A Schulze-Bonhage

Universitätsklinikum Freiburg, Freiburg an der Elbe, Lower Saxony, Germany

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Publications (158)332.85 Total impact

  • Andreas Schulze-Bonhage
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    ABSTRACT: 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 &amp Toxicology 06/2015; DOI:10.1517/17425255.2015.1061504 · 2.93 Impact Factor
  • Brain Stimulation 03/2015; 8(2):418. DOI:10.1016/j.brs.2015.01.333 · 5.43 Impact Factor
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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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    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. Robust IU-onset-related changes in spectral magnitude could be observed in high gamma frequencies (70-150 Hz) on the inferior lateral convexity and in the superior temporal cortex regardless of the IU content. A comparison of the topography of these responses with mouth motor and speech areas identified by electrocortical stimulation showed that IUs might be of use for extraoperative mapping of eloquent cortex (average sensitivity: 44.4%, average specificity: 91.1%). High gamma responses specific to memory-related IU subclasses were observed in the inferior parietal and prefrontal regions. IU-based analysis of ECoG recordings during non-experimental communication thus elicits 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 · 2.90 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; DOI:10.1007/s11065-014-9255-8 · 5.40 Impact Factor
  • Andreas Schulze-Bonhage
    Seizure 03/2014; 23(6). DOI:10.1016/j.seizure.2014.02.013 · 2.06 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
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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. · 3.16 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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    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
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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. An online image processing algorithm using a 3D camera is presented for facilitating the tedious and time consuming visual image inspection by traditional long term video footage required to determine optimal electrical stimulation parameters. See our companion paper describing the 2D solution in this journal.
    NER'2013 - IEEE Neural Engineering NER 2013., San Diego; 11/2013
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    ABSTRACT: Fiber tractography is increasingly used in the preoperative evaluation of endangered fiber bundles. From a clinical point of view, an accurate and methodologically transparent procedure is desired. Our aim was to evaluate the recently described global tracking algorithm compared with other established methods, such as deterministic and probabilistic tractography.MATERIALS AND METHODS:Twenty patients, candidates for excision of epileptogenic lesions, were subjected to higher-angular resolution diffusion imaging-based fiber tractography. Seed points were created without manual bias, predominantly by FreeSurfer and voxel-based atlases. We focused on 2 important fiber bundles, namely the descending motor pathways and the optic radiation. Postoperatively, the accuracy of the predicted fiber route was controlled by structural MR imaging and by inflicted functional deficits.RESULTS: Among the 3 evaluated methods, global tracking was the only method capable of reconstructing the full extent of the descending motor pathways, including corticobulbar fibers from the area of face representation. Still, probabilistic tractography depicted the optic radiation better, especially the Meyer loop. The deterministic algorithm performed less adequately.CONCLUSIONS:The probabilistic method seems to be the best balance between computational time and effectiveness and seems to be the best choice in most cases, particularly for the optic radiation. If, however, a detailed depiction of the fiber anatomy is intended and tract crossings are implicated, then the computationally time-consuming global tracking should be preferred.
    American Journal of Neuroradiology 10/2013; 35(2). DOI:10.3174/ajnr.A3752 · 3.68 Impact Factor
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    R Zelmann, J M Lina, A Schulze-Bonhage, J Gotman, J Jacobs
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    ABSTRACT: High frequency oscillations (HFOs) are emerging as biomarkers of epileptogenicity. They have been shown to originate from small brain regions. Surprisingly, spontaneous HFOs can be recorded from the scalp. To understand how is it possible to observe these small events on the scalp, one avenue is the analysis of the cortical correlates at the time of scalp HFOs. Using simultaneous scalp and intracranial recordings of 11 patients, we studied the spatial distribution of scalp events on the cortical surface. For typical interictal epileptiform discharges the subdural distributions were, as expected, spatially extended. On the contrary, for scalp HFOs the subdural maps corresponded to focal sources, consisting of one or a few small spatial extent activations. These topographies suggest that small cortical areas generated the HFOs seen on the scalp. Similar scalp distributions corresponded to distinct distributions on a standard 1 cm subdural grid and averaging similar scalp HFOs resulted in focal subdural maps. The assumption that a subdural grid "sees" everything that contributes to the potential of nearby scalp contacts was not valid for HFOs. The results suggest that these small extent events are spatially undersampled with standard scalp and grid inter-electrode distances. High-density scalp electrode distributions seem necessary to obtain a solid sampling of HFOs on the scalp. A better understanding of the influence of spatial sampling on the observation of high frequency brain activity on the scalp is important for their clinical use as biomarkers of epilepsy.
    Brain Topography 10/2013; DOI:10.1007/s10548-013-0321-y · 2.52 Impact Factor
  • Clinical Neurophysiology 10/2013; 124(10):e181. DOI:10.1016/j.clinph.2013.04.318 · 2.98 Impact Factor
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    ABSTRACT: Analyzing single trial brain activity remains a challenging problem in the neurosciences. We gain purchase on this problem by focusing on globally synchronous fields in within-trial evoked brain activity, rather than on localized peaks in the trial-averaged evoked response (ER). We analyzed data from three measurement modalities, each with different spatial resolution: magnetoencephalogram (MEG), electroencephalogram (EEG) and electrocorticogram (ECoG). We first characterized the ER in terms of summation of phase and amplitude components over trials. Both contributed to the ER, as expected, but the ER topography was dominated by the phase component. This means the ER topography is akin to an interference pattern in phase across trials. Hence the observed topography of cross-trial phase will not accurately reflect the phase topography within trials. To assess the organization of within-trial phase, traveling wave (TW) components were quantified by computing the phase gradient. TWs were intermittent but ubiquitous in the within-trial evoked brain activity. At most task-relevant times and frequencies, the within-trial phase topography was described better by a TW than by the trial-average of phase. The trial-average of the TW components also reproduced the topography of the ER; we suggest that the ER topography arises, in large part, as an average over TW behaviours. These findings were consistent across the three measurement modalities. We conclude that, while phase is critical to understanding the topography of event-related activity, the preliminary step of collating cortical signals across trials can obscure the TW components in brain activity and lead to an underestimation of the coherent motion of cortical fields.
    NeuroImage 06/2013; DOI:10.1016/j.neuroimage.2013.01.016 · 6.13 Impact Factor

Publication Stats

1k Citations
332.85 Total Impact Points

Institutions

  • 2008–2014
    • Universitätsklinikum Freiburg
      • Epilepsy Centre
      Freiburg an der Elbe, Lower Saxony, Germany
  • 1999–2014
    • University of Freiburg
      • Institute of Psychology
      Freiburg, Baden-Württemberg, Germany
  • 2000–2012
    • University of Bonn
      • Department of Neurobiology
      Bonn, North Rhine-Westphalia, Germany