Background: Stress is associated with activation of the sympathetic nervous system, and can lead to lasting alterations in autonomic function and in extreme cases symptoms of posttraumatic stress disorder (PTSD). Vagal nerve stimulation (VNS) is a potentially useful tool as a modulator of autonomic nervous system function, however currently available implantable devices are limited by cost and inconvenience. Objective: The purpose of this study was to assess the effects of transcutaneous cervical VNS (tcVNS) on autonomic responses to stress. Methods: Using a double-blind approach, we investigated the effects of active or sham tcVNS on peripheral cardiovascular and autonomic responses to stress using wearable sensing devices in 24 healthy human participants with a history of exposure to psychological trauma. Participants were exposed to acute stressors over a three-day period, including personalized scripts of traumatic events, public speech, and mental arithmetic tasks. Results: tcVNS relative to sham applied immediately after traumatic stress resulted in a decrease in sympathetic function and modulated parasympathetic/sympathetic autonomic tone as measured by increased pre-ejection period (PEP) of the heart (a marker of cardiac sympathetic function) of 4.2 ms (95% CI 1.6e6.8 ms, p < 0.01), decreased peripheral sympathetic function as measured by increased photoplethysmogram (PPG) amplitude (decreased vasoconstriction) by 47.9% (1.4e94.5%, p < 0.05), a 9% decrease in respiratory rate (À14.3 to À3.7%, p < 0.01). Similar effects were seen when tcVNS was applied after other stressors and in the absence of a stressor. Conclusion: Wearable sensing modalities are feasible to use in experiments in human participants, and tcVNS modulates cardiovascular and peripheral autonomic responses to stress.
Cardiac time intervals are important hemodynamic indices and provide information about left ventricular performance. Phonocardiography (PCG), impedance cardiography (ICG), and recently, seismocardiography (SCG) have been unobtrusive methods of choice for detection of cardiac time intervals and have potentials to be integrated into wearable devices. The main purpose of this study was to investigate the accuracy and precision of beat-to-beat extraction of cardiac timings from the PCG, ICG and SCG recordings in comparison to multimodal echocardiography (Doppler, TDI, and M-mode) as the gold clinical standard. Recordings were obtained from 86 healthy adults and in total 2,120 cardiac cycles were analyzed. For estimation of the pre-ejection period (PEP), 43% of ICG annotations fell in the corresponding echocardiography ranges while this was 86% for SCG. For estimation of the total systolic time (TST), these numbers were 43, 80, and 90% for ICG, PCG, and SCG, respectively. In summary, SCG and PCG signals provided an acceptable accuracy and precision in estimating cardiac timings, as compared to ICG.
Over the last several years, there has been a growing interest in neural implants for the study and diagnostics of neurological disorders as well as for the symptomatic treatment of central nervous system related diseases. One of the major challenges is the trade-off between small electrode sizes for high selectivity between single neurons and large electrode-tissue interface areas for excellent stimulation and recording properties. This paper presents an approach of increasing the real surface area of the electrodes by creating a surface microstructure. Two major novelties let this work stand out from existing approaches which mainly make use of porous coatings such as platinum black or iridium oxide, or Poly(3,4-ethylenedioxythiophene) (PEDOT). Roughening is carried out by a dry etching process on the silicon electrode core before being coated by a sputtered platinum layer, eliminating complicated deposition processes as for the materials described above. The technology is compatible with any commonly used coating material. In addition, the surface roughening is compatible with high aspect ratio penetrating electrode arrays such as the well-established Utah electrode array, whose unique geometry presents a challenge in the surface modification of active electrode sites. The dry etching process is well characterized and yields a high controllability of pore size and depth. This paper confirms the superior electrochemical properties including impedance, charge injection capacity, and charge storage capacity of surface engineered electrode arrays compared to conventional arrays over a period of 12 weeks. Furthermore, mechanical stability of the modified electrodes was tested by implantation in the brain of a recently deceased rat. In conclusion, the larger interface surface of the electrodes does not only decrease the impedance which should lead to enhanced Signal to noise ratio (SNR) for recording purposes, but also yields higher charge injection capacities, which improve the stimulation characteristics of the implants.
Background: Vagal Nerve Stimulation (VNS) has been shown to be efficacious for the treatment of depression, but to date, VNS devices have required surgical implantation, which has limited widespread implementation. Methods: New noninvasive VNS (nVNS) devices have been developed which allow external stimulation of the vagus nerve, and their effects on physiology in patients with stress-related psychiatric disorders can be measured with brain imaging, blood biomarkers, and wearable sensing devices. Advantages in terms of cost and convenience may lead to more widespread implementation in psychiatry, as well as facilitate research of the physiology of the vagus nerve in humans. nVNS has effects on autonomic tone, cardiovascular function, inflammatory responses, and central brain areas involved in modulation of emotion, all of which make it particularly applicable to patients with stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD) and depression, since dysregulation of these circuits and systems underlies the symptomatology of these disorders. Results: This paper reviewed the physiology of the vagus nerve and its relevance to modulating the stress response in the context of application of nVNS to stress-related psychiatric disorders. Conclusions: nVNS has a favorable effect on stress physiology that is measurable using brain imaging, blood biomarkers of inflammation, and wearable sensing devices, and shows promise in the prevention and treatment of stress-related psychiatric disorders.
In various applications such as neural prostheses or solar cells, there is a need to alter the surface morphology of high aspect ratio structures so that the real surface area is greater than geometrical area. The change in surface morphology enhances the devices functionality. One of the applications of altering the surface morphology is of neural implants such as the Utah electrode array (UEA) that communicate with single neurons by charge injection induced stimulation or by recording electrical neural signals. For high selectivity between single cells of the nervous system, the electrode surface area is required to be as small as possible, while the impedance is required to be as low as possible for good signal to noise ratios (SNR) during neural recording. For stimulation, high charge injection and charge transfer capacities of the electrodes are required, which increase with the electrode surface. Traditionally, researchers have worked with either increasing the roughness of the existing metallization (Platinum grey, black) or other materials such as Iridium Oxide and PEDOT. All of these previously investigated methods lead to more complicated metal deposition processes that are difficult to control and often have a critical impact on the mechanical properties of the metal films. Therefore, a modification of the surface underneath the electrode’s coating will increase its surface area while maintaining the standard and well controlled metal deposition process. In this work, the surfaces of the Silicon micro-needles were engineered by creating a defined microstructure on the electrodes surface using several methods such as Laser ablation, focused ion beam, sputter etching, reactive ion etching (RIE) and deep reactive ion etching (DRIE). The surface modification processes were optimized for the high aspect ratio Silicon structures of the UEA. The increase in real surface area while maintaining the geometrical surface area was verified using scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). The best results were obtained by DRIE induced surface morphology. Decreases in impedance values of electrodes up to 76 % indicate the successful surface engineering of the high aspect ratio Silicon structures.
Background: Traumatic stress can have lasting effects on neurobiology and result in psychiatric conditions such as posttraumatic stress disorder (PTSD). We hypothesize that non-invasive cervical vagal nerve stimulation (nVNS) may alleviate trauma symptoms by reducing stress sympathetic reactivity. This study examined how nVNS alters neural responses to personalized traumatic scripts. Methods: Nineteen participants who had experienced trauma but did not have the diagnosis of PTSD completed this double-blind sham-controlled study. In three sequential time blocks, personalized traumatic scripts were presented to participants immediately followed by either sham stimulation (n = 8; 0–14 V, 0.2 Hz, pulse width = 5s) or active nVNS (n = 11; 0–30 V, 25 Hz, pulse width = 40 ms). Brain activity during traumatic scripts was assessed using High Resolution Positron Emission Tomography (HR-PET) with radiolabeled water to measure brain blood flow. Results: Traumatic scripts resulted in significant activations within the bilateral medial and orbital prefrontal cortex, premotor cortex, anterior cingulate, thalamus, insula, hippocampus, right amygdala, and right putamen. Greater activation was observed during sham stimulation compared to nVNS within the bilateral prefrontal and orbitofrontal cortex, premotor cortex, temporal lobe, parahippocampal gyrus, insula, and left anterior cingulate. During the first exposure to the trauma scripts, greater activations were found in the motor cortices and ventral visual stream whereas prefrontal cortex and anterior cingulate activations were more predominant with later script presentations for those subjects receiving sham stimulation. Conclusion: nVNS decreases neural reactivity to an emotional stressor in limbic and other brain areas involved in stress, with changes over repeated exposures suggesting a shift from scene appraisal to cognitively processing the emotional event.
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