Dorsolateral Pons Research Articles

Role of the pontine respiratory group in the suppression of cough by codeine in cats

Codeine was microinjected into the area of the Kölliker-Fuse nucleus and the adjacent lateral parabrachial nucleus, within the pontine respiratory group in 8 anesthetized cats. Electromyograms (EMGs) of the diaphragm (DIA) and abdominal muscles (ABD), esophageal pressures (EP), and blood pressure were recorded and analyzed during mechanically induced tracheobronchial cough. Unilateral microinjections of 3.3 mM codeine (3 injections, each 37 ± 1.2 nl) had no significant effect on the cough number. However, the amplitudes of the cough ABD EMG, expiratory EP and, to a lesser extent, DIA EMG were significantly reduced. There were no significant changes in the temporal parameters of the cough. Control microinjections of artificial cerebrospinal fluid in 6 cats did not show a significant effect on cough data compared to those after codeine microinjections. Codeine-sensitive neurons in the rostral dorsolateral pons contribute to controlling cough motor output, likely through the central pattern generator of cough.

Neural Control of REM Sleep and Motor Atonia: Current Perspectives.

Since the formal discovery of rapid eye movement (REM) sleep in 1953, we have gained a vast amount of knowledge regarding the specific populations of neurons, their connections, and synaptic mechanisms regulating this stage of sleep and its accompanying features. This article discusses REM sleep circuits and their dysfunction, specifically emphasizing recent studies using conditional genetic tools. Sublaterodorsal nucleus (SLD) in the dorsolateral pons, especially the glutamatergic subpopulation in this region (SLDGlut), are shown to be indispensable for REM sleep. These neurons appear to be single REM generators in the rodent brain and may initiate and orchestrate all REM sleep events, including cortical and hippocampal activation and muscle atonia through distinct pathways. However, severalcell groups in the brainstem and hypothalamus may influence SLDGlut neuron activity, thereby modulating REM sleep timing, amounts, and architecture. Damage to SLDGlut neurons or their projections involved in muscle atonia leads to REM behavior disorder, whereas the abnormal activation of this pathway during wakefulness may underlie cataplexy in narcolepsy. Despite some opposing views, it has become evident that SLDGlut neurons are the sole generators of REM sleep and its associated characteristics. Further research should prioritize a deeper understanding of their cellular, synaptic, and molecular properties, as well as the mechanisms that trigger their activation during cataplexy and make them susceptible in RBD.

Opioid suppression of an excitatory pontomedullary respiratory circuit by convergent mechanisms.

Opioids depress breathing by inhibition of interconnected respiratory nuclei in the pons and medulla. Mu opioid receptor (MOR) agonists directly hyperpolarize a population of neurons in the dorsolateral pons, particularly the Kölliker-Fuse (KF) nucleus, that are key mediators of opioid-induced respiratory depression. However, the projection target and synaptic connections of MOR-expressing KF neurons are unknown. Here, we used retrograde labeling and brain slice electrophysiology to determine that MOR-expressing KF neurons project to respiratory nuclei in the ventrolateral medulla, including the preBötzinger complex (preBötC) and rostral ventral respiratory group (rVRG). These medullary-projecting, MOR-expressing dorsolateral pontine neurons express FoxP2 and are distinct from calcitonin gene-related peptide-expressing lateral parabrachial neurons. Furthermore, dorsolateral pontine neurons release glutamate onto excitatory preBötC and rVRG neurons via monosynaptic projections, which is inhibited by presynaptic opioid receptors. Surprisingly, the majority of excitatory preBötC and rVRG neurons receiving MOR-sensitive glutamatergic synaptic input from the dorsolateral pons are themselves hyperpolarized by opioids, suggesting a selective opioid-sensitive circuit from the KF to the ventrolateral medulla. Opioids inhibit this excitatory pontomedullary respiratory circuit by three distinct mechanisms-somatodendritic MORs on dorsolateral pontine and ventrolateral medullary neurons and presynaptic MORs on dorsolateral pontine neuron terminals in the ventrolateral medulla-all of which could contribute to opioid-induced respiratory depression.

Fentanyl effects on respiratory neuron activity in the dorsolateral pons.

Opioids suppress breathing through actions in the brainstem, including respiratory-related areas of the dorsolateral pons, which contain multiple phenotypes of respiratory patterned neurons. The discharge identity of dorsolateral pontine neurons that are impacted by opioids is unknown. To address this, single neuronal units were recorded in the dorsolateral pons of arterially perfused in situ rat preparations that were perfused with an apneic concentration of the opioid agonist fentanyl, followed by the opioid antagonist naloxone (NLX). Dorsolateral pontine neurons were categorized based on respiratory-associated discharge patterns, which were differentially affected by fentanyl. Inspiratory neurons and a subset of inspiratory/expiratory phase-spanning neurons were either silenced or had reduced firing frequency during fentanyl-induced apnea, which was reversed upon administration of naloxone. In contrast, the majority of expiratory neurons continued to fire tonically during fentanyl-induced apnea, albeit with reduced firing frequency. In addition, pontine late-inspiratory and postinspiratory neuronal activity were absent from apneustic-like breaths during the transition to fentanyl-induced apnea and the naloxone-mediated transition to recovery. Thus, opioid-induced deficits in respiratory patterning may occur due to reduced activity of pontine inspiratory neurons, whereas apnea occurs with loss of all phasic pontine activity and sustained tonic expiratory neuron activity.NEW & NOTEWORTHY Opioids can suppress breathing via actions throughout the brainstem, including the dorsolateral pons. The respiratory phenotype of dorsolateral pontine neurons inhibited by opioids is unknown. Here, we describe the effect of the highly potent opioid fentanyl on the firing activity of these dorsolateral pontine neurons. Inspiratory neurons were largely silenced by fentanyl, whereas expiratory neurons were not. We provide a framework whereby this differential sensitivity to fentanyl can contribute to respiratory pattern deficits and apnea.

Gata2, Nkx2-2 and Skor2 form a transcription factor network regulating development of a midbrain GABAergic neuron subtype with characteristics of REM-sleep regulatory neurons.

The midbrain reticular formation (MRF) is a mosaic of diverse GABAergic and glutamatergic neurons that have been associated with a variety of functions, including sleep regulation. However, the molecular characteristics and development of MRF neurons are poorly understood. As the transcription factor, Gata2 is required for the development of all GABAergic neurons derived from the embryonic mouse midbrain, we hypothesized that the genes expressed downstream of Gata2 could contribute to the diversification of GABAergic neuron subtypes in this brain region. Here, we show that Gata2 is required for the expression of several GABAergic lineage-specific transcription factors, including Nkx2-2 and Skor2, which are co-expressed in a restricted group of post-mitotic GABAergic precursors in the MRF. Both Gata2 and Nkx2-2 function is required for Skor2 expression in GABAergic precursors. In the adult mouse and rat midbrain, Nkx2-2-and Skor2-expressing GABAergic neurons locate at the boundary of the ventrolateral periaqueductal gray and the MRF, an area containing REM-off neurons regulating REM sleep. In addition to the characteristic localization, Skor2+ cells increase their activity upon REM-sleep inhibition, send projections to the dorsolateral pons, a region associated with sleep control, and are responsive to orexins, consistent with the known properties of midbrain REM-off neurons.

Opioid inhibition of projection‐specific, respiratory‐related pontomedullary neurons

Opioids depress breathing by inhibition of inter‐connected respiratory nuclei in the pons and medulla. We have previously shown that mu opioid receptor (MOR) agonists hyperpolarize a population of neurons in the dorsolateral pons due to activation of G protein‐mediated inwardly rectifying potassium conductance. However, we do not know the projection target of MOR‐expressing, dorsolateral pontine neurons, if they project at all. Here, we show that MOR‐expressing, dorsolateral pontine neurons project to core respiratory nuclei in the ventrolateral medulla, identifying projection‐related heterogeneity of dorsolateral pontine neurons vulnerable to opioid inhibition. First, retrograde DIO‐eGFP injections into the ventrolateral medulla of oprm1‐cre mice showed that dorsolateral pontine neurons project to the Bötzinger complex (BötC), pre‐Bötzinger complex (preBötC), and rostral ventral respiratory group (rVRG), and are distinct from calcitonin gene‐related peptide (CGRP)‐expressing parabrachial neurons. Second, we performed whole‐cell, voltage‐clamp recordings from dorsolateral pontine Kölliker‐Fuse neurons that were retrogradely labeled by fluorescent bead injections into the ventrolateral medulla of wild‐type mice. MOR‐mediated outward currents were identified in dorsolateral pontine neurons that project to the BötC, preBötC, and rVRG, confirming that these projection neurons are functionally inhibited by MORs and vulnerable to opioid inhibition. Together, these approaches demonstrate that MOR‐expressing, dorsolateral pontine neurons project to medullary respiratory nuclei and further unravel mechanisms of opioid‐induced respiratory depression.

Brainstem Infarction and Vertebral Artery Vasculopathy After Ramsay Hunt Syndrome.

A 45-year-old man presented with right auricle rash, facial weakness, otalgia, deafness, and transient dizzy spells. He had leftward spontaneous, bidirectional gaze-evoked and unsuppressed leftward head-shaking nystagmus in head-shaking tilt suppression test (Figure 1). MRI results showed a subacute infarct on the right dorsolateral pons and medulla oblongata and incomplete flow void in the right vertebral artery. After acyclovir and dexamethasone therapy, the ischemic lesion and vascular narrowing on MRI vanished and the patient's symptoms disappeared (Figure 2). Concomitant intracranial vasculopathy and brainstem stroke may occur in Ramsay Hunt syndrome,1,2 which could be easily missed but possibly detected by careful eye movement assessments.

How I do it: horizontal fissure approach to the middle cerebellar peduncle.

The horizontal fissure approach is a workhorse for brainstem lesions in the central and dorsolateral pons and middle cerebellar peduncle (MCP). The cerebellopontine fissure is a V-shaped fissure with a superior and inferior limb between the cerebellum, pons, and MCP. The horizontal or petrosal fissure is at the apex of the cerebellopontine fissure and extends laterally to divide the petrosal surface of the cerebellum into superior and inferior parts. Splitting this fissure exposes the posterolateral aspect of the MCP without excessive retraction or transgression of the cerebellum. We demonstrate and describe the horizontal fissure operative approach to the middle cerebellar peduncle for resection of a pontine cavernoma with illustrative figures and operative video. Splitting the horizontal (petrosal) fissure of the cerebellum brings the middle cerebellar peduncle into view behind the root entry zone of the trigeminal nerve, providing an expanded, safe corridor to the central and dorsolateral pons.

Paramedian Supracerebellar Infratentorial Approach for Pontine Cavernoma: 2-Dimensional Operative Video.

We describe the case of a 26-yr-old male who presented with headaches, dizziness, and left hemi-hypoesthesia in addition to being COVID-19 positive. The patient was found to have a large hemorrhage in the right dorsolateral pons that was found to be due to a pontine cavernous malformation. The patient underwent a right-sided paramedian supracerebellar infratentorial approach for resection of this lesion with preservation of the developmental venous anomaly. We present the operative video with a specific focus on approach selection, anatomic illustrations, and technical nuances. The literature on the timing of brainstem cavernoma surgery is reviewed.1-4 The patient's postoperative clinical course and postoperative imaging are reviewed. The patient gave informed consent for the procedure and verbal consent for being part of this submission and the publication of their image.

Opioid sensitivity of projection‐specific Kölliker‐Fuse neurons

Opioid-induced respiratory depression is the primary cause of death in individuals who overdose on opioids. Respiration is controlled by a highly interconnected neural network located in the pons and medulla. The Kölliker-Fuse nucleus (KF), located in the dorsolateral pons, is an essential part of this network. It projects to core respiratory nuclei in the ventrolateral medulla, and is a key mediator of opioid-induced respiratory depression. We have previously shown that mu opioid receptor (MOR) agonists hyperpolarize a population of neurons in the KF due to activation of G protein-mediated inwardly rectifying conductance. However, we do not know the projection target of the opioid-sensitive KF neurons, or if they project at all. Given the extensive projections from the KF to medullary respiratory rhythm generators, we hypothesize that opioid-sensitive KF neurons project to respiratory rhythm generators. To test this hypothesis, we used two different approaches. First, retrograde AAV-DIO-eGFP (retrograde-AAV-hSyn-DIO-eGFP, 100 nL, Addgene) was unilaterally injected into the Bötzinger complex (BötC), pre-Bötzinger complex (preBötC), or rostral ventral respiratory group (rVRG) of Oprm1-cre mice to retrogradely-label MOR-expressing KF neurons. KF-containing brain slices were imaged for the presence or absence of retrogradely-labeled, GFP-expressing neurons. These results demonstrate that MOR-expressing KF neurons project to the BötC, preBötC and rVRG. Second, fluorescent beads (FluoSpheres 580/605, ThermoFisher) were injected into the BötC, preBötC or rVRG of wild-type mice. Whole-cell voltage-clamp recordings were made from retrogradely-labeled KF neurons contained in brain slices. MOR-mediated outward currents were identified in KF neurons that project to the BötC, preBötC, and rVRG, confirming that KF projection neurons are functionally inhibited by MORs. Together, these approaches demonstrate that opioid-sensitive KF neurons project to the BötC, preBötC, and rVRG. Opioid inhibition of these projections could affect respiratory output in different ways (i.e. respiratory rate, amplitude, gain, and pattern) depending on the projection target. The results of this study identify projection-related heterogeneity of dorsolateral pontine neurons vulnerable to opioid inhibition, and further unravel mechanisms of opioid-induced respiratory depression.

Inspiratory and Phase‐Spanning Dorsolateral Pontine Neurons Are Silent During Fentanyl‐Induced Apnea

Overdoses caused by the opioid agonist fentanyl have increased exponentially in recent years. These overdose deaths are the result of inadequate ventilation. While much research has focused on opioid modulation of medullary respiratory nuclei, pontine mediated effects of opioids have received less attention. Given the interconnectivity of the pontine Kölliker-Fuse/Parabrachial complex (KF/PB) with rhythmogenic nuclei in the medulla, their involvement in controlling respiratory rate and pattern, and their sensitivity to opioids, we investigate the role they play in opioid mediated respiratory depression and hypothesize that dorsolateral pontine inspiratory, phase-spanning, and post-inspiratory neurons are silenced by opioids. To address this, we have done single unit recordings in the working heart brainstem in situ rat preparation. Dorsolateral pontine neural units (n=48) were recorded extracellularly and systemically exposed to fentanyl and then the opioid antagonist naloxone. A phase-fraction 2-D histogram (heatmap) was generated to compare all unit's action potential spiking over respiratory phases and during periods following fentanyl administration. Each neural unit was categorized at baseline into 4 main groups of discharge identity: Inspiratory, Expiratory, Phase-spanning, and Tonic. Systemic application of fentanyl (300nM) resulted in a consistent decline in fictive respiratory output, transitioned to fast shallowing breathing, and eventually resulted in cessation of respiratory output (apnea). Out of 48 extracellular single unit recordings in the dorsolateral pons, 25 (52%) were completely silent (firing frequency of 0 Hz) suggesting post-synaptic opioid receptor activation during fentanyl-induced apnea; 17/20 inspiratory, 6/12 phase spanning (4/9 IE & 2/3 EI), 1/13 expiratory (1/5 Post I Dec) and 1/3 tonic neurons. To note, many neurons that were not completely silenced by opioids did fire at a much lower firing frequency, suggesting pre-synaptic opioid receptors also contribute to opioid-induced loss of pontine neural activity. Our hypothesis was partially supported, as the majority of inspiratory neurons (17/20) and a subpopulation of phase-spanning neurons (6/12) were completely silenced by fentanyl. Surprisingly post-inspiratory neurons were mainly insensitive to opioids (4/5). These results suggest that loss of post-inspiratory activity with DAMGO injection into the KF may depend critically on post-synaptic inhibition of inspiratory and a subset of IE phase-spanning neurons, which in turn, could decrease local pre-synaptic excitation of post-inspiratory neurons. The majority of pontine expiratory neurons were not silenced by fentanyl (12/13). Due to the KF/PB role in expiratory duration, sustained activity of pontine expiratory neurons may facilitate sustained apnea during opioid overdose. These results warrant further investigation into the contribution of the dorsolateral pons in respiratory pattern formation and opioid-induced respiratory depression.

Sevoflurane depresses neurons in the medial parabrachial nucleus by potentiating postsynaptic GABAA receptors and background potassium channels

Despite persistent clinical use for over 170 years, the neuronal mechanisms by which general anesthetics produce hypnosis remain unclear. Previous studies suggest that anesthetics exert hypnotic effects by acting on endogenous arousal circuits. Recently, it has been shown that the medial parabrachial nucleus (MPB) is a novel wake-promoting component in the dorsolateral pons. However, it is not known whether and how the MPB contributes to anesthetic-induced hypnosis. Here, we investigated the action of sevoflurane, a widely used volatile anesthetic agent that best represents the drug class of halogenated ethers, on MPB neurons in mice. Using in vivo fiber photometry, we found that the population activities of MPB neurons were inhibited during sevoflurane-induced loss of consciousness. Using in vitro whole-cell patch-clamp recordings, we revealed that sevoflurane suppressed the firing rate of MPB neurons in concentration-dependent and reversible manners. At a concentration equal to MAC of hypnosis, sevoflurane potentiated synaptic GABAA receptors (GABAA-Rs), and the inhibitory effect of sevoflurane on the firing rate of MPB neurons was completely abolished by picrotoxin, which is a selective GABAA-R antagonist. At a concentration equivalent to MAC of immobility, sevoflurane directly hyperpolarized MPB neurons and induced a significant decrease in membrane input resistance by increasing a basal potassium conductance. Moreover, pharmacological blockade of GABAA-Rs in the MPB prolongs induction and shortens emergence under sevoflurane inhalation at MAC of hypnosis. These results indicate that sevoflurane inhibits MPB neurons through postsynaptic GABAA-Rs and background potassium channels, which contributes to sevoflurane-induced hypnosis.

Roles of glutamate and GABA of the Kölliker-Fuse nucleus in generating the cardiovascular chemoreflex.

The Kölliker-Fuse (KF) nucleus is a part of the parabrachial complex, located in the dorsolateral pons. It is involved in the chemoreflex-evoked cardiovascular and respiratory changes, but the role of GABA and glutamate in cardiovascular chemoreflex has not been shown yet. This study was performed to determine the role of GABA, glutamate, and their interaction in the KF, in cardiovascular chemoreflex in anesthetized rat. The antagonists were microinjected into the KF, and arterial pressure, heart rate, and single-unit responses were recorded simultaneously. The chemoreflex was evoked by i.v. injection of KCN, consisted of a short pressor followed by long bradycardia responses. Both responses were significantly attenuated by injection of a synaptic blocker (CoCl2) into the KF, confirming involvement of the KF in generating the reflex. Microinjection of AP5, an NMDA receptor antagonist, into the KF significantly attenuated the pressor and bradycardia responses, while blocking the AMPA receptors by CNQX had no significant effect. Blockade of GABAA receptors by bicuculline methiodide (BMI) potentiated both responses. Co-injection of BMI and CNQX potentiated the responses too. Co-injection of BMI and AP5 had no significant effect on the pressor response but significantly attenuated the bradycardia response. In conclusion, the KF plays a role in generating cardiovascular chemoreflex via its glutamate NMDA but not AMPA receptors. GABA inhibits both components of this reflex through GABAA receptors. There is an interaction between GABAA and NMDA receptors in regulating the bradycardia response of the reflex. Single-unit results were also presented which were correlated with and supported the homodynamic findings.

Neurochemistry of the Kölliker‐Fuse nucleus from a respiratory perspective

The Kölliker-Fuse nucleus (KF) is a functionally distinct component of the parabrachial complex, located in the dorsolateral pons of mammals. The KF has a major role in respiration and upper airway control. A comprehensive understanding of the KF and its contributions to respiratory function and dysfunction requires an appreciation for its neurochemical characteristics. The goal of this review is to summarize the diverse neurochemical composition of the KF, focusing on the neurotransmitters, neuromodulators, and neuropeptides present. We also include a description of the receptors expressed on KF neurons and transporters involved in each system, as well as their putative roles in respiratory physiology. Finally, we provide a short section reviewing the literature regarding neurochemical changes in the KF in the context of respiratory dysfunction observed in SIDS and Rett syndrome. By over-viewing the current literature on the neurochemical composition of the KF, this review will serve to aid a wide range of topics in the future research into the neural control of respiration in health and disease.

Glutamate levels and perfusion in pons during migraine attacks: A 3T MRI study using proton spectroscopy and arterial spin labeling

Migraine is a complex disorder, involving peripheral and central brain structures, where mechanisms and site of attack initiation are an unresolved puzzle. While abnormal pontine neuronal activation during migraine attacks has been reported, exact implication of this finding is unknown. Evidence suggests an important role of glutamate in migraine, implying a possible association of pontine hyperactivity to increased glutamate levels. Migraine without aura patients were scanned during attacks after calcitonin gene-related peptide and sildenafil in a double-blind, randomized, double-dummy, cross-over design, on two separate study days, by proton magnetic resonance spectroscopy and pseudo-continuous arterial spin labeling at 3T. Headache characteristics were recorded until 24 h after drug administrations. Twenty-six patients were scanned during migraine, yielding a total of 41 attacks. Cerebral blood flow increased in dorsolateral pons, ipsilateral to pain side during attacks, compared to outside attacks (13.6%, p = 0.009). Glutamate levels in the same area remained unchanged during attacks (p = 0.873), while total creatine levels increased (3.5%, p = 0.041). In conclusion, dorsolateral pontine activation during migraine was not associated with higher glutamate levels. However, the concurrently increased total creatine levels may suggest an altered energy metabolism, which should be investigated in future studies to elucidate the role of pons in acute migraine.

Opioid sensitivity of projection‐specific Kölliker‐Fuse neurons

Opioid‐induced respiratory depression is the primary cause of death in individuals who overdose on opioids. Respiration is controlled by a highly interconnected neural network located in the pons and medulla. The Kölliker‐Fuse nucleus (KF), located in the dorsolateral pons, is an essential part of this network and projects to core respiratory nuclei in the ventrolateral medulla. Opioids injections into the KF disturb respiratory rate, volume, and pattern. Deletion of opioid receptors from KF neurons attenuates morphine‐induced respiratory depression. These studies suggest that the KF is a critical site in opioid‐induced respiratory depression. Mu opioid receptor agonists hyperpolarize a population of neurons in the KF due to activation of G protein‐mediated inwardly rectifying conductance. However, we do not know the projection target of the opioid‐sensitive KF neurons. Given the extensive projections from the KF to medullary respiratory rhythm generators, we hypothesize that opioid‐sensitive KF neurons project to respiratory rhythm generators. Fluorescent beads (FluoSpheres 580/605, ThermoFisher) were injected into the Bötzinger complex (BötC), pre‐Bötzinger complex (preBötC), and rostral ventral respiratory group (rVRG) of mice. Whole‐cell voltage‐clamp recordings were made from retrograde‐labeled KF neurons contained in brain slices. Mu opioid receptor‐mediated outward currents were identified in KF neurons that project to the preBötC, and rVRG, but not in KF neurons that project to the BötC. Opioid‐sensitive connections between the KF and respiratory rhythm generators may be a possible mechanism by which opioids reduce respiratory rate.Support or Funding InformationR00, DA038069

Overview of pharmacological mechanisms controlling micturition in the central nervous system

The functions of the lower urinary tract, to storage and periodically release urine, are dependent on the activity of smooth and striated muscles in the bladder, urethra and external urethral sphincter. This activity is in turn controlled by neural circuits not only in the periphery, but also in the central nervous system (CNS). During urine storage, the outlet is closed and the bladder smooth muscle is quiescent by the neural control mechanism mainly organized in the spinal cord. When bladder volume reaches the micturition threshold, activation of a micturition center in the dorsolateral pons (the pontine micturition center) induces micturition through activation of sacral parasympathetic (pelvic) nerves. The brain rostral to the pons (diencephalon and cerebral cortex) is also involved in excitatory and inhibitory regulation of the micturition reflex. Various transmitters including dopamine, serotonin, norepenephrine, GABA, excitatory and inhibitory amino acids, opioids and acetylcholine are implicated in the modulation of the micturition reflex in the CNS. Therefore, injury or neurodegenerative diseases of the CNS as well as drugs can produce bladder and urethral dysfunctions such as urinary frequency, urgency and incontinence or inefficient bladder emptying.

2019 Ludwig Lecture: Rhythms in sympathetic nerve activity are a key to understanding neural control of the cardiovascular system.

This review is based on the Carl Ludwig Distinguished Lecture, presented at the 2019 Experimental Biology Meeting in Orlando, FL, and provides a snapshot of >40 years of work done in collaboration with the late Gerard L. Gebber and colleagues to highlight the importance of considering the rhythmic properties of sympathetic nerve activity (SNA) and brain stem neurons when studying the neural control of autonomic regulation. After first providing some basic information about rhythms, I describe the patterns and potential functions of rhythmic activity recorded from sympathetic nerves under various physiological conditions. I review the evidence that these rhythms reflect the properties of central sympathetic neural networks that include neurons in the caudal medullary raphe, caudal ventrolateral medulla, caudal ventrolateral pons, medullary lateral tegmental field, rostral dorsolateral pons, and rostral ventrolateral medulla. The role of these brain stem areas in mediating steady-state and reflex-induced changes in SNA and blood pressure is discussed. Despite the common appearance of rhythms in SNA, these oscillatory characteristics are often ignored; instead, it is common to simply quantify changes in the amount of SNA to make conclusions about the function of the sympathetic nervous system in mediating responses to a variety of stimuli. This review summarizes work that highlights the need to include an assessment of the changes in the frequency components of SNA in evaluating the cardiovascular responses to various manipulations as well as in determining the role of different brain regions in the neural control of the cardiovascular system.

Surgical treatment of pontine cavernous malformations via subtemporal transtentorial and intradural anterior transpetrosal approaches.

The aim of this study was to report our surgical experience on resection of the pontine cavernous malformations (CMs) via subtemporal transtentorial approach (STTA) and intradural anterior transpetrosal approach (ATPA). Clinical data were retrospectively reviewed in 61 patients with pontine CMs that were surgically treated by the STTA and the intradural ATPA. The surgical procedures, complications, and outcomes were analyzed. The study consists of 61 patients with a total of 61 pontine CMs. Other than 4 lesions located medially in the pons, all CMs were in the lateral pons with a left or right lateral epicenter (the left/right ratio was 22/35). Totally, 11 patients (18.0%) with lesions located in the upper pons were treated by the STTA, and 50 patients (82.0%) with lesions involving the lower pons were treated by the intradural ATPA. Postoperatively, the complete resection was achieved in 58 patients (95.1%) and incomplete resection in 3 patients (4.9%). Twenty-seven patients (44.3%) suffered from a new or worsened neurological deficit in the immediate postoperative period, and 8 patients (13.1%) encountered a non-neural complication, including rebleeding, cerebrospinal fluid leak, intracranial infection, and pulmonary infection, and 3 patients had contusion of temporal lobe. With a mean follow-up of 54.2months, the patients' neurological condition had improved in 43 cases (71.6%), not changed in 10 cases (16.7%), and worsened in 7 cases (11.7%), respectively. The Karnofsky Performance Scale (KPS) score evaluated at the last time for per patient was significantly better than their baseline status (t = 6.677, p < 0.001). However, 21 patients (35.0%) suffered from a new or worsened persistent postoperative deficit. The lateral and anterolateral pons can be exposed well by the subtemporal transtentorial and intradural anterior transpetrosal approaches. Lesions of CMs located in the lateral pons, including ventrolateral and dorsolateral pons, could be totally removed by these two lateral approaches with an acceptable surgical morbidity.

Fluctuating Regional Brainstem Diffusion Imaging Measures of Microstructure across the Migraine Cycle.

The neural mechanisms responsible for the initiation and expression of migraines remain unknown. Although there is growing evidence of changes in brainstem anatomy and function between attacks, very little is known about brainstem function and structure in the period immediately prior to a migraine. The aim of this investigation is to use brainstem-specific analyses of diffusion weighted images to determine whether the brainstem pain processing regions display altered structure in individuals with migraine across the migraine cycle, and in particular immediately prior to a migraine. Diffusion tensor images (29 controls, 36 migraineurs) were used to assess brainstem anatomy in migraineurs compared with controls. We found that during the interictal phase, migraineurs displayed greater mean diffusivity (MD) in the region of the spinal trigeminal nucleus (SpV), dorsomedial pons (dmPons)/dorsolateral pons (dlPons), and midbrain periaqueductal gray matter (PAG)/cuneiform nucleus (CNF). Remarkably, the MD returned to controls levels during the 24-h period immediately prior to a migraine, only to increase again within the three following days. Additionally, fractional anisotropy (FA) was significantly elevated in the region of the medial lemniscus/ventral trigeminal thalamic tract in migraineurs compared with controls over the entire migraine cycle. These data show that regional brainstem anatomy changes over the migraine cycle, with specific anatomical changes occurring in the 24-h period prior to onset. These changes may contribute to the activation of the ascending trigeminal pathway by either an increase in basal traffic or by sensitizing the trigeminal nuclei to external triggers, with activation ultimately resulting in perception of head pain during a migraine attack.