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Glossopharyngeal neuralgia due to vertebrobasilar dolichoectasia is a rare form of neuropathic pain, and presents diagnostic and therapeutic challenges. Clinical presentation: A 67-yearold man presented with severe burning pain in the left oral cavity, with no explanatory findings during dental and ear, nose, and throat evaluations. Temporomandibular joint examination revealed tenderness, and panoramic radiographs showed a noncontributory periapical radiolucency. Magnetic resonance imaging/magnetic resonance angiography revealed abnormally tortuous vertebral arteries compressing the glossopharyngeal nerves and the brainstem. Topical lidocaine reduced pain, confirming glossopharyngeal neuralgia. Carbamazepine was initially ineffective, but at 200 mg pain reduced from 90 to 20 on the visual analog scale. The patient requested and underwent microvascular decompression surgery, which eliminated his pain. Conclusion: When the vertebral artery compresses the glossopharyngeal nerve, the pain is more intense, attributed to its thicker vascular structure. Local anesthetic testing aids in identifying glossopharyngeal neuralgia. Dental practitioners must be skilled in diagnostics and possess anatomical knowledge for accurate evaluation and referral of throat and ear pain. [ABSTRACT FROM AUTHOR]

Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2.

Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1-3. In endogenous taurine metabolism, dedicated enzymes are involved in the biosynthesis of taurine from cysteine and in the downstream metabolism of secondary taurine metabolites4,5. One taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by stimuli that alter taurine or acetate flux, including endurance exercise7, dietary taurine supplementation8 and alcohol consumption6,9. So far, the identities of the enzymes involved in N-acetyltaurine metabolism, and the potential functions of N-acetyltaurine itself, have remained unknown. Here we show that the body mass index associated orphan enzyme phosphotriesterase-related (PTER)10 is a physiological N-acetyltaurine hydrolase. In vitro, PTER catalyses the hydrolysis of N-acetyltaurine to taurine and acetate. In mice, PTER is expressed in the kidney, liver and brainstem. Genetic ablation of Pter in mice results in complete loss of tissue N-acetyltaurine hydrolysis activity and a systemic increase in N-acetyltaurine levels. After stimuli that increase taurine levels, Pter knockout mice exhibit reduced food intake, resistance to diet-induced obesity and improved glucose homeostasis. Administration of N-acetyltaurine to obese wild-type mice also reduces food intake and body weight in a GFRAL-dependent manner. These data place PTER into a central enzymatic node of secondary taurine metabolism and uncover a role for PTER and N-acetyltaurine in body weight control and energy balance.

Exaggerated airway constriction triggered by repeated exposure to allergen, also called hyperreactivity, is a hallmark of asthma. Whereas vagal sensory neurons are known to function in allergen-induced hyperreactivity1-3, the identity of downstream nodes remains poorly understood. Here we mapped a full allergen circuit from the lung to the brainstem and back to the lung. Repeated exposure of mice to inhaled allergen activated the nuclei of solitary tract (nTS) neurons in a mast cell-, interleukin-4 (IL-4)- and vagal nerve-dependent manner. Single-nucleus RNA sequencing, followed by RNAscope assay at baseline and allergen challenges, showed that a Dbh+ nTS population is preferentially activated. Ablation or chemogenetic inactivation of Dbh+ nTS neurons blunted hyperreactivity whereas chemogenetic activation promoted it. Viral tracing indicated that Dbh+ nTS neurons project to the nucleus ambiguus (NA) and that NA neurons are necessary and sufficient to relay allergen signals to postganglionic neurons that directly drive airway constriction. Delivery of noradrenaline antagonists to the NA blunted hyperreactivity, suggesting noradrenaline as the transmitter between Dbh+ nTS and NA. Together, these findings provide molecular, anatomical and functional definitions of key nodes of a canonical allergen response circuit. This knowledge informs how neural modulation could be used to control allergen-induced airway hyperreactivity.

Chronic neuropathic pain can result from nervous system injury and can persist in the absence of external stimuli. Although ongoing pain characterizes the disorder, in many individuals, the intensity of this ongoing pain fluctuates dramatically. Previously, it was identified that functional magnetic resonance imaging signal covariations between the midbrain periaqueductal gray (PAG) matter, rostral ventromedial medulla (RVM), and spinal trigeminal nucleus are associated with moment-to-moment fluctuations in pain intensity in individuals with painful trigeminal neuropathy (PTN). Since this brainstem circuit is modulated by higher brain input, we sought to determine which cortical sites might be influencing this brainstem network during spontaneous fluctuations in pain intensity. Over 12 min, we recorded the ongoing pain intensity in 24 PTN participants and classified them as fluctuating (n = 13) or stable (n = 11). Using a PAG seed, we identified connections between the PAG and emotional-affective sites such as the hippocampal and posterior cingulate cortices, the sensory-discriminative posterior insula, and cognitive-affective sites such as the dorsolateral prefrontal (dlPFC) and subgenual anterior cingulate cortices that were altered dependent on spontaneous high and low pain intensity. Additionally, sliding-window functional connectivity analysis revealed that the dlPFC-PAG connection anticorrelated with perceived pain intensity over the entire 12 min period. These findings reveal cortical systems underlying moment-to-moment changes in perceived pain in PTN, which likely cause dysregulation in the brainstem circuits previously identified, and consequently alter the appraisal of pain across time.

Background and aimsThe precise roles of screen media activity (SMA) and sleep problems in relation to child/adolescent psychopathology remain ambiguous. We investigated temporal relationships among sleep problems, SMA, and psychopathology and potential involvement of thalamus-prefrontal-cortex (PFC)-brainstem structural covariation.MethodsThis study utilized data from the Adolescent Brain Cognitive Development study (n = 4,641 ages 9-12) at baseline, Year1, and Year2 follow-up. Cross-Lagged Panel Models (CLPMs) investigated reciprocal predictive relationships between sleep duration/problems, SMA, and psychopathology symptoms. A potential mediating role of baseline Thalamus-PFC-brainstem covariation on SMA-externalizing relationships was examined.ResultsParticipants were divided into discovery (n = 2,359, 1,054 girls) and replication (n = 2,282, 997 girls) sets. CLPMs showed 1) bidirectional associations between sleep duration and SMA in late childhood, with higher frequency SMA predicting shorter sleep duration (β = -0.10 [95%CI: -0.16, -0.03], p = 0.004) and vice versa (β = -0.11 [95%CI: -0.18, -0.05], p < 0.001); 2) externalizing symptoms at age 10-11 predicting sleep problems (β = 0.11 [95%CI: 0.04, 0.19], p = 0.002), SMA (β = 0.07 [95%CI: 0.01, 0.13], p = 0.014), and internalizing symptoms (β = 0.09 [95%CI: 0.05, 0.13], p < 0.001) at age 11-12; and 3) externalizing behavior at age 10-11 partially mediating the relationship between baseline thalamus-PFC-brainstem covariation and SMA at age 11-12 (indirect effect = 0.032 [95%CI: 0.003, 0.067], p-value = 0.030). Findings were replicable.ConclusionWe found bi-directional SMA-sleep-duration associations in late childhood. Externalizing symptoms preceded future SMA and sleep disturbances and partially mediated relationships between structural brain covariation and SMA. The findings emphasize the need for understanding individual differences and developing and implementing integrated strategies addressing both sleep concerns and screen time to mitigate potential impacts on psychopathology.

Somatic and sympathetic tones fluctuate together seamlessly across daily behaviors. In this issue of Cell, Zhang et al. describe populations of spinal projecting neurons in the rostral ventromedial medulla (rVMM) that harmonize somatic motor function and sympathetic activation. The coordinated regulation plays a vital role in supporting behaviors associated with various arousal states.

The relationship between heart failure and diabetes is intricate and bidirectional. Individuals with diabetes face an elevated risk of developing heart failure due to factors like insulin resistance, chronic inflammation, and metabolic irregularities. Elevated blood sugar levels can harm blood vessels and nerves, culminating in the buildup of fatty deposits in arteries, atherosclerosis, and hypertension, which significantly contribute to heart failure. Furthermore, diabetes can adversely impact the structure and function of the heart muscle, impairing its pumping capacity. Conversely, heart failure can also contribute to the onset of diabetes by disrupting the bodys metabolic processes and amplifying insulin resistance. The complex interaction between these conditions mandates a comprehensive approach to managing individuals with both diabetes and heart failure, underscoring the importance of addressing both aspects for enhanced patient outcomes. Although existing pharmacological treatments are limited and frequently associated with undesirable side effects, acupuncture has established itself as a traditional practice with a legacy. It remains a supplementary option for treating cardiovascular diseases. Heart failure and diabetes are both heavily associated with chronic upregulation of the sympathetic nervous system, which has been identified as a pivotal factor in the progression of disease. Mechanistic interplays such as the attenuation of central nitric oxide signaling may interfere with the production or availability of nitric oxide in key areas of the central nervous system, including the brainstem and hypothalamus. This review will delve into the current understanding of acupuncture on the autonomic nervous system and offer insights into its potential role in the future treatment landscape for diabetes and heart failure.

It remains elusive whether lesions and inflammation in the sub/juxtacortical white matter reflect cortical and/or meningeal pathologies. Elucidating this could have implications for MRI monitoring as sub/juxtacortical lesions are detectable by routine MRI, while cortical lesions and meningeal inflammation are not. By large‐area microscopy, we quantified total and mixed active plaque loads along with densities and sizes of perivascular mononuclear infiltrates (infiltrates) in the sub/juxtacortical white matter ≤2 mm from the cortex, intra‐cortically and in the meninges. Data were related to ante‐mortem clinical parameters in a false discovery rate‐corrected analysis. We compared 12 patients with primary progressive multiple sclerosis (PPMS) and 15 with secondary progressive MS to 22 controls. Fifteen patients and 11 controls contributed with hemispheric sections. Sections were stained with haematoxylin–eosin, for myelin and for microglia/macrophages. B cells and T cells were confirmed in a subset. Immunoglobulin G depositions in selected cortical plaques resembled depositions described before in “slowly expanding” plaques in the white matter. We quantified plaque activity by measuring microglia‐dominated and macrophage‐dominated areas. Sub/juxtacortical plaques (load and activity) reflected plaque activity in the cerebral cortex. Plaque activity and infiltrates were more pronounced in the sub/juxtacortical white matter than in the cerebral cortex while conversely, the total plaque load was highest in the cortex. Infiltrates correlated trans‐cortically and sub/juxtacortical plaque activity reflected cortical and meningeal infiltrates. Sub/juxtacortical infiltrate sizes correlated with shorter survival after progression onset. Two patients with PPMS and putatively fatal brain stem lesions argue against incidental findings. Trans‐cortical inflammatory flares and plaque activity may be pathogenic in progressive MS. We suggest emphasis on sub/juxtacortical MRI lesions as plausible surrogates for cortical and meningeal pathologies and, when present, as indicators for cognitive testing. [ABSTRACT FROM AUTHOR]

Anesthesia modifies sensory representations in the thalamo-cortical circuit but is considered to have a milder impact on peripheral sensory processing. Here, tracking the same neurons across wakefulness and isoflurane or ketamine medetomidine anesthesia, we show that the amplitude and sign of single neuron responses to sounds are massively modified by anesthesia in the cochlear nucleus of the brainstem, the first relay of the auditory system. The reorganization of activity is so profound that decoding of sound representation under anesthesia is not possible based on awake activity. However, population-level parameters, such as average tuning strength and population decoding accuracy, are weakly affected by anesthesia, explaining why its effect has previously gone unnoticed when comparing independently sampled neurons. Together, our results indicate that the functional organization of the auditory brainstem largely depends on the network state and is ill-defined under anesthesia. This demonstrates a remarkable sensitivity of an early sensory stage to anesthesia, which is bound to disrupt downstream processing. [ABSTRACT FROM AUTHOR]

Diffuse intrinsic pontine glioma (DIPG) is a highly lethal tumor that occurs in the brain stem. At present, there is no effective drug for DIPG. In this work, Na/K‐ATPase inhibitor‐ouabain (OB) is found to efficiently kill H3K27M‐mutated DIPG at low doses, inhibit tumor cell proliferation, reduce tumor stemness for the first time, demonstrating its potential as a chemotherapy drug for DIPG. In order to increase the blood–brain barrier (BBB) permeability and tumor accumulation of OB, acidic‐responsive engineered exosomes loaded with OB (OB@EXO‐LCCP) are constructed, which increase the accumulation of OB within the tumor microenvironment of DIPG and efficiently deliver OB to DIPG cells to achieve targeted killing effect. In in vitro experiments, OB@EXO‐LCCP is able to release OB in an acid‐responsive manner and effectively kill DIPG tumor cells. In in vivo experiments, OB@EXO‐LCCP significantly inhibits DIPG growth and prolongs the overall survival of DIPG‐bearing mice. Overall, OB@EXO‐LCCP can promote the BBB permeability and tumor‐targeting ability of OB, thereby enhancing its DIPG‐killing ability and reducing its toxicity. This study provides technical and theoretical information for the precision therapy of DIPG. [ABSTRACT FROM AUTHOR]

Saccades are rapid eye movements that are used by all species with good vision. In this study, we set out to characterize the complete repertoire of larval zebrafish horizontal saccades to gain insight into their contributions to visually guided behavior and underlying neural control. We identified five saccade types, defined by systematic differences in kinematics and binocular coordination, which were differentially expressed across a variety of behavioral contexts. Conjugate saccades formed a large group that serves at least four functions. These include fast phases of the optokinetic nystagmus, visual scanning in stationary animals, and shifting gaze in coordination with body turns. In addition, we discovered a previously undescribed pattern of eye-body coordination in which small conjugate saccades partially oppose head rotation to maintain gaze during forward locomotion. Convergent saccades were coordinated with body movements to foveate prey targets during hunting. Detailed kinematic analysis showed that conjugate and convergent saccades differed in the millisecond coordination of the eyes and body and followed distinct velocity main sequence relationships. This challenges the prevailing view that all horizontal saccades are controlled by a common brainstem circuit and instead indicates saccade-type-specific neural control. • Kinematic analysis of thousands of rapid eye movements reveals five saccade types • Conjugate saccades have at least four identifiable visual functions • Convergent saccades are coordinated with body movements to foveate prey • Distinct main sequence relationships imply saccade-type-specific neural control Dowell et al. characterize the repertoire of saccadic eye movements of larval zebrafish and examine their coordination with swims during visuomotor behaviors. Differences in timing, kinematics, and velocity main sequences indicate that different saccade types are controlled by distinct patterns of brainstem activity. [ABSTRACT FROM AUTHOR]

Background: The commonest echocardiographic measurement, left ventricular ejection fraction, can not necessarily predict mortality of recipients following heart transplantation potentially due to afterload dependency. Afterload‐independent left ventricular stroke work index (LVSWI) is alternatively recommended by the current guideline; however, pulmonary artery catheters are rarely inserted in organ donors in most jurisdictions. We propose a novel non‐invasive echocardiographic parameter, Pressure‐Strain Product (PSP), as a potential surrogate of catheter‐based LVSWI. This study aimed to investigate if PSP could correlate with catheter‐based LVSWI in an ovine model of brain stem death (BSD) donors. The association between PSP and myocardial mitochondrial function in the post‐transplant hearts was also evaluated. Methods: Thirty‐one female sheep (weight 47 ± 5 kg) were divided into two groups; BSD (n = 15), and sham neurologic injury (n = 16). Echocardiographic parameters including global circumferential strain (GCS) and global radial strain (GRS) and pulmonary artery catheter‐based LVSWI were simultaneously measured at 8‐timepoints during 24‐h observation. PSP was calculated as a product of GCS or GRS, and mean arterial pressure for PSPcirc or PSPrad, respectively. Myocardial mitochondrial function was evaluated following 6‐h observation after heart transplantation. Results: In BSD donor hearts, PSPcirc (n = 96, rho =.547, p <.001) showed the best correlation with LVSWI among other echocardiographic parameters. PSPcirc returned AUC of.825 to distinguish higher values of cardiomyocyte mitochondrial function (cut‐off point; mean value of complex 1,2 O2 Flux) in post‐transplant hearts, which was greater than other echocardiographic parameters. Conclusions: PSPcirc could be used as a surrogate of catheter‐based LVSWI reflecting mitochondrial function. [ABSTRACT FROM AUTHOR]

Simple Summary: Nasopharynx cancer treatment often involves radiation therapy, but choosing the best method can be challenging. This study compares two advanced radiation techniques: one using X-rays and another using protons. Both aim to target the tumor while sparing healthy tissues, but their effectiveness can vary based on the cancer's location and stage. Researchers want to determine which technique works best for different patients, particularly those with cancer close to sensitive brain structures. By analyzing treatment plans for 28 patients, we developed guidelines to help doctors choose the most suitable technique. This research could lead to more personalized and effective treatments, potentially improving outcomes and quality of life for patients with nasopharynx cancer. The findings may also help healthcare providers use resources more efficiently, benefiting both patients and the broader medical community. Background: Proton therapy requires caution when treating patients with targets near neural structures. Intuitive and quantitative guidelines are needed to support decision-making concerning the treatment modality. This study compared dosimetric profiles of intensity-modulated proton therapy (IMPT) and intensity-modulated radiation therapy (IMRT) using helical tomotherapy (HT) for adaptive re-planning in cT3-4 nasopharyngeal cancer (NPCa) patients, aiming to establish criteria for selecting appropriate treatment modalities. Methods: HT and IMPT plans were generated for 28 cT3-4 NPCa patients undergoing definitive radiotherapy. Dosimetric comparisons were performed for target coverage and high-priority organs at risk (OARs). The correlation between dosimetric parameters and RT modality selection was analyzed with the target OAR distances. Results: Target coverages were similar, while IMPT achieved better dose spillage. HT was more favorable for brainstem D1, optic chiasm Dmax, optic nerves Dmax, and p-cord D1. IMPT showed advantages for oral cavity Dmean. Actually, 14 IMPT and 14 HT plans were selected as adaptive plans, with IMPT allocated to most cT3 patients (92.9% vs. 42.9%, p = 0.013). The shortest distances from the target to neural structures were negatively correlated with OAR doses. Receiver operating characteristic curve analyses were carried out to discover the optimal cut-off values of the shortest distances between the target and the OARs (temporal lobes and brainstem), which were 0.75 cm (AUC = 0.908, specificity = 1.00) and 0.85 cm (AUC = 0.857, specificity = 0.929), respectively. Conclusions: NPCa patients with cT4 tumor or with the shortest distance between the target and critical neural structures < 0.8 cm were suboptimal candidates for IMPT adaptive re-planning. These criteria may improve resource utilization and clinical outcomes. [ABSTRACT FROM AUTHOR]

We report the clinical findings of mVEMP responses in conjunction with cVEMPs and oVEMPs in an individual with Wallenberg syndrome. The results indicated that the degree of abnormality in mVEMP was comparatively higher than in cVEMPs and oVEMPs. mVEMPs can offer valuable insights into the Wallenberg syndrome's brainstem pathophysiology. [ABSTRACT FROM AUTHOR]

To assess deafness in term infant with birth asphyxia by otoacoustic emission and brain stem evoked response audiometry. A Prospective observational study was done at Tertiary care government hospital from 15/02/2021 to 15/10/2022.Total 130 patients were included in the study by consecutive sampling method. All the patients fulfilling the inclusion criteria during the study period were included. After explaining the aims, objectives and methods of study, written informed consent was obtained from the parents to undergo Otoacoustic Emission (OAE) and Brain Stem Evoked Response Audiometry Test (BERA). Data was entered in case record form. Collected data was analysed by appropriate statistical methods. Hearing impairment was present in eight (6.15%) asphyxiated term infants. A mild degree of hearing loss was seen in three (37.5%), a moderate degree of hearing loss was seen in four (50%), severe degree of hearing loss was seen in one (12.5%) asphyxiated term infant. In asphyxiated term infants, no significant difference in hearing loss was seen with respect to gender, Obstetrics history, and type of delivery. Significant difference in hearing loss was seen in antenatal Diabetes mellitus, hypertension, family history of SNHL and APGAR Score less than 6. Severe degree of hearing loss was seen in prolonged labour and HTN mother. Significant difference in hearing loss was seen in antenatal Diabetes mellitus, hypertension, family history of SNHL and APGAR Score less than 4 and 6 in one and five minutes respectively. Severe degree of hearing loss was seen in prolonged labour and HTN mother. [ABSTRACT FROM AUTHOR]

AbstractObjectiveDesignStudy sampleResultsConclusionsTo compare the performance of a selection of machine learning algorithms, trained to label peaks I, III, and V of the auditory brainstem response (ABR) waveform. An additional algorithm was trained to provide a confidence measure related to the ABR wave latency estimates.Secondary data analysis of a previously published ABR dataset. Five types of machine learning algorithm were compared within a nested k-fold cross-validation procedure.A set of 482 suprathreshold ABR waveforms were used. These were recorded from 81 participants with audiometric thresholds within normal limits.A convolutional recurrent neural network (CRNN) outperformed the other algorithms evaluated. The algorithm labelled 95.9% of ABR waves within ±0.1 ms of the target. The mean absolute error was 0.025 ms, averaged across the outer validation folds of the nested cross-validation procedure. High confidence levels were generally associated with greater wave-labelling accuracy.Machine learning algorithms have the potential to assist clinicians with ABR interpretation. The present work identifies a promising machine learning approach, but any algorithm to be used in clinical practice would need to be trained on a large, accurately labelled, heterogeneous dataset and evaluated in clinical settings in follow-on work. [ABSTRACT FROM AUTHOR]

Background: Stereotactic approaches to diffuse intrinsic pontine gliomas (DIPGs) remain essential due to advances in molecular biology and management, necessitating tissue sampling. Here we present an effective technique with a biopsy by robot-assisted transcerebellar approach. Method: Our procedure was performed using the ROSA robotic system and the OARM CT scan, which provided stereotactic conditions for this transcerebellar approach to brainstem lesions. Conclusion: The robot-assisted transcerebellar stereotactic approach remains essential to provide complications for biopsy of brainstem lesions. [ABSTRACT FROM AUTHOR]

Introduction: LMNB1-related autosomal dominant leukodystrophy (ADLD) is a slowly progressive neurodegenerative disorder caused by overexpression of LMNB1. We retrospectively reviewed charts of all ADLD patients seen at Mayo Clinic. Methods: All available data from molecularly confirmed ADLD patients was reviewed. Results: Of eight patients identified, three were male. Age at symptom onset ranged from 33 to 64 years. In males, the first symptom was erectile dysfunction (2/3) or neurogenic bladder (1/3) and, in females, weakness (3/5), bladder dysfunction (2/5), or depression (1/5). Diagnostic delay from symptom onset was a median of 6 (IQR 2.3–10) years. Other reported symptoms included cognitive difficulties (8/8), fatigue (7/8), sleep issues (4/8), mood disturbances (5/8), tremor (4/8), and migraine (4/8). Family history was positive in 6. All eight patients had LMNB1 duplication. Eighteen brain MRIs were reviewed from 7 patients. All showed symmetric confluent T2W deep cerebral and periventricular white matter hyperintensities with involvement of the posterior limb of the internal capsule, corpus callosum, corticospinal tract in brain stem, and superior and middle cerebellar peduncles. Seven spine MRIs from six patients showed moderate diffuse atrophy of the spinal cord. Conclusion: Typical clinical symptoms and characteristic MRI changes should prompt genetic testing for ADLD. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether idiopathic intracranial hypertension (IIH) may affect white matter integrity and optic pathways by using diffusion tensor imaging (DTI) and to correlate the DTI metrics with intracranial pressure (ICP). Methods: This study is a retrospective case–control study. A total of 42 patients who underwent lumbar puncture and those with elevated ICP, meeting the diagnostic criteria for IIH, were included in the study. All patients had supportive magnetic resonance imaging findings for the diagnosis of IIH. The headache control group comprised 36 patients who presented to the Neurology Department with infrequent episodic tension‐type headache, had a normal neurologic examination, and had clinical and radiological findings suggestive of normal ICP. For each patient with IIH, clinical findings and ophthalmological measurements were recorded. The apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) values were calculated using a region of interest‐based method in different white matter tracts and optic pathways and compared. Results: A total of 42 patients diagnosed with IIH (three males, 39 females), with a mean (standard deviation [SD] age of 38.1 (8.9) years), and 36 headache controls (10 males, 26 females, mean [SD] age; 38.1 [9.4] years) were included in the study. The mean (SD) body mass index (BMI) of the patients with IIH was 25.2 (1.9) kg/m2, and the mean (SD) BMI of the headache controls was 23.3 (1.5) kg/m2 (p < 0.001). Decreased FA values and increased RD values in the cingulum were detected in patients with IIH compared to the headache controls (p = 0.003, Cohen's d = 0.681; p = 0.002 Cohen's d = −0.710). Decreased AD values in the left and right superior cerebellar peduncle and increased ADC values in the middle cerebellar peduncle were detected in patients with IIH compared to the headache controls (p < 0.001, Cohen's d = 0.961; p = 0.009, Cohen's d = 0.607; p = 0.015, Cohen's d = −0.564). Increased ADC and RD values and decreased FA values in optic nerve were detected in patients with IIH (p = 0.010, Cohen's d = −0.603; p = 0.004, Cohen's d = −0.676; p = 0.015 Cohen's d = 0.568). A positive correlation was found between the cerebrospinal fluid pressure and ADC values of the left and right superior and left inferior longitudinal fasciculus, genu of the corpus callosum, and right optic radiation (r = 0.43, p = 0.005; r = 0.31, p = 0.044; r = 0.39, p = 0.010; r = 0.35, p = 0.024; r = 0,41, p = 0.007). There was a positive correlation between the retinal nerve fiber layer thickness and the ADC values of the optic nerve (r = 0.32, p = 0.039). Conclusions: Intracranial hypertension can be associated with deteriorated DTI values, which might be interpreted as a sign of impaired white matter microstructural integrity in many brain regions beyond the periventricular white matter. Pressure‐induced edema and axonal degeneration may be the potential underlying mechanisms of this microstructural damage. Plain Language Summary: Females of reproductive age with obesity are disproportionately affected by idiopathic intracranial hypertension (IIH), and the incidence of this diagnosis is increasing along with the prevalence of obesity. We do not yet understand how IIH develops, but dysregulation of intracranial pressure is an important area of research interest, so we hypothesized that increased intracranial pressure may affect white matter microstructure and optic pathways in patients with IIH. Using data from a specialized imaging technique, we found that patients with IIH may have impaired white matter microstructural integrity in several areas of the brain and microstructural alterations in the optic nerve. [ABSTRACT FROM AUTHOR]

Brainstem cavernous malformations are benign subset of cerebral cavernous malformations, which need a special intervention owing to being vital and complex. The diffusion tensor imaging technique, a well-recognized neuroimaging tool, can visualize the white matter tracts and their surroundings and provide promising surgical outcomes. This systematic review and meta-analysis evaluated the effect of preoperative diffusion tensor imaging in patients undergoing surgical resection of brainstem cavernous malformations. Five databases, including PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar, were searched using a comprehensive search strategy to find any article matching our inclusion criteria. We used Comprehensive Meta-Analysis (CMA) software to analyze the collected data, get the evidence, and report the results as event rate (ER), with their 95% confidence interval (CI). Twenty-eight studies involving 467 patients matched our criteria and 19 studies entered the analysis. Our analysis showed that, in patients undergoing surgical resection of brainstem cavernous malformations assisted by preoperative diffusion tensor imaging, 82.21% achieved total resection. About 12.4% of patients achieved partial resection, 65.65% improved, 8.07% worsened, 25.04% showed no change, 3.59% experienced postoperative re-bleeding, and 0.87% died. The utilization of preoperative diffusion tensor imaging significantly increased the proportion of improved patients and decreased the proportion of worsened patients. However, further controlled research is needed to draw a definite conclusion about the usefulness of its role. [ABSTRACT FROM AUTHOR]

Objectives: Basilar artery occlusion (BAO) may be etiologically attributed to embolism or in situ thrombosis due to basilar stenosis (BS). Patients with BAO due to BS (BAOS) are known to have worse outcomes than patients with embolic occlusions (BAOE). BAOS occurs more proximally in the basilar artery (BA) than BAOE. We hypothesize that differing brain stem infarct patterns contribute to outcome differences between these stroke etiologies. Methods: This retrospective study includes 199 consecutive patients with BAO who received endovascular treatment at a single center. Final infarction in brain parenchyma dependent on the posterior circulation was graded semiquantitatively on magnetic resonance imaging (MRI). Associations to underlying stenosis and angiographic and clinical outcome variables were tested. The primary endpoint was early good clinical outcome (EGCO, mRS score ≤ 3 at discharge). Results: Infarct extension of the medulla oblongata (OR = 0.25; 95% CI = 0.07–0.86; p = 0.03), the inferior pons (OR = 0.328; 95% CI = 0.17–0.63; p = 0.001), the superior pons (OR = 0.57; 95% CI = 0.33–0.99; p = 0.046), and the occipital lobes (OR = 0.46; 95% CI = 0.26–0.80; p = 0.006) negatively predicted EGCO. Infarct extension for other posterior-circulation-dependent brain regions was not independently associated with unfavorable early outcomes. Patients with BAOS had more proximal occlusions and greater infarct volumes in the inferior brain stem. Successful reperfusion (mTICI 2b-3) occurred more often in patients with BAOE than in BAOS (BAOE: 131 (96.3%); BAOS: 47 (83.9%), p = 0.005). Conclusion: Unfavorable early outcomes in patients with BAOS may be explained by a higher likelihood of inferior brain stem infarcts and lower rates of reperfusion success. Clinical relevance statement: Basilar artery occlusion due to underlying stenosis is associated with a poorer prognosis than that caused by embolism; these results suggest that aggressive endovascular therapy, usually involving the placement of a permanent stent, may be warranted in these patients. Key Points: Inferior brain stem and occipital infarcts are prognostically unfavorable in basilar artery occlusion. Basilar artery occlusion due to stenosis occurs more proximally and is associated with worse outcomes. Differentiating etiologies of basilar artery occlusion may influence how aggressively treated the occlusion is. [ABSTRACT FROM AUTHOR]

Background: Enteral nimodipine is the most evidence-based and widely used drug for the treatment of delayed cerebral ischemia and is known to have various neuroprotective functions. However, the neuroprotective mechanism of nimodipine still remains unclear, and the effects of nimodipine remain ambiguous. Herein, we studied the effect of enteral nimodipine on endothelial apoptosis after subarachnoid hemorrhage (SAH). Methods: SAH was experimentally introduced in white rabbits (n = 42) that were grouped as follows: enteral nimodipine (SAH-nimodipine group, n = 14), a control that received normal saline (SAH-saline group, n = 13), and a control without hemorrhage (control group, n = 15). On the third day after SAH induction, the brain stem, including the vertebrobasilar vascular system, was extracted. The effects of enteral nimodipine were analyzed by group using histopathologic analysis, including immunohistochemical staining of apoptosis-related proteins (Bcl2 [anti-apoptotic] and Bax [pro-apoptotic]). Results: Cytoplasmic vacuolation of smooth muscle cells was observed in two SAH hemorrhagic groups and was more prominent in the SAH-saline group. Endothelial desquamation was observed only in the SAH-saline group. For the basilar artery, expression of Bcl2 and Bax in the SAH-nimodipine group was lower than that in the SAH-saline group, but significant differences were not observed (pBcl2 = 0.311 and pBax = 0.720, respectively). In penetrated arterioles, the expression of Bax in the SAH-nimodipine group was significantly lower than that of the SAH-saline group (p < 0.001). The thickness of the tunica media in the basilar artery was thinner in the SAH-nimodipine group than in the SAH-saline group (p < 0.001). Conclusions: This study suggests that enteral nimodipine may have a neuroprotective function by inhibiting endothelial apoptosis in small arterioles and preventing smooth muscle cell proliferation in large arteries. [ABSTRACT FROM AUTHOR]

Cocaine is a frequently abused and highly addictive drug that damages brain health and imposes substantial social and economic costs. Acupuncture has been used in the treatment of cocaine addiction and has been shown to improve abnormal mental and motor states. This article mainly focuses on the neurobiological mechanisms involving the central nervous system (CNS) and peripheral nervous system (PNS) that underlie the effects of acupuncture in the treatment of cocaine addiction. The central dopamine system is a key player in acupuncture treatment of cocaine addiction; the ventral tegmental area (VTA)—nucleus accumbens (NAc) signaling pathway, which has a modulatory influence on behavior and psychology after chronic use of cocaine, is a significant target of acupuncture action. Moreover, acupuncture alleviates cocaine-induced seizures or acute psychomotor responses through the paraventricular thalamus and the lateral habenula (LHb)—rostromedial tegmental (RMTg) nucleus circuits. The data suggest that acupuncture can impact various cocaine-induced issues via stimulation of diverse brain areas; nevertheless, the interconnection of these brain regions and the PNS mechanisms involved remain unknown. In this review, we also discuss the effects of specific acupuncture protocols on cocaine addiction and note that variations in needling modalities, current intensities and traditional acupuncture point locations have led to different experimental results. Therefore, standardized acupuncture protocols (with respect to stimulation methods, point locations and number of sessions) may become particularly important in future studies. [ABSTRACT FROM AUTHOR]

Primary cilia (PC) are microtubules-based, independent antennal-like sensory organelles, that are seen in most vertebrate cells of different types, including astrocytes and neurons. They send signals to cells to control many physiological and cellular processes by detecting changes in the extracellular environment. Parkinson's disease (PD), a neurodegenerative disease that progresses over time, is primarily caused by a gradual degradation of the dopaminergic pathway in the striatum nigra, which results in a large loss of neurons in the substantia nigra compact (SNpc) and a depletion of dopamine (DA). PD samples have abnormalities in the structure and function of PC. The alterations contribute to the cause, development, and recovery of PD via influencing signaling pathways (SHH, Wnt, Notch-1, α-syn, and TGFβ), genes (MYH10 and LRRK2), defective mitochondrial function, and substantia nigra dopaminergic neurons. Thus, restoring the normal structure and physiological function of PC and neurons in the brain are effective treatment for PD. This review summarizes the function of PC in neurodegenerative diseases and explores the pathological mechanisms caused by PC alterations in PD, in order to provide references and ideas for future research. [ABSTRACT FROM AUTHOR]

Our body temperature is normally kept within a narrow range of 1°C. For example, if our body temperature rises, such as in a hot environment or due to strenuous exercise, our thermoregulatory system will trigger a powerful heat defense response with vasodilation, sweating, and lowered metabolism. During fever, which often involves body temperatures of up to 41°C, this heat defense mechanism is apparently inhibited; otherwise, the rising body temperature would be immediately combated, and fever would not be allowed to develop. New evidence suggests how and where this inhibition takes place. In two consecutive studies from Cheng et al. and Xu et al., it has been shown that prostaglandin E2, which generates fever by acting on thermosensory neurons in the preoptic hypothalamus, also acts on neurons in the brainstem parabrachial nucleus, which receive temperature information from temperature-activated spinal cord neurons and relay this information to the thermoregulatory center in the hypothalamus to either induce cold or heat defenses. By acting on the same type of prostaglandin E2 receptor that is critical for fever generation in the preoptic hypothalamus, the EP3 receptor, prostaglandin E2 inhibits the signaling of the heat-responsive parabrachial neurons, while stimulating the cold-responsive neurons. These novel findings thus show that prostaglandin E2, by binding to the same receptor subtype in the parabrachial nucleus as in the preoptic hypothalamus, adjusts the sensitivity of the thermosensory system in a coordinated manner to allow the development of febrile body temperatures. [ABSTRACT FROM AUTHOR]

Background: The study explored the differences in audiological and non-audiological characteristics between congenital, early-onset, and late-onset auditory neuropathy spectrum disorder (ANSD). Ninety-five individuals diagnosed with ANSD were included in the study. They were divided into three groups congenital ANSD—children (30 individuals, 60 ears), adults with early-onset ANSD (30 individuals, 56 ears), and adults with late-onset ANSD (35 individuals, 62 ears). The non-audiological characteristics (gender, laterality, and risk factors) and audiological characteristics (behavioral and electrophysiological measures) were compared between the three groups. Results: Discriminant analyses showed that the pure tone average, audiogram configuration, and speech thresholds were the best auditory predictors of onset-based group differences in ANSD (congenital and early-onset versus late-onset ANSD). While the congenital and early-onset group showed poorer pure-tone and speech thresholds, along with flat configuration, the late-onset group demonstrated relatively better thresholds and other configurations (rising, tent-shaped, cookie-bite). In addition, long latency responses were delayed or absent in children with congenital ANSD, indicative of onset coding deficits at the cortical level. Conclusions: The study highlights the audiological differences between congenital, early-, and late-onset ANSD groups. These differences could be because of variations in etiology, pathophysiology, site of lesion, or genetic variability between the groups, which needs to be explored further. [ABSTRACT FROM AUTHOR]

Background: The growing concern for player safety in rugby has led to an increased focus on head impacts. Previous laboratory studies have shown that rugby headgear significantly reduces peak linear and rotational accelerations compared to no headgear. However, these metrics may have limited relevance in assessing the effectiveness of headgear in preventing strain-based brain injuries like concussions. This study used an instantaneous deep-learning brain injury model to quantify regional brain strain mitigation of rugby headgear during drop tests. Tests were conducted on flat and angled impact surfaces across different heights, using a Hybrid III headform and neck. Results: Headgear presence generally reduced the peak rotational velocities, with some headgear outperforming others. However, the effect on peak regional brain strains was less consistent. Of the 5 headgear tested, only the newer models that use open cell foams at densities above 45 kg/m3 consistently reduced the peak strain in the cerebrum, corpus callosum, and brainstem. The 3 conventional headgear that use closed cell foams at or below 45 kg/m3 showed no consistent reduction in the peak strain in the cerebrum, corpus callosum, and brainstem. Conclusions: The presence of rugby headgear may be able to reduce the severity of head impact exposure during rugby. However, to understand how these findings relate to brain strain mitigation in the field, further investigation into the relationship between the impact conditions in this study and those encountered during actual gameplay is necessary. [ABSTRACT FROM AUTHOR]

The present study examined the medium‐ and long‐term effects of early environmental enrichment (EE) on neuromotor, nociceptive, cognitive, behavioral, and neurochemical parameters in newborn rats repeatedly exposed to morphine. The study employed 90 Wistar rats: 10 adult nulliparous females and 80 male pups. Litter was split into standard and EE housing. Following, half of each litter received saline (S) or morphine (M) injections, resulting in four groups: SC + S, EE + S, SC + M, and EE + M. EE was applied from PND1 to PND21, while morphine or saline was given daily (5 μg/s.c.) from PND8 to PND14. Neuromotor development was similar between groups. In the OF test, morphine reduced outer and total crossings, whereas EE increased inner crossings and rearings. Adult rats showed a decrease in outer and total crossings and grooming and an increase in rearing. EE increased the number of protected and unprotected head dipping. Adult rats showed an increase in protected head dipping. Adult rats showed a lower recognition index, and, when exposed to EE, a lower anxiety index and analgesia. EE increased brainstem and hippocampal BDNF levels. Adult rats had increased hypothalamus, spinal cord, and brainstem BDNF levels, an increase in the spinal cord, and decreased hypothalamus TNF‐α levels. This study demonstrated that early‐life EE raises BDNF levels in the brainstem and hippocampus of rats and modifies their behaviors (such as nociception, exploration, and anxiety) in a state‐dependent manner (morphine and age). [ABSTRACT FROM AUTHOR]

This comprehensive longitudinal study explored for the first time the interrelations between neonatal brainstem abnormalities, focused attention (FA), and learning—following a preterm cohort (N = 175; 46.3% female; predominantly White) from birth (2003–2006) to 17 years. The findings indicated that FA during early childhood was associated with language outcomes in toddlerhood (n = 131) and academic and attention self‐report indices in late adolescence (n = 44). Pilot assessments indicated that FA at 17 years (n = 25) was also associated with concurrent academic and attention functioning. Structural equation modeling analyses revealed that neonatal brainstem functioning, manifested in auditory brainstem response patterns, was associated with early‐life FA competence, which affected learning development. Implications underscore the essential role of early brainstem function and FA in shaping childhood learning trajectories. [ABSTRACT FROM AUTHOR]

Background: Dementia can be caused by numerous different diseases that present variable clinical courses and reveal multiple patterns of brain atrophy, making its accurate early diagnosis by conventional examinative means challenging. Although highly accurate and powerful, magnetic resonance imaging (MRI) currently plays only a supportive role in dementia diagnosis, largely due to the enormous volume and diversity of data it generates. AI-based software solutions/algorithms that can perform automated segmentation and volumetry analyses of MRI data are being increasingly used to address this issue. Numerous commercial and non-commercial software solutions for automated brain segmentation and volumetry exist, with FreeSurfer being the most frequently used. Objectives: This Review is an account of the current situation regarding the application of automated brain segmentation and volumetry to dementia diagnosis. Methods: We performed a PubMed search for "FreeSurfer AND Dementia" and obtained 493 results. Based on these search results, we conducted an in-depth source analysis to identify additional publications, software tools, and methods. Studies were analyzed for design, patient collective, and for statistical evaluation (mathematical methods, correlations). Results: In the studies identified, the main diseases and cohorts represented were Alzheimer's disease (n = 276), mild cognitive impairment (n = 157), frontotemporal dementia (n = 34), Parkinson's disease (n = 29), dementia with Lewy bodies (n = 20), and healthy controls (n = 356). The findings and methods of a selection of the studies identified were summarized and discussed. Conclusion: Our evaluation showed that, while a large number of studies and software solutions are available, many diseases are underrepresented in terms of their incidence. There is therefore plenty of scope for targeted research. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a globally prevalent neurodegenerative disorder, primarily characterized by muscle rigidity, resting tremor, and bradykinesia. The incidence of PD is rapidly escalating worldwide. Numerous studies have been conducted on the application of magnetic resonance imaging (MRI) in investigating the substantia nigra (SN) in PD patients. However, to date, no bibliometric analysis has been performed on this specific research area. Therefore, this study aimed to provide a comprehensive analysis of the current status in MRI research on the SN in PD patients. Materials and methods: MRI study records related to the SN in PD patients from 2001 to 2024 were searched by using the Web of Science Core Collection (WOSCC) database and then the CiteSpace and VOSviewer were used to conduct bibliometric analysis. Results: Our analysis found that the number of published articles related studies on MRI of the SN in PD showed an overall upward trend over the past decade, in which Lehericy, Stephane, Du, Guangwei, and Huang, Xuemei are the top three authors with the most articles. Additionally, United States, China and Germany are the main contributors to MRI studies of SN in PD. And Shanghai Jiao Tong University, University of Florida and Seoul National University are the leading institutions in the field. Finally, the keyword analysis showed that the hotspots and trends of research in this field are mainly concentrated in quantitative susceptibility mapping, neuroimaging, and neuromelanin-sensitive MRI. Conclusion: These analysis identified the most influential authors, institutions, countries and research hotspots in the field of SN-MRI research in PD, which has reference significance for the research interest in this field and provides a new idea for PD prevention. [ABSTRACT FROM AUTHOR]

Introduction: Auditory training (AT) exercises as the main part of auditory rehabilitation have emerged as a promising method for enhancing auditory perception and communication skills in individuals with hearing impairments or difficulties in auditory processing. Through AT, the central auditory nervous system (CANS) undergoes changes that optimize neural circuits, resulting in improved auditory perception. Auditory-evoked potentials (AEPs), including the auditory brainstem responses (ABRs) and cortical auditory-evoked potentials (CAEPs), offer objective measurements of neural responses and serve as valuable biomarkers to assess the effectiveness of AT. Methods: For this systematic review, we conducted a comprehensive search in multiple databases, including MEDLINE (via PubMed), Science Direct, Web of Science, and SciELO, up until August 18, 2023. There were no study type restrictions or limitations on publication time. Following a careful assessment of the article quality and their alignment with the inclusion and exclusion criteria, a total of 25 articles were selected for inclusion in this study. Results: Based on the findings of the reviewed studies, it has been reported that AT exercises lead to an increase in the amplitude of waves in both brainstem and cortical AEPs, with the exception of P1 and N2 waves. Furthermore, it has been observed that the latency of these responses decreases following AT. Conclusion: The application of brainstem and cortical AEPs as objective electrophysiological tools holds promise in assessing the effectiveness of AT exercises and confirming the selected approach for AT. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusion Patients may undergo anatomical changes during radiotherapy, leading to an underdosing of the target or overdosing of the organs at risk (OARs).This study developed a deep‐learning method to predict the tumor response of patients with nasopharyngeal carcinoma (NPC) during treatment. This method can predict the anatomical changes of a patient.The participants included 230 patients with NPC. The data included planning computed tomography (pCT) and routine cone‐beam CT (CBCT) images. The CBCT image quality was improved to the CT level using an advanced method. A long short‐term memory network‐generative adversarial network (LSTM‐GAN) is proposed, which can harness the forecasting ability of LSTM and the generation ability of GAN. Four models were trained to predict the anatomical changes that occurred in weeks 3–6 and named LSTM‐GAN‐week 3 to LSTM‐GAN‐week 6. The pCT and CBCT were used as input, and the tumor target volumes (TVs) and OARs were delineated on the predicted and real images (ground truth). Finally, the models were evaluated using contours and dosimetry parameters.The proposed method predicted the anatomical changes, with a dice similarity coefficient above 0.94 and 0.90 for the TVs and surrounding OARs, respectively. The dosimetry parameters were close between the prediction and ground truth. The deviations in the prescription, minimum, and maximum doses of the tumor targets were below 0.5 Gy. For serial organs (brain stem and spinal cord), the deviations in the maximum dose were below 0.6 Gy. For parallel organs (bilateral parotid glands), the deviations in the mean dose were below 0.8 Gy.The proposed method can predict the tumor response to radiotherapy in the future such that adaptation can be scheduled on time. This study provides a proactive mechanism for planning adaptation, which can enable personalized treatment and save clinical time by anticipating and preparing for treatment strategy adjustments. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine important predictors of fifth-year Expanded Disability Status Scale (EDSS) scores in multiple sclerosis (MS) patients using machine learning. Patients and methods: In this retrospective study, the XGBoost basic model was developed to predict five-year EDSS scores in 1,000 patients (317 males, 683 females; mean age: 43.4±10.9 years; range, 18 to 76 years) with MS between January 1999 and December 2020. Patients were categorized based on the initial symptoms of MS onset: brainstem symptoms, optic symptoms, spinal symptoms, or supratentorial symptoms. In the next stage, important predictors of fifth-year EDSS scores were determined and ranked by their importance using the SHAP (SHapley Additive exPlanations) algorithm, which is a machine learning method. Results: For patients with optic symptoms at onset, second-year EDSS scores, age, and first-year pyramidal functions were identified as the most important variables, respectively. In contrast, for those with spinal symptoms at onset, second-year pyramidal functions, age, and second-year ambulation were important predictors. In the patients with brainstem symptoms at onset, age, first-year EDSS scores, and first-year bowel and bladder functions were determined as important variables. Additionally, for patients with supratentorial symptoms at onset, second-year pyramidal functions, second-year EDSS scores, and age were the top predictors. Conclusion: The results provided valuable insights into predictors of fifth-year EDSS scores in patients with MS grouped by their initial symptoms. Our findings indicate that the ranking of importance of functional system evaluations varies among patients with MS based on their initial symptoms, with age as a significant predictor for all symptom groups. [ABSTRACT FROM AUTHOR]

Objective: Patients with anorexia nervosa (AN) are often anxious, display inflexible behavior and disrupted reward processing. Emerging evidence suggests that gut dysbiosis in patients contributes to the disease phenotype and progression. Methods: In a preclinical study, we explored whether AN‐derived microbiota impacts cognitive flexibility, anxiety, and dopamine signaling using fecal microbiota transplantation (FMT) in tyrosine hydroxylase‐cre rats. We performed probabilistic reversal learning task (PRLT) at the baseline, after antibiotic treatment, and following FMT from patients with AN and controls. We assessed flexible behavior, task engagement, and ventral tegmental area (VTA) dopamine signaling during and in the absence of reward. Furthermore, anxiety‐like behavior was evaluated with open field (OF) and elevated plus maze (EPM) tests. Results: Neither antibiotic‐induced dysbiosis nor AN FMT led to significant alterations in the number of reversals or lever press strategies after reinforced or nonreinforced lever presses (win and lose‐stay) in the PRLT. However, the number of initiated trials decreased after antibiotic treatment while remaining unchanged after FMT. No significant differences were observed in VTA dopamine activity, anxiety measures in the OF and EPM tests. Microbiome analysis revealed limited overlap between the microbiota of the donors and recipients. Discussion: No evidence was found that the microbiota of patients compared to controls, nor a depleted microbiome impacts cognitive flexibility. Nonetheless, antibiotic‐induced dysbiosis resulted in reduced task engagement during the PRLT. The relatively low efficiency of the FMT is a limitation of our study and highlights the need for improved protocols to draw robust conclusions in future studies. Public Significance: While our study did not reveal direct impacts of AN‐associated gut microbiota on cognitive flexibility or anxiety behaviors in our preclinical model, we observed a decrease in task engagement after antibiotic‐induced dysbiosis, underscoring that the presence of a gut microbiome matters. Our findings underscore the need for further refinement in FMT protocols to better elucidate the complex interplay between gut microbiota and behaviors characteristic of anorexia nervosa. [ABSTRACT FROM AUTHOR]

Myocardial ischemia causes the release of bradykinin, which activates afferent nerve endings in the ventricular epicardium. This elicits a sympathetically mediated increase in arterial pressure and heart rate, referred to as the cardiogenic sympathetic afferent reflex. The rostroventrolateral medulla (RVLM) is a key sympathetic brain stem site for regulating cardiovascular activity. This study aimed to determine the importance of non‐barosensitive nociception sympathetic activity and the role of glutamate receptor activation of RVLM neurons in the cardiogenic sympathetic afferent reflex. We tested the hypothesis that inhibition of barosensitive sympathetic activity attenuates but does not abolish the reflex response to cardiac visceral afferents. Renal sympathetic nerve activity (RSNA), arterial pressure, and heart rate responses to epicardial bradykinin application were recorded in anesthetized rats before and after bilateral RVLM microinjection of either GABAA agonist muscimol, ionotropic glutamate receptor antagonist kynurenic acid, N‐methyl‐d‐aspartate (NMDA) receptor antagonist 2‐amino‐5‐ phosphonopentanoic acid (AP5), or non‐NMDA antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX). Baroreceptor loading‐induced inhibition of barosensitive activity attenuated the bradykinin‐induced RSNA response (93 ± 14% increase) and tachycardia (18 ± 3 bpm). While RVLM muscimol microinjection abolished the RSNA response (1.6 ± 4.2% from baseline, 0.49 ± 0.38 μV*s), surprisingly, it did not abolish the tachycardia (27 ± 4 bpm). Kynurenic acid microinjection blocked the arterial pressure and RSNA responses, while AP5 or CNQX only attenuated the responses. These data suggest that nociception‐sensitive sympathetic activity that does not appear to be barosensitive is also involved in the cardiogenic sympathetic afferent reflex. Importantly, while muscimol and kynurenic acid abolished the arterial pressure and RSNA response, neither affected the tachycardia, suggesting an alternate cardiac pathway independent of RVLM. [ABSTRACT FROM AUTHOR]

Background: The most compact portion of the corpus callosum (CC) is the corpus splenium (CS). Purpose: To evaluate the connection between clinical and demographic features to determine whether neuroimaging findings will be permanent or temporary in CS patients. Material and Methods: We enrolled 93 patients (age range = 18–86 years) with CS lesions. Demographic and clinical information were recorded. We examined the lesions depending on the location. Group 1 (n = 20) had lesions limited to the CS (egg-shaped or round); group 2 (n = 15) had "boomerang sign" lesions; and group 3 (n = 58) had splenium involvement in conditions affecting the whole brain (Boomerang sign+ plus). Results: Group 1 had a lower mean age, shorter disease duration, and fewer persistent lesions than others (P < 0.01, P < 0.001, and P < 0.001, respectively). The mean disease onset age (in years) in group 1 was higher than that of the other groups (P < 0.045). Group 2 had lower potassium (K) (P < 0.003) and red cell distribution width levels (P < 0.029) than the other groups. Age <41.5 years (P < 0.001), age at illness initiation <48.5 years (P < 0.002), disease duration <5.5 months (P < 0.001), and eosinophil level <0.29 uL (P 0.014) all point to temporary lesions. Conclusion: Cases with limited CS lesions have younger onset ages, lower disease onset ages, and shorter disease durations. Age, age of disease onset, disease duration, and eosinophil level are risk variables that affect whether CS lesions are permanent or temporary. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease. Current detection methods can only confirm the diagnosis at the onset of the disease, missing the critical window for early treatment. Recent studies using animal models have found that detecting changes in miRNA sites can predict the onset and severity of the disease in its early stages, facilitating early diagnosis and treatment. miRNAs show expression changes in motor neurons that connect the brain, spinal cord, and brain stem, as well as in the skeletal muscle in mouse models of ALS. Clinically, expression changes in some miRNAs in patients align with those in mouse models, such as the upregulation of miR-29b in the brain and the upregulation of miR-206 in the skeletal muscle. This study provides an overview of some miRNA study findings in humans as well as in animal models, including SOD1, FUS, TDP-43, and C9orf72 transgenic mice and wobbler mice, highlighting the potential of miRNAs as diagnostic markers for ALS. miR-21 and miR-206 are aberrantly expressed in both mouse model and patient samples, positioning them as key potential diagnostic markers in ALS. Additionally, miR-29a, miR-29b, miR-181a, and miR-142-3p have shown aberrant expression in both types of samples and show promise as clinical targets for ALS. Finally, miR-1197 and miR-486b-5p have been recently identified as aberrantly expressed miRNAs in mouse models for ALS, although further studies are needed to determine their viability as diagnostic targets. [ABSTRACT FROM AUTHOR]

Gliomas of the brainstem represent a small percentage of central nervous system gliomas in adults. Due to the proximity of the tumor to critical structures, radical surgery is highly challenging and limited to selected cases. In addition, postoperative treatments, which become exclusive to non-operable patients, do not guarantee satisfactory disease control, making the progression of the disease inevitable. Currently, there is a lack of therapeutic options to control tumor growth after the diagnosis of recurrence. The rarity of these tumors, their distinct behavioral characteristics, and the limited availability of tumor tissue necessary for the development of prognostic and predictive biomarkers contribute to the absence of a standardized approach for treating recurrent brainstem gliomas. A salvage radiotherapy (RT) retreatment could represent a promising approach for recurrent brainstem gliomas. However, to date, it has been mainly evaluated in pediatric cases, with few experiences available to assess the most appropriate RT dose, safety, and clinical responses in adult patients. This comprehensive review aims to identify instances of adult patients with recurrent brainstem gliomas subjected to a secondary course of RT, with a specific focus on the analysis of treatment-related toxicity and outcomes. Through this investigation, we endeavor to contribute valuable insights into the viability and efficacy of salvage RT retreatment in managing recurrent brainstem gliomas in the adult population. [ABSTRACT FROM AUTHOR]

The auditory brainstem response (ABR) can be used to evaluate hearing sensitivity of animals. However, typical measurement protocols are time-consuming. Here, an adaptive algorithm is proposed for efficient ABR threshold estimation. The algorithm relies on the update of the predicted hearing threshold from a Gaussian process model as ABR data are collected using iteratively optimized stimuli. To validate the algorithm, ABR threshold estimation is simulated by adaptively subsampling pre-collected ABR datasets. The simulated experiment is performed on 5 datasets of mouse, budgerigar, gerbil, and guinea pig ABRs (27 ears). The datasets contain 68–106 stimuli conditions, and the adaptive algorithm is configured to terminate after 20 stimuli conditions. The algorithm threshold estimate is compared against human rater estimates who visually inspected the full waveform stacks. The algorithm threshold matches the human estimates within 10 dB, averaged over frequency, for 15 of the 27 ears while reducing the number of stimuli conditions by a factor of 3–5 compared to standard practice. The intraclass correlation coefficient is 0.81 with 95% upper and lower bounds at 0.74 and 0.86, indicating moderate to good reliability between human and algorithm threshold estimates. The results demonstrate the feasibility of a Bayesian adaptive procedure for rapid ABR threshold estimation. [ABSTRACT FROM AUTHOR]

Listeners exhibit varying levels of tolerance for background noise during speech communication. It has been proposed that low tolerance of background noise may be the consequence of abnormally amplified gain in the central auditory system (CAS). Here, using a dataset of young adults with normal hearing thresholds, we asked whether central gain mechanisms might also explain cases of hypertolerance of background noise, as well as cases of reduced, but not abnormal, tolerance. We used the auditory brainstem response to derive a measure of CAS gain (wave V/wave I ratio) to compare listeners' background noise tolerance while listening to speech, grouping them into three categories: hyper, high, and medium tolerance. We found that hypertolerant listeners had reduced CAS gain compared to those with high tolerance. This effect was driven by wave V not wave I. In addition, the medium tolerant listeners trended toward having reduced wave I and reduced wave V amplitudes and generally higher levels of exposure to loud sound, suggestive of the early stages of noise-compromised peripheral function without an apparent compensatory increase in central gain. Our results provide physiological evidence that 1) reduced CAS gain may account for hypertolerance of background noise but that 2) increased CAS gain is not a prerequisite for medium tolerance of background noise. NEW & NOTEWORTHY: Our findings strengthen the proposed mechanistic connection between background noise tolerance and auditory physiology by suggesting a link between hypertolerance and reduced central auditory gain, measured by the auditory brainstem response. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the characteristics of auditory processing (AP) in preschool children with attention-deficit/hyperactivity disorder (ADHD) using the speech auditory brainstem response (speech-ABR), which provides insights into the AP of speech signals in the central auditory nervous system (CANS). Method: A total of 84 preschool children diagnosed with ADHD, aged 4-6 years, were matched with 84 typically developing (TD) children based on gender and age. All children underwent speech-ABR testing, cognitive assessment using the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition or the Wechsler Intelligence Scale for Children-Fourth Edition, and a continuous performance test. Results: Children with ADHD exhibited significantly longer latencies of speech-ABR waveforms V, A, and D compared to TD children. Multiple linear regression analysis showed that the latencies of speech-ABR waves V, A, and D were affected by the presence of ADHD, but not by the full-scale intelligence quotient. Conclusions: This study revealed that preschool children with ADHD exhibited abnormal AP of speech signals in their CANS. The findings suggest that speech-ABR can be utilized as a reliable measure to evaluate AP ability in this population, as it remains unaffected by cognitive or attentional factors. The transient response (V, A) of speech-ABR was found to be a significant predictor of ADHD in a clinical setting. Early assessment of AP abnormalities via speech-ABR is recommended in preschool-age children to develop targeted interventions for ADHD. [ABSTRACT FROM AUTHOR]

The insular cortex is an important hub for sensory and emotional integration. It is one of the areas consistently found activated during pain. While the insular's connections to the limbic system might play a role in the aversive and emotional component of pain, its connections to the descending pain system might be involved in pain intensity coding. Here, we used anterograde tracing with viral expression of mCherry fluorescent protein, to examine the connectivity of insular axons to different brainstem nuclei involved in the descending modulation of pain in detail. We found extensive connections to the main areas of descending pain control, namely, the periaqueductal gray (PAG) and the raphe magnus (RMg). In addition, we also identified an extensive insular connection to the parabrachial nucleus (PBN). Although not as extensive, we found a consistent axonal input from the insula to different noradrenergic nuclei, the locus coeruleus (LC), the subcoereuleus (SubCD) and the A5 nucleus. These connections emphasize a prominent relation of the insula with the descending pain modulatory system, which reveals an important role of the insula in pain processing through descending pathways. [ABSTRACT FROM AUTHOR]

Purpose: Magnetic resonance imaging (MRI), electric compound action potential (eCAP), and electric auditory brainstem response (eABR) are among the routine assessments performed before and/or after cochlear implantation. The objective of this review was to systematically summarize and critically appraise existing evidence of the prognostic value of eCAP, eABR, and MRI for predicting post--cochlear implant (CI) speech perception outcomes in children, with a particular focus on the lesion site. Method: The present systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. Three electronic databases (ProQuest, PubMed, and Scopus) were searched with no restrictions on language, publication status, or year of publication. Studies on children identified with sensorineural hearing loss, auditory neuropathy spectrum disorder, cochlear nerve deficiency, or cochleovestibular nerve abnormalities reporting the relevance of eCAP, eABR, and/or MRI results to CI speech perception outcomes were included. The literature search yielded 1,887 publications. Methodological quality and strength of evidence were assessed by the Crowe Critical Appraisal Tool and the Grading of Recommendations Assessment, Development, and Evaluation tool, respectively. Results: Of the 25 included studies, the relevance of eCAP, eABR, and/or MRI findings to post-CI speech perception outcomes was reported in 10, 11, and 11 studies, respectively. The studies were strongly in support of the prognostic value of eABR and MRI for CI outcomes. However, the relevance of eCAP findings to speech perception outcomes was uncertain. Conclusion: Despite the promising findings, caution is warranted in interpreting them due to the observational and retrospective design of the included studies, as well as the heterogeneity of the population and the limited control of confounding factors within these studies. Supplemental Material: https://doi.org/10.23641/asha.26169859 [ABSTRACT FROM AUTHOR]

• We used eye tracking to investigate the effect of early Huntington's disease on saccadic movements, pupil reaction and blink production. • HD patients showed significant changes in all three behaviors while watching short videos in a free-viewing task. • This suggests brain stem degeneration at an early stage of the disease detectable with a simple free viewing task. Video-based eye tracking was used to investigate saccade, pupil, and blink abnormalities among patients with Huntington's disease (HD) who watched sequences of short videos. HD, an autosomal dominant neurodegenerative disorder resulting from a CAG mutation on chromosome 4, produces motor and cognitive impairments including slow or irregular eye movements, which have been studied using structured tasks. To explore how HD affects eye movements under instruction free conditions, we assessed 22 HD patients and their age matched controls in a 10-minute video-based free viewing task. Patients with HD experienced a significant reduction in saccade exploration rate following video clip transitions, an increase in pupil reactions to luminance changes after clip transitions, and a significant higher blink rate throughout the task compared to the control group. These results show that HD has a significant impact on how patients visually explore and respond to their environment under unconstrained and ecologically natural conditions. Eye tracking in HD patients revealed saccadic, pupil, and blink abnormalities in early HD patients, suggestive of brain circuitry abnormalities that probably involve brain stem deficits. Further research should explore the impact of these changes on the quality of life of the patients affected by the disease. [ABSTRACT FROM AUTHOR]

• Auditory brainstem responses to paired-click stimuli were obtained from 57 adults. • Significant correlations were found between the second-click response and the participant's age or their word intelligibility. • The second-click response using the paired-click stimulation paradigm could be useful for detecting cochlear synaptopathy. This study aimed to evaluate whether auditory brainstem response (ABR) using a paired-click stimulation paradigm could serve as a tool for detecting cochlear synaptopathy (CS). The ABRs to single-clicks and paired-clicks with various inter-click intervals (ICIs) and scores for word intelligibility in degraded listening conditions were obtained from 57 adults with normal hearing. The wave I peak amplitude and root mean square values for the post-wave I response within a range delayed from the wave I peak (referred to as the RMS post-w1) were calculated for the single- and second-click responses. The wave I peak amplitudes did not correlate with age except for the second-click responses at an ICI of 7 ms, and the word intelligibility scores. However, we found that the RMS post-w1 values for the second-click responses significantly decreased with increasing age. Moreover, the RMS post-w1 values for the second-click responses at an ICI of 5 ms correlated significantly with the scores for word intelligibility in degraded listening conditions. The magnitude of the post-wave I response for the second-click response could serve as a tool for detecting CS in humans. Our findings shed new light on the analytical methods of ABR for quantifying CS. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to survey astrocyte and microglial activation across four brain regions in a mouse model of chronic migraine. Background: Chronic migraine is a leading cause of disability, with higher rates in females. The role of central nervous system neurons and glia in migraine pathophysiology is not fully elucidated. Preclinical studies have shown abnormal glial activation in the trigeminal nucleus caudalis of male rodents. No current reports have investigated glial activation in both sexes in other important brain regions involved with the nociceptive and emotional processing of pain. Methods: The mouse nitroglycerin model of migraine was used, and nitroglycerin (10 mg/kg) or vehicle was administered every other day for 9 days. Prior to injections on days 1, 5, and 9, cephalic allodynia was determined by periorbital von Frey hair testing. Immunofluorescent staining of astrocyte marker, glial fibrillary protein (GFAP), and microglial marker, ionized calcium binding adaptor molecule 1 (Iba1), in male and female trigeminal nucleus caudalis, periaqueductal gray, somatosensory cortex, and nucleus accumbens was completed. Results: Behavioral testing demonstrated increased cephalic allodynia in nitroglycerin‐ versus vehicle‐treated mice. An increase in the percent area covered by GFAP+ cells in the trigeminal nucleus caudalis and nucleus accumbens, but not the periaqueductal gray or somatosensory cortex, was observed in response to nitroglycerin. No significant differences were observed for Iba1 staining across brain regions. We did not detect significant sex differences in GFAP or Iba1 quantification. Conclusions: Immunohistochemical analysis suggests that, at the time point tested, immunoreactivity of GFAP+ astrocytes, but not Iba1+ microglia, changes in response to chronic migraine‐associated pain. Additionally, there do not appear to be significant differences between males and females in GFAP+ or Iba1+ cells across the four brain regions analyzed. Plain Language Summary: The aim of this study was to determine if supportive immune cells in the brains of males and females are altered in an animal model of chronic migraine. Mice in the chronic migraine group showed significant activation of astrocytes, but not microglia, in male and female mice in pain and emotion‐processing brain regions. These results suggest that some supportive cells in the brain may play a role in regulating chronic migraine. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes acute necrotizing encephalopathy (ANE), which has a high mortality rate and severe sequelae. This study aimed to identify ANE early and evaluate the usefulness of tocilizumab in ANE treatment. We retrospectively included eight paeefediatric ANE cases infected with SARS-CoV-2 at Xi'an Children's Hospital, China, from December 1, 2022 to May 1, 2023. A literature search was performed using the PUBMED, SPRING, SCOPUS, and EMBASE databases. This study included eleven patients. Clinical characteristics, laboratory test results, imaging features, and treatment options were analysed. Eight of the 19 cases (42 %) died, one (5 %) recovered, and nine (47 %) improved with residual neurological dysfunction. Eighteen patients presented with fever, with 56 % having ≥40 °C. Twelve patients (63 %) presented with dysfunction consciousness. Eight (42 %) patients experienced frequent convulsions. All eight patients in our hospital had elevated procalcitonin levels (mean: 21.32 ng/mL, range: 0.10–89.40 ng/mL). Alanine aminotransferase levels were elevated (mean: 632.81 U/L, range: 13.00–2251.00 U/L) in six patients. Seven patients showed elevated uric acid levels(mean: 396.50 μmol/L, range: 157.00–660.00 μmol/L). Brain imaging indicated that all the patients had symmetrical injuries to the bilateral thalami, accompanied by symmetrical injuries in the cerebrum, cerebellum, basal ganglia, and brain stem. Compared with the classical treatment (n = 9), the combination with tocilizumab (n = 6) showed a statistically difference in mortality (p = 0.028 < 0.05). The typical clinical manifestations of ANE in children with SARS-CoV-2 infection are acute onset with high fever, frequent convulsions and rapidly worsening disturbance of consciousness. Tocilizumab treatment could reduces mortality in ANE. • The mortality rate of ANE caused by SARS-CoV-2 was 42 %. • Main symptoms are high fever, frequent convulsions and rapidly worsening consciousness. • The thalamus and brainstem are the most common sites of injury. • Treatment with tocilizumab can help reduce the mortality. [ABSTRACT FROM AUTHOR]

Brainstem metastases are challenging to manage owing to the critical neurological structures involved. Although stereotactic radiotherapy (SRT) offers targeted high doses while minimizing damage to adjacent normal tissues, the optimal dose fractionation remains undefined. This study evaluated the efficacy and safety of multifraction SRT with an inhomogeneous dose distribution. This retrospective study included 31 patients who underwent 33 treatments for 35 brainstem lesions using linear accelerator-based multifraction SRT (30 Gy in five fractions, 35 Gy in five fractions or 42 Gy in 10 fractions) with an inhomogeneous dose distribution (median isodose, 51.9%). The outcomes of interest were local failure, toxicity and symptomatic failure. The median follow-up time after brainstem SRT for a lesion was 18.6 months (interquartile range, 10.0–24.3 months; range, 1.8–39.0 months). Grade 2 toxicities were observed in two lesions, and local failure occurred in three lesions. No grade 3 or higher toxicities were observed. The 1-year local and symptomatic failure rates were 8.8 and 16.7%, respectively. Toxicity was observed in two of seven treatments with a gross tumor volume (GTV) greater than 1 cc, whereas no toxicity was observed in treatments with a GTV less than 1 cc. No clear association was observed between the biologically effective dose of the maximum brainstem dose and the occurrence of toxicity. Our findings indicate that multifraction SRT with an inhomogeneous dose distribution offers a favorable balance between local control and toxicity in brainstem metastases. Larger multicenter studies are needed to validate these results and determine the optimal dose fractionation. [ABSTRACT FROM AUTHOR]