Rostral Brainstem Research Articles

Infants with neonatal Chronic Lung Disease are associated with delayed auditory conduction in the rostral brainstem after term

AimsVery Low Birthweight (VLBW) infants with neonatal Chronic Lung Disease (CLD) have been found to have functional impairment of the brainstem auditory pathway at term. This study investigated the functional status of the brainstem auditory pathway in VLBW infants with CLD after term for any abnormality. MethodsFifty-two VLBW infants were recruited at 50 weeks of Postconceptional Age: 25 with neonatal CLD and 27 without CLD. None had any other major complications to minimize confounding effects. Brainstem Auditory Evoked Responses were studied at 21‒91/s click rates. ResultsCompared with those without CLD, VLBW infants with CLD had relatively shorter latencies of BAER waves I and III, associated with a slightly lower BAER threshold. Wave V latency and I‒V interpeak interval did not differ significantly between the two groups of infants. The I‒III interval in infants with CLD was shorter than in those without CLD at 91/s clicks. However, the III‒V interval was significantly longer than in those without CLD at all click rates (all p < 0.05). There were no significant differences in the amplitudes of BAER wave components between the two groups of infants. ConclusionsThe main BAER abnormality in VLBW infants with CLD was a prolonged III‒V interval. Auditory conduction is delayed or impaired at more central regions of the brainstem in CLD infants. After term central auditory function is adversely affected by neonatal CLD. Monitoring post-term change is required to provide valuable information for post-term care of CLD infants.

Acute necrotizing encephalopathy of childhood secondary to parainfluenza infection: A review of two cases

IntroductionAcute necrotizing encephalopathy (ANE) of childhood is a rare inflammatory syndrome, classically associated with preceding febrile illness and followed by fulminant neurological deterioration including encephalopathy, seizures, and focal neurological deficits with multifocal lesions of the thalami, rostral brainstem, and cerebral and cerebellar gray and white matter. ANE is distinctly associated with significant rates of neurological sequelae and death. Multiple infectious and parainfectious etiologies have been associated with ANE, notably influenza A. Case ReportWe report two cases of ANE associated with parainfluenza infection. Both children were treated with high-dose methylprednisolone and intravenous immunoglobulin, and one treated with tocilizumab. However, both patients suffered rapid neurological deterioration and death despite aggressive intervention. ConclusionWe present two cases of ANE with rapid neurological deterioration and death despite aggressive medical therapy. Rapid treatment with immunomodulatory treatments can lead to symptomatic recovery of variable degree in some patients. While high-dose steroids, intravenous immunoglobulin, and plasma exchange are common therapies for ANE, some case reports have suggested interleukin-6 (IL-6) blockade with tocilizumab can be beneficial. We report the nineteenth documented child in pediatric literature treated for ANE with tocilizumab, who did not respond to treatment, suggesting the response is heterogeneous and warrants additional investigation.

Rapid, activity-dependent co-release of GABA and glycine in the mouse brainstem

Presympathetic neurons in the ventrolateral and ventromedial medulla (VLM/VMM) control the sympathetic tone, and GABA was identified as a primary mechanism for sympathoinhibition. Intriguingly, there is evidence that both GABA and glycine efficiently inhibit sympathetic tone; however, the mechanism of glycine release is unknown. In this study, we tested the hypothesis that GABA and glycine are co-released in the VLM/VMM. Glycine is recycled by glycine transporter 2 (GlyT2), which is a reliable marker of glycinergic neurons. Therefore, we crossed heterozygous GlyT2Cre mice with floxed channelrhodopsin 2 (ChR2-EYFP) mice to generate GlyT2 reporter mice (GlyT2ChR2/EYFP), which were used to determine the mechanism of glycine release and reveal the location of glycinergic neurons. Whole-cell patch-clamp recordings from presympathetic VLM/VMM neurons revealed that GABA mediates most spontaneous inhibitory postsynaptic currents (sIPSCs); whereas increased activity of inhibitory inputs promotes the release of glycine. Light stimulation of glycinergic fibers expressing ChR2 in GlyT2ChR2/EYFP mice evoked IPSCs (eIPSCs) with glycinergic and GABAergic components. Bath application of GABAA receptors antagonist (bicuculline, 10 μM) decreased the amplitude of eIPSCs, suggesting that approximately 70% of the eIPSCs are generated by glycine. Moreover, blockade of GlyT2 partially diminished the glycinergic component of the light-evoked IPSCs. Using GlyT2ChR2/EYFP mice, we found that glycinergic fibers are abundant throughout the rostral brainstem, and GlyT2-expressing neurons were distributed within the ventral gigantocellular nucleus and medial reticular formation. Immunofluorescence labeling of glycine receptor subunits in the VLM/VMM revealed the expression of two prevalent forms of glycine receptors formed by α1 and α3. In summary, we found that GABA and glycine are co-released in the VLM/VMM, and blockage of GlyT2 decreased the amplitude of light-evoked IPSCs, suggesting that GABA and glycine are likely located in separate vesicles. Our data provide evidence for the co-inhibition of presympathetic neurons in the VLM/VMM by GABA and glycine and suggest that GABA controls the threshold excitability, while glycine is released on demand to increase the strength of inhibition. Supported by: NIDDK122842 and Tulane Brain Institute Marko Spark Innovation Research Fund This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Immune Checkpoint Inhibitors Related New Onset Myasthenia Gravis: Case Series (P4-5.028)

<h3>Objective:</h3> Immune checkpoint inhibitors (ICI), such as cytotoxic lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis are treatment for several malignancies. Myasthenia gravis (MG) is a rare but life-threatening adverse event of ICI. <h3>Background:</h3> With ICI single agent use, 42 cases of new-onset MG are reported in literature, among those, 14 patients developed severe respiratory failure and required intubation whereas 10 patients died. Combination ICI-induced MG was reported in 7 cases, with at least 2 cases complicated by respiratory failure and 1 death. A better outcome was observed in patients who received intravenous immunoglobulin (IVIG) or plasmapheresis (PLEX) as first-line therapy than in those who received steroids alone (95% vs 63% improvement of MG symptoms). <h3>Design/Methods:</h3> Case series and literature review <h3>Results:</h3> <h3>Case 1:</h3> 87-year-old woman with stage IV adenocarcinoma of colon received pembrolizumab. Ten days after second dose she presented with worsening new onset bilateral ptosis (left&gt;right) and dysphagia, seropositive with acetylcholine receptor antibodies. There was no significant improvement after a course of IVIG in combination with high dose steroids. A trial of pyridostigmine could not be completed due to symptomatic bradycardia and hospice care was started thirty-eight days after first dose of pembrolizumab. <h3>Case 2:</h3> 73-year-old man with metastatic melanoma, received 2 doses of combined ipilimumab and nivolumab. Fifteen days after second dose, he presented with worsening dysphagia, dysarthria, fatigable generalized weakness and shortness of breath, seronegative for MG antibodies. Symptoms improved dramatically with IVIG. His course was complicated by rostral brainstem ischemic stroke and discharged to hospice ninety-four days after the first dose of combined ipilimumab and nivolumab <h3>Conclusions:</h3> Evidence is limited and data from a large cohort of patients is needed to recognize and manage this fatal complication. <b>Disclosure:</b> Dr. Habib has nothing to disclose. Dr. Ahmed has nothing to disclose. Dr. Al-Awwad has nothing to disclose. Sarah Sung, MD has nothing to disclose.

Altered maturation in brainstem neural conduction in very premature babies with fetal growth restriction.

Using maximum length sequence brainstem auditory evoked response (MLS BAER) to study brainstem neural conduction and maturation in fetal growth restriction (FGR) babies born very prematurely and assess the effect of FGR on brainstem neural maturation. MLS BAER was recorded and analyzed at a mean 40 week postmenstrual age in babies born at 27-32 week gestation without other major perinatal conditions or problems. The data were compared between babies with FGR (n = 30) and age-matched babies without FGR (n = 34) to define any differences. A notable difference in MLS BAER was found in interpeak intervals between the babies with FGR and those without FGR. The FGR babies manifested significantly shortened I-III interval, moderately prolonged III-V interval, and significantly decreased III-V/I-III interval ratio. The slope of the I-III interval-rate function in FGR babies was moderately decreased, relative to that in the babies without FGR. FGR babies born very prematurely are associated with accelerated or precocial neural maturation at caudal brainstem regions, but moderately delayed maturation at rostral brainstem regions. The altered brainstem neural maturation is different from previously reported mildly delayed maturation in FGR babies born less prematurely, and may have important implication for neurodevelopmental outcome. This first MLS BAER study in FGR found that brainstem neural maturation in very premature FGR babies differed from age-matched non-FGR babies. Neural maturation in very premature FGR babies is accelerated or precocial at caudal brainstem regions but moderately delayed at rostral brainstem regions. The altered maturation is different from previously reported mild delay in brainstem neural maturation in FGR babies born less prematurely. FGR exerts a major and differential effect on brainstem neural maturation in babies born very prematurely. This alteration in very premature FGR babies may have important implication for their neurodevelopment.

Body Lateropulsion and Pusher Behavior

The relationship between postural disturbance and vertical perception after cerebrovascular disease remains unclear and studies have only recently begun to be conducted. On the other hand, the symptomatic aspect is evident: body lateropulsion is ipsilateral in the case of caudal brainstem lesions and contralateral in the case of rostral brainstem and cerebral hemispheric lesions. In addition, patients with cerebral hemispheric lesions sometimes show“pusher behavior” in which they resist any attempt to correct their posture and push the body back to the paralyzed side using the healthy limbs, as they have a fear of deviation to the healthy side. The pusher behavior is always accompanied by hemiplegia and is detected in about 10% of cases of hemispheric vascular lesions.

Subtemporal Approach and Its Infratentorial Extension: Review and a Comparative Analysis of Different Techniques.

Introduction Surgical resection of lesions occupying the incisural space is challenging. In a comparative fashion, we aimed to describe the anatomy and surgical approaches to the tentorial incisura and to the rostral brainstem via the intradural subtemporal approach and its infratentorial extensions. Methods Six fresh human head specimens (12 sides) were prepared for the microscopic dissection of the tentorial incisura using the intradural subtemporal approach and its infratentorial extensions. Endoscope was used to examine the anatomy of the region inadequately exposed with the microscope. Image-guided navigation was used to confirm bony structures visualized around the petrous apex. Results Standard subtemporal approach provides surgical access to the supratentorial brainstem above the pontomesencephalic sulcus and to the lateral surface of the cerebral peduncle. The linear or triangular tentorial divisions can provide access to the infratentorial space below the pontomesencephalic sulcus. The triangular tentorial flap in comparison with the linear incision obstructs the exposure of anterior incisural space and of the prepontine cistern. Visualization of the brainstem below the trigeminal nerve can be achieved by the anterior petrosectomy. Conclusion Infratentorial extension of the intradural subtemporal approach is technically demanding due to critical neurovascular structures and a relatively narrow corridor. In-depth anatomical knowledge is essential for the selection of the appropriate operative approach and safe surgical resections of lesions.

Degenerate brainstem circuitry after combined physiochemical exposure to jet fuel and noise

ABSTRACT Degenerate neural circuits exhibit “different” circuit properties yet produce similar circuit outcomes (many-to-one) which ensures circuit robustness and complexity. However, neuropathies may hijack degeneracy to yield robust and complex pathological circuits. The aim of the current study was to test the hypothesis that physiochemical exposure to combined jet fuel and noise might induce degeneracy in the brainstem. The auditory brainstem of pigmented rats was used as a model system. The animals were randomized into the following experimental groups: Fuel+Noise, fuel-only, noise-only, and control. Ascending volume conductance from various auditory brainstem regions were evaluated simultaneously with peripheral nervous system (PNS) input to brainstem circuitry. Data demonstrated normal PNS inputs for all groups. However, the Fuel+Noise exposure group produced different caudal brainstem circuit properties while rostral brainstem circuitry initiated outputs that were similar to that of control. This degenerative effect was specific to Fuel+Noise exposure, since neither noise-alone or fuel-alone produced the same result. Degeneracy in the auditory brainstem is consistent with perceptual abnormalities, such as poor speech discrimination (hear but not understand), tinnitus (ringing in the ear), hyperacusis (hypersensitivity to even low-level sound), and loudness intolerance. Therefore, a potential consequence of Fuel+Noise exposure among military and civilian populations may be evidenced as increased rates of super-threshold auditory perceptual abnormalities. This is particularly important because to date, the ototoxic profile of Fuel+Noise exposure has remained unresolved.

Restoring Shank3 in the rostral brainstem of shank3ab\u2212/\u2212 zebrafish autism models rescues sensory deficits

People with Phelan-McDermid Syndrome, caused by mutations in the SHANK3 gene, commonly exhibit reduced responses to sensory stimuli; yet the changes in brain-wide activity that link these symptoms to mutations in the shank3 gene remain unknown. Here we quantify movement in response to sudden darkness in larvae of two shank3 zebrafish mutant models and show that both models exhibit dampened responses to this stimulus. Using brain-wide activity mapping, we find that shank3−/− light-sensing brain regions show normal levels of activity while sensorimotor integration and motor regions are less active. Specifically restoring Shank3 function in a sensorimotor nucleus of the rostral brainstem enables the shank3−/− model to respond like wild-type. In sum, we find that reduced sensory responsiveness in shank3−/− models is associated with reduced activity in sensory processing brain regions and can be rescued by restoring Shank3 function in the rostral brainstem. These studies highlight the importance of Shank3 function in the rostral brainstem for integrating sensory inputs to generate behavioral adaptations to changing sensory stimuli.

Auditory brainstem responses to high-resolution audio sounds: Effects of anti-alias filters

Despite the superior technical specifications of high-resolution audio in comparison to conventional compact discs (CDs) and digital versatile discs (DVDs), whether and how high-resolution audio leads to an improved subjective listening experience remains unclear. The sound quality of conventional digital formats is deteriorated by temporal blur, which is caused by a high-cut filter applied to avoid aliasing of a digital sound source, resulting in spurious artificial sound energy before and after the actual sound onset. Using sound materials of high-resolution audio grade, this study investigated the effects of filter-induced temporal blur on the auditory neural pathway from the cochlea through the rostral brainstem by measuring the auditory brainstem responses (ABRs) of participants with normal hearing. The participants (N = 24) listened to 0.1-ms clicks, with and without a high-cut filter of 22 kHz or 11 kHz applied to them. The amplitudes and latencies of five ABR waves (<10 ms) revealed no significant effects caused by filtering. The participants could not distinguish between the original and the 22-kHz filtered click sounds, while they could distinguish between the original and the 11-kHz filtered sounds. These results indicate that a CD-level anti-alias filter does not affect initial auditory processing and the sound difference is not discernible, at least for artificial sounds with a simple acoustic structure.

Computed tomographic and magnetic resonance imaging of a coup contrecoup traumatic brain injury in a horse

Computed tomographic and magnetic resonance imaging of a coup contrecoup traumatic brain injury in a horse

Exposing distinct subcortical components of the auditory brainstem response evoked by continuous naturalistic speech.

Speech processing is built upon encoding by the auditory nerve and brainstem, yet we know very little about how these processes unfold in specific subcortical structures. These structures are deep and respond quickly, making them difficult to study during ongoing speech. Recent techniques have begun to address this problem, but yield temporally broad responses with consequently ambiguous neural origins. Here, we describe a method that pairs re-synthesized 'peaky' speech with deconvolution analysis of electroencephalography recordings. We show that in adults with normal hearing the method quickly yields robust responses whose component waves reflect activity from distinct subcortical structures spanning auditory nerve to rostral brainstem. We further demonstrate the versatility of peaky speech by simultaneously measuring bilateral and ear-specific responses across different frequency bands and discuss the important practical considerations such as talker choice. The peaky speech method holds promise as a tool for investigating speech encoding and processing, and for clinical applications.

Brainstem volumetric integrity in preclinical and prodromal Alzheimer’s disease

AbstractBackgroundAutopsy‐based neuropathological studies have suggested the tau pathology observed in Alzheimer’s disease (AD) originates in brainstem nuclei, but no studies to date have quantified brainstem volumes in clinical populations with biomarker‐confirmed mild cognitive impairment (MCI) or dementia due to AD or determined the value of brainstem volumetrics in predicting dementia risk. The present study examined whether MRI‐based brainstem sub‐structural volumes differ between cognitively normal (CN) older adults and those with MCI or dementia due to AD, and whether early preclinical brainstem volumes predict future progression to dementia.MethodAlzheimer’s Disease Neuroimaging Initiative participants diagnosed as CN (n=822), MCI (n=543), or AD (n=300) underwent baseline T1‐weighted structural MRI scanning with variable clinical follow‐up (6‐120 months). A subset of participants completed baseline fasting lumbar puncture to quantify levels of amyloid‐beta 1‐42 and phospho‐tau. We employed region‐of‐interest and voxel‐based morphometric methods to assess differences between clinically‐diagnosed and biomarker‐defined groups in volumes of the whole brainstem, midbrain, pons, and locus coeruleus. Longitudinal Cox regression analyses determined value of baseline brainstem sub‐structure volumes in predicting progression to a future clinical diagnosis of AD dementia.ResultCompared with CN individuals, we observed smaller regional volumes in whole brainstem, midbrain, pons, and locus coeruleus regions in patients clinically diagnosed with MCI and AD, and specifically within the midbrain in biomarker‐confirmed cases. Brainstem‐masked voxel‐wise comparisons confirmed volume reduction of a dorsal rostral brainstem region corresponding to the locus coeruleus in MCI and AD relative to CN, as well as in CN who progressed to AD dementia versus those that did not progress to AD dementia. In a preclinical risk analysis, cognitively normal individuals who later progressed to AD dementia exhibited smaller baseline midbrain volumes than individuals who did not develop dementia, and longitudinal analyses indicated smaller midbrain and locus coeruleus volumes conferred greater risk of progression.ConclusionOur study indicated that brainstem MRI changes are detectible in preclinical and prodromal populations. Our findings are consistent with the neuropathological observation that AD‐related pathology occurs early in brainstem nuclei and further suggest the clinical relevance of brainstem sub‐structural volumes for preclinical and prodromal AD populations.

Serotonergic Modulation of Locomotor Activity From Basal Vertebrates to Mammals.

During the last 50 years, the serotonergic (5-HT) system was reported to exert a complex modulation of locomotor activity. Here, we focus on two key factors that likely contribute to such complexity. First, locomotion is modulated directly and indirectly by 5-HT neurons. The locomotor circuitry is directly innervated by 5-HT neurons in the caudal brainstem and spinal cord. Also, indirect control of locomotor activity results from ascending projections of 5-HT cells in the rostral brainstem that innervate multiple brain centers involved in motor action planning. Second, each approach used to manipulate the 5-HT system likely engages different 5-HT-dependent mechanisms. This includes the recruitment of different 5-HT receptors, which can have excitatory or inhibitory effects on cell activity. These receptors can be located far or close to the 5-HT release sites, making their activation dependent on the level of 5-HT released. Here we review the activity of different 5-HT nuclei during locomotor activity, and the locomotor effects of 5-HT precursors, exogenous 5-HT, selective 5-HT reuptake inhibitors (SSRI), electrical or chemical stimulation of 5-HT neurons, genetic deletions, optogenetic and chemogenetic manipulations. We highlight both the coherent and controversial aspects of 5-HT modulation of locomotor activity from basal vertebrates to mammals. This mini review may hopefully inspire future studies aiming at dissecting the complex effects of 5-HT on locomotor function.

Evidence for the role of the dorsal ventral lateral posterior thalamic nucleus connectivity in deep brain stimulation for Gilles de la Tourette syndrome

Gilles de la Tourette syndrome (GTS) can manifest as debilitating, medically-refractory tics for which deep brain stimulation (DBS) of the centromedian-parafascicular complex (CM) can provide effective treatment. However, patients have reported benefit with activation of contacts dorsal to the CM and likely in the ventro-lateral thalamus (VL). At our institution, a case of a robust and durable response in a GTS patient required stimulation in the CM and more dorsally. We explore the structural connectivity of thalamic subregions associated with GTS using diffusion MRI tractography. Diffusion weighted images from 40 healthy Human Connectome Project (HCP) subjects and our GTS patient were analyzed. The VL posterior nucleus (VLp) and the CM were used as seeds for whole-brain probabilistic tractography. Leads were localized via linear registration of pre-/post-operative imaging and cross-referenced with the DBS Intrinsic Template Atlas. Tractography revealed high streamline probability from the CM and VLp to the superior frontal gyrus, rostral middle frontal gyrus, brainstem, and ventral diencephalon. Given reported variable responses to DBS along the thalamus, we segmented the VLp based on its connectivity profile. Ventral and dorsal subdivisions emerged, with streamline probability patterns differing between the dorsal VLp and CM. The CM, the most reported DBS target for GTS, and the dorsal VLp have different but seemingly complimentary connectivity profiles as evidenced by our patient who, at 1-year post-operatively, had significant therapeutic benefit. Stimulation of both regions may better target reward and motor circuits, resulting in enhanced symptom control for GTS.

Speech-ABR in contralateral noise: A potential tool to evaluate rostral part of the auditory efferent system

In parallel with the auditory afferent system, the auditory efferent system is active in all parts of the auditory pathways from auditory cortex to the cochlea. The auditory efferent system has two main segments: the rostral and the caudal parts. The rostral part, which starts from the cortical centers to thalamic nuclei and continues into collicular pathways in rostral brainstem, which sends its neural fibers to the main collicular nuclei especially inferior colliculus. The caudal part includes the olivocochlear bundle, which originates from the superior olivary complex and terminates on the cochlear hair cells. Most studies about the auditory efferent system have focused only on the caudal part using otoacoustic emission suppression test. Speech-evoked auditory brainstem response (S-ABR) as an electrophysiologic test that uses speech stimuli to simulate real-life auditory conditions, reflects the performance of rostral brainstem centers, so structurally seems to be an appropriate candidate to examine the rostral part of the auditory efferent system. Our hypothesis is that S-ABR in noisy condition, a typical condition for stimulating the auditory efferent system, has the potential to be used as an objective noninvasive electrophysiologic test for studying the rostral auditory efferent system in diagnosis and treatment/rehabilitation follow-ups. In addition, S-ABR can potentially reflect higher-order auditory functions and the effects of their dysfunctions on the lower brainstem. This characteristic makes S-ABR even more suitable tool for evaluation of the efferent system. To evaluate our hypothesis, Eighteen normal hearing subjects in the age range of 18–25 were tested in a pilot study for S-ABR in quiet mode and three signal to noise ratios of +10,0 and −10 for both ears. Then we checked the correlation between the results of S-ABR in different conditions and scores of auditory behavioral tests that auditory efferent system is involved in them: Consonant-Vowel perception in noise, dichotic Consonant-Vowel-Consonant and sound lateralization in noise. The results of our pilot study showed a significant correlation between S-ABR changes in noise with the scores of the behavioral tests in noisy or dichotic situations. Findings of the current study suggest that S-ABR with specific contralateral noise can be an appropriate option for evaluating the performance of rostral part of the auditory efferent system and may be suitable for top-down auditory training follow-ups, although the generalization of these results needs further studies in different groups with different auditory processing abnormalities or skills.

First Implant-Induced Changes in Rostral Brainstem Impair Second Implant Outcomes in Sequential Bilateral Cochlear Implant Children With Long Inter-Implant Delay.

Long-term unilateral use of a cochlear implant (CI) induces abnormal maturation of the rostral brainstem innervating the contralateral ear. In sequential bilateral CI children with long inter-implant delay, both sides of auditory cortices were dominantly activated by the first CI, but mechanisms of this abnormal development of the auditory system remain unclear. Fifteen sequential bilateral CI children with long delay (mean ± SD, 28.7 ± 12.1 mo) underwent electrically evoked auditory brainstem response (EABR) testing using each of the first and second CI (CI1 and CI2, respectively), immediately after the second implantation. CI1 and CI2 were implanted at age of 23.7 ± 9.6 and 53.1 ± 12.1 months (mean ± SD), respectively. Apical-to-basal difference in electrically evoked interwave III-V latencies (eIII-eV slope) which decreases with implant use was compared between the CI1 and CI2 sides. Their speech perception scores were evaluated 3 years after the second implantation. eIII-eV slopes evoked by the CI2 showed less mature pattern than those by the CI1. This CI2 versus CI1 difference in eIII-eV slopes, however, reduced as the inter-implant delay was prolonged, suggesting CI1-induced maturation of the rostral brainstem innervating the second ear before the second implantation. The smaller CI2 versus CI1 difference in eIII-eV slopes at the second implantation was correlated to poorer outcomes using the CI2 than the CI1. In this population, long-term unilateral CI use induced re-organization of the rostral brainstem innervating the second ear, which affected hearing outcomes using the CI2. Evaluation of eIII-eV slopes at the second implantation may be useful to predict hearing outcomes with CI2.

Superior Cervical Ganglion: Axonal Passage and Inputs

Axons of the rostral middle (MCG) and inferior (ICG) cervical ganglion were reported to bypass the superior cervical ganglion (SCG). However, the distribution of these neurons has not been determined. Meanwhile, it has been inconsistent with the distribution of the preganglionic neurons of the SCG. To examine the above issues, we recently injected wheat germ agglutinin- horseradish peroxidase (WGA-HRP) into the entire or partial (rostral or caudal) SCG of the rat (Anatomical Record, 301:1906-1916, 2018). By preparing complete whole-mounts of the sympathetic tissues and sections of the brainstem and spinal cord, we labeled neurons that are distributed evenly in the MCG (left: 258 ＞ right: 121) ICG (left: 848, right: 681) and CST (up to 770). It is found specifically a novel cervical ganglion and termed it as the ＂pre-middle cervical ganglion＂ (pMCG) that is located rostral to the MSG and sends axons (left: 120 ＞ right: 82) to bypass the SCG. In addition to the preganglionic neurons in the cervical (C1-C4) and thoracic (T1-T4) segments, we also labeled neurons (233) that extend dendrites into the vestibular nuclear complex and locate in the intermediate reticular nuclei (96%) and perifacial zone (4%) of the brainstem ranging from Bregma -10.0 to -11.0 mm, mainly in -10.80 mm. With tracer injection into the rostral or caudal SCG, we labeled neurons correspondingly in the brainstem, C1-C2 or T1-T2. These data indicated that many neurons in pMCG, MCG and ICG run rostrally within the CST to project to their peripheral targets rather than segmentally via the closest rami. For their close anatomical location, neurons in pMCG and MCG may have similar or complementary function. Numerous neurons in the CST and caudal cervical ganglia provide bypass axons via SCG may imply special function that is useful for electroceuticals. The newly identified preganglionic neurons located in the rostral brainstem may be involved in the vestibulo-autonomic interaction for their extending dendrites into the vestibular nuclear complex that has been known to form an interaction pathway with the vagal complex.

Heat Stress Modulates Brain Monoamines and Their Metabolites Production in Broiler Chickens Co-Infected with Clostridium perfringens Type A and Eimeria spp.

Heat stress has been related to the impairment of behavioral and immunological parameters in broiler chickens. However, the literature is not clear on the involvement of neuroimmune interactions in a heat stress situation associated with bacterial and parasitic infections. The present study evaluated the production of monoamines and their metabolites in brain regions (rostral pallium, hypothalamus, brain stem, and midbrain) in broiler chickens submitted to chronic heat stress and/or infection and co-infection with Eimeria spp. and Clostridium perfringens type A. The heat stress and avian necrotic enteritis (NE) modulated the neurochemical profile of monoamines in different areas of the central nervous system, in particular, those related to the activity of the hypothalamus-hypophysis-adrenal (HPA) axis that is responsible for sickness behavior. C. perfringens and/or Eimeria infection, heat stress increased 5-hydroxytryptamine (5-HT), 4,4 dihydroxyphenylacetic acid (DOPAC), and DOPAC/dopamine (DA) in the rostral pallium; 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), homovanillic acid (HVA), HVA/DA, DOPAC/DA, and 5-hydroxyindoleacetic acid (5-HIAA)/5-HT in the hypothalamus; MHPG, 5-HIAA/5-HT, DOPAC/DA, and HVA/DA in the midbrain; and MHPG, DOPAC, HVA, HVA/DA, DOPAC/DA, and 5-HIAA/5-HT in the brainstem. Heat stress decreased noradrenaline + norepinephrine (NOR + AD) in all brain regions analyzed; 5-HT in the hypothalamus, midbrain, and brainstem; and DA in the midbrain. The results also showed the existence and activity of the brain-gut axis in broiler chickens. The brain neurochemical profile and corticosterone production are consistent with those observed in chronic stressed mammals, in animals with sickness behavior, and an overloading of the HPA axis.

On corticopetal-corticofugal loops of the new early filter: from cell assemblies to the rostral brainstem.

On corticopetal-corticofugal loops of the new early filter : from cell assemblies to the rostral brainstem