Gerd-Helge Schneider

• Charité Universitätsmedizin Berlin

People with Parkinsons disease suffer from levodopa-induced dyskinesia, adversely to chronic dopaminergic medication. These involuntary movements affect quality of life and are linked to lowered motor inhibition in the cortico-basal-ganglia motor network during hyperdopaminergic states. Several cortical and subcortical spectral biomarkers are assoc...

Deep brain stimulation is a brain circuit intervention that can modulate distinct neural pathways for the alleviation of neurological symptoms in patients with brain disorders. In Parkinson’s disease, subthalamic deep brain stimulation clinically mimics the effect of dopaminergic drug treatment, but the shared pathway mechanisms on cortex – basal g...

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in patients with Parkinsons disease. Using functional MRI, optimal DBS response networks have been characterized. However, neural activity associated with Parkinsonian symptoms is magnitudes faster than what can be resolved by this method. While both spatial and t...

Finely tuned gamma (FTG) oscillations from the subthalamic nucleus (STN) and cortex in Parkinson’s disease (PD) patients undergoing deep brain stimulation (DBS) are often associated with dyskinesia. Recently it was shown that DBS entrains gamma activity at 1:2 of the stimulation frequency; however, the functional role of this signal is not yet full...

Subthalamic deep brain stimulation (STN-DBS) provides unprecedented spatiotemporal precision for the treatment of Parkinson's disease (PD), allowing for direct real-time state-specific adjustments. Inspired by findings from optogenetic stimulation in mice, we hypothesized that STN-DBS effects on movement speed depend on ongoing movement kinematics...

Background Subthalamic beta oscillations are a biomarker for bradykinesia and rigidity in Parkinson's disease (PD), incorporated as a feedback signal in adaptive deep brain stimulation with potential for guiding electrode contact selection. Understanding their longitudinal stability is essential for successful clinical implementation. Objectives W...

Parkinson's disease is linked to increased beta oscillations in the subthalamic nucleus, which correlate with motor symptoms. However, findings across studies have varied. Our standardized analysis of multicenter datasets reveals that insufficient sample sizes contributed to these discrepancies - a challenge we address by pooling datasets into one...

Background Pallidal neurostimulation is an effective treatment for severe isolated dystonia, but long‐term data from clinical trials are lacking. Objectives To evaluate long‐term efficacy and safety of pallidal neurostimulation in patients with isolated generalized or segmental dystonia. Methods Extension study of the prospective multicenter tria...

Subthalamic (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) patients not only improves kinematic parameters of movement but also modulates cognitive control in the motor and non‐motor domain, especially in situations of high conflict. The objective of this study was to investigate the relationship between DBS‐induced changes in funct...

Dystonia is a hyperkinetic movement disorder that has been associated with an imbalance towards the direct pathway between striatum and internal pallidum, but the neuronal underpinnings of this abnormal basal ganglia pathway activity remain unknown. Here, we report invasive recordings from ten dystonia patients via deep brain stimulation electrodes...

Background Segmented electrodes for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson’s disease (PD) enable directional current steering leading to expanded programming options. Objective This retrospective study covering a longitudinal period of up to 7 years compares the efficacy of segmented and non-segmented leads in m...

Background Postoperative delirium (POD) is a serious complication following deep brain stimulation (DBS) but only received little attention. Its main risk factors are higher age and preoperative cognitive deficits. These are also main risk factors for long-term cognitive decline after DBS in Parkinson’s disease (PD). Objective To identify risk fac...

The ability to initiate volitional action is fundamental to human behaviour. Loss of dopaminergic neurons in Parkinson's disease is associated with impaired action initiation, also termed akinesia. Both dopamine and subthalamic deep brain stimulation (DBS) can alleviate akinesia, but the underlying mechanisms are unknown. An important question is w...

Finely tuned gamma oscillations have been recorded from the subthalamic nucleus and cortex in Parkinson's disease patients undergoing deep brain stimulation and are often associated with dyskinesia. More recently, it was shown that deep brain stimulation entrains finely tuned gamma to 1/2 of the stimulation frequency; however, the functional role o...

Deep brain stimulation (DBS) is a brain circuit intervention that can modulate distinct neural pathways for the alleviation of neurological symptoms in patients with brain disorders. In Parkinson's disease, subthalamic DBS clinically mimics the effect of dopaminergic drug treatment, but the shared pathway mechanisms on cortex-basal ganglia networks...

Subthalamic beta band activity (13–35 Hz) is known as a real-time correlate of motor symptom severity in Parkinson’s disease (PD) and is currently explored as a feedback signal for closed-loop deep brain stimulation (DBS). Here, we investigate the interaction of movement, dopaminergic medication, and deep brain stimulation on subthalamic beta activ...

Background Additional stimulation of the substantia nigra (SNr) has been proposed to target axial symptoms and gait impairment in patients with Parkinson’s disease (PD). Objective This study aimed to characterize effects of combined deep brain stimulation (DBS) of the subthalamic nucleus (STN) and SNr on gait performance in PD and to map stimulati...

The ability to initiate movement is fundamental to human behavior. Loss of dopaminergic neurons in Parkinson’s disease (PD) is associated with impaired movement initiation, also termed akinesia. Dopamine and subthalamic deep brain stimulation (DBS) can alleviate akinesia, but the underlying mechanisms are unknown. We recorded invasive neural activi...

Subthalamic beta band activity (13-35 Hz) is known as a real-time correlate of motor symptom severity in Parkinson’s disease (PD) and is currently explored as a feedback signal for closed-loop deep brain stimulation (DBS). Here, we investigate the interaction of movement, dopaminergic medication, and deep brain stimulation on subthalamic beta activ...

Background Deep brain stimulation ( DBS ) is an effective treatment option for patients with Parkinson's disease ( PD ). However, clinical programming remains challenging with segmented electrodes. Objective Using novel sensing‐enabled neurostimulators, we investigated local field potentials ( LFPs ) and their modulation by DBS to assess whether e...

Dystonia is a hyperkinetic movement disorder that has been associated with an imbalance towards the direct pathway between striatum and internal pallidum. To date, the neuronal underpinnings of this abnormal basal ganglia pathway activity and its link to dystonic symptoms remain unknown. Here, we report invasive recordings from ten dystonia patient...

Background: Deep brain stimulation (DBS) has been increasingly used in the management of dyskinetic cerebral palsy (DCP). Data on long-term effects and the safety profile are rare. Objectives: We assessed the efficacy and safety of pallidal DBS in pediatric patients with DCP. Methods: The STIM-CP trial was a prospective, single-arm, multicente...

Background: Pallidal deep brain stimulation (DBS) effectively alleviates symptoms in dystonia patients, but may induce movement slowness as a side-effect. In Parkinson's disease, hypokinetic symptoms have been associated with increased beta oscillations (13-30 Hz). We hypothesize that this pattern is symptom-specific, thus accompanying DBS-induced...

Background: Subthalamic nucleus (STN) beta (13 - 35 Hz) activity is a biomarker reflecting motor state in Parkinson's disease (PD). Adaptive deep brain stimulation (DBS) aims to use beta activity for therapeutic adjustments, but many aspects of beta activity in real-life situations are unknown. Objective: The aim was to investigate Christmas-rel...

Pathologically increased beta power has been described as a biomarker for Parkinson’s disease (PD) and related to prolonged bursts of subthalamic beta synchronization. Here, we investigate the association between subthalamic beta dynamics and motor impairment in a cohort of 106 Parkinson’s patients in the ON- and OFF-medication state, using two dif...

Introduction and goal: The investigation of gender differences in treatment response is crucial for effective personalized therapies. With only 30%, women are underrepresented in trials for deep brain stimulation (DBS) in Parkinson's disease (PD). It is therefore important to evaluate gender-specific outcomes of DBS in PD in order to improve thera...

Background: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone. Objective: This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility asse...

Background Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is highly effective in controlling motor symptoms in patients with Parkinson's disease. However, correct selection of stimulation parameters is pivotal to treatment success and currently follows a time-consuming and demanding trial-and-error process. We aimed to assess treatme...

Introduction Subthalamic Deep Brain Stimulation (STN-DBS) is a safe and well-established therapy for the management of motor symptoms refractory to best medical treatment in patients with Parkinson's disease (PD). Early intervention is discussed especially for Early-onset PD (EOPD) patients that present with an age of onset ≤ 45–50 years and see th...

Purpose There is a high demand on spinal surgery in patients with Parkinson’s disease (PD) but the results are sobering. Although detailed clinical and radiological diagnostics were carried out with great effort and expense, the biodynamic properties of the spine of PD patients have never been considered. We propose a noninvasive method to quantify...

Objectives The aim of this study was to identify and systematically analyze relevant literature on surgical site infections (SSIs) associated with implantable pulse generator (IPG) procedures for deep brain stimulation (DBS). Materials and Methods In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,...

Deep brain stimulation (DBS) has become a well-established treatment modality for Parkinson’s disease (PD), especially regarding motor fluctuations, dyskinesias, and tremor. Although postural abnormalities (i.e., Camptocormia [CC] and Pisa syndrome [Pisa]) are known to be a major symptom of PD as well, the influence of DBS on postural abnormalities...

Introduction Pallidal DBS is an established treatment for severe isolated dystonia. However, its use in disabling and treatment-refractory tardive syndromes (TS) including tardive dyskinesia and tardive dystonia (TD) is less well investigated and long-term data remain sparse. This observational study evaluates long-term effects of deep brain stimul...

Current efforts to optimize subthalamic deep brain stimulation in Parkinson's disease patients aim to harness local oscillatory activity in the beta frequency range (13–35 Hz) as a feedback-signal for demand-based adaptive stimulation paradigms. A high prevalence of beta peak activity is prerequisite for this approach to become routine clinical pra...

Background Pathologically increased beta power has been described as a biomarker for Parkinson’s disease (PD) and related to prolonged bursts of subthalamic beta synchronization. Methods Here, we investigate the association between subthalamic beta dynamics and motor impairment in a cohort of 106 Parkinson’s patients in the ON- and OFF-medication...

Introduction: Dystonia is a network disorder in which aberrant signaling maybe associated with an imbalance between direct and indirect pathway activity. Invasive recordings from the internal pallidum (Globus pallidus internus, GPi), the major output structure of the basal ganglia, have described exaggerated oscillatory activity in the low frequenc...

Introduction Using cognitive control, humans can flexibly influence behavior based on set goals, which includes overriding impulses by inhibiting automatic responses in a conflicting environment. The basal ganglia have been hypothesized as an integral part in a cortico-subcortical network that modulates inhibitory control in both motor and non-moto...

Introduction: Beta power in subthalamic local field potentials (LFPs) is a well established biomarker for bradykinesia-rigidity in idiopathic Parkinson's Disease (IPS) and is a promising feedback signal for adaptive deep brain stimulation (DBS). However, the effect of directional stimulation on this biomarker has not yet been elaborated. With new D...

Background Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is highly effective in controlling motor symptoms in patients with Parkinson’s Disease (PD). However, correct selection of stimulation parameters is pivotal to treatment success and currently follows a time-consuming and demanding trial-and-error process. We conducted a double...

Dystonia is a debilitating disease with few treatment options. One effective option is deep brain stimulation (DBS) to the internal pallidum. While cervical and generalized forms of isolated dystonia have been targeted with a common approach to the posterior third of the nucleus, large-scale investigations regarding optimal stimulation sites and po...

Adaptive deep brain stimulation (aDBS) is a promising concept for feedback-based neurostimulation, with the potential of clinical implementation with the sensing-enabled Percept neurostimulator. We aim to characterize chronic electrophysiological activity during stimulation and to validate beta-band activity as a biomarker for bradykinesia. Subthal...

Objective With a growing appreciation for interindividual anatomical variability and patient‐specific brain connectivity, advanced imaging sequences offer the opportunity to directly visualize anatomical targets for deep brain stimulation (DBS). The lack of quantitative evidence demonstrating their clinical utility, however, has hindered their broa...

Background: With increasing prevalence of Parkinson's disease (PD), instrumentation surgery of the thoracolumbar spine of PD patients grows in importance. Poor operative results with high rates of revision surgery have been reported. The goal of this study was to compare the biomechanical complications of thoracolumbar instrumentation surgery of p...

Background: Patients with dyskinetic cerebral palsy are often severely impaired with limited treatment options. The effects of deep brain stimulation (DBS) are less pronounced than those in inherited dystonia but can be associated with favorable quality of life outcomes even in patients without changes in dystonia severity. Objective: The aim is...

Introduction Subthalamic DBS in Parkinson's disease has been associated with cognitive decline in few cases. Volume reduction of the nucleus basalis of Meynert (NBM) seems to precede cognitive impairment in Parkinson's disease. In this retrospective study, we evaluated NBM volume as a predictor of cognitive outcome 1 year after subthalamic DBS. Me...

Objective: With a growing appreciation for interindividual anatomical variability and patient-specific brain connectivity, advanced imaging sequences offer the opportunity to directly visualize anatomical targets for deep brain stimulation (DBS). The lack of quantitative evidence demonstrating their clinical utility, however, has hindered their bro...

Introduction: Deep brain stimulation (DBS) has become a well-established treatment modality for a variety of conditions over the last decades. Multiple surgeries are an essential part in the postoperative course of DBS patients if nonrechargeable implanted pulse generators (IPGs) are applied. So far, the rate of subclinical infections in this fiel...

Dystonia is a debilitating disease with few conservative treatment options but many types of isolated dystonia can be effectively treated using deep brain stimulation (DBS) to the internal pallidum. While cervical and generalized forms of isolated dystonia have been targeted with a common approach to the posterior third of the nucleus, large-scale...

Introduction: Deep brain stimulation (DBS) is a highly efficacious treatment for essential tremor (ET). Still, the optimal anatomical target in the (sub)thalamic area is a matter of debate. The aim of this study was to determine the optimal target of DBS for ET regarding beneficial clinical outcome and impact on activities of daily living as well...

Introduction: Deep brain stimulation (DBS) has been an established surgical procedure in the field of functional neurosurgery for many years. The experimental electrophysiological method of local field potential (LFP) recordings in postsurgically externalized patients has made substantial contributions to the better understanding of pathophysiolog...

Background Biomarkers for future adaptive deep brain stimulation still need evaluation in clinical routine. Here, we aimed to assess stimulation‐induced modulation of beta band activity and clinical symptoms in a Parkinson’s disease patient during chronic neuronal sensing using a novel implantable pulse generator. Methods Subthalamic activity was...

Objective Investigate the relationship between implant location and neural signal contamination with electrocardiographic (ECG) activity in bidirectional implantable neurostimulation systems used to evaluate closed-loop stimulation for neurological diseases. Methods Electric field modelling was used to predict the relevance of implant location to...

Objective Observational study to evaluate long‐term effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) and the ventral intermediate thalamic nucleus (VIM) on patients with medically refractory myoclonus dystonia (MD). Background More recently, pallidal as well as thalamic DBS have been applied successfully in MD but long...

The subthalamic nucleus is part of a global stopping network that also includes the presupplementary motor area and inferior frontal gyrus of the right hemisphere. In Parkinson's disease, subthalamic deep brain stimulation improves movement initiation and velocity, but its effect on stopping of ongoing movement is unknown. Here, we examine the rela...

Objective Observational study to evaluate the long-term motor and non-motor effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) on medically refractory dystonia. Background Dystonia is a chronic disease affecting mainly young patients with a regular life expectancy and lifelong need for therapy. Pallidal DBS is an establi...

A computer reconstruction summarizing data from patients with deep brain stimulation of the subthalamic nucleus (orange) for Parkinson disease, showing fiber tracts, identified by diffusion tensor imaging, that were associated with stimulation sites that improved (red) or worsened (blue) depressive symptoms. For details see Irmen et al., pp. 962–97...

Objective Subthalamic nucleus deep brain stimulation (STN‐DBS) in Parkinson's disease (PD) not only stimulates focal target structures but also affects distributed brain networks. The impact this network modulation has on non‐motor DBS effects is not well‐characterized. By focusing on the affective domain, we systematically investigate the impact o...

Background: In frame-based stereotactic surgery, intraoperative imaging is crucial. It generally follows a workflow including preoperative MRI and intraoperative frame-based CT. The intraoperative transport of the anesthetized and intubated patient to and from the CT unit can be time-consuming and cumbersome. Here, we report the first 50 patients...

Background: Deep brain stimulation (DBS) is an approved therapy option for movement disorders such as Parkinson's disease (PD), essential Tremor (ET), and dystonia. While current research focuses on rechargeable implantable pulse generators (IPGs), little is known about changes of the motor functions after IPG replacement and the consequences of a...

Objective Subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s Disease (PD) not only stimulates focal target structures but also affects distributed brain networks. The impact this network modulation has on non-motor DBS effects is not well characterized. By focusing on the affective domain, we systematically investigate the impact o...

Background: Programming algorithms have never been tested for outcome. The EARLYSTIM study showed superior outcomes of deep brain stimulation of the subthalamic nucleus (STN-DBS) over best medical treatment in early Parkinson's disease (PD). Patients were programmed according to common guidelines but customized for each patient. Methods: Stimula...

Deep brain stimulation of the internal globus pallidus is a highly effective and established therapy for primary generalized and cervical dystonia, but therapeutic success is compromised by a non-responder rate of up to 25%, even in carefully-selected groups. Variability in electrode placement and inappropriate stimulation settings may account for...

Background: Data on pediatric DBS is still limited because of small numbers in single center series and lack of systematic multi-center trials. Objectives: We evaluate short- and long-term adverse events (AEs) of patients undergoing deep brain stimulation (DBS) during childhood and adolescence. Methods: Data collected by the German registry on...

Localization of highest beta power.

Burst properties within movement blocks.

Normal cognition is an established selection criteria for subthalamic (STN) deep brain stimulation (DBS) in Parkinson’s disease (PD), while concern has been raised as to aggravated cognitive decline in PD patients following STN-DBS. The present longterm study investigates cognitive status in all patients (n = 104) suffering from PD, who were treate...

Bradykinesia is reported to correlate with subthalamic beta power (13–35 Hz) recorded at rest in Parkinson's disease (PD). Pilot studies suggest adaptive deep brain stimulation triggered by amplitude threshold crossings of beta activity defined at rest is effective. This is puzzling, given that beta is suppressed during repetitive movements when br...

Objective: To investigate predictors for improvement of disease-specific quality of life (QOL) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) with early motor complications. Methods: We performed a secondary analysis of data from the previously published EARLYSTIM study, a prospective randomized tr...

Background STN‐DBS effectively treats motor symptoms of advanced PD. Nonmotor cognitive symptoms, such as impaired impulse control or decision making, may either improve or worsen with DBS. A potential mediating factor of DBS‐induced modulation of cognition is the electrode position within the STN with regard to functional subareas of parallel moto...

Background: Exaggerated beta power has been discussed as a disease‐specific biomarker for Parkinson's disease (PD) and has recently been suggested to rely on prolonged bursts of subthalamic beta synchronization. Objective: In this study, we test whether prolonged bursts are disease specific for beta activity in PD by comparison to oscillatory activ...

Introduction: Growing evidence suggests that pallidal deep brain stimulation represents a potential new therapeutic avenue in tardive dystonia/dyskinesia, but controlled and blinded randomized studies (RCT) are missing. The present RCT compares dystonia/dyskinesia severity of pallidal neurostimulation in patients with tardive dystonia using a dela...

Dopamine exerts modulatory signals on cortex-basal ganglia circuits to enable flexible motor control. Parkinson's disease is characterized by a loss of dopaminergic innervation in the basal ganglia leading to complex motor and non-motor symptoms. Clinical symptom alleviation through dopaminergic medication and deep brain stimulation in the subthala...

We set out to investigate whether beta oscillations in the human basal ganglia are modulated during reinforcement learning. Based on previous research, we assumed that beta activity might either reflect the magnitudes of individuals’ received reinforcements (reinforcement hypothesis), their reinforcement prediction errors (dopamine hypothesis) or t...

Background: Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson's disease, reports on behavioural outcomes are controversial, which represents a major challenge when counselling candidates for subthalamic stimulation. We aimed to assess changes in behaviour in patients with Parkinson's disease receiving...