@article{BinderLangePozzietal.2023, author = {Binder, Tobias and Lange, Florian and Pozzi, Nicol{\`o} and Musacchio, Thomas and Daniels, Christine and Odorfer, Thorsten and Fricke, Patrick and Matthies, Cordula and Volkmann, Jens and Capetian, Philipp}, title = {Feasibility of local field potential-guided programming for deep brain stimulation in Parkinson's disease: a comparison with clinical and neuro-imaging guided approaches in a randomized, controlled pilot trial}, series = {Brain Stimulation}, volume = {16}, journal = {Brain Stimulation}, number = {5}, doi = {10.1016/j.brs.2023.08.017}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350280}, pages = {1243-1251}, year = {2023}, abstract = {Highlights • Beta-Guided programming is an innovative approach that may streamline the programming process for PD patients with STN DBS. • While preliminary findings from our study suggest that Beta Titration may potentially mitigate STN overstimulation and enhance symptom control, • Our results demonstrate that beta-guided programming significantly reduces programming time, suggesting it could be efficiently integrated into routine clinical practice using a commercially available patient programmer. Background Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced Parkinson's disease (PD). Clinical outcomes after DBS can be limited by poor programming, which remains a clinically driven, lengthy and iterative process. Electrophysiological recordings in PD patients undergoing STN-DBS have shown an association between STN spectral power in the beta frequency band (beta power) and the severity of clinical symptoms. New commercially-available DBS devices now enable the recording of STN beta oscillations in chronically-implanted PD patients, thereby allowing investigation into the use of beta power as a biomarker for DBS programming. Objective To determine the potential advantages of beta-guided DBS programming over clinically and image-guided programming in terms of clinical efficacy and programming time. Methods We conducted a randomized, blinded, three-arm, crossover clinical trial in eight Parkinson's patients with STN-DBS who were evaluated three months after DBS surgery. We compared clinical efficacy and time required for each DBS programming paradigm, as well as DBS parameters and total energy delivered between the three strategies (beta-, clinically- and image-guided). Results All three programming methods showed similar clinical efficacy, but the time needed for programming was significantly shorter for beta- and image-guided programming compared to clinically-guided programming (p < 0.001). Conclusion Beta-guided programming may be a useful and more efficient approach to DBS programming in Parkinson's patients with STN-DBS. It takes significantly less time to program than traditional clinically-based programming, while providing similar symptom control. In addition, it is readily available within the clinical DBS programmer, making it a valuable tool for improving current clinical practice.}, language = {en} } @article{ContarinoSmitvandenDooletal.2016, author = {Contarino, Maria Fiorella and Smit, Marenka and van den Dool, Joost and Volkmann, Jens and Tijssen, Marina A. J.}, title = {Unmet Needs in the Management of Cervical Dystonia}, series = {Frontiers in Neurology}, volume = {7}, journal = {Frontiers in Neurology}, number = {165}, doi = {10.3389/fneur.2016.00165}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165225}, year = {2016}, abstract = {Cervical dystonia (CD) is a movement disorder which affects daily living of many patients. In clinical practice, several unmet treatment needs remain open. This article focuses on the four main aspects of treatment. We describe existing and emerging treatment approaches for CD, including botulinum toxin injections, surgical therapy, management of non-motor symptoms, and rehabilitation strategies. The unsolved issues regarding each of these treatments are identified and discussed, and possible future approaches and research lines are proposed.}, language = {en} } @article{DeebGiordanoRossietal.2016, author = {Deeb, Wissam and Giordano, James J. and Rossi, Peter J. and Mogilner, Alon Y. and Gunduz, Aysegul and Judy, Jack W. and Klassen, Bryan T. and Butson, Christopher R. and Van Horne, Craig and Deny, Damiaan and Dougherty, Darin D. and Rowell, David and Gerhardt, Greg A. and Smith, Gwenn S. and Ponce, Francisco A. and Walker, Harrison C. and Bronte-Stewart, Helen M. and Mayberg, Helen S. and Chizeck, Howard J. and Langevin, Jean-Philippe and Volkmann, Jens and Ostrem, Jill L. and Shute, Jonathan B. and Jimenez-Shahed, Joohi and Foote, Kelly D. and Wagle Shukla, Aparna and Rossi, Marvin A. and Oh, Michael and Pourfar, Michael and Rosenberg, Paul B. and Silburn, Peter A. and de Hemptine, Coralie and Starr, Philip A. and Denison, Timothy and Akbar, Umer and Grill, Warren M. and Okun, Michael S.}, title = {Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies}, series = {Frontiers in Integrative Neuroscience}, volume = {10}, journal = {Frontiers in Integrative Neuroscience}, number = {38}, doi = {10.3389/fnint.2016.00038}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168493}, year = {2016}, abstract = {This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field.}, language = {en} } @article{DelVecchioHanafiPozzietal.2023, author = {Del Vecchio, Jasmin and Hanafi, Ibrahem and Pozzi, Nicol{\´o} Gabriele and Capetian, Philipp and Isaias, Ioannis U. and Haufe, Stefan and Palmisano, Chiara}, title = {Pallidal recordings in chronically implanted dystonic patients: mitigation of tremor-related artifacts}, series = {Bioengineering}, volume = {10}, journal = {Bioengineering}, number = {4}, issn = {2306-5354}, doi = {10.3390/bioengineering10040476}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313498}, year = {2023}, abstract = {Low-frequency oscillatory patterns of pallidal local field potentials (LFPs) have been proposed as a physiomarker for dystonia and hold the promise for personalized adaptive deep brain stimulation. Head tremor, a low-frequency involuntary rhythmic movement typical of cervical dystonia, may cause movement artifacts in LFP signals, compromising the reliability of low-frequency oscillations as biomarkers for adaptive neurostimulation. We investigated chronic pallidal LFPs with the Percept\(^{TM}\) PC (Medtronic PLC) device in eight subjects with dystonia (five with head tremors). We applied a multiple regression approach to pallidal LFPs in patients with head tremors using kinematic information measured with an inertial measurement unit (IMU) and an electromyographic signal (EMG). With IMU regression, we found tremor contamination in all subjects, whereas EMG regression identified it in only three out of five. IMU regression was also superior to EMG regression in removing tremor-related artifacts and resulted in a significant power reduction, especially in the theta-alpha band. Pallido-muscular coherence was affected by a head tremor and disappeared after IMU regression. Our results show that the Percept PC can record low-frequency oscillations but also reveal spectral contamination due to movement artifacts. IMU regression can identify such artifact contamination and be a suitable tool for its removal.}, language = {en} } @article{FriedrichEldebakeyRoothansetal.2022, author = {Friedrich, Maximilian U. and Eldebakey, Hazem and Roothans, Jonas and Capetian, Philipp and Zwergal, Andreas and Volkmann, Jens and Reich, Martin}, title = {Current-dependent ocular tilt reaction in deep brain stimulation of the subthalamic nucleus: Evidence for an incerto-interstitial pathway?}, series = {European Journal of Neurology}, volume = {29}, journal = {European Journal of Neurology}, number = {5}, doi = {10.1111/ene.15257}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318700}, pages = {1545 -- 1549}, year = {2022}, abstract = {Background and purpose The aim was to characterize a combined vestibular, ocular motor and postural syndrome induced by deep brain stimulation (DBS) of the subthalamic nucleus in a patient with Parkinson's disease. Methods In a systematic DBS programming session, eye, head and trunk position in roll and pitch plane were documented as a function of stimulation amplitude and field direction. Repeat ocular coherence tomography was used to estimate ocular torsion. The interstitial nucleus of Cajal (INC), zona incerta (ZI) and ascending vestibular fibre tracts were segmented on magnetic resonance imaging using both individual and normative structural connectomic data. Thresholded symptom-associated volumes of tissue activated (VTA) were calculated based on documented stimulation parameters. Results Ipsilateral ocular tilt reaction and body lateropulsion as well as contralateral torsional nystagmus were elicited by the right electrode in a current-dependent manner and subsided after DBS deactivation. With increasing currents, binocular tonic upgaze and body retropulsion were observed. Symptoms were consistent with an irritative effect on the INC. Symptom-associated VTA was found to overlap with the dorsal ZI and the ipsilateral vestibulothalamic tract, while lying rather distant to the INC proper. A ZI-to-INC 'incerto-interstitial' tract with contact to the medial-uppermost portion of the VTA could be traced. Conclusion Unilateral stimulation of INC-related circuitry induces an ipsilateral vestibular, ocular motor and postural roll-plane syndrome, which converts into a pitch-plane syndrome when functional activation expands bilaterally. In this case, tractography points to an incerto-interstitial pathway, a tract previously only characterized in non-human primates. Directional current steering proved useful in managing this rare side effect.}, language = {en} } @article{Gonzalez‐EscamillaMuthuramanReichetal.2019, author = {Gonzalez-Escamilla, Gabriel and Muthuraman, Muthuraman and Reich, Martin M. and Koirala, Nabin and Riedel, Christian and Glaser, Martin and Lange, Florian and Deuschl, G{\"u}nther and Volkmann, Jens and Groppa, Sergiu}, title = {Cortical network fingerprints predict deep brain stimulation outcome in dystonia}, series = {Movement Disorders}, volume = {34}, journal = {Movement Disorders}, number = {10}, doi = {10.1002/mds.27808}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213532}, pages = {1536 -- 1545}, year = {2019}, abstract = {Background Deep brain stimulation (DBS) is an effective evidence-based therapy for dystonia. However, no unequivocal predictors of therapy responses exist. We investigated whether patients optimally responding to DBS present distinct brain network organization and structural patterns. Methods From a German multicenter cohort of 82 dystonia patients with segmental and generalized dystonia who received DBS implantation in the globus pallidus internus, we classified patients based on the clinical response 3 years after DBS. Patients were assigned to the superior-outcome group or moderate-outcome group, depending on whether they had above or below 70\% motor improvement, respectively. Fifty-one patients met MRI-quality and treatment response requirements (mean age, 51.3 ± 13.2 years; 25 female) and were included in further analysis. From preoperative MRI we assessed cortical thickness and structural covariance, which were then fed into network analysis using graph theory. We designed a support vector machine to classify subjects for the clinical response based on individual gray-matter fingerprints. Results The moderate-outcome group showed cortical atrophy mainly in the sensorimotor and visuomotor areas and disturbed network topology in these regions. The structural integrity of the cortical mantle explained about 45\% of the DBS stimulation amplitude for optimal response in individual subjects. Classification analyses achieved up to 88\% of accuracy using individual gray-matter atrophy patterns to predict DBS outcomes. Conclusions The analysis of cortical integrity, informed by group-level network properties, could be developed into independent predictors to identify dystonia patients who benefit from DBS.}, language = {en} } @article{GulbertiMollHameletal.2015, author = {Gulberti, A. and Moll, C.K.E. and Hamel, W. and Buhmann, C. and Koeppen, J.A. and Boelmans, K. and Zittel, S. and Gerloff, C. and Westphal, M. and Schneider, T.R. and Engel, A.K.}, title = {Predictive timing functions of cortical beta oscillations are impaired in Parkinson's disease and influenced by L-DOPA and deep brain stimulation of the subthalamic nucleus Impaired beta-band timing functions in PD}, series = {NeuroImage: Clinical}, volume = {9}, journal = {NeuroImage: Clinical}, doi = {10.1016/j.nicl.2015.09.013}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150049}, pages = {436-449}, year = {2015}, abstract = {Cortex-basal ganglia circuits participate in motor timing and temporal perception, and are important for the dynamic configuration of sensorimotor networks in response to exogenous demands. In Parkinson's disease (PD) patients, rhythmic auditory stimulation (RAS) induces motor performance benefits. Hitherto, little is known concerning contributions of the basal ganglia to sensory facilitation and cortical responses to RAS in PD. Therefore, we conducted an EEG study in 12 PD patients before and after surgery for subthalamic nucleus deep brain stimulation (STN-DBS) and in 12 age-matched controls. Here we investigated the effects of levodopa and STN-DBS on resting-state EEG and on the cortical-response profile to slow and fast RAS in a passive-listening paradigm focusing on beta-band oscillations, which are important for auditory-motor coupling. The beta-modulation profile to RAS in healthy participants was characterized by local peaks preceding and following auditory stimuli. In PD patients RAS failed to induce pre-stimulus beta increases. The absence of pre-stimulus beta-band modulation may contribute to impaired rhythm perception in PD. Moreover, post-stimulus beta-band responses were highly abnormal during fast RAS in PD patients. Treatment with levodopa and STN-DBS reinstated a post-stimulus beta-modulation profile similar to controls, while STN-DBS reduced beta-band power in the resting-state. The treatment-sensitivity of beta oscillations suggests that STN-DBS may specifically improve timekeeping functions of cortical beta oscillations during fast auditory pacing.}, language = {en} } @article{KremerPauwelsPozzietal.2021, author = {Kremer, Naomi I. and Pauwels, Rik W. J. and Pozzi, Nicol{\`o} G. and Lange, Florian and Roothans, Jonas and Volkmann, Jens and Reich, Martin M.}, title = {Deep Brain Stimulation for Tremor: Update on Long-Term Outcomes, Target Considerations and Future Directions}, series = {Journal of Clinical Medicine}, volume = {10}, journal = {Journal of Clinical Medicine}, number = {16}, issn = {2077-0383}, doi = {10.3390/jcm10163468}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244982}, year = {2021}, abstract = {Deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus is one of the main advanced neurosurgical treatments for drug-resistant tremor. However, not every patient may be eligible for this procedure. Nowadays, various other functional neurosurgical procedures are available. In particular cases, radiofrequency thalamotomy, focused ultrasound and radiosurgery are proven alternatives to DBS. Besides, other DBS targets, such as the posterior subthalamic area (PSA) or the dentato-rubro-thalamic tract (DRT), may be appraised as well. In this review, the clinical characteristics and pathophysiology of tremor syndromes, as well as long-term outcomes of DBS in different targets, will be summarized. The effectiveness and safety of lesioning procedures will be discussed, and an evidence-based clinical treatment approach for patients with drug-resistant tremor will be presented. Lastly, the future directions in the treatment of severe tremor syndromes will be elaborated.}, language = {en} } @article{MaaroufNeudorferElMajdoubetal.2016, author = {Maarouf, Mohammad and Neudorfer, Clemens and El Majdoub, Faycal and Lenartz, Doris and Kuhn, Jens and Sturm, Volker}, title = {Deep Brain Stimulation of Medial Dorsal and Ventral Anterior Nucleus of the Thalamus in OCD: A Retrospective Case Series}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {8}, doi = {10.1371/journal.pone.0160750}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166830}, pages = {e0160750}, year = {2016}, abstract = {Background The current notion that cortico-striato-thalamo-cortical circuits are involved in the pathophysiology of obsessive-compulsive disorder (OCD) has instigated the search for the most suitable target for deep brain stimulation (DBS). However, despite extensive research, uncertainty about the ideal target remains with many structures being underexplored. The aim of this report is to address a new target for DBS, the medial dorsal (MD) and the ventral anterior (VA) nucleus of the thalamus, which has thus far received little attention in the treatment of OCD. Methods In this retrospective trial, four patients (three female, one male) aged 31-48 years, suffering from therapy-refractory OCD underwent high-frequency DBS of the MD and VA. In two patients (de novo group) the thalamus was chosen as a primary target for DBS, whereas in two patients (rescue DBS group) lead implantation was performed in a rescue DBS attempt following unsuccessful primary stimulation. Results Continuous thalamic stimulation yielded no significant improvement in OCD symptom severity. Over the course of thalamic DBS symptoms improved in only one patient who showed "partial response" on the Yale-Brown Obsessive Compulsive (Y-BOCS) Scale. Beck Depression Inventory scores dropped by around 46\% in the de novo group; anxiety symptoms improved by up to 34\%. In the de novo DBS group no effect of DBS on anxiety and mood was observable. Conclusion MD/VA-DBS yielded no adequate alleviation of therapy-refractory OCD, the overall strategy in targeting MD/VA as described in this paper can thus not be recommended in DBS for OCD. The magnocellular portion of MD (MDMC), however, might prove a promising target in the treatment of mood related and anxiety disorders.}, language = {en} } @article{PasosSteigerwaldReichetal.2019, author = {Pasos, Uri E. Ramirez and Steigerwald, Frank and Reich, Martin M. and Matthies, Cordula and Volkmann, Jens and Reese, Ren{\´e}}, title = {Levodopa modulates functional connectivity in the upper beta band between bubthalamic nucleus and muscle activity in tonic and phasic motor activity patterns in Parkinson's disease}, series = {Frontiers in Human Neuroscience}, volume = {13}, journal = {Frontiers in Human Neuroscience}, number = {223}, doi = {10.3389/fnhum.2019.00223}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201540}, year = {2019}, abstract = {Introduction: Striatal dopamine depletion disrupts basal ganglia function and causes Parkinson's disease (PD). The pathophysiology of the dopamine-dependent relationship between basal ganglia signaling and motor control, however, is not fully understood. We obtained simultaneous recordings of local field potentials (LFPs) from the subthalamic nucleus (STN) and electromyograms (EMGs) in patients with PD to investigate the impact of dopaminergic state and movement on long-range beta functional connectivity between basal ganglia and lower motor neurons. Methods: Eight PD patients were investigated 3 months after implantation of a deep brain stimulation (DBS)-system capable of recording LFPs via chronically-implanted leads (Medtronic, ACTIVA PC+S®). We analyzed STN spectral power and its coherence with EMG in the context of two different movement paradigms (tonic wrist extension vs. alternating wrist extension and flexion) and the effect of levodopa (L-Dopa) intake using an unbiased data-driven approach to determine regions of interest (ROI). Results: Two ROIs capturing prominent coherence within a grand average coherogram were identified. A trend of a dopamine effect was observed for the first ROI (50-150 ms after movement start) with higher STN-EMG coherence in medicated patients. Concerning the second ROI (300-500 ms after movement start), an interaction effect of L-Dopa medication and movement task was observed with higher coherence in the isometric contraction task compared to alternating movements in the medication ON state, a pattern which was reversed in L-Dopa OFF. Discussion: L-Dopa medication may normalize functional connectivity between remote structures of the motor system with increased upper beta coherence reflecting a physiological restriction of the amount of information conveyed between remote structures. This may be necessary to maintain simple movements like isometric contraction. Our study adds dynamic properties to the complex interplay between STN spectral beta power and the nucleus' functional connectivity to remote structures of the motor system as a function of movement and dopaminergic state. This may help to identify markers of neuronal activity relevant for more individualized programming of DBS therapy.}, language = {en} }