Wavelet-Based Muscle Artefact Noise Reduction for Short Latency rTMS Evoked Potentials.

This paper presents a new method of reducing the noise in the EEG response signal recorded during repetitive transcranial magnetic stimulation (rTMS). This noise is principally composed of the residual stimulus artefact and millivolt amplitude compound muscle action potentials (CMAP) recorded from the scalp muscles and precludes analysis of the cortical evoked potentials, especially during the first 20-ms post stimulus. The proposed method uses the wavelet transform with a fourth-order Daubechies mother wavelet and a novel coefficient reduction algorithm based on cortical amplitude thresholds. Four other mother wavelets as well as digital filtering have been tested, and the Coiflets 2 and 3 also found to be effective with Coiflet 3 results marginally better than Daubechies 4. The approach has been tested using data recorded from 16 normal subjects during a study of cortical sensitivity to rTMS at different cortical locations using stimulation amplitudes, frequencies, and sites typically used in clinical practice to treat major depressive disorder.

Sensory nerve cross-anastomosis and electrical muscle stimulation synergistically enhance functional recovery of chronically denervated muscle.

BACKGROUND: Long-term muscle denervation leads to severe and irreversible atrophy coupled with loss of force and motor function. These factors contribute to poor functional recovery following delayed reinnervation. The authors' previous work demonstrated that temporarily suturing a sensory nerve to the distal motor stump (called sensory protection) significantly reduces muscle atrophy and improves function following reinnervation. The authors have also shown that 1 month of electrical stimulation of denervated muscle significantly improves function and reduces atrophy. In this study, the authors tested whether a combination of sensory protection and electrical stimulation would enhance functional recovery more than either treatment alone. METHODS: Rat gastrocnemius muscles were denervated by cutting the tibial nerve. The peroneal nerve was then sutured to the distal tibial stump following 3 months of treatment (i.e., electrical stimulation, sensory protection, or both). Three months after peroneal repair, functional and histologic measurements were taken. RESULTS: All treatment groups had significantly higher muscle weight (p<0.05) and twitch force (p<0.001) compared with the untreated group (denervated), but fiber type composition did not differ between groups. Importantly, muscle weight and force were significantly greater in the combined treatment group (p<0.05) compared with stimulation or sensory protection alone. The combined treatment also produced motor unit counts significantly greater than sensory protection alone (p<0.05). CONCLUSIONS: The combination treatment synergistically reduces atrophy and improves reinnervation and functional measures following delayed nerve repair, suggesting that these approaches work through different mechanisms. The authors' research supports the clinical use of both modalities together following peripheral nerve injury.

Electrical muscle stimulation after immediate nerve repair reduces muscle atrophy without affecting reinnervation.

INTRODUCTION: Electrical stimulation of denervated muscle has been shown to minimize atrophy and fibrosis and increase force in animal and human models. However, electrical stimulation after nerve repair is controversial due to questions of efficacy. METHODS: Using a rat model, we investigated the efficacy of short-term electrical muscle stimulation for increasing reinnervation and preventing muscle atrophy. After tibial nerve transection and immediate repair with the fibular nerve, 1 month of electrical stimulation was applied 5 days/week for 1 hour to the gastrocnemius muscle via implanted electrodes. RESULTS: After 2 months of further recovery without stimulation, muscle weights, twitch forces, and type I fiber areas were significantly greater in stimulated animals than in repaired controls without stimulation. Motor unit size and numbers were not different between the 2 groups. CONCLUSIONS: Short-term electrical muscle stimulation after nerve repair significantly reduces muscle atrophy and does not affect motor reinnervation.

A machine learning approach using EEG data to predict response to SSRI treatment for major depressive disorder.

OBJECTIVE: The problem of identifying, in advance, the most effective treatment agent for various psychiatric conditions remains an elusive goal. To address this challenge, we investigate the performance of the proposed machine learning (ML) methodology (based on the pre-treatment electroencephalogram (EEG)) for prediction of response to treatment with a selective serotonin reuptake inhibitor (SSRI) medication in subjects suffering from major depressive disorder (MDD). METHODS: A relatively small number of most discriminating features are selected from a large group of candidate features extracted from the subject's pre-treatment EEG, using a machine learning procedure for feature selection. The selected features are fed into a classifier, which was realized as a mixture of factor analysis (MFA) model, whose output is the predicted response in the form of a likelihood value. This likelihood indicates the extent to which the subject belongs to the responder vs. non-responder classes. The overall method was evaluated using a "leave-n-out" randomized permutation cross-validation procedure. RESULTS: A list of discriminating EEG biomarkers (features) was found. The specificity of the proposed method is 80.9% while sensitivity is 94.9%, for an overall prediction accuracy of 87.9%. There is a 98.76% confidence that the estimated prediction rate is within the interval [75%, 100%]. CONCLUSIONS: These results indicate that the proposed ML method holds considerable promise in predicting the efficacy of SSRI antidepressant therapy for MDD, based on a simple and cost-effective pre-treatment EEG. SIGNIFICANCE: The proposed approach offers the potential to improve the treatment of major depression and to reduce health care costs.

Application of wavelet based denoising techniques to rTMS evoked potentials.

This paper presents a new method of removing noise from the EEG response signal recorded during repetitive transcranial magnetic stimulation (rTMS). This noise is principally composed of the residual stimulus artifact and mV amplitude compound muscle action potentials recorded from the scalp muscles and precludes analysis of the cortical evoked potentials, especially during the first 15 ms post stimulus. The method uses the wavelet transform with a fourth order Daubechies mother wavelet and a novel coefficient reduction algorithm based on cortical amplitude thresholds. The approach has been tested and two methods of coefficient reduction compared using data recorded during a study of cortical sensitivity to rTMS at different scalp locations.

A New System and Paradigm for Chronic Stimulation of Denervated Rat Muscle.

Traditionally, animal studies employing electrical stimulation for conditioning denervated muscle rely on 24-hour-based stimulation paradigms, most employing implantable stimulators. While these stimulators provide the necessary current to cause muscular contraction, they have problems with battery life, programmability, and long-term robustness. Continuous 24-hour stimulation, while shown to be effective in animals, is not easily translatable to a clinical setting. It is also difficult to evaluate animal comfort and muscular contraction throughout a 24-hour period. We have developed a system and stimulation paradigm that can stimulate up to five animals at one time for one hour per day. The constant current stimulator is a USB-powered device that can, under computer control, output trains of pulses with selectable shapes, widths, durations and repetition rates. It is an external device with no implantable parts in the animal except for the stimulating electrodes. We tested the system on two groups of rats with denervated gastrocnemius muscles. One group was stimulated using a one-hour-per-day, 5-days-per-week stimulation paradigm for one month, while the other group had electrodes implanted but received no stimulation. Muscle weight and twitch force were significantly larger in the stimulated group than the non-stimulated group. Presently, we are using the stimulator to investigate electrical stimulation coupled with other therapeutic interventions that can minimize functional deficits after peripheral nerve injuries.

Determining the effects of electrical stimulation on functional recovery of denervated rat gastrocnemius muscle using motor unit number estimation.

The use of electrical muscle stimulation to treat denervated muscle prior to delayed reinnervation has been widely debated. There is evidence showing both positive and negative results following different protocols of electrical stimulation. In this study we investigated the role electrical stimulation has on muscle reinnervation following immediate and delayed nerve repair using motor unit estimation techniques. Rat gastrocnemius muscle was denervated and repaired using the peroneal nerve either immediately or following three-months with and without electrical stimulation. Motor unit counts, average motor unit sizes, and maximum compound action potentials were measured three-months following peroneal nerve repair. Motor unit counts in animals that were denervated and stimulated were significantly higher than those that were denervated and not stimulated. Both average motor unit sizes and maximum compound action potentials showed no significant differences between denervated and denervated-stimulated animals. These results provide evidence that electrical stimulation prior to delayed nerve repair increases muscle receptivity to regenerating axons and may be a worthwhile treatment for peripheral nerve injuries.

Dorsolateral prefrontal cortex sensitivity to rTMS.

This paper presents the preliminary results of a study to determine dorsolateral prefrontal cortex sensitivity to rTMS stimulation presented at clinically accepted amplitudes, frequencies and locations. A specially developed EEG system with 10-20 electrode locations was used to record the short latency magnetically evoked potentials. Sixteen normal subjects were stimulated using 10 Hz for the left hemisphere and 1 Hz for the right. The evoked potentials recorded for left sided stimulation were significantly larger than for the right sided stimulation. Further, the stimulation energies, though within the range used clinically for the treatment of depression were insufficient to excite evoked potentials in several subjects.

A pilot study to determine whether machine learning methodologies using pre-treatment electroencephalography can predict the symptomatic response to clozapine therapy.

OBJECTIVE: To investigate whether applying advanced machine learning (ML) methodologies to pre-treatment electroencephalography (EEG) data can predict the response to clozapine therapy in adult subjects suffering from chronic schizophrenia. METHODS: Pre-treatment EEG data are collected in 23+14 schizophrenic adults. Treatment outcome, after at least one year follow-up, is determined using clinical ratings by a trained clinician blind to EEG results. First, a feature selection scheme is employed to select a reduced subset of features extracted from the subjects' EEG that is most statistically relevant to our treatment-response prediction. These features are then entered into a classifier, which is realized in the form of a kernel partial least squares regression method that performs response prediction. Various scales, including the positive and negative syndrome scale (PANSS) are used as treatment-response indicators. RESULTS: We determined that a set of discriminating EEG features do exist. A low-dimensional representation of the feature space showed significant clustering into clozapine responder and non-responder groups. The minimum level of performance of the proposed prediction methodology, tested over a range of conditions using the leave-one-out cross-validation method using the original 23 subjects, with further testing in an independent sample of 14 subjects, was 85%. CONCLUSIONS: These findings indicate that analysis of pre-treatment EEG data can predict the clinical response to clozapine in treatment resistant schizophrenia. SIGNIFICANCE: If replicated in a larger population, this novel approach to EEG analysis may assist the clinician in determining treatment-efficacy.

A novel approach using tendon vibration of the human flexor carpi radialis muscle to study spinal reflexes.

Although most muscle spindle investigations have used the cat model and invasive measurement techniques, several investigators have used microneurography to record from the Ia and II fibres in humans during tendon vibration. In these studies the muscle spindle primary endings are stimulated using transverse vibration of the tendon at reflex sub-threshold amplitudes. Others have used low amplitude vibration and the stretch evoked M-wave response to determine reflex properties during both agonist and antagonist voluntary contractions. In the past we have developed a PC based instrument that uses Labview and a linear servomotor to study tendon reflex properties by recording stretch evoked M-wave responses from single tendon taps or electrical stimuli to the afferent nerve. In this paper we describe a further development of this system to provide precise vibrations of the tendon up to 65 Hz with amplitudes up to 4 mm. The resultant M-wave train is extracted from background noise via phase coherent subtractive filtering. Test results from vibrating the human distal flexor carpi radialis tendon at 10 and 30 Hz, for relaxed, slight flexion and slight extension, are also presented.

Design and testing of an instrumentation system to reduce stimulus pulse amplitude requirements during FES.

Functional Electrical Stimulation (FES) has been used for decades to restore muscle function following neural trauma. Another promising use has been to maintain or increase muscle strength following injury. Unfortunately in the latter case there is considerable stimulation pain for the sensorially intact subject during effective levels of stimulation using surface electrodes. Recent research [1][2] has suggested using a constant long (up to 10 ms) low amplitude or ramped conditioning pulse just prior to the high amplitude stimulus pulse (100 - 200 microsec) to reduce the excitably of sensory nerve fibers. However, commercial muscle stimulators cannot be easily modified to provide such complex pulse patterns and flexible pulse train control. We have designed and implemented a novel, very flexible LabVIEW based monophasic constant current muscle stimulator that provides pulse trains with long duration prepulses and high voltage stimulus pulses with selectable shapes, amplitudes, durations and frequencies. As well, the stimulator system includes an isolated EMG amplifier to record the evoked M-waves, which are used to estimate the fraction of muscle motor units being stimulated. We are presently testing this system, by stimulating the median nerve of human subjects and measuring the evoked M-waves for a range of stimulus pulse amplitudes, preceded by either ramped or rectangular low amplitude prepulses. The results indicate that, rather than inhibiting the activation of motor axons, as has been suggested [4], the prepulses at very low amplitudes excite these axons to subthreshold levels. The amplitudes of the stimulus pulses can then be significantly reduced while still achieving high levels of muscle activation.

Tendon reflexes elicited using a computer controlled linear motor tendon hammer.

We present a novel instrumentation system for studying tendon and spinal reflexes using a commercial linear servo-motor as a precisely controlled tendon hammer. The system uses a LabVIEW-based program to both control electrical or mechanical stimuli and record and measure the resulting M and H waves. The hammer can deliver tendon taps with selected velocities, durations, frequencies and excursions. Preliminary results for both soleus and flexor carpi radialis muscles show that impact velocity is an important variable in eliciting tendon reflexes. As expected, the tendon reflex amplitude was also found to be dependent on excursion depth, but not as significantly as hammer velocity. Other stimulus paradigms are also presently being investigated.

The use of the wavelet transform in EMG M-wave pattern classification.

A system was previously designed to obtain estimates of the number of motor units (MUNE) in a superficial muscle and hence number of functioning motor neurons to that muscle. This method uses incremental stimulation of a motor nerve and subsequent recognition and classification of the elicited M-waves. In this earlier work we used the Fourier power coefficients as pattern classifiers. The presented work compares the Fourier transform classifier results with those obtained using a wavelet transform classifier. Data to test the two approaches were obtained from the thenar muscles of ten normal subjects. The results show that the wavelet transform is superior to the Fourier in classifying M-waves with significantly improved inter and intra-class variances.

The effects of pulse configuration on magnetic stimulation.

A study is presented in which the authors have examined the effects of pulse configuration, stimulation intensity, and coil current direction during magnetic stimulation. Using figure-8 and circular coils, the median nerve was stimulated at the cubital fossa and at the wrist of 10 healthy volunteers, and the response amplitude and site of stimulation were determined. The key findings of this study are in agreement with other researchers' findings and confirm that biphasic stimulating pulses produce significantly higher M-wave amplitudes than monophasic stimulating pulses for the same stimulus intensity. Mean response amplitudes for biphasic stimuli applied by both coils at the elbow and wrist are consistently higher for the normal current direction. Mean response amplitudes for monophasic pulses are almost always higher for reversed currents. The site for effective stimulation (the position of the virtual cathode) cannot be defined within a fixed distance from the center of the coil (3 to 4 cm), as has been suggested by other researchers, but was found to vary depending on the coil current amplitude and direction as well as the degree of inhomogeneity of the tissues surrounding the nerve. There is a statistically significant relationship between virtual cathode shift and stimulus intensity for biphasic and monophasic pulses. Reversing the coil current direction has no statistically significant effect on the virtual cathode position. Virtual cathode shifts can be measured for biphasic and monophasic stimulations using a figure-8 coil at the wrist and the elbow. However, such a shift is difficult to determine with a circular coil.