Coordination and timing in repetitive movements have been intensively investigated in diverse experimental settings for understanding the underlying basic mechanisms in healthy controls. On this basic research side, there are mainly two... more
Coordination and timing in repetitive movements have been intensively investigated in diverse experimental settings for understanding the underlying basic mechanisms in healthy controls. On this basic research side, there are mainly two theoretical models: the Wing-Kristofferson (WK) model and the Haken-Kelso-Bunz (HKB) model. On the clinical side of the research, several efforts have been spent on quantitatively assessing gait and other repetitive movements such as tapping, especially as an outcome measure of clinical trials in diverse neurological disorders. Nevertheless, Parkinson’s disease (PD) remains the predominant disorder in the clinical literature in this context, as the tremor activity and the changes in the gait are both common symptoms in PD. Although there are motion recording systems for data acquisition in clinical settings, the tools for analysis and quantification of the extracted time-series offered by these systems are severely restricted. Therefore, we introduce...
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Background: The current pandemic requires hospitals to ensure care not only for the growing number of COVID-19 patients but also regular patients. Hospital resources must be allocated accordingly.Objective: To provide hospitals with a... more
Background: The current pandemic requires hospitals to ensure care not only for the growing number of COVID-19 patients but also regular patients. Hospital resources must be allocated accordingly.Objective: To provide hospitals with a planning model to optimally allocate resources to intensive care units given a certain incidence of COVID-19 cases.Methods: The analysis included 334 cases from four adjacent counties south-west of Munich. From length of stay and type of ward [general ward (NOR), intensive care unit (ICU)] probabilities of case numbers within a hospital at a certain time point were derived. The epidemiological situation was simulated by the effective reproduction number R, the infection rates in mid-August 2020 in the counties, and the German hospitalization rate. Simulation results are compared with real data from 2nd and 3rd wave (September 2020–May 2021).Results: With R = 2, a hospitalization rate of 17%, mitigation measures implemented on day 9 (i.e., 7-day inciden...
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Primary tinnitus has a severe negative influence on the quality of life of a substantial portion of the general population. When acoustic coordinated reset (CR) neuromodulation stimuli are delivered for several hours per day over several... more
Primary tinnitus has a severe negative influence on the quality of life of a substantial portion of the general population. When acoustic coordinated reset (CR) neuromodulation stimuli are delivered for several hours per day over several weeks a clinically significant symptom reduction in patients with primary tonal tinnitus has been reported by several clinical sites. Here, we reported the first case where CR neuromodulation was delivered through a hearing aid. A 52-year-old man with chronic primary tonal tinnitus was previously considered untreatable with sound therapy. He initially received the classic CR treatment protocol with signals delivered with the separate proprietary device with his hearing aids removed during treatment. He was subsequently treated with the therapy being deployed through a set of contemporary hearing aids. After 5 months of classic CR treatment with the separate custom device, the THI and VASL/A scores worsened by 57% and 13%/14%, respectively. Using the...
Sound-based tinnitus intervention stimuli include broad-band noise signals with subjectively adjusted bandwidths used as maskers delivered by commercial devices or hearing aids, environmental sounds broadly described and delivered by both... more
Sound-based tinnitus intervention stimuli include broad-band noise signals with subjectively adjusted bandwidths used as maskers delivered by commercial devices or hearing aids, environmental sounds broadly described and delivered by both consumer devices and hearing aids, music recordings specifically modified and delivered in a variety of different ways, and other stimuli. Acoustic coordinated reset neuromodulation therapy for tinnitus reduction has unique and more stringent requirements compared to all other sound-based tinnitus interventions. These include precise characterization of tinnitus pitch and loudness, and effective provision of patient-controlled daily therapy signals at defined frequencies, levels, and durations outside of the clinic. The purpose of this study was to evaluate an approach to accommodate these requirements including evaluation of a mobile device, validation of an automated tinnitus pitch-matching algorithm and assessment of a patient's ability to c...
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Purpose. Primary tinnitus has a severe negative influence on the quality of life of a significant portion of the general population. Acoustic coordinated reset neuromodulation is designed to induce a long-lasting reduction of tinnitus... more
Purpose. Primary tinnitus has a severe negative influence on the quality of life of a significant portion of the general population. Acoustic coordinated reset neuromodulation is designed to induce a long-lasting reduction of tinnitus symptoms. To test acoustic coordinated reset neuromodulation as a treatment for chronic, tonal tinnitus under real life conditions, an outpatient study “RESET Real Life” was commissioned by ANM GmbH. Herein we present the results of this study.Methods. In a prospective, open-label, nonrandomized, noncontrolled multicenter clinical study with 200 chronic tinnitus patients, tinnitus questionnaire TBF-12 and Global Clinical Improvement-Impression Scale (CGI-I7) are used to study the safety and efficacy of acoustic coordinated reset neuromodulation. 189 patients completed the last 12-month visit, 11 patients dropped out (8 because of nontreatment related reasons; 2 because tinnitus did not change; and 1 because tinnitus got louder).Results. Acoustic coordi...
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... Christian Hauptmann14, Annette Gail2, and Fotios Giannakopoulos3 ... in Physiology and Medicine, Department of Physiology, McGill University, 3655 Drummond Street, Montreal, Quebec ... for the widely observed decrease of the... more
... Christian Hauptmann14, Annette Gail2, and Fotios Giannakopoulos3 ... in Physiology and Medicine, Department of Physiology, McGill University, 3655 Drummond Street, Montreal, Quebec ... for the widely observed decrease of the outstanding frequency in the EEG diagram during ...
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Purpose. Primary tinnitus has a severe negative influence on the quality of life of a significant portion of the general population. Acoustic coordinated reset neuromodulation is designed to induce a long-lasting reduction of tinnitus... more
Purpose. Primary tinnitus has a severe negative influence on the quality of life of a significant portion of the general population. Acoustic coordinated reset neuromodulation is designed to induce a long-lasting reduction of tinnitus symptoms. To test acoustic coordinated reset neuromodulation as a treatment for chronic, tonal tinnitus under real life conditions, an outpatient study " RESET Real Life " was commissioned by ANM GmbH. Herein we present the results of this study. Methods. In a prospective, open-label, nonrandomized, noncontrolled multicenter clinical study with 200 chronic tinnitus patients, tinnitus questionnaire TBF-12 and Global Clinical Improvement-Impression Scale (CGI-I7) are used to study the safety and efficacy of acoustic coordinated reset neuromodulation. 189 patients completed the last 12-month visit, 11 patients dropped out (8 because of nontreatment related reasons; 2 because tinnitus did not change; and 1 because tinnitus got louder). Results. A...
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To describe the quantitative treatment outcomes of patients undergoing acoustic coordinated reset (CR) neuromodulation at a single independent audiology practice over a 22- to 26-week period as part of an open label, non-randomized,... more
To describe the quantitative treatment outcomes of patients undergoing acoustic coordinated reset (CR) neuromodulation at a single independent audiology practice over a 22- to 26-week period as part of an open label, non-randomized, non-controlled observational study. Sixty-six patients with subjective tonal tinnitus were treated with acoustic CR neuromodulation with a retrospective review of patient records being performed in order to identify changes of visual analog scale (VAS, n = 66) and in the score of the tinnitus handicap questionnaire (THQ, n = 51). Patients had their tinnitus severity recorded prior to the initiation of therapy using the tinnitus handicap inventory in order to categorize patients into slight up to catastrophic impact categories. THQ and VAS for tinnitus loudness/annoyance were obtained at the patient's initial visit, at 10-14 and 22-26 weeks. Visual analog scale scores were significantly improved, demonstrating a 25.8% mean reduction in tinnitus loudne...
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Neuroimaging studies have identified networks of brain areas and oscillations associated with tinnitus perception. However, how these regions relate to perceptual characteristics of tinnitus, and how oscillations in various frequency... more
Neuroimaging studies have identified networks of brain areas and oscillations associated with tinnitus perception. However, how these regions relate to perceptual characteristics of tinnitus, and how oscillations in various frequency bands are associated with communications within the tinnitus network is still incompletely understood. Recent evidence suggests that apart from changes of the tinnitus severity the changes of tinnitus dominant pitch also have modulating effect on the underlying neuronal activity in a number of brain areas within the tinnitus network. Therefore, in a re-analysis of an existing dataset, we sought to determine how the oscillations in the tinnitus network in the various frequency bands interact. We also investigate how changes of tinnitus loudness, annoyance and pitch affect cross-frequency interaction both within and between nodes of the tinnitus network. Results of this study provide, to our knowledge, the first evidence that in tinnitus patients, aside f...
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Deep brain stimulation (DBS) is an effective therapy for medically refractory movement disorders like Parkinson's disease. The electrodes, implanted in the target area within the human brain, generate an electric field which activates... more
Deep brain stimulation (DBS) is an effective therapy for medically refractory movement disorders like Parkinson's disease. The electrodes, implanted in the target area within the human brain, generate an electric field which activates nerve fibers and cell bodies in the vicinity. Even though the different target nuclei display considerable differences in their anatomical structure, only few types of electrodes are currently commercially available. It is desirable to adjust the electric field and in particular the volume of tissue activated around the electrode with respect to the corresponding target nucleus in a such way that side effects can be reduced. Furthermore, a more selective and partial activation of the target structure is desirable for an optimal application of novel stimulation strategies, e.g., coordinated reset neuromodulation. Hence we designed a DBS electrode with a segmented design allowing a more selective activation of the target structure. We created a finit...
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... Christian Hauptmann14, Annette Gail2, and Fotios Giannakopoulos3 ... in Physiology and Medicine, Department of Physiology, McGill University, 3655 Drummond Street, Montreal, Quebec ... for the widely observed decrease of the... more
... Christian Hauptmann14, Annette Gail2, and Fotios Giannakopoulos3 ... in Physiology and Medicine, Department of Physiology, McGill University, 3655 Drummond Street, Montreal, Quebec ... for the widely observed decrease of the outstanding frequency in the EEG diagram during ...
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We present a novel method for desynchronization of strongly synchronized population of interacting oscillators. It is based on nonlinear delayed feedback, works on demand with vanishing amount of stimulation, and is robust with respect to... more
We present a novel method for desynchronization of strongly synchronized population of interacting oscillators. It is based on nonlinear delayed feedback, works on demand with vanishing amount of stimulation, and is robust with respect to parameter variations. We suggest our method for mild and effective deep brain stimulation in neurological diseases characterized by pathological cerebral synchronization.
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Different stimulation techniques are introduced which specifically modulate the slow synaptic dynamics in a neuronal network model of the subthalamic nucleus with activity dependent synaptic plasticity. A modeling approach is utilized to... more
Different stimulation techniques are introduced which specifically modulate the slow synaptic dynamics in a neuronal network model of the subthalamic nucleus with activity dependent synaptic plasticity. A modeling approach is utilized to investigate the effects of the different stimulation techniques. In particular, the short-term and long-term outcome is studied in a mathematical model for a population of bursting STN neurons subject to synaptic plasticity with symmetric spike timing characteristics. In our mathematical model in the absence of stimulation synchronized network states with strong connectivity (modeling disease states) as well as desynchronized states with weak connectivity (modeling healthy states) are stable. We demonstrate that different stimulation techniques induce an anti-kindling by shifting the target population to a weakly connected, desynchronized state. Intriguingly, long-term anti-kindling can even be achieved although during stimulus delivery the neuronal synchrony hardly decreases or even slightly increases. The therapeutic index and the impact of inhibition, calculated to compare the different stimulation techniques, indicate that coordinated rest stimulation might be particularly robust and reliable. The presented stimulation strategies and the results of our modeling study might have strong implications in the context of deep brain stimulation.
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Deep brain stimulation (DBS) has been applied in more than 70000 patients worldwide during the last two decades. The main target is the subthalamic nucleus (STN) for the treatment of motor complications in late stage... more
Deep brain stimulation (DBS) has been applied in more than 70000 patients worldwide during the last two decades. The main target is the subthalamic nucleus (STN) for the treatment of motor complications in late stage Parkinson's disease (PD). Positive results in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated non-human primates have set the grounds for its successful translation to PD patients. Since then, this model has allowed gaining significant insights in the underlying mechanisms of action of DBS and is currently being used for the development of new stimulation techniques. Altogether, this underpins the high potential of this preclinical model for future translation of DBS research in PD.
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ABSTRACT
We present a novel, particularly robust technique for effective desynchronization of neuronal populations in the presence of noise. For this, delayed feedback signals are administered in a spatially coordinated way via at least two... more
We present a novel, particularly robust technique for effective desynchronization of neuronal populations in the presence of noise. For this, delayed feedback signals are administered in a spatially coordinated way via at least two stimulation sites using different delays for each stimulation site, respectively. For medical applications different variants of this approach are developed. These techniques are numerically tested in a physiologically realistic model. We propose our methods as novel, particularly mild and effective stimulation protocols for the therapy of patients suffering from Parkinson's disease, essential tremor or epilepsy.
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Recently, multisite delayed feedback stimulation was proposed as a novel method for mild and effective deep brain stimulation in neurological diseases characterized by pathological cerebral synchronization. To develop the mathematical... more
Recently, multisite delayed feedback stimulation was proposed as a novel method for mild and effective deep brain stimulation in neurological diseases characterized by pathological cerebral synchronization. To develop the mathematical background of this technique we propose a continuous medium model of globally coupled phase oscillators in the form of a delayed integro-differential equation. This model provides a convenient description of