Subthalamic Nucleus Deep Brain Research Articles

Noise removal of deep brain stimulation artifacts in subthalamic nucleus neurons local field induced electrical potentials

This study presents a noise-removal technique for the microelectrode signals of subthalamic-nuclei (STN) neurons acquired by MER machine through electrical stimulations with subthalamic-nuclei deep brain stimulation/or stimulator (STN-DBS) in local field potentials (LFPs). We proposed a novel method for the removal of induced stimuli-artifacts triggered by pulse-generators differed in typical LFPs (low-frequency potentials) signals. The method is processed and tested for accuracy and computed for execution in vitro-states. Results indicated that the stimulus-artifacts are well suppressed by this method. And also it is tested in vivo-states of Parkinson’s disease (PD) subjects (patients). It is applied to process signals of LFPs gathered intra operatively from PDs to preliminarily explore quantitative dependencies-of beta-band synchronous variations within STN, DBS parameters (stimulus-intensity, stimulus-voltage, frequency, and amplitude pulse-width). Findings showed that the DBS process can overcome excessive beta-frequency (30Hz) activity plus that the degree of reduction rises with increasing DBS current in the range-of 1-3Volts then boosting stimulus-frequency within a range of 60-120Hz. The method offers scientific-research and technical support for exploring the instant effect by induced electrical stimulations in the Parkinson brain activities and it can be utilized as a research tool in the future technologies.

Comparison of Subthalamic Nucleus and Globus Pallidus Deep Brain Stimulation in Parkinson’s Disease: A Systematic Review

Background: Deep Brain Stimulation (DBS) is regarded as a viable therapeutic choice for Parkinson’s Disease (PD). The two most common sites for DBS are the Subthalamic Nucleus (STN) and Globus Pallidus (GPi). In this study, the clinical effectiveness of these two targets was compared. Methods: A systematic literature search in electronic databases were restricted to English language publications 2010 to 2021. Specified MeSH terms were searched in all databases. Studies that evaluated the Unified Parkinson’s Disease Rating Scale (UPDRS) III were selected by meeting the following criteria: (1) had at least three months follow-up period; (2) compared both GPi and STN DBS; (3) at least five participants in each group; (4) conducted after 2010. Study quality assessment was performed using the Modified Jadad Scale. Results: 3577 potentially relevant articles were identified 3569 were excluded based on title and abstract, duplicate and unsuitable article removal. Eight articles satisfied the inclusion criteria and were scrutinized (458 PD patients). Majority of studies reported no statistically significant between-group difference for improvements in UPDRS III scores. Conclusions: Although there were some results in terms of action tremor, rigidity, and urinary symptoms, which indicated that STN DBS might be a better choice or regarding the adverse effects, GPi seemed better; but it cannot be concluded that one target is superior. Other larger randomized clinical trials with longer follow-up periods and control groups are needed to decide which target is more efficient for stimulation and imposes fewer adverse effects on the patients.

Comparison of direct MRI guided versus atlas-based targeting for subthalamic nucleus and globus pallidus deep brain stimulation

Purpose The subthalamic nucleus (STN) and globus pallidus internus (GPi) targets for deep brain stimulation (DBS) can be defined by atlas coordinates or direct visualisation of the target on MRI. The aim of this study was to evaluate geometric differences between atlas-based targeting and MRI-guided direct targeting. Methods One-hundred-nine Parkinson’s disease or dystonia patients records who underwent DBS surgery between 2005 and 2016 were prospectively reviewed. MRI-guided direct targeting coordinates was used to implant 205 STN and 64 GPi electrodes and compared with atlas-based coordinates. Results The directly targeted coordinates (mean, SD, range) for STN were x: [9.9 ± 1.1 (7.1 − 13.2)], y: [−0.8 ± 1.1 (−4.2 − 2)] and z: [−4.7 ± 0.53 (−5.9 – −3.2)]. The mean value for the STN was 2.1 mm more medial (p < 0.0001), 1.2 mm more anterior (p < 0.0001) and 0.7 mm more ventral (p < 0.0001) than the atlas target. The targeted coordinates for GPi were x: [22.3 ± 2.0 (17.8 − 26.1)], y: [−0.2 ± 2.2 (−4.5 − 3.4)], z: [−4.3 ± 0.8 (−6.2 – −2.3)]. The mean value for the GPi was 2.2 mm (p < 0.001) more posterior and 0.3 mm (p < 0.01) more ventral than the atlas-based coordinates. Conclusion MRI-guided targeting may be more accurate than atlas-based targeting due to individual variations in anatomy.

Programming parameter analysis of subthalamic deep brain stimulation for the treatment of Parkinson′s disease

Objective To analyze the changes in stimulation parameters post subthalamic nucleus(STN) deep brain stimulation (DBS) for the treatment of Parkinson′s disease. Methods Ninety-five cases of patients with Parkinson′s disease treated with STN-DBS at Department of Neurosurgery, Zhongnan Hospital of Wuhan University from November 2011 to June 2017 were analyzed retrospectively. The stimulation parameters of 95 patients were as follows: the monopolar stimulation was main (98.3%, 175/178), The stimulus contacts were mainly in the upper STN (90.9%, 171/188), and most of them were single contact stimulation (94.4%, 168/178). Patients were evaluated in 3 months, 6 months, 1 year and 2 years. The primary outcome was assessed included the post-operation parameters, the unified Parkinson′s disease rating scale Ⅲ(UPDRS-Ⅲ), the improvement rate[(preoperative score-postoperative score) / preoperative score × 100%], the stimulus energy(voltage2×frequency×pulsewidth/impedance×1 s), the stimulation-related adverse events. Results The electrodes of 95 patients were implanted into preset targets based on intraoperative microelectrode recording and postoperative MRI images.The score of UPDRS-Ⅲ was (12.7 ±6.7)points, which was better than that before operation(P<0.05), and the improvement rate was (70.7±12.1)%. During the follow-up period, the improvement rate of UPDRS-Ⅲ decreased gradually (F=2.421, P=0.048). The voltage increased gradually (F=24.633, P<0.001), the pulse width increased slightly (F=3.118, P=0.015), but the frequency did not change significantly (F=1.332, P=0.257). The energy increased gradually (P<0.05), the contacts in zona incerta (ZI) increased gradually (P<0.05), the bipolar stimulation increased slightly (P<0.05), and the double contacts gradually increased gradually (P<0.05). During the follow-up period, a total of 35 patients developed stimulation-related adverse events, including 14 patients with troublesome dyskinesia, 4 patients with gait disorder or disequilibrium, 1 patients with anxiety and depression, 2 patients with dysphagia or drinking cough, 8 patients with hallucinations, 1 patient with hypophrenia, 2 patients with increased excitability, 1 patient with eye opening difficulty. Conclusions With the passage of time in the treatment of Parkinson′s disease with STN-DBS, the stimulation voltage and energy increased gradually, and the stimulation mode of double contacts increased gradually, but it was still dominated by unipolar stimulation, and the upper part of STN is the best stimulus site. Key words: Parkinson disease; Subthalamic nucleus; Deep brain stimulation; Post-operation programming

Effect of STN-DBS frequency on cortical excitability and motor performance in Parkinson's disease

Introduction Eighty Hertz vs. 130 Hz stimulation have a different effect on axial symptoms in some patients on chronic subthalamic nucleus (STN) deep brain stimulation in patients with Parkinson's disease (PD). This could be linked to a direct effect of the frequency of stimulation on the STN itself, and indirectly measured by means of transcranial magnetic stimulation. Our goal is to evaluate the effect of 80 Hz vs. 130 Hz frequency on cortical excitability and bradykinesia. Material and methods We conducted a double-blind crossover study in 15 patients with advanced PD treated with DBS for at least 6 months. Mean ± SD age was 63.3 ± 6.6 years and disease duration 15.5 ± 5.2 years. The time since surgery was 4.45 ± 3.9 years. The patients were stimulated with 80 Hz or 130 Hz randomly for 3 weeks and then switched to the other frequency for 3 more weeks. Adjustments of voltage were made according to the best clinical effect. Cortical excitability was measured in the first dorsal interosseous muscle with Short intracortical inhibition (SICI). In total, the patients were assessed 6 times. Proximal and distal movement task were also assessed. Results Both frequencies of stimulation improved distal bradykinesia to an equal extent. However, 80 Hz was less effective than high frequency stimulation in normalising SICI, however, bradykinesia of proximal arm/shoulder movements was improved more by 80 Hz compared to 130 Hz. Conclusions Stimulation of STN at 80 Hz and 130 Hz may have different effects on proximal and distal muscle control. One hundred and thirty Hertz may have a small advantage for distal hand muscles, whereas 80 Hz is more effective in improving proximal muscle function.

Deep brain stimulation of bilateral subthalamic nucleus for the treatment of drug-refractory Meige syndrome

Objective To explore the therapeutic effect of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in the treatment of refractory Meige syndrome (MS). Methods A total of 32 patients with MS who underwent STN-DBS at Department of Functional Neurosurgery, Aviation General Hospital of China Medical University from May 2014 to July 2017 were retrospectively enrolled into this study. The Burke-Fahn-Marsden Dystonia Disorder Scale (BFMDRS) was used to assess the improvement of clinical symptoms. The patient′s programmed parameters were documented as well. Results All 32 patients were successfully operated. No serious complications such as intracranial hemorrhage, wound infection, allergic reaction or electrical stimulator equipment failure occurred during perioperative period. Ten patients (31.3%) had varying degrees of dyskinesia during postoperative programing, which was improved at a certain level after adjustment of programmed parameters. One patient (3.1%) had psychiatric symptoms after surgery, and the mental symptoms disappeared 3 days after treatment. The postoperative follow-up time was >12 months. The improvement rates (median) of BFMDRS scores at 3, 6, and 12 months after surgery were 76.9%, 81.4%, and 82.8%, respectively. Among them, 18 patients were followed up for >24 months, and the improvement rate (median) was 82.5% at 24 months after surgery. All 32 patients were treated with unipolar stimulation mode, which was changed to double negative stimulation mode in 2 cases due to poor effects. The stimulation voltage was 0.8-3.4 V at 12 months postoperatively, the stimulation pulse width was 50-90 μs, and the stimulation frequency was 100-175 Hz. There was no significant increase or decrease in the programmed parameters of 32 patients between 3 and 12 months post operation. Conclusions STN-DBS seems safe and effective for patients with drug-resistant MS. Postoperative programming is relatively easy with parameters varying in a small scope. Key words: Meige syndrome; Dystonia; Subthalamic nucleus; Deep brain stimulation; Prognosis

Efficacy comparison of subthalamic and globus pallidus internus deep brain stimulation in Parkinson′s disease with dyskinesia

Objective To compare the therapeutic effects of subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) on Parkinson′s disease (PD) with levodopa-induced dyskinesia (LID), and to explore the possible underlying mechanism. Methods A total of 27 PD patients with LID treated with STN and GPi-DBS from August 2015 to October 2017 at Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University were retrospectively enrolled. Among them, 14 underwent STN-DBS and 13 underwent GPi-DBS. Patients were evaluated preoperatively and every 6, 12, 18 months after surgery. The primary outcome was assessed based on the Unified Dyskinesia Rating Scale (UDysRS). The secondary outcome was investigated according to the Unified Parkinson Disease Rating Scale part Ⅲ (UPDRS-Ⅲ), levodopa equivalent dose (LED), stimulation parameters and side effects. Results Both STN-DBS and GPi-DBS group showed significant improvement in LID, while GPi-DBS exerted higher LID improvement (F=15.326, P 0.05). The improvement of UPDRS-Ⅲ at the 18 month follow-up was 44.7%±20.0% and 45.7%±17.1%, respectively for STN and GPi-DBS. The LED reduction rate was higher in STN-DBS group (F=4.693, P<0.05). The LED reduction rate at the 18 month follow-up was[M(P25, P75)] 44.8(26.7, 80.2)%and 14.0(0, 41.3)%, respectively for STN and GPi-DBS.The stimulation voltage and pulse width of the GPi-DBS group were higher than those of the STN-DBS group (F values were 4.435 and 21.415 respectively, P<0.05). In the STN-DBS group, there were 5 cases of stimulation induced dyskinesia (SID), 1 case of electrode fracture, and 1 case of incision infection.There were 1 case of SID and 1 case of bradykinesia in the GPi-DBS group. Conclusions Both STN and GPi-DBS could improve dyskinesia. Compared with STN-DBS, GPi-DBS seems to have a stronger effect on improvement of LID. The anti-dyskinesia effect of STN-DBS may be related to drug reduction and adjustment of stimulation sites, while GPi-DBS might exert a direct anti-dyskinesia effect. Key words: Deep brain stimulation; Subthalamic nucleus; Globus pallidus internus; Levodopa-induced dyskinesia; Levodopa equivalent dose

Distributed Global Functional Connectivity Networks Predict Responsiveness to L-DOPA and Subthalamic Deep Brain Stimulation

Abstract INTRODUCTION Brain circuit dysfunction in Parkinson's disease (PD) involves an extensive global network. A distinctive basal ganglia resting-state functional connectivity (rsFC) pattern has been linked with the ranked response to L-DOPA. We therefore sought to investigate global rsFC patterns associated with response to L-DOPA and to subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with advanced PD. METHODS A total of 19 patients underwent 3-Tesla resting-state functional magnetic resonance imaging (rsfMRI) in the ON-medication state prior to STN DBS. Improvement in UPDRS-III hemibody scores were assessed following L-DOPA therapy and STN DBS. Global rsFC was measured between regions-of-interest (ROIs) defined by the Automated Anatomical Labeling (AAL) atlas and the Montreal Neurologic Institute (MNI) PD25 subcortical atlas. Seed- and network-level correlations were made with an FDR-P &lt; .005. Graph theoretical analysis was performed with an analysis threshold of FDR-P &lt; .005; and then looking at the top 15% of edges. RESULTS Response to L-DOPA and to DBS displayed cerebellar desynchronization with bilateral thalami and synchronization with bilateral ventromedial prefrontal cortices (vmPFC). L-DOPA response was additionally associated with desynchronization between the vmPFC and the fusiform gyrus. Meanwhile, DBS response was associated with more widespread areas, which have been implicated in visuomotor control and planning. Graph theory analysis revealed that DBS response was inversely related to global efficiency of the thalamus and putamen bilaterally. No significant graph metrics were found relative to L-DOPA response. CONCLUSION Response to DBS and to L-DOPA share similar characteristics, particularly in cerebello-thalamo-cortical circuits, including those that play a role in planning, learning, decision-making, and reward-based behavior. Preservation of distributed networks involved in visuomotor control and network integration of striatothalamocortical circuits appear to predict DBS response. These findings shed a light on the mechanism of action of DBS and L-DOPA and may help serve as useful treatment response biomarkers.

Asymmetric Deep Brain Stimulation Electrodes for Parkinson's Disease: A Pilot Study of Symptom-Tailored Stimulation

Abstract INTRODUCTION Bilateral subthalamic nucleus (STN) and globus pallidus interna (GPi) deep brain stimulation (DBS) are well established targets for the management of Parkinson's disease (PD). Each target has its own advantage, we presume the simultaneous unilateral STN and contralateral GPi DBS may compromise side effects of bilateral stimulation and keep each nucleus and its own efficacy on the motor and nonmotor symptoms. METHODS Eight patients with idiopathic PD with this kind of procedure were retrospectively reviewed. Motor, nonmotor symptoms, quality of life were measured before surgery, 6 mo, 1-yr post surgery under following conditions: medication on and off, bilateral stimulation on and off, unilateral STN stimulation on. Medication and stimulation parameters were noted. RESULTS Unilateral STN and contralateral GPi DBS significantly improved the UPDRS-? scores, with a 45% reduction at 6 mo and a 43% reduction at 1 yr. In total, 41% of levodopa equivalent daily dose was reduced at 1-yr follow-up. In the medication on condition, bilateral stimulation improved axial symptoms by 28.4% at 1-yr follow-up. In total, 3 m TUG (Time-Up Go test) improved by 41% at 6-mo follow-up compared to baseline, which lasts for 1 yr. In total, 64% reduction was found between baseline and 1-yr follow-up in gait and fall questionnaires. No deterioration was found in nonmotor measurements. No adverse events other than stimulation related were reported. CONCLUSION Our results provide the first evidence that supports unilateral STN and contralateral GPi DBS might be effective and safe in advanced PD patients. Future efforts are needed to explore the potential advantage in axial and cognitive symptoms in long term.

Editors' note: Deep brain stimulation improves restless legs syndrome in patients with Parkinson disease

In the article “Deep brain stimulation improves restless legs syndrome in patients with Parkinson disease,” Dr. Klepitskaya et al. reported sustained improvement in symptoms of restless legs syndrome (RLS) over 2 years in 22 patients with Parkinson disease (PD) who underwent subthalamic nucleus (STN) deep brain stimulation (DBS), despite a decrease in dopaminergic treatment. Drs. Marques et al. point out that the article misinterpreted the results of their previous study, which showed an emergence of RLS in patients with PD with a higher dose of dopamine agonists and a lower decrease in dopaminergic treatment after STN DBS. They discuss the paradoxical findings of STN DBS apparently improving preexisting RLS but causing emergence of RLS in some patients with PD and the need for further research. In response, Dr. Klepitskaya acknowledges these comments including the misinterpretation. A correction appears on page 871. In the article “Deep brain stimulation improves restless legs syndrome in patients with Parkinson disease,” Dr. Klepitskaya et al. reported sustained improvement in symptoms of restless legs syndrome (RLS) over 2 years in 22 patients with Parkinson disease (PD) who underwent subthalamic nucleus (STN) deep brain stimulation (DBS), despite a decrease in dopaminergic treatment. Drs. Marques et al. point out that the article misinterpreted the results of their previous study, which showed an emergence of RLS in patients with PD with a higher dose of dopamine agonists and a lower decrease in dopaminergic treatment after STN DBS.

Editors' note: Mystery Case: Bilateral temporal crescent sparing after cardiac arrest

In their Mystery Case, Lindegger et al. presented the unique visual fields of a middle-aged man who complained of tunnel vision 6 months following a cardiac arrest. One challenge to the case was the appearance of the Goldmann perimetry findings, which are nearly the opposite of what would be seen in a lesion affecting the optic chiasm. Instead of having bitemporal loss of vision, the patient had sparing of the most peripheral temporal visual fields with additional sparing of the binocular central fields. Among the 394 survey responses to the case, only 22% of readers correctly localized the lesion to the bilateral calcarine cortex (38% localized the lesion incorrectly to the chiasm). Dr. Rosenberg, a neuro-ophthalmologist, appropriately considers these Goldmann visual field findings controversial, and even contrary to our current understanding of visual pathways. Sparing of the far peripheral nasal fields and crossing of the vertical meridian peripherally would be untenable for bilateral occipital lobe lesions and probably explains why the survey participants had great difficulty localizing the lesion. Lindegger et al. respond that the manual perimetry was performed by an experienced technician, but that some of these atypical visual field findings may have resulted from the fixation losses and cognitive impairment that follows cardiac arrest. In the article “Deep brain stimulation improves restless legs syndrome in patients with Parkinson disease,” Dr. Klepitskaya et al. reported sustained improvement in symptoms of restless legs syndrome (RLS) over 2 years in 22 patients with Parkinson disease (PD) who underwent subthalamic nucleus (STN) deep brain stimulation (DBS), despite a decrease in dopaminergic treatment. Drs. Marques et al. point out that the article misinterpreted the results of their previous study, which showed an emergence of RLS in patients with PD with a higher dose of dopamine agonists and a lower decrease in dopaminergic treatment after STN DBS.

Kinematic Metrics from a Wireless Stylus Quantify Tremor and Bradykinesia in Parkinson's Disease.

A fundamental challenge in the clinical care of Parkinson disease (PD) is the current dependence on subjective evaluations of tremor and bradykinesia. New technologies offer the ability to evaluate motor deficits using purely objective measures. The aim of this study was to develop and evaluate the efficacy of a wireless stylus (Cleveland Clinic Stylus) with an embedded motion sensor to quantitatively assess tremor and bradykinesia in patients with PD with subthalamic nucleus (STN) deep brain stimulation (DBS). Twenty-one subjects were tested in various on and off DBS conditions while holding the Cleveland Clinic Stylus while at rest, maintaining a postural hold, and during a movement task. Kinematic metrics were calculated from the motion sensor data, including 3D angular velocity and 3D acceleration data, and were compared between the on and off conditions. Generalized estimating equations (GEEs) were used to determine the relationship between kinematic metrics and MDS-Unified Parkinson's Disease Rating Scale Motor III (UPDRS-III) subscores. Kinematic metrics from the rest and postural tasks were significantly related to the UPDRS-III subscores of tremor (p < 0.001 for all metrics), and kinematic metrics from the movement task were significantly related to the UPDRS-III subscore of bradykinesia (p < 0.001 for 3/7 metrics). Kinematic metrics (7/9) showed a significant effect of stimulation setting (range: p < 0.03– < 0.0001) across the three tasks, indicating significant improvements from DBS in these measures. The Cleveland Clinic Stylus provided quantitative kinematic measures of tremor and bradykinesia severity and detected significant improvements in these measures from medication and DBS therapy. This low-cost, easy-to-use tool can provide objective measures that will improve clinical care of PD patients by providing a more reliable and objective evaluation of movement symptoms, disease progression, and effects of therapy in and outside the clinical setting.

F182. Intraoperative local field potential recordings from deep brain stimulation electrodes help predict efficacy of subthalamic nucleus stimulation in patients with Parkinson’s disease

Introduction Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for advanced Parkinson’s disease (PD). Two electrophysiological techniques aid identification of the optimal target. One is to record neuronal activity with microelectrodes (MER). The other is to record the local field potential (LFP) from the DBS electrode used for chronic stimulation. The relative predictive value of the two techniques is yet to be established. Methods We combined MER and LFP recordings during STN electrode implantation in 18 PD patients. The LFP was recorded from the DBS electrode as it descended in 1 mm steps through the STN. The upper border of the STN identified by MER and the depth of the highest beta peak (HBP) recorded by the DBS electrode were correlated with the depth of chronic stimulation and with stimulation efficacy determined later. Results The HBP in the LFP recorded with the DBS electrode predicted the optimal contact for chronic stimulation slightly better than the upper border of the STN identified by MER, and the prediction remained after accounting for the depth of the upper border of the STN identified by MER. In addition, only the difference in depth between the HBP and the site of chronic stimulation significantly predicted the therapeutic efficacy of DBS with respect to contralateral bradykinesia-rigidity hemibody scores. Conclusion Our results confirm the predictive value of the DBS electrode recorded LFP and strengthen the argument that LFP patterns may help aid DBS targeting and programming.

Improving UPDRS and Efficacy of DBS with Microelectrode Recording of Subthalamic-Nuclei Deep Brain Stimulation (STN-DBS)-Classification and Prediction

Improving UPDRS and Efficacy of DBS with Microelectrode Recording of Subthalamic-Nuclei Deep Brain Stimulation (STN-DBS)-Classification and Prediction

EP 37. Impedance changes occur during threshold measurements in subthalamic nucleus (STN) deep brain stimulation patients

Background In previous work (Carcieri et al.), we observed impedance changes during the measurement of efficacy and side effect thresholds in seven DBS patients. This study investigates a larger group of subjects with more frequent impedance measurements to better characterize the time course of the effect and tests whether electrode impedance varies during the measurement of efficacy and side effect thresholds in DBS patients. Methods Twenty-four patients, implanted in the STN with a current-controlled DBS system (Boston Scientific Corporation) for at least 3 months, were stimulated on 4 different electrode combinations using one or two active electrodes and amplitude was adjusted to measure thresholds. At the beginning and end of threshold measurements, impedance was measured. Average stimulation duration was under 20 min, and amplitude was increased to 5 mA on average. Results Analysis reveals that turning stimulation ON resulted in an immediate reduction in impedance for 41/48 active electrodes, with a maximum decrease of 27%. The inactive electrodes showed a mean impedance decrease of 1%. For the active electrodes, the minimum impedance decrease was 2.8%, and the overall average decrease was 13.1%. Conclusions Deep brain stimulation in the normal range for measurement of thresholds may result in large and rapid impedance changes on the active electrodes. Impedance changes of this magnitude and time scale may have clinical relevance for some patients.

Improving dystonia among NBIA patients with subthalamic or pallidal nucleus deep brain stimulation

Improving dystonia among NBIA patients with subthalamic or pallidal nucleus deep brain stimulation

P80. Effects of deep brain stimulation on active and observational feedback learning in Parkinson’s disease

Decisions about how to respond optimally in daily life are often guided by learning from consequences of chosen actions. Response-outcome associations can be learned by active responding to a stimulus or by observing responses and associated consequences in others. There is evidence that, depending on medication status, patients with Parkinson’s disease (PD) are relatively impaired in tasks requiring active learning from feedback. Regarding subthalamic nucleus (STN) deep brain stimulation (DBS), an increasingly utilized and highly effective treatment option for PD-symptoms, effects on learning are less clear. There are first indications of enhanced active feedback learning with STN stimulation due to a suggested modulatory effect of STN-DBS on the dorsal striatum, which is involved in linking own actions and outcomes. The aim of the present investigation was to compare the effect of DBS on active and observational feedback learning in patients with PD. Since learning by observation may depend less on the dorsal striatum, we hypothesized that STN stimulation affects learning of associations during active but not observational feedback learning. Twenty PD patients with STN-DBS and 20 age-matched controls performed active and observational feedback learning tasks. PD patients, remaining on their regular dopaminergic medication, completed both tasks ON and OFF-stimulation. During the active learning task, subjects had to respond to abstract visual stimuli with either the left or the right hand by button press. After each response, they received positive or negative feedback. During the observational learning task, subjects observed responses and accompanying outcomes of another person. Test phases consisting of trials without feedback served to assess learning of stimulus–response-outcome associations. We will present preliminary results regarding the effects of STN-DBS on observational and active feedback learning in PD patients. The findings will be discussed in light of the need to further understand not only motor but also cognitive effects of DBS in PD patients.

Cognitive Changes after Deep Brain Stimulation in Parkinson’s Disease: A Critical Review

Concern about cognitive worsening, especially after subthalamic nucleus (STN) deep brain stimulation (DBS) has been reported in Parkinson’s disease (PD) patients, although it has not been deemed severe enough to discredit DBS as a powerful tool in the armamentarium against PD. We here provide an in-depth and critical review of the current literature on this topic, summarizing the available data on the impact of STN and globus pallidus interna (GPi) DBS on each of the following cognitive domains: language, executive function, attention and concentration, memory, visual function, psychomotor and processing speed, and global cognition; then looking in more details into controlled studies as well as studies directly comparing GPi and STN DBS. We conclude that worsening of one or more cognitive function is rare and subtle after DBS in PD patients, without negative impact on quality of life, and that there is very little data supporting that STN DBS has a worse cognitive outcome than Gpi DBS.

Effects of Simultaneous Bilateral Subthalamic Nucleus and Pedunculopontine Nucleus Deep Brain Stimulation on Saccades in Advanced Parkinson Disease

Effects of Simultaneous Bilateral Subthalamic Nucleus and Pedunculopontine Nucleus Deep Brain Stimulation on Saccades in Advanced Parkinson Disease

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.