramural Research at the National Institute on Deafness and other Communication Disorders.
The authors have no conflicts of interest to declare.