The assessment of a novel electrical stimulation waveform recently introduced for the treatment of overactive bladder.

Transdermal amplitude modulated signal (TAMS) is a novel electrical stimulus which has been recently introduced for the treatment of overactive bladder (OAB) syndrome. It has been suggested that it has advantages over conventional waveforms by providing more effective penetration of the skin to enhance the efficacy of therapy. As there is no literature which supports this, we performed this study to evaluate potential advantages of the TAMS signal for electrical stimulation of subcutaneous nerves as compared to conventional stimuli. The stimuli were applied on forearms of ten healthy volunteers and electrical parameters of stimuli and sensation measurements were recorded. None of the recorded electrical parameters showed significant differences (paired t-test p ≥ 0.250) between the TAMS and conventional waveforms. Similarly, the mean sensation recorded at motor threshold level and at 50% of maximal motor response level showed no differences (paired t-test p = 0.242 and p = 0.687 respectively). It is unlikely, based on the results of this study, that TAMS provides any enhancement of the efficacy of conventional stimuli. We would recommend that further studies are carried out to clearly demonstrate in man what, if any, advantages the TAMS waveform has over conventional stimulation before it is widely deployed into clinical practice.

The effect of the impedance of a thin hydrogel electrode on sensation during functional electrical stimulation.

Surface functional electrical stimulation results in stimulation of cutaneous receptors and discomfort. The degree of non-uniformity of current distribution in the cutaneous layers in the vicinity of the electrode may influence the sensation experienced. This paper describes the effects on sensation of a thin, high impedance electrode designed to reduce the non-uniformity of current distribution. Sensation associated with stimulation via a self-adhesive electrode with much higher impedance than conventional electrodes was compared with a low impedance electrode in a single-blinded, crossover study. The high impedance electrode does not alter either the current at which sensation is first registered. However, at higher currents, the high impedance electrode allows 9% more current to be passed for an equivalent sensation to that experienced with the conventional electrode. A 28% decrease in discomfort with the use of the high impedance electrode was also reported.

Towards magnetic detection electrical impedance tomography: data acquisition and image reconstruction of current density in phantoms and in vivo.

The objective of magnetic detection electrical impedance tomography (MD-EIT) is to reconstruct in vivo images of conductivity from magnetic field measurements taken around the body. MD-EIT is performed by applying an alternating current, at one of a range of frequencies, to a conducting object through a pair of electrodes fixed to the surface of the object. Magnetic field measurements recorded by search coils at a number of positions around the object are used to determine the current distribution that is generating the magnetic field. From this distribution, a conductivity map of a cross-section of the object can be reconstructed. This paper describes the development of an MD-EIT data acquisition system and discusses the related image reconstruction issues. The ill-conditioned nature of the inverse problem is examined and a number of image reconstruction methods are compared. The technical feasibility of MD-EIT data collection and image reconstruction is demonstrated with example images of current density from both phantom and human data.

The acute effect of magnetic stimulation of the pelvic floor on involuntary detrusor activity during natural filling and overactive bladder symptoms.

OBJECTIVE: To evaluate the effect of magnetic stimulation of the pelvic floor (MSPF) on involuntary detrusor activity observed during natural filling, and on the overactive bladder symptom complex. PATIENTS AND METHODS: Eighteen women with detrusor overactivity on conventional cystometry underwent ambulatory urodynamic monitoring over two filling cycles. Fluid intake was standardized, provocative manoeuvres applied at regular intervals and symptoms documented contemporaneously. During the second filling cycle MSPF was delivered whenever the detrusor pressure increased by > 5 cmH2O. The women were subsequently treated with MSPF for 6 weeks; their lower urinary tract symptoms were assessed before and after treatment. RESULTS: Comparing the second (stimulated) cycle with the first (unstimulated) cycle, cystometric capacity was higher (373 vs 224 mL, P < 0.03). and involuntary detrusor activity of shorter duration (370 vs 427 s, P < 0.82) and lower amplitude (53 vs 63 cmH2O, P < or = 0.05). All women tolerated the procedure comfortably, but nine found it too time-consuming and withdrew. In the nine women who completed treatment there was no consistent change in overactive bladder symptoms. CONCLUSIONS: In this pilot study, MSPF during natural filling was associated with a decrease in the amplitude of involuntary detrusor contractions and a significant increase in cystometric capacity. However, MSPF had a variable effect on sensations of urgency, both acutely and after treatment, and currently there is no evidence to suggest that MSPF has an enduring effect on symptoms of the overactive bladder.

Transcranial magnetic stimulation. Which part of the current waveform causes the stimulation?

To investigate the mechanism of transcranial magnetic stimulation (TMS), we compared the directional effects of two stimulators (Magstim 200 and Magstim Super Rapid). First, stimulating visual cortex and facial nerve with occipital mid-line TMS, we found that, for a particular coil orientation, these two stimulators affected a particular neural structure in opposite hemispheres and that, to affect a particular neural structure in a particular hemisphere, these two stimulators required opposite coil orientations. Second, stimulating a membrane-simulating circuit, we found that, for a particular coil orientation, these two stimulators resulted in a peak induced current of the same polarity but in a peak induced charge accumulation of opposite polarity. We suggest that the critical parameter in TMS is the amplitude of the induced charge accumulation rather than the amplitude of the induced current. Accordingly, TMS would be elicited just before the end of the first (Magstim 200) and second (Magstim Super Rapid) phase of the induced current rather than just after the start of the first phase of the induced current.

Surface electromyography using electrode arrays: a study of motor neuron disease.

The use of electromyography (EMG) is limited, particularly in the investigation of children, by the invasive nature of needle electrodes. Surface electrode techniques are an attractive alternative but the detected signals are greatly influenced by volume conductor effects, thus making their interpretation problematic. Using finite element analysis we investigated the relationship between surface potential distribution and motor unit depth, incorporating anisotropic conductivity to model muscle tissue and a range of subcutaneous fat thicknesses. The modeling results were used to analyze data recorded with a 16-channel surface electrode array, from 10 normals subjects and 12 patients with motor neuron disease. Differences in the motor units between the two groups were statistically significant (P < 0.01) and are consistent with reinnervation and increased motor unit territory in the patient group. This noninvasive technique shows promise as a more acceptable alternative to the use of conventional needle electrodes for neurophysiological investigations.

The effect of static magnetic fields on the rate of calcium/calmodulin-dependent phosphorylation of myosin light chain.

This study reports an attempt to confirm a published and well-defined biological effect of magnetic fields. The biological model investigated was the phosphorylation of myosin light chain in a cell free system. The rate of phosphorylation has been reported to be affected in an approximately linear manner by static magnetic field strengths in the range 0-200 microT. We performed three series of experiments, two to test the general hypothesis and a third that was a direct replication of published work. We found no effect of static magnetic field strength on the rate of phosphorylation. Hence, we were unable to confirm that weak static magnetic fields affect the binding of calcium to calmodulin. In view of the difficulty we and other authors have had making independent verifications of claimed biological effects of magnetic fields, we would urge caution in the interpretation of published data until they have been independently confirmed. There are still few well defined biological effects of low level magnetic fields that have been successfully transferred to an independent laboratory.

Recombinant human CD40 ligand inhibits simian immunodeficiency virus replication: a role for interleukin- 16.

CD40 ligand (CD40L), expressed on activated T cells, binds its receptor, CD40, on dendritic cells, B cells, and monocytes/ macrophages. Human immunodeficiency virus (HIV)-infected individuals exhibit normal B-cell CD40 expression but diminished expression of CD40L on CD4 + T cells. Thus, we studied recombinant human CD40L (huCD40L) in an in vitro rhesus macaque model of acquired immunodeficiency syndrome (AIDS). huCD40L induced peripheral blood mononuclear cell (PBMC) proliferation independent of mitogenic cytokines and led to a 70% reduction in p27 production by simian immunodeficiency virus (SIV) mac239 infected PBMCs (P < 0.05). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed reduced expression of SIV gag and increased expression of interleukin (IL)-16 mRNA. Supernatants from huCD40L-stimulated PBMC and control cultures contained similar amounts of IL-16, suggesting an intracellular antiviral effect by IL-16. Phytohemagglutinin (PHA)-stimulated PBMCs similarly cultured with huCD40L showed only slight increases in chemokine production (P > 0.05). These results suggest that huCD40L inhibits replication (antigen and mRNA production) of SIVmac239. This response involves huCD40L induction of IL16 mRNA expression and appears to be independent of beta-chemokines.

An artefact desynchroniser for use with visual evoked potential stimulators.

When recording visual evoked potentials elicited by a CRT raster display, driven from a frame-synchronised stimulus generator, artefacts caused by magnetic fields originating from the CRT field coils may seriously contaminate the recordings. This interference cannot be removed by signal averaging as it is time locked to the frame rate of the CRT. The circuit described here effectively desynchronises the interference, enabling the signal averaging process to reduce the artefact without the bandwidth restriction and resultant distortion of the recording which would be caused by lowpass filtering.

Magnetic impedance tomography.

Tissue can be characterized by its electrical impedance, especially if measurement can be extended over a range of frequencies. Recently, there has been a great deal of interest in imaging the distribution of electrical impedance through the technique of electrical impedance tomography (EIT). However, EIT has a number of practical problems relating to the placement of electrodes on the body. Such contacts are not required to collect magnetic field data around an object through which current is flowing and thus this approach may be more practical than EIT in the clinical environment. This paper describes the technique of magnetic impedance tomography (MIT), which allows reconstruction of the current distribution from magnetic field measurements. The reconstruction techniques used to generate the images and the prototype data collection system are described. Images produced using data collected from discrete and distributed current phantoms and the thorax during human respiration are presented.

Measurement of the activating function of magnetic stimulation using combined electrical and magnetic stimuli.

The technique of combined magnetic and electrical stimulation of a peripheral nerve was used to determine the effectiveness of the combined stimulus and its dependence on the relative positioning of electrodes and stimulator coil along the axis of the nerve. The results were used to determine the magnetic stimulation-activating function of a long, straight nerve in the arm, and are shown to be consistent with published theoretical models constructed under conditions of simplified tissue geometry. With appropriate positioning of the two stimulators and similar tissue current waveforms, both enhancement and inhibition of an electrical stimulus were demonstrated and the maximum amplitude of the combined stimulus approached the arithmetic sum of that produced by each stimulator individually.

Electricity, magnetism and the body: some uses and abuses.

The human body can be regarded as an extraordinarily complex electrical machine. It will respond to externally applied electromagnetic stimuli and aspects of its functionality can be interrogated electromagnetically to aid in diagnosis. The paper describes examples of interactions between electromagnetism and the body. The hazards of electric shock are considered along with the use of the defibrillator for restarting the heart. Electromagnetic therapies are discussed in the light of the disappointing lack of objective evidence to support claims for their effectiveness. Finally, two examples of new diagnostic techniques using electromagnetic energy are described. Electrical impedance tomography produces cross-sectional images of the distribution of electrical impedance in the body and magnetic nerve stimulation uses currents induced by large magnetic field pulses to stimulate nerves and the human brain without causing pain.

Evaluation of the motor and sensory components of the pudendal nerve.

Extensive neurophysiological investigations consisting of different techniques to evaluate the efferents and afferents of the pudendal nerve were carried out in 27 healthy subjects. These investigations included motor evoked potential recordings from the external anal sphincter in response to magnetic stimulation of the cortex and lumbosacral roots, measurement of sacral reflex latency to magnetic and electrical stimulation, and cortical sensory evoked potential recording after stimulation of the dorso-genital nerve and anal canal. Motor latencies after transcranial magnetic stimulation to the anal sphincter were 25.1 +/- 2.9 msec at rest and 20.9 +/- 2.0 msec with voluntary sphincter contraction (facilitation). Motor latency after lumbosacral root stimulation was 3.7 +/- 1.0 msec. Mean sacral reflex latency after magnetic stimulation was 43.8 +/- 11.2 msec and was significantly longer than after electrical stimulation (37.0 +/- 7.2 msec; P < 0.05). P1 latency of the sensory evoked potentials after dorso-genital nerve stimulation was 40 +/- 3 msec and was significantly shorter than after anal stimulation 46 +/- 3 msec (P < 0.01). Evoked potential recording allows us to study both upper and lower motor neuron components to the anal sphincter. The present study paves the way for the combined application of these tests in the evaluation of disorders of the pelvic floor.

Magnetic fields and intracellular calcium: effects on lymphocytes exposed to conditions for 'cyclotron resonance'.

There are a number of claims in the literature that specific combinations of low-level DC and AC magnetic fields can cause biologically significant effects. The combinations of fields required to elicit these responses fulfil the theoretical conditions for classical cyclotron resonance of the selected ion. Because of the biological importance of calcium ions any effects on them are of particular interest, for instance the claimed increase in calcium uptake by electromagnetically exposed lymphocytes. We have measured the intracellular calcium concentration, by means of a sensitive fluorescent probe, during a 60 min exposure of mouse lymphocytes to 'cyclotron resonance' conditions for calcium ions. 'Resonance' conditions at two frequencies (16 Hz and 50 Hz) were tested, with a range of DC field amplitudes used to shift the frequency up to 25% either side of the calculated optimum. Treatment of the lymphocytes with concanavalin A was used as a positive control and caused a significant increase in intracellular calcium concentration. No change in intracellular calcium concentration could be detected when lymphocytes were exposed to 'cyclotron resonance' conditions or to the other magnetic field combinations used.

The effect of low-frequency pulsed magnetic fields on chick embryonic growth.

There are many claims made for biological effects of low-frequency pulsed magnetic fields ranging from beneficial to harmful, but few have been independently verified. The ubiquitous nature of both natural and man-made magnetic fields makes the possibility of biological interaction a potentially important subject. We have investigated the claimed stimulatory action of low-frequency pulsed magnetic fields, of a type used clinically, on the growth of embryonic chicks. Four day old embryos were exposed to a magnetic field, peak field strength 2.1 mT pulsed in 5 ms bursts repeated at 15 Hz, for 100 h. Embryo weights and long-bone lengths were compared to sham-exposed controls. Particular care was taken to reduce temperature differences between the test and control groups because this model has a known sensitivity to small temperature changes. We found no increase in embryonic growth due to this low-frequency pulsed magnetic field and hence have been unable to confirm earlier findings by other workers using the same model. We conclude that rigorous design of experimental protocol and a full description of the physical parameters are essential in studies purporting to show effects of electromagnetic fields if the results are to be confirmed by other workers.

An introduction to the basic principles of magnetic nerve stimulation.

Magnetic nerve stimulation is a new method for the noninvasive stimulation of neuromuscular tissue. The technique, developed at the University of Sheffield, United Kingdom, is being increasingly used for both clinical studies and basic research, with some 500 stimulators presently in use worldwide. This paper looks at the development of magnetic stimulation as a clinical tool. The basic physics principles of the technique are outlined, and the different magnetic field waveforms, coil geometrics, and orientations that can be used are discussed. The depth of penetration of magnetic stimulation is compared to that of conventional electrical stimulation using surface electrodes. It is shown that the former generates lower electric fields at the surface of the body, resulting in greater penetration and the ability to stimulate deep nerves without pain. Magnetic stimulation has several other advantages over electrical stimulation, including being able to stimulate the human brain without discomfort due to the magnetic fields passing through the skull without attenuation. These advantages, along with the limitations of the technique, are discussed. Finally, data relating to the safety of brain stimulation are summarised in terms of the electromagnetic parameters used. It is concluded that the present generation of magnetic stimulators do not cause acute hazards, provided their electrical and mechanical design meets the relevant electromedical safety standards.

Magnetic nerve stimulation: the effect of waveform on efficiency, determination of neural membrane time constants and the measurement of stimulator output.

We describe the first investigation into the effect on stimulation efficiency of varying the output of a commercial magnetic stimulator based on our original clinical design. Over the range of magnetic field waveforms considered, it is shown that the stored energy required to achieve stimulation, both cortically and in the periphery, varies by approximately 2:1. Greater efficiency is obtained by using shorter risetime magnetic fields. This results in more effective stimuli for the same stored energy, or, for the same stimulus, a decrease in energy storage, power dissipation and peak currents, thus simplifying hardware design. A novel method of processing the data obtained from different waveforms is presented which enables neural membrane time constant to be calculated. Data from normal subjects is presented showing both peripheral and neural time constants to be of order 150 microseconds. The cortical measurements represent the first non-invasive determination of cortical membrane time constant in man. Time constant measurements using magnetic stimulation may be clinically useful because they give information concerning the electrical properties of the nervous system not available from present techniques. Finally a method of quantifying the output of magnetic stimulators and coils is described which enables laboratory comparisons to be made, and takes into account magnetic field waveforms and coil geometry. The proposed symbol for this new measurement is Et150 with units volt seconds/meter.