An Investigation of Neural Stimulation Efficiency With Gaussian Waveforms

Objective: Previous computational studies predict that Gaussian shaped waveforms use the least energy to activate nerves. The primary goal of this study was to examine the claimed potential of up to 60% energy savings with these waveforms over a range of phase widths (50- $200~\mu \text{s}$ ) in an animal model. Methods: The common peroneal nerve of anaesthetized rats was stimulated via monopolar and bipolar electrodes with single stimuli. The isometric peak twitch force of the extensor digitorum longus muscle was recorded to indicate the extent of neural activation. The energy consumption, charge injection and maximum instantaneous power values required to reach 50% neural activation were compared between Gaussian pulses and standard rectangular stimuli. Results: Energy savings in the 50- $200~\mu \text{s}$ range of phase widths did not exceed 17% and were accompanied by significant increases in maximum instantaneous power of 110-200%. Charge efficiency was found to be increased over the whole range of tested phase widths with Gaussian compared to rectangular pulses and reached up to 55% at 1ms phase width. Conclusion: These findings challenge the claims of up to 60% energy savings with Gaussian like stimulation waveforms. The moderate energy savings achieved with the novel waveform are accompanied with considerable increases in maximal instantaneous power. Larger power sources would therefore be required, and this opposes the trend for implant miniaturization. Significance: This is the first study to comprehensively investigate stimulation efficiency of Gaussian waveforms. It sheds new light on the practical potential of such stimulation waveforms

The Effect of Sub-Threshold Pre-Pulses on Neural Activation Depends on Electrode Configuration

IEEE Objective: Published research on nerve stimulation with sub-threshold conditioning pre-pulses is contradictory. Like most early research on electrical stimulation (ES), the pioneer work on the use of pre-pulses was modelled and measured only for monopolar electrodes. However, many contemporary ES applications, including miniaturized neuromodulation implants, known as electroceuticals, operate in bipolar mode. Methods: We compared depolarizing (DPPs) and hyperpolarizing (HPPs) pre-pulses on neural excitability in rat nerve with monopolar and bipolar electrodes. The rat common peroneal nerve was stimulated with biphasic stimuli with and without ramp and square DPPs or HPPs of 1, 5 and 10ms duration and 10% - 20% of the amplitude of the following pulse. Results: The effects were opposite for the monopolar and bipolar configurations. With monopolar electrodes DPPs increased the amplitude required to activate 50% of the motoneuron pool (between 0.7% and 10.3%) and HPPs decreased the threshold (between 1.7% and 4.7%). With bipolar electrodes both pre-pulse types had the opposite effect: DPPs decreased thresholds (between 1.8% and 5.5%) whereas HPPs increased thresholds (between 0.5% and 4.1%). Electroneurograms from the stimulated nerve revealed spatial and temporal differences in action potential generation for monopolar and bipolar electrodes. In bipolar biphasic stimulation, excitation first occurred at the return electrode as a response to the transition between the cathodic and anodic phase. Conclusion: These data help to resolve the contradictions in the published data over two decades. Significance: They also show that fundamental research carried out in monopolar configuration is not directly applicable to contemporary bipolar ES applications

On the Rate of Synthesis of Individual Proteins within and between Different Striated Muscles of the Rat

The turnover of muscle protein is responsive to different (patho)-physiological conditions but little is known about the rate of synthesis at the level of individual proteins or whether this varies between different muscles. We investigated the synthesis rate of eight proteins (actin, albumin, ATP synthase alpha, beta enolase, creatine kinase, myosin essential light chain, myosin regulatory light chain and tropomyosin) in the extensor digitorum longus, diaphragm, heart and soleus of male Wistar rats (352 ± 30 g body weight). Animals were assigned to four groups (n = 3, in each), including a control and groups that received deuterium oxide (2H2O) for 4 days, 7 days or 14 days. Deuterium labelling was initiated by an intraperitoneal injection of 10 μL/g body weight of 99.9% 2H2O-saline, and was maintained by administration of 5% (v/v) 2H2O in drinking water provided ad libitum. Homogenates of the isolated muscles were analysed by 2-dimensional gel electrophoresis and matrix-assisted laser desorption ionisation time of flight mass spectrometry. Proteins were identified against the SwissProt database using peptide mass fingerprinting. For each of the eight proteins investigated, the molar percent enrichment (MPE) of 2H and rate constant (k) of protein synthesis was calculated from the mass isotopomer distribution of peptides based on the amino acid sequence and predicted number of exchangeable C–H bonds. The average MPE (2.14% ± 0.2%) was as expected and was consistent across muscles harvested at different times (i.e., steady state enrichment was achieved). The synthesis rate of individual proteins differed markedly within each muscle and the rank-order of synthesis rates differed among the muscles studied. After 14 days the fraction of albumin synthesised (23% ± 5%) was significantly (p < 0.05) greater than for other muscle proteins. These data represent the first attempt to study the synthesis rates of individual proteins across a number of different striated muscles

Concentric lamellae - novel microanatomical structures in the articular calcified cartilage of mice.

The structure, ultrastructure and function of hyaline articular cartilage (HAC) and subchondral bone (SCB), and their involvement in the pathogenesis of osteoarthritis (OA) have been extensively researched. However, much less attention has been focused on the intervening tissue, articular calcified cartilage (ACC) and its role in the initiation and progression of OA. Using both light microscopy (LM) and transmission electron microscopy (TEM), a study of ACC in wild type (WT) mice, and mice with genetic osteoarthropathies (AKU) was undertaken to further understand the role played by ACC in the early stages of OA.Tibio-femoral joints were obtained from BALB/c WT and BALB/c AKU mice aged between 7 and 69 weeks. One joint was processed for routine histological analysis. The tip of the medial femoral condyle (MFC), which contained HAC, ACC, and SCB, was dissected from the contra-lateral joint and processed for TEM.In WT and AKU mice novel microanatomical structures, designated concentric lamellae, were identified surrounding chondrocytes in the ACC. The lamellae appeared to be laid down in association with advancement of the tidemark indicating they may be formed during calcification of cartilage matrix. The lamellae were associated with hypertrophic chondrocytes throughout the ACC.Novel microanatomical structures, termed concentric lamellae, which were present around hypertrophic chondrocytes in the ACC are described for the first time. Their apparent association with mineralisation, advancement of the tidemark, and greater abundance in a model of osteoarthropathy indicate their formation could be important in the pathogenesis of OA and AKU

The end of the unique myocardial band: Part I. Anatomical considerations

The concept of the ‘unique myocardial band’, which proposes that the ventricular myocardial cone is arranged like skeletal muscle, provides an attractive framework for understanding haemodynamics. The original idea was developed by Francisco Torrent-Guasp. Using boiled hearts and blunt dissection, Torrent-Guasp created a single band of ventricular myocardium extending from the pulmonary trunk to the aortic root, with the band thus constructed encircling both ventricular cavities. Cooked hearts can, however, be dissected in many ways. In this review, we show that the band does not exist as an anatomical entity with defined borders. On the contrary, the ventricular cardiomyocytes are aggregated end to end and by their branching produce an intricate meshwork. Across the thickness of the left ventricular wall, the chains of cardiomyocytes exhibit a gradually changing helical angle, with a circumferential zone formed in the middle. There is no abrupt change in helical angle, as could be expected if the wall was constructed of opposing limbs of a single wrapped band, nor does the long axis of the cardiomyocytes consistently match with the long axis of the unique myocardial band. There are, furthermore, no connective tissue structures that could be considered to demarcate its purported boundaries. The unique myocardial band should be consistent with evolution, and although the ventricular wall of fish and reptiles has one or several distinct layers, a single band is not found. In 1965, Lev and Simpkins cautioned that the ventricular muscle mass of a cooked heart can be dissected almost at the whim of the anatomist. We suggest that the unique myocardial band should have ended there

Surface electrical stimulation for facial paralysis is not harmful

Introduction: Does electrical stimulation (ES) of denervated muscles delay or prevent reinnervation, or increase synkinesis? This retrospective study evaluated the outcome with and without ES of patients with acutely denervated facial muscles. Methods: The effect of ES was analyzed in two experiments: In 39 patients (6 with home-based ES, median 17.5 months) undergoing facial nerve reconstruction surgery (FNRS). Time to recovery of volitional movements was analyzed. The second experiment involved 13 patients (7 with ES, median 19 months) during spontaneous reinnervation. Sunnybrook and eFACE scoring provided functional outcome measures. Results: No difference in time of reinnervation after FNRS was found between the patients with and without ES (median (IQR) 4.5(3.0, 5.25) vs. 5.7(3.5, 9.5) months; p=0.2). After spontaneous reinnervation less synkinesis was noted (Sunnybrook synkinesis: 3.0(2.0, 3.0) vs. 5.5(4.75, 7.0); p=0.02) with ES. Discussion: We find no evidence that ES prevents or delays reinnervation or increases synkinesis in facial paralysis

Electrical stimulation modulates Wnt signaling and regulates genes for the motor endplate and calcium binding in muscle of rats with spinal cord transection

Background Spinal cord injury (SCI) results in muscle atrophy and a shift of slow oxidative to fast glycolytic fibers. Electrical stimulation (ES) at least partially restores muscle mass and fiber type distribution. The objective of this study was to was to characterize the early molecular adaptations that occur in rat soleus muscle after initiating isometric resistance exercise by ES for one hour per day for 1, 3 or 7 days when ES was begun 16 weeks after SCI. Additionally, changes in mRNA levels after ES were compared with those induced in soleus at the same time points after gastrocnemius tenotomy (GA). Results ES increased expression of Hey1 and Pitx2 suggesting increased Notch and Wnt signaling, respectively, but did not normalize RCAN1.4, a measure of calcineurin/NFAT signaling, or PGC-1ß mRNA levels. ES increased PGC-1α expression but not that of slow myofibrillar genes. Microarray analysis showed that after ES, genes coding for calcium binding proteins and nicotinic acetylcholine receptors were increased, and the expression of genes involved in blood vessel formation and morphogenesis was altered. Of the 165 genes altered by ES only 16 were also differentially expressed after GA, of which 12 were altered in the same direction by ES and GA. In contrast to ES, GA induced expression of genes related to oxidative phosphorylation. Conclusions Notch and Wnt signaling may be involved in ES-induced increases in the mass of paralyzed muscle. Molecular adaptations of paralyzed soleus to resistance exercise are delayed or defective compared to normally innervated muscle