Andrea A Kühn

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

Prof. Dr. med.

About

487
Publications
94,932
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15,378
Citations
Additional affiliations
January 2007 - present
Charité Universitätsmedizin Berlin
Position
  • Consultant
July 2002 - September 2007
University College London

Publications

Publications (487)
Article
Full-text available
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...
Article
Full-text available
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...
Article
Full-text available
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...
Article
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...
Article
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...
Article
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,...
Article
Full-text available
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...
Preprint
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...
Article
Full-text available
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...
Article
Full-text available
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...
Article
Full-text available
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...
Article
Full-text available
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...
Article
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...
Article
Full-text available
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...
Article
Full-text available
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...
Article
Full-text available
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...
Preprint
Full-text available
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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
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...
Article
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)...
Article
Deep brain stimulation (DBS) offers the unique opportunity to record human neural population activity as multiunit activity and local field potentials (LFP) directly from the target area in the depth of the brain. This has led to important discoveries through characterization of pathological activity patterns and identification of motor and cogniti...
Article
Full-text available
The subthalamic nucleus (STN) is a primary target for deep brain stimulation in Parkinson's disease (PD). Although small in size, the STN is commonly partitioned into sensorimotor, cognitive/associative, and limbic subregions based on its structural connectivity profile to cortical areas. We investigated whether such a regional specialization is al...
Preprint
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...
Article
Full-text available
Freezing of gait is a debilitating symptom in advanced Parkinson’s disease and responds heterogeneously to treatments such as deep brain stimulation. Recent studies indicated that cortical dysfunction is involved in the development of freezing, while evidence depicting the specific role of the primary motor cortex in the multi-circuit pathology of...
Preprint
Full-text available
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...
Preprint
Deep brain stimulation procedures offer an invaluable opportunity to study disease through intracranial recordings from awake patients. Herein, 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 wit...
Article
Full-text available
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...
Article
Full-text available
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...
Article
Background Deep Brain Stimulation (DBS) has been proven to alleviate motor symptoms in Parkinson's Disease (PD). Regarding non-motor symptoms, however, inconsistencies have been reported, on whether DBS causes reductions in well-being and functioning. To assess motor and non-motor impairment in DBS-patients, the Deep Brain Stimulation Impairment Sc...
Article
Full-text available
Introduction Premonitory urges in Tourette disorder are often linked to altered somatosensory processing, which might include deficits in metacognition. We explored tactile and visual metacognitive ability in people with Tourette disorder and healthy control participants. Methods Patients with Tourrete disorder and healthy control participants com...
Preprint
Background Beta band activity in the subthalamic local field potential (LFP) is correlated with Parkinson’s disease (PD) symptom severity, and is the therapeutic target and feedback signal for adaptive deep brain stimulation (aDBS). While clinically relevant beta fluctuations in PD patients are well characterised on shorter timescales and in the cl...
Article
Full-text available
Background: Subthalamic nucleus deep brain stimulation (STN-DBS) effectively treats motor symptoms and quality of life (QoL) of advanced and fluctuating early Parkinson's disease. Little is known about the relation between electrode position and changes in symptom control and ultimately QoL. Objectives: The relation between the stimulated part o...
Article
Full-text available
Objective: To obtain individual clinical and neuroimaging data of patients undergoing Deep Brain Stimulation for essential tremor from five different European centers to identify predictors of outcome and to identify an optimal stimulation site. Methods: We analysed retrospectively baseline covariates, pre- and postoperative clinical tremor scor...
Article
Full-text available
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 br...
Article
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...
Article
Full-text available
Brain lesions are a rare cause of tic disorders. However, they can provide unique insights into tic pathophysiology and can also inform on possible neuromodulatory therapeutic targets. Based on a systematic literature review, we identified 22 cases of tics causally attributed to brain lesions and employed ‘lesion network mapping’ to interrogate whe...
Article
Full-text available
Deep Brain Stimulation (DBS) is an efficacious treatment option for an increasing range of brain disorders. To enhance our knowledge about the mechanisms of action of DBS and to probe novel targets, basic research in animal models with DBS is an essential research base. Beyond nonhuman primate, pig, and mouse models, the rat is a widely used animal...
Chapter
Electrophysiological recordings have allowed characterizing real-time neurophysiological biomarkers of disease states as well as pathophysiological changes in functional connectivity in movement disorders. Moreover, they have shed light on one of the mechanism of action of DBS—the suppression of pathological oscillatory network activity. In hypokin...
Chapter
Connectomic deep brain stimulation (DBS) research in the context of cognitive neuroscience investigates brain connections related to cognitive functions like learning or memory. Specifically, the effects DBS have on a cognitive function can be related to brain connectivity by use of neuroimaging data, e.g. through assessment of structural connectiv...
Chapter
Dystonia is a hyperkinetic movement disorder associated with loss of inhibition, abnormal plasticity, dysfunctional sensorimotor integration, and brain oscillatory dysfunctions at cortical and subcortical levels of the central nervous system. Hence, dystonia is considered a network disorder that can, in many cases, be efficiently treated by pallida...
Article
Full-text available
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...
Article
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...
Article
Full-text available
At the group-level, deep brain stimulation leads to significant therapeutic benefit in a multitude of neurological and neuropsychiatric disorders. At the single-patient level, however, symptoms may sometimes persist despite “optimal” electrode placement at established treatment coordinates. This may be partly explained by limitations of disease-cen...
Preprint
Full-text available
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...
Preprint
Full-text available
Deep brain stimulation (DBS) is an established therapy for patients with Parkinson’s disease. In silico computer models for DBS allow to pre-select a set of potentially optimal stimulation parameters. If efficacious, they could further carry insight into the mechanism of action of DBS and foster the development of more efficient stimulation approac...
Preprint
Full-text available
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...
Preprint
Full-text available
At the group-level, deep brain stimulation leads to significant therapeutic benefit in a multitude of neurological and neuropsychiatric disorders. At the single-patient level, however, symptoms may sometimes persist despite "optimal" electrode placement at established treatment coordinates. This may be partly explained by limitations of disease-cen...
Article
Full-text available
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...
Book
Full-text available
The book is available here: https://www.elsevier.com/books/connectomic-deep-brain-stimulation/horn/978-0-12-821861-7
Article
A recent advancement in the field of neuromodulation is to adapt stimulation parameters according to pre-specified biomarkers tracked in real-time. These markers comprise short and transient signal features, such as bursts of elevated band power. To capture these features, instantaneous measures of phase and/or amplitude are employed, which inform...
Article
Full-text available
The subthalamic nucleus and internal pallidum are main target sites for deep brain stimulation in Parkinson’s disease. Multiple trials that investigated subthalamic versus pallidal stimulation were unable to settle on a definitive optimal target between the two. One reason could be that the effect is mediated via a common functional network. To tes...