Deep brain implantable microelectrode arrays for detection and functional localization of the subthalamic nucleus in rats with Parkinson’s disease

The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.

Sex modulates the outcome of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease

There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease,the effects of sex on treatment outcome are still unclear.The aim of this retrospective observational study,was to examine sex differences in motor symptoms,nonmotor symptoms,and quality of life after subthalamic nucleus deep brain stimulation.Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00±8.01 years(55 men and 35 women).Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test,and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex.We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation.Restless legs syndrome was alleviated to a greater extent in men than in women.Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation.Furthermore,Hoehn-Yahr stage was positively correlated with the treatment response in men,while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women.In conclusion,women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms,non-motor symptoms,and quality of life.We found sex-specific factors,i.e.,Hoehn-Yahr stage and levodopa equivalent dose,that were related to motor improvements.These findings may help to guide subthalamic nucleus deep brain stimulation patient selection,prognosis,and stimulation programming for optimal therapeutic efficacy in Parkinson’s disease.

Five-year follow-up of 23 asymmetrical Parkinson's disease patients treated with unilateral subthalamic nucleus stimulation

In this study, 23 asymmetrical Parkinson＇s disease patients were treated with unilateral deep brain stimulation of the subthalamic nucleus and followed up for 5 years. At 5 years after stimulation treatment, Unified Parkinson＇s Disease Rating Scale II, III and axial symptom scores in the off-drug condition were significantly increased compared those at baseline. However, total Unified Parkinson＇s Disease Rating Scale II, III and axial symptom scores were significantly lower with stimulation-on compared with the synchronous stimulation-off state in off-drug condition, and the motor symptoms of contralateral side limbs were effectively controlled. Only low Hoehn-Yahr stage was correlated with good long-term postoperative improvement in motor symptoms. The mean levodopa-equivalent daily dose after stimulation treatment was significantly lower than that before treatment, but dyskinesias became worse. Our experimental findings indicate that unilateral deep brain stimulation of the subthalamic nucleus is an effective treatment for improving motor symptoms in well selected asymmetrical Parkinson＇s disease patients presenting no severe axial symptoms and dyskinesias.

Chronic deep brain stimulation of the subthalamic nucleus in a monkey model of hemiparkinsonian Dynamic alterations of extracellular fluid dopamine levels in corpus striatum

BACKGROUND： Although experimental studies have utilized high-frequency stimulation in animal models, few reports have focused on long-term subthalamic nucleus deep brain stimulation （STN DBS） in Parkinson＇s disease （PD） animal models. OBJECTIVE： The present study simulated long-term DBS system and utilized microdialysis technology to study the influence of STN DBS on levels of extracellular dopamine （DA） and its metabolites, homovanillic acid （HVA） and dihydroxy phenyl acetic acid, in the corpus striatum of a hemiparkinsonian monkey model. DESIGN, TIME AND SETTING： A controlled animal study was performed at the Neurosurgery Laboratory, Changhai Hospital of the Second Military Medical University of Chinese PLA between January 2004 and December 2007. MATERIALS： 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyrindinewas （MPTP） purchased from Sigma, USA. Type-3389 DBS electrode and type-7246 pulse generator were provided by Medtronic, USA. METHODS： Hemiparkinsonism was induced in 2 male, adult Rhesus Macaque monkeys through unilateral internal carotid artery infusion of MPTP. Following model establishment, stimulation electrodes were implanted in the right STN, and chronic high-frequency stimulation （60 μs pulse width, 130 Hz frequency, and 1.5 2.0 V pressure） was performed. MAIN OUTCOME MEASURES： Prior to, and 2 hours, 8 hours, 1 week, 1 month, and 2 months after DBS, samples were collected from the caudate nucleus and putamen using microdialysis technology Extracellular levels of DA and its metabolites were measured using high-performance liquid chromatography and electrochemical detection （HPLC-ECD） methods. RESULTS： At 8 hours, 1 week, 1 month, and 2 months after DBS, DA levels in the putamen and caudate nucleus were increased on the electrode-implanted side by 39%, 91%, 111%, and 114% and 31%, 91%, 106%, and 102%, respectively. The DA turnover rate （HVA/DA） was increased in the putamen and caudate nucleus by 186% and 91%, respectively, at 8 hours after DBS, while there was no significant difference at 1 week, 1 month, and 2 months after DBS. CONCLUSION： Effective, chronic, high frequency DBS increased extracellular DA levels in the corpus striatum, which could be one of mechanisms involved in the effects of STN DBS.

Chaotic electrical stimulation of the subthalamic nucleus-mossy fiber sprouting, epileptic seizures, and brain electrical activity in pentylenetetrazol-kindled rats

BACKGROUND： Previous studies have demonstrated that appropriate interventions can alter brain electrical activity of epileptic patients prior to and during a seizure, leading to maintenance of a highly chaotic state, thereby inhibiting abnormal epileptic discharges, and eventually controlling epileptic seizure. OBJECTIVE： This study was designed to observe the effects of chaotic electrical stimulation to the subthalamic nucleus on mossy fiber sprouting, epileptic seizures, and electrical discharges, and to summarize the most suitable intervention. DESIGN, TIME AND SETTING： This randomized grouping, neuroelectrophysiological study was performed at the Laboratory of Neurology, Union Hospital Affiliated to Fujian Medical University in September 2007. MATERIALS： Fifty-five healthy, male, Sprague Dawley rats were subjected to an epileptic model by an intraperitoneal injection of pentylenetetrazol. The YC-2 programmed electrical stimulator was provided by Chengdu Instrument Factory, China; the video electroencephalographic system （KT-88-2400） and 24-hour active electroencephalographic system were products of Contec Medical System Co., Ltd., China; pentylenetetrazol was purchased from Sigma, USA. METHODS： The present interventional method consisted of electrical stimulation to the subthalamic nucleus with an intensity of 500 μA, pulse width 0.05 ms, frequency 30 Hz, and a duration of 20 minutes for 14 successive days. Fifty-five rats were divided into 6 groups： （1） pre-stimulation （n = 10）, pentylenetetrazol was administered and 30 minutes later, chaotic electrical stimulation was performed; （2） synchronous stimulation （n = 10）, rats received pentylenetetrazol and chaotic electrical stimulation concurrently; （3） post-administration stimulation （n = 10）, after pentylenetetrazol administration, chaotic electrical stimulation was performed immediately after cessation of a seizure; （4） sham-stimulation （n = 10）, following pentylenetetrazol administration, an electrode was connected to the stimulator, but electrical stimulation was not performed; （5） control （n = 10）, pentylenetetrazol administration, but no electrode was implanted; （6） blank control （n = 50）, administration of the same amount of physiological saline and chaotic electrical stimulation. MAIN OUTCOME MEASURES： Timm-stained granule change was scored. Simultaneously, electroencephalography was performed to acquire seizure counts and time course of epileptic discharge within 24 hours. RESULTS： Timm scores were lower in the electrically stimulated rats than in the non-stimulated rats （P 〈 0.01）. Timm scores were lowest in the synchronous stimulation group. When the rats suffered from tonic clonic seizure, the electroencephalogram primarily showed a persistent spike-slow wave and sharp wave. For the electrically stimulated rats, the mean values of seizure counts and time course of epileptic discharge during each hour were noticeably decreased compared with the non-stimulated rats. The synchronous stimulation group, however, had the lowest seizure counts and the shortest time course, followed by the pre-stimulation group, and lastly the post-administration stimulation group. Significant differences existed among the groups （P 〈 0.01）. Compared with the pre-stimulation group and the post-administration stimulation group, the latent period of grades Ⅰ and Ⅳ epileptic seizures was significantly prolonged, and the time course of tonic clonic seizure, as well as total time course, were significantly shortened in the synchronous stimulation group （P 〈 0.01）. CONCLUSION： Simultaneous administration of pentylenetetrazol together with chaotic electrical stimulation produced the greatest inhibitory effects on epileptic seizures. This is possibly related to inhibition of abnormal mossy fiber spouting in the hippocampus.

Deep brain stimulation of the subthalamic nucleus treats Parkinson's disease through enhancing metabolic activity of the corpus striatum Verification by single photon emission computed tomography and positron emission tomography

BACKGROUND： Subthalamic nucleus deep brain stimulation （STN DBS） for Parkinson＇s disease （PD） has achieved good effects, but to date the mechanism of STN DBS remains poorly understood STN DBS may increase dopamine levels or metabolic activity of the corpus striatum. OBJECTIVE： To validate the effects of STN DBS on dopamine metabolism and glucose metabolism in the corpus striatum of hemiparkinsonian monkeys using single photon emission computed tomography （SPECT） and position emission tomography （PET）. DESIGN, TIME AND SET＇rING： A controlled animal study was performed at the Neurosurgery Laboratory, Changhai Hospital of the Second Military Medical University of Chinese PLA between January 2004 and December 2007. METHODS： Hemiparkinsonism was induced in adult Rhesus Macaque monkeys, which exhibit similar characteristics of PD in humans, through unilateral internal carotid artery infusion of 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyrindine. Following model establishment, stimulation electrodes were implanted in the right STN, and chronic high-frequency stimulation （60 μs pulse width, 130 Hz frequency, and 1.5-2.0 V pressure） was performed. MAIN OUTCOME MEASURES： The changes in dopamine transporter （DAT）, D2 receptor （D2R）, and glucose metabolism in the corpus striatum following STN DBS were observed using SPECT and PET. RESULTS： SPECT examination showed that DAT specific binding in the right corpus striatum was increased at 3 months after DBS compared with prior to stimulation, and D2R specific binding in the right corpus striatum gradually decreased near levels on the left （non-electrode-implanted） side within 3 months after DBS. PET examination showed that the glucose metabolism in the right corpus striatum was markedly increased at 3 months after effective DBS. Hemiparkinsonism monkeys showed improved left limb rigidity, increased activities, and stable gait under chronic high-frequency stimulation. CONCLUSION： STN DBS increased striatal DAT, decreased D2R, and enhanced glucose metabolism, suggesting that chronic, high-frequency STN stimulation enhanced the metabolic activity of the corpus striatum, a mechanism for improving the PD symptoms of hemiparkinsonian monkeys.

Involvement of GABAergic pathway on inhibition of subthalamic nucleus high-frequency stimulation of spontaneous firing activity in substantia nigra pars reticulata neurons in a rat model of Parkinson's disease

BACKGROUND： Subthalamic nucleus-high frequency stimulation （STN-HFS） plays an important role in the treatment of Parkinson＇s disease, but the mechanisms underlying STN-HFS remain unclear. Some studies have demonstrated that STN stimulation inhibits the firing activity of substantia nigra pars reticulata neurons. OBJECTIVE： To investigate the effects of different-frequency STN stimulation and microiontophoresis of gamma-aminobutyric acid （GABA） and its antagonist, bicuculline, on spontaneous firing activity in a rat model of Parkinson＇s disease, and to analyze the action pathway of high frequency stimulation in firing activity inhibition of substantia nigra pars reticulata neurons. DESIGN, TIME AND SETTING： This neuroelectrophysiological, animal experiment was performed at the Electrophysiology Laboratory of Liaoning Medical University, China from March to August 2008. MATERIALS： 6-hydroxydopamine （6-OHDA） （Sigma, USA）, A320R isolated stimulus and DAM80 preamplifier （World Precision Instruments, USA）, 6400A microiontophoresis apparatus （Dagan, USA）, and Spike 2 biological signal acquisition system （CED, UK） were used in this study. METHODS： A total of 20 Sprague Dawley rats were used to establish a Parkinson＇s disease model via injection of 6-OHDA into the right striatum. Electrical stimulation （0.06-ms width, 0.4-mA intensity 20-200-Hz frequency, 5-second train duration） was delivered to the subthalamic nucleus. Peripheral channels were separately filled with GABA （pH 3.5, 0.2 mol/L）, bicuculline （pH 4.0, 0.01 mol/L）, and NaCI （pH 7.0, 3 mol/L）. The electrode was positioned with a WK-2 microelectrode propulsion device, and was slowly inserted into the substantia nigra pars reticulata to record spontaneous firing activity of substantia nigra pars reticulata neurons. MAIN OUTCOME MEASURES： The number and firing rate of substantia nigra pars reticulata neurons which were either inhibited or excited were measured. RESULTS： Substantia nigra pars reticulata neurons were inhibited by STN stimulation. The proportion of inhibited substantia nigra pars reticulata neurons increased with increasing stimulation frequency. GABA had a tonic inhibitory effect on substantia nigra pars reticulata neurons. Microiontophoresis of bicuculline suppressed the inhibitory effect of STN-HFS on 67% （4/6） of substantia nigra pars reticulata neurons. CONCLUSION： STN-HFS ameliorated abnormal activity in substantia nigra pars reticulata neurons via the inhibitory effect of GABA treatment in a rat model of Parkinson＇s disease.

Effects of various frequency electrical stimulation of the dorsal raphe nucleus on spontaneous firing activities in the rat subthalamic nucleus

BACKGROUND： Some investigations have demonstrated that exogenous 5-hydroxytryptamine increases the spontaneous firing rate of subthalamic nucleus （STN） neurons in the rat brain. OBJECTIVE： To validate the effect of electrical stimulation to the dorsal raphe nucleus （DRN） on the neuronal activities of the STN in rats, as well as analyze the differences in the effects of electrical stimulation at various frequencies. DESIGN, TIME AND SETTING： Experiments were performed from March 2007 to June 2007 in the Electrophysiology Laboratory of Liaoning Medical University with a randomized controlled animal study design. MATERIALS： Twenty-four healthy male Sprague-Dawley （SD） rats, weighing 250-350 g, were selected for this study. An A320R constant electrical stimulator was purchased from World Precision Instruments Company （USA）; a Spike 2 biological signal acquisition system was purchased from British CED Company. METHODS： Twenty-four SD rats were randomly assigned into a model group and a normal group, with 12 rats in each group. To mimic Parkinson＇s disease, rats in the model group were injected with 4μL of 6-hydroxydopamine into the right striatum, then received deep brain stimulation. Rats in the normal group received deep brain stimulation in same brain region without modeling. Electrical stimulation （width, 0.06 ms; intensity, 0.2-0.6 mA; frequency, 20-130 Hz; train duration, 5 seconds） was delivered to the DRN. MAIN OUTCOME MEASURES： The firing rates of STN neurons were observed by extracellular recording using a biological signal acquisition system. RESULTS： DRN-high-frequency stimulation （DRN-HFS） induced excitation in 59% of the STN neurons in the normal group and 50% of the STN neurons in the model group; mean firing rates increased significantly from （7.14±0.75） and （7.94 ± 0.61） Hz to （11.17 ±1.49） and （12.11 ± 1.05） Hz, respectively （P 〈 0.01）. Spontaneous firing rate increased significantly in 53% of neurons in normal rats in a frequency-dependent manner when stimulation frequency was in the range 80-130 Hz. CONCLUSION： DRN-HFS induced an excitatory effect on the spontaneous activity of STN neurons in both normal and PD rats. There was a frequency-dependent effect of electrical stimulation of the DRN on spontaneous firing activities in STN neurons.

High-frequency Stimulation of Subthalamic Nucleus for Treatment of Parkinson's Disease

Degeneration and death of the neurons of the substantia nigra can cause a deficit in brain dopamine, leading to loss of movement control The subthalamic nucleus is a junction of basal ganglia neural circuit and can regulate the efferent information of basal ganglia and control motor activity. High-frequency stimulation of the subthalamic nucleus can alter dopamine levels as well as related factor expression in the corpus striatum and thereby improve the symptoms of Parkinson＇s disease.

Long-term Efficacy of Subthalamic Nucleus Deep Brain Stimulation in Parkinson＇s Disease： A 5-year Follow-up Study in China

Background： Subthalarnic nucleus deep brain stimulation （STN DBS） is effective against advanced Parkinson＇s disease （PD）, allowing dramatic improvement of Parkinsonism, in addition to a significant reduction in medication. Here we aimed to investigate the long-term effect of STN DBS in Chinese PD patients, which has not been thoroughly studied in China. Meihods： Ten PD patients were assessed before DBS and followed up 1, 3, and 5 years later using Unified Parkinson＇s Disease Rating Scale Part Ⅲ （UPDRS Ill）, Parkinson＇s Disease Questionnatire-39, Parkinson＇s Disease Sleep Scale-Chinese Version, Mini-mental State Examination, Montreal Cognitive Assessment, Hamilton Anxiety Scale and Hamilton Depression Scale. Stimulation parameters and drug dosages were recorded at each follow-up. Data were analyzed using the ANOVA for repeated measures. Resulis： In the ＂oft＂ state （off medication）, DBS improved UPDRS Ill scores by 35.87% in 5 years, compared with preoperative baseline （P 〈 0.001 ）. In the ＂on＂ state （on medication）, motor scores at 5 years were similar to the results of preoperative levodopa challenge test. The quality of life is improved by 58.18% （P 〈 0.001 ） from baseline to 3 years and gradually declined afterward. Sleep, cognition, and emotion were mostly unchanged. Levodopa equivalent daily dose was reduced from 660.4 ± 210.1 mg at baseline to 310.6 ± 158.4 mg at 5 years （by 52.96%, P 〈 0.001 ）. The average pulse width, frequency and amplitude at 5 years were 75.0 ± 18.21 Its, 138.5 ± 19.34 Hz, and 2.68 ± 0.43 V, respectively. Conclusions： STN DBS is an effective intervention for PD, although with other studies, patients in our study required lower voltage and associated with a slightly diminished efficacy after 5 years. Compared medication for satisfactory symptom control.

Influence of deep brain stimulation of the subthalamic nucleus on cognitive function in patients with Parkinson's disease

Deep brain stimulation （DBS） is an effective technique for treating Parkinson＇s disease （PD） in the middle and advanced stages. The subthalamic nucleus （STN） is the most common target for clinical treatment using DBS. While STN-DBS can significantly improve motor symptoms in PD patients, adverse cognitive effects have also been reported. The specific effects of STN-DBS on cognitive function and the related mechanisms remain unclear. Thus, it is imperative to identify the influence of STN-DBS on cognition and investigate the potential mechanisms to provide a clearer view of the various cognitive sequelae in PD patients. For this review, a literature search was performed using the following inclusion criteria： （1） at least 10 patients followed for a mean of at least 6 months after surgery since the year 2006; （2） pre- and postoperative cognitive data using at least one standardized neuropsychological scale; and （3） adequate reporting of study results using means and standard deviations. Of -170 clinical studies identified, 25 cohort studies （including 15 self-controlled studies, nine intergroup controlled studies, and one multi-center, randomized control experiment） and one meta- analysis were eligible for inclusion. The results suggest that the precise mechanism of the changes in cognitive function after STN-DBS remains obscure, but STN-DBS certainly has effects on cognition. In particular, a progressive decrease in verbal fluency after STN-DBS is consistently reported and although executive function is unchanged in the intermediate stage postoperatively, it tends to decline in the early and later stages. However, these changes do not affect the improvements in quality of life. STN-DBS seems to be safe with respect to cognitive effects in carefully-selected patients during a follow-up period from 6 months to 9 years.

Effects of bilateral subthalamic nucleus stimulation on resting-state cerebral glucose metabolism in advanced Parkinson’s disease

Background The major neuropathological symptoms of Parkinson’s disease (PD) consist of a loss of pigmented dopaminergic neurons in the substantia nigra and the presence of Lewy bodies. This study was to investigate the effects of bilateral subthalamic nucleus (STN) stimulation on resting-state cerebral glucose metabolism in advanced PD, and investigate the mechanism of deep brain stimulation (DBS). Methods Seven consecutive advanced PD patients (4 men and 3 women, mean age 64±4 years, mean H-Y disability rating 4.4±0.65) receiving bilateral STN DBS underwent 18F-fluorodeoxyglucose ( 18F-FDG)/positron-emission tomography (PET) examinations at rest both preoperatively and one month postoperatively, with STN stimulation still on. The unified PD rating scale was used to evaluate the clinical state under each condition. Statistical parametric mapping (SPM) was used to investigate the regional cerebral metabolic rates of glucose (rCMRGlu) during STN stimulation, and to compare these values to rCMRGlu preoperation. Results STN stimulation clearly improved clinical symptoms in all patients. A significant increase in rCMRGlu was found in the bilateral lentiform nucleus, brainstem (midbrain and pons), bilateral premotor area (BA6), parietal-occipital cortex, and anterior cingulated cortex, and a marked decrease in rCMRGlu was noted in the left limbic lobe and bilateral inferior frontal cortex (P<0.05). Conclusion Bilateral STN stimulation may activate the projection axon from the STN, improving clinical symptoms in advanced PD patients by improving both ascending and descending pathways from the basal ganglia and increasing the metabolism of higher-order motor control in the frontal cortex.

Subthalamic nucleus deep brain stimulation for Parkinson’s disease: 8 years of follow-up

Objective:The short-term benefits of bilateral stimulation of the subthalamic nucleus(STN)in patients with advanced Parkinson’s disease(PD)are well documented,but long-term benefits are still uncertain.The aim of this study is to evaluate the outcome of 8 years of bilateral STN stimulation to PD patients.Methods:In this study,31 consecutive PD patients were treated with bilateral STN stimulation.Their functional status was measured using the Activities of Daily Living section of the Unified Parkinson’s Disease Rating Scale(UPDRS-ADL)at drug on(with medication)and drug off(without medication)states preoperatively and at 1,5,and 8 years postoperatively.In addition,Levodopa equivalent doses and stimulation parameters were also assessed.Results:After 8 years of STN stimulation,the UPDRS-ADL scores were improved by 4%at drug off status(P>0.05)and 22%at drug on status(P<0.05)compared with baseline;the levodopa daily doses were reduced by 28%(P<0.05)compared with baseline;the stimulation voltage and pulse width were not changed,but the stimulation frequency was decreased remarkably compared with the 5 years of follow-up.Adverse events were observed in 6 patients,including misplacement of the electrode and skin erosion requiring further surgery.All events were resolved without permanent sequelae.2 patients died of aspiration pneumonia 6 and 7 years after surgery.Conclusions:The marked improvement in UPDRS-ADL scores were still observed after 8 years of bilateral STN stimulation with medication.

Subthalamic deep brain stimulation for Parkinson＇s disease： correlation of active contacts and electrophysiologically mapped subthalamic nucleus

Background Subthalamic 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. Methods We 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. Results The average position of the 40 active contacts was （11.7±1.2） mm lateral, （0.6±1.3） mm anterior, and （0.7±1.4） mm vertical to the midcommissural point. The dorsal margin of the STN was （11.6±1.1） mm lateral, （0.2±1.1） mm anterior, and （1.3±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. Conclusions The 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.

Factors predicting the instant effect of motor function after subthalamic nucleus deep brain stimulation in Parkinson’s disease

Background:Subthalamic nucleus deep brain stimulation(STN-DBS)is an effective treatment for Parkinson’s disease(PD),the predictive effect of levodopa responsiveness on surgical outcomes was confirmed by some studies,however there were different conclusions about that through long-and short-term follow-ups.We aimed to investigate the factors which influence the predictive value of levodopa responsiveness,and discover more predictive factors of surgical outcomes.Methods:Twenty-three PD patients underwent bilateral STN-DBS and completed our follow-up.Clinical evaluations were performed 1 week before and 3 months after surgery.Results:STN-DBS significantly improved motor function of PD patients after 3 months;preoperative levodopa responsiveness and disease subtype predicted the effect of DBS on motor function;gender,disease duration and duration of motor fluctuations modified the predictive effect of levodopa responsiveness on motor improvement;the duration of motor fluctuations and severity of preoperative motor symptoms modified the predictive effect of disease subtype on motor improvement.Conclusions:The intensity of levodopa responsiveness served as a predictor of motor improvement more accurately in female patients,patients with shorter disease duration or shorter motor fluctuations;PD patients with dominant axial symptoms benefit less from STN-DBS compared to those with limb-predominant symptoms,especially in their later disease stage.

Deep brain stimulation of the subthalamic nucleus for essential tremor

Essential tremor （ET）, characterized by a postural and/or kinetic tremor and primarily manifested in theupper extremities, head, and other parts of the body, is one of the most common neurological disorders.1 The traditional target for the neurosurgical treatment of ET, the ventral intermedius nucleus （Vim） of the thalamus, has confirmed that chronic deep brain stimulation （DBS1 is an effective, standard, and primary procedure for ET. However, the loss of tremor suppression due to tolerance of chronic Vim stimulation, accompanied by other adverse effects, such as paresthesias, dysarthria, dysequilibrium, hyperhidrosis, and localized pain, has necessitated changes in the stimulation target in some patients.

Internal Pallidum and Subthalamic Nucleus Deep Brain Stimulation for Oromandibular Dystonia

Dystonia is a neurologic disorder characterized by sustained involuntary movements or abnormal posture. Oromandibular dystonia is a form of focal dystonia that is characterized by forceful contractions of face, jaw, or tongue.

Research progress in the efficacy of deep brain stimulation with different targets in Parkinson's disease

Parkinson's disease(PD)is a chronic progressive neurodegenerative disease.Deep brain stimulation(DBS)is an effective treatment for patients with advanced PD.There are many DBS targets for PD,including subthalamic nucleus(STN),globus pallidus(GPi),meso-ventral thalamic nucleus(VIM),pontine peduncle nucleus(PPN),posterior subthalamic region(PSA)and zonation of undetermined zone(ZI).This paper summarizes the efficacy of each target in the treatment of PD with DBS,not only makes a systematic analysis and comparison of motor symptoms,but also makes a detailed description of the efficacy of non-motor symptoms,so as to provide a personalized treatment basis for PD patients to select appropriate target targets in DBS.

The treatment of Parkinson's disease with deep brain stimulation: current issues

Deep brain stimulation has become a well-established symptomatic treatment for Parkinson＇s disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients＇ mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.

Neurosurgery in Parkinson's disease:Social adjustment, quality of life and coping strategies

Subthalamic nucleus deep brain stimulation has become a standard neurosurgical therapy for ad- vanced Parkinson＇s disease. Subthalamic nucleus deep brain stimulation can dramatically improve the motor symptoms of carefully selected patients with this disease. Surprisingly, some specific dimensions of quality of life, ＂psychological＂ aspects and social adjustment do not always improve, and they could sometimes be even worse. Patients and their families should fully understand that subthalamic nucleus deep brain stimulation can alter the motor status and time is needed to readapt to their new postoperative state and lifestyles. This paper reviews the literatures regarding effects of bilateral subthalamic nucleus deep brain stimulation on social adjustment, quality of life and coping strategies in patients with Parkinson＇s disease. The findings may help to understand the psychoso-cial maladjustment and poor improvement in quality of life in some Parkinson＇s disease patients.