Xth Cranial Nerves Research Articles

Familial dysautonomia.

Familial dysautonomia (FD) is an autosomal recessive hereditary sensory and autonomic neuropathy (HSAN, type 3) expressed at birth with profound sensory loss and early death. The FD founder mutation in the ELP1 gene arose within the Ashkenazi Jews in the sixteenth century and is present in 1:30 Jews of European ancestry. The mutation yield a tissue-specific skipping of exon 20 and a loss of function of the elongator-1 protein (ELP1), which is essential for the development and survival of neurons. Patients with FD produce variable amounts of ELP1 in different tissues, with the brain producing mostly mutant transcripts. Patients have excessive blood pressure variability due to the failure of the IXth and Xth cranial nerves to carry baroreceptor signals. Neurogenic dysphagia causes frequent aspiration leading to chronic pulmonary disease. Characteristic hyperadrenergic "autonomic crises" consisting of brisk episodes of severe hypertension, tachycardia, skin blotching, retching, and vomiting occur in all patients. Progressive features of the disease include retinal nerve fiber loss and blindness, and proprioceptive ataxia with severe gait impairment. Chemoreflex failure may explain the high frequency of sudden death in sleep. Although 99.5% of patients are homozygous for the founder mutation, phenotypic severity varies, suggesting that modifier genes impact expression. Medical management is currently symptomatic and preventive. Disease-modifying therapies are close to clinical testing. Endpoints to measure efficacy have been developed, and the ELP1 levels are a good surrogate endpoint for target engagement. Early intervention may be critical for treatment to be successful.

A Step Further-The Role of Trigeminocardiac Reflex in Therapeutic Implications: Hypothesis, Evidence, and Experimental Models.

The trigeminocardiac reflex (TCR) is a well-recognized brainstem reflex that represents a unique interaction between the brain and the heart through the Vth and Xth cranial nerves and brainstem nuclei. The TCR has mainly been reported as an intraoperative phenomenon causing cardiovascular changes during skull-base surgeries. However, it is now appreciated that the TCR is implicated during non-neurosurgical procedures and in nonsurgical conditions, and its complex reflex pathways have been explored as potential therapeutic options in various neurological and cardiovascular diseases. This narrative review presents an in-depth overview of hypothetical and experimental models of the TCR phenomenon in relation to the Vth and Xth cranial nerves. In addition, primitive interactions between these 2 cranial nerves and their significance are highlighted. Finally, therapeutic models of the complex interactions of the TCR and areas for further research will be considered.

The Role of Serotonin in Singultus: A Review.

The use of dopamine receptor blockers for chronic singultus treatment is based—at least partially—on circular thinking: chlorpromazine is FDA-approved for hiccups, chlorpromazine is a neuroleptic, neuroleptics are dopamine receptor blockers, and therefore hiccup is due to dopaminergic dysfunction. Chlorpromazine interacts with high affinity with a multitude of receptors and ion channels. This promiscuity is the basis for many of the therapeutic effects and adverse drug reactions of this drug. While an involvement of dopamine is certain, it is by no means clear that dopaminergic dysfunction is the hallmark of singultus. The common denominator of most remedies for transient hiccup is their ability to activate the vagus nerve. Both afferent and efferent vagal activity and the central integration of the Xth cranial nerve function are modulated, inter alia, via serotonergic mechanisms; beneficial (therapeutic) effects for hiccup are to be expected from serotonin (5-HT) receptor subtype ligands that enhance vagal activity. Taken together, it appears that the ability to increase vagus output is mainly associated with 5-HT1A, 5-HT3, and 5-HT7 agonists and with 5-HT2C antagonists. The plausibility of the serotonergic singultus hypothesis is examined against available pharmacokinetic, pharmacodynamic, and clinical data for a number of drugs.

B.05 Hemi-laryngopharyngeal spasm (HELPS) syndrome: The discovery, cure, and characterization of a new neurological condition

Background: We published the world’s first case of hemi-laryngpharyngeal spasm (HELPS) syndrome cured by microvascular decompression (MVD) of the Xth cranial nerve in 2016. We now present a small cohort of patients (n=3) successfully treated with surgery in order to better delineate the common characteristics of this syndrome, diagnostic tests of choice, nuances of their surgical care and outcomes of their treatment. Methods: The history and physical examination of three patients with HELPS syndrome are presented. Pre-operative laryngoscopy, neuroimaging, response to botox and intra-operative videos are detailed. Post-operative outcome and complications are presented. Results: Each patient reported similar motor (choking) and sensory (coughing) features in their history. Episodic choking relentlessly progressed over the years until it occurred while sleeping and with frightening severity prompting tracheostomy in one patient and intubation in another. A “tickling” sensation deep in the throat triggered episodic coughing that worsened over the years until it occurred while sleeping and with frightening severity (syncope and incontinence). Conclusions: A review of the literature suggests that patients with similar symptoms, often called episodic laryngospasm in the past, have been treated with psychotherapy or antacids. With the recognition that a clearly defined subset of these patients have HELPS syndrome, we can offer them the potential of a neurosurgical cure.

Postdeglutitive residue in vagus nerve paralysis and its association with feeding style.

The objective of this study is to compare the postdeglutitive pharyngeal residues between Xth cranial nerve paralysis (XNP) and isolated recurrent laryngeal nerve paralysis (RLNP) to elucidate the association with feeding style. This study enrolled 15 XNP patients with injuries at the brainstem level (Group I) and 26 patients with RLNP (Group II). All subjects underwent videofluoroscopic swallowing studies (VFSS). The pyriform sinus (PS) and vallecula residues were quantified. The symmetry of the affected versus non-affected sides was compared in both groups. Feeding style at the time of VFSS was also examined. The intra-rater correlation coefficients for all of the data, including the areas of both the vallecula and pyriform sinus on the affected and non-affected sides, were 0.88-0.92 (p<0.001), reflecting high consistency of the evaluation. In Group I, there was significantly (p<0.01) more residue in the PS, but not vallecula, compared to the respective non-affected sides, while in Group II there were no significant differences in residue between the affected and non-affected sides for either the vallecula or PS. Comparing Groups I and II, there was significant (p<0.01) residue on the affected side in the PS but not the vallecula. There was a significant correlation between dependency on a feeding tube and XNP (p<0.01, Chi-square test). XNP at the brainstem level may cause significantly increased residue in the PS compared to RLNP. This might increase the dependency on a feeding tube with XNP.

Vagoglossopharyngeal neuralgia revealed through predominant digestive vagal manifestations. Case report and literature review

Vagoglossopharyngeal neuralgia is a rare pathology whose atypical forms, dominated by syncopal manifestations, are still rarer. Although the territory of the vagus nerve involves, beyond the cardiovascular system, the respiratory and the digestive systems, there is no report in literature of atypical forms other than syncopal. Therefore, the authors were prompted to report the case of a patient whose vagoglossopharyngeal neuralgia was predominantly revealed by digestive symptoms. A 58-year-old patient presented with stereotypical severe digestive disturbances including nausea, vomiting and diarrhoea. High definition cranial MRI showed a neurovascular conflict between the posterior inferior cerebellar artery and the IXth and Xth nerves, on the right side. A microsurgical decompression was carried out which confirmed the vascular compression and successful transposition of the artery. One year after the surgery, the patient was free from all painful and digestive symptoms. A survey of the literature did not find any reference to digestive symptoms together with the neuralgia; only a syncopal type of cardiac symptoms related to the parasympathetic nervous system were described. The hypothesis was that the revealing digestive symptoms are linked to a similar parasympathetic mechanism, implying the visceral component of the Xth cranial nerve.

SPARCL1-containing neurons in the human brainstem and sensory ganglion

Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is a member of the osteonectin family of proteins. In this study, immunohistochemistry for SPARCL1 was performed to obtain its distribution in the human brainstem, cervical spinal cord, and sensory ganglion. SPARCL1-immunoreactivity was detected in neuronal cell bodies including perikarya and proximal dendrites, and the neuropil. The motor nuclei of the IIIrd, Vth, VIth, VIIth, IXth, Xth, XIth, and XIIth cranial nerves and spinal nerves contained many SPARCL1-immunoreactive (-IR) neurons with medium-sized to large cell bodies. Small and medium-sized SPARCL1-IR neurons were distributed in sensory nuclei of the Vth, VIIth, VIIIth, IXth, and Xth cranial nerves. In the medulla oblongata, the dorsal column nuclei also had small to medium-sized SPARCL1-IR neurons. In addition, SPARCL1-IR neurons were detected in the nucleus of the trapezoid body and pontine nucleus within the pons and the arcuate nucleus in the medulla oblongata. In the cervical spinal cord, the ventral horn contained some SPARCL1-IR neurons with large cell bodies. These findings suggest that SPARCL1-containing neurons function to relay and regulate motor and sensory signals in the human brainstem. In the dorsal root (DRG) and trigeminal ganglia (TG), primary sensory neurons contained SPARCL1-immunoreactivity. The proportion of SPARCL1-IR neurons in the TG (mean ± SD, 39.9 ± 2.4%) was higher than in the DRG (30.6 ± 2.1%). SPARCL1-IR neurons were mostly medium-sized to large (mean ± SD, 1494.5 ± 708.3 μm2; range, 320.4–4353.4 μm2) in the DRG, whereas such neurons were of various cell body sizes in the TG (mean ± SD, 1291.2 ± 532.8 μm2; range, 209.3–4326.4 μm2). There appears to be a SPARCL1-containing sensory pathway in the ganglion and brainstem of the spinal and trigeminal nervous systems.

Results of the ROADSTER multicenter trial of transcarotid stenting with dynamic flow reversal

This report presents the 30-day results of the Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) multicenter trial and evaluates the safety and efficacy of ENROUTE Transcarotid NPS (Silk Road Medical Inc, Sunnyvale, Calif), a novel transcarotid neuroprotection system that provides direct surgical common carotid access and cerebral embolic protection via high-rate flow reversal during carotid artery stenting (CAS). A prospective, single-arm, multicenter clinical trial was performed to evaluate the use of the ENROUTE Transcarotid NPS during CAS procedures performed in patients considered to be at high risk for complications from carotid endarterectomy. Symptomatic patients with ≥50% stenosis and asymptomatic patients with ≥70% stenosis were eligible to be treated with any U.S. Food and Drug Administration-approved carotid artery stent. The primary end point was the composite of all stroke, myocardial infarction (MI), and death at 30days postprocedure as defined in the Food and Drug Administration-approved study protocol. Secondary end points included cranialnerve injury; 30-day stroke, death, stroke/death, and MI; acute device, technical, and procedural success; and access site complications. All major adverse events were adjudicated by an independent clinical events committee. Between November 2012 and July 2014, 208 patients were enrolled at 18 sites. Sixty-seven patients were enrolled as lead-in cases, and 141 were enrolled in the pivotal phase. In the pivotal cohort, 26% were symptomatic and 75% were asymptomatic. Acute device and technical success were 99% (140 of 141). By hierarchical analysis, the all-stroke rate in the pivotal group was 1.4% (2 of 141), stroke and death was 2.8% (4 of 141), and stroke, death and MI was 3.5% (5 of 141). One patient (0.7%) experienced postoperative hoarseness from potential Xth cranial nerve injury, which completely resolved at the 6-month follow-up visit. The results of the ROADSTER trial demonstrate that the use of the ENROUTE Transcarotid NPS is safe and effective at preventing stroke during CAS. The overall stroke rate of 1.4% is the lowest reported to date for any prospective, multicenter clinical trial of CAS.

Distribution and innervation of putative peripheral arterial chemoreceptors in the red-eared slider (Trachemys scripta elegans).

Peripheral arterial chemoreceptors have been isolated to the common carotid artery, aorta, and pulmonary artery of turtles. However, the putative neurotransmitters associated with these chemoreceptors have not yet been described. The goal of the present study was to determine the neurochemical content, innervations, and distribution of putative oxygen-sensing cells in the central vasculature of turtles and to derive homologies with peripheral arterial chemoreceptors of other vertebrates. We used tract tracing together with immunohistochemical markers for cholinergic cells (vesicular acetylcholine transporter [VAChT]), tyrosine hydroxylase (TH; the rate-limiting enzyme in catecholamine synthesis), and serotonin (5HT) to identify putative oxygen-sensing cells and to determine their anatomical relation to branches of the vagus nerve (Xth cranial nerve). We found potential oxygen-sensing cells in all three chemosensory areas innervated by branches of the Xth cranial nerve. Cells containing either 5HT or VAChT were found in all three sites. The morphology and size of these cells resemble glomus cells found in amphibians, mammals, tortoises, and lizards. Furthermore, we found populations of cholinergic cells located at the base of the aorta and pulmonary artery that are likely involved in efferent regulation of vessel resistance. Catecholamine-containing cells were not found in any of the putative chemosensitive areas. The presence of 5HT- and VAChT-immunoreactive cells in segments of the common carotid artery, aorta, and pulmonary artery appears to reflect a transition between cells containing the major neurotransmitters seen in fish (5HT) and mammals (ACh and adenosine).

Vago-glossopharyngeal neuralgia: a literature review of neurosurgical experience.

Glossopharyngeal neuralgia (GPN), or better named vago-glossopharyngeal neuralgia (VGPN), is a rare disorder amounting to 1 % of the incidence of trigeminal neuralgia (TN). Pain is paroxysmal, of the electrical shooting type, and mainly provoked by stimulation of the pharynx or deep throat, especially during swallowing. Due to its rarity, VGPN is often misdiagnosed. The front line of medical treatment is based on anticonvulsants. Surgery should be considered when the pain is refractory to medications. In most patients, the cause is neurovascular conflict on root entry zone (REZ) or midcistern portion, of the IXth and/or Xth cranial nerves. Compressive vessels can be evidenced by means of a high sensibility and a high specificity resolution MR imaging in most centers. Present consensus is that the first option of neurosurgical treatment be microvascular decompression. In patients with precarious general conditions, stereotactic radiosurgery may be considered. Also, thermo-rhizotomy at the pars nervosa of foramen jugularis or tractotomy-nucleotomy at brainstem may be alternatives, but these methods entail a significant risk of deficits. In this article, the authors reviewed the main literature series on neurosurgical treatments of this disease.

EHMTI-0376. Trigeminovascular sensitisation by chronic subdural haemorrhage: four clinical paediatric cases

Background Sensitisation of the trigeminal nerve (TG) has been extensively studied as a potential mechanism of migraine. Meningeal nociceptors project onto second order neurones of the trigeminocervical complex (TCC) via glutamate neurotransmission. Sensitisation of trigeminal afferents causes massive release of glutamate and central sensitisation. The TCC connects with the VII, IX and Xth cranial nerve nuclei, and participates in the trigeminocardiac reflex which is particularly important in the young .

Clonal analyses in the anterior pre-placodal region: implications for the early lineage bias of placodal progenitors

Cranial ectodermal placodes, a vertebrate innovation, contribute to the adenohypophysis and peripheral nervous system of the head, including the paired sense organs (eyes, nose, ears) and sensory ganglia of the Vth, VIIth, IXth and Xth cranial nerves. Fate-maps of groups of cells in amphibians, teleosts and amniotes have demonstrated that all placodes have a common origin in a horseshoe shaped territory, known as the preplacodal region (PPR), which surrounds the presumptive neural plate of the late gastrula/early neurula stage embryo. Given the extensive regional overlap of progenitors for different placodes in the chick embryo, it has been a matter of debate as to whether individual cells in the PPR are truly multipotent progenitors, with regard to placodal identity, or rather are lineage-biased or restricted to a specific placodal type prior to overt differentiation. Utilizing clonal analyses in vivo, we demonstrate here that the anterior PPR comprises some precursors that contribute either to the olfactory or lens placode well before they are spatially segregated or committed to either of these placodal fates. This suggests that lineage bias towards a specific placodal fate may coincide with induction of the PPR.

Botulinum toxin treatment of severe dysphagia following brainstem stroke

Objective: To evaluate botulinum toxin treatment of hyperactive upper esophageal sphincter after first-time brainstem stroke. Design: A retrospective study. Subjects: Twelve patients with long standing dysphagia after brainstem vascular injury admitted to the rehabilitation department of a medical centre. Methods: All patients underwent clinical examination, videofluoroscopic study of swallowing and electromyography. Botulinum toxin was injected percutaneously under electromyographic guide. Outcomes were measured after two weeks and through a long follow up programme, which ranged from two to ten years. Results: A total of 75% of patients (9 of 12) had favourable outcomes. Two patients showed long lasting functional benefits after only one botulinum toxin injection, while seven patients required further treatments to maintain an adequate oral intake. In seven cases it was possible to remove percutaneous endoscopic gastrostomy. No relevant complications were observed. Conclusion: Botulinum toxin can improve severe dysphagia with elective hyperactivity of the upper esophageal sphincter in patients with or without unilateral paresis of the inferior constrictor muscle and in absence of a nuclear involvement of the IXth and Xth cranial nerves. The outcome could be unsatisfactory in the cases of oral phase involvement, bilateral lesion of the inferior constrictor muscle and when there is velopharyngeal insufficiency.

Endoscopic Myringotomy and Ventilation Tube Insertion under Topical Anesthesia

Endoscopic Myringotomy and Ventilation Tube Insertion under Topical Anesthesia

Early Unilateral Laryngeal Paralysis After Pulmonary Resection With Mediastinal Dissection for Cancer

The purpose of this study was to document the symptoms, evolution, management, and outcome in a large series of patients with an early unilateral laryngeal paralysis after mediastinal lymph node dissection and pulmonary resection for cancer. In this retrospective series of 69 patients, treatment relied on isolated speech therapy in 18 patients and surgical medialization of the paralyzed vocal cord in 51 patients. Duration of follow-up varied from 2 to 109 months, with a mean duration of 15 months. Treatment included isolated speech therapy and laryngeal medialization in 18 patients and 51 patients, respectively. Symptoms included swallowing impairment and dysphonia noted in 63.7% and 98.5% of patients, respectively. Recovery of motion of the paralyzed larynx varied from 2.8% in patients in whom the operative report mentioned that the inferior laryngeal or Xth cranial nerve had been transected, to 23.5% in patients in whom the operative report did not mention nerve transection. Recovery of motion did not occur past the ninth month that followed thoracic surgery. When performed, medialization of the paralyzed larynx resulted in an overall 95.4% and 96% improvement rate for swallowing impairment and dysphonia, respectively, but 1 patient also died of aspiration-related pneumonia. In patients with an early unilateral laryngeal paralysis after pulmonary resection with mediastinal lymph node dissection for cancer, laryngeal medialization has a beneficial impact on swallowing, speech, and voice, resulting in a better quality of life. Persistent swallowing impairment after laryngeal medialization must be managed aggressively, given the risk for delayed pneumonia and even death from aspiration.

The formation of the superior and jugular ganglia: Insights into the generation of sensory neurons by the neural crest

The superior and jugular ganglia (S/JG) are the proximal ganglia of the IXth and Xth cranial nerves and the sensory neurons of these ganglia are neural crest derived. However, it has been unclear the extent to which their differentiation resembles that of the Dorsal Root Ganglia (DRGs). In the DRGs, neural crest cells undergo neuronal differentiation just after the onset of migration and there is evidence suggesting that these cells are pre-specified towards a sensory fate. We have analysed sensory neuronal differentiation in the S/JG. We show, in keeping with previous studies, that neuronal differentiation initiates long after the cessation of neural crest migration. We also find no evidence for the existence of migratory neural crest cells pre-specified towards a sensory phenotype prior to ganglion formation. Rather our results suggest that sensory neuronal differentiation in the S/JG is the result of localised spatiotemporal cues.

水痘帯状疱疹ウイルスによる多発脳神経障害をきたした３例

Varicella-Zoster virus infection sometimes causes multiple nerve paralysis. We report three cases of multiple cranial nerve paralysis due to Varicella-Zoster virus infection. The first patient, a 58-year-old man, presented with right otalgia, dysphagia and hoarseness. There were painful vesicles on the right auricle, and clinical examination demonstrated right hearing impairment and right vocal paralysis. There was no facial palsy. He was diagnosed with VIIIth, IXth and Xth cranial nerve palsy. The second patient, a 60-year-old woman, presented with right otalgia, vertigo, right hearing loss, and dysphagia. There were painful vesicles on the right auricle, and clinical examination demonstrated right hearing impairment, right canal paralysis and deviation of the tongue. Right facial palsy appeared on the 5th disease day. She was diagnosed with VIIth, VIIIth and XIIth cranial nerve palsy. The third patient, a 70-year-old woman, presented with right otalgia and dysphagia. There were painful vesicles on the right auricle and in the larynx, and clinical examination demonstrated soft palatine paralysis, right vocal cord paralysis and atrophy of the right sternocleidomastoid muscle. She was diagnosed with IXth, Xth and XIth cranial nerve palsy. Serum antibody titers for Varicella-Zoster virus were significantly elevated in all patients. All patients were successfully treated with intravenous or oral steroid and intravenous acyclovir.Varicella- Zoster virus infection should be considered, particularly if unilateral cranial nerve palsy with pain is identified.

The Combined Transmastoid Retro- and Infralabyrinthine Transjugular Transcondylar Transtubercular High Cervical Approach for Resection of Glomus Jugulare Tumors

In Reply: We appreciate the comments by Dr. Sanna regarding our article (1). We recognize Dr. Sanna has much experience with these tumors and that, as cranial base surgeons, we should work as a team of neurosurgeons, otologists, and occasionally, head and neck surgeons and plastic surgeons. We also agree that one of the most important issues is the exposure and control of the internal carotid artery. We tailor the approach in terms of the retrojugular, transjugular, or infrajugular exposure with regard to the size and extension of the tumor. If the jugular foramen tumor is mainly intradural, we perform the combined transtemporal, transmastoid, and retrosigmoid intradural procedure for the resection of the intradural portion. If the jugular bulb is already occluded and the tumor has both intradural and jugular foramen components, we perform a combined intradural and extradural exposure. If the tumor is extensive, such as a glomus jugulare tumor involving the infrajugular component, infratemporal carotid artery, and jugular bulb, we do a combined transmastoid infralabyrinthine and combined transtemporal transjugular and infrajugular transcondylar and high cervical exposure. For extensive glomus jugular tumors, we always expose the high-cervical internal carotid artery for proximal control. We also expose the C7 infratemporal carotid artery in front of the jugular bulb by drilling the inferior bony tympanic ring and translocating the facial nerve anteriorly. The most important aspect of cranial base surgery in this region is to avoid causing facial nerve palsy, swallowing disturbance, or voice hoarseness. We specifically choose to not reroute the facial nerve to avoid postoperative facial nerve palsy. We instead translocate the descending fallopian and stylomastoid foramen segments of the facial nerve approximately 5 mm anteriorly to provide adequate exposure of the infratemporal carotid artery. In our experience, it has not been necessary to reroute the facial nerve as Dr. Fisch recommends. Meticulous attention is given to preservation of the IXth and Xth lower cranial nerves around the carotid artery as well as the preservation of the pars nervosa of the jugular bulb floor. Our results from 53 cases of jugular foramen neuromas demonstrate that 75% of patients have normal or nearly normal swallowing function after surgery. For the 30 cases of glomus jugulare tumors, 64% of patients have normal or nearly normal swallowing function after surgery. We perform either gross total or radical subtotal resection of glomus jugulare tumors. The patient may have some residual infiltration around the carotid artery in a minority of cases; however, we monitor the residual glomus tumor around the infratemporal high cervical carotid in follow-up examinations, and in many of these cases, the tumor shows no growth over a follow-up period of 5 to 10 years. If we see significant growth, the patient is referred for stereotactic radiotherapy or radiosurgery. Most jugular foramen tumors, neurinomas, meningiomas, or glomus jugulare tumors are benign. We do not recommend subadventitial dissection of the internal carotid artery because of the high risk of carotid rupture and other carotid complications. In our experience of removing 30 cases of glomus jugulare tumors, we achieved gross total resection in 24 cases (80%), nearly total resection in 2 cases (6.7%), and subtotal resection (some tumor remains adherent to the pars nervosa or around the infratemporal internal carotid artery) in 4 cases (13.3%). New or worsened nerve deficit of the facial nerve was observed in 20% of the patients (most Grade II or III), and deficit of the IXth and Xth cranial nerves was noted in 27% of patients. Most of the patients with IXth and Xth cranial nerve deficit improved with thyroplasty procedures. There was no mortality in this series. We thank Drs. Mario Sanna and Sean Flannigan for their valuable comments and appreciate the opportunity to clarify the rationale for our microanatomical joint neurosurgical-otolaryngological approach to lesions of this area. Takanori Fukushima Raleigh, North Carolina William T. Couldwell Salt Lake City, Utah

Effects of medullary Raphé stimulation on fictive lung ventilation during development in Rana catesbeiana

To better understand serotonergic modulation of air breathing during bullfrog development, we measured changes in fictive lung ventilation frequency associated with focal stimulation of the rostral region of the medullary Raphé neurons. Electrical (3 to 33 Hz) and chemical (glutamate microinjections; 0.5 mol l(-1), 0.3-10 nl) activation of Raphé neurons was performed in brainstem preparations from three developmental stages (pre- and metamorphic tadpoles and adult frogs). Fictive lung ventilation was recorded extracelluarly from the Vth and Xth cranial nerves. Electrical stimulation of Raphé neurons caused a frequency-dependent increase in lung burst frequency in pre-metamorphic tadpoles only. In metamorphic tadpoles, an increase in fictive lung ventilation was observed at 20 Hz only. Electrical stimulation had no effect in preparations from adult frogs. Glutamate microinjections elicited similar responses as a lung burst frequency increase was observed in the pre-metamorphic group only. Regardless of the stimulation technique used, the increase in fictive lung ventilation was attenuated by the selective 5-HT3 antagonist tropisetron (5-20 micromol l(-1)). Results from immunohistochemical analysis of the Raphé region stimulated do not correlate with functional data as the number of 5-HT immunoreactive neurons within this region increases during development. We conclude that, in this preparation, stimulation of lung ventilation by the medullary Raphé is restricted to early (pre-metamorphic) stages.

A phylogenetic journey through the vague and ambiguous Xth cranial nerve: A commentary on contemporary heart rate variability research

Contemporary heart rate variability research is discussed within a historical context. Implicit in this history is the discovery that the central nervous system regulates the heart and how information regarding neural regulation of the heart is imbedded in the beat-to-beat heart rate pattern. As methodologies have become more sensitive to neural regulation and as theories have expanded to integrate behavior and psychological processes with neurobiological principles, researchers are becoming better positioned to successfully understand how neurovisceral processes mediate the expression of health and disease. The contributions to this special issue describe research representing different levels of scientific inquiry and focus on different features of the complex neural feedback system that are manifested in the robust relationships between heart rate variability and several behavioral, psychological, physiological, and health processes. This article provides a commentary to these contributions.