Andrea A Kühn

Charité Universitätsmedizin Berlin | Charité · Department of Neurology with Chair in Experimental Neurology/BNIC

The dichotomy between the hypo-versus hyperkinetic nature of Parkinson’s disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. Investigate differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections. GPi neurons were...

The dichotomy between the hypo-versus hyperkinetic nature of Parkinson’s disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. Investigate differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections. GPi neurons were...

Obesity is an enormous health problem, and many patients do not respond to any of the available therapies. Deep brain stimulation (DBS) is currently investigated as a potential treatment for morbid obesity. In this study, we tested the hypothesis that high-frequency DBS targeting the nucleus accumbens (NAc) shell region reduces food intake and weig...

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...

Background Progressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients. Objectives To explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegene...

Parkinson’s disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the inves...

Parkinson’s disease (PD) is associated with excessive beta activity in the basal ganglia. Brain sensing implants aim to leverage this biomarker for demand-dependent adaptive stimulation. Sleep disturbance is among the most common non-motor symptoms in PD, but its relationship with beta activity is unknown. To investigate the clinical potential of b...

Objective In the fourth year of the COVID-19 pandemic, mortality rates decreased, but the risk of neuropsychiatric disorders remained the same, with a prevalence of 3.8% of pediatric cases, including movement disorders (MD) and ataxia. Methods In this study, we report on a 10-year-old girl with hemichorea after SARS-CoV-2 infection and immunostain...

Background: Protein synthesis is a tightly controlled process, involving a host of translation-initiation factors and microRNA-associated repressors. Variants in the translational regulator EIF2AK2 were first linked to neurodevelopmental-delay phenotypes, followed by their implication in dystonia. Recently, de novo variants in EIF4A2, encoding euk...

Background Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective and evidence-based treatment for idiopathic Parkinson's disease (iPD). A minority of patients does not sufficiently benefit from STN-DBS. Objective The predictive validity of the levodopa challenge for individual patients is analyzed. Methods Data from patients...

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...

In patients with Parkinson’s disease (PD), suppression of beta and increase in gamma oscillations in the subthalamic nucleus (STN) have been associated with both levodopa treatment and motor functions. Recent results suggest that modulation of the temporal dynamics of theses oscillations (bursting activity) might contain more information about path...

Introduction: Deep brain stimulation (DBS) is an established treatment in patients of various ages with pharmaco-resistant neurological disorders. Surgical targeting and postoperative programming of DBS depend on the spatial location of the stimulating electrodes in relation to the surrounding anatomical structures, and on electrode connectivity t...

Bradykinesia is a cardinal hallmark of Parkinson’s disease (PD). Improvement in bradykinesia is an important signature of effective treatment. Finger tapping is commonly used to index bradykinesia, albeit these approaches largely rely on subjective clinical evaluations. Moreover, recently developed automated bradykinesia scoring tools are proprieta...

Introduction: Dystonia is a movement disorder of variable etiology and clinical presentation and is accompanied by tremor in about 50% of cases. Monogenic causes in dystonia are rare, but also in the group of non-monogenic dystonias 10-30% of patients report a family history of dystonia. This points to a number of patients currently classified as...

Deep brain stimulation (DBS) is an effective treatment and has provided unique insights into the dynamic circuit architecture of brain disorders. This Review illus- trates our current understanding of the pathophysiology of movement disorders and their underlying brain circuits that are modulated with DBS. It proposes princi- ples of pathological n...

The frontal cortex is involved in motor, cognitive, and affective brain functions. In humans, however, neuroanatomy-function mappings are predominantly derived from correlative neuroimaging studies. Hence, exactly which frontal domains causally mediate which function remains largely elusive. Herein, we leverage a strategy that allows for causal inf...

Introduction Deep brain stimulation (DBS) is an established treatment in patients with pharmaco-resistant neurological disorders of different ages. Surgical targeting and postoperative programming of DBS depend on the spatial location of the stimulating electrodes in relation to the surrounding anatomical structures and on electrode connectivity to...

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...

Every decision that we make involves a conflict between exploiting our current knowledge of an action's value or exploring alternative courses of action that might lead to a better, or worse outcome. The sub-cortical nuclei that make up the basal ganglia have been proposed as a neural circuit that may contribute to resolving this explore-exploit 'd...

Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of cl...

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...

Background Inpatient as well as outpatient care does often not meet PD-patients’ individual needs. Introduction Day-clinic concepts encompassing a multidisciplinary team as well as therapy adjustments accompanying everyday demands aim at filling this gap. Methods This is a retrospective study on short-term effects of a 3 week multidisciplinary re...

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...

Technological advances of Deep Brain Stimulation (DBS) within the subthalamic nucleus (STN) for Parkinson’s disease (PD) provide increased programming options with higher programming burden. Reducing the effort of DBS optimization requires novel programming strategies. The objective of this study was to evaluate the feasibility of a semi-automatic...

The first commercially sensing enabled deep brain stimulation (DBS) devices for the treatment of movement disorders have recently become available. In the future, such devices could leverage machine learning based brain signal decoding strategies to individualize and adapt therapy in real-time. As multi-channel recordings become available, spatial...

Deep brain stimulation (DBS) provides symptomatic relief in a growing number of neurological indications, but local synaptic dynamics in response to electrical stimulation related to the DBS mechanism of action have not been fully characterized.

The temporal discrimination threshold (TDT) has been established as a biomarker of impaired temporal processing and endophenotype in various forms of focal dystonia patients, such as cervical dystonia, writer’s cramp or blepharospasm. The role of TDT in musician’s dystonia (MD) in contrast is less clear with preceding studies reporting inconclusive...

Background Deep brain stimulation (DBS) provides symptomatic relief in a growing number of neurological indications, but local synaptic dynamics in response to electrical stimulation that may relate to its mechanism of action have not been fully characterized. Objective The objectives of this study were to (1) study local synaptic dynamics during...

Background: Deep brain stimulation (DBS) is an established therapy for patients with Parkinson’s disease. In silico computer models for DBS hold the potential to inform a selection of stimulation parameters. In recent years, the focus has shifted towards DBS-induced firing in myelinated axons, deemed particularly relevant for the external modulatio...

Purpose The decision for subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD) relies on clinical predictors. Whether genetic variables could predict favourable or unfavourable decisions is under investigation. Objective First, we aimed to reproduce the previous observation that SNCA rs356220 was associated with favourable STN-D...

Deep brain stimulation procedures offer an invaluable opportunity to study disease through intracranial recordings from awake patients. Here, we address the relationship between single-neuron and aggregate-level (local field potential; LFP) activities in the subthalamic nucleus (STN) and thalamic ventral intermediate nucleus (Vim) of patients with...

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,...

Lead-DBS is an open-source, semi-automatized and widely applied software tool facilitating precise localization of deep brain stimulation electrodes both in native as well as in standardized stereotactic space. While automatized preprocessing steps within the toolbox have been tested and validated in previous studies, the interrater reliability in...

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, suing two di...

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...

Beta-band activity in the subthalamic local field potential (LFP) is correlated with Parkinson’s disease (PD) symptom severity and is the therapeutic target of deep brain stimulation (DBS). While beta fluctuations in PD patients are well characterized on shorter timescales, it is not known how beta activity evolves around the diurnal cycle, outside...

Background Gait disturbances are frequent side effects related to chronic thalamic deep brain stimulation (DBS) that may persist beyond cessation of stimulation. Objective We investigate the temporal dynamics and clinical effects of an overnight unilateral withdrawal of DBS on gait disturbances. Methods 10 essential tremor (ET) patients with gait...

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...

This review is part of the series on the clinical neurophysiology of movement disorders. It focuses on Parkinson’s disease and parkinsonism. The topics covered include the pathophysiology of tremor, rigidity and bradykinesia, balance and gait disturbance and myoclonus in Parkinson’s disease. The use of electroencephalography, electromyography, long...

Background: Deep Brain Stimulation (DBS) electrode implant trajectories are stereotactically defined using preoperative neuroimaging. To validate the correct trajectory, microelectrode recordings (MER) or local field potential recordings (LFP) can be used to extend neuroanatomical information (defined by magnetic resonance imaging) with neurophysio...

Computation of the instantaneous phase and amplitude via the Hilbert Transform is a powerful tool of data analysis. This approach finds many applications in various science and engineering branches but is not proper for causal estimation because it requires knowledge of the signal’s past and future. However, several problems require real-time estim...

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 Adaptive deep brain stimulation (DBS) aims at improving DBS therapy by adjusting stimulation amplitude to patient specific biomarkers tracked in real-time. In Parkinson’s disease (PD), a promising closed-loop approach exploits fast fluctuations of beta power (beta bursts) in subthalamic local field potentials (LFP). With this method, s...

Introduction: Neurocircuits are involved in the motor, cognitive, and affective dysfunctions of multiple brain disorders. Functional segregation into these domains has been widely defined on a fronto-cortical basis. However, despite considerable interaction, these functional domains remain partitioned to some extent at (sub)thalamic levels (1). To...

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: Tremor is defined as an involuntary, rhythmic oscillatory movement of a body part and represents one of the most common symptoms in movement disorders, existing across several diseases. Particularly, in advanced states of tremor-related diseases such as Parkinson’s disease (PD) and Essential tremor syndrome (ET), response to pharmacot...

Background: Deep brain stimulation (DBS) provides symptomatic relief in a growing number of neurological indications, but local synaptic dynamics in response to electrical stimulation that may relate to its mechanism of action have not been fully characterized. Objective: The objectives of this study were to (1) study local synaptic dynamics during...

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...

Question: Finding the optimal deep brain stimulation (DBS) parameters out of a multitude of possible combinations by trial-and-error is time-consuming and requires highly trained medical personnel. We developed an automated algorithm to identify optimal stimulation settings in Parkinson’s disease (PD) patients treated with subthalamic nucleus (STN)...