Subthalamic Nucleus In Patients Research Articles

Evoked resonant neural activity long-term dynamics can be reproduced by a computational model with vesicle depletion

Subthalamic deep brain stimulation (DBS) robustly generates high-frequency oscillations known as evoked resonant neural activity (ERNA). Recently the importance of ERNA has been demonstrated through its ability to predict the optimal DBS contact in the subthalamic nucleus in patients with Parkinson's disease. However, the underlying mechanisms of ERNA are not well understood, and previous modelling efforts have not managed to reproduce the wealth of published data describing the dynamics of ERNA. Here, we aim to present a minimal model capable of reproducing the characteristics of the slow ERNA dynamics published to date. We make biophysically-motivated modifications to the Kuramoto model and fit its parameters to the slow dynamics of ERNA obtained from data. Our results demonstrate that it is possible to reproduce the slow dynamics of ERNA (over hundreds of seconds) with a single neuronal population, and, crucially, with vesicle depletion as one of the key mechanisms behind the ERNA frequency decay in our model. We further validate the proposed model against experimental data from Parkinson's disease patients, where it captures the variations in ERNA frequency and amplitude in response to variable stimulation frequency, amplitude, and to stimulation pulse bursting. We provide a series of predictions from the model that could be the subject of future studies for further validation.

Mechanisms and consequences of weight gain after deep brain stimulation of the subthalamic nucleus in patients with Parkinson’s disease

Body weight gain in combination with metabolic alterations has been observed after deep brain stimulation (DBS) of subthalamic nucleus (STN) in patients with Parkinson’s disease (PD), which potentially counteracts the positive effects of motor improvement. We aimed to identify stimulation-dependent effects on motor activities, body weight, body composition, energy metabolism, and metabolic blood parameters and to determine if these alterations are associated with the local impact of DBS on different STN parcellations. We assessed 14 PD patients who underwent STN DBS (PD-DBS) before as well as 6- and 12-months post-surgery. For control purposes, 18 PD patients under best medical treatment (PD-CON) and 25 healthy controls (H-CON) were also enrolled. Wrist actigraphy, body composition, hormones, and energy expenditure measurements were applied. Electrode placement in the STN was localized, and the local impact of STN DBS was estimated. We found that STN DBS improved motor function by ~ 40% (DBS ON, Med ON). Weight and fat mass increased by ~ 3 kg and ~ 3% in PD-DBS (all P ≤ 0.005). fT3 (P = 0.001) and insulin levels (P = 0.048) increased solely in PD-DBS, whereas growth hormone levels (P = 0.001), daily physical activity, and VO2 during walking were decreased in PD-DBS (all P ≤ 0.002). DBS of the limbic part of the STN was associated with changes in weight and body composition, sedentary activity, insulin levels (all P ≤ 0.040; all r ≥ 0.56), and inversely related to HOMA-IR (P = 0.033; r = − 0.62). Daily physical activity is decreased after STN DBS, which can contribute to weight gain and an unfavorable metabolic profile. We recommend actigraphy devices to provide feedback on daily activities to achieve pre-defined activity goals.

Long-term efficacy of deep brain stimulation of the subthalamic nucleus in patients with pharmacologically intractable epilepsy: a case series of six patients.

Epilepsy is one of the widespread neurological illnesses, and about 20-40% of epilepsy patients are pharmacoresistant. We aimed to assess the long-term efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) for drug-resistant epilepsy. We included pharmacologically intractable epilepsy patients who had STN-DBS at the Chinese People's Liberation Army General Hospital between June 2016 and December 2018. We retrospectively evaluated pre- and postoperative clinical outcomes, including seizure frequency, seizure type, anti-seizure medication, cognitive function, anatomical target coordinates, stimulation parameters, and adverse events following the surgical procedure. Six patients with a mean follow-up of 49.3 ± 10.2 months, were included. Seizure frequency decreased by an average of 64.0% after STN-DBS at last year follow-up (p = 0.046), and one patient (1/6) achieved seizure-free status. For seizure type, anti-seizure medication, and cognitive function, there were no significant differences between pre-and post-operation (p > 0.05). In terms of stimulation parameters, the pulse width, amplitude, and frequency were 58.3 ± 9.4 μsec, 2.5 ± 0.7 V, and 122.5 ± 15.7 Hz, respectively. None of the patients showed normal electroencephalography during the electroencephalography reexamination. There were no surgery-related complications, and chronic STN stimulation was generally well tolerated in five patients. However, one patient (1/6) had a difficulty of dyskinesia in the right arm. In conclusion, neuromodulation of the STN by DBS is a promising option for patients with pharmacologically intractable epilepsy, especially for whose epileptic zone originates mainly from the frontoparietal region and who are unsuitable for resective surgery. Further prospective multicenter studies with a larger sample size are necessary for further exploration.

Morphometric Analysis of Subthalamic Nuclei in Patients of Deep Brain Stimulation in Parkinson’s Disease

Morphometric Analysis of Subthalamic Nuclei in Patients of Deep Brain Stimulation in Parkinson’s Disease

Profiling the low-beta characteristics of the subthalamic nucleus in early- and late-onset Parkinson's disease.

Low-beta oscillation (13-20 Hz) has rarely been studied in patients with early-onset Parkinson's disease (EOPD, age of onset ≤50 years). We aimed to explore the characteristics of low-beta oscillation in the subthalamic nucleus (STN) of patients with EOPD and investigate the differences between EOPD and late-onset Parkinson's disease (LOPD). We enrolled 31 EOPD and 31 LOPD patients, who were matched using propensity score matching. Patients underwent bilateral STN deep brain stimulation (DBS). Local field potentials were recorded using intraoperative microelectrode recording. We analyzed the low-beta band parameters, including aperiodic/periodic components, beta burst, and phase-amplitude coupling. We compared low-beta band activity between EOPD and LOPD. Correlation analyses were performed between the low-beta parameters and clinical assessment results for each group. We found that the EOPD group had lower aperiodic parameters, including offset (p = 0.010) and exponent (p = 0.047). Low-beta burst analysis showed that EOPD patients had significantly higher average burst amplitude (p = 0.016) and longer average burst duration (p = 0.011). Furthermore, EOPD had higher proportion of long burst (500-650 ms, p = 0.008), while LOPD had higher proportion of short burst (200-350 ms, p = 0.007). There was a significant difference in phase-amplitude coupling values between low-beta phase and fast high frequency oscillation (300-460 Hz) amplitude (p = 0.019). We found that low-beta activity in the STN of patients with EOPD had characteristics that varied when compared with LOPD, and provided electrophysiological evidence for different pathological mechanisms between the two types of PD. These differences need to be considered when applying adaptive DBS on patients of different ages.

Effects of Deep Brain Stimulation on Lower Urinary Tract Function in Neurological Patients

BackgroundDeep brain stimulation (DBS) has clear beneficial effects on motor signs in movement disorders, but much less is known about its impact on lower urinary tract (LUT) function. ObjectiveTo evaluate the effects of DBS on LUT function in patients affected by movement disorders. Design, setting, and participantsWe prospectively enrolled 58 neurological patients affected by movement disorders, who were planned to receive DBS. InterventionDBS in the globus pallidus internus, ventral intermediate nucleus of the thalamus, or subthalamic nucleus. Outcome measurements and statistical analysisSubjective symptom questionnaires (International Prostate Symptom Score) and objective urodynamic studies were carried out before implantation of the DBS leads and several months after surgery. After DBS surgery, urodynamic investigations were performed with DBS ON as well as DBS OFF. Results and limitationsWe enrolled patients suffering from Parkinson’s disease (n = 39), dystonia (n = 11), essential tremor (n = 5), Holmes tremor (n = 2), and multiple sclerosis with tremor (n = 1). DBS of the globus pallidus internus resulted in worsening of LUT symptoms in 25% (four of 16) of the cases. DBS of the subthalamic nucleus in patients with Parkinson’s disease led to normalization of LUT function in almost 20% (six of 31 patients), while a deterioration was seen in only one (3%) patient. DBS of the ventral intermediate nucleus of the thalamus improved LUT function in two (18%) and deteriorated it in one (9%) patient with tremor. ConclusionsDBS effects on LUT varied with stimulation location, highly warranting patient counseling prior to DBS surgery. However, more well-designed, large-volume studies are needed to confirm our findings. Patient summaryIn this report, we looked at outcomes of deep brain stimulation on lower urinary tract function. We found that outcomes varied with stimulation location, concluding that counseling of patients about the effects on lower urinary tract function is highly recommended prior to surgery.

Comparison of subthalamic nucleus borders determined by high-resolution MRI and microelectrode recording

Background . Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an acknowledged efficient and safe method of treatment of advanced stages of Parkinson’s disease. The traditional way of intraoperative target verification is a combination of microelectrode recording (MER) and intraoperative macrostimulation. The appearance of high-field tomographs, new sequences, and methods of computer processing of the obtained images raises the question whether it’s necessary to use intraoperative verification of the target. Objective . The aim of the study was to analyze the comparability of 3T MRI data and microelectrode registration data in determining the boundaries of the subthalamic nucleus in patients with Parkinson's disease. Material and methods . 20 patients who have been undergone 3T MRI for preoperative planning for STN-DBS were included in the study. We determined the upper and lower boundaries of 40 subthalamic nuclei in high-resolution T2 and SWAN modes and compared these data with the data obtained during surgery using the MER. Results . The discrepancy between the MED and 3T MRI data when determining the upper STN border was 1.2 mm in SWAN mode and 1 mm in high-resolution T2 mode. The lower border of the subthalamic nucleus could be determined with an accuracy of 0.85 in SWAN mode and 0.75 mm in T2 mode. The groups didn’t have significant differences (Wilcoxon sign-rank test, p > 0.05). Conclusion . 3T MRI in high-resolution T2 and SWAN modes demonstrated high comparability with microelectrode data in determining the upper boundary, lower boundary and middle of the subthalamic nucleus, which makes it possible to use it as a method for direct STN imaging.

Bilateral stimulation of the subthalamic nucleus under local and general anaesthesia

Introduction. Bilateral stimulation of the subthalamic nucleus (STN) is successfully used to treat advanced stages of Parkinson's disease. The standard surgical technique includes microelectrode recording and intraoperative stimulation. The introduction of 3T MRI into clinical practice and new impulse sequences have led to the question of whether the surgery can be performed under general anaesthesia.
 Aim of the study: to compare the efficacy and safety of bilateral stimulation of STN in patients with Parkinson's disease, using 3T MRI under local and general anaesthesia.
 Materials and methods. This prospective, randomized controlled study included 40 patients, who underwent electrode implantation using 3T MRI. The patients in the main group (n = 20) had electrodes implanted under general anaesthesia, while the control group (n = 20) had local anaesthesia, intraoperative stimulation and microelectrode recording. The patients motor status, quality of life, cognitive function and required levodopa dose were evaluated after 6 months.
 Results. The results of 6 months of stimulation were obtained from 30 patients (15 from the main group and 15 from the control group). Reduced motor impairment was observed in both groups as measured on the UPDRS III scale during the 'off' time, with a reduction of 68.7% in the main group and 74.7% in the control group. Improved quality of life, reduced drug-induced motor complications and a reduction in the levodopa dose were also comparable in both groups. No intraoperative haemorrhagic complications were recorded during the study.
 Conclusions. Preliminary analysis of the data showed that with high-quality visualization of the STN, electrode implantation under anaesthesia is equally effective to awake surgery.

Striatal dopamine transporter availability and individual clinical course within the 1-year follow-up of deep brain stimulation of the subthalamic nucleus in patients with Parkinson's disease.

Degeneration of dopaminergic neurons in the substantia nigra projecting to the striatum is responsible for the motor symptoms in Parkinson's disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established procedure to alleviate these symptoms in advanced PD. Yet the mechanism of action, especially the effects of STN-DBS on the availability of striatal dopamine transporter (DAT) as a marker of nigrostriatal nerve cell function, remains largely unknown. The aim of this study was therefore to evaluate whether 1) DAT availability changes within 1 year of STN-DBS and 2) the clinical outcome can be predicted based on preoperative DAT availability. Twenty-seven PD patients (mean age 62.7 ± 8.9 years; mean duration of illness 13.0 ± 4.9 years; PD subtypes: akinetic-rigid, n = 11; equivalence, n = 13; and tremor-dominant, n = 3) underwent [123I]FP-CIT SPECT preoperatively and after 1 year of STN-DBS. DAT availability as determined by the specific binding ratio (SBR) was assessed by volume of interest (VOI) analysis of the caudate nucleus and the putamen ipsilateral and contralateral to the clinically more affected side. Unified Parkinson's Disease Rating Scale (UPDRS) III scores improved significantly (mean preoperative on medication 25.6 ± 12.3, preoperative off medication 42.3 ± 15.2, postoperative on medication/off stimulation 41.4 ± 13.2, and postoperative on medication/on stimulation 16.1 ± 9.4; preoperative on medication vs postoperative on medication/on stimulation, p = 0.006), while the levodopa-equivalent daily dose was reduced (mean preoperative 957 ± 440 mg vs postoperative 313 ± 189 mg, p < 0.001). The SBR did not differ significantly before and 1 year after DBS, regardless of PD subtype. Preoperative DAT availability was not related to the change in UPDRS III score, but the change in DAT availability was significantly correlated with the change in UPDRS III score (contralateral head of the caudate VOI, p = 0.014; contralateral putamen VOI, p = 0.018). Overall, DAT availability did not change significantly after 1 year of STN-DBS. However, on an individual basis, the improvement in UPDRS III score was associated with an increase in DAT availability, whereas DAT availability before STN-DBS surgery did not predict the clinical outcome. Whether a subtype-specific pattern of preoperative DAT availability can become a reliable predictor of successful STN-DBS must be evaluated in larger study cohorts.

Effect of bilateral deep brain stimulation on the subthalamic nucleus on patients with Parkinson's disease: An observational and non-blinded study

ObjectiveThis study analyzed the influence of subthalamic nucleus deep brain stimulation (DBS) in motor parameters and patients' quality of life with Parkinson's disease (PD) evaluated before and after 12 months of the surgical procedure. MethodsA cohort of 20 patients with PD who underwent DBS implantation in the subthalamic nucleus was included. Pre and on-DBS postoperative data in on and off-medication periods related to motor functions and quality of life, from the application of validated scales, were collected to verify possible relationships between changes in these parameters and the surgical procedure. ResultsA significant decrease in the Hoehn and Yahr scale disease stage and in the levodopa equivalent dose (p < 0.001) was verified in the off-medication period when we compared baseline and post-12 months data. A significant decrease in dyskinesias (p = 0.009) was observed during the on-medication period by evaluating the UDysRS scale. Concerning motor functions verified through the UPDRS-III scale, it was obtained a significant reduction in total scores (p = 0.001), besides a decrease in rigidity scores for upper and lower limbs (p < 0.05) during the on-medication period. During the off-medication period, scores of UPDRS-III demonstrated a significant decrease, except for the ones related to speech and amplitude of resting tremor. Regarding the quality-of-life assessment, scores obtained from PDQ-39 showed that, after 12 months of electrode implantation, there was a significant decrease in mobility, daily living activity, and stigma parameters (p < 0.05). ConclusionsResults obtained allow us to conclude that DBS of the subthalamic nucleus in patients with PD improves motor function in both on and off-medication periods, improvement of the disease stage in the off-medication period, with no change in the on-medication period, also an improvement in the patient's self-reported quality of life and a significant reduction in the dose of L-DOPA.

Balance between competing spectral states in subthalamic nucleus is linked to motor impairment in Parkinson's disease.

Exaggerated local field potential bursts of activity at frequencies in the low beta band are a well-established phenomenon in the subthalamic nucleus of patients with Parkinson’s disease. However, such activity is only moderately correlated with motor impairment. Here we test the hypothesis that beta bursts are just one of several dynamic states in the subthalamic nucleus local field potential in Parkinson’s disease, and that together these different states predict motor impairment with high fidelity.Local field potentials were recorded in 32 patients (64 hemispheres) undergoing deep brain stimulation surgery targeting the subthalamic nucleus. Recordings were performed following overnight withdrawal of anti-parkinsonian medication, and after administration of levodopa. Local field potentials were analysed using hidden Markov modelling to identify transient spectral states with frequencies under 40 Hz.Findings in the low beta frequency band were similar to those previously reported; levodopa reduced occurrence rate and duration of low beta states, and the greater the reductions, the greater the improvement in motor impairment. However, additional local field potential states were distinguished in the theta, alpha and high beta bands, and these behaved in an opposite manner. They were increased in occurrence rate and duration by levodopa, and the greater the increases, the greater the improvement in motor impairment. In addition, levodopa favoured the transition of low beta states to other spectral states. When all local field potential states and corresponding features were considered in a multivariate model it was possible to predict 50% of the variance in patients’ hemibody impairment OFF medication, and in the change in hemibody impairment following levodopa. This only improved slightly if signal amplitude or gamma band features were also included in the multivariate model. In addition, it compares with a prediction of only 16% of the variance when using beta bursts alone.We conclude that multiple spectral states in the subthalamic nucleus local field potential have a bearing on motor impairment, and that levodopa-induced shifts in the balance between these states can predict clinical change with high fidelity. This is important in suggesting that some states might be upregulated to improve parkinsonism and in suggesting how local field potential feedback can be made more informative in closed-loop deep brain stimulation systems.

The Accuracy of Direct Targeting Using Fusion of MR and CT Imaging for Deep Brain Stimulation of the Subthalamic Nucleus in Patients with Parkinson's Disease.

In 33 consecutive patients with Parkinson's disease (PD) undergoing awake deep brain stimulation (DBS) without microelectrode recording (MER), we assessed and validated the precision and accuracy of direct targeting of the subthalamic nucleus (STN) using preoperative magnetic resonance imaging (MRI) and stereotactic computed tomography (CT) image fusion combined with immediate postoperative stereotactic CT and postoperative MRI, and we report on the side effects and clinical results up to 6 months' follow-up. Preoperative nonstereotactic MRI and stereotactic CT images were merged and used for planning the trajectory and final lead position. Immediate postoperative stereotactic CT and postoperative nonstereotactic MRI provided the validation of the final electrode position. Changes in the Unified Parkinson's Disease Rating Scale III (UPDRS III) scores and the levodopa equivalent daily doses (LEDD) and appearance of adverse side effects were assessed. The mean Euclidian distance (ED) error between the planned position and the final position of the lead in the left STN was 1.69 ± 0.82 mm and that in the right STN was 2.12 ± 1.00. The individual differences between planned and final position in each of the three coordinates were less than 2 mm. The UPDRS III scores improved by 75% and LEDD decreased by 45%. Few patients experienced complications, such as postoperative infection (n = 1), or unwanted side effects, such as emotional instability (n = 1). Our results confirm that direct targeting of an STN on stereotactic CT merged with MRI could be a valid method for placement the DBS electrode. The magnitude of our targeting error is comparable with the reported errors when using MER and other direct targeting approaches.

Targeting of the Subthalamic Nucleus in Patients with Parkinson's Disease Undergoing Deep Brain Stimulation Surgery.

Precise stereotactic targeting of the dorsolateral motor part of the subthalamic nucleus (STN) is paramount for maximizing clinical effectiveness and preventing side effects of deep brain stimulation (DBS) in patients with advanced Parkinson’s disease. With recent developments in magnetic resonance imaging (MRI) techniques, direct targeting of the dorsolateral part of the STN is now feasible, together with visualization of the motor fibers in the nearby internal capsule. However, clinically relevant discrepancies were reported when comparing STN borders on MRI to electrophysiological STN borders during microelectrode recordings (MER). Also, one should take into account the possibility of a 3D inaccuracy of up to 2 mm of the applied stereotactic technique. Pneumocephalus and image fusion errors may further increase implantation inaccuracy. Even when implantation has been successful, suboptimal lead anchoring on the skull may cause lead migration during follow-up. Meticulous pre- and intraoperative imaging is therefore indispensable, and so is postoperative imaging when the effects of DBS deteriorate during follow-up. Thus far, most DBS centers employ MRI targeting, multichannel MER, and awake test stimulation in STN surgery, but randomized trials comparing surgery under local versus general anesthesia and additional studies comparing MER-STN borders to high-field MRI-STN may change this clinical practice. Further developments in imaging protocols and improvements in image fusion processes are needed to optimize placement of DBS leads in the dorsolateral motor part of the STN in Parkinson’s disease.

Deep brain stimulation electrode position impact on parkinsonian non-motor symptoms.

In this study we evaluated the impact of location of deep brain stimulation electrode active contact in different parts of the subthalamic nucleus on improvement of non-motor symptoms in patients with Parkinson's disease. The subthalamic nucleus was divided into two (dorsolateral/ventromedial) and three (dorsolateral, medial, ventromedial) parts. 37 deep brain stimulation electrodes were divided according to their active contact location. Correlation between change in non-motor symptoms before and one and four months after deep brain stimulation electrode implantation and the location of active contact was made. In dividing the subthalamic nucleus into three parts, no electrode active contact was placed ventromedially, 28 active contacts were located in the medial part and 9 contacts were placed dorsolaterally. After one and four months, no significant difference was found between medial and dorsolateral positions. In the division of the subthalamic nucleus into two parts, 13 contacts were located in the ventromedial part and 24 contacts were placed in the dorsolateral part. After one month, significantly greater improvement in the Non-motor Symptoms Scale for Parkinson's disease (P=0.045) was found on dorsolateral left-sided stimulation, but no significant differences between the ventromedial and dorsolateral positions were found on the right side. This study demonstrated the relationship between improvement of non-motor symptoms and the side (hemisphere, left/right) of the deep brain stimulation electrode active contact, rather than its precise location within specific parts of the subthalamic nucleus in patients treated for advanced Parkinson's disease.

Influence of Anesthesia and Clinical Variables on the Firing Rate, Coefficient of Variation and Multi-Unit Activity of the Subthalamic Nucleus in Patients with Parkinson's Disease.

Background: Microelectrode recordings (MER) are used to optimize lead placement during subthalamic nucleus deep brain stimulation (STN-DBS). To obtain reliable MER, surgery is usually performed while patients are awake. Procedural sedation and analgesia (PSA) is often desirable to improve patient comfort, anxiolysis and pain relief. The effect of these agents on MER are largely unknown. The objective of this study was to determine the effects of commonly used PSA agents, dexmedetomidine, clonidine and remifentanil and patient characteristics on MER during DBS surgery. Methods: Data from 78 patients with Parkinson’s disease (PD) who underwent STN-DBS surgery were retrospectively reviewed. The procedures were performed under local anesthesia or under PSA with dexmedetomidine, clonidine or remifentanil. In total, 4082 sites with multi-unit activity (MUA) and 588 with single units were acquired. Single unit firing rates and coefficient of variation (CV), and MUA total power were compared between patient groups. Results: We observed a significant reduction in MUA, an increase of the CV and a trend for reduced firing rate by dexmedetomidine. The effect of dexmedetomidine was dose-dependent for all measures. Remifentanil had no effect on the firing rate but was associated with a significant increase in CV and a decrease in MUA. Clonidine showed no significant effect on firing rate, CV or MUA. In addition to anesthetic effects, MUA and CV were also influenced by patient-dependent variables. Conclusion: Our results showed that PSA influenced neuronal properties in the STN and the dexmedetomidine (DEX) effect was dose-dependent. In addition, patient-dependent characteristics also influenced MER.

Unsupervised clustering reveals spatially varying single neuronal firing patterns in the subthalamic nucleus of patients with Parkinson's disease

IntroductionSubthalamic nucleus (STN) is an effective target for deep brain stimulation (DBS) to reduce the motor symptoms of Parkinson's disease (PD). It is important to identify firing patterns within the structure for a better understanding of the electro-pathophysiology of the disease. Using recently established metrics, our study aims to autonomously identify the discharge patterns of individual cells and examine their spatial distribution within the STN. MethodsWe recorded single unit activity (SUA) from 12 awake PD patients undergoing a standard clinical DBS surgery. Three extracted features from raw SUA (local variation, bursting index and prominence of peak) were used with k-means clustering to achieve the aforementioned unsupervised grouping of firing patterns. Results279 neurons were isolated and four distinct firing patterns were identified across patients: tonic (11%), irregular (55%), periodic (9%) and non-periodic bursts (25%). The mean firing rates for irregular discharges were significantly lower (p < 0.05) than the rest. Tonic firings were significantly ventral (p < 0.05) while periodic (p < 0.05) and non-periodic (p < 0.01) bursts were dorsal. The percentage of periodically bursting neurons in dorsal region and entire STN were significantly correlated with off state UPDRS tremor scores (r = 0.51, p = 0.04) and improvement in bradykinesia and rigidity (r = 0.57, p = 0.02) respectively. ConclusionStrengthening the application of unsupervised clustering for firing patterns of individual cells, this study shows a unique spatial affinity of tonic activity towards the ventral and bursting activity towards the dorsal region of STN in PD patients. This spatial preference, together with the correlation of clinical scores, can provide a clue towards understanding Parkinsonian symptom generation.

A systematic review of body mass gain after deep brain stimulation of the subthalamic nucleus in patients with Parkinson's disease.

This systematic review investigated the effects of deep brain stimulation of the subthalamic nucleus on extent and time course of body mass changes in patients with Parkinson's disease. A computerized search identified relevant articles using a priori defined inclusion and exclusion criteria. A descriptive analysis was calculated for the main outcome parameters body mass and BMI. Thirty-eight out of 206 studies fulfilled the inclusion criteria (979 patients aged 59.0±7.5 years). Considering the longest follow-up time for each study, body mass and BMI showed a mean increase across studies of +5.71kg (p < .0001; d = 0.64) and +1.8kg/m2 (p < .0001; d = 1.61). The time course of body mass gain revealed a continuous increase ranging from +3.25kg (d = 0.69) at 3 months, +3.88kg (d = 0.21) at 6 months, +6.35kg (d = 0.72) at 12 months, and +6.11kg (d = 1.02) greater than 12 months. Changes in BMI were associated with changes in disease severity (r = 0.502, p = .010) and pharmacological treatment (r = 0.440, p = .0231). Data suggest that body mass gain is one of the most common side effects of deep brain stimulation going beyond normalization of preoperative weight loss. Considering the negative health implications of overweight, we recommend the development of tailored therapies to prevent overweight and associated metabolic disorders following this treatment.

Variable- versus constant-frequency deep-brain stimulation in patients with advanced Parkinson\u2019s disease: study protocol for a randomized controlled trial

BackgroundDeep-brain stimulation targeting the subthalamic nucleus (STN) can be used to treat motor symptoms and dyskinesia in the advanced stages of Parkinson’s disease (PD). High-frequency stimulation (HFS) of the STN can lead to consistent, long-term improvement of PD symptoms. However, the effects of HFS on the axial symptoms of PD, specifically freezing of gait, can be limited or cause further impairment. While this can be alleviated via relatively low-frequency stimulation (LFS) in selected patients, LFS does not control all motor symptoms of PD. Recently, the National Engineering Laboratory for Neuromodulation reported preliminary findings regarding an efficient way to combine the advantages of HFS and LFS to form variable-frequency stimulation (VFS). However, this novel therapeutic strategy has not been formally tested in a randomized trial.Methods/designWe propose a multicenter, double-blind clinical trial involving 11 study hospitals and an established deep-brain stimulation team. The participants will be divided into a VFS and a constant-frequency stimulation group. The primary outcome will be changes in stand–walk–sit task scores after 3 months of treatment in the “medication off” condition. Secondary outcome measures include specific item scores on the Freezing of Gait Questionnaire and quality of life. The aim of this trial is to investigate the efficacy and safety of VFS compared with constant-frequency stimulation.DiscussionThis is the first randomized controlled trial to comprehensively evaluate the effectiveness and safety of VFS of the STN in patients with advanced PD. VFS may represent a new option for clinical treatment of PD in the future.Trial registrationClinicalTrials.gov, NCT03053726. Registered on February 15, 2017.

Automatic Segmentation of the Subthalamic Nucleus: A Viable Option to Support Planning and Visualization of Patient-Specific Targeting in Deep Brain Stimulation.

Automatic segmentation is gaining relevancy in image-based targeting of neural structures. To evaluate its feasibility, we retrospectively analyzed the concordance of magnetic resonance imaging (MRI)-based automatic segmentation of the subthalamic nucleus (STN) and intraoperative microelectrode recordings (MERs). Electrodes (n=60) for deep brain stimulation were implanted in the STN of patients (n=30; median age 57 yr) with Parkinson disease (n=29) or rapid-onset dystonia parkinsonism (n=1). Elements (Brainlab, Munich, Germany) were used to segment the STN, using 2 volumetric T1 (±contrast) and volumetric T2 images as input. The stereotactic computed tomography was coregistered with the imaging, and the original stereotactic coordinates were imported. MERs (0.5-1 mm steps) along the anterior, central, and lateral trajectories were used to determine differences between the image-segmented STN boundary and MER-based STN entry and exit. Of 175 trajectories, 105 penetrated or touched (≤0.7 mm) the STN. The overall median deviation between the segmented STN boundary and electrophysiological recordings was 1.1 mm for MER-based STN entry and 2.0 mm for STN exit. Regarding the entry point of the STN, there was no statistically significant difference between MRI-based automatic segmentation and the electrophysiological trajectories analyzed with intraoperative MER. The exit point was significantly different between both methods in the central and lateral trajectories. MRI-based automatic segmentation of the STN is a viable, patient-specific targeting approach that can be used alongside traditional targeting methods in deep brain stimulation to support preoperative planning and visualization of target structures and aid postoperative optimization of programming.

Letter to the Editor Regarding “Statistical Shape Analysis of Subthalamic Nucleus in Patients with Parkinson’s Disease”

Letter to the Editor Regarding “Statistical Shape Analysis of Subthalamic Nucleus in Patients with Parkinson’s Disease”