Non-lesional treatments for tremor in Parkinson's disease: A systematic review and meta-analysis.

INTRODUCTION: Tremor is often perceived as severely disabling by patients with idiopathic Parkinson's disease (iPD) and yet ranges among the most difficult symptoms to treat. To date, no comprehensive analysis of non-lesional therapies to manage tremor in iPD exists to base recommendations upon. We therefore present a systematic literature review and meta-analysis assessing the efficacy/effectiveness and safety of non-lesional treatments for tremor in iPD. METHODS: Three electronic databases were searched using a combination of title/abstract keywords complemented by hand-searching of reference lists. A random-effects meta-analysis of standardized mean change scores was conducted where appropriate. RESULTS: Some 114 studies met inclusion criteria involving 8045 patients. The meta-analysis revealed an overall reduction of standardized mean change scores by (-0.93 [CI: -1.42; -0.43], p < 0.001) by 14 different dopaminergic and non-dopaminergic classes of agents. No significant differences were identified between direct comparisons. Subgroup analysis comparing dopamine receptor agonists resulted in superior effects of pramipexole and rotigotine compared with ropinirole. There was little cumulative evidence to support the use of individual non-pharmacological interventions for tremor, except for electrical stimulation. CONCLUSIONS: The results of this meta-analysis suggest a large but nonspecific effect of established pharmacological therapies on tremor in iPD. Based on high-quality studies, there is sufficient evidence to support that levodopa, dopamine receptor agonists, and monoamine oxidase inhibitors provide tremor relief in most patients, while evidence supporting other treatments is less well established. Sufficient evidence to draw conclusions on effects of non-lesional treatments in cases with refractory tremor is lacking.

Visual perturbation of balance suggests impaired motor control but intact visuomotor processing in Parkinson's disease.

Postural instability marks one of the most disabling features of Parkinson's disease (PD), but it only reveals itself after affected brain areas have already been significantly damaged. Thus there is a need to detect deviations in balance and postural control before visible symptoms occur. In this study, we visually perturbed balance in the anterior-posterior direction using sinusoidal oscillations of a moving room in virtual reality at different frequencies. We tested three groups: individuals with PD under dopaminergic medication, an age-matched control group, and a group of young healthy adults. We tracked their center of pressure and their full-body motion, from which we also extracted the center of mass. We investigated sway amplitudes and applied newly introduced phase-locking analyses to investigate responses across participants' bodies. Patients exhibited significantly higher sway amplitudes as compared with the control subjects. However, their sway was phase locked to the visual motion like that of age-matched and young healthy adults. Furthermore, all groups successfully compensated for the visual perturbation by phase locking their sway to the stimulus. As frequency of the perturbation increased, distribution of phase locking (PL) across the body revealed a shift of the highest PL values from the upper body toward the hip region for young healthy adults, which could not be observed in patients and elderly healthy adults. Our findings suggest an impaired motor control, but intact visuomotor processing in early stages of PD, while less flexibility to adapt postural strategy to different perturbations revealed to be an effect of age rather than disease.NEW & NOTEWORTHY A better understanding of visuomotor control in Parkinson's disease (PD) potentially serves as a tool for earlier diagnosis, which is crucial for improving patient's quality of life. In our study, we assess body sway responses to visual perturbations of the balance control system in patients with early-to-mid stage PD, using motion tracking along with recently established phase-locking techniques. Our findings suggest patients at this stage have an impaired muscular stability but intact visuomotor control.

Antisaccades in Parkinson's Disease: A Meta-Analysis.

The usefulness of eye-tracking tasks as potential biomarkers for motor or cognitive disease burden in Parkinson's disease (PD) has been subject of debate for many years. Several studies suggest that the performance in the antisaccade task may be altered in patients with PD and associated with motor disease severity or executive dysfunction. In this meta-analysis, random effects models were used to synthesize the existing evidence on antisaccade error rates and latency in PD. Furthermore, meta-regressions were performed to assess the role of motor and cognitive disease severity, dopaminergic medication and methodological factors. Additionally, the impact of acute levodopa administration and activation of deep brain stimulation was evaluated in two separate sub-analyses.This meta-analysis confirms that antisaccade latency and error rate are significantly increased in PD. Disease duration, Unified Parkinson's disease rating scale score and Hoehn and Yahr stage mediate the effect of PD on antisaccade latency with higher motor burden being associated with increased antisaccade latency.Acute administration of levodopa had no significant effects on antisaccade performance in a small number of eligible studies. Deep brain stimulation in the subthalamic nucleus, on the other hand, may alter the speed accuracy trade-off supporting an increase of impulsivity following deep brain stimulation in PD.According to the results of the meta-analysis, antisaccade latency may provide a potential marker for disease severity and progression in PD which needs further confirmation in longitudinal studies.

Deep brain stimulation: Connectivity profile for bradykinesia alleviation.

OBJECTIVE: Subthalamic deep brain stimulation may alleviate bradykinesia in Parkinson patients. Research suggests that this stimulation effect may be mediated by brain networks like the corticocerebellar loop. This study investigated the connectivity between stimulation sites and cortical and subcortical structures to identify connections for effective stimulation. METHODS: We retrospectively investigated 21 patients with Parkinson disease with bilateral subthalamic deep brain stimulation. Stimulation effectiveness in reducing bradykinesia, tremor, and rigidity was evaluated for each electrode contact in brain hemispheres contralateral to the affected hemibody. Dysarthric side effects were also examined. Probabilistic tractography based on diffusion-weighted imaging was performed in individual patient-specific brains using electrode contacts as seeds. Connectivity profiles of contacts with effective and noneffective stimulation were compared. RESULTS: Connectivity profiles of effective and noneffective contacts differed. Moreover, the connectivity profile for bradykinesia differed from that for rigidity, tremor, or dysarthria. Regarding bradykinesia, effective contacts were significantly more often connected with the ipsilateral superior cerebellar peduncle and the ipsilateral dentate nucleus, which correspond to the ipsilateral portion of the cerebellothalamocortical pathway. Rigidity was mitigated by stimulation of ascending brainstem and intralaminar thalamic connections. Tremor alleviation was related to connections with the internal capsule (anterior limb) and the pallidum. Dysarthric side effects were associated with connections to the supplementary motor area and the decussating cerebellothalamocortical pathway. INTERPRETATION: Whereas bradykinesia seems to be mitigated by stimulation of the ascending, ipsilateral cerebellothalamocortical pathway, stimulation of the descending corticopontocerebellar pathway may be ineffective. Rigidity, tremor, and dysarthric side effects seem to be influenced by different neural networks. ANN NEUROL 2019;85:852-864.

[Update on diagnostics and therapy of idiopathic Parkinson's disease]. / Neues zu Diagnostik und Therapie des idiopathischen Parkinson-Syndroms.

At least 300,000 people with idiopathic Parkinson's disease are living in Germany. Due to the demographic change the number of affected patients is expected to increase continuously. This article presents the evidence-based diagnostics and therapy of idiopathic Parkinson's disease. It provides an overview especially on new findings and developments in recent years.

The Swedish National Facility for Magnetoencephalography Parkinson's disease dataset.

Parkinson's disease (PD) is characterised by a loss of dopamine and dopaminergic cells. The consequences hereof are widespread network disturbances in brain function. It is an ongoing topic of investigation how the disease-related changes in brain function manifest in PD relate to clinical symptoms. We present The Swedish National Facility for Magnetoencephalography Parkinson's Disease Dataset (NatMEG-PD) as an Open Science contribution to identify the functional neural signatures of Parkinson's disease and contribute to diagnosis and treatment. The dataset contains whole-head magnetoencephalographic (MEG) recordings from 66 well-characterised PD patients on their regular dose of dopamine replacement therapy and 68 age- and sex-matched healthy controls. NatMEG-PD contains three-minute eyes-closed resting-state MEG, MEG during an active movement task, and MEG during passive movements. The data includes anonymised MRI for source analysis and clinical scores. MEG data is rich in nature and can be used to explore numerous functional features. By sharing these data, we hope other researchers will contribute to advancing our understanding of the relationship between brain activity and disease state or symptoms.

Oscillatory and non-oscillatory features of the magnetoencephalic sensorimotor rhythm in Parkinson's disease.

Parkinson's disease (PD) is associated with changes in neural activity in the sensorimotor alpha and beta bands. Using magnetoencephalography (MEG), we investigated the role of spontaneous neuronal activity within the somatosensory cortex in a large cohort of early- to mid-stage PD patients (N = 78) on Parkinsonian medication and age- and sex-matched healthy controls (N = 60) using source reconstructed resting-state MEG. We quantified features of the time series data in terms of oscillatory alpha power and central alpha frequency, beta power and central beta frequency, and 1/f broadband characteristics using power spectral density. Furthermore, we characterised transient oscillatory burst events in the mu-beta band time-domain signals. We examined the relationship between these signal features and the patients' disease state, symptom severity, age, sex, and cortical thickness. PD patients and healthy controls differed on PSD broadband characteristics, with PD patients showing a steeper 1/f exponential slope and higher 1/f offset. PD patients further showed a steeper age-related decrease in the burst rate. Out of all the signal features of the sensorimotor activity, the burst rate was associated with increased severity of bradykinesia, whereas the burst duration was associated with axial symptoms. Our study shows that general non-oscillatory features (broadband 1/f exponent and offset) of the sensorimotor signals are related to disease state and oscillatory burst rate scales with symptom severity in PD.

Cluster analysis reveals distinct patterns of saccade impairment and their relation to cognitive profiles in Parkinson's disease.

Saccade performance has been reported to be altered in Parkinson's disease (PD), however, with a large variability between studies as both motor and cognitive impairment interfere with oculomotor control. The aim of this study was to identify different patterns in saccade alterations in PD using a data-driven approach and to explore their relationship with cognitive phenotypes. Sixty-one participants with PD and 25 controls performed eye-tracking (horizontal and vertical prosaccades, antisaccades) and neuropsychological testing. Hierarchical cluster analysis was applied to the eye-tracking data to subsequently compare the clusters based on demographical, clinical and cognitive characteristics. The three identified clusters of saccade alterations differed in cognitive profiles from healthy controls, but not in PD-related motor symptoms or demographics. The rate of directive errors in the antisaccade task was increased in clusters 1 and 2. Further, cluster 1 was defined by a general disinhibition of reflexive saccades and executive dysfunction in the neuropsychological evaluation. In cluster 2, prolonged saccade latencies and hypometria were accompanied by multidomain cognitive impairment. The cluster 3 showed increased antisaccade latency and vertical hypometria despite lack of evidence for cognitive impairment. Our results suggest that there may be at least two opposing patterns of saccade alterations associated with cognitive impairment in PD, which may explain some of the contradictory results of previous studies.

High (130 Hz)- and mid (60 Hz)-frequency deep brain stimulation in the subthalamic nucleus differentially modulate response inhibition: A preliminary combined EEG and eye tracking study.

While deep brain stimulation (DBS) in the subthalamic nucleus (STN) improves motor functions in Parkinson's disease (PD), it may also increase impulsivity by interfering with the inhibition of reflexive responses. The aim of this study was to investigate if varying the pulse frequency of STN-DBS has a modulating effect on response inhibition and its neural correlates. For this purpose, 14 persons with PD repeated an antisaccade task in three stimulation settings (DBS off, high-frequency DBS (130 Hz), mid-frequency DBS (60 Hz)) in a randomized order, while eye movements and brain activity via high-density EEG were recorded. On a behavioral level, 130 Hz DBS stimulation had no effect on response inhibition measured as antisaccade error rate, while 60 Hz DBS induced a slight but significant reduction of directional errors compared with the DBS-off state and 130 Hz DBS. Further, stimulation with both frequencies decreased the onset latency of correct antisaccades, while increasing the latency of directional errors. Time-frequency domain analysis of the EEG data revealed that 60 Hz DBS was associated with an increase in preparatory theta power over a midfrontal region of interest compared with the off-DBS state which is generally regarded as a marker of increased cognitive control. While no significant differences in brain activity over mid- and lateral prefrontal regions of interest emerged between the 60 Hz and 130 Hz conditions, both stimulation frequencies were associated with a stronger midfrontal beta desynchronization during the mental preparation for correct antisaccades compared with DBS off-state which is discussed in the context of potentially enhanced proactive recruitment of the oculomotor network. Our preliminary findings suggest that mid-frequency STN-DBS may provide beneficial effects on response inhibition, while both 130 Hz- and 60 Hz STN-DBS may promote voluntary actions at the expense of slower reflexive responses.

Stimulation of non-motor subthalamic nucleus impairs selective response inhibition via prefrontal connectivity.

Given the inconsistent results in the past, there is an ongoing debate whether and how deep brain stimulation in the subthalamic nucleus modifies cognitive control processes like response inhibition in persons with Parkinson's disease. In this study, we examined how the location of the stimulation volume within the subthalamic nucleus affects the performance in an antisaccade task but also how its structural connectivity is related to response inhibition. Antisaccade error rates and latencies were collected in 14 participants on and off deep brain stimulation in a randomized order. Stimulation volumes were computed based on patient-specific lead localizations using preoperative MRI and postoperative CT scans. Structural connectivity of the stimulation volumes with pre-defined cortical oculomotor control regions as well as whole-brain connectivity was estimated using a normative connectome. We showed that the detrimental effect of deep brain stimulation on response inhibition, measured as antisaccade error rate, depended upon the magnitude of the intersection of volumes of activated tissue with the non-motor subregion of the subthalamic nucleus and on its structural connectivity with regions of the prefrontal oculomotor network including bilateral frontal eye fields and right anterior cingulate cortex. Our results corroborate previous recommendations for avoidance of stimulation in the ventromedial non-motor subregion of the subthalamic nucleus which connects to the prefrontal cortex to prevent stimulation-induced impulsivity. Furthermore, antisaccades were initiated faster with deep brain stimulation when the stimulation volume was connected to fibres passing the subthalamic nucleus laterally and projecting onto the prefrontal cortex, indicating that improvement of voluntary saccade generation with deep brain stimulation may be an off-target effect driven by stimulation of corticotectal fibres directly projecting from the frontal and supplementary eye fields onto brainstem gaze control areas. Taken together, these findings could help implement individualized circuit-based deep brain stimulation strategies that avoid impulsive side effects while improving voluntary oculomotor control.

Pupil light reflex dynamics in Parkinson's disease.

Introduction: Visual disturbance is common symptom in Parkinson's disease (PD), and defective pupil light reflex (PLR) is an anticipated contributing factor that may be associated to the presence of autonomic dysfunction, which is a common non-motor feature of PD. Studies investigating the intercorrelation between PLR and dysautonomia in PD are limited. Methods: The aim of this study was to investigate differences of PLR parameters, measured by eye-tracker, between patients with PD, with and without signs of dysautonomia, and healthy controls (HC). In total, 43 HC and 50 patients with PD were recruited and PLR parameters were measured with Tobii Pro Spectrum, during a long (1,000 ms) and a short (100 ms) light stimulus. Presence of orthostatic hypotension (OH) was used as proxy marker of dysautonomia. Linear mixed-effects model and non-parametric comparative statistics were applied to investigate differences among groups. Results: Peak constriction velocity was slower in PD compared with HC, after adjustment for age and sex in the mixed model, and the difference was greater in the subgroup of PD with OH (unadjusted). Dilation amplitude and velocity were also gradually slower in HC vs. PD without OH vs. PD with OH (unadjusted for confounders). In the mixed model, age was significant predictor of dilation response. Discussion: Our results support previous observations on defective PLR in PD, evaluated with eye-tracker, and show a possible association with autonomic dysfunction. Further studies with more patients and rigorous evaluation of autonomic dysfunction are needed to validate these findings.

Neural correlates of impaired response inhibition in the antisaccade task in Parkinson's disease.

Deficits in response inhibition are a central feature of the highly prevalent dysexecutive syndrome found in Parkinson's disease (PD). Such deficits are related to a range of common clinically relevant symptoms including cognitive impairment as well as impulsive and compulsive behaviors. In this study, we explored the cortical dynamics underlying response inhibition during the mental preparation for the antisaccade task by recording magnetoencephalography (MEG) and eye-movements in 21 non-demented patients with early to mid-stage Parkinson's disease and 21 age-matched healthy control participants (HC). During the pre-stimulus preparatory period for antisaccades we observed: Taken together, the results indicate that alterations in pre-stimulus prefrontal alpha and beta activity hinder proactive response inhibition and in turn result in higher error rates and prolonged response latencies in PD.

Neurocognitive profile of adults with the Norrbottnian type of Gaucher disease.

INTRODUCTION: Gaucher disease (GD) is a monogenic, lysosomal storage disorder, classified according to the presence of acute (type 2), chronic (type 3), or no (type 1) neurological manifestations. The Norrbottnian subtype of neuronopathic GD type 3 (GD3) is relatively frequent in the northern part of Sweden. It exhibits a wide range of neurological symptoms but is characterized by extended life expectancy compared to GD3 in other countries. The aim of our study was to describe the cognitive profile of adult patients with Norrbottnian GD3. MATERIALS AND METHODS: Ten patients with GD3 (five males and five females) underwent neurocognitive testing with the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). RBANS consists of different short tests that assess Immediate Memory, Visuospatial and Constructional function, Language, Attention, and Delayed Memory. General neurological symptoms of the patients were assessed with the modified severity scoring tool. RESULTS: Patients (median age 41.5 range 24-57) performed lower than average in all cognitive domains. The overall index score was low (median 58.5, Interquartile range [IQR] 25.5), with the most profound deficit in attention (median 57, IQR 32.5) and immediate memory (median 76.5, IQR 13). Higher scores were found in language (median 83, IQR 21.5), delayed memory (median 81, IQR 41), and visuospatial/constructional function (median 86, IQR 32.35). CONCLUSION: Norrbottnian GD3 patients showed a unique neurocognitive profile with low overall performance, mostly derived from low scores in attention and memory domains whereas language and visuospatial/constructional ability were relatively spared.

Visual Perturbation Suggests Increased Effort to Maintain Balance in Early Stages of Parkinson's to be an Effect of Age Rather Than Disease.

Postural instability marks a prevalent symptom of Parkinson's disease (PD). It often manifests in increased body sway, which is commonly assessed by tracking the Center of Pressure (CoP). Yet, in terms of postural control, the body's Center of Mass (CoM), and not CoP is what is regulated in a gravitational field. The aim of this study was to explore the effect of early- to mid-stage PD on these measures of postural control in response to unpredictable visual perturbations. We investigated three cohorts: (i) 18 patients with early to mid-stage PD [Hoehn & Yahr stage (1-3); 1.94 ± 0.70]; (ii) a group of 15 age-matched controls (ECT); and (iii) a group of 12 young healthy adults (YCT). Participants stood on a force plate to track their CoP, while the movement of their entire body was recorded with a video-based motion tracking system to monitor their CoM. A moving room paradigm was applied through a head-mounted virtual reality headset. The stimulus consisted of a virtual tunnel that stretched in the anterior-posterior direction which either remained static or moved back and forth in an unpredictable fashion.We found differences in mean sway amplitude (MSA) and mean velocities of CoP and CoM between the groups under both conditions, with higher MSA of CoP and CoM for PD and higher mean velocities of both variables for PD and ECT when compared with YCT. Visual perturbation increased mean CoP velocity in all groups but did not have effects on mean CoM velocity or MSA. While being significantly lower for the young adults, the net effect of visual perturbation on mean CoP velocity was similar between patients with PD and age-matched controls. There was no effect of the visual perturbation on mean CoM velocity for any of the groups.Our simultaneous assessment of CoP and CoM revealed that postural control is reflected differently in CoM and CoP. As the motion of CoM remained mostly unaffected, all groups successfully counteracted the perturbation and maintained their balance. Higher CoP velocity for PD and ECT revealed increased corrective motion needed to achieve this, which however was similar in both groups. Thus, our results suggest increased effort, expressed in CoP velocity, to be an effect of age rather than disease in earlier stages of PD.

Age at Parkinson's disease onset modulates the effect of levodopa on response inhibition: Support for the dopamine overdose hypothesis from the antisaccade task.

The antisaccade task is an established eye-tracking paradigm to explore response inhibition. While many studies showed that antisaccade performance is impaired in Parkinson's disease (PD), the effect of dopaminergic medication is still an area of debate. According to the dopamine overdose hypothesis, intrinsic basal dopamine levels in ventral parts of the striatum determine whether levodopa intake has beneficial or detrimental effects on dopamine-dependent cognitive tasks. The objective of this study was therefore to explore the effect of several disease-related factors on changes in antisaccade performance after levodopa intake in PD. Thirty-five individuals with PD (and 30 healthy controls) performed antisaccades in OFF and ON medication state. Multiple linear regressions were calculated to predict the change in antisaccade latency, directive errors and express saccade rate based on age at PD onset, disease duration, levodopa-equivalent daily dose, motor symptom severity and executive functions. Levodopa intake did not alter antisaccade performance on a group level. However, the effect of levodopa was differentially modulated by age at PD onset and motor symptom severity. Earlier disease onset and milder motor symptoms in OFF medication state were associated with reduced response inhibition capacity after levodopa intake measured as increased express saccade and error rates. Our results indicate that levodopa may have opposing effects on oculomotor response inhibition dependent on the age at PD onset and motor disease severity. Assuming less dopaminergic loss in ventral parts of the striatum in early compared to late onset PD, these findings support the dopamine overdose hypothesis.

Imaging-based programming of subthalamic nucleus deep brain stimulation in Parkinson's disease.

BACKGROUND: The need for imaging-guided optimization of Deep Brain Stimulation (DBS) parameters is increasing with recent developments of sophisticated lead designs offering highly individualized, but time-consuming and complex programming. OBJECTIVE: The objective of this study was to compare changes in motor symptoms of Parkinson's Disease (PD) and the corresponding volume of the electrostatic field (VEsF) achieved by DBS programming using GUIDE XT™, a commercially available software for visualization of DBS leads within the patient-specific anatomy from fusions of preoperative magnetic resonance imaging (MRI) and postoperative computed tomography (CT) scans, versus standard-of-care clinical programming. METHODS: Clinical evaluation was performed to identify the optimal set of parameters based on clinical effects in 29 patients with PD and bilateral directional leads for Subthalamic Nucleus (STN) DBS. A second DBS program was generated in GUIDE XT™ based on a VEsF optimally located within the dorsolateral STN. Reduction of motor symptoms (Movement Disorders Society Unified Parkinson's Disease Rating Scale, MDS-UPDRS) and the overlap of the corresponding VEsF of both programs were compared. RESULTS: Clinical and imaging-guided programming resulted in a significant reduction in the MDS-UPDRS scores compared to off-state. Motor symptom control with GUIDE XT™-derived DBS program was non-inferior to standard clinical programming. The overlap of the two VEsF did not correlate with the difference in motor symptom reduction by the programs. CONCLUSIONS: Imaging-guided programming of directional DBS leads using GUIDE XT™ is possible without computational background and leads to non-inferior motor symptom control compared with clinical programming. DBS programs based on patient-specific imaging data may thus serve as starting point for clinical testing and may promote more efficient DBS programming.

Natural Reading in Parkinson's Disease With and Without Mild Cognitive Impairment.

Background: Patients with Parkinson's disease (PD) show eye movement abnormalities and frequently complain about difficulties in reading. So far, it is unclear whether basal ganglia dysfunction or cognitive impairment has a greater impact on eye movements during reading. Objective: To analyze eye movement behavior during a natural reading task with respect to cognitive state and dopaminergic therapy in PD and healthy controls. Methods: Eye movements of 59 PD patients and 29 age- and education-matched healthy controls were recorded during mute, self-paced reading of a text. 25 cognitively normal PD patients performed the task additionally in off medication state. Clinical assessment included a comprehensive neuropsychological test battery and the motor section of MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Results: PD-mild cognitive impairment (MCI) was diagnosed in 21 patients. Reading speed was significantly reduced in PD-MCI compared to healthy controls and PD patients without MCI due to higher numbers of progressive saccades. Cognitively intact PD patients showed no significant alterations of reading speed or eye movement pattern during reading. The fixation duration tended to be prolonged in PD compared to healthy controls and decreased significantly after levodopa intake. Scores for executive functions, attention, and language correlated with reading speed in the PD group. Conclusion: The present study is the first to reveal (1) reduced reading speed with altered reading pattern in PD with MCI and (2) a relevant impact of levodopa on fixation duration during reading in PD. Further research is needed to determine whether therapeutic interventions, e.g., levodopa or neuropsychological training, improve the subjective reading experience for patients with PD.

Visualization of volume of tissue activated modeling in a clinical planning system for deep brain stimulation.

BACKGROUND: Pathway activating models try to describe stimulation spread in deep brain stimulation (DBS). Volume of tissue activated (VTA) models are simplified model variants allowing faster and easier computation. Our study aimed to investigate, how VTA visualization can be integrated into a clinical workflow applying directional electrodes using a standard clinical DBS planning system. METHODS: Twelve patients underwent DBS, using directional electrodes for bilateral subthalamic nucleus (STN) stimulation in Parkinson's disease. Preoperative 3T magnetic resonance imaging was used for automatic visualization of the STN outline, as well as for fiber tractography. Intraoperative computed tomography was used for automatic lead detection. The Guide XT software, closely integrated into the DBS planning software environment, was used for VTA calculation and visualization. RESULTS: VTA visualization was possible in all cases. The percentage of VTA covering the STN volume ranged from 25% to 100% (mean ± standard deviation: 60% ± 25%) on the left side and from 0% to 98% (51% ± 30%) on the right side. The mean coordinate of all VTA centers was: 12.6 ± 1.2 mm lateral, 2.1 ± 1.2 mm posterior, and 2.3 ± 1.4 mm inferior in relation to the midcommissural point. Stimulation effects can be compared to the VTA visualization in relation to surrounding structures, potentially facilitating programming, which might be especially beneficial in case of suboptimal lead placement. CONCLUSIONS: VTA visualization in a clinical planning system allows an intuitive adjustment of the stimulation parameters, supports programming, and enhances understanding of effects and side effects of DBS.