Previous studies have shown that electroacupuncture (EA) promotes recovery of motor function in Parkinson's disease (PD). However the mechanisms are not completely understood. Clinically, the subthalamic nucleus (STN) is a critical target for deep brain stimulation treatment of PD, and vesicular glutamate transporter 1 (VGluT1) plays an important role in the modulation of glutamate in the STN derived from the cortex. In this study, a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD was treated with 100 Hz EA for 4 weeks. Immunohistochemical analysis of tyrosine hydroxylase (TH) showed that EA treatment had no effect on TH expression in the ipsilateral striatum or substantia nigra pars compacta, though it alleviated several of the parkinsonian motor symptoms. Compared with the hemi-parkinsonian rats without EA treatment, the 100 Hz EA treatment significantly decreased apomorphine-induced rotation and increased the latency in the Rotarod test. Notably, the EA treatment reversed the 6-OHDA-induced down-regulation of VGluT1 in the STN. The results demonstrated that EA alleviated motor symptoms and up-regulated VGluT1 in the ipsilateral STN of hemi-parkinsonian rats, suggesting that up-regulation of VGluT1 in the STN may be related to the effects of EA on parkinsonian motor symptoms via restoration of function in the cortico-STN pathway.
Adrenergic Agents ; toxicity ; Animals ; Apomorphine ; pharmacology ; Disease Models, Animal ; Dopamine Agonists ; pharmacology ; Electroacupuncture ; methods ; Functional Laterality ; drug effects ; Male ; Medial Forebrain Bundle ; injuries ; Motor Activity ; drug effects ; physiology ; Neurons ; drug effects ; metabolism ; Oxidopamine ; toxicity ; Parkinson Disease, Secondary ; chemically induced ; physiopathology ; therapy ; Rats ; Rats, Sprague-Dawley ; Subthalamic Nucleus ; drug effects ; metabolism ; pathology ; Tyrosine 3-Monooxygenase ; metabolism ; Up-Regulation ; drug effects ; physiology ; Vesicular Glutamate Transport Protein 1 ; metabolism

The dysfunction of subthalamic nucleus is the main cause of Parkinson's disease. Local field potentials in human subthalamic nucleus contain rich physiological information. The present study aimed to quantify the oscillatory and dynamic characteristics of local field potentials of subthalamic nucleus, and their modulation by the medication therapy for Parkinson's disease. The subthalamic nucleus local field potentials were recorded from patients with Parkinson's disease at the states of on and off medication. The oscillatory features were characterised with the power spectral analysis. Furthermore, the dynamic features were characterised with time-frequency analysis and the coefficient of variation measure of the time-variant power at each frequency. There was a dominant peak at low beta-band with medication off. The medication significantly suppressed the low beta component and increased the theta component. The amplitude fluctuation of neural oscillations was measured by the coefficient of variation. The coefficient of variation in 4-7 Hz and 60-66 Hz was increased by medication. These effects proved that medication had significant modulation to subthalamic nucleus neural oscillatory synchronization and dynamic features. The subthalamic nucleus neural activities tend towards stable state under medication. The findings would provide quantitative biomarkers for studying the mechanisms of Parkinson's disease and clinical treatments of medication or deep brain stimulation.
Antiparkinson Agents ; therapeutic use ; Beta Rhythm ; Electrodes ; Evoked Potentials ; Humans ; Oscillometry ; Parkinson Disease ; drug therapy ; physiopathology ; Subthalamic Nucleus ; physiopathology ; Theta Rhythm

Pathological neural activity in subthalamic nucleus (STN) is closely related to the symptoms of Parkinson' s disease. Local field potentials (LFPs) recordings from subthalamic nucleus show that power spectral peaks exist at tremor, double tremor and tripble tremor frequencies, respectively. The interaction between these components in the multi-frequency tremor may be related to the generation of tremor. To study the linear and nonlinear relationship between those components, we analyzed STN LFPs from 9 Parkinson's disease patients using time frequency, cross correlation, Granger casuality and bi-spectral analysis. Results of the time-frequency analysis and cross-frequency correlation analysis demonstrated that the power density of those components significantly decreased as the alleviation of tremor and cross-correlation (0.18-0.50) exists during tremor period. Granger causality of the time-variant amplitude showed stronger contribution from tremor to double tremor components, and contributions from both tremor and double tremor components to triple tremor component. Quadratic phase couplings among these three components were detected by the bispectral approaches. The linear and nonlinear relationships existed among the multi-components and certainly confirmed that the dependence cross those frequencies and neurological mechanism of tremor involved complicate neural processes.
Action Potentials ; Electromyography ; Humans ; Parkinson Disease ; physiopathology ; Subthalamic Nucleus ; physiopathology ; Tremor ; physiopathology

PURPOSE: As Parkinson's disease (PD) can be considered a network abnormality, the effects of deep brain stimulation (DBS) need to be investigated in the aspect of networks. This study aimed to examine how DBS of the bilateral subthalamic nucleus (STN) affects the motor networks of patients with idiopathic PD during motor performance and to show the feasibility of the network analysis using cross-sectional positron emission tomography (PET) images in DBS studies. MATERIALS AND METHODS: We obtained [15O]H2O PET images from ten patients with PD during a sequential finger-to-thumb opposition task and during the resting state, with DBS-On and DBS-Off at STN. To identify the alteration of motor networks in PD and their changes due to STN-DBS, we applied independent component analysis (ICA) to all the cross-sectional PET images. We analysed the strength of each component according to DBS effects, task effects and interaction effects. RESULTS: ICA blindly decomposed components of functionally associated distributed clusters, which were comparable to the results of univariate statistical parametric mapping. ICA further revealed that STN-DBS modifies usage-strengths of components corresponding to the basal ganglia-thalamo-cortical circuits in PD patients by increasing the hypoactive basal ganglia and by suppressing the hyperactive cortical motor areas, ventrolateral thalamus and cerebellum. CONCLUSION: Our results suggest that STN-DBS may affect not only the abnormal local activity, but also alter brain networks in patients with PD. This study also demonstrated the usefulness of ICA for cross-sectional PET data to reveal network modifications due to DBS, which was not observable using the subtraction method.
Aged ; Brain/*radionuclide imaging ; Cross-Sectional Studies ; Deep Brain Stimulation/*methods ; Female ; Functional Laterality/*physiology ; Humans ; Male ; Middle Aged ; Parkinson Disease/radionuclide imaging/*therapy ; Positron-Emission Tomography ; Severity of Illness Index ; Subthalamic Nucleus/*physiopathology

Adult ; Deep Brain Stimulation ; Essential Tremor ; physiopathology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Subthalamic Nucleus ; physiology

BACKGROUNDSubthalamic deep brain stimulation (STN-DBS) has been shown to be effective in the treatment of Parkinson's disease. The site for permanent stimulation is still in debate. This study aimed to assess the position of active contacts in relation to the subthalamic nucleus.

METHODSWe reviewed the location of 40 electrodes in 34 patients who underwent STN-DBS. The position of electrode was evaluated by postoperative magnetic resonance imaging (MRI). The position of active contacts was compared with the subthalamic nucleus (STN) determined by intraoperative electrophysiological mapping and postoperative MRI.

RESULTSThe average position of the 40 active contacts was (11.7 + or - 1.2) mm lateral, (0.6 + or - 1.3) mm anterior, and (0.7 + or - 1.4) mm vertical to the midcommissural point. The dorsal margin of the STN was (11.6 + or - 1.1) mm lateral, (0.2 + or - 1.1) mm anterior, and (1.3 + or - 1.1) mm vertical to the midcommissural point. When compared with the dorsal margin of the STN, the active contacts were located more dorsally (P = 0.033) and anteriorly (P = 0.012), no significant difference was found in the lateral direction (P = 0.107). When compared with the position of the STN, 26 (65%) of active contacts were located in the region dorsal to the STN, only 13 (32.5%) were located in the upper two-thirds portion of STN.

CONCLUSIONSThe site for permanent stimulation appears to be in the subthalamic region dorsal to the STN, close to the dorsal margin of the STN. Besides the dorsal portion of the STN, other structures such as fields of Forel H and zona incerta may also be involved in the therapeutic benefit of deep brain stimulation.

Adult ; Aged ; Deep Brain Stimulation ; Electrophysiology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Parkinson Disease ; pathology ; physiopathology ; therapy ; Subthalamic Nucleus ; pathology ; physiopathology

AIMTo investigate the neuroprotective effects of lesion and high frequency stimulation(HFS) of the subthalamic nucleus (SIN) on the substantia nigra pars compacta(SNc) neurons and its probable mechanism.

METHODSThe PD models were induced by unilateral administration of 6-hydroxydopamine into right substantia nigra in rats. After the high-frequence stimulation to SIN and injection of ibotenic acid to STN on PD rats, the changes of behavior were observed. The substantia nigra neurons were detected by using special-dyeing, TUNEL techniques and immunohistochemistry methods.

RESULTSIn the stimulation group, the apoptotic rate was significantly lower than PD model group and lesion group (P < 0.05). Compared with normal rats, model group and lesion one had the similar results of expression of Bcl-2, Bax and their ratio, which were lower expression of Bcl-2, higher expression of Bax and the decrease of their ratio (P < 0.05). In the stimulation group, the expression of Bcl-2 and Bcl-2/Bax were much higher than model group and lesion group. The number of apoptotic neurons of rats in lesion group was smaller than model ones (P < 0.05), but there was no significant difference in expression of Bcl-2, Bax and their ratio (P > 0.05).

CONCLUSIONLesion or HFS of STN have the neuroprotective effects on SNc neurons of PD rats, and HFS has a better long-term effect.

Animals ; Electric Stimulation ; Male ; Neurons ; physiology ; Oxidopamine ; Parkinson Disease, Secondary ; chemically induced ; physiopathology ; therapy ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; physiopathology ; Subthalamic Nucleus ; physiopathology ; bcl-2-Associated X Protein ; metabolism

AIMTo research the spontaneous firing activities during different-frequency stimulation of subthalamic nucleus and microelectrophoresis GABA, Glu and their antagons respectively, approaching the mechanism of DBS in the treatment of Parkinson's disease further.

METHODSUsing extracellular recording to investigate the effect of different-frequency stimulation of STN and microelectrophoresis several drugs on the spontaneous firing activities of the SNr neurons.

RESULTSFor STN stimulation at low frequency, there was no difference on the spontaneous firing activities of SNr neurons between pro-stimulation and meta-stimulation (P > 0.05). With the increasing of stimulation frequency, most of the SNr neurons were inhibited. While during the STN stimulation frequency at high-frequency, the firing rates of inhibited SNr neurons were changed (P < 0.05). Glu had catatonic excitement effect on the SNr neurons, whereas GABA had tonic inhibition effect. 80% of SNr neurons which were inhibited by STN-HFS were not inhibited by STN-HFS on the basis of excitatory effect of BIC.

CONCLUSIONTo treat the motor symptoms of PD, when SIN is selected as the target nucleus, the electrical stimulation with high-frequency should be chosen. It is possible that SIN-HFS modulate the activity of SNr by inhibitory effect of GABA predominantly.

Action Potentials ; physiology ; Animals ; Electric Stimulation ; Electrophoresis ; methods ; Glutamic Acid ; administration & dosage ; pharmacology ; Male ; Neurons ; physiology ; Parkinson Disease ; physiopathology ; therapy ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; physiology ; Subthalamic Nucleus ; physiology ; gamma-Aminobutyric Acid ; administration & dosage ; pharmacology

The present study was designed to investigate the function and mechanism of high-frequency stimulation (HFS) of the parafascicular nucleus (PF) used as a therapeutic approach for Parkinson's disease (PD). PD rat model was built by injecting 6-hydroxydopamine (6-OHDA) into the substartia nigra pars compacta of adult male Sprague-Dawley rats. Using the ethological methods, we examined the effect of electrical stimulation of PF on the apomorphine-induced rotational behavior in PD rats. Moreover, Electrophysiological recordings were made in rats to investigate the effects of electrical stimulation of PF on the neuronal activities of the subthalamic nucleus (STN) and the ventromedial nucleus (VM). Our results showed that one week after HFS (130 Hz, 0.4 mA, 5 s) of PF, there was significant improvement in apomorphine-induced rotational behavior in PD rats. HFS of PF caused an inhibition of the majority of neurons (84%) recorded in the STN in PD rats. The majority of cells recorded in the VM of the thalamus responded to the HFS with an increase in their unitary discharge activity (81%). These effects were in a frequency-dependent manner. Only stimulus frequencies above 50 Hz were effective. Furthermore, employing microelectrophoresis, we demonstrated that glutamatergic and GABAergic afferent nerve fibers converged on the same STN neurons. These results show that the HFS of PF induces a reduction of the excitatory glutamatergic output from the PF which in turn results in deactivation of STN neurons. The reduction in tonic inhibitory drive from the basal ganglia induces a disinhibition of activity in the VM, a motor thalamic nucleus. In conclusion, the results suggest that HFS of PF may produce a therapeutic effect in PD rats, which is mediated by the nuclei of PF, STN and VM.
Action Potentials ; physiology ; Animals ; Electric Stimulation ; Intralaminar Thalamic Nuclei ; physiopathology ; Male ; Neurons ; physiology ; Parkinson Disease ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Subthalamic Nucleus ; physiopathology ; Ventral Thalamic Nuclei ; physiopathology

AIMTo observe the effect of cortical spreading depression (CSD) on the spontaneous firing activities of neurons of subthalamic nucleus (STN) in normal and model rat of Parkinson's disease (PD).

METHODSExtracellular recording was used to research the neuronal electric activities in subthalamic neurons. The changes of the discharge rates of subthalamic neurons were observed in control and PD rats after intracortical microinjection of KCl solution.

RESULTSThe discharge rates of subthalamic neurons in control and PD rats were (9.78 +/- 0.71) Hz and (23.81 +/- 1.08) Hz, respectively. The discharge rate of PD rats was increased significantly when compared with those of the control rats and the percentage of neurons discharging in bursts was obviously higher than those of control rats (P < 0.01). After a long latent period secondary to intracortical injection of KCl solution, the discharge rates in both group of subthalamic neurons were decreased apparently, then recovered slowly.

CONCLUSIONThe discharge rate and bursting pattern are increased in PD rats and these abnormal activities can be improved by cortical depression. This result indicates that the changes in cortical excitability may be one of the factors increasing the activity of STN in PD.

Animals ; Cortical Spreading Depression ; physiology ; Male ; Neurons ; Parkinson Disease ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Subthalamic Nucleus ; physiology