Chronic subthalamic nucleus stimulation and striatal D2 dopamine receptors in Parkinson's disease - A [C-11]-raclopride PET study
ABSTRACT Subthalamic nucleus (STN) stimulation mechanism of action remains a matter for debate. In animals, an increased striatal dopamine (DA) release due to STN stimulation has been reported.
To determine in Parkinson's disease (PD) patients using positron emission tomography (PET) and [11C]-Raclopride, whether STN stimulation induces a striatal DA release.
Nine PD patients with bilateral STN stimulation were enrolled and underwent two [11C]-Raclopride PET scans. The scans were randomly performed in off and on stimulation conditions. Striatal [11C]-Raclopride binding potential (BP) was calculated using regions of interest and statistical parametric mapping.
For PD patients, the mean [(11C]-Raclopride BP (+/- SD) were, in Off stimulation condition: 1.7 +/- 0.3 for the right caudate nucleus, 1.8 +/- 0.4 for the left caudate nucleus, 2.6 +/- 0.5 for the right putamenand 2.6 +/- 0.5 for the left putamen. In On stimulation condition: 1.7 +/- 0.4 for the right caudate nucleus, 1.9 +/- 0.5 for the left caudate nucleus, 2.8 +/- 0.7 for the right putamen and 2.7 +/- 0.8 for the left putamen. No significant difference of BP related to the stimulation was noted.
STN stimulation does not produce significant variations of striatal DA release as assessed by PET and [11C]-Raclopride.
- SourceAvailable from: sciencedirect.com
[Show abstract] [Hide abstract]
- "Binding of this tracer is inversely proportional to levels of extracellular dopamine (Laruelle, 2000). After a period when the stimulation has been turned off and L-dopa withdrawn, STN-HFS in one side does not induce differences in [ 11 C] raclopride binding between the two striata (Abosch et al., 2003; Hilker et al., 2003b; Strafella et al., 2003b; Thobois et al., 2003). Therefore, there is no evidence for STN stimulation inducing dopamine release in humans. "
ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor, cognitive, neuropsychiatric, autonomic, and other nonmotor symptoms. Deep brain stimulation (DBS) at high frequency is now considered the most effective neurosurgical therapy for movement disorders, especially PD. An electrode is chronically implanted in a particular area of the brain and, when continuously stimulated, it significantly alleviates motor symptoms. In Parkinson's disease, the common target nuclei of high frequency stimulation (HFS) are the basal ganglia nuclei, such as the internal segment of the pallidum and the subthalamic nucleus (STN), with a preference for the STN in recent years. Two fundamental mechanisms have been proposed to underlie the beneficial effects of HFS: either silencing or excitation of STN neurons. This article highlights the recent views concerned with the mechanisms of DBS. Although the efficacy of DBS for the motor symptoms of advanced PD is well established, the effects of DBS on the cognitive and neuropsychiatric symptoms are less clear. The cognitive aspects of DBS for PD have recently been of considerable clinical and pathophysiological interest. This article also reviews the published literature on the cognitive aspects of DBS for PD.Brain Research Reviews 05/2010; 65(1):1-13. DOI:10.1016/j.brainresrev.2010.04.010 · 5.93 Impact Factor
[Show abstract] [Hide abstract]
- "Another study also indicated that STN HFS in MPTP-treated monkeys provided about 20% neuroprotection to DAergic cells (Wallace et al., 2007). Thus, although clinical findings reported that STN HFS failed to improve DA outflow in PD patients or increase the survival of DAergic cells (Hilker et al., 2003; Thobois et al., 2003), most of the studies in animal models with partial DA lesion are in agreement with an activation/preservation of the DAergic system by STN HFS. However, this effect is unlikely to participate to the thera peutic action in late stages of PD, when patients usually undergo HFS, due to the already extensive loss of DAergic neurons. "
ABSTRACT: Loss of the dopaminergic input to the striatum, characterizing Parkinson's disease, leads to the hyper-activity of two key nuclei of the basal ganglia (BG): the subthalamic nucleus (STN) and the internal segment of the globus pallidus (GPi). The anatomo-physiological organization of the BG and their output suggested that interfering with such hyper-activity could restore motor function and improve parkinsonism. Several animal models in rodents and primates, as well as clinical studies and neurosurgical treatments, have confirmed such hypothesis. This chapter will review the physiological and behavioural data obtained by inactivating the GPi or the STN by means of lesions, pharmacological approaches and deep brain stimulation. The consequences of these treatments will be examined at levels ranging from cellular to complex behavioural changes. Some of this experimental evidence suggested new and effective clinical treatments for PD, which are now routinely used worldwide. However, further studies are necessary to better understand the consequences of GPi and STN manipulation especially at the cognitive level in order to improve functional neurosurgical treatments for Parkinson's disease by minimizing risks of side-effects.Progress in brain research 01/2010; 183:235-58. DOI:10.1016/S0079-6123(10)83012-2 · 5.10 Impact Factor
[Show abstract] [Hide abstract]
- "Some animal studies have suggested that STN DBS could increase the extracellular content of striatal dopamine release (Bruet et al, 2001). However this was not confirmed using PET studies and [ 11 C]-raclopride, a D2 dopamine antagonist ligand (Strafella et al, 2003b; Thobois et al, 2003). Nevertheless, this does not rule out the idea of increased striatal DA release with STN DBS. "
ABSTRACT: Deep brain stimulation (DBS) represents a major advance in the treatment of various severe movement disorders or neuropsychiatric diseases. Our understanding of the mechanism of action of this surgical treatment has greatly benefited from functional imaging studies. Most of these studies have been conducted in patients with Parkinson's disease (PD) treated by bilateral subthalamic nucleus (STN) stimulation. These studies have notably underlined the fact that STN stimulation influences motor, limbic, or associative cortical-subcortical loops in various (sometimes contradictory) ways. We present an up-to-date review of the information provided by functional imaging studies in surgery for PD, dystonia, tremor, as well as in psychiatric disorders such as depression or obsessive-compulsive disorder. On the basis of this information, proposed mechanisms of action of DBS are discussed, as well as the need for additional approaches such as improved anatomical localization of the contact used for stimulation or a better understanding of the electrical distribution around the electrode.Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 08/2009; 29(11):1743-54. DOI:10.1038/jcbfm.2009.111 · 5.34 Impact Factor