A Schulze-Bonhage

University of Freiburg, Freiburg, Baden-Württemberg, Germany

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Publications (167)355.48 Total impact

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    ABSTRACT: Pathological changes in excitability of cortical tissue commonly underlie the initiation and spread of seizure activity in patients suffering from epilepsy. Accordingly, monitoring excitability and controlling its degree using antiepileptic drugs (AEDs) is of prime importance for clinical care and treatment. To date, adequate measures of excitability and action of AEDs have been difficult to identify. Recent insights into ongoing cortical activity have identified global levels of phase synchronization as measures that characterize normal levels of excitability and quantify any deviation therefrom. Here, we explore the usefulness of these intrinsic measures to quantify cortical excitability in humans. First, we observe a correlation of such markers with stimulation-evoked responses suggesting them to be viable excitability measures based on ongoing activity. Second, we report a significant covariation with the level of AED load and a wake-dependent modulation. Our results indicate that excitability in epileptic networks is effectively reduced by AEDs and suggest the proposed markers as useful candidates to quantify excitability in routine clinical conditions overcoming the limitations of electrical or magnetic stimulation. The wake-dependent time course of these metrics suggests a homeostatic role of sleep, to rebalance cortical excitability.
    Proceedings of the National Academy of Sciences 11/2015; DOI:10.1073/pnas.1513716112 · 9.67 Impact Factor
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    ABSTRACT: Purpose This study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623). Methods Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS. Results Sixty-six seizures (n = 16 patients) were available from the EMU for analysis. In 37 seizures (n = 14 patients) a ≥20% heart rate increase was found and 11 (n = 5 patients) were associated with ictal tachycardia (iTC, 55% or 35 bpm heart rate increase, minimum of 100 bpm). Multiple CBSDA settings achieved a sensitivity of ≥80%. False positives ranged from 0.5 to 7.2/h. 27/66 seizures were stimulated within ±2 min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale) showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months (p < 0.05). Patient-scored seizure severity (total SSQ score) showed significant improvement at 3 and 6 months. Quality of life (total QOLIE-31-P score) showed significant improvement at 12 months. The responder rate (≥50% reduction in seizure frequency) at 12 months was 29.6% (n = 8/27). Safety profiles were comparable to prior VNS trials. Conclusions The investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients.
    Seizure 09/2015; 32. DOI:10.1016/j.seizure.2015.08.011 · 1.82 Impact Factor
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    ABSTRACT: Epilepsy is both a disease of the brain and the mind. Here, we present the first of two papers with extended summaries of selected presentations of the Third International Congress on Epilepsy, Brain and Mind (April 3-5, 2014; Brno, Czech Republic). Epilepsy in history and the arts and its relationships with religion were discussed, as were overviews of epilepsy and relevant aspects of social cognition, handedness, accelerated forgetting and autobiographical amnesia, and large-scale brain networks. Copyright © 2015. Published by Elsevier Inc.
    Epilepsy & Behavior 08/2015; 50. DOI:10.1016/j.yebeh.2015.06.044 · 2.26 Impact Factor
  • Andreas Schulze-Bonhage ·
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    ABSTRACT: Epilepsy is a chronic disease which affects 1% of the population worldwide. As treatment is required for many years or decades, the long-term efficacy and tolerability of antiepileptic drugs are particularly important. Zonisamide (ZNS) is a second-generation antiepileptic drug with a unique structure and multiple mechanisms of action. Here, recently published long-term outcomes of patient cohorts with focal epilepsy undergoing ZNS treatment are discussed. Whereas ZNS monotherapy maintains similar seizure control efficacy to carbamazepine after 2 years of treatment, seizure-free rates are low in pharmacoresistant patients undergoing late adjunctive therapy. In preselected patient populations derived from double-blind studies, long-term seizure reduction and responder rates support sustained ZNS efficacy, good adherence and long-term retention. Adverse effects include somnolence and weight decrease, but data suggest that long-term treatment with ZNS is safe with only rare newly occurring adverse effects, and good long-term tolerability also regarding mood, behavior, cognition and bone maturation.
    Expert Review of Neurotherapeutics 07/2015; 15(8). DOI:10.1586/14737175.2015.1065179 · 2.78 Impact Factor
  • Andreas Schulze-Bonhage ·
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    ABSTRACT: Introduction: Epilepsies are among the most common diseases of the CNS. As available antiepileptic drugs do not successfully control seizures in one-third of these patients, the development of drugs with new mechanisms of action is an urgent requirement. Areas covered: Preclinical and clinical data of the recently released antiepileptic drug perampanel are reviewed based on search in medical databases with special reference to its mechanism of action and to its pharmacokinetic properties relevant for clinical treatment. Pharmacodynamically, perampanel is a noncompetitive AMPA-receptor antagonist exerting its antiepileptic properties by modulating glutamatergic synaptic excitation. Pharmacokinetically, perampanel is characterized by a short Tmax but slow hepatic metabolism and a mean plasma half-life of 105 h, allowing for once-daily dosing. Perampanel has shown antiepileptic properties in several animal models of seizures and epilepsy, and in clinical studies significantly reducing partial-onset seizures in a dose range from 4 to 12 mg/day both in blinded short-term and in open-label long-term extension trials even in highly pharmacoresistant patients. Aside from adverse effects of dizziness and somnolence, neuropsychiatric disturbances have been reported in patient subgroups, making careful clinical monitoring during uptitration recommendable. Expert opinion: The use of perampanel focusing on control of abnormal synaptic excitation profits from favorable pharmacokinetics and from proven efficacy and overall good tolerability also in patient populations nonresponsive to treatment with previously available antiepileptic drugs.
    Expert Opinion on Drug Metabolism & Toxicology 06/2015; 11(8):1-9. DOI:10.1517/17425255.2015.1061504 · 2.83 Impact Factor
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    ABSTRACT: Technological advances are dramatically advancing translational research in Epilepsy. Neurophysiology, imaging, and metadata are now recorded digitally in most centers, enabling quantitative analysis. Basic and translational research opportunities to use these data are exploding, but academic and funding cultures prevent this potential from being realized. Research on epileptogenic networks, antiepileptic devices, and biomarkers could progress rapidly if collaborative efforts to digest this "big neuro data" could be organized. Higher temporal and spatial resolution data are driving the need for novel multidimensional visualization and analysis tools. Crowd-sourced science, the same that drives innovation in computer science, could easily be mobilized for these tasks, were it not for competition for funding, attribution, and lack of standard data formats and platforms. As these efforts mature, there is a great opportunity to advance Epilepsy research through data sharing and increase collaboration between the international research community.
    Journal of clinical neurophysiology: official publication of the American Electroencephalographic Society 06/2015; 32(3):235-239. DOI:10.1097/WNP.0000000000000159 · 1.43 Impact Factor
  • K.H. Somerlik-Fuchs · U.G. Hofmann · T. Stieglitz · A. Schulze-Bonhage ·

    Brain Stimulation 03/2015; 8(2):418. DOI:10.1016/j.brs.2015.01.333 · 4.40 Impact Factor
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    Kh Somerlik-Fuchs · O Christ · M Duempelmann · Ug Hofmann · T Stieglitz · A Schulze-Bonhage ·
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    ABSTRACT: BrainLinks-BrainTools aims to develop smart devices to inter-face with the brain. Among these, closed-loop stimulation devices promise new chances for patients suffering from pharmacoresistant epilepsy, assuming that effective stimula-tion parameters can be found. As the mechanisms of electrical brain stimulations are complex and poorly understood, animal experiments are needed to obtain insight into optimal parame-ter settings. Besides these, the loop can only be closed by reli-able seizure detection and prediction algorithms with high performance and at the same time low computational complex-ity. We present our results in this respect, based on the widely accepted kainate model, thought to resemble human temporal lobe epilepsy. More than 400 seizures could be recorded in more than 2500 h of synchronized video-EEG-acquisition. Video-and EEG-based detection algorithms were pro-grammed and seizure prediction methods tested. Those with the best performance in regard to reliability, celerity and pow-er consumption will be used in a closed-loop setup. This is a first step to evaluate closed-loop stimulation approaches and therewith widening possibilities for future clinical applications.
    MBEC, Dubrovnik; 10/2014
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    Johanna Derix · Olga Iljina · Johanna Weiske · Andreas Schulze-Bonhage · Ad Aertsen · Tonio Ball ·
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    ABSTRACT: Exchange of thoughts by means of expressive speech is fundamental to human communication. However, the neuronal basis of real-life communication in general, and of verbal exchange of ideas in particular, has rarely been studied until now. Here, our aim was to establish an approach for exploring the neuronal processes related to cognitive “idea” units (IUs) in conditions of non-experimental speech production. We investigated whether such units corresponding to single, coherent chunks of speech with syntactically-defined borders, are useful to unravel the neuronal mechanisms underlying real-world human cognition. To this aim, we employed simultaneous electrocorticography (ECoG) and video recordings obtained in pre-neurosurgical diagnostics of epilepsy patients. We transcribed non-experimental, daily hospital conversations, identified IUs in transcriptions of the patients’ speech, classified the obtained IUs according to a previously-proposed taxonomy focusing on memory content, and investigated the underlying neuronal activity. In each of our three subjects, we were able to collect a large number of IUs which could be assigned to different functional IU subclasses with a high inter-rater agreement. IU-related responses of brain activity showed significant modulations of the spectral magnitude in high gamma frequencies (70-150 Hz) in mouth motor, language, and higher-order association areas. Neuronal responses specific to different IU subclasses were observed in the inferior parietal and prefrontal cortex. Thus, IU-based analysis of ECoG recordings during non-experimental communication elicited topographically- and functionally-specific effects. We conclude that segmentation of spontaneous real-world speech in linguistically-motivated units is a promising strategy for elucidating the neuronal basis of mental processing during non-experimental communication.
    Frontiers in Human Neuroscience 06/2014; 8:383. DOI:10.3389/fnhum.2014.00383 · 3.63 Impact Factor
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    ABSTRACT: Recent evidence suggests that some seizures are preceded by preictal changes that start from minutes to hours before an ictal event. Nevertheless an adequate statistical evaluation in a large database of continuous multiday recordings is still missing. Here, we investigated the existence of preictal changes in long-term intracranial recordings from 53 patients with intractable partial epilepsy (in total 531 days and 558 clinical seizures). We describe a measure of brain excitability based on the slow modulation of high-frequency gamma activities (40-140 Hz) in ensembles of intracranial contacts. In prospective tests, we found that this index identified preictal changes at levels above chance in 13.2% of the patients (7/53), suggesting that results may be significant for the whole group (p < 0.05). These results provide a demonstration that preictal states can be detected prospectively from EEG data. They advance understanding of the network dynamics leading to seizure and may help develop novel seizure prediction algorithms.
    Scientific Reports 04/2014; 4:4545. DOI:10.1038/srep04545 · 5.58 Impact Factor
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    B Metternich · F Buschmann · K Wagner · A Schulze-Bonhage · L Kriston ·
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    ABSTRACT: Testing of verbal fluency is currently part of standard presurgical neuropsychological assessment for patients with focal epilepsy. However, to date no systematic review has been conducted on semantic (SVF) and phonemic verbal fluency (PVF) in this patient group. The present review compares verbal fluency between healthy control subjects and subgroups of adult presurgical patients with focal epilepsy according to lateralisation and localisation of the dysfunction. PubMed was searched with a comprehensive search string. Abstracts of all studies and full-texts of potentially relevant studies were screened. Study quality was assessed by independent raters according to predefined criteria. 39 studies were included. Meta-analyses were performed to compare SVF and PVF across groups of patients with temporal (TLE) and frontal lobe epilepsy (FLE) as well as healthy controls (HC). Both patients with left- and right sided TLE were impaired on SVF and PVF compared to HC. Patients with left-sided TLE were slightly more impaired than patients with right-sided TLE. Patients with FLE showed a larger impairment in PVF than patients with TLE, whereas on SVF there was no difference between FLE and TLE. For TLE comparisons the study pool seems to have been sufficient, whereas more studies are needed to verify results for FLE. Semantic verbal fluency might not differentiate between FLE and TLE. While verbal fluency impairment was anticipated, especially in left-sided TLE and FLE patients, the impairment in patients with right-sided TLE was larger than expected. Results are discussed with regard to neuropsychological theory and practice.
    Neuropsychology Review 03/2014; 24(4). DOI:10.1007/s11065-014-9255-8 · 4.59 Impact Factor
  • Andreas Schulze-Bonhage ·

    Seizure 03/2014; 23(6). DOI:10.1016/j.seizure.2014.02.013 · 1.82 Impact Factor
  • G. Leonhardt · A. Schulze-Bonhage ·
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    ABSTRACT: Die elektrische Stimulation der Hirnnerven V und X ist ein bislang palliatives Therapieverfahren für Epilepsiepatienten, die durch Medikamente nicht anfallsfrei werden, sich nicht für eine Operation eignen oder diese ablehnen. Sie bewirkt durch Aktivierung von Hirnstammkernen und des aufsteigenden Aktivierungssystem im Hirnstamm (,,ascending reticular activating system“, ARAS) eine Desynchronisierung kortikaler Aktivität. Ihre antikonvulsive Wirkung ist im Tierversuch gut belegt. Drei kleinere nichtrandomisierte Studien an Patienten mit pharmakorefraktären Epilepsien und eine Studie an Patienten mit pharmakorefraktären Depressionen belegten eine gute Wirksamkeit. Die bisher einzige randomisierte Phase-II-Studie bei Epilepsien, in der das Verfahren gegen eine aktive Kontrolle getestet wurde, zeigte erst zum letzten Untersuchungszeitpunkt (nach 18 Wochen) eine statistische Überlegenheit der Verumgruppe bei einem initial hohen Placeboeffekt der aktiven Kontrolle. Eine Phase-III-Studie ist in Planung. Eigene Erfahrungen mit dieser Methode lassen auf eine gute Verträglichkeit und Akzeptanz schließen. Ein positiver Einfluss auf die Stimmung wird von den meisten Patienten berichtet. Für die Bewertung der antikonvulsiven Wirkung sind die Anwendungen noch zu kurz und Patientenzahlen zu klein.
    Zeitschrift für Epileptologie 02/2014; 27(1). DOI:10.1007/s10309-013-0345-z
  • A. Schulze-Bonhage ·

    Zeitschrift für Epileptologie 02/2014; 27(1). DOI:10.1007/s10309-013-0338-y
  • K.H. Somerlik-Fuchs · T. Stieglitz · A. Schulze-Bonhage ·
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    ABSTRACT: Die Hirnstimulation hat das Potenzial, Linderung bei bislang untherapierbaren neurologischen Krankheiten zu erzielen. Die Erfolge bei der Behandlung von Bewegungsstörungen haben dazu beigetragen, dass viele Forschungsgruppen die elektrische Stimulation weiteruntersuchen und ihren Einsatz u. a. auch für die Therapie von Epilepsien prüfen. Die Arbeit mit Tiermodellen ist dabei essenziell. Da die Effekte elektrischer Stimulationen auf Hirngewebe sehr komplex sind und der mögliche Parameterraum groß ist, können optimale Paradigmen nur durch tierexperimentelle Studien systematisch entwickelt werden. Angesichts der multifaktoriellen Ätiologie von Epilepsien können unterschiedliche Modelle dazu dienen, die Krankheit bestmöglich nachzubilden. Diese Übersichtsarbeit stellt verschiedene Epilepsiemodelle dar, die zur Erprobung von Stimulationstherapien verwendet wurden, und erörtert, welche Stimulationsparadigmen das größte Potenzial gezeigt haben.
    Zeitschrift für Epileptologie 01/2014; 27(1). DOI:10.1007/s10309-013-0339-x
  • V.A. Coenen · B. Mädler · C.E. Elger · A. Schulze-Bonhage · H. Urbach · P.C. Reinacher ·
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    ABSTRACT: Die tiefe Hirnstimulation (,,deep brain stimulation“, DBS) zur Behandlung der Epilepsie im Nucleus anterior thalami (ANT) ist seit 2010 in Europa zugelassen. Obschon sie für alle fokalen Epilepsien zugelassen ist, stellt sich die Frage, ob bestimmte kortikale Epilepsieursprungsorte (z. B. frontal und temporal) besser als andere für diese Therapie empfänglich sind.Mithilfe der Diffusions-Tensor-Faserbahn-Traktographie (DTI-FT) sollte die Konnektivität des ANT und benachbarter Kerne mit anderen Hirnregionen bei zu implantierenden Patienten untersucht werden.Eine Serie von 8 Patienten wurde nach etablierten Kriterien für die ANT-DBS ausgewählt und vorher mit DTI-FT (3 T, 32 bzw. 61 Richtungen) untersucht. Die ANT-DBS erfolgte stereotaktisch über eine transventrikuläre Route und in Vollnarkose. Die Elektrodenpositionen wurden postoperativ mithilfe der Spiralcomputertomographie (SCT) dargestellt. Traktographisch wurde bei dieser standardisierten Implantationstechnik jeder der DBS-Elektroden-Kontakte als ,,Seed“-Region ausgewählt und traktographisch untersucht. Die ermittelten Fasertrakte wurden in ein Standardgehirn (ICBM-152) projiziert und ihr detailierter Verlauf ausgewertet.Mehr oberflächlich in Bezug zum ANT gelegene Elektrodenkontakte affektieren/rekrutieren Fasertrakte, die vorwiegend nach temporal oder frontal konnektieren. Tiefer gelegene Kontakte treffen Fasertrakte, die vorwiegend in den Hirnstamm und hier zum periaquäduktalen Grau sowie in den präfrontalen Kortex konnektieren.Obschon eine klinische Auswertung bisher nicht zur Verfügung steht, lässt die Konnektivitätsanalyse mithilfe der DTI-FT Rückschlüsse auf eine mögliche Verbesserung der Patientenselektion für die ANT-DBS zu. Nach den vorliegenden Ergebnissen sollte eine frontal oder temporal entstehende Epilepsie besser auf die ANT-DBS reagieren als andere Formen. Unter der Annahme einer über die direkte Modulation oder Rekrutierbarkeit vermittelten Wirkung sollte mit der Stimulation tieferer Elektrodenkontakte nach eigenen Ergebnissen eine Zunahme psychiatrischer Komplikationen (z. B. Depression) zu erwarten sein.
    Zeitschrift für Epileptologie 01/2014; 27(1). DOI:10.1007/s10309-013-0343-1
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    Clinical EEG and neuroscience; 12/2013
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    Clinical EEG and neuroscience: official journal of the EEG and Clinical Neuroscience Society (ENCS) 12/2013; 44(4):E1-121. · 2.22 Impact Factor
  • M. Ihle · B. Schelter · J. Timmer · A. Schulze-Bonhage ·

    Proceedings of the 5th International Workshop on Seizure Prediction; 11/2013
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    Olaf Christ · Karin H Somerlik-Fuchs · Thomas Stieglitz · Andreas Schulze-Bonhage · Ulrich G Hofmann ·
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    ABSTRACT: Temporal lobe epilepsy is the most common cause of drug-resistant seizures. Electrical stimulation seems to be a promising alternative to the classical anteromesial temporal resection. Our work aims at improving and validating ther-apeutic approaches for treating temporal lobe epilepsy using high-frequency stimulation. The relative phase clustering index (rPCI) is used to describe the epileptogenicity of a brain region and seizure prediction. A 2D image processing algorithm is presented for facilitating the tedious and time consuming visual image inspection of long term video footage required to determine optimal electrical stimulation parameters. See our companion paper describing the 3D solution in this journal.
    NER'2013 - IEEE Neural Engineering NER 2013., San Diego; 11/2013

Publication Stats

2k Citations
355.48 Total Impact Points


  • 2002-2015
    • University of Freiburg
      • Institute of Psychology
      Freiburg, Baden-Württemberg, Germany
  • 2008-2014
    • Universitätsklinikum Freiburg
      • Epilepsy Centre
      Freiburg an der Elbe, Lower Saxony, Germany
    • Bernstein Center for Computational Neuroscience Berlin
      Berlín, Berlin, Germany
  • 2000-2012
    • University of Bonn
      • Department of Neurobiology
      Bonn, North Rhine-Westphalia, Germany