Modular pulse synthesizer for transcranial magnetic stimulation with fully adjustable pulse shape and sequence.

The temporal shape of a pulse in transcranial magnetic stimulation (TMS) influences which neuron populations are activated preferentially as well as the strength and even direction of neuromodulation effects. Furthermore, various pulse shapes differ in their efficiency, coil heating, sensory perception, and clicking sound. However, the available TMS pulse shape repertoire is still very limited to a few biphasic, monophasic, and polyphasic pulses with sinusoidal or near-rectangular shapes. Monophasic pulses, though found to be more selective and stronger in neuromodulation, are generated inefficiently and therefore only available in simple low-frequency repetitive protocols. Despite a strong interest to exploit the temporal effects of TMS pulse shapes and pulse sequences, waveform control is relatively inflexible and only possible parametrically within certain limits. Previously proposed approaches for flexible pulse shape control, such as through power electronic inverters, have significant limitations: The semiconductor switches can fail under the immense electrical stress associated with free pulse shaping, and most conventional power inverter topologies are incapable of generating smooth electric fields or existing pulse shapes. Leveraging intensive preliminary work on modular power electronics, we present a modular pulse synthesizer (MPS) technology that can, for the first time, flexibly generate high-power TMS pulses (one-side peak ∼4000 V, ∼8000 A) with user-defined electric field shape as well as rapid sequences of pulses with high output quality. The circuit topology breaks the problem of simultaneous high power and switching speed into smaller, manageable portions, distributed across several identical modules. In consequence, the MPS TMS techology can use semiconductor devices with voltage and current ratings lower than the overall pulse voltage and distribute the overall switching of several hundred kilohertz among multiple transistors. MPS TMS can synthesize practically any pulse shape, including conventional ones, with fine quantization of the induced electric field (⩽17% granularity without modulation and ∼300 kHz bandwidth). Moreover, the technology allows optional symmetric differential coil driving so that the average electric potential of the coil, in contrast to conventional TMS devices, stays constant to prevent capacitive artifacts in sensitive recording amplifiers, such as electroencephalography. MPS TMS can enable the optimization of stimulation paradigms for more sophisticated probing of brain function as well as stronger and more selective neuromodulation, further expanding the parameter space available to users.

Noninvasive Detection of Motor-Evoked Potentials in Response to Brain Stimulation Below the Noise Floor-How Weak Can a Stimulus Be and Still Stimulate.

Motor-evoked potentials (MEP) are one of the most important responses to brain stimulation, such as supra-threshold transcranial magnetic stimulation (TMS) and electrical stimulation. The understanding of the neurophysiology and the determination of the lowest stimulation strength that evokes responses requires the detection of even smallest responses, e.g., from single motor units, but available detection and quantization methods are rather simple and suffer from a large noise floor. The paper introduces a more sophisticated matched-filter detection method that increases the detection sensitivity and shows that activation occurs well below the conventional detection level. In consequence, also conventional threshold definitions, e.g., as 50 µV median response amplitude, turn out to be substantially higher than the point at which first detectable responses occur. The presented method uses a matched-filter approach for improved sensitivity and generates the filter through iterative learning from the presented data. In contrast to conventional peak-to-peak measures, the presented method has a higher signal-to-noise ratio (≥14 dB). For responses that are reliably detected by conventional detection, the new approach is fully compatible and provides the same results but extends the dynamic range below the conventional noise floor. The underlying method is applicable to a wide range of well-timed biosignals and evoked potentials, such as in electroencephalography.

Optimization of magnetic neurostimulation waveforms for minimum power loss.

Magnetic stimulation is a key tool in experimental brain research and several clinical applications. Whereas coil designs and the spatial field properties have been intensively studied in the literature, the temporal dynamics of the field has received little attention. The available pulse shapes are typically determined by the relatively limited capabilities of commercial stimulation devices instead of efficiency or optimality. Furthermore, magnetic stimulation is relatively inefficient with respect to the required energy compared to other neurostimulation techniques. We therefore analyze and optimize the waveform dynamics with a nonlinear model of a mammalian motor axon for the first time, without any pre-definition of waveform candidates. We implemented an unbiased and stable numerical algorithm using variational calculus in combination with a global optimization method. This approach yields very stable results with comprehensible characteristic properties, such as a first phase which reduces ohmic losses in the subsequent pulse phase. We compare the energy loss of these optimal waveforms with the waveforms generated by existing magnetic stimulation devices.

Circuit topology and control principle for a first magnetic stimulator with fully controllable waveform.

Magnetic stimulation pulse sources are very inflexible high-power devices. The incorporated circuit topology is usually limited to a single pulse type. However, experimental and theoretical work shows that more freedom in choosing or even designing waveforms could notably enhance existing methods. Beyond that, it even allows entering new fields of application. We propose a technology that can solve the problem. Even in very high frequency ranges, the circuitry is very flexible and is able generate almost every waveform with unrivaled accuracy. This technology can dynamically change between different pulse shapes without any reconfiguration, recharging or other changes; thus the waveform can be modified also during a high-frequency repetitive pulse train. In addition to the option of online design and generation of still unknown waveforms, it amalgamates all existing device types with their specific pulse shapes, which have been leading an independent existence in the past years. These advantages were achieved by giving up the common basis of all magnetic stimulation devices so far, i.e., the high-voltage oscillator. Distributed electronics handle the high power dividing the high voltage and the required switching rate into small portions.

Comparison of coil designs for peripheral magnetic muscle stimulation.

The recent application of magnetic stimulation in rehabilitation is often said to solve key drawbacks of the established electrical method. Magnetic fields cause less pain, allow principally a better penetration of inhomogeneous biologic tissue and do not require skin contact. However, in most studies the evoked muscle force has been disappointing. In this paper, a comparison of a classical round circular geometry, a commercial muscle-stimulation coil and a novel design is presented, with special emphasis on the physical field properties. These systems show markedly different force responses for the same magnetic energy and highlight the enormous potential of different coil geometries. The new design resulted in a slope of the force recruiting curve being more than two and a half times higher than the other coils. The data were analyzed with respect to the underlying physical causes and field conditions. After a parameter-extraction approach, the results for the three coils span a two-dimensional space with clearly distinguishable degrees of freedom, which can be manipulated nearly separately and reflect the two main features of a field; the peak amplitude and its decay with the distance.

Fasciated nerve-muscle explants for in vitro comparison of magnetic and electrical neuromuscular stimulation.

Neuromuscular stimulation has become a central technique for research and clinical efforts in rehabilitation, but available devices still do not show the needed performance in strength and selectivity for this approach. However, the knowledge about the exact intramuscular structure formed by the axons, muscle fibers with their different metabolism types and properties as well as the motoric endplates in between is still too rough for purely theoretical optimization. In this text, we present an experimental setup for parametrized studies of the spatial and temporal degrees of freedom (DOF) in electrical as well as magnetic stimulation. For clarification of the physiologic background, nerve-muscle explants are dissected and kept on life support in a nutrient system with glucose and oxygen supply. The setup provides two-channel EMG signals and a dynamic force signal. The design was adapted to meet the conditions for physical compatibility with magnetic stimulation and allows coil position sweeps with four (three translational and one rotational) DOF. The setup provides access to essential boundary conditions and means to simulate lesions as well as the influence of drugs. Besides with the presented setup, comparisons and even combined application of magnetic and electrical stimulation become possible on the level of the neuromuscular system. Finally, this approach shall help to improve rehabilitation by peripheral stimulation after nerve lesions. The focus of this text lies on the setup and the nutrition which will entail particular studies in the sequel.

[Test-retest reliability of a German language multidimensional assessment instrument in elderly probands]. / Test-Retest-Reliabilität eines deutschsprachigen multidimensionalen Assessmentinstruments bei älteren Personen.

Most geriatric assessment instruments have been developed in the English language. Translated versions might differ in their psychometric properties. We analyzed the test-retest reliability and internal consistency of a German instrument for multidimensional geriatric assessment that was based on a newly developed English version. A group of 100 over 75-year-old community-dwelling persons (mean age 83.0 years, 81% women) in Hamburg (n = 26) and Ulm (n = 51), Germany, and Berne (n = 23), Switzerland was interviewed twice by the same trained interviewers with a one week interval. We administered questions on general health, chronic disorders, basic and instrumental activities of daily living, urinary incontinence, nutrition, falls, pain, the social support/network and preventive care measures. In addition, the Functional Status Questionnaire, the Physical Activity Scale for the Elderly, the Geriatric Oral Health Assessment Index, the Visual Function Questionnaire, the Hearing Handicap Inventory for the Elderly and the Geriatric Depression Scale were administered. Cohen's kappa was good to excellent (0.64 < or = kappa < or = 0.89) with only three exceptions (pain questions, kappa = 0.53; questions on preventive care services, kappa = 0.51; and one of the questions on recent falls, kappa = 0.44). Cronbach alpha (internal consistency) was good to excellent for all domains (0.76 < or = alpha < or = 0.95). The study results confirm good test-retest reliability of the German version of this multidimensional geriatric assessment instrument. Adapted versions of this instrument can be used for different purposes, e.g., preventive home visits, outpatient geriatric assessments or epidemiological studies in older persons.

[A multidimensional questionnaire as a component of preventive geriatric assessment: comparison of self-assessment version with the interview version]. / Ein multidimensionaler Fragebogen als Bestandteil eines präventiven geriatrischen Assessments: Vergleich der Selbstausfüllerversion mit der Interviewversion.

In an earlier study we have shown good internal consistency and test-retest-reliability of a newly developed German-language instrument in the interviewer-administered version. The aim of this study was to test the reliability of a self-administered version compared to the original interviewer-administered version of our newly developed German-language instrument. We recruited a group of 50 over 75-year-old community-dwelling persons in Hamburg, Germany (N = 25) and Berne, Switzerland (N = 25). The questionnaire contains items on: self-perceived health, chronic conditions, basic and instrumental activities of daily living, urinary incontinence, nutrition, recent falls, pain, the social support/network and preventive-care measures. In addition, the Functional Status Questionnaire, the Physical Activity Scale for the Elderly, the Geriatric Oral Health Assessment Index, the Visual Function Questionnaire, the Hearing Handicap Inventory for the Elderly and the Geriatric Depression Scale were administered. Cohen's Kappa (self-administered version compared to the interviewer-administered version) was good to excellent (0.69-1.0) with only three exceptions (physical activity kappa = 0.49, basic activities kappa = 0.54 and oral health kappa = 0.54). For the domains activities of daily living, oral health, visual function and depression the self-administered version detected significantly more problems than the interview. In the future the self-administered version of this assessment instrument can be used for various purposes, e.g. (annual) preventive geriatric assessment for outpatients and other community-dwelling persons and epidemiological studies in older persons.

[Preventive home visits for elderly patients: development and pilot testing of a multidimensional assessment instrument]. / Präventive Hausbesuche im Alter: Entwicklung und Pilottestung eines multidimensionalen Abklärungsinstruments.

Preventive home visits with multidimensional geriatric assessment have been shown to delay or prevent the onset of disability and reduce nursing home admissions in older people. The purpose of the present study was to develop and test a multidimensional instrument for in-home preventive assessments in older persons. In developing the instrument, we conducted a systematic literature review of risk factors for functional status decline and of appropriate instruments for measuring these risk factors. Based on an Expert Panel using a modified Delphi process [1] the risk factor domains for functional status decline were chosen, [2] the instruments for evaluating each of the included risk factor domains were selected, and [3] the individual instruments were combined into one comprehensive assessment instrument. A German language version of the original English version of the instrument was developed based on translation, backtranslation, and cultural adaptation. The feasibility of use of the new instrument was evaluated in a field test in 150 people aged 75 years and older in Hamburg, Ulm, Germany, and Bern, Switzerland. The instrument was well accepted by the older persons. The prevalence of risk factors for functional status decline in these populations (e.g., physical inactivity, urinary incontinence, vision impairment) was high. There was also a high prevalence of underuse of preventive care measures (e.g., no pneumococcal vaccination in over 95 percent of persons). These preliminary results support the possible usefulness of this instrument for conducting preventive home visits or for epidemiological purposes (e.g., prevention surveillance). In a next phase, the test-retest reliability of the instrument, and the feasibility and reliability of self-administration as compared to interviewer administration will be described in a separate paper.

[Falls in elderly patients--assessment of falls with reference to etiology and prevention]. / Stürze älterer Menschen--von Sturzassessment zu Abklärung und Prävention.

Falls have been identified as a major risk factor for disability. There is an increasing risk of falls and fall-related injuries in the elderly due to a decline in mobility and due to multimorbidity. Intrinsic and extrinsic factors lead to falls with and without syncope. Among nursing-home residents intrinsic factors are the main cause of falls, whereas community-dwelling elderly are more likely to fall because of environment (extrinsic) factors. Assessment of falls must be detailed, multidimensional and function-orientated, and aimed at identifying the causes of the index fall and risk-factors for further falls. As the risk of falling increases linearly with the number of abnormalities contributing to decreased mobility (mental status, mood, decline in sensory inputs, neurological and musculosceletal affections), identifying all risk factors increases the chance of successful intervention. Prevention of fall-related sequalae and further falls is the major goal of therapy. Primary prevention should be included in the scope of future strategies. The basis of successful intervention is fall-assessment, risk-factor assessment, causative therapy, if possible, as well as individually adapted function-orientated therapy programs, and, if at all possible, endurance and resistance training.

[Backache: state-of-the-art from a biopsychosocial viewpoint]. / Rückenschmerzen: "State-of-the-art" aus biopsychosozialer Sicht.

The state-of-the-art in the diagnosis and therapy of low back pain is presented from a biopsychosocial point of view. Among low back pain patients, those dominate in whom psychosocial factors play an eminent role. The early comprehensive (biopsychosocial) integrative diagnosis is essential for further development of the illness. Conversion pain, psychoprosthetic pain and pain-proneness are the most important concepts for establishing a round diagnostic assessment and realistic therapeutic measures.