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1.
Patients with Parkinson's disease (PD) commonly exhibit difficulties performing simultaneous tasks and levodopa has been shown to improve the performance of these movements to a greater extent than movements performed in isolation. The aim of this study was to compare the effects of acute unilateral pallidal lesions (nine patients) and bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) (eight patients) with levodopa therapy (ten patients) on the performance of isolated versus bilateral simultaneous repetitive movements. The STN group was assessed with and without DBS both on and off levodopa. The two tasks employed were maximally paced button tapping (Tap) and wrist pronation-supination (WPS) movements. During the off drug state (12–14 h after the last oral dose of levodopa), the performance of simultaneous Tap and WPS movements in all three groups was significantly slower and more irregular than when each movement was performed in isolation. For example, WPS velocity decreased by at least 37% (P<0.05) with concomitant Tap. Following levodopa, pallidotomy or STN DBS, WPS velocity was increased during the simultaneous task to a greater extent than in the isolated task. All treatments also improved WPS velocity and increased the regularity of movement during concomitant Tap (P<0.01). The findings indicate that, like levodopa, surgical therapies can improve the performance of simultaneous tasks more than isolated tasks. These observations suggest that the excessive neuronal activity and/or abnormal firing patterns in the globus pallidus internus that is found in parkinsonian patients contribute to difficulties in the execution of complex motor tasks. Electronic Publication  相似文献   

2.
Growing evidence suggests that spontaneous oscillatory low-frequency synchronization in the subthalamic nuclei (STN) may modulate motor performance in patients with Parkinson’s disease (PD). To explore this in more detail, 15 PD patients chronically implanted with deep brain stimulation (DBS) electrodes in both STN were stimulated bilaterally at 5, 10, 20, 50 and 130 Hz and the effects of the DBS on self-initiated isometric elbow flexion (FLEX) and finger pinch (PINCH) were compared to performance without DBS. Baseline performance was very much impaired. Peak force was significantly greater during 130 and 10 Hz stimulation when compared to no stimulation in both tasks. Cumulative sums of the changes in mean rising force and peak force in the two tasks upon stimulation at 10 and 20 Hz demonstrated that patients improved their performance on stimulation, except for those with the best performance off stimulation who deteriorated with stimulation at 20 Hz. Thus, no effect was detected with 20 Hz stimulation at the group level. The current study highlights the need to consider the baseline performance of a subject in a given task when determining the effects of low-frequency STN stimulation in PD patients. It also demonstrates that stimulation at 10 Hz can improve motor function in subjects with poor baseline function.  相似文献   

3.

Purpose

To evaluate the effect of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on levodopa-induced peak-dose dyskinesia in patients with Parkinson''s disease (PD).

Materials and Methods

A retrospective review was conducted on patients who underwent STN DBS for PD from May 2000 to July 2012. Only patients with levodopa-induced dyskinesia prior to surgery and more than 1 year of available follow-up data after DBS were included. The outcome measures included the dyskinesia subscore of the Unified Parkinson''s Disease Rating Scale (UPDRS) part IV (items 32 to 34 of UPDRS part IV) and the levodopa equivalent daily dose (LEDD). The patients were divided into two groups based on preoperative to postoperative LEDD change at 12 months after the surgery: Group 1, LEDD decrease >15%; Group 2, all other patients. Group 2 was further divided by the location of DBS leads.

Results

Of the 100 patients enrolled, 67 were in Group 1, while those remaining were in Group 2. Twelve months after STN DBS, Groups 1 and 2 showed improvements of 61.90% and 57.14%, respectively, in the dyskinesia subscore. Group 1 was more likely to experience dyskinesia suppression; however, the association between the groups and dyskinesia suppression was not statistically significant (p=0.619). In Group 2, dyskinesia was significantly decreased by stimulation of the area above the STN in 18 patients compared to stimulation of the STN in 15 patients (p=0.048).

Conclusion

Levodopa-induced dyskinesia is attenuated by STN DBS without reducing the levodopa dosage.  相似文献   

4.
Parkinson's disease (PD) is highly comorbid with sleep dysfunction. In contrast to motor symptoms, few therapeutic interventions exist to address sleep symptoms in PD. Subthalamic nucleus (STN) deep brain stimulation (DBS) treats advanced PD motor symptoms and may improve sleep architecture. As a proof of concept toward demonstrating that STN‐DBS could be used to identify sleep stages commensurate with clinician‐scored polysomnography (PSG), we developed a novel artificial neural network (ANN) that could trigger targeted stimulation in response to inferred sleep state from STN local field potentials (LFPs) recorded from implanted DBS electrodes. STN LFP recordings were collected from nine PD patients via a percutaneous cable attached to the DBS lead, during a full night's sleep (6–8 hr) with concurrent polysomnography (PSG). We trained a feedforward neural network to prospectively identify sleep stage with PSG‐level accuracy from 30‐s epochs of LFP recordings. Our model's sleep‐stage predictions match clinician‐identified sleep stage with a mean accuracy of 91% on held‐out epochs. Furthermore, leave‐one‐group‐out analysis also demonstrates 91% mean classification accuracy for novel subjects. These results, which classify sleep stage across a typical heterogenous sample of PD patients, may indicate spectral biomarkers for automatically scoring sleep stage in PD patients with implanted DBS devices. Further development of this model may also focus on adapting stimulation during specific sleep stages to treat targeted sleep deficits.  相似文献   

5.
Objectives: The occurrence of postural and balance disorders is a frequent feature in advanced forms of Parkinson’s disease (PD). However, the pathological substrate of these disturbances is poorly understood. Methods: In the present work, we investigated the evolution of posturometric parameters [center of pressure (CoP) displacement and CoP area] and axial scores between the pre-operative period and 3 months post-operative in seven PD patients who underwent bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). Results: After surgery, the patients leaned backwards much more regardless of the STN stimulation, suggesting that surgery could have a deleterious effect on postural adaptation. During the post-operative period, the improvement in axial and postural scores was similar under levodopatherapy and DBS. On the other hand, DBS of the STN significantly reduced the CoP displacement and the CoP area, whereas levodopatherapy tended only to reduce the CoP displacement and to increase the CoP area significantly. Conclusions: These data suggest that DBS of the STN and levodopa do not act on the same neurological systems involved in posture regulation. DBS of the STN could improve posture via a direct effect on the pedunculopontine nucleus, which is known to be involved in posture regulation.  相似文献   

6.
The effect of chronic high frequency deep brain stimulation (DBS) on rest tremor was investigated in subjects with Parkinson’s disease (PD). Eight PD subjects with high amplitude tremor (Group 1) and eight PD subjects with low amplitude tremor (Group 2, used as a reference group) were examined by a clinical neurologist and tested with a velocity laser to quantify time and frequency domain characteristics of tremor. Possible rebound effects in rest tremor when DBS was stopped for 60 min were also explored. Participants received DBS of the internal globus pallidus (GPi) (n=7), the subthalamic nucleus (STN) (n=6) or the ventrointermediate nucleus of the thalamus (Vim) (n=3). Tremor was recorded with a velocity laser under two conditions of DBS (on–off) and two conditions of medication (l-Dopa on–off). Correlations between clinical and experimental results for tremor amplitude was 0.70 with no medication and no stimulation. In Group 1, DBS decreased tremor amplitude but also increased spectral concentration and median frequency significantly. Under medication, the changes in tremor with and without stimulation were not statistically significant (Group 1). When stimulation was stopped for 60 min, a rebound in tremor amplitude was observed and median frequency remained stable in Group 1. None of the comparisons examined produced significant effects in Group 2. Taken together, these results suggest that beyond its effect on tremor amplitude DBS acted also on tremor frequency and did not modify tremor characteristics in subjects with low amplitude tremor.  相似文献   

7.
The aim of the present study was to assess the effect of bilateral subthalamic nucleus (STN) stimulation and dopaminergic medication on speed of mental processing and motor function. Thirty-nine patients suffering from advanced Parkinson disease (PD) were operated on. Motor function and reaction time (RT) performance [simple RT (SRT) and complex RT (CRT)] were evaluated under four experimental conditions with stimulation (stim) and medication (med) on and off: stim-on/med-on, stim-on/med-off, stim-off/med-off and stim-off/med-on. In the last condition, the patients received either low medication (usual dose) or high medication (suprathreshold dose). STN stimulation improved the motor performance in the SRT and CRT tasks. Furthermore, STN deep brain stimulation (DBS) also improved response preparation as shown by the significant improvement of the RT performance in the SRT task. This effect of STN DBS on the RT performance in the SRT task was greater as compared with the CRT task. This is due to the more complex information processing that is required in the CRT task as compared to the SRT task. These data suggest that treatment of STN hyperactivity by DBS improves motor function, confirming earlier reports, but has a differential effect on cognitive functions. The STN seems to be an important modulator of cognitive processing and STN DBS can differentially affect motor and associative circuits.  相似文献   

8.
In order to robustly analyze the gait of Parkinson’s disease (PD) patients, a new gait phase discrimination method was developed for analyzing the three-axis accelerations of the ankle during walking. The magnitude of acceleration was compared with the lowpass-filtered signal of itself and pseudo foot-flat phases were determined. Four narrow windows were made sequentially and adaptively from the pseudo foot-flat phases. Each window contained a characteristic peak that discriminated the gait phases. From these windows, the initial contact (IC) point and end contact (EC) point were determined by finding the maximal point in the proximal–distal acceleration. Seven healthy individuals and 17 PD patients were subjected to a walking test on level ground for a distance of 6.5 m with the wearable activity monitoring system (W-AMS). Foot pressure and movement images were simultaneously recorded as references. The ICs and ECs detected by the proposed algorithm were compared with the manually marked events in the foot pressure signals. In healthy subjects, all the ICs and ECs were correctly detected. In the PD group, the detection accuracy was 97.6% for the ICs and 99.4% for the ECs. Based on these results, this novel method holds promise for use in monitoring temporal gait parameters continuously in PD patients, which will subsequently allow for the evaluation of motor fluctuations in PD patients.  相似文献   

9.
Epilepsy and Parkinson’s disease (PD) are common neurological disorders. Both epilepsy and PD are potentially progressive disabling diseases that can be treated with the established therapy of deep brain stimulation (DBS). The difference in therapy is target selection and stimulation parameter modulation. The anterior nucleus of the thalamus (ANT) is chosen for intractable epilepsy and the subthalamic nucleus (STN) is chosen for PD. Long-term stable symptom control of STN–DBS can be seen in PD patients while the positive effect of ANT-DBS can be observed in epilepsy patients. Experimental data and clinical evidence have been reported that indicate the neuroprotective property of STN–DBS could be found in PD patients. Therefore, we hypothesize that the neuroprotective benefits of ANT–DBS may be present in epilepsy patients.  相似文献   

10.
Postural instability and gait difficulty (PIGD) are commonly observed in advanced Parkinson’s disease. The neuronal mechanism of PIGD is not fully understood. Dysfunction of the pedunculopontine nucleus (PPN) might be a possible cause of these symptoms. The autopsy studies of subjects with PIGD revealed a neurodegenerative process involving mainly PPN cholinergic neurons. The PPN participates in the locomotion processes by initiation, modulation and execution of stereotyped patterns of movement. The standard neurosurgical treatment of PD is subthalamic deep brain stimulation (STN DBS). Clinical results revealed low efficiency of STN DBS on PIGD. Preliminary results of simultaneous PPN and STN DBS are very promising. Only a few reports have been published until now; a significant improvement of PIGD was observed in both ON and OFF L-dopa states.  相似文献   

11.
The pedunculopontine nucleus (PPN) lies within the brainstem reticular formation and is involved in the motor control of gait and posture. Interest has focused recently on the PPN as a target for implantation of chronic deep brain stimulation (DBS) electrodes for Parkinson’s disease (PD) and progressive supranuclear palsy (PSP) therapy. The aim of this study was to examine the neurophysiology of the human PPN region and to identify neurophysiological landmarks that may aid the proper placement of DBS electrodes in the nucleus for the treatment of PD and PSP. Neuronal firing and local field potentials were recorded simultaneously from two independently driven microelectrodes during stereotactic neurosurgery for implantation of a unilateral DBS electrode in the PPN in five PD patients and two PSP patients. Within the PPN region, the majority (57%) of the neurons fired randomly while about 21% of the neurons exhibited ‘bursty’ firing. In addition, 21% of the neurons had a long action potential duration and significantly lower firing rate suggesting they were cholinergic neurons. A change in firing rate produced by passive and/or active contralateral limb movement was observed in 38% of the neurons that were tested in the PPN region. Interestingly, oscillatory local field potential activity in the beta frequency range (∼25 Hz) was also observed in the PPN region. These electrophysiological characteristics of the PPN region provide further support for the proposed role of this region in motor control. It remains to be seen to what extent the physiological characteristics of the neurons and the stimulation-evoked effects will permit reliable identification of PPN and determination of the optimal target for DBS therapy.  相似文献   

12.
Multiple studies have shown bilateral improvement in motor symptoms in Parkinson disease (PD) following unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal segment of the globus pallidus, yet the mechanism(s) underlying this phenomenon are poorly understood. We hypothesized that STN neuronal activity is altered by contralateral STN DBS. This hypothesis was tested intraoperatively in humans with advanced PD using microelectrode recordings of the STN during contralateral STN DBS. We demonstrate alterations in the discharge pattern of STN neurons in response to contralateral STN DBS including short latency, temporally precise, stimulation frequency-independent responses consistent with antidromic activation. Furthermore, the total discharge frequency during contralateral high frequency stimulation (160 Hz) was greater than during low frequency stimulation (30 Hz) and the resting state. These findings demonstrate complex responses to DBS and imply that output activation throughout the basal ganglia-thalamic-cortical network rather than local inhibition is a therapeutic mechanism of DBS.  相似文献   

13.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). The mechanism is poorly understood. High-frequency STN DBS has been reported to affect motor cortex excitability in a complex way, but the timing between STN stimuli and changes in motor cortical (M1) excitability has not been investigated. We examined the time course of changes in motor cortical excitability following single pulse STN DBS. We studied 14 PD patients with implanted DBS electrodes in the STN, 2 patients with electrodes in internal globus pallidus (GPi), and 1 patient with an electrode in the sensory thalamus. Transcranial magnetic stimulation (TMS) was delivered to the M1 ipsilateral to the DBS with induced currents either in the anterior-posterior direction in the brain to evoke indirect (I) waves or in the lateral-medial direction to activate corticospinal axons directly. Single pulse stimulation through the DBS contacts preceded the TMS by 0-10 ms. Surface EMG was recorded from the contralateral first dorsal interosseous muscle. Three milliseconds after STN stimulation, the motor evoked potential (MEP) amplitudes produced by anterior-posterior current were significantly larger than control responses, while the responses to lateral-medial currents were unchanged. Similar facilitation also occurred after GPi stimulation, but not with thalamic stimulation. Single pulse STN stimulation facilitates the M1 at short latencies. The possible mechanisms include antidromic excitation of the cortico-STN fibers or transmission through the basal ganglia-thalamocortical pathway.  相似文献   

14.
The aim of this study was to assess the relative torque (a percentage of the maximal capacity of torque production) at the ankle joint in young and elderly adults during different postural tasks of increasing difficulty. Seven young (~22 years old) and seven older (~80 years old) men took part in this investigation. Maximal agonist torque was estimated from resultant and antagonist torques in both populations in plantar-flexion (PF) and dorsi-flexion (DF). The sum of PF and DF maximal agonist torques was considered as the maximal capacity of torque production. The centre of pressure (CoP) displacement was analysed during Normal Quiet Stance, Romberg and One Leg Balance. During maximal contractions and postural tasks, the electromyographic (EMG) activity was simultaneously recorded on the triceps surae and tibialis anterior muscles. We observed that the maximal capacity of torque production was negatively correlated with the CoP displacement, whatever the population and the postural tasks. The relative torque during all postural tasks was positively correlated with the CoP displacement in both populations. Moreover, older adults needed more EMG activity than young adults to produce the same torque. From this knowledge, one can assume that increasing strength in the muscles of the ankle joint may improve postural stability in older adults; this might have implications in the prevention of falls in elderly persons and in rehabilitation programs for elderly people who have already fallen.  相似文献   

15.
Stimulation-induced inhibition of neuronal firing in human subthalamic nucleus   总被引:10,自引:0,他引:10  
The subthalamic nucleus (STN) is an important component of the basal ganglia (BG) and plays a major role in the pathogenesis of Parkinsons disease (PD). Hyperactivity of STN as a consequence of the loss of dopaminergic inputs to the BG is believed to be a major factor in producing the motor symptoms of PD. High-frequency (HF) deep brain stimulation (DBS) of the STN has recently become an important treatment in PD patients where medications no longer provide satisfactory therapy. However, the mechanisms underlying DBS therapy are unknown, and there is seemingly conflicting data suggesting inhibition or excitation of STN neurons. This study directly examined the effects of stimulation in STN on the activity of STN neurons in PD patients during functional stereotactic mapping prior to insertion of DBS electrodes. Electrical stimulation in STN was investigated in twelve PD patients by recording the neural activity of a cell in STN with one electrode while applying current pulses through a second electrode located about 600 µm away. Stimulation at high frequencies (100–300 Hz) was found to produce inhibition following the stimulus train in 42% of the 60 cells tested. Inhibition during the train was seen in 13 of 15 neurons where it was possible to detect such activity. Furthermore, in 44% of the cases where HF stimulation produced inhibition there was an early inhibition followed by rebound excitation and a further inhibitory period, suggesting that the inhibitions observed are due to hyperpolarization. In eight of the 25 neurons inhibited by HF stimulation, the effects of single stimuli were determined and revealed that in seven of these there was an inhibitory period of 15–20 ms following each stimulus. Thus, the present findings suggest that local HF stimulation inhibits many STN neurons. However, these studies could not determine whether the stimulus also directly excited the cell and/or its axon, but other recent findings suggest that this is likely the case. Therefore, the overall effects of DBS stimulation in STN are likely to be inhibition of intrinsic and synaptically mediated activity, and its replacement by regular high-frequency firing.  相似文献   

16.
In the present study we investigated tension regulation in the human soleus (SOL) muscle during controlled lengthening and shortening actions. Eleven subjects performed plantar flexor efforts on an ankle torque motor through 30° of ankle displacement (75°–105° internal ankle angle) at lengthening and shortening velocities of 5, 15 and 30° · s−1. To isolate the SOL from the remainder of the triceps surae, the subject's knee was flexed to 60° during all trials. Voluntary plantar flexor efforts were performed under two test conditions: (1) maximal voluntary activation (MVA) of the SOL, and (2) constant submaximal voluntary activation (SVA) of the SOL. SVA trials were performed with direct visual feedback of the SOL electromyogram (EMG) at a level resulting in a torque output of 30% of isometric maximum. Angle-specific (90° ankle angle) torque and EMG of the SOL, medial gastrocnemius (MG) and tibialis anterior (TA) were recorded. In seven subjects from the initial group, the test protocol was repeated under submaximal percutaneous electrical activation (SEA) of SOL (to 30% isometric maximal effort). Lengthening torques were significantly greater than shortening torques in all test conditions. Lengthening torques in MVA and SVA were independent of velocity and remained at the isometric level, whereas SEA torques were greater than isometric torques and increased at higher lengthening velocities. Shortening torques were lower than the isometric level for all conditions. However, whereas SVA and SEA torques decreased at higher velocities of shortening, MVA torques were independent of velocity. These results indicate velocity- and activation-type-specific tension regulation in the human SOL muscle. Accepted: 11 October 1999  相似文献   

17.
In this paper, a new method for quantification of rigidity in elbow joint of Parkinsonian patients is introduced. One of the most known syndromes in Parkinson’s disease (PD) is increased passive stiffness in muscles, which leads to rigidity in joints. Clinical evaluation of stiffness in wrist and/or elbow, commonly used by clinicians, is based on Unified Parkinson’s Disease Rating System (UPDRS). Subjective nature of this method may influence the accuracy and precision of evaluations. Hence, introducing an objective standard method based on quantitative measurements may be helpful. A test rig was designed and fabricated to measure range of motion and viscous and elastic components of passive stiffness in elbow joint. Measurements were done for 41 patients and 11 controls. Measures were extracted using Matlab-R14 software and statistic analyses were done by Spss-13. Relation between each computed measure and the level of illness were analyzed. Results showed a better correlation between viscous component of stiffness and UPDRS score compared to the elastic component. Results of this research may help to introduce a standard objective method for evaluation of PD.  相似文献   

18.
Subthalamic nucleus deep brain stimulation (STN DBS) ameliorates motor symptoms of Parkinson's disease, but the precise mechanism is still unknown. Here, using a large animal (pig) model of human STN DBS neurosurgery, we utilized fast-scan cyclic voltammetry in combination with a carbon-fiber microelectrode (CFM) implanted into the striatum to monitor dopamine release evoked by electrical stimulation at a human DBS electrode (Medtronic 3389) that was stereotactically implanted into the STN using MRI and electrophysiological guidance. STN electrical stimulation elicited a stimulus time-locked increase in striatal dopamine release that was both stimulus intensity- and frequency-dependent. Intensity-dependent (1–7 V) increases in evoked dopamine release exhibited a sigmoidal pattern attaining a plateau between 5 and 7 V of stimulation, while frequency-dependent dopamine release exhibited a linear increase from 60 to 120 Hz and attained a plateau thereafter (120–240 Hz). Unlike previous rodent models of STN DBS, optimal dopamine release in the striatum of the pig was obtained with stimulation frequencies that fell well within the therapeutically effective frequency range of human DBS (120–180 Hz). These results highlight the critical importance of utilizing a large animal model that more closely represents implanted DBS electrode configurations and human neuroanatomy to study neurotransmission evoked by STN DBS. Taken together, these results support a dopamine neuronal activation hypothesis suggesting that STN DBS evokes striatal dopamine release by stimulation of nigrostriatal dopaminergic neurons.  相似文献   

19.
In Parkinson’s disease, the subthalamic nucleus (STN) is a common target for functional neurosurgery. Recent investigations have suggested that physiological non-motor stimuli may dramatically alter STN firing properties. By maintaining long-lasting micro-recordings of STN single units in Parkinson’s disease (PD) patients, here we show that the neurons that are responsive to passive movements are also strongly modulated by altered vigilance state (awake vs. sleep). In addition, sleep was characterized by a distinctive irregular train-like firing pattern. These findings suggest that the reduction of the somato-sensory input modifies rigidity and, hence, STN discharge mode. Further, it is suggested that specific STN electrophysiological features are potential targets for future therapeutic interventions.  相似文献   

20.
Recent studies suggest that beta (15-30 Hz) oscillatory activity in the subthalamic nucleus (STN) is dramatically increased in Parkinson's disease (PD) and may interfere with movement execution. Dopaminergic medications decrease beta activity and deep brain stimulation (DBS) in the STN may alleviate PD symptoms by disrupting this oscillatory activity. Depth recordings from PD patients have demonstrated beta oscillatory neuronal and local field potential (LFP) activity in STN, although its prevalence and relationship to neuronal activity are unclear. In this study, we recorded both LFP and neuronal spike activity from the STN in 14 PD patients during functional neurosurgery. Of 200 single- and multiunit recordings 56 showed significant oscillatory activity at about 26 Hz and 89% of these were coherent with the simultaneously recorded LFP. The incidence of neuronal beta oscillatory activity was significantly higher in the dorsal STN (P = 0.01) and corresponds to the significantly increased LFP beta power recorded in the same region. Of particular interest was a significant positive correlation between the incidence of oscillatory neurons and the patient's benefit from dopaminergic medications, but not with baseline motor deficits off medication. These findings suggest that the degree of neuronal beta oscillatory activity is related to the magnitude of the response of the basal ganglia to dopaminergic agents rather than directly to the motor symptoms of PD. The study also suggests that LFP beta oscillatory activity is generated largely within the dorsal portion of the STN and can produce synchronous oscillatory activity of the local neuronal population.  相似文献   

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