Brainstem Pathways Research Articles

TDCS Cranial Nerve Co-Stimulation: Unveiling Brainstem Pathways Involved in Trigeminal Nerve Direct Current Stimulation in Rats.

The effects of transcranial direct current stimulation (tDCS) are typically attributed to the polarization of cortical neurons by the weak electric fields it generates in the cortex. However, emerging evidence indicates that certain tDCS effects may be mediated through the co-stimulation of peripheral or cranial nerves, particularly the trigeminal nerve (TN), which projects to critical brainstem nuclei that regulate the release of various neurotransmitters throughout the central nervous system. Despite this, the specific pathways involved remain inadequately characterized. In this study, we examined the effects of acute transcutaneous TN direct current stimulation (TN-DCS) on tonic (i.e. mean spike rate and spike rate over time) and phasic (number of bursts, spike rate per burst, burst duration, and inter-burst interval) activities while simultaneously recording single-neuron activity across three brainstem nuclei in rats: the locus coeruleus (LC), dorsal raphe nucleus (DRN), and median raphe nucleus (MnRN). We found that TN-DCS significantly modulated tonic activity in the LC, with notable interactions between stimulation amplitude, polarity, and time epoch affecting mean spike rates. Similar effects were observed in the DRN regarding tonic activity. Further, phasic activity in the LC was influenced by TN-DCS, with changes in burst number, duration, and inter-burst intervals linked to stimulation parameters. Conversely, MnRN tonic activity following TN-DCS remained unchanged. Importantly, xylocaine administration to block TN abolished the effects on tonic activities in both the LC and DRN. These results suggest that tDCS effects may partially arise from indirect modulation of the TN, leading to altered neuronal activity in DRN and LC. Besides, the differential changes in tonic and phasic LC activities underscore their complementary roles in mediating TN-DCS effects on higher cortical regions. This research bears significant translational implications, providing mechanistic insights that could enhance the efficacy of tDCS applications and deepen our understanding of its neurophysiological effects.

Disorders of gut-brain interaction through the lens of polyvagal theory.

This paper introduces a metric capable of tracking a hypothetical brainstem "switching" mechanism involved in regulating the afferent influence of blood pressure on the vagal efferent control of heart rate. In theory, this metric could be applied to evaluate the "efficiency" of brainstem pathways involved in common mechanisms of autonomic function involving the vagal influences on the gut as well as the heart. Thus, by exploring the dynamic "efficiency" of the brainstem feedback circuit linking heart rate to posture, a clinically relevant index of vagal flexibility might be extracted that would provide a generalizable window into the vagal regulation of both the heart and gut. Recent research supports this contention and has documented that this metric, VE, appears to covary with disorders of the gut. Clinical application of this metric might identify individual vulnerabilities that frequently reflect symptoms assumed to have features of a dysregulated autonomic nervous system (i.e., dysautonomia). If this is confirmed by additional research, then this objective measure of neural regulation of autonomic function might provide insight into the pathogenesis of disorders of gut-brain interaction.

Atlas-based assessment of hypomyelination: Quantitative MRI in Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease (PMD) is a rare childhood hypomyelinating leukodystrophy. Quantification of the pronounced myelin deficit and delineation of subtle myelination processes are of high clinical interest. Quantitative magnetic resonance imaging (qMRI) techniques can provide in vivo insights into myelination status, its spatial distribution, and dynamics during brain maturation. They may serve as potential biomarkers to assess the efficacy of myelin-modulating therapies. However, registration techniques for image quantification and statistical comparison of affected pediatric brains, especially those of low or deviant image tissue contrast, with healthy controls are not yet established. This study aimed first to develop and compare postprocessing pipelines for atlas-based quantification of qMRI data in pediatric patients with PMD and evaluate their registration accuracy. Second, to apply an optimized pipeline to investigate spatial myelin deficiency using myelin water imaging (MWI) data from patients with PMD and healthy controls. This retrospective single-center study included five patients with PMD (mean age, 6 years ± 3.8) who underwent conventional brain MRI and diffusion tensor imaging (DTI), with MWI data available for a subset of patients. Three methods of registering PMD images to a pediatric template were investigated. These were based on (a) T1-weighted (T1w) images, (b) fractional anisotropy (FA) maps, and (c) a combination of T1w, T2-weighted, and FA images in a multimodal approach. Registration accuracy was determined by visual inspection and calculated using the structural similarity index method (SSIM). SSIM values for the registration approaches were compared using a t test. Myelin water fraction (MWF) was quantified from MWI data as an assessment of relative myelination. Mean MWF was obtained from two PMDs (mean age, 3.1 years ± 0.3) within four major white matter (WM) pathways of a pediatric atlas and compared to seven healthy controls (mean age, 3 years ± 0.2) using a Mann-Whitney U test. Our results show that visual registration accuracy estimation and computed SSIM were highest for FA-based registration, followed by multimodal, and T1w-based registration (SSIMFA = 0.67 ± 0.04 vs. SSIMmultimodal = 0.60 ± 0.03 vs. SSIMT1 = 0.40 ± 0.14). Mean MWF of patients with PMD within the WM pathways was significantly lower than in healthy controls MWFPMD = 0.0267 ± 0.021 vs. MWFcontrols = 0.1299 ± 0.039. Specifically, MWF was measurable in brain structures known to be myelinated at birth (brainstem) or postnatally (projection fibers) but was scarcely detectable in other brain regions (commissural and association fibers). Taken together, our results indicate that registration accuracy was highest with an FA-based registration pipeline, providing an alternative to conventional T1w-based registration approaches in the case of hypomyelinating leukodystrophies missing normative intrinsic tissue contrasts. The applied atlas-based analysis of MWF data revealed that the extent of spatial myelin deficiency in patients with PMD was most pronounced in commissural and association and to a lesser degree in brainstem and projection pathways.

Interplay between subthalamic nucleus and spinal cord controls parkinsonian nociceptive disorders.

Pain is a non-motor symptom that impairs quality of life in Parkinson's patients. Pathological nociceptive hypersensitivity in patients could be due to changes in the processing of somatosensory information at the level of the basal ganglia, including the subthalamic nucleus (STN), but the underlying mechanisms are not yet defined. Here, we investigated the interaction between the STN and the dorsal horn of the spinal cord (DHSC), by first examining the nature of STN neurons that respond to peripheral nociceptive stimulation and the nature of their responses under normal and pathological conditions. Next, we studied the consequences of deep brain stimulation (DBS) of the STN on the electrical activity of DHSC neurons. Then, we investigated whether the therapeutic effect of STN-DBS would be mediated by the brainstem descending pathway involving the rostral ventromedial medulla (RVM). Finally, to better understand how the STN modulates allodynia, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) expressed in the STN. The study was carried out on the 6-OHDA rodent model of Parkinson's disease, obtained by stereotactic injection of the neurotoxin into the medial forebrain bundle of rats and mice. In these animals, we used motor and nociceptive behavioral tests, in vivo electrophysiology of STN and wide dynamic range (WDR) DHSC neurons in response to peripheral stimulation, deep brain stimulation of the STN and the selective DREADD approach. Vglut2-ires-cre mice were used to specifically target and inhibit STN glutamatergic neurons. STN neurons are able to detect nociceptive stimuli, encode their intensity and generate windup-like plasticity, like WDR neurons in the DHSC. These phenomena are impaired in dopamine-depleted animals, as the intensity response is altered in both spinal and subthalamic neurons. Furthermore, As with L-Dopa, STN-DBS in rats ameliorated 6-OHDA-induced allodynia, and this effect is mediated by descending brainstem projections leading to normalization of nociceptive integration in DHSC neurons. Furthermore, this therapeutic effect was reproduced by selective inhibition of STN glutamatergic neurons in Vglut2-ires-cre mice. Our study highlights the centrality of the STN in nociceptive circuits, its interaction with the DHSC and its key involvement in pain sensation in Parkinson's disease. Furthermore, our results provide for the first-time evidence that subthalamic DBS produces analgesia by normalizing the responses of spinal WDR neurons via descending brainstem pathways. These effects are due to direct inhibition, rather than activation of glutamatergic neurons in the STN or passage fibers, as shown in the DREADDs experiment.

Disrupted Resting-State Functional Connectivity and Effective Connectivity of the Nucleus Accumbens in Chronic Low Back Pain: A Cross-Sectional Study.

Chronic low back pain (cLBP) is a recurring and intractable disease that is often accompanied by emotional and cognitive disorders such as depression and anxiety. The nucleus accumbens (NAc) plays an important role in mediating emotional and cognitive processes and analgesia. This study investigated the resting-state functional connectivity (rsFC) and effective connectivity (EC) of NAc and its subregions in cLBP. Thirty-four cLBP patients and 34 age- and sex-matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based rsFC and Dynamic Causal Modelling (DCM) were used to examine the alteration of the rsFC and EC of the NAc. Our results showed that the cLBP group had increased rsFC of the bilateral NAc-left superior frontal cortex (SFC), orbital frontal cortex (OFC), left angular gyrus, the left NAc-bilateral middle temporal gyrus, as well as decreased rsFC of left NAc-left supramarginal gyrus, right precentral gyrus, left cerebellum, brainstem (medulla oblongata), and right insula pathways compared with the HC; the results of the subregions were largely consistentwiththe whole NAc. In addition, the rsFC of the left NAc-left SFC was negatively correlated with Hamilton's Depression Scale (HAMD) scores (r = -0.402, p = 0.018), and the rsFC of left NAc-OFC was positively correlated with present pain intensity scores (r = 0.406, p = 0.017) in the cLBP group. DCM showed that the cLBP group showed significantly increased EC from the left cerebellum to the right NAc (p = 0.012) as compared with HC. Overall, our findings demonstrate aberrant rsFC and EC between NAc and regions that are associated with emotional regulation and cognitive processing in individuals with cLBP, underscoring the pivotal roles of emotion and cognition in cLBP.

Comparison of MRI findings of hypothalamic-optic chiasmatic gliomas and craniopharyngiomas.

Differential diagnosis of hypothalamic-optic chiasmatic gliomas (HOCGs) and craniopharyngiomas on magnetic resonance imaging (MRI) can be quite challenging. To compare the MRI features of HOCGs and cranipharyngiomas. Patients diagnosed with HOCG or craniopharyngioma in histopathological evaluation between 2012 and 2022 and who underwent preoperative contrast-enhanced brain MRI were included. Various MRI features were retrospectively evaluated for each lesion: T2-weighted imaging and fluid attenuation inversion recovery hyperintensity, calcification, cystic change, T1-weighted (T1W) imaging hyperintensity of the cystic component, hemorrhage, involvement of sellar, suprasellar or other adjacent structures, lobulated appearance, presence of hydrocephalus, and contrast enhancement pattern. Apparent diffusion coefficient (ADC) values were also evaluated and compared. Among 38 patients included, 13 (34%) had HOCG and 25 (66%) had craniopharyngioma. Craniopharyngiomas had a significantly higher rate of cystic changes, calcification, and T1W imaging hyperintensity of the cystic component than HOCGs (P <0.05). Of HOCGs, 92% had chiasm involvement, 23% had optic nerve involvement, and 31% had brain stem involvement. On the other hand, chiasm involvement was observed in 8% of craniopharyngiomas, but none had optic nerve and/or brain stem involvement (P <0.05). While 62% (8/13) of HOCGs had diffuse homogeneous enhancement, 80% (20/25) of craniopharyngiomas had a diffuse heterogeneous enhancement pattern. Mean ADC values were significantly higher in craniopharyngiomas compared to HOCGs (2.1 vs. 1.6 ×10-3mm2/s, P <0.05). Although some neuroimaging findings may overlap, features such as presence of cyst and calcification, brain stem and optic pathway involvement, different enhancement patterns, and ADC values may be helpful in the differential diagnosis of HOCGs and craniopharyngiomas.

Activity in the pontine reticular nuclei scales with handgrip force in humans.

The neural pathways that contribute to force production in humans are currently poorly understood, as the relative roles of the corticospinal tract and brainstem pathways, such as the reticulospinal tract (RST), vary substantially across species. Using functional magnetic resonance imaging (fMRI), we aimed to measure activation in the pontine reticular nuclei (PRN) during different submaximal handgrip contractions to determine the potential role of the PRN in force modulation. Thirteen neurologically intact participants (age: 28 ± 6 yr) performed unilateral handgrip contractions at 25%, 50%, 75% of maximum voluntary contraction during brain scans. We quantified the magnitude of PRN activation from the contralateral and ipsilateral sides during each of the three contraction intensities. A repeated-measures ANOVA demonstrated a significant main effect of force (P = 0.012, [Formula: see text] = 0.307) for PRN activation, independent of side (i.e., activation increased with force for both contralateral and ipsilateral nuclei). Further analyses of these data involved calculating the linear slope between the magnitude of activation and handgrip force for each region of interest (ROI) at the individual-level. One-sample t tests on the slopes revealed significant group-level scaling for the PRN bilaterally, but only the ipsilateral PRN remained significant after correcting for multiple comparisons. We show evidence of task-dependent activation in the PRN that was positively related to handgrip force. These data build on a growing body of literature that highlights the RST as a functionally relevant motor pathway for force modulation in humans.NEW & NOTEWORTHY In this study, we used a task-based functional magnetic resonance imaging (fMRI) paradigm to show that activity in the pontine reticular nuclei scales linearly with increasing force during a handgrip task. These findings directly support recently proposed hypotheses that the reticulospinal tract may play an important role in modulating force production in humans.

Evaluation of cochlear and auditory brainstem functions in COVID-19 patients; a case control study

BackgroundMany viral infections can cause hearing loss due to affection of cochlear hair cells or neurogenic pathway. Although, the damage secondary to viral infections is mainly cochlear affection; auditory brainstem can be affected as well. It was predicted that SARS-COV-2 infection can similarly affect the auditory system. This study aimed to detect affection in auditory system and if present investigate the possible site of lesion (up to the level of the brain stem) in relation to COVID-19 infection.MethodsThis is a case control study, where the study group constituted of thirty adults, diagnosed with COVID-19 at least 2 weeks prior to testing and up to 6 months, without previous auditory complaints pre-COVID-19 or other risk factors that could affect the auditory pathway. Fifteen adult participants that were age and gender matched to the study group with no previous history of covid-19 infection constituted the control group. Audiological evaluations done to all participants were pure-tone and speech audiometry, tympanometry, transient-evoked otoacoustic emission with and without contralateral suppression and auditory brainstem response measurements.ResultsThe study group showed significantly worse pure tone thresholds at high frequencies 4 and 8 kHz (p < 0.01), significantly worse transient-evoked otoacoustic emission signal to noise ratio at 2800 Hz and 4000 Hz (p < 0.05) and significantly lower total suppression index (p<0.05). On the other hand, there was no significant difference between both groups in auditory brainstem response wave latencies (p > 0.05).ConclusionCOVID-19 had subtle effect on cochlear basal turn, and it is shown that the auditory efferent system may also be affected, while the auditory nerve and afferent brainstem pathways seems to be spared. Moreover, the absence of the symptoms of auditory dysfunction postcovid-19 does not guarantee normal auditory functions.

Clinical Potential of Transcranial Focused Ultrasound for Neurorehabilitation in Pediatric Cancer Survivors.

Cancer survivors are at a high risk for treatment-related late effects, particularly neurocognitive impairment in the attention and executive function domains. These can be compounded in pediatric populations still undergoing neural development, which has increased interest in survivorship studies and neurorehabilitation approaches to mitigate these effects. Cognitive training regimens have shown promise as a therapeutic intervention for improving cognitive function. Therapist-guided and computerized training programs with adaptive paradigms have been successfully implemented in pediatric populations, with positive outcomes on attention and working memory. Another interventional approach is neuromodulation to alter plasticity. Transcranial electrical stimulation can modulate cortical surface activity, and cranial nerve stimulation alters autonomic activity in afferent brainstem pathways. However, they are more systemic in nature and have diffuse spatial targeting. Transcranial focused ultrasound (tFUS) modulation overcomes these limitations with high spatial specificity and the ability to target deeper brain regions. In this review, we discuss the efficacy of tFUS for modulating specific brain regions and its potential utility to augment cognitive training programs as a complementary intervention.

Soft Tissue Conduction Activates the Auditory Pathway in the Brain.

Soft tissue conduction is a mode of hearing which differs from air and bone conduction since the soft tissues of the body convey the audio-frequency vibrations to the ear. It is elicited by inducing soft tissue vibrations with an external vibrator applied to sites on the body or by intrinsic vibrations resulting from vocalization or the heartbeat. However, the same external vibrator applied to the skin sites also excites cutaneous mechanoreceptors, and attempts have been made to assist patients with hearing loss by audio-tactile substitution. The present study was conducted to assess the contribution of the auditory nerve and brainstem pathways to soft tissue conduction hearing. The study involved 20 normal hearing students, equipped with ear plugs to reduce the possibility of their response to air-conducted sounds produced by the external vibrator. Pure tone audiograms and speech reception (recognition) thresholds were determined in response to the delivery of the stimuli by a clinical bone vibrator applied to the cheek, neck and shoulder. Pure tone and speech recognition thresholds were obtained; the participants were able to repeat the words they heard by soft tissue conduction, confirming that the auditory pathways in the brain had been stimulated, with minimal involvement of the somatosensory pathways.

Evaluation of intracranial stereotactic treatment plans: a comparison study of CyberKnife and TrueBeam systems

Abstract Background: Stereotactic radiotherapy (SRT) for patients with intracranial tumours are delivered using a dedicated platform or a conventional linear accelerator with a flattening filter-free beam. Materials and methods: This study compares treatment plans with intracranial tumours. A total of 29 patients were treated on CyberKnife and planned using the Accuray Precision. The same structure sets ws then exported to Varian Eclipse, and plans were made using a 6 MV FFF beam. Both plans were compared for parameters of target coverage, homogeneity index (HI), new conformity index (nCI), gradient index, selectivity index (SI), volumetric and OAR doses. Results: The treatment plans made for CyberKnife exhibit better results in terms of nCI (1·168 ± 0·08 versus 1·173 ± 0·077), SI (0·885 ± 0·05 versus 0·877 ± 0·05) and GI (3·64 ± 0·5 versus 4·45 ± 1·25), while HI values are better for TrueBeam. For OAR doses, in 65·5% and 72% of treatment plans, brainstem and optic pathways received lower doses on CyberKnife, respectively. In terms of dose spillage, Truebeam plans are better for very low doses (V5%), while for V10%, V20% and V50% CyberKnife plans are better. Conclusion: CyberKnife is a better modality for the delivery of SRS/SRT to intracranial tumours except for dose homogeneity where TrueBeam offered better results.

Body Mass Index, but not Visceral Abdominal Obesity and Insulin Resistance, Negatively Impacts White Matter Microstructure in Midlife

AbstractBackgroundMidlife obesity, as evidenced by high body mass index (BMI), is increasingly understood as a risk factor for development of Alzheimer’s disease. Importantly, visceral fat, by producing adipokines, contributes to inflammation as well as insulin resistance, mechanisms involved in development of Alzheimer’s disease. Herein, we aimed to assess association of white matter microstructure, measured by Diffusion tensor imaging (DTI), with obesity and abdominal adipose tissue composition at midlife.MethodA total of 34 middle‐aged (age: 51.27 ± 6.12 years, BMI: 32.28 ± 6.39 kg/m2), cognitively normal participants, underwent bloodwork, brain and abdominal MRI. Insulin resistance status was assessed using Homeostatic Model Assessment for Insulin Resistance. Abdominal visceral and subcutaneous adipose tissue (VAT, SAT) were automatically segmented using VOXel Analysis Suite (Voxa) and VAT/SAT ratio was calculated. A diffusion spectrum imaging scheme with a total of 98 diffusion samplings and a voxel size of 2 mm was acquired. Using DSI studio (https://dsi‐studio.labsolver.org/), the diffusion data were reconstructed using generalized q‐sampling imaging and the tensor metrics were calculated. Fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, RD, respectively) for white matter tracts were compared across study groups using one‐way ANOVA. Multiple regression models with sex, age, and education as covariates were used to assess the association of BMI, VAT/SAT ratio, and HOMA‐IR with DTI metrics.ResultOur data showed that BMI was negatively associated with AD values in right inferior fronto‐occipital fasciculus, tapetum and forceps major of Corpus Callosum (CC), superior and middle cerebellar peduncle, and bilateral reticular tract. The negative association of BMI with AD values in tapetum of CC was significant only in women. Right reticular tract MD and superior cerebellar peduncle MD and RD values were also significantly associated with BMI. There were no significant associations between neither of diffusion metrics and VAT/SAT ratio or HOMA‐IR.ConclusionAssociation of midlife obesity with lower axonal diffusivity, reflective of lower white matter integrity, with differential patterns in men and women especially in CC, is in line with previous findings in healthy individuals. Reduced axonal diffusivity in reticular and brain stem pathways could be indicative of early dysregulations observed in Alzheimer’s disease.

Distinct spatiotemporal brainstem pathways of outcome valence during reward- and punishment-based learning

Learning to seek rewards and avoid punishments, based on positive and negative choice outcomes, is essential for human survival. Yet, the neural underpinnings of outcome valence in the human brainstem and the extent to which they differ in reward and punishment learning contexts remain largely elusive. Here, using simultaneously acquired electroencephalography and functional magnetic resonance imaging data, we show that during reward learning the substantia nigra (SN)/ventral tegmental area (VTA) and locus coeruleus are initially activated following negative outcomes, while the VTA subsequently re-engages exhibiting greater responses for positive than negative outcomes, consistent with an early arousal/avoidance response and a later value-updating process, respectively. During punishment learning, we show that distinct raphe nucleus and SN subregions are activated only by negative outcomes with a sustained post-outcome activity across time, supporting the involvement of these brainstem subregions in avoidance behavior. Finally, we demonstrate that the coupling of these brainstem structures with other subcortical and cortical areas helps to shape participants' serial choice behavior in each context.

Mitochondrial Disorders and MRI of the Brain in Patients with Leukoencephalophathy with Brainstem and Spinal Cord Involvement and Lactate Elevation in Moscow Region

leukoencephalopathy with lesions of the brainstem and spinal cord and increased lactate levels (LBSL) is a hereditary autosomal recessive disease caused by a mutation in the DARS2 gene, with a heterogeneous lesion of the white matter of the brain involving the brainstem and spinal pathways, an increase in lactate in abnormal white matter. Objective. The purpose of the study is to evaluate the features of brain MRI and mitochondrial disorders in adult patients with PE-FMF. Material and methods. An observation of three adult patients from the Moscow region with a hereditary mitochondrial disease of leukoencephalopathy with damage to the brainstem and spinal cord and an increase in lactate level (LBSL) is presented. The diagnosis was confirmed by molecular diagnostics. An MRI examination of the brain was performed on an MRI tomograph with a magnetic field induction of 3.0 T For the cytochemical study of the activity of mitochondrial enzymes in peripheral blood lymphocytes, the method proposed by A.G.E. Pearse modified by R.P. Narcissov. Results. The clinical picture of the disease is similar to multiple sclerosis. MRI of the brain showed more pronounced diffuse changes in the white matter. In all patients, dysfunction of the respiratory chain of mitochondria was noted. Conclusion. Taking into account the data obtained, patients are shown energotropic therapy (idebenone and carnitine preparations). Thus, when doubtful cases in the diagnosis of multiple sclerosis, LBSL should be excluded.

Distinct topographic organization and network activity patterns of corticocollicular neurons within layer 5 auditory cortex.

The auditory cortex (AC) modulates the activity of upstream pathways in the auditory brainstem via descending (corticofugal) projections. This feedback system plays an important role in the plasticity of the auditory system by shaping response properties of neurons in many subcortical nuclei. The majority of layer (L) 5 corticofugal neurons project to the inferior colliculus (IC). This corticocollicular (CC) pathway is involved in processing of complex sounds, auditory-related learning, and defense behavior. Partly due to their location in deep cortical layers, CC neuron population activity patterns within neuronal AC ensembles remain poorly understood. We employed two-photon imaging to record the activity of hundreds of L5 neurons in anesthetized as well as awake animals. CC neurons are broader tuned than other L5 pyramidal neurons and display weaker topographic order in core AC subfields. Network activity analyses revealed stronger clusters of CC neurons compared to non-CC neurons, which respond more reliable and integrate information over larger distances. However, results obtained from secondary auditory cortex (A2) differed considerably. Here CC neurons displayed similar or higher topography, depending on the subset of neurons analyzed. Furthermore, specifically in A2, CC activity clusters formed in response to complex sounds were spatially more restricted compared to other L5 neurons. Our findings indicate distinct network mechanism of CC neurons in analyzing sound properties with pronounced subfield differences, demonstrating that the topography of sound-evoked responses within AC is neuron-type dependent.

Vestibular reflexes in essential tremor: abnormalities of ocular and cervical vestibular-evoked myogenic potentials are associated with the cerebellum and brainstem involvement.

This study utilized cervical vestibular-evoked myogenic potentials tests (cVEMP) and ocular vestibular-evoked myogenic potentials tests (oVEMP) to investigate the vestibulocollic and vestibuloocular reflex arcs and to evaluate cerebellar and brainstem involvement) in essential tremor (ET). Eighteen cases with ET and 16 age- and gender-matched healthy control subjects (HCS) were included in the present study. Otoscopic and neurologic examinations were performed on all participants, and both cervical and ocular VEMP tests were performed. Pathological cVEMP results were increased in the ET group (64.7%) compared to the HCS (41,2%; p > 0.05). The latencies of P1 and N1 waves were shorter in the ET group than in HCS (p = 0.01 and p = 0.001). Pathological oVEMP responses were significantly higher in the ET group (72.2%) compared to the HCS (37.5%; p = 0.01). There was no statistically significant difference in oVEMP N1-P1 latencies between groups (p > 0.05). Because the ET group had high pathological responses to the oVEMP, but not the cVEMP, the upper brainstem pathways may be more affected by ET.

A cross-sectional study of severe acute malnutrition impact on auditory evoked potentials in children age 6–59 months

Background: Malnutrition is a public health concern in India. According to NFHS-5, the number of children under 5 years who are stunted (less height-for-age) and underweight (less weight-for-age) in India, are 35.5% and 32.1%, respectively. Many researchers reported that malnutrition affects myelination and neural maturation of the auditory brainstem pathway. Aims and Objectives: In this study, auditory evoked potential (AEP) parameters were studied in severly acute malnutrition (SAM) children of 6 months to &lt;5 years of age. Materials and Methods: Fifty children, with severely malnourished (Their weighted age was 51–60% of the expected weight, and height for age &lt;85% of the expected height) and 50 healthy children (with weight &gt;80% of expected with normal height for their age), aged 6–59 months were included in the study. The parameters of AEPs were recorded using RMS-EMG EP MARK II, a 4-channel machine. Results: In our study, 30 (60%) males and 20 (40%) females had severe acute malnutrition. There were significant differences in the mean latencies of the waves I to V and the mean interpeak latencies (IPLs) of the waves I-III and I-V on the right and left ears between the study and control groups (P&lt;0.05). The mean IPLs of I-III and I-V on the right side were found to be longer in the SAM group than in the control group (P&lt;0.05. While the mean absolute peak latencies of wave, I found prolonged on both ears in the children with SAM (P&lt;0.05). Conclusion: In the present study, severely acute malnourished children showed changes in AEPs characterized by absolute wave prolonged latencies and interpeak intervals compared with normally nourished children.

Eye Movement and Coma Recovery after Cardiac Arrest (P1-7.006)

<h3>Objective:</h3> To characterize eye movements in comatose patients after cardiac arrest (CA). <h3>Background:</h3> Most patients resuscitated from CA present with altered levels of consciousness due to brain injury. One potential marker of arousal recovery is evidence of eye movements. Brainstem pathways and thalamocortical projections responsible for eye movements share similar anatomic structures responsible for arousal. Our aim is to quantify eye movements using electro-oculography (EOG) data from patients presenting with CA. <h3>Design/Methods:</h3> We are conducting a retrospective study of patients presenting within 24 hours of CA. We identify eye movements on EOG over a period of up to 72 hours, excluding periods of clinical care, sedation, and epileptiform activity. We will study the association of eye movement frequency and the following outcomes by two weeks: 1. Present corneal or pupillary reflex; 2. Eye opening (to stimuli or spontaneously); 3. Command following. Patients are excluded if they have ophthalmoplegia, dementia, or traumatic brain injury. We will compare eye movement frequency in our comatose cohort to a separate cohort of non-comatose patients who underwent sleep studies. <h3>Results:</h3> Our preliminary data consists of 100 patients, mean (± SD) age of 60.2 (± 15.3) years and 38% were female. By 2 weeks, 85% had a pupillary reflex, 75% had a corneal reflex, 43% opened eyes to stimuli, and 21% followed commands. Of 151.5 hours of EOG time across four patients, we preliminarily found eye movements present in 0.56% of total time, with a median of 0.73% and range of 0% to 2.29%. This is comparable to our cohort of 47 patients who underwent sleep studies, with eye movements present in 3.2% of N2, 2.9% of N3, and 19.8% of REM. <h3>Conclusions:</h3> Eye movements in comatose patients may be indicative of recovery potential. Understanding these differences could have prognostic significance and help in triaging care and family discussions. <b>Disclosure:</b> The institution of Mr. Cronin has received research support from American Heart Association. Miss Hwang has nothing to disclose. The institution of an immediate family member of Miss Wack has received research support from Canon Medical Systems USA, Inc. Brian Pugsley has nothing to disclose. Mary Russo has nothing to disclose. Dr. Greer has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Thieme, Inc. Dr. Greer has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for multiple. The institution of Dr. Greer has received research support from Becton Dickenson, Inc. Dr. Greer has received publishing royalties from a publication relating to health care. Dr. Ong has nothing to disclose.

Network Architecture of Verticality Processing in the Human Thalamus.

Thalamic dysfunction in lesions or neurodegeneration may alter verticality perception and lead to postural imbalance and falls. The aim of the current study was to delineate the structural and functional connectivity network architecture of the vestibular representations in the thalamus by multimodal magnetic resonance imaging. Seventy-four patients with acute unilateral isolated thalamic infarcts were studied prospectively with emphasis on the perception of verticality (tilts of the subjective visual vertical [SVV]). We used multivariate lesion-symptom mapping based on support-vector regression to determine the thalamic nuclei associated with ipsiversive and contraversive tilts of the SVV. The lesion maps were used to evaluate the white matter disconnection and whole brain functional connectivity in healthy subjects. Contraversive SVV tilts were associated with lesions of the ventral posterior lateral/medial, ventral lateral, medial pulvinar, and medial central/parafascicular nuclei. Clusters associated with ipsiversive tilts were located inferiorly (ventral posterior inferior nucleus) and laterally (ventral lateral, ventral posterior lateral, and reticular nucleus) to these areas. Distinct ascending vestibular brainstem pathways terminated in the subnuclei for ipsi- or contraversive verticality processing. The functional connectivity analysis showed specific patterns of cortical connections with the somatomotor network for lesions with contraversive tilts, and with the core multisensory vestibular representations (areas Ri, OP2-3, Ig, 3av, 2v) for lesions with ipsiversive tilts. The functional specialization may allow both a stable representation of verticality for sensorimotor integration and flexible adaption to sudden changes in the environment. A targeted modulation of this circuitry could be a novel therapeutic strategy for higher level balance disorders of thalamocortical origin. ANN NEUROL 2023.

Imbalance of Essential Metals in Traumatic Brain Injury and Its Possible Link with Disorders of Consciousness.

Dysfunction of the complex cerebral networks underlying wakefulness and awareness is responsible for Disorders of Consciousness (DoC). Traumatic Brain Injury (TBI) is a common cause of DoC, and it is responsible for a multi-dimensional pathological cascade that affects the proper functioning of the brainstem and brain consciousness pathways. Iron (Fe), Zinc (Zn), and Copper (Cu) have a role in the neurophysiology of both the ascending reticular activating system, a multi-neurotransmitter network located in the brainstem that is crucial for consciousness, and several brain regions. We aimed to summarize the role of these essential metals in TBI and its possible link with consciousness alterations. We found that TBI alters many neuronal molecular mechanisms involving essential metals, causing neurodegeneration, neural apoptosis, synaptic dysfunction, oxidative stress, and inflammation. This final pattern resembles that described for Alzheimer's disease (AD) and other neurological and psychiatric diseases. Furthermore, we found that amantadine, zolpidem, and transcranial direct current stimulation (tDCS)-the most used treatments for DoC recovery-seem to have an effect on essential metals-related pathways and that Zn might be a promising new therapeutic approach. This review summarizes the neurophysiology of essential metals in the brain structures of consciousness and focuses on the mechanisms underlying their imbalance following TBI, suggesting their possible role in DoC. The scenario supports further studies aimed at getting a deeper insight into metals' role in DoC, in order to evaluate metal-based drugs, such as metal complexes and metal chelating agents, as potential therapeutic options.