Brainstem Level Research Articles

The Lateralized Vestibular Stimulation: Effect on Mood, Cognition, and Autonomic States in Mental Disorders

The vestibular system in the inner ear senses the body's movements, which is essential for regulating reflex movements and body balance at the brain stem level. Still, it is also critical in regulating high brain functions, including mental states, motivation, mood, cognition, and reasoning. This article reviews the neuro-functional effects of lateralized vestibular stimulation in three main brain areas involved in mental disorders: the parieto–insular–vestibular cortex (PIVC), the hippocampus, and the hypothalamus. We discuss its implications for the performance of high-demanding works and possible therapeutic applications in psychiatric patients.

Musicianship Modulates Cortical Effects of Attention on Processing Musical Triads.

Background: Many studies have demonstrated the benefits of long-term music training (i.e., musicianship) on the neural processing of sound, including simple tones and speech. However, the effects of musicianship on the encoding of simultaneously presented pitches, in the form of complex musical chords, is less well established. Presumably, musicians' stronger familiarity and active experience with tonal music might enhance harmonic pitch representations, perhaps in an attention-dependent manner. Additionally, attention might influence chordal encoding differently across the auditory system. To this end, we explored the effects of long-term music training and attention on the processing of musical chords at the brainstem and cortical levels. Method: Young adult participants were separated into musician and nonmusician groups based on the extent of formal music training. While recording EEG, listeners heard isolated musical triads that differed only in the chordal third: major, minor, and detuned (4% sharper third from major). Participants were asked to correctly identify chords via key press during active stimulus blocks and watched a silent movie during passive blocks. We logged behavioral identification accuracy and reaction times and calculated information transfer based on the behavioral chord confusion patterns. EEG data were analyzed separately to distinguish between cortical (event-related potential, ERP) and subcortical (frequency-following response, FFR) evoked responses. Results: We found musicians were (expectedly) more accurate, though not faster, than nonmusicians in chordal identification. For subcortical FFRs, responses showed stimulus chord effects but no group differences. However, for cortical ERPs, whereas musicians displayed P2 (~150 ms) responses that were invariant to attention, nonmusicians displayed reduced P2 during passive listening. Listeners' degree of behavioral information transfer (i.e., success in distinguishing chords) was also better in musicians and correlated with their neural differentiation of chords in the ERPs (but not high-frequency FFRs). Conclusions: Our preliminary results suggest long-term music training strengthens even the passive cortical processing of musical sounds, supporting more automated brain processing of musical chords with less reliance on attention. Our results also suggest that the degree to which listeners can behaviorally distinguish chordal triads is directly related to their neural specificity to musical sounds primarily at cortical rather than subcortical levels. FFR attention effects were likely not observed due to the use of high-frequency stimuli (>220 Hz), which restrict FFRs to brainstem sources.

Effect of Level and Frequency of Forward Masker on Auditory Brainstem Response.

Forward masking (FM) is characterized by the perception of a signal being reduced or wholly masked due to a preceding sound (masker) of the same or different frequencies that offers a challenge for the auditory system to resolve. Considering that the off-frequency masker is expected to undergo linear processing compared to the on-frequency masker at the signal place, it reflects the peripheral auditory systems' compressive response. Thus, the present study focused on employing FM electrophysiological analogous such as auditory brainstem responses (ABR) to the behavioral masking experiments to objectively measure the frequency and level of processing in the auditory system, from the periphery to the brainstem level. The study was an observational research on 21 female volunteers. ABR was obtained using a tone-on-tone FM paradigm for 1000- and 4000-Hz probe stimuli. An experiment used two forward maskers, on-frequency and off-frequency, with varying levels from 50 to 70 dB SPL. A progressive shift for Vth peak latency and reduction in response amplitude was observed in proportion to the increase of masker level for both the probe stimuli and the masking experiments. However, ABR responses in neither masking condition were observed to differ between 60 and 70 dB SPL. FM ABR experiments are an assessment tool for estimating frequency and level processing in the auditory system, providing good efficiency, reliability, and less subject bias compared to behavioral measures.

Age-dependent deficits of auditory brainstem responses in juvenile Neurexin1α knockout rats.

Abnormal sensory processing is core to neuropsychiatric and neurodevelopmental disorders, such as schizophrenia and autism spectrum disorders. Developing efficient therapies requires understanding the basic sensory pathways and identifying circuit abnormalities during early development. Auditory brainstem responses (ABRs) are well-established biomarkers for auditory processing on the brainstem level. Beyond their advantage of being easily applicable in clinics (given their non-invasive nature), ABRs have high reproducibility in rodents and translate well to humans (e.g. wave identity), despite species differences (e.g. wave features). We hypothesized that ABRs would reveal sensory abnormalities in neurodevelopmental models with construct validity, such as Neurexin1α knockout (Nrxn1α KO) rats during their development. In a previous study, adult Nrxn1α KO rats showed altered cortical auditory-evoked potentials and impaired prediction error to auditory stimuli (Janz in Transl Psychiat, 12:455, 2022 ). This study used ABR measurements to assess brainstem physiology during auditory processing in Nrxn1α KO rats and their wild-type littermates. Therefore, we followed the development trajectories of ABRs from the age of 3weeks to 12weeks longitudinally. We found that juvenile Nrxn1α KO rats (3weeks of age) show altered ABRs, which normalized during further development. This alteration was confined to increased latency in waves II, III, and IV of the ABRs, suggesting impaired auditory processing on the level of the superior olivary complex and inferior colliculus. In conclusion, our results suggest that early but transient deficits in the processing of auditory information on the level of the brainstem are present in Nrxn1α KO rats, which may contribute to later cortical auditory processing deficits observed in adulthood. Our study emphasizes the value of ABRs as a functional readout of auditory brainstem circuit function with potential value as a translational biomarker.

Advancements in Pharmacological Interventions and Novel Therapeutic Approaches for Amyotrophic Lateral Sclerosis.

(1) Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease in which the patient suffers from an affection of both upper and lower motor neurons at the spinal and brainstem level, causing a progressive paralysis that leads to the patient's demise. Gender is also considered a predisposing risk factor for developing the disease. A brief review of the pathophysiological mechanisms of the disease is also described in this work. Despite the fact that a cure for ALS is currently unknown, there exists a variety of pharmacological and non-pharmacological therapies that can help reduce the progression of the disease over a certain period of time and alleviate symptoms. (2) We aim to analyze these pharmacological and non-pharmacological therapies through a systematic review. A comprehensive, multidisciplinary approach to treatment is necessary. (3) Drugs such as riluzole, edaravone, and sodium phenylbutyrate, among others, have been investigated. Additionally, it is important to stay updated on research on new drugs, such as masitinib, from which very good results have been obtained. (4) Therapies aimed at psychological support, speech and language, and physical therapy for the patient are also available, which increase the quality of life of the patients.

Long-lasting behavioral and neurochemical effects of early-life environmental enrichment in rats submitted to neonatal morphine administration.

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 (5μg/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).

Simultaneous cortical, subcortical, and brainstem mapping of sensory activation.

Nonpainful tactile sensory stimuli are processed in the cortex, subcortex, and brainstem. Recent functional magnetic resonance imaging studies have highlighted the value of whole-brain, systems-level investigation for examining sensory processing. However, whole-brain functional magnetic resonance imaging studies are uncommon, in part due to challenges with signal to noise when studying the brainstem. Furthermore, differentiation of small sensory brainstem structures such as the cuneate and gracile nuclei necessitates high-resolution imaging. To address this gap in systems-level sensory investigation, we employed a whole-brain, multi-echo functional magnetic resonance imaging acquisition at 3T with multi-echo independent component analysis denoising and brainstem-specific modeling to enable detection of activation across the entire sensory system. In healthy participants, we examined patterns of activity in response to nonpainful brushing of the right hand, left hand, and right foot (n= 10 per location), and found the expected lateralization, with distinct cortical and subcortical responses for upper and lower limb stimulation. At the brainstem level, we differentiated the adjacent cuneate and gracile nuclei, corresponding to hand and foot stimulation respectively. Our findings demonstrate that simultaneous cortical, subcortical, and brainstem mapping at 3T could be a key tool to understand the sensory system in both healthy individuals and clinical cohorts with sensory deficits.

The Current Status and Trends of Research Related to Vestibular Disorders, Vertigo, and Cognitive Impairment in the Elderly Population: A Bibliometric Analysis.

Background: The vestibular system not only supports reflex function at the brainstem level, but is also associated with higher levels of cognitive function. Vertigo due to vestibular disorders may lead to or be associated with cognitive dysfunction. Patients with deficits of both vestibular as well as cognitive function may be at particularly high risk for events like falls or certain diseases, such as Alzheimer's. Objective: To analyze the current state of research and trends in the global research literature regarding the correlation between vestibular disorders, vertigo, and cognitive impairment. Methods: We utilized Bibliometrix package to search databases including PubMed, Web of Science, etc for search terms. Results: Databases were searched up to December 15, 2022, and a total of 2222 publications were retrieved. Ultimately, 53 studies were included. A total of 261 authors published in 38 journals and conferences with an overall increasing annual growth rate of 6.94%. The most-published journal was Frontiers in Neurology. The most-published country was the United States, followed by Italy and Brazil. The most-published institution was Johns Hopkins University with a total of 13 articles. On performing trend analysis, we found that the most frequent focus of research in this field include the testing of vestibular perception, activation of the brain-related cortex, and the influence of stimulus-triggered vestibular snail reflex on visual space. The potential focal points are the risk of falling and the ability to extract spatial memory information, and the focus of research in recent decades has revolved around balance, falling, and Alzheimer's disease. Conclusions: Vestibular impairment in older adults affects cognitive function, particularly immediate memory, visuospatial cognition, and attention, with spatial cognition being the most significantly affected. In the future, virtual reality-based vestibular rehabilitation techniques and caloric stimulation could be potential interventions for the treatment of cognitive impairment.

SubSol-HIe is an AMPK-dependent hypoxia-responsive subnucleus of the nucleus tractus solitarius that coordinates the hypoxic ventilatory response and protects against apnoea in mice

Functional magnetic resonance imaging (fMRI) suggests that the hypoxic ventilatory response is facilitated by the AMP-activated protein kinase (AMPK), not at the carotid bodies, but within a subnucleus (Bregma -7.5 to -7.1 mm) of the nucleus tractus solitarius that exhibits right-sided bilateral asymmetry. Here, we map this subnucleus using cFos expression as a surrogate for neuronal activation and mice in which the genes encoding the AMPK-α1 (Prkaa1) and AMPK-α2 (Prkaa2) catalytic subunits were deleted in catecholaminergic cells by Cre expression via the tyrosine hydroxylase promoter. Comparative analysis of brainstem sections, relative to controls, revealed that AMPK-α1/α2 deletion inhibited, with right-sided bilateral asymmetry, cFos expression in and thus activation of a neuronal cluster that partially spanned three interconnected anatomical nuclei adjacent to the area postrema: SolDL (Bregma -7.44 mm to -7.48 mm), SolDM (Bregma -7.44 mm to -7.48 mm) and SubP (Bregma -7.48 mm to -7.56 mm). This approximates the volume identified by fMRI. Moreover, these nuclei are known to be in receipt of carotid body afferent inputs, and catecholaminergic neurons of SubP and SolDL innervate aspects of the ventrolateral medulla responsible for respiratory rhythmogenesis. Accordingly, AMPK-α1/α2 deletion attenuated hypoxia-evoked increases in minute ventilation (normalised to metabolism), reductions in expiration time, and increases sigh frequency, but increased apnoea frequency during hypoxia. The metabolic response to hypoxia in AMPK-α1/α2 knockout mice and the brainstem and spinal cord catecholamine levels were equivalent to controls. We conclude that within the brainstem an AMPK-dependent, hypoxia-responsive subnucleus partially spans SubP, SolDM and SolDL, namely SubSol-HIe, and is critical to coordination of active expiration, the hypoxic ventilatory response and defence against apnoea.

Whole brain pattern of iron accumulation in REM sleep behavior disorder.

Isolated REM sleep behavior disorder (iRBD) is an early stage of synucleinopathy with most patients progressing to Parkinson's disease (PD) or related conditions. Quantitative susceptibility mapping (QSM) in PD has identified pathological iron accumulation in the substantia nigra (SN) and variably also in basal ganglia and cortex. Analyzing whole-brain QSM across iRBD, PD, and healthy controls (HC) may help to ascertain the extent of neurodegeneration in prodromal synucleinopathy. 70 de novo PD patients, 70 iRBD patients, and 60 HCs underwent 3 T MRI. T1 and susceptibility-weighted images were acquired and processed to space standardized QSM. Voxel-based analyses of grey matter magnetic susceptibility differences comparing all groups were performed on the whole brain and upper brainstem levels with the statistical threshold set at family-wise error-corrected p-values <.05. Whole-brain analysis showed increased susceptibility in the bilateral fronto-parietal cortex of iRBD patients compared to both PD and HC. This was not associated with cortical thinning according to the cortical thickness analysis. Compared to iRBD, PD patients had increased susceptibility in the left amygdala and hippocampal region. Upper brainstem analysis revealed increased susceptibility within the bilateral SN for both PD and iRBD compared to HC; changes were located predominantly in nigrosome 1 in the former and nigrosome 2 in the latter group. In the iRBD group, abnormal dopamine transporter SPECT was associated with increased susceptibility in nigrosome 1. iRBD patients display greater fronto-parietal cortex involvement than incidental early-stage PD cohort indicating more widespread subclinical neuropathology. Dopaminergic degeneration in the substantia nigra is paralleled by susceptibility increase, mainly in nigrosome 1.

Serotonergic neurotransmission mediated cognitive dysfunction in two mouse models of sepsis-associated encephalopathy.

Patients with sepsis-associated encephalopathy (SAE) often exhibit cognitive impairments. Despite this, the underlying mechanisms of SAE remain largely unexplored. Here, we explored the role of serotonergic neurotransmission in cognitive dysfunction of two mouse models of SAE. The mouse models of SAE were established by injection of lipopolysaccharide (LPS, 10 mg/kg, intraperitoneal) and cecal ligation puncture (CLP) respectively. Barnes maze, new object recognition test and open field test were used to evaluate the effects of fluoxetine (selective serotonin reuptake inhibitor) and cyproheptadine (nonselective 5-HT2 receptor antagonist) on cognition and motor activity of mice. Additionally, WAY100635 (5-HT1A receptor antagonist) was co-administered with fluoxetine to explore the mechanism underlying effect of fluoxetine on cognitive impairments of SAE. Enzyme-linked immunosorbent assay (ELISA) was performed to determine 5-HT levels in hippocampus, brainstem and frontal lobe of experimental groups. Both LPS-induced sepsis and CLP induced sepsis resulted in a notable learning deficit. Fluoxetine ameliorated, while cyproheptadine aggravated, cognitive impairment in two classic mouse models of SAE. The cognition-enhancing effect of fluoxetine is reversed by WAY100635. Decreased 5-HT levels in hippocampus, brainstem and frontal lobe were observed in LPS septic model and CLP septic model. Notably, both fluoxetine and cyproheptadine significantly increased 5-HT levels in those brain regions in LPS septic model. Additionally, fluoxetine significantly increased 5-HT levels in frontal lobe of CLP septic model. Our study demonstrated that serotonergic neurotransmission plays a significant role in mechanisms underlying cognitive impairment in SAE. These findings contribute to identification of novel targets to prevent and arrest cognitive impairment in SAE.

Systematic review and co-ordinate based meta-analysis to summarize the utilization of functional brain imaging in conjunction with human models of peripheral and central sensitization.

Functional magnetic resonance imaging, in conjunction with models of peripheral and/or central sensitization, has been used to assess analgesic efficacy in healthy humans. This review aims to summarize the use of these techniques to characterize brain mechanisms of hyperalgesia/allodynia and to evaluate the efficacy of analgesics. Searches were performed (PubMed-Medline, Cochrane, Web of Science and Clinicaltrials.gov) to identify and review studies. A co-ordinate based meta-analysis (CBMA) was conducted to quantify neural activity that was reported across multiple independent studies in the hyperalgesic condition compared to control, using GingerALE software. Of 217 publications, 30 studies met the inclusion criteria. They studied nine different models of hyperalgesia/allodynia assessed in the primary (14) or secondary hyperalgesia zone (16). Twenty-three studies focused on neural correlates of hyperalgesic conditions and showed consistent changes in the somatosensory cortex, prefrontal cortices, insular cortex, anterior cingulate cortex, thalamus and brainstem. The CBMA on 12 studies that reported activation coordinates for a contrast comparing the hyperalgesic state to control produced six activation clusters (significant at false discovery rate of 0.05) with more peaks for secondary (17.7) than primary zones (7.3). Seven studies showed modulation of brain activity by analgesics in five of the clusters but also in four additional regions. This meta-analysis revealed substantial but incomplete overlap between brain areas related to neural mechanisms of hyperalgesia and those reflecting the efficacy of analgesic drugs. Studies testing in the secondary zone were more sensitive to evaluate analgesic efficacy on central sensitization at brainstem or thalamocortical levels. Experimental pain models that provide a surrogate for features of pathological pain conditions in healthy humans and functional imaging techniques are both highly valuable research tools. This review shows that when used together, they provide a wealth of information about brain activity during pain states and analgesia. These tools are promising candidates to help bridge the gap between animal and human studies, to improve translatability and provide opportunities for identification of new targets for back-translation to animal studies.

Unilateral periocular spasm.

Hemifacial spasm is an uncontrollable, recurrent facial muscular contraction that typically occurs on one side of the face, cannot be suppressed, and can last the entire day and during sleep. The most common underlying cause of facial nerve compression is an enlarged or abnormal tracking blood vessel at the brainstem level. Clinical diagnoses are frequently based on a patient's medical history and physical examination. Before deciding on a course of action, however, an electromyogram and MRI are performed to determine the underlying cause. Due to its high effectiveness (success rates of 85% to 95%) and low frequency of adverse reactions, botulinum toxin is the preferred therapy for hemifacial spasm and can provide transient symptomatic alleviation. Surgical microvascular decompression is a therapeutic approach that targets the underlying cause of this condition and has an average success rate of 85%.

Brainstem auditory evoked potential variability in unmedicated schizophrenic patients

Background: Schizophrenia (SCZ) is one of the most incapacitating and financially disastrous medical conditions and ranks among the most severe and burdensome diseases in the world due to the onset, progression, and frequency of disability. Few researches have been reported that SCZ is linked to a number of neurophysiological abnormalities, including changes in brainstem auditory evoked potentials (BAEPs). Aims and Objectives: The current study aimedto measure brainstem function using BAEPs in patients with SCZ and compare their findings with healthy controls. Materials and Methods: A cross-sectional case–control study was conducted on 51 schizophrenic drug-naive patients selected from the outpatient department of psychiatry, fulfilling the diagnostic criteria of DSM-IV, aged 18-28 years, male and female, with a matching control group of 50 subjects recruited from patients’ relatives. For assessing the severity of SCZ, the positive and negative syndrome scale was utilized. The BAEPs were recorded using a brainstem-evoked response audiometry (BERA) device (NeuroStim-NS 2). Data were analyzed using Independent t-test and Mann–Whitney test based on normality. P-value was considered significant at P &lt; 0.05, P &lt; 0.01 level. Results: A significant difference was observed in patients and control group BAEPs. The absolute latency of waves I and III in the right ear, waves I and V, IPL I-III in the left ear was shown to be significantly different. The results demonstrate that the patient group’s mean latency was higher than the controls. Conclusion: Based on findings, it was concluded that abnormal BAEPs in schizophrenic patients might be attributed to their primary symptom of discontinuity in perceptual and other cerebral functions and slower transmission in the lower brainstem auditory pathway and decreased activity at the brainstem level.

The Effects of a Home Personal Computer-based Auditory Training Program on the Binaural Listening Skills of Children With Specific Learning Disability: A Protocol for a Randomized Clinical Trial

Background and Objectives: A high prevalence of central auditory processing disorders has been reported in children with learning disabilities. One of the crucial auditory processing disorders in these children is a binaural processing problem. Binaural hearing leads to improved auditory performance in noisy situations. This research aims to develop an auditory training program based on binaural interaction at the brainstem level and to investigate its effect on the binaural listening skills of children with a specific learning disability. Methods: After developing the rehabilitation program and determining its validity, this intervention study is conducted in three stages. The first stage includes baseline assessments, the second stage includes the implementation of rehabilitation intervention and the third stage consists of the re-implementation of the tests of the first stage once immediately after intervention and then once after 45 days of training. Masking level differences (MLD), Persian auditory recognition of words in noise (PARWIN), and binaural speech-auditory brainstem response (Speech-ABR) tests are the primary outcome measures. Persian randomized dichotic digits test (PRDDT), Persian pediatric competing word test (PPCWT), Persian pediatric competing sentences test (PPCST), and Persian version of the auditory processing disorder questionnaire (APDQ-P) were included as secondary outcome measures. The sample size in each intervention and control group was 15 people and the duration of training was 3 months. Conclusion: Considering the importance of brainstem function in binaural hearing, it is recommended to investigate the effectiveness of the developed binaural interaction training program in improving hearing in background noise in children with specific learning disabilities.

MRI evaluation of trigeminal neuralgia patients in a rural hospital of central India

Background Trigeminal neuralgia is characterized by repetitive paroxysmal electric shock-like pain in the trigeminal nerve distribution. The most common cause implicated in this condition is neurovascular conflict, primarily by the superior cerebellar artery in the prepontine cistern. Other common causes include cerebellopontine angle tumours and aneurysms at the brainstem level. Magnetic resonance imaging (MRI) is the imaging modality of choice in evaluating trigeminal neuralgia, with 3D-FIESTA (Fast Imaging employing steady-state acquisition) being the mainstay for assessing neurovascular conflict. This study’s objective is to assess the role of MRI in evaluating trigeminal neuralgia and to study the spectrum of MRI findings associated with various causes. Methods The study type is a cross-sectional observational prospective study conducted at Acharya Vinoba Bhave Rural Hospital, Sawangi, on 41 patients coming to the Radiology department with clinical suspicion of trigeminal neuralgia. Descriptive statistics will summarize participants’ imaging characteristics. At the same time, comparison tests will be employed to assess the association between imaging features and diagnosis of MRI with the distribution of patient symptoms, laterality, aetiology, artery, and branch of trigeminal nerve involved. Considering ethical concerns, participants’ privacy will be protected, and all data will be handled with the utmost confidentiality.

Quantitative brainstem and spinal MRI in amyotrophic lateral sclerosis: implications for predicting noninvasive ventilation needs.

Respiratory complications resulting from motor neurons degeneration are the primary cause of death in amyotrophic lateral sclerosis (ALS). Predicting the need for non-invasive ventilation (NIV) in ALS is important for advance care planning and clinical trial design. The aim of this study was to assess the potential of quantitative MRI at the brainstem and spinal cord levels to predict the need for NIV during the first six months after diagnosis. Forty-one ALS patients underwent MRI and spirometry shortly after diagnosis. The need for NIV was monitored according to French health guidelines for 6 months. The performance of four regression models based on: clinical variables, brainstem structures volumes, cervical spinal measurements, and combined variables were compared to predict the need for NIV within this period. Both the clinical model (R2 = 0.28, AUC = 0.85, AICc = 42.67, BIC = 49.8) and the brainstem structures' volumes model (R2 = 0.30, AUC = 0.85, AICc = 40.13, BIC = 46.99) demonstrated good predictive performance. In addition, cervical spinal cord measurements model similar performance (R2 = 0.338, AUC = 0.87, AICc = 37.99, BIC = 44.49). Notably, the combined model incorporating predictors from all three models yielded the best performance (R2 = 0.60, AUC = 0.959, AICc = 36.38, BIC = 44.8). These findings are supported by observed positive correlations between brainstem volumes, cervical (C4/C7) cross-sectional area, and spirometry-measured lung volumes. Our study shows that brainstem volumes and spinal cord area are promising measures to predict respiratory intervention needs in ALS.

Reduction of Distortion Artifacts in Brain MRI Using a Field Map-based Correction Technique in Diffusion-weighted Imaging

PurposeThe aim of this study was to evaluate the image quality and feasibility of a field map-based technique to correct for susceptibility-induced geometric distortions which are typical for diffusion EPI brain imaging.MethodsWe prospectively included 52 patients during clinical routine in this single-center study. All scans were performed on a 3T MRI. Patients’ indications for MRI mainly consisted of suspected stroke due to the clinical presentation. For the morphological comparison of the corrected and uncorrected EPI diffusion, three experienced radiologists assessed the image quality of the sequences in a blinded and randomized fashion using a Likert scale (1 being poor; 5 being excellent). To ensure comparability of the two methods, an additional quantitative analysis of the apparent diffusion coefficient (ADC) was performed.ResultsCorrected EPI diffusion was rated significantly superior in all the selected categories: overall level of artifacts (p < 0.001), degree of distortion at the frontal, temporal, occipital and brainstem levels (p < 0.001), conspicuousness of ischemic lesions (p < 0.001), image quality (p < 0.001), naturality (p < 0.001), contrast (p < 0.001), and diagnostic confidence (p < 0.001).ConclusionCorrected EPI diffusion offers a significant reduction of geometric distortion in all evaluated brain regions and an improved conspicuousness of ischemic lesions. Image quality, overall artifacts, naturality, contrast and diagnostic confidence were also rated superior in comparison to uncorrected EPI diffusion.

The medullary serotonergic centres involved in cardiorespiratory control are disrupted by fetal growth restriction.

Fetal growth restriction (FGR) is associated with cardiovascular and respiratory complications after birth and beyond. Despite research showing a range of neurological changes following FGR, little is known about how FGR affects the brainstem cardiorespiratory control centres. The primary neurons that release serotonin reside in the brainstem cardiorespiratory control centres and may be affected by FGR. At two time points in the last trimester of sheep brain development, 110 and 127days of gestation (0.74 and 0.86 of gestation), we assessed histopathological alterations in the brainstem cardiorespiratory control centres of the pons and medulla in early-onset FGR versus control fetal sheep. The FGR cohort were hypoxaemic and asymmetrically growth restricted. Compared to the controls, the brainstem of FGR fetuses exhibited signs of neuropathology, including elevated cell death and reduced cell proliferation, grey and white matter deficits, and evidence of oxidative stress and neuroinflammation. FGR brainstem pathology was predominantly observed in the medullary raphé nuclei, hypoglossal nucleus, nucleus ambiguous, solitary tract and nucleus of the solitary tract. The FGR groups showed imbalanced brainstem serotonin and serotonin 1A receptor abundance in the medullary raphé nuclei, despite evidence of increased serotonin staining within vascular regions of placentomes collected from FGR fetuses. Our findings demonstrate both early and adaptive brainstem neuropathology in response to placental insufficiency. KEY POINTS: Early-onset fetal growth restriction (FGR) was induced in fetal sheep, resulting in chronic fetal hypoxaemia. Growth-restricted fetuses exhibit persistent neuropathology in brainstem nuclei, characterised by disrupted cell proliferation and reduced neuronal cell number within critical centres responsible for the regulation of cardiovascular and respiratory functions. Elevated brainstem inflammation and oxidative stress suggest potential mechanisms contributing to the observed neuropathological changes. Both placental and brainstem levels of 5-HT were found to be impaired following FGR.

Neuroinflammation in Pathogenesis of Audiogenic Epilepsy: Altered Proinflammatory Cytokine Levels in the Rats of Krushinsky–Molodkina Seizure-Prone Strain

Neuroinflammation plays an important role in epileptogenesis, however, most studies are performed using pharmacological models of epilepsy, while there are only few data available for non-invasive, including genetic, models. The levels of a number of pro-inflammatory cytokines were examined in the Krushinsky-Molodkina (KM) rat strain with high audiogenic epilepsy (AE) proneness (intense tonic seizure fit in response to loud sound) and in the control strain "0" (not predisposed to AE) using multiplex immunofluorescence magnetic assay (MILLIPLEX map Kit). Cytokine levels were determined in the dorsal striatum tissue and in the brain stem. Background levels of IL-1β, IL-6, and TNF-α in the dorsal striatum of the KM rats were significantly lower than in the rats "0" (by 32.31, 27.84, and 38.87%, respectively, p < 0.05, 0.05, and 0.01), whereas no inter-strain differences in the levels of these metabolites were detected in the brain stem in the "background" state. Four hours after sound exposure, the TNF-α level in the dorsal striatum of the KM rats was significantly lower (by 38.34%, p < 0.01) than in the "0" rats. In the KM rats, the dorsal striatal levels of IL-1β and IL-6 were significantly higher after the sound exposure and subsequent seizure fit, compared to the background (35.29 and 50.21% increase, p < 0.05, 0.01, respectively). In the background state the IL-2 level in the KM rats was not detected, whereas after audiogenic seizures its level was 14.01 pg/ml (significant difference, p < 0.01). In the KM rats the brain stem levels of IL-1β and TNF-α after audiogenic seizures were significantly lower than in the background (13.23 and 23.44% decrease, respectively, p < 0.05). In the rats of the "0" strain, the levels of cytokines in the dorsal striatum after the action of sound (which did not induce AE seizures) were not different from those of the background, while in the brain stem of the "0" strain the levels of IL-1β were lower than in the background (40.28%, p < 0.01). Thus, the differences between the background levels of cytokines and those after the action of sound were different in the rats with different proneness to AE. These data suggest involvement of the analyzed cytokines in pathophysiology of the seizure state, namely in AE seizures.