To understand the events underlying the clinical efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN), electrophysiological recordings and microdialysis evaluations were carried out in the substantia nigra pars reticulata (SNr), one of the two basal ganglia (BG) nuclei targeted by STN output, in patients with Parkinson's disease (PD). Clinically effective STN-DBS caused a significant increase of the SNr firing rate. The poststimulus histogram (PSTH) showed an excitation peak at 1.92-3.85 ms after the STN stimulus. The spontaneous discharge of SNr neurons was driven at the frequency of the stimulation (130 Hz), as shown in the autocorrelograms (AutoCrl). The fast Fourier transform (FFT) analysis showed a peak at 130 Hz, and a less pronounced second one at 260 Hz. Accordingly, in the distribution of the interspike intervals (ISIs), the mode was earlier, and skewness more asymmetric. Biochemically, the increased excitatory driving from the STN was reflected by a clear-cut increase in cyclic guanosine 3',5'-monophosphate (cGMP) levels in the SNr. These results indicate that the beneficial effect of DBS in PD patients is paralleled with a stimulus-synchronized activation of the STN target, SNr. Our findings suggest that, during STN-DBS, a critical change towards a high-frequency oscillatory discharge occurs.

No abstract

A correct balance between endocannabinoid and dopamine-dependent systems is believed to underlie physiological motor control. We measured the levels of the endocannabinoid anandamide in the cerebrospinal fluid of Parkinson's disease (PD) patients. Subjects were divided into three groups: newly diagnosed de novo patients, subjects undergoing drug withdrawal, and patients under pharmacological therapy. These groups were compared to age-matched control subjects. Anandamide levels in untreated patients were more than doubled as compared to controls. However, chronic dopaminergic replacement restored control anandamide levels. Abnormal anandamide increase might reflect a compensatory mechanism occurring in course of PD, aimed at normalizing dopamine depletion.

Our study suggests that PPTg-DBS plays an important role in reorganizing regular sleep in PD patients.