Comparative study of platinum electroplating to improve micro gold electrode arrays with LCP laminate.

Decoding the cellular network interaction of neurons and glial cells are important in the development of new therapies for diseases of the central nervous system (CNS). Electrophysiological in vivo studies in mice will help to understand the highly complex network. In this paper, the optimization of epidural liquid crystal polymer (LCP) electrodes for different platinum electroplating parameters are presented and compared. Constant current and pulsed current electroplating varied in strength and duration was used to decrease the electrode impedance and to increase the charge storage capacity (CSCC). In best cases, both methods generated similar results with an impedance reduction of about 99%. However, electroplating with pulsed currents was less parameter-dependent than the electroplating with constant current. The use of ultrasound was essential to generate platinum coatings without plating defects. Electrode model parameters extracted from the electrode impedance reflected the increase in surface porosity due to the electroplating processes.

Versatile Surface Electrodes for Combined Electrophysiology and Two-Photon Imaging of the Mouse Central Nervous System.

Understanding and modulating CNS function in physiological as well as pathophysiological contexts remains a significant ambition in research and clinical applications. The investigation of the multifaceted CNS cell types including their interactions and contributions to neural function requires a combination of the state-of-the-art in vivo electrophysiology and imaging techniques. We developed a novel type of liquid crystal polymer (LCP) surface micro-electrode manufactured in three customized designs with up to 16 channels for recording and stimulation of brain activity. All designs include spare central spaces for simultaneous 2P-imaging. Nanoporous platinum-plated contact sites ensure a low impedance and high current transfer. The epidural implantation of the LCP micro-electrodes could be combined with standard cranial window surgery. The epidurally positioned electrodes did not only display long-term biocompatibility, but we also observed an additional stabilization of the underlying CNS tissue. We demonstrate the electrode's versatility in combination with in vivo 2P-imaging by monitoring anesthesia-awake cycles of transgenic mice with GCaMP3 expression in neurons or astrocytes. Cortical stimulation and simultaneous 2P Ca2+ imaging in neurons or astrocytes highlighted the astrocytes' integrative character in neuronal activity processing. Furthermore, we confirmed that spontaneous astroglial Ca2+ signals are dampened under anesthesia, while evoked signals in neurons and astrocytes showed stronger dependency on stimulation intensity rather than on various levels of anesthesia. Finally, we show that the electrodes provide recordings of the electrocorticogram (ECoG) with a high signal-to noise ratio and spatial signal differences which help to decipher brain activity states during experimental procedures. Summarizing, the novel LCP surface micro-electrode is a versatile, convenient, and reliable tool to investigate brain function in vivo.

Test-retest reproducibility of a combined physical and cognitive stressor.

When studying the factors which influence stress reactivity in within-subject designs, test-retest reproducibility data is needed to estimate power and sample size. We report such data regarding a new experimental stress protocol, based on simultaneous application of the socially evaluated, bilateral feet Cold Pressor Test (CPT) and the Paced Auditory Serial Addition Task (PASAT). Cardiovascular, neuroendocrine, and subjective (affective) stress responses of 32 healthy males were measured twice, at an interval of one week. The novel protocol induced substantial stress reactivity in all parameters at both test and retest. Cardiovascular reactivity remained unchanged, but cortisol and subjective responses were lower at second stress exposure, with high test-retest stability of neuroendocrine (r>.7) and cardiovascular measures (r = .5 to r = .9). PASAT performance improved. Response attenuation suggests habituation-like and/or learning effects. Data provided by our study demonstrate feasibility and power of this stress protocol for investigating changes in stress reactivity in repeated, within-subject designs.

Validation of an automated bilateral feet cold pressor test.

The Cold Pressor Test (CPT) is often used in psychobiological research. However, the classical CPT version (unilateral hand immersion into ice-water) involves some disadvantages: hands may be needed for further applications, attentional drift towards the affected sensory hemi-field and/or physiological activation of the contralateral hemisphere may produce a laterality bias. Furthermore, instruction-induced motor activity may bias physiologic reactivity. To avoid these problems, a fully automated bilateral feet CPT was developed and tested for validity and feasibility. The test procedure is based on computerized control of water influx and efflux. This allows for maximal standardization and precise timing. Furthermore, water is kept in permanent flow to prohibit formation of stable temperature layers in skin proximity. Laterality bias, instructions effects and motor responses (e.g. lifting feet out of a water basin) are avoided. In a counterbalanced within-subject design, 28 healthy male students were exposed to the CPT and to a warm water control (CNT) condition twice, one week apart. Cardiovascular parameters, salivary cortisol and subjective ratings (stress, arousal and pain) were assessed before, during, and after interventions. The CPT profoundly affected physiology as well as subjective ratings. Expectation effects (immediately before testing) were small. Furthermore, post-CPT (presumably compensatory/counter-regulatory) effects on heart rate and stroke volume were found. In conclusion, the automated bilateral feet CPT is a valid and feasible stress test modification. Hemodynamic, subjective and endocrine stress responses are substantial, suggesting that this test version represents an advanced and suitable tool in human stress research.

Modeling and Simulations in Time Domain of a Stimulation Set-up for Cortical Applications.

Electrical stimulation is used for example to treat neuronal disorders and depression with deep brain stimulation or transcranial electrical stimulation. Depending on the application, different electrodes are used and thus different electrical characteristics exist, which have to be handled by the stimulator. Without a measuring device the user would have to rely on the stimulator being able to deliver the needed stimulation signal. Therefore, the objective of this paper is to present a method to increase the level of confidence with characterization and modelling of the electrical behavior by using the example of one channel of our stimulation device for experimental use. In several simulation studies with an electrode model with values in a typical range for cortical applications the influence of the load onto the stimulator and the possibility to pre-estimate measuring signals in complex networks are shown.

Total mesorectal excision--does the choice of dissection technique have an impact on pelvic autonomic nerve preservation?

BACKGROUND: The aim of this experimental study was to assess the quality of pelvic autonomic nerve preservation of different dissection techniques. MATERIAL AND METHODS: Twelve pigs underwent low anterior rectal resection (LARR) with scissors, ultracision, monopolar diathermy, and waterjet, each in three animals. Assessment of pelvic autonomic nerve preservation was carried out by stimulation of the pelvic splanchnic nerves under electromyography of the internal anal sphincter (IAS). Neurostimulation was performed bilaterally after posterior dissection, after complete mesorectal dissection, and after rectal resection. RESULTS: Stimulation resulted in significantly increased amplitudes of the time-based electromyographic signal of the IAS, confirming nerve preservation. The stimulation results after complete mesorectal dissection showed comparable median amplitude increases for dissection with scissors (10.34 µV (interquartile range [IQR], 5.58; 14.74)) and ultracision (9.79 µV (IQR, 7.63; 11.6)). Lower amplitude increases were observed for monopolar diathermy (4.47 µV (IQR, 2.52; 10.46)) and waterjet (0.61 µV (IQR, 0.07; 2.11)) (p = 0.038). All animals undergoing dissection with scissors, ultracision, and monopolar diathermy had bilateral positive results. Of three animals undergoing LARR with waterjet, one had bilateral positive results. Two had unilateral negative results, indicating incomplete nerve preservation. CONCLUSION: Scissors, ultracision, and monopolar diathermy might have comparable nerve-sparing potentials and differed from waterjet.

Total mesorectal excision with intraoperative assessment of internal anal sphincter innervation provides new insights into neurogenic incontinence.

BACKGROUND: The aim of this prospective study was to assess internal anal sphincter (IAS) innervation in patients undergoing total mesorectal excision (TME) by intraoperative neuromonitoring (IONM). STUDY DESIGN: Fourteen patients underwent TME. IONM was carried out through pelvic splanchnic nerve stimulation under continuous electromyography of the IAS. Anorectal function was assessed with the digital rectal examination scoring system and a standardized questionnaire. RESULTS: Nine of 11 patients who underwent low anterior resection had positive IONM results, with stimulation-induced increased IAS electromyographic amplitudes (median 0.23 µV (interquartile range [IQR] 0.05, 0.56) vs median 0.89 µV (IQR 0.64, 1.88), p < 0.001) after TME. The patients with the positive IONM results were continent after stoma closure. Of 2 patients with negative IONM results, 1 had fecal incontinence after closure of the defunctioning stoma and received a permanent sigmoidostomy. In the other patient the defunctioning stoma was deemed permanent due to decreased anal sphincter function. In 3 patients who underwent abdominoperineal excision, IONM assessed denervation of the IAS after performance of the abdominal part. CONCLUSIONS: This study demonstrated that IONM of IAS innervation in rectal cancer patients is feasible and may predict neurogenic fecal incontinence.

New backstrap vagus electrode for continuous intraoperative neuromonitoring in thyroid surgery.

INTRODUCTION: Continuous intraoperative neuromonitoring (CIONM) via vagal nerve stimulation allows real-time surveillance of the recurrent laryngeal nerve during thyroid surgery. However, for effective CIONM, subtle changes in recurrent laryngeal nerve conductivity have to be detected. A newly developed stimulation electrode that provides stable nerve stimulation and safe application is presented. METHODS: For electrode validation, current distribution was simulated with the finite element method. Mechanical characteristics were assessed through bench testing. Clinical evaluation was initiated with 11 thyroid surgeries. RESULTS: Experimental and clinical results led to the development of a tripolar gold/polyimide electrode mounted onto a backstrap-shaped silicone body. It facilitated rapid electrode implantation and extraction (median implantation time 4 ± 19 seconds). Peak extraction force was 570 mN. Median supramaximal stimulation currents were 2.00 ± 0.95 mA and resulted in reliable electromyogram responses (median 3.1 ± 3.0 mV). No intraoperative electrode dislocations occurred, and no postoperative nerve palsy was observed. CONCLUSION: The new backstrap vagal stimulation electrode meets the requirements for reliable CIONM.

Intraoperative pelvic nerve stimulation performed under continuous electromyography of the internal anal sphincter.

PURPOSE: The aim of this animal study was to investigate the effect of intraoperative pelvic nerve stimulation on internal anal sphincter electromyographic signals in order to evaluate its possible use for neuromonitoring during nerve-sparing pelvic surgery. METHODS: Eight pigs underwent low anterior rectal resection. The intersphincteric space was exposed, and the internal (IAS) and external anal sphincter (EAS) were identified. Electromyography of both sphincters was performed with bipolar needle electrodes. Intermittent bipolar electric stimulation of the inferior hypogastric plexus and the pelvic splanchnic nerves was carried out bilaterally. The recorded signals were analyzed in its frequency spectrum. RESULTS: In all animals, electromyographic recordings of IAS and EAS were successful. Intraoperative nerve stimulation resulted in a sudden amplitude increase in the time-based electromyographic signals of IAS (1.0 (0.5-9.0) µV vs. 4.0 (1.0-113.0) µV) and EAS (p < 0.001). The frequency spectrum of IAS in the resting state ranged from 0.15 to 5 Hz with highest activity in median at 0.77 Hz (46 cycles/min). Pelvic nerve stimulation resulted in an extended spectrum ranging from 0.15 to 20 Hz. EAS signals showed higher frequencies mainly in a range of 50 to 350 Hz. However, after muscle relaxation with pancuronium bromide, only the low frequency spectrum of the IAS signals was still present. CONCLUSIONS: Intraoperative verification of IAS function by stimulation of pelvic autonomic nerves is possible. The IAS electromyographic response could be used to monitor pelvic autonomic nerve preservation.

Assessment of biocompatibility of chronically implanted polyimide and platinum intrafascicular electrodes.

Longitudinal intrafascicular electrodes (LIFEs) are electrodes designed to be placed inside the peripheral nerve to improve stimulation selectivity and to increase the recording signal-to-noise ratio. We evaluated the functional and morphological effects of either Pt wire LIFEs or polyimide-based thin-film LIFEs implanted in the rat sciatic nerve for 3 mo. The newly designed thin-film LIFEs are more flexible, can be micromachined and allow placement of more active electrode sites than conventional Pt LIFEs. Functional results at 1 mo indicated an initial decline in the nerve conduction velocity and in the amplitude of muscle responses, which recovered during the following 2 mo towards normal values. Morphological results showed that both types of LIFEs induced a mild scar response and a focal but chronic inflammatory reaction, which were limited to a small area around the electrode placed in the nerve. Both types of LIFEs can be considered biocompatible and cause reversible, minimal nerve damage.