Effects of five years of chronic STN stimulation on muscle strength and movement speed

This study examined the long-term effects of chronic subthalamic nucleus (STN) deep brain stimulation (DBS) using both clinical evaluation and laboratory motor control measures. Over a 5-year time period, changes in the motor section of the Unified Parkinson’s Disease Rating Scale (UPDRS) and movement speed and strength at the ankle joint were evaluated on and off STN DBS in eight patients with Parkinson’s disease (PD). Four patients were also studied at the elbow joint. Patients with PD originally received unilateral STN DBS between years 2001 and 2003. They were re-evaluated after 5 years of long-term STN DBS between years 2006–2008. At baseline (year 0) and after 5 years, patients with PD were tested off treatment and on STN DBS. In each testing condition, patients performed ballistic, single degree of freedom ankle dorsiflexion and ankle plantarflexion movements and peak velocity was calculated. Patients also performed maximal voluntary contractions at the ankle joint in both directions, and peak torque was calculated. Results showed increased motor UPDRS scores from year 0 to year 5, but STN DBS was efficacious in reducing them. In contrast to the increase in motor UPDRS scores, motor control results showed a marked improvement in peak velocity and peak torque over the 5-year time period in the off treatment condition, and STN DBS was efficacious by improving both peak velocity and peak torque. The current findings suggest that 5 years of chronic STN DBS can have beneficial effects on the motor system over the long term in discrete motor tasks in which maximal effort and maximal neural output is required.     

Differential effects of subthalamic nucleus stimulation in advanced Parkinson disease on reaction time performance

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.     

Evolution of postural stability after subthalamic nucleus stimulation in Parkinson’s disease: a combined clinical and posturometric study

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.     

Effect of Subthalamic Deep Brain Stimulation on Levodopa-Induced Dyskinesia in Parkinson's Disease

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.     

The impact of low-frequency stimulation of subthalamic region on self-generated isometric contraction in patients with Parkinson’s disease

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.     

Neuropsychological functioning following bilateral subthalamic nucleus stimulation in Parkinson's disease.

The cognitive effects of subthalamic nucleus (STN) stimulation in Parkinson's disease (PD) have been examined. However, there are no reported studies that evaluate, by incorporating a disease control group, whether neuropsychological performance in surgical patients changes beyond the variability of the assessment measures. To examine this issue, 17 PD patients were tested before and after bilateral STN stimulator implantation, both on and off stimulation. Eleven matched PD controls were administered the same repeatable neuropsychological test battery twice. Relative to changes seen in the controls, the surgery for electrode placement mildly adversely affected attention and language functions. STN stimulation, per se, had little effect on cognition. The STN DBS procedure as a whole resulted in a mild decline in delayed verbal recall and language functions. There were no surgery, stimulation, or procedure effects on depression scale scores. In contrast to these group findings, one DBS patient demonstrated significant cognitive decline following surgery.     

Effect of subthalamic nucleus deep brain stimulation on axial motor control and protective arm responses in Parkinson's disease

Stereotactic surgical interventions for Parkinson's disease (PD) can considerably improve appendicular motor signs, but their effect on axial motor signs--especially balance control under optimal drug therapy--remains unclear. Here, we investigated the effect of bilateral subthalamic nucleus (STN) stimulation on levodopa-resistant axial and appendicular postural impairment in PD. Fourteen patients (11 with young-onset PD) and 18 age-matched controls were included. Patients were tested after intake of a suprathreshold levodopa dose, ensuring optimal response to drug therapy, and with stimulators both turned on and off. Balance control was assessed using multidirectional dynamic posturography. Outcome measures included full body kinematics and surface electromyography of paraspinal and deltoid muscles. Patients with stimulators turned off showed early decreased trunk roll with a loss of directional dependency, followed by increased and abnormally directed--i.e. destabilizing--trunk roll. Pelvis pitch motion showed decreased directional dependency in these patients. The abnormal trunk motion was not corrected by STN stimulation, but directional dependency of both trunk and pelvis motion partially improved, along with a general decrease in muscle activity. Even with stimulators off, protective arm movements were similar in the optimally treated patients and controls, indicating that these appendicular signs respond better to dopaminergic treatment than axial motor control. Our findings indicate that instability in PD results from a reduced flexibility of the trunk and pelvis that is largely resistant to STN stimulation combined with optimal drug treatment. These postural abnormalities are therefore likely associated with non-dopaminergic pathology. In contrast, protective arm movements did appear to be levodopa-responsive. Future studies should focus on identifying subgroups of optimal responders, particularly patients with levodopa-induced dyskinesias.     

Activation of subthalamic neurons by contralateral subthalamic deep brain stimulation in Parkinson disease

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.     

Gait and postural instability in Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus

In late stage Parkinson's disease (PD), medical treatment may not control the symptoms adequately, and the patient may become eligible for bilateral high frequency deep brain stimulation (DBS) in the subthalamic nucleus (STN). The effect of STN DBS on gait and postural instability is not always as predictable as the effect on clinical symptoms tremor, rigidity and bradykinesia. This may relate to the type of gait disorder or the stimulating electrode localization in the STN. We sought to evaluate the effect of STN DBS on gait performance during overground walking and gait initiation--assessed with 3D optokinetic movement analyses--and to compare the DBS effect with stimulation site localized on peri-operative MRI. The stimulation sites were grouped according to STN borders visualised on pre-operative MRI, and the active stimulation site was compared with clinical improvement and gait parameters. STN DBS is associated with improved movement amplitude while movement duration may be unaffected by both disease and stimulation. This may imply an improvement primarily on hypokinesia including gait hypokinesia.     

Influence of Propofol and Fentanyl on Deep Brain Stimulation of the Subthalamic Nucleus

We investigated the effect of propofol and fentanyl on microelectrode recording (MER) and its clinical applicability during subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. We analyzed 8 patients with Parkinson''s disease, underwent bilateral STN DBS with MER. Their left sides were done under awake and then their right sides were done with a continuous infusion of propofol and fentanyl under local anesthesia. The electrode position was evaluated by preoperative MRI and postoperative CT. The clinical outcomes were assessed at six months after surgery. We isolated single unit activities from the left and the right side MERs. There was no significant difference in the mean firing rate between the left side MERs (38.7±16.8 spikes/sec, n=78) and the right side MERs (35.5±17.2 spikes/sec, n=66). The bursting pattern of spikes was more frequently observed in the right STN than in the left STN. All the electrode positions were within the STNs on both sides and the off-time Unified Parkinson''s Disease Rating Scale part III scores at six months after surgery decreased by 67% of the preoperative level. In this study, a continuous infusion of propofol and fentanyl did not significantly interfere with the MER signals from the STN. The results of this study suggest that propofol and fentanyl can be used for STN DBS in patients with advanced Parkinson''s disease improving the overall experience of the patients.

Graphical Abstract

相似文献   

Bilateral stimulation of the subthalamic nucleus has differential effects on reactive and proactive inhibition and conflict-induced slowing in Parkinson’s disease

It has been proposed that the subthalamic nucleus (STN) mediates response inhibition and conflict resolution through the fronto-basal ganglia pathways. Our aim was to compare the effects of deep brain stimulation (DBS) of the STN on reactive and proactive inhibition and conflict resolution in Parkinson’s disease using a single task. We used the conditional Stop signal reaction time task that provides the Stop signal reaction time (SSRT) as a measure of reactive inhibition, the response delay effect (RDE) as a measure of proactive inhibition and conflict-induced slowing (CIS) as a measure of conflict resolution. DBS of the STN significantly prolonged SSRT relative to stimulation off. However, while the RDE measure of proactive inhibition was not significantly altered by DBS of the STN, relative to healthy controls, RDE was significantly lower with DBS off but not DBS on. DBS of the STN did not alter the mean CIS but produced a significant differential effect on the slowest and fastest RTs on conflict trials, further prolonging the slowest RTs on the conflict trials relative to DBS off and to controls. These results are the first demonstration, using a single task in the same patient sample, that DBS of the STN produces differential effects on reactive and proactive inhibition and on conflict resolution, suggesting that these effects are likely to be mediated through the impact of STN stimulation on different fronto-basal ganglia pathways: hyperdirect, direct and indirect.     

Eye movement-related responses of neurons in human subthalamic nucleus

Intraoperative microelectrode single unit recordings are routinely made in the subthalamic nucleus (STN) of awake and alert Parkinsons disease (PD) patients during surgery for implantation of deep brain stimulation (DBS) electrodes. These recordings not only assist in determining the optimal target for electrode implantation, but also offer the unique opportunity to study movement-evoked responses from the basal ganglia. We report on the responses of human STN neurons to eye movements from eight PD patients (five men and three women). Twenty percent (18/89) of tested STN neurons showed responses to eye movements. Patients made pro-saccades, voluntary saccades or smooth pursuit eye movements in four directions: up, down, left, right. The majority of STN neurons (72% or 13/18), that responded to eye movements were found in the ventral half of the nucleus, while 58% (22/38) of STN neurons that had somatic responses were found in the dorsal half of the nucleus. The firing rate for STN oculomotor neurons was 33±15 Hz (n=18), which was not different from that reported previously for STN neurons. Most neurons only responded to eye movements in a single direction, but 17% (3/18) showed responses to more than one direction. The majority of responses (17/18) to eye movements were increases in firing rate although one neuron did show a pause in firing with eye movement onset. The phasic changes in firing rate in response to eye movement usually occurred up to 250 ms following eye movement onset. Neurons were found that showed task-specific responses to cued versus self-paced saccades, responded to both passive limb movement and voluntary eye movement, and appeared to show either visual or attentional responses. These human physiological data, in conjunction with previous anatomical studies, suggest that the STN might have an oculomotor role. Although there is no evidence that STN is responsible for driving eye movements, it may have a role in either sensory feedback, corollary discharge, or in focusing the substantia nigra pars reticulata to allow a saccade to occur through disinhibition of the superior colliculus.     

Effects of pallidal deep brain stimulation and levodopa treatment on reaction-time performance in Parkinson’s disease

Basal ganglia-thalamocortical circuits play an important role in movement preparation and execution. Tracer, single-cell, and lesion studies in monkeys suggest the existence of topologically segregated motor and nonmotor basal ganglia cortical circuits. In this study we used deep brain stimulation (DBS) of the posteroventrolateral globus pallidus internus (GPi) in patients with Parkinson's disease to elucidate the function of the GPi in human sensorimotor behavior. This question was investigated by comparing the influence of DBS on patients' performance in various reaction-time tasks that differed with respect to cognitive but not motor requirements. As a main result, DBS improved performance on the different tasks independently of the complexity of the involved cognitive processing functions. Furthermore, the observed effects did not depend on the modality of the processed information. These results suggest that the functional state of the posteroventrolateral GPi selectively affects the motor stage in simple sensorimotor acts, because this stage was the only stage involved in all investigated tasks. In addition to DBS, we manipulated the levodopa medication state of the PD patients. In contrast to DBS, levodopa effects on reaction times were less consistent. Levodopa improved reaction times in choice reaction tasks significantly, while affecting reaction times in a simple reaction task to a lesser extent. Error analysis revealed that the medication-dependent reaction-time improvement in the choice reaction tasks was accompanied by an increase in errors, suggesting a shift of the speed-accuracy criteria of the patients. A similar pattern of results was not observed for the DBS effects. Taken together, our data are in agreement with recent findings in monkeys that indicate a topological organization of the GPi in which motor functions are localized in posterolateral regions apart from cognitive regions. Furthermore, our data show a way to uncover the subcortical-cortical circuitry serving human sensorimotor behavior.     

Temporal coordination of the arms during bilateral simultaneous and sequential movements in patients with chronic hemiparesis

Upper extremity (UE) hemiparesis results in decreased movement speed and impaired coordination leading to functional limitations and disability. The effects of UE hemiparesis on bilateral functional reaching have not been studied even though most activities of daily living are bilateral tasks. We examined the characteristics of bilateral simultaneous (SIM-B) and bilateral sequential paretic-lead (SEQ-P) and nonparetic-lead (SEQ-NP) functional reaching tasks at preferred and fast speeds. Sixteen patients with chronic hemiparesis completed three bilateral reaching tasks as fast as possible. A subset of eight participants attempted to complete the tasks at both preferred and fastest possible speeds. Paretic (P) and nonparetic (NP) arms were not different from each other in movement time (MT) or peak velocity in the SIM-B condition. MT and peak velocity differed between the two arms during both SEQ tasks. P MT was shorter and NP MT longer in the SIM-B task compared to SEQ-P and SEQ-NP. The P arm MT was the shortest when moving with the NP arm in a simultaneous task compared to both P and NP lead sequential movements. Despite hemiparesis, the two arms demonstrate a temporal coupling when moving simultaneously. When attempting to move at fastest speed, P arm MT time is better when reaching before or with the NP arm than when reaching after the NP arm showing coupling to the NP limb and increased speed of movement. These coupling effects support the rationale for bilateral arm training for individuals with UE hemiparesis.     

Electrode position and the clinical outcome after bilateral subthalamic nucleus stimulation

We compared the surgical outcome with electrode positions after bilateral subthalamic nucleus (STN) stimulation surgery for Parkinson's disease. Fifty-seven patients treated with bilateral STN stimulations were included in this study. Electrode positions were determined in the fused images of preoperative MRI and postoperative CT taken at six months after surgery. The patients were divided into three groups: group I, both electrodes in the STN; group II, only one electrode in the STN; group III, neither electrode in the STN. Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr stage, and activities of daily living scores significantly improved at 6 and 12 months after STN stimulation in both group I and II. The off-time UPDRS III speech subscore significantly improved (1.6 ± 0.7 at baseline vs 1.3 ± 0.8 at 6 and 12 months, P < 0.01) with least L-dopa equivalent daily dose (LEDD) (844.6 ± 364.1 mg/day at baseline; 279.4 ± 274.6 mg/day at 6 months; and 276.0 ± 301.6 mg/day at 12 months, P < 0.001) at 6 and 12 months after STN deep brain stimulation (DBS) in the group I. Our findings suggest that the better symptom relief including speech with a reduced LEDD is expected in the patients whose electrodes are accurately positioned in both STN.     

Bilateral assessment of functional tasks for robot-assisted therapy applications

This article presents a novel evaluation system along with methods to evaluate bilateral coordination of arm function on activities of daily living tasks before and after robot-assisted therapy. An affordable bilateral assessment system (BiAS) consisting of two mini-passive measuring units modeled as three degree of freedom robots is described. The process for evaluating functional tasks using the BiAS is presented and we demonstrate its ability to measure wrist kinematic trajectories. Three metrics, phase difference, movement overlap, and task completion time, are used to evaluate the BiAS system on a bilateral symmetric (bi-drink) and a bilateral asymmetric (bi-pour) functional task. Wrist position and velocity trajectories are evaluated using these metrics to provide insight into temporal and spatial bilateral deficits after stroke. The BiAS system quantified movements of the wrists during functional tasks and detected differences in impaired and unimpaired arm movements. Case studies showed that stroke patients compared to healthy subjects move slower and are less likely to use their arm simultaneously even when the functional task requires simultaneous movement. After robot-assisted therapy, interlimb coordination spatial deficits moved toward normal coordination on functional tasks.     

Pedunculopontine nucleus deep brain stimulation in Parkinson’s disease

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.     

Single pulse stimulation of the human subthalamic nucleus facilitates the motor cortex at short intervals

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.     

Brain tissue energy dependence of CaM kinase IV cascade activation during hypoxia in the cerebral cortex of newborn piglets

Using an anti-cue keypress task, we examined executive control in Parkinson's disease (PD) patients treated with deep brain stimulation (DBS) of the subthalamic nucleus (STN) and dopaminergic medication. Across sessions, we varied stimulation (on, off) and dopaminergic medication (on, off). Reaction time (RT) results of the PD patients and their age-matched controls showed a consistent pattern of RT costs and benefits generated by anti-cues with short and long preparation intervals, respectively. This pattern was evident in all sessions, except when DBS stimulation and medication were off. In this condition PD patients showed no RT benefits. These findings are discussed in terms of an executive control process that suppresses the automatic but inappropriate response activation generated by anti-cues. In PD this mechanism is severely compromised but it can be remediated by dopaminergic medication and DBS, suggesting an essential role of the basal ganglia in the selection and suppression of competing responses.     

Effect of deep brain stimulation on amplitude and frequency characteristics of rest tremor in Parkinson’s disease

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.