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Purpose Transcranial magnetic stimulation (TMS) is a neurophysiological technique with a long established pedigree of safety, tolerability, and efficacy. Initially TMS was used to study the function of the cerebral cortex, but it has now become a treatment for migraine, one of the most common and debilitating neurological conditions. In this review we discuss the scientific background and development of the technique. We explore its application for the treatment of migraine and ponder the possible mechanisms of action in this most common neurological condition. Overview: The generation of brief magnetic pulses by a suitable coil can induce electrical fields in the body. When applied to the cerebral cortex, currents are painlessly induced in cortical neurons. These currents can lead to neuronal depolarization and may influence cortical excitability by means that are as yet not fully understood. This ability to modulate cortical excitability has been exploited as a treatment for migraine with aura. Aura is implicated in the pathophysiology of migraine. Experimental studies have shown that transcranial magnetic pulses can block waves of cortical spreading depression – the experimental equivalent of migrainous aura. Discussion Migraine is a debilitating condition characterized by headache, nausea, and sensory hypersensitivity. It may affect up to 15% of the population, yet current drug treatments are often poorly tolerated. Clinical studies have shown that TMS is an effective treatment for migraine. In addition, it has the added advantages of being safe and well tolerated by patients.

Objective To determine whether theta burst repetitive transcranial magnetic stimulation is an effective treatment for chronic tinnitus compared with a control stimulus. Study design A two-arm, single-blind, randomized controlled trial comparing an active treatment group to a placebo control group. Setting Neurotology department of a tertiary referral center. Patients Forty new and existing patients with chronic unilateral or bilateral tinnitus were recruited from specialist hearing and balance clinics. Interventions The subjects were randomized into two groups representing the treatment and sham subcategories. Two 40 second trains, 15 minutes apart of transcranial stimulation was provided using a super rapid stimulator (2.2. Tesla, Magstim Inc., Wales, UK) using a circular delivery coil. Treatment was provided over 5 consecutive days. Main outcome measure Tinnitus functional index (TFI) scores were recorded before treatment, immediately after treatment, 2 weeks, and at 4 weeks following treatment and compared. Results TFI scores were analyzed using the Shapiro-Wilk test and found to be normally distributed. A paired Student t test was then performed. Both the active treatment group and control group had a significant improvement in their TFI scores following treatment; however, there was no significant difference between active treatment and sham treatment groups. Conclusion This study demonstrated a significant placebo effect following treatment with sham therapy and may suggest that repetitive transcranial magnetic stimulation does not have a therapeutic use in treating chronic tinnitus.

Hydrogel electrodes are commonly used for functional and other electrical stimulation applications since the hydrogel layer has been shown to considerably reduce the perception of stimulation compared to dry electrodes. However, these hydrogel electrodes must be changed regularly as they dry out or become contaminated with skin cells and sweat products, thus losing their adhesiveness and resistive properties. Dry electrodes are longer lasting but are more uncomfortable due to unequal current distribution (current hogging). We hypothesise that if current through a dry electrode is equally shared amongst an array of small sub-electrodes, current hogging and thus the sensitivity perceived due to stimulation will be reduced. We constructed an 8 × 8 array of millimetre sized dry electrodes that could either be activated as individual current sources, or together as one large source. A study was performed with 13 participants to investigate the differences in sensation between the two modes of operation. The results showed that 12 out of 13 participants found the new (distributed-constant-current) approach allowed higher stimulation for the same sensation. The differences in sensation between single and multiple sources became larger with higher intensity levels.

We reviewed the literature on transcutaneous electrical nerve stimulation (TENS) used as a therapy for overactive bladder (OAB) symptoms, with a particular focus on: stimulation site, stimuli parameters, neural structures thought to be targeted, and the clinical and urodynamic outcomes achieved. The majority of studies used sacral or tibial nerve stimulation. The literature suggests that, whilst TENS therapy may have neuromodulation effects, patient are unlikely to benefit to a significant extent from a single application of TENS and indeed clear benefits from acute studies have not been reported. In long-term studies there were differences in the descriptions of stimulation intensity, strategy of the therapy, and positioning of the electrodes, as well as in the various symptoms and pathology of the patients. Additionally, most studies were uncontrolled and hence did not evaluate the placebo effect. Little is known about the underlying mechanism by which these therapies work and therefore exactly which structures need to be stimulated, and with what parameters. There is promising evidence for the efficacy of a transcutaneous stimulation approach, but adequate standardisation of stimulation criteria and outcome measures will be necessary to define the best way to administer this therapy and document its efficacy.

Functional electrical stimulation has been shown to be a safe and effective means of correcting drop foot of central neurological origin. However, despite recent technological advances, the set-up of surface stimulators remains a challenge for many users with drop foot. The automation of the setup process through the use of electrode arrays has been proposed as a way to address this problem. This paper describes a series of research and clinical studies which have led to the first demonstration of unsupervised automated setup of an electrode-array based drop foot stimulator. Finally, future research plans are discussed.

Objective: Gradiometers have the advantage of increasing measuring sensitivity, which is particularly useful in magnetic induction spectroscopy (MIS) for bio-impedance measurements. Traditional gradiometers use a pair of field sensing coils equally distant and on opposite sides of a drive coil, which provides high immunity to interference. In this paper, a ferrite-cored coaxial gradiometer probe of 29 mm diameter has been developed for measuring the impedance spectra of cervical tissues in vivo. Approach: It consists of a ferrite rod with outer ferrite confinement screening in order to eliminate the signals from surrounding tissue. The magnetic screening efficiency was compared with an air-cored gradiometer probe. For both gradiometer probes, a drive coil and two sensing coils were wound on a borosilicate glass former aligned coaxially with two sensing coils equidistant from the drive coil. The signal sensitivity of those two MIS gradiometers has been measured using saline samples with a conductivity range between 0.1 and 1.1 S m−1. Finite element methods using COMSOL Multiphysics have been used to simulate the distribution of sensitivity to conductivity over the face of each probe and with depth. Main Results: The ferrite-cored probe has a sensitivity confined to the volume defined by the gap between the ferrite core and outer tube of ferrite while the air-cored probe without any magnetic shielding had a wide sensitivity over the face and the side of the probe. Four saline samples and one of distilled water with conductivities from 0.1 to 1.1 S m−1 have been used to make conductivity measurements at frequencies of 50 kHz, 100 kHz, and 300 kHz. The measurement accuracy of the air-cored MIS probe was 0.09 S m−1 at 50 kHz, improving to 0.05 S m−1 at 300 kHz. For the ferrite-cored MIS probe, the measurement accuracy was 0.28 S m−1 at 50 kHz, improving to 0.04 S m−1 at 300 kHz. Significance: In vivo measurements on human hand have been performed using both types of gradiometers and the conductivity is consistent with reported data.

Functional electrical stimulation has been shown to be a safe and effective means of correcting foot 12 drop of central neurological origin. Current surface-based devices typically consist of a single channel stimulator, 13 a sensor for determining gait phase and a cuff, within which is housed the anode and cathode. The cuff-mounted 14 electrode design reduces the likelihood of large errors in electrode placement, but the user is still fully responsible 15 for selecting the correct stimulation level each time the system is donned. Researchers have investigated different 16 approaches to automating aspects of setup and/or use, including recent promising work based on iterative learning 17 techniques. This paper reports on the design and clinical evaluation of an electrode array-based FES system for 18 the correction of drop foot, ShefStim. The paper reviews the design process from proof of concept lab-based study, 19 through modelling of the array geometry and interface layer to array search algorithm development. Finally, the 20 paper summarises two clinical studies involving patients with drop foot. The results suggest that the ShefStim 21 system with automated setup produces results which are comparable with clinician setup of conventional systems. 22 Further, the final study demonstrated that patients can use the system without clinical supervision. When used 23 unsupervised, setup time was 14 minutes (9 minutes for automated search plus 5 minutes for donning the 24 equipment), although this figure could be reduced significantly with relatively minor changes to the design.

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.

Functional electrical stimulation is commonly used to correct drop foot following stroke or multiple sclerosis. This technique is successful for many patients, but previous studies have shown that a significant minority have difficulty identifying correct sites to place the electrodes in order to produce acceptable foot movement. Recently there has been some interest in the use of 'virtual electrodes', the process of stimulating a subset of electrodes chosen from an array, thus allowing the site of stimulation to be moved electronically rather than physically. We have developed an algorithm for automatically determining the best site of stimulation and tested it on a computer linked to a small, battery-powered prototype stimulator with 64 individual output channels. Stimulation was delivered via an 8×8 array adhered to the leg by high-resistivity self-adhesive hydrogel. Ten participants with stroke (ages 53-71 years) and 11 with MS (ages 40-80 years) were recruited onto the study and performed two walks of 10 m for each of the following conditions: own setup (PS), clinician setup (CS), automated setup (AS) and no stimulation (NS). The PS and CS conditions used the participant's own stimulator with two conventional electrodes; the AS condition used the new stimulator and algorithm. Outcome measures were walking speed, foot angle at initial contact and the Borg Rating of Perceived Exertion. Mean walking speed with no stimulation was 0.61 m/s; all FES setups significantly increased speed relative to this (AS p0.05, PS p0.01, CS p0.01). Speed for PS (0.72 m/s) was faster than both AS (0.65 m/s, p0.01) and CS (0.68 m/s, p0.05). Frontal plane foot orientation at heel-strike was more neutral for AS (0.3° everted) than in the NS (11.2° inverted, p0.01), PS (4.5° inverted, p0.05) and CS (3.1° inverted, p0.05) conditions. Dorsiflexion angles for AS (4.2°) were larger than NS (-3.0°, p0.01), not different to PS (4.3°, p0.05) and less dorsiflexed than CS (6.0°, p0.05). This proof of principle study has demonstrated that automated setup of an array stimulator produces results broadly comparable to clinician setup. Slower walking speed for automated and clinician setups compared to the participants' own setup may be due to the participants' lack of familiarity with responses different to their usual setups. Automated setup using the method described here seems sufficiently reliable for future longer-term investigation outside the laboratory and may lead to FES becoming more viable for patients who, at present, have difficulty setting up conventional stimulators.

Adjustments to movement in response to changes in our surroundings are common in everyday behavior. Previous research has suggested that the left pre-motor cortex (PMC) is specialized for the temporal control of movement and may play a role in temporal error correction. The aim of this study was to determine the role of the left PMC in sensorimotor timing and error correction using theta burst transcranial magnetic stimulation (TBS). In Experiment 1, subjects performed a sensorimotor synchronization task (SMS) with the left and the right hand before and after either continuous or intermittent TBS (cTBS or iTBS). Timing accuracy was assessed during synchronized finger tapping with a regular auditory pacing stimulus. Responses following perceivable local timing shifts in the pacing stimulus (phase shifts) were used to measure error correction. Suppression of the left PMC using cTBS decreased timing accuracy because subjects tapped further away from the pacing tones and tapping variability increased. In addition, error correction responses returned to baseline tap–tone asynchrony levels faster following negative shifts and no overcorrection occurred following positive shifts after cTBS. However, facilitation of the left PMC using iTBS did not affect timing accuracy or error correction performance. Experiment 2 revealed that error correction performance may change with practice, independent of TBS. These findings provide evidence for a role of the left PMC in both sensorimotor timing and error correction in both hands. We propose that the left PMC may be involved in voluntarily controlled phase correction responses to perceivable timing shifts.

Safe and effective transcranial magnetic stimulation (TMS) requires accurate intensity calibration. Output is typically calibrated to individual motor cortex excitability and applied to nonmotor brain areas, assuming that it captures a site nonspecific factor of excitability. We tested this assumption by correlating the effect of TMS at motor and visual cortex. In 30 participants, we measured motor threshold (MT) and phosphene threshold (PT) at the scalp surface and at coil-scalp distances of 3.17, 5.63, and 9.03 mm. We also modeled the effect of TMS in a simple head model to test the effect of distance. Four independent tests confirmed a significant correlation between PT and MT. We also found similar effects of distance in motor and visual areas, which did not correlate across participants. Computational modeling suggests that the relationship between the effect of distance and the induced electric field is effectively linear within the range of distances that have been explored empirically. We conclude that MT-guided calibration is valid for nonmotor brain areas if coil-cortex distance is taken into account. For standard figure-of-eight TMS coils connected to biphasic stimulators, the effect of cortical distance should be adjusted using a general correction factor of 2.7% stimulator output per millimeter.

Computational models have been be used to estimate the electric and magnetic fields induced by transcranial magnetic stimulation (TMS) and can provide valuable insights into the location and spatial distribution of TMS stimulation. However, there has been little translation of these findings into practical TMS research. This study uses the International 10-20 EEG electrode placement system to position a standard figure-of-eight TMS coil over 13 commonly adopted targets. Using a finite element method and an anatomically detailed and realistic head model, this study provides the first pictorial and numerical atlas of TMS-induced electric fields for a range of coil positions. The results highlight the importance of subject-specific gyral folding patterns and of local thickness of subarachnoid cerebrospinal fluid (CSF). Our modelling shows that high electric fields occur primarily on the peaks of those gyri which have only a thin layer of CSF above them. These findings have important implications for inter-individual generalizability of the TMS-induced electric field. We propose that, in order to determine with accuracy the site of stimulation for an individual subject, it is necessary to solve the electric field distribution using subject-specific anatomy obtained from a high-resolution imaging modality such as MRI.

Gravitational forces may lead to local changes in subarachnoid cerebrospinal fluid (CSF) layer thickness, which has important implications for neurophysiological modulation and recording techniques. This study examines the effect of gravitational pull associated with different head positions on the distribution of subarachnoid CSF using structural magnetic resonance imaging. Images of seven subjects in three different positions (supine, left lateral and prone) were statistically compared. Results suggest that subarachnoid CSF volume decreases on the side of the head closest to the ground, due to downward brain movement with gravity. These findings warrant future research into currently unexplored gravitation-induced changes in regional subarachnoid CSF thickness.

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.

In three experiments, we investigated the role of the cerebellum in sub- and suprasecond time perception by using repetitive transcranial magnetic stimulation (rTMS). In Experiment 1, subjects underwent four 8-min 1-Hz rTMS sessions in a within-subject design. rTMS sites were the medial cerebellum (real and sham rTMS), left lateral cerebellum, and right lateral cerebellum. Following each rTMS session, subjects completed a subsecond temporal bisection task (stimuli in the range 400–800 msec). Compared with sham rTMS, rTMS applied over the right lateral or medial cerebellum induced a leftward shift of the psychophysical function (perceived lengthening of time). In Experiment 2, a separate sample of subjects underwent the identical rTMS procedure and completed a suprasecond bisection task (stimuli in the 1000–2000 msec range). In this experiment, rTMS to the cerebellar sites did not produce any significant changes compared with sham rTMS. Experiment 3 employed a within-subject design to replicate findings from Experiments 1 and 2. Subjects underwent four rTMS conditions (sub- and suprabisection tasks following medial cerebellar and sham rTMS). rTMS induced a significant leftward shift of psychophysical function in the subsecond bisection, but not in the suprasecond bisection. In this study, we have demonstrated that transient cerebellar stimulation can differently affect the ability to estimate time intervals below and above a duration of 1 sec. The results of this study provide direct evidence for the role of the cerebellum in processing subsecond time intervals. This study further suggests that the perception of sub- and suprasecond intervals is likely to depend upon distinct neural systems.

OBJECTIVE To assess the feasibility of using a novel form of multichannel electrical stimulation, termed Sensory Barrage Stimulation (SBS) for the treatment of spasticity affecting the elbow flexor muscles and to compare this with conventional single-channel TENS stimulation. MATERIALS AND METHODS Altogether ten participants with spasticity of the flexor muscles of the elbow of Grade 2 or above on the Modified Ashworth Scale (MAS) were recruited to this crossover double blind randomized trial. The participants received two intervention sessions (SBS and TENS), one week apart in a randomized order. Both interventions were applied over the triceps brachii on the affected arm for a duration of 60 minutes. Spasticity was measured using the MAS. Secondary outcome measures were self-reported change in spasticity, measured on a visual analog scale (VAS, 0-100), and therapist-rated strength of elbow extension and strength of elbow flexion. Measurements were taken immediately before each intervention was applied, immediately after the intervention, and one hour after the intervention. RESULTS Immediately after stimulation spasticity showed a significant reduction for both TENS and SBS groups assessed by MAS -0.9 ± 0.2 vs. -1.1 ± 0.2 and by VAS -15 ± 3 vs. -31 ± 8. For SBS this improvement in MAS was still present at one hour after the stimulation, but not for TENS. Altogether seven SBS responders and four TENS responders were identified. CONCLUSIONS This study demonstrates the feasibility and practicality of applying the new concept of SBS. Promising results indicate it causes a reduction in spasticity.

To appraise the application of accepted good practice guidance on public involvement in assistive technology research and to identify its impact on the research team, the public, device and trial design.Critical reflection and within-project evaluation were undertaken in a case study of the development of a functional electrical stimulation device. Individual and group interviews were undertaken with lay members of a 10 strong study user advisory group and also research team members.Public involvement was seen positively by research team members, who reported a positive impact on device and study designs. The public identified positive impact on confidence, skills, self-esteem, enjoyment, contribution to improving the care of others and opportunities for further involvement in research. A negative impact concerned the challenge of engaging the public in dissemination after the study end.The public were able to impact significantly on the design of an assistive technology device which was made more fit for purpose. Research team attitudes to public involvement were more positive after having witnessed its potential first hand. Within-project evaluation underpins this case study which presents a much needed detailed account of public involvement in assistive technology design research to add to the existing weak evidence base.The evidence base for impact of public involvement in rehabilitation technology design is in need of development. Public involvement in co-design of rehabilitation devices can lead to technologies that are fit for purpose. Rehabilitation researchers need to consider the merits of active public involvement in research.

Several studies have investigated the neural basis of effortful emotion regulation (ER) but the neural basis of automatic ER has been less comprehensively explored. The present study investigated the neural basis of automatic ER supported by ‘implementation intentions’. 40 healthy participants underwent fMRI while viewing emotion-eliciting images and used either a previously-taught effortful ER strategy, in the form of a goal intention (e.g., try to take a detached perspective), or a more automatic ER strategy, in the form of an implementation intention (e.g., “If I see something disgusting, then I will think these are just pixels on the screen!”), to regulate their emotional response. Whereas goal intention ER strategies were associated with activation of brain areas previously reported to be involved in effortful ER (including dorsolateral prefrontal cortex), ER strategies based on an implementation intention strategy were associated with activation of right inferior frontal gyrus and ventro-parietal cortex, which may reflect the attentional control processes automatically captured by the cue for action contained within the implementation intention. Goal intentions were also associated with less effective modulation of left amygdala, supporting the increased efficacy of ER under implementation intention instructions, which showed coupling of orbitofrontal cortex and amygdala. The findings support previous behavioural studies in suggesting that forming an implementation intention enables people to enact goal-directed responses with less effort and more efficiency.

Although evidence is controversial, exposure to environmental power-frequency magnetic fields is of public concern. Cells respond to some abnormal physiological conditions by producing cytoprotective heat-shock (or stress) proteins. In this study, we determined whether exposure to power-frequency magnetic fields in the range 0-100 microT rms either alone or concomitant with mild heating induced heat-shock protein gene expression in human leukocytes, and we compared this response to that induced by heat alone. Samples of human peripheral blood were simultaneously exposed to a range of magnetic-field amplitudes using a regimen that was designed to allow field effects to be distinguished from possible artifacts due to the position of the samples in the exposure system. Power-frequency magnetic-field exposure for 4 h at 37 degrees C had no detectable effect on expression of the genes encoding HSP27, HSP70A or HSP70B, as determined using reverse transcriptase-PCR, whereas 2 h at 42 degrees C elicited 10-, 5- and 12-fold increases, respectively, in the expression of these genes. Gene expression in cells exposed to power-frequency magnetic fields at 40 degrees C was not increased compared to cells incubated at 40 degrees C without field exposure. These findings and the extant literature suggest that power-frequency electromagnetic fields are not a universal stressor, in contrast to physical agents such as heat.

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

A Crawford transverse electro-magnetic (TEM) cell, used for RF exposure of in vitrocell cultures to examine any pathological effects, is modelled using an original high resolution finite-difference time-domain (FDTD) code at cellular handset frequencies. The standard scalar specific absorption rate (SAR) dosimetry parameter is augmented by new vector parameters of field polarization type and phase, and an easily comprehensible way of displaying these data as polar plots is used. It is shown that whilst the incident field in the empty TEM cell has plane wave properties, the exposure field in a blood sample is not a TEM plane wave, nor is it representative of the near field produced by a mobile handset. It is suggested that the exposure field vector properties need to be quantified and controlled in the TEM cell, and experimentation performed to assess whether there is a differential cellular stress response to these parameters in addition to SAR level. Copyright © 2002 John Wiley & Sons, Ltd.

Objective\ud \ud To investigate the feasibility of unsupervised community use of an array-based automated setup functional electrical stimulator for current foot-drop functional electrical stimulation (FES) users.\ud \ud Design\ud \ud Feasibility study.\ud \ud Setting\ud \ud Gait laboratory and community use.\ud \ud Participants\ud \ud Participants (N=7) with diagnosis of unilateral foot-drop of central neurologic origin (>6mo) who were regular users of a foot-drop FES system (>3mo).\ud \ud Intervention\ud \ud Array-based automated setup FES system for foot-drop (ShefStim).\ud \ud Main Outcome Measures\ud \ud Logged usage, logged automated setup times for the array-based automated setup FES system and diary recording of problems experienced, all collected in the community environment. Walking speed, ankle angles at initial contact, foot clearance during swing, and the Quebec User Evaluation of Satisfaction with Assistive Technology version 2.0 (QUEST version 2.0) questionnaire, all collected in the gait laboratory.\ud \ud Results\ud \ud All participants were able to use the array-based automated setup FES system. Total setup time took longer than participants' own FES systems, and automated setup time was longer than in a previous study of a similar system. Some problems were experienced, but overall, participants were as satisfied with this system as their own FES system. The increase in walking speed (N=7) relative to no stimulation was comparable between both systems, and appropriate ankle angles at initial contact (N=7) and foot clearance during swing (n=5) were greater with the array-based automated setup FES system.\ud \ud Conclusions\ud \ud This study demonstrates that an array-based automated setup FES system for foot-drop can be successfully used unsupervised. Despite setup's taking longer and some problems, users are satisfied with the system and it would appear as effective, if not better, at addressing the foot-drop impairment. Further product development of this unique system, followed by a larger-scale and longer-term study, is required before firm conclusions about its efficacy can be reached.

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.

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.

Subjective assessment of emotional valence is typically associated with both brain activity and autonomic arousal. Accurately assessing emotional salience is particularly important when perceiving threat. We sought to characterize the neural correlates of the interaction between behavioral and autonomic responses to potentially threatening visual and auditory stimuli. Twenty-five healthy male subjects underwent fMRI scanning whilst skin conductance responses (SCR) were recorded. One hundred and eighty pictures, sentences, and sounds were assessed as "harmless" or "threatening." Individuals' stimulus-locked, phasic SCRs and trial-by-trial behavioral assessments were entered as regressors into a flexible factorial design to establish their separate autonomic and behavioral neural correlates, and convolved to examine psycho-autonomic interaction (PAI) effects. Across all stimuli, "threatening," compared with "harmless" behavioral assessments were associated with mainly frontal and precuneus activation with specific within-modality activations including bilateral parahippocampal gyri (pictures), bilateral anterior cingulate cortex (ACC) and frontal pole (sentences), and right Heschl's gyrus and bilateral temporal gyri (sounds). Across stimulus modalities SCRs were associated with activation of parieto-occipito-thalamic regions, an activation pattern which was largely replicated within-modality. In contrast, PAI analyses revealed modality-specific activations including right fusiform/parahippocampal gyrus (pictures), right insula (sentences), and mid-cingulate gyrus (sounds). Phasic SCR activity was positively correlated with an individual's propensity to assess stimuli as "threatening." SCRs may modulate cognitive assessments on a "harmless-threatening" dimension, thereby modulating affective tone and hence behavior.

We sought to establish the effects on cognitive performance and autonomic arousal of a multi-electrode transcutaneous electrical sensory stimulator compared with single-electrode stimulation. Progressing from a feasibility study (n = 10) to a repeated-measures, within-subject study (n = 67), healthy, right-handed participants (34 male, mean age 28 ± 11.5 yrs.) received four separate predictable (“lines” or “ring”) or unpredictable (“fly” or “random”) complex electrical stimulation patterns to the non-dominant forearm via 24 individually programmable electrodes, or single-electrode stimulation. During stimulation, participants in the main study performed a series of cognitively demanding tests or a two-point discrimination task and had their autonomic arousal (skin conductance response) monitored. Single-electrode “first felt” current intensity decreased from distal to proximal forearm, was positively correlated with forearm circumference and was lower in females. Single-electrode stimulation was associated with a significant decline in two-point discrimination performance. There were no significant autonomic arousal or cognitive performance differences between complex patterns, but all patterns were associated with greater autonomic arousal than single-electrode stimulation. In conclusion, gender and forearm location and circumference significantly influence perception-levels for electrical current. Future research should examine whether the induction of increased autonomic arousal, via multi-electrode complex patterns, has improved therapeutic application, compared with single-electrode stimulation.

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 ofelectric 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.

CEREBELLAR FUNCTIONS IN TWO TYPES OF PERCEPTUAL TIMING WERE ASSESSED: the absolute (duration-based) timing of single intervals and the relative (beat-based) timing of rhythmic sequences. Continuous transcranial magnetic theta-burst stimulation (cTBS) was applied over the medial cerebellum and performance was measured adaptively before and after stimulation. A large and significant effect was found in the TBS (n = 12) compared to the SHAM (n = 12) group for single-interval timing but not for the detection of a regular beat or a deviation from it. The data support the existence of distinct perceptual timing mechanisms and an obligatory role of the cerebellum in absolute interval timing with a functional dissociation from relative timing of interval within rhythmic sequences based on a regular beat.

Functional electrical stimulation is commonly used to restore function in post-stroke patients in upper and lower limb applications. Location of the electrodes can be a problem hence some research groups have begun to experiment with electrode arrays. Electrode arrays are interfaced with a thin continuous hydrogel sheet which is high resistivity to reduce transverse currents between electrodes in the array. Research using electrode arrays has all been conducted in a laboratory environment over short time periods but it is suspected that this approach will not be feasible over longer time periods due to changes in hydrogel resistivity. High resistivity hydrogel samples were tested by leaving them in contact with the skin over a seven day period. The samples became extremely conductive with resistivities reaching around 10-50 Ωm. The effect of these resistivity changes was studied using finite element analysis to solve for the stationary current quasi-static electric field gradient in the tissue. Electrical stimulation efficiency and focality were calculated for both a high and low resistivity electrode-skin interface layer at different tissue depths. The results showed that low resistivity hydrogel produced significant decreases in stimulation efficiency and focality compared to high resistivity hydrogel.

Our ability to interact physically with objects in the external world critically depends on temporal coupling between perception and movement (sensorimotor timing) and swift behavioral adjustment to changes in the environment (error correction). In this study, we investigated the neural correlates of the correction of subliminal and supraliminal phase shifts during a sensorimotor synchronization task. In particular, we focused on the role of the cerebellum because this structure has been shown to play a role in both motor timing and error correction. Experiment 1 used fMRI to show that the right cerebellar dentate nucleus and primary motor and sensory cortices were activated during regular timing and during the correction of subliminal errors. The correction of supraliminal phase shifts led to additional activations in the left cerebellum and right inferior parietal and frontal areas. Furthermore, a psychophysiological interaction analysis revealed that supraliminal error correction was associated with enhanced connectivity of the left cerebellum with frontal, auditory, and sensory cortices and with the right cerebellum. Experiment 2 showed that suppression of the left but not the right cerebellum with theta burst TMS significantly affected supraliminal error correction. These findings provide evidence that the left lateral cerebellum is essential for supraliminal error correction during sensorimotor synchronization.

Spectrofluorimetry is used as an optical assay to investigate whether exposure of bovine serum albumin (BSA) to electromagnetic fields (EMF) causes structural changes in the protein distinct from any caused by heating alone. Such changes would alter the fluorescence spectrum of the BSA, and could indicate a potential for EMF induced altered biological activity of proteins in-vivo. No directly EMF induced fluorescence variations are observed under a 10 minute TETRA burst exposure paradigm at room temperature. An additional structure to the TEM Cell, which increases electric field strength around the cuvette area by a factor of 18, has also been designed.

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.

Bovine serum albumin is exposed to a low frequency electric field and spectrofluorimetry then used as an assay for changes in protein structure. Any such changes occurring in analogous proteins may be biologically significant in-vivo. Oscillatory fluorescence variations synchronized with the electric field bursts are observed but the cause of these is unclear.

Discomfort experienced during surface functional electrical stimulation (FES) is thought to be partly a result of localised high current density in the skin underneath the stimulating electrode. This paper describes a finite element (FE) model to predict skin current density distribution in the region of the electrode during stimulation andits application to the identification of electrode properties that may act to reduce sensation. The FE model results showed that the peak current density was located in an area immediately under the stratum corneum, adjacent to a sweat duct. A simulation of surface FES via a high resistivity electrode showed a reduction in this peak current density, when compared with that with a low resistivity electrode.

An acute rise in blood pressure has been reported in normal volunteers during exposure to signals from a mobile phone handset. To investigate this finding further we carried out a double blind study in 120 healthy volunteers (43 men, 77 women) in whom we measured mean arterial pressure (MAP) during each of six exposure sessions. At each session subjects were exposed to one of six different radio frequency signals simulating both GSM and TETRA handsets in different transmission modes. Blood catechols before and after exposure, heart rate variability during exposure, and post exposure 24 h ambulatory blood pressure were also studied. Despite having the power to detect changes in MAP of less than 1 mmHg none of our measurements showed any effect which we could attribute to radio frequency exposure. We found a single statistically significant decrease of 0.7 mmHg (95% CI 0.3–1.2 mmHg, P = .04) with exposure to GSM handsets in sham mode. This may be due to a slight increase in operating temperature of the handsets when in this mode. Hence our results have not confirmed the original findings of an acute rise in blood pressure due to exposure to mobile phone handset signals. In light of this negative finding from a large study, coupled with two smaller GSM studies which have also proved negative, we are of the view that further studies of acute changes in blood pressure due to GSM and TETRA handsets are not required. Bioelectromagnetics 28:433–438, 2007. © 2007 Wiley-Liss, Inc.

The coordinated migration of keratinocytes is crucial to cutaneous wound healing; failure of keratinocytes to migrate into a wound can lead to chronic non-healing wounds. Keratinocyte migration can be influenced by applied electrical fields. Our aim was to investigate whether keratinocyte migration could be accelerated by applying an induced biphasic pulsed electrical field. We developed two in vitro biological systems models for this purpose: a keratinocyte colony-forming model and a reconstituted skin wound healing model with biphasic pulsed currents. Our in vitro skin models were capable of generating trans-epithelial potentials (TEP) similar to in vivo mammalian skin. Histological examination of the wound healing model also indicated that re-epithelialization occurred in a similar manner to that seen in vivo, although no evidence of a reconstitution of a basement membrane was seen during the 14 days in vitro experimental period. We found that growth of keratinocyte colonies and keratinocyte migration in an in vitro wound bed were not significantly affected by induced short duration biphasic pulsed currents at a frequency of 0.5 Hz of 100 and 200 mV/mm. Bioelectromagnetics. © 2006 Wiley-Liss, Inc.

One approach to improving the gait of patients with foot drop is the use of functional electrical stimulation (FES) as a neural prosthesis. However, there remain limitations with the current clinically used technology and the paper describes some recent developments addressing some of these problems. The paper describes initial work on an alternative surface-based solution and recent developments of an implantable two channel stimulator.