Frequency-Specific Effects of Noninvasive Median Nerve Stimulation on Gastric Slow Wave Activity in Humans.

OBJECTIVES: The present study explored the effects of different frequencies of noninvasive median nerve stimulation (nMNS) on two autonomic responses: gastric slow waves under water-loading condition and heart rate variability (HRV). To the best of our knowledge, this is the first study to document the effects of different frequencies of nMNS on gastric slow waves (GSW) in humans under 5-minute water-loading condition. MATERIALS AND METHODS: Twenty healthy adult participants were fitted with a noninvasive body-surface gastric mapping, electrocardiogram (ECG), and a transcutaneous electrical nerve stimulation device and administered with four different nMNS frequencies (placebo-0 Hz, 40 Hz, 120 Hz, and 200 Hz) on four separate counterbalanced days. After the baseline and stimulation periods, a 5-minute water-load test was applied, and a post-water-load period also is recorded for ECG and GSW activity. Time-domain HRV parameters are analyzed with repeated-measures one-way analysis of variance (ANOVA) and a post hoc Tukey multiple comparison test. Parameters that failed normality tests underwent a Freidman test with a post hoc Dunn multiple comparison test. GSW data are analyzed with repeated-measures mixed-effects ANOVA. RESULTS: In empty stomach (baseline vs stimulation), only the 40-Hz frequency statistically significantly (p = 0.0129) increased GSW amplitude in comparison with its own baseline. In full (distended) stomach, 40-Hz and 200-Hz stimulations showed a statistically significant difference (post hoc multiple comparison adjusted, p = 0.0016 and p = 0.0183, respectively) in the Gastric Rhythm Index in comparison with the change obtained by placebo stimulation (baseline vs poststimulation periods); 120-Hz nMNS showed a statistically significant difference (p = 0.0300) in the stress index in comparison with the decrease observed in the placebo group. However, 120-Hz nMNS did not induce a statistically significant change in gastric electrical activity compared to placebo stimulation. The nMNS did not follow the linear "dose-response" relationship between nMNS frequency and gastric/HRV parameters. CONCLUSIONS: The 40-Hz and 200-Hz nMNS frequencies showed the most promising results in response to gastric distension, in addition to 40 Hz for an empty stomach. Further research is essential to explore the potential therapeutic effects of these frequencies on gastric diseases such as gastroparesis, gastroesophageal reflux disease, and functional dyspepsia that can be used in wrist wearables.

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping.

OBJECTIVES: Transcutaneous auricular vagus nerve stimulation (TaVNS) is a supplementary treatment for gastric symptoms resulting from dysrhythmias. The main objective of this study was to quantify the effects of 10, 40, and 80 Hz TaVNS and sham in healthy individuals in response to a 5-minute water-load (WL5) test. MATERIALS AND METHODS: Eighteen healthy volunteers aged between 21 and 55 years (body mass index: 27.1 ± 3.2) were recruited. Each subject fasted for up to eight hours and participated in four 95-minute sessions, which consisted of 30 fasted baseline, 30 minutes TaVNS, WL5, and 30 minutes post-WL5. Heart rate variability was assessed using sternal electrocardiogram. Body-surface gastric mapping and bloating (/10) were recorded. One-way ANOVA with post hoc Tukey test was performed to test the difference between TaVNS protocols in terms of frequency, amplitude, bloating scores, root mean square of the successive differences (RMSSD), and stress index (SI). RESULTS: On average, the subjects consumed 526 ± 160 mL of water, with volume ingested correlated to bloating (mean score 4.1 ± 1.8; r = 0.36, p = 0.029). In general, the reduction in frequency and rhythm stability during the post-WL5 period in sham was normalized by all three TaVNS protocols. Both 40- and 80-Hz protocols also caused increases in amplitude during the stim-only and/or post-WL5 periods. RMSSD increased during the 40-Hz protocol. SI increased during the 10-Hz protocol but decreased during the 40- and 80-Hz protocols. CONCLUSION: TaVNS proved effective in normalizing gastric dysrhythmias by WL5 in healthy subjects by altering both parasympathetic and sympathetic pathways.

Non-Contact Assessment of Swallowing Dysfunction Using Smartphone Captured Skin Displacements.

Early and accurate dysphagia diagnosis is essential for reducing the risk of associated co-morbidities and mortalities. Barriers to current evaluation methods may alter the effectiveness of identifying at-risk patients. This preliminary study evaluates the feasibility of using iPhone X-captured videos of swallowing as a non-contact dysphagia screening tool. Video recordings of the anterior and lateral necks were captured simultaneously with videofluoroscopy in dysphagic patients. Videos were analyzed using an image registration algorithm (phase-based Savitzky-Golay gradient correlation (P-SG-GC)) to determine skin displacements over hyolaryngeal regions. Biomechanical swallowing parameters of hyolaryngeal displacement and velocity were also measured. Swallowing safety and efficiency were assessed by the Penetration Aspiration Scale (PAS), Residue Severity Ratings (RSR), and the Normalized Residue Ratio Scale (NRRS). Anterior hyoid excursion and horizontal skin displacements were strongly correlated with swallows of a 20 mL bolus (rs = 0.67). Skin displacements of the neck were moderately to very strongly correlated with scores on the PAS (rs = 0.80), NRRS (rs = 0.41-0.62), and RSR (rs = 0.33). This is the first study to utilize smartphone technology and image registration methods to produce skin displacements indicating post-swallow residual and penetration-aspiration. Enhancing screening methods provides a greater chance of detecting dysphagia, reducing the risk of negative health impacts.

Prediction and detection of virtual reality induced cybersickness: a spiking neural network approach using spatiotemporal EEG brain data and heart rate variability.

Virtual Reality (VR) allows users to interact with 3D immersive environments and has the potential to be a key technology across many domain applications, including access to a future metaverse. Yet, consumer adoption of VR technology is limited by cybersickness (CS)-a debilitating sensation accompanied by a cluster of symptoms, including nausea, oculomotor issues and dizziness. A leading problem is the lack of automated objective tools to predict or detect CS in individuals, which can then be used for resistance training, timely warning systems or clinical intervention. This paper explores the spatiotemporal brain dynamics and heart rate variability involved in cybersickness and uses this information to both predict and detect CS episodes. The present study applies deep learning of EEG in a spiking neural network (SNN) architecture to predict CS prior to using VR (85.9%, F7) and detect it (76.6%, FP1, Cz). ECG-derived sympathetic heart rate variability (HRV) parameters can be used for both prediction (74.2%) and detection (72.6%) but at a lower accuracy than EEG. Multimodal data fusion of EEG and sympathetic HRV does not change this accuracy compared to ECG alone. The study found that Cz (premotor and supplementary motor cortex) and O2 (primary visual cortex) are key hubs in functionally connected networks associated with both CS events and susceptibility to CS. F7 is also suggested as a key area involved in integrating information and implementing responses to incongruent environments that induce cybersickness. Consequently, Cz, O2 and F7 are presented here as promising targets for intervention.

Machine learning methods for the study of cybersickness: a systematic review.

This systematic review offers a world-first critical analysis of machine learning methods and systems, along with future directions for the study of cybersickness induced by virtual reality (VR). VR is becoming increasingly popular and is an important part of current advances in human training, therapies, entertainment, and access to the metaverse. Usage of this technology is limited by cybersickness, a common debilitating condition experienced upon VR immersion. Cybersickness is accompanied by a mix of symptoms including nausea, dizziness, fatigue and oculomotor disturbances. Machine learning can be used to identify cybersickness and is a step towards overcoming these physiological limitations. Practical implementation of this is possible with optimised data collection from wearable devices and appropriate algorithms that incorporate advanced machine learning approaches. The present systematic review focuses on 26 selected studies. These concern machine learning of biometric and neuro-physiological signals obtained from wearable devices for the automatic identification of cybersickness. The methods, data processing and machine learning architecture, as well as suggestions for future exploration on detection and prediction of cybersickness are explored. A wide range of immersion environments, participant activity, features and machine learning architectures were identified. Although models for cybersickness detection have been developed, literature still lacks a model for the prediction of first-instance events. Future research is pointed towards goal-oriented data selection and labelling, as well as the use of brain-inspired spiking neural network models to achieve better accuracy and understanding of complex spatio-temporal brain processes related to cybersickness.

Non-contact neuromodulation of the human autonomic nervous system function via different odors: Sex, menstrual cycle, and odor dose- and duration-specific effects.

In recent decades, it has been uncovered that the autonomic nervous system (ANS) can be influenced using non-contact neuromodulation via odor stimulation. Increasing parasympathetic-vagal activation of the ANS is integral to improving the sympathovagal balance between the sympathetic- and parasympathetic nervous systems, which is often imbalanced in several chronic inflammatory disorders, such as rheumatoid arthritis and inflammatory bowel diseases. Although research into olfactory stimulation has been observed on the ANS, it is still lacking in the exploration of odor concentration and odor-specific effects. This is particularly the case as research has not utilized specified tools, such as the olfactometer to provide precise odor delivery. Furthermore, no research has compared the results in separate sex cohorts to investigate the role of sex or the menstrual stage on the subsequent interactions. In this study, we investigated the olfactory stimulation effects of four natural odors (mushroom, lavender, jasmine, and rose) in three concentrations (low, moderate, and high) on the ANS. To observe activity from the ANS, we used an electrocardiogram (ECG) based heart rate variability (HRV) and eye-tracker technology (pupil diameter). We found for the first time in literature that there were acute dose- and duration-specific odor effects of odors on the ANS. We also found sex and menstrual cycle effects in this interaction. Furthermore, there were stark distinctions in sympathovagal activity dependent ANS activation (HRV) in comparison to the oculomotor nerve-parasympathetic/cervical sympathetic nerves dependent ANS responses (pupil diameter). Sympathovagal activity dependent HRV showed odor, sex, and menstrual-stage interactions in both divisions of the ANS while the pupil responses only indicated increased sympathetic activation. These results shed light on the use of odor-specific stimulation to modulate the ANS activity in the context of sex and the menstrual stage. Future studies should be performed using a chronic odor delivery design to investigate the long-term effects of odors on the ANS. Clinical trial registration: Australian New Zealand Clinical Trials Registry, identifier [ACTRN12622000415707].

Hand Pronation-Supination Movement as a Proxy for Remotely Monitoring Gait and Posture Stability in Parkinson's Disease.

The Unified Parkinson's Disease Rating Scale (UPDRS) is a subjective Parkinson's Disease (PD) physician scoring/monitoring system. To date, there is no single upper limb wearable/non-contact system that can be used objectively to assess all UPDRS-III motor system subgroups (i.e., tremor (T), rigidity (R), bradykinesia (B), gait and posture (GP), and bulbar anomalies (BA)). We evaluated the use of a non-contact hand motion tracking system for potential extraction of GP information using forearm pronation-supination (P/S) motion parameters (speed, acceleration, and frequency). Twenty-four patients with idiopathic PD participated, and their UPDRS data were recorded bilaterally by physicians. Pearson's correlation, regression analyses, and Monte Carlo validation was conducted for all combinations of UPDRS subgroups versus motion parameters. In the 262,125 regression models that were trained and tested, the models within 1% of the lowest error showed that the frequency of P/S contributes to approximately one third of all models; while speed and acceleration also contribute significantly to the prediction of GP from the left-hand motion of right handed patients. In short, the P/S better indicated GP when performed with the non-dominant hand. There was also a significant negative correlation (with medium to large effect size, range: 0.3-0.58) between the P/S speed and the single BA score for both forearms and combined UPDRS score for the dominant hand. This study highlights the potential use of wearable or non-contact systems for forearm P/S to remotely monitor and predict the GP information in PD.

Investigation of the Optimal Parameters of Median Nerve Stimulation Using a Variety of Stimulation Methods and Its Effects on Heart Rate Variability: A Systematic Review.

OBJECTIVES: There is a wealth of literature supporting the use of median nerve stimulation (MNS) for modulating autonomic nervous system (ANS) dysfunction such as in hypoxia, recovery after heart valve replacement, ischemia, and cardiac contractibility. Heart rate variability (HRV) is considered a gold standard for measuring autonomic modulation and dynamic nonlinear ANS processes through the use of an electrocardiogram (ECG). Although the use of MNS on HRV in animals and humans has been documented, optimal stimulation parameters are yet to be outlined. MATERIALS AND METHODS: This review aims to synthesize findings of neurostimulation using MNS on animals and humans while observing HRV using an ECG. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines with search parameters of "Median nerve stimulation," "Neiguan," "PC-6," "HRV," "Heart rate variability," and "Heart-rate variability" observing on animals and human subjects, we found a total of 17 eligible articles. RESULTS: In this review, changing two parameters, that is, stimulation frequency and side of stimulation, appears to be the most influential in effecting frequency-domain ECG analysis of HRV. However, it is evident from this review that to perform an effective comparison of the effects of MNS on HRV, more detailed reports of the studies are required. CONCLUSIONS: Finding the optimal stimulation parameters for MNS is crucial for improving HRV. This will in turn contribute to normalizing ANS function impaired in numerous clinical conditions, such as epilepsy or diabetes.

Directional effects of whole-body spinning and visual flow in virtual reality on vagal neuromodulation.

BACKGROUND: Neural circuits allow whole-body yaw rotation to modulate vagal parasympathetic activity, which alters beat-to-beat variation in heart rate. The overall output of spinning direction, as well as vestibular-visual interactions on vagal activity still needs to be investigated. OBJECTIVE: This study investigated direction-dependent effects of visual and natural vestibular stimulation on two autonomic responses: heart rate variability (HRV) and pupil diameter. METHODS: Healthy human male subjects (n = 27) underwent constant whole-body yaw rotation with eyes open and closed in the clockwise (CW) and anticlockwise (ACW) directions, at 90°/s for two minutes. Subjects also viewed the same spinning environments on video in a VR headset. RESULTS: CW spinning significantly decreased parasympathetic vagal activity in all conditions (CW open p = 0.0048, CW closed p = 0.0151, CW VR p = 0.0019,), but not ACW spinning (ACW open p = 0.2068, ACW closed p = 0.7755, ACW VR p = 0.1775,) as indicated by an HRV metric, the root mean square of successive RR interval differences (RMSSD). There were no direction-dependent effects of constant spinning on sympathetic activity inferred through the HRV metrics, stress index (SI), sympathetic nervous system index (SNS index) and pupil diameter. Neuroplasticity in the CW eyes closed and CW VR conditions post stimulation was observed. CONCLUSIONS: Only one direction of yaw spinning, and visual flow caused vagal nerve neuromodulation and neuroplasticity, resulting in an inhibition of parasympathetic activity on the heart, to the same extent in either vestibular or visual stimulation. These results indicate that visual flow in VR can be used as a non-electrical method for vagus nerve inhibition without the need for body motion in the treatment of disorders with vagal overactivity. The findings are also important for VR and spinning chair based autonomic nervous system modulation protocols, and the effects of motion integrated VR.

Human and Human-Interfaced AI Interactions: Modulation of Human Male Autonomic Nervous System via Pupil Mimicry.

Pupillary alterations in virtual humans induce neurophysiological responses within an observer. Technological advances have enabled rapid developments in artificial intelligence (AI), from verbal systems, to visual AI interfaces with the ability to express, and respond to emotional states of a user. Visual AI interfaces are able to change their physical parameters, such as pupil diameter. Pupillary changes can alter heart rate, however, effects on heart rate variability (HRV) are unknown. HRV, is an autonomic, non-conscious parameter which monitors sympathetic and parasympathetic nervous system (PNS) activity. N = 34 male participants aged between 19-33 were subjected to a number of conditions such as pupil dilation, constriction and blushing. The present research is the first to investigate the effects of virtual human interactions on human HRV. Outcomes of this study were obtained using eye tracking and HRV measurements. Pupil dilation relative to constriction presented in the female virtual partner induced a significant right pupillary diameter increase (p = 0.041) in human observers. Additionally, female virtual partner pupil constriction relative to dilation induced a significant increase in participants' PNS HRV response (p = 0.036). These findings indicate the ability of a female virtual interaction partner to modulate parasympathetic autonomic functioning in young healthy male humans. This allows first insights into the effects of interacting with virtual AI interaction partners, on human autonomic functioning, and may aid development of future virtual humans, and their implementation into relevant clinical settings.

Optimized Electrode Placements for Non-invasive Electrical Stimulation of the Olfactory Bulb and Olfactory Mucosa.

The olfactory system is known to be dysfunctional in the early stages of Parkinson's disease (PD) and Alzheimer's disease (AD). It is also shown that intact olfactory function can be a key role player for regaining consciousness after brain injuries. Modulation of the olfactory regions has been attempted successfully with electrical stimulation over the years, either directly (transethmoidally, intraoperatively, internasally, etc.) or indirectly through the vagus nerve. We sought to develop a means of delivering optimized electrical stimulation to the olfactory region in a non-invasive fashion and in a way that is simpler, easier, and less cumbersome. The ultimate goal was to develop a system that would allow easier testing in future clinical trials presenting an opportunity to fully develop this potential treatment option. We devised six potential electrode placements leveraging commonly accepted facts of electrical stimulation, easier access through relatively higher conductive pathways into the brain, and practicality. Using an ultra-high-resolution finite element model, we screened each one of these montages for their ability to target the olfactory regions primarily and thereafter for select sub-cortical regions implicated in the pathogenesis of PD and AD. Modeling results indicate that some placements do result in inducing meaningful electric field magnitudes in the regions of interest. A practical headgear concept is proposed to realize the most ideal configuration. Our results pave the way for developing the first non-invasive electrical stimulation wearable system for targeting the olfactory regions which can help to alleviate the symptoms or suppress the progression of these neurological disorders.

Neuromodulation of the Pineal Gland via Electrical Stimulation of Its Sympathetic Innervation Pathway.

Stimulation of the pineal gland via its sympathetic innervation pathway results in the production of N-acetylserotonin and melatonin. Melatonin has many therapeutic roles and is heavily implicated in the regulation of the sleep-wake cycle. In addition, N-acetylserotonin has recently been reported to promote neurogenesis in the brain. Upregulation of these indoleamines is possible via neuromodulation of the pineal gland. This is achieved by electrical stimulation of structures or fibres in the pineal gland sympathetic innervation pathway. Many studies have performed such pineal neuromodulation using both invasive and non-invasive methods. However, the effects of various experimental variables and stimulation paradigms has not yet been reviewed and evaluated. This review summarises these studies and presents the optimal experimental protocols and stimulation parameters necessary for maximal upregulation of melatonin metabolic output.

A Randomised Control Trial and Comparative Analysis of Multi-Dimensional Learning Tools in Anatomy.

This article presents the results of a study that examined students' ability to retain what they have learned in an anatomy course after thirty days via using various learning tools for twenty minutes. Fifty-two second-year medical students were randomly assigned to three learning tools: text-only, three-dimension visualisation in a two-dimensional screen (3DM), or mixed reality (MR). An anatomy test lasting for twenty minutes measuring spatial and nominal knowledge was taken immediately after the learning intervention and another thirty days later. Psychometric tests were also used to measure participants' memory, reasoning and concentration abilities. Additionally, electroencephalogram data was captured to measure the participants' awakeness during the learning session. Results of this study showed that the MR group performed poorly in the nominal questions compared to the other groups; however, the MR group demonstrated higher retention in both the nominal and spatial type information for at least a month compared to the other groups. Furthermore, participants in the 3DM and MR groups reported increased engagement. The results of this study suggest that three-dimensional visualiser tools are likely to enhance learning in anatomy education. However, the study itself has several limitations; some include limited sample size and various threats to internal validity.

The effects of low-and high-frequency non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) on gastric slow waves evaluated using in vivo high-resolution mapping in porcine.

BACKGROUNDS: Gastric motility is regulated by an electrophysiological activity called slow-wave and neuronal innervations by the vagus nerve. Transcutaneous auricular vagal nerve stimulation (taVNS) has been demonstrated to have therapeutic potential for a wide range of medical conditions, including the management of gastric dysfunctions. The main objective of this study was to gain a better understanding of how non-invasive neuromodulation influences gastric slow wave under in vivo conditions. METHODS: TaVNS protocols were applied in conjunction with 192-channel gastric bioelectrical mapping in porcine subjects under general anesthesia. The spatiotemporal profiles of gastric slow wave were assessed under two different taVNS protocols at 10 and 80 Hz. KEY RESULTS: The taVNS protocols effectively altered the interval and amplitude of gastric slow waves, but not the velocity or the percentage of spatial dysrhythmias. In the subjects that responded to the protocols, the 10 Hz protocol was shown to normalize slow-wave propagation pattern in 90% of the subjects, whereas the 80 Hz protocol was shown to inhibit slow waves in 60% of the subjects. CONCLUSIONS AND INFERENCES: Chronic responses of gastric motility and slow waves in response to taVNS should be investigated using non-invasive means in conscious subjects in future.

Concerning Auricular Vagal Nerve Stimulation: Occult Neural Networks.

Auricular vagal nerve stimulation (AVNS) is an evolving neuromodulation technology that has a wide range of therapeutic applications across multiple disciplines of medical science. To date, AVNS results had been interpreted in the context of a monolog concept of the auricular branch of the vagus nerve (ABVN): that this is the sole network of the mechanism of action and/or structure in the auricular area of the stimulation in the context of activations in the brainstem nuclei, including the nucleus tractus solitarius (NTS), locus coeruleus (LC), trigeminal brainstem nuclei, and the nucleus cuneatus. This review considers the overlooked aspects of neural networks, connections, hijacking axons from cranial nerves and cervical sympathetic ganglions, the inhomogeneous distribution of perivascular sympathetic nerves, and intrinsic/extrinsic auricular muscles in the auricular zone that can explain the vagal and non-vagal nucleus activations in AVNS. In addition, the unique cortical representation of the human ear and interspecies differences in the auricula are discussed. The detailed auricular anatomy of the AVNS zone explored in the present study references structural and functional neural network information to overcome default designs and misinterpretations of existing research on AVNS to provide a better foundation for future investigations that use this modality.

Afferent projections of the subthalamic nucleus in the rat: emphasis on bilateral and interhemispheric connections.

The subthalamic nucleus (STN) is important for normal movement as well as in movement disorders. The STN is a target nuclei in patients with advanced Parkinson's disease (PD). Deep brain stimulation (DBS) is a standard surgical treatment for PD. Although DBS results in a significant reduction in motor disability, several negative side effects have been reported. Thus, to understand the side effects of DBS the connection of the STN should be well known. Therefore, the present study aims to re­examine the STN with an emphasis on poorly­ or un­documented connections. Furthermore, the bilateral and interhemispheric connections of the STN are evaluated. Fifteen male albino rats received injections of Fluoro­Gold retrograde and biotinylated dextran amine anterograde tracers into the STN. Following a 7-10 day survival period, the animals were processed according to the relevant protocol for each tracer. The present study demonstrates ipsilateral connections of the STN with cortical regions (i.e., infralimbic, cingulate, frontal, piriform, primary motor, primary sensory, insular and retrosplenial cortices), the endopiriform nucleus, basal ganglia related structures (i.e., caudate putamen, globus pallidus, ventral pallidum, nucleus accumbens, claustrum and substantia innominata) and the deep cerebellar nuclei (i.e., lateral, anterior interposed). Bilateral connections of the STN were observed with limbic (amygdala, bed nucleus of stria terminalis), hypothalamic (ventromedial, posterior, anterior, lateral and mammillary) thalamic (thalamic reticular nucleus), epithalamic (habenular nucleus), and brainstem structures (superior colliculus, substantia nigra, spinal nucleus of the trigeminal nerve, red nucleus, dorsal raphe nucleus, pedunculopontine tegmental nuclei). Interhemispheric connections between left and right STN were also observed. The present study fills important gaps in connectivity of the STN. In particular, we report STN connectivity with cortical areas (i.e., piriform, endopiriform and insular), claustrum, hypothalamic, thalamic reticular, cerebellar, habenular, trigeminal, red, cuneate and gracile nuclei and substantia innominate. These connections, which have not been previously described or poorly described, provide new routes that can alter the conceptual architecture of the basal ganglia circuitry and may modify our view of the functional identity of the STN.

Peri-arterial Autonomic Innervation of the Human Ear.

Auricular vasomotor responses are considered to be signs of clinical conditions including migraine. The mechanisms of auricular vasomotor control are still debatable. This study aimed at investigating perivascular co-transmitters of vasomotor control in the auricle. Another aim was to provide three-dimensional arterial maps of the auricle, as a proxy of periarterial autonomic innervation. Twelve paired human auricles were used to visualize the arteries following Spalteholz clearing and µ-CT-based reconstruction. Perivascular innervation staining was conducted using anti-tyrosine hydroxylase (TH), anti-neuropeptide Y (NPY), anti-vasoactive intestinal peptide (VIP) and anti-choline acetyl transferase (ChAT). The combined Spalteholz technique and µ-CT revealed a highly consistent arrangement of the auricular vasculature. The superficial temporal (STA) and posterior auricular artery (PAA) supply the helical rim arcade and arcade, with the STA mainly forming the superior and the PAA forming the middle and inferior auricular artery. Co-existence of sympathetic NPY+ and TH+ terminals mediating vasoconstriction, and VIP+ and ACh+ indicating cholinergic vasodilatation, was found in the perivascular zone. The presence of both sympathetic vasoconstriction and cholinergic co-innervation for active vasodilatation was shown in the perivascular auricular zone. Assuming that the highly-consistent vasculature gives way to these terminals, this periarterial innervation may be found spread out across the helix.

Comparison of cerebral ventricular volumes and cortical thicknesses in normal rats and Genetic Absence Epilepsy (GAERS): A developmental study.

Ventricular enlargement and cortical atrophy have been associated with various central nervous system diseases. The aim of the present study was to measure the volumes of the lateral (LV) and third (3V) ventricles and to determine the cortical thickness for the motor (MCx), somatosensory (SSCx), visual (VCx) and auditory (AuCx) cortex and the striatum of Wistar rats, in a developmental series at 10, 20, 30, and 60 days postnatal, and to compare them with similar data from genetic absence epilepsy rats from Strasbourg (GAERS). Serial sections were taken from the brains of Wistar and GAERS animals and were Nissl stained. Photographs were taken from specific sections of the brain for measurements of ventricular volume, cortical and striatal thickness. The image-j computer program was used for the volume and thickness measurements. The data was statistically analyzed by 3-way ANOVA using SPSS 15. Comparison of the measurements of GAERS and Wistar animals showed no statistically significant differences at any of the developmental stages regarding the ventricular (LV and 3V) volumes. However, at P60 and P30 of the MCx, P30 of the SSCx, P20 of the VCx and AuCx showed a significantly thinner cortical thickness in the GAERS than in the Wistar animals. The striatal measurements showed significant decrease in thickness of the striatum at P30 and P60. Further, brain size measurements (between the two temporal poles) showed significant decrease in the size at P30 and P60 of GAERS animals. The presence of thinner cortical and striatal thicknesses and smaller brain size in GAERS animals may suggests that these changes could be involved in the mechanism of epileptogenicity or be a result of the epileptogenicity.

Cervical vagus nerve morphometry and vascularity in the context of nerve stimulation - A cadaveric study.

Vagus nerve stimulation (VNS) has become a well-established therapy for epilepsy and depression, and is emerging to treat inflammatory disease, with the cervical vagus nerve (CVN) as major stimulation site. CVN morphometries are missing for VNS, considering its variability. Morphometric data were obtained from CVNs in 27 cadavers, including branching patterns and histology. Cross-sectional area, greater and lesser diameters averaged 7.2 ± 3.1 mm2, 5.1 ± 1.5 and 4.1 ± 1.3 mm, and were ≤11.0 mm2, ≤7.0 and ≤5.8 mm in 90% of the specimens, respectively. Midline distance (position lateral to the laryngeal eminence) and skin distance (anterior-posterior from skin) averaged 34.5 ± 6.2 and 36.2 ± 9.4 mm, ≤49.0 and ≤41.0 mm in 90%, respectively. Nerve dimensions and surface topography correlated closely, but without gender-, side- or branching-dependent differences. The nerve fascicle number averaged 5.2 ± 3.5. Vagal arteries were observed in 49% of the cases. Negative correlations were found for age and cross-sectional area, as well as subperineural vessel count. Detailed anatomical data on the CVN and its vascularity are given, forming the morphometric basis for VNS refinement, filling an evident gap in light of the CVN being a structure with variable positions and branching. A 35 × 35-mm rule may apply for the CVN position, irrespective of branching or positional variation.