Brainstem Level Research Articles

Humanized ApoE4 Female Mice Exhibit a More Robust Hypoxic Ventilatory Response Than Female E3 Mice

Breathing is essential to life and can be easily disrupted by many adverse events. Disorders such as high cervical spinal cord injury (SCI) and sleep apnea can decrease quality of life and enhance the ill effects of comorbidities like Alzheimer’s disease (AD). Previous studies have shown an increase in cognitive impairments in subjects with both sleep apnea and AD. Apolipoprotein E (ApoE) is a protein found throughout the body and central nervous system (CNS) that is involved in the regulation and transport of cholesterol and lipids. Out of the three APOE human alleles (E2, E3, and E4), the E4 allele has been implicated in the early onset and higher risk of AD when compared to E2 or E3. Previous research in our lab has shown that the interaction between APOE genotype and sex has different effects on breathing motor plasticity following a cervical SCI in mice. However, it is unknown how baseline respiratory pattern and capability differs between uninjured individuals expressing either ApoE4 or E3, specifically under hypoxic conditions. Unpublished data from our lab has examined these differences in male mice, showing that E4 male mice have high variation in respiratory pattern, as well as a less robust response to hypoxia. Using ApoE as our independent variable, we measured respiratory parameters of female C57/BL6 ApoE3 and ApoE4 humanized mice using whole body plethysmography (WBP), hypothesizing that ApoE3 animals would display a greater baseline respiratory rate and have a more adaptive, heightened response to hypoxic exposure than those expressing ApoE4. Preliminary data comparing E3 female animals (n=8) and E4 female animals (n=8) showed differences across several key measurements. Interestingly, ApoE4 humanized female mice had a more robust response to hypoxic exposure that failed to persist following cessation of hypoxia. However, at baseline, E4 female animals showed no differences in respiratory pattern in contrast to our previously collected male ApoE4 data. These results indicate a critical role of the APOE genotype in the regulation of breathing and response to hypoxic conditions which differs between males and females. To further understand this distinction, future experiments will examine differences in levels of brainstem and spinal cord serotonin expression between ApoE3 and E4 males and females, as well as plasticity following injury in areas high in ApoE expression.

P 85 Impaired pain processing on a brainstem level in patients with complex regional pain syndrome

Introduction: The complex regional pain syndrome (CRPS) is a chronic pain condition, which can follow limb trauma and is accompanied with sensorimotor dysfunction 1 . Current pathophysiological concepts assume local inflammatory processes that lead to peripheral and central sensitization of the nociceptive system 2 . Secondary maladaptive alterations of cortical sensorimotor excitability and disinhibition are well-established but little is known about the contribution of the brainstem. Preliminary evidence for altered brainstem excitability to trigeminal afferent stimulation was recently provided 3,4 . This study uses a more comprehensive assessment of the nociceptive blink reflex (NBR) to assess the interaction of brainstem excitability and habituation to painful stimuli. Methods : 14 CRPS patients (10 female, 53 ± 17.6 years) and 10 controls (HCs; 9 female, 52±18.3) received assessments of pain and the NBR (R2 component, 2 trials, 10 stimuli/trial, interstimulus interval 3-5s). The R2 area (R2a) and habituation (R2h; gradient of R2a against stimulus order) were measured for the stimulated/non-stimulated side (_s/_ns). Results : Pain levels were 5,0±1,5/10 at rest and 7,2±2,1/10 during movements. ANOVA revealed a significant group effect for patients vs. controls (F=4.0; p=0.015). Post hoc tests were corrected for multiple comparisons and showed exceeding excitability (R2a_s: t=2.42, p=0.048; R2a_ns: t=2.98, p= 0.028) and impaired habituation (R2h_s: t=2.45, p=0.044; R2h_ns t=2.60, p=0.036). No significant associations of both disease duration and pain levels with NBR measurements could be obtained. Discussion : We here provide first evidence of altered NBR excitability and habituation indicating altered pain processing on a brainstem level. These results complement previous findings by demonstrating disinhibition as a source of increased brainstem excitability to painful stimulation remote from the limb directly affected by CRPS 4 . Future investigations are needed for a better understanding of the brainstem and its role in the pathophysiology of CRPS. The potential of the NBR as clinical biomarker, as it has been demonstrated in other pain diseases, should also be clarified in further investigation 5 . Literature: 1 Veldman PH et al. Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. Lancet 1993. 2 Eldufani J et al. A medical mystery of CRPS. Heliyon. 2020. 3 Thiele A, et al. Treatment with calcitonin gene-related peptide antibodies modifies brainstem excitability and habituation to nociceptive trigeminal stimulation in migraineurs. CEPHALALGIA. 2021. 4 Drummond P et al. The Source of Hemisensory Disturbances in CRPS, The Clinical Journal of Pain: 2021. 5 De Marinis M et al. Decreased habituation of the R2component of the blink reflex in migraine patients. Clinical neurophysiology. 2003.

Peripheral Purinergic Modulation in Pediatric Orofacial Inflammatory Pain Affects Brainstem Nitroxidergic System: A Translational Research.

Physiology of orofacial pain pathways embraces primary afferent neurons, pathologic changes in the trigeminal ganglion, brainstem nociceptive neurons, and higher brain function regulating orofacial nociception. The goal of this study was to investigate the nitroxidergic system alteration at brainstem level (spinal trigeminal nucleus), and the role of peripheral P2 purinergic receptors in an experimental mouse model of pediatric inflammatory orofacial pain, to increase knowledge and supply information concerning orofacial pain in children and adolescents, like pediatric dentists and pathologists, as well as oro-maxillo-facial surgeons, may be asked to participate in the treatment of these patients. The experimental animals were treated subcutaneously in the perioral region with pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS), a P2 receptor antagonist, 30 minutes before formalin injection. The pain-related behavior and the nitroxidergic system alterations in the spinal trigeminal nucleus using immunohistochemistry and western blotting analysis have been evaluated. The local administration of PPADS decreased the face-rubbing activity and the expression of both neuronal and inducible nitric oxide (NO) synthase isoforms in the spinal trigeminal nucleus. These results underline a relationship between orofacial inflammatory pain and nitroxidergic system in the spinal trigeminal nucleus and suggest a role of peripheral P2 receptors in trigeminal pain transmission influencing NO production at central level. In this way, orofacial pain physiology should be elucidated and applied to clinical practice in the future.

HP01: Usefulness of auditory brainstem evoked response in the assessment of bilirubin-induced auditory toxicity in infants with jaundice: A case-control study

To assess ABR alterations due to hyperbilirubinemia in jaundiced infants compared to a control group. Background: Bilirubin-induced neurotoxicity has predilection to specific areas of the brain including the auditory pathway structures. These latter are assessed by auditory brainstem evoked response (ABR). Methods: This was a retrospective study including two groups: jaundiced infants (G1) and age-matched (p>0.05) infants without jaundice (G2). All infants underwent ABR on each ear to screen deafness. Responses obtained at 90 dB were studied. Responses of G2 were normal. The Mann-Whitney U test was used to compare the responses between the two groups. Results: Twenty infants (40 ears) were included with a mean age of 33.5±13 months. G1 and G2 included 18 and 20 ears, respectively. Wave-I latency was significantly more prolonged in G1 (1.71±0.2 ms) compared to G2 (1.56±0.1 ms) with p=0.02. There was no difference in I-III interpeak interval (IPL). The III-V IPL was significantly increased in G1 (2.04±0.1 ms) compared to G2 (1.92±0.1 ms) with p=0.04. I-V IPL was more prolonged in G1. Discussion: Both peripheral and central auditory pathways may be altered in infants with jaundice. Bilirubin-induced toxicity may affect the inner part of the ear. The central dysfunction may occur at the brainstem level between the bulbo-protuberant junction and the inferior colliculus. This may be due to the hyperbilirubinemia-induced changes in the central synaptic transmission. Conclusion: Hyperbilirubinemia-induced auditory toxicity can occur at different levels of the auditory pathway. Therefore, there is a need for an early ABR assessment in jaundiced infants.

Comparing Sound-Field Speech-Auditory Brainstem Response Components between Cochlear Implant Users with Different Speech Recognition in Noise Scores

ObjectivesMany studies have suggested that cochlear implant (CI) users vary in terms of speech recognition in noise. Studies in this field attribute this variety partly to subcortical auditory processing. Studying speech-Auditory Brainstem Response (speech-ABR) provides good information about speech processing; thus, this work was designed to compare speech-ABR components between two groups of CI users with good and poor speech recognition in noise scores. Materials & MethodsThe present study was conducted on two groups of CI users aged 8-10 years old. The first group (CI-good) consisted of 15 children with prelingual CI who had good speech recognition in noise performance. The second group (CI-poor) was matched with the first group, but they had poor speech recognition in noise performance. The speech-ABR test in a sound-field presentation was performed for all the participants. Results The speech-ABR response showed more delay in C, D, E, F, O latencies in CI-poor than CI-good users (P <0.05), meanwhile no significant difference was observed in initial wave (V(t= -0.293, p= 0.771 and A (t= -1.051, p= 0.307). Analysis in spectral-domain showed a weaker representation of fundamental frequency as well as the first formant and high-frequency component of speech stimuli in the CI users with poor auditory performance.ConclusionsResults revealed that CI users who showed poor auditory performance in noise performance had deficits in encoding the periodic portion of speech signals at the brainstem level. Also, this study could be as physiological evidence for poorer pitch processing in CI users with poor speech recognition in noise performance.

The effect of vitamin E supplementation on brain tissue element levels in epileptic rats.

The aim of this study was to investigate how the application of vitamin E affected the levels of chemical elements in the brain tissues of epilepsy-induced rats. The sample of 40 adult male rats was separated into 4 equal groups: Group 1: control, Group 2: vitamin E; Group 3: penicillin to promote epileptic form activity and Group 4: penicillin + vitamin E. After three months of treatment, an Atomic Absorption Spectrophotometer was used to analyze the presence of the elements in brain tissue sections (brain, brainstem, cerebellum) of the decapitated animals. The levels of magnesium in the groups that received vitamin E (G2 and 4) were significantly higher than in the control group (G1) and the first epilepsy group (G3) (p.05).Chrome and zinc levels in brain, brainstem, and cerebellum tissue of the two epilepsy groups (G3-4) decreased significantly compared to the control group (G1) and the vitamin E group (G2) (p.05). The levels of copper in the brainstem and lead in the cerebellum of the first epilepsy group (G3) were higher than in all other groups (p.05). The findings showed that the application of vitamin E in experimental epilepsy may have a limited effect on element metabolism in brain tissue. A decline in zinc levels in the brain, brainstem and cerebellum tissues in epilepsy groups constitutes another result of our study. This should be examined further to determine whether decreased levels of zinc play a role in epilepsy pathogenesis.

Application of neurohabilitation therapy in a six-month-old pediatric patient as a treatment for neurodevelopmental delay (clinical case)

Objectives: To stop the neurodevelopmental delay of a six-month-old pediatric patient through the application of Neurohabilitation Therapy. To analyze the evolution with early detection, adherence to treatment and the participation of the baby's family nucleus, for the improvement of his neurodevelopment. To demonstrate the efficiency of the application of Neurohabilitation Therapy in six-month-old pediatric patients. Methodology: Type of study: quasi-experimental descriptive study with quantitative approach and prospective longitudinal design. Contributions: The treatment was efficient to stop neurodevelopmental delay, negative responses were obtained in 3/3 reflexes at spinal level, 8/8 reflexes at brain stem level, in automatic movement reactions 2/3 negative responses and 1/3 positive response. According to Amiel Tison's neurological examination of the 1st year of life, scores of 0 were obtained in cranial growth, relational life, passive tone, motor skills and primary reflexes, indicating that the infant's neurodevelopment is normal according to age.

Potamogeton perfoliatus L. Extract Attenuates Neuroinflammation and Neuropathic Pain in Sciatic Nerve Chronic Constriction Injury-Induced Peripheral Neuropathy in Rats.

Sciatic nerve injury is often associated with neuropathic pain and neuroinflammation in the central and peripheral nervous systems. In our previous work, Potamogeton perfoliatus L. displayed anti-inflammatory, antipyretic and analgesic properties, predominantly via the inhibition of COX-2 enzyme and attenuation of oxidative stress. Herein, we extended our investigations to study the effects of the plant’s extract on pain-related behaviors, oxidative stress, apoptosis markers, GFAP, CD68 and neuro-inflammation in sciatic nerve chronic constriction injury (CCI) rat model. The levels of the pro-inflammatory marker proteins in sciatic nerve and brainstem were measured with ELISA 14 days after CCI induction. Pretreatment with the extract significantly attenuated mechanical and cold allodynia and heat hyperalgesia with better potential than the reference drug, pregabalin. In addition, CCI lead to the overexpression of prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), tumor necrosis alpha (TNFα), nuclear factor κB (NF-κB), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and NADPH oxidase-1 (NOX-1) and decreased the catalase level in sciatic nerve and brainstem. The observed neuro-inflammatory changes were accompanied with glial cells activation (increased GFAP and CD68 positive cells), apoptosis (increased Bax) and structural changes in both brainstem and sciatic nerve. The studied extract attenuated the CCI-induced neuro-inflammatory changes, oxidative stress, and apoptosis while it induced the expression of Bcl-2 and catalase in a dose dependent manner. It also decreased the brainstem expression of CD68 and GFAP indicating a possible neuroprotection effect. Taking together, P. perfoliatus may be considered as a novel therapy for neuropathic pain patients after performing the required clinical trials.

Cortical and subcortical processing of speech in cochlear implant recipients with Auditory Neuropathy Spectrum Disorder

Abstract Background Cochlear implantation (CI) is now recognized as one of the possible lines of interventions in ANSD patients to improve their hearing and speech communication. Desynchronized of the auditory information is the most widely accepted mechanism in ANSD. Objectives To study speech processing in the brainstem level as measured by speech-auditory brainstem response (S-ABR) in ANSD and CAEP P1 in ANSD subjects fitted with CIs and the results will be compared to SNHL subjects fitted with unilateral CIs. Subjects and method A total number of 45 subjects were included classified into three groups (one control and two study groups). The control group 16 subjects, age ranged from 5 to 29.5 years with mean of (11.1 years) with normal peripheral hearing sensitivity. The study group comprised 29 children who underwent cochlear implantation. It was subdivided into two subgroups: Group (SNHL) ;their age ranged from2.9 to 15.5 years with mean of (7.7 years) and group (ANSD); Their age ranged from 3.2 to 29 years with mean of (9.3 years) They were subjected to detailed history taking, aided warble-tone sound field audiometry, Questionnaire and Speech-evoked potentials (P1 &amp;c-ABR) recording evoked by the 150-ms synthesized /da/ syllable stimulus. Results C-ABR waves were detected in 100% of control group, 75% of SNHL group and 53.8% of ANSD group. A statistically significant differences existed between the control group and the two study subgroups regarding the P1 latencies. While; there were no statistically significant differences between {SNHL group &amp;ANSD}. Sound-field S-ABR in the CI recipients showed delayed latencies in both SNHL group &amp;ANSD group comparable to the control group with more delay in ANSD group than SNHL group. Finally, the neural phase locking was significantly higher in CI recipients due to electrical artifact. Conclusions • There were no statistically significant differences between {SNHL group &amp; ANSD group} regarding P1 latency. • C-ABR waves were detected in 75% of SNHL group and 53.8% of ANSD group with delayed latencies and higher amplitude than control group with more delay in ANSD group than SNHL group. The findings of sound-field S-ABR demonstrated that CI recipients have neural encoding deficits in temporal and spectral domains at the brainstem level; therefore, the sound-field S-ABR can be considered an efficient clinical procedure to assess the speech processing in ANSD subjects fitted with cochlear implant.

Brain region specificity in reactive oxygen species production and maintenance of redox balance

The brain produces various reactive oxygen species in enzymatic and non-enzymatic reactions as a by-product of metabolism and/or for redox signaling. Effective antioxidant system in the brain cells maintains redox balance. However, neurons and glia from some brain regions are more vulnerable to oxidative stress in ischemia/reperfusion, epilepsy, and neurodegenerative disorders than the rest of the brain. Using fluorescent indicators in live cell imaging and confocal microscopy, we have measured the rate of cytosolic and mitochondrial reactive oxygen species production, lipid peroxidation, and glutathione levels in cortex, hippocampus, midbrain, brain stem and cerebellum in acute slices of rat brain. We have found that the basal rate of ROS production is at its highest in brain stem and cerebellum, and that it is mainly generated by glial cells. Activation of neurons and glia by glutamate and ATP led to maximal rates of ROS production in the midbrain compared to the rest of the brain. Mitochondrial ROS had only minor implication to the total ROS production with maximal values in the cortex and minimal in the midbrain. The basal rate of lipid peroxidation was higher in the midbrain and hippocampus, while the GSH level was similar in most brain regions with the lowest level in the midbrain. Thus, the rate of ROS production, lipid peroxidation and the level of GSH vary across brain regions.

Experimental evidence of a functional relationship within the brainstem trigeminocervical complex in humans.

The existence of a trigeminocervical complex has been suggested based on animal data, but only indirect evidence exists in humans. We investigated the functional relationship between the trigeminal and the occipital region by stimulating one region and measuring electrical pain thresholds (EPTs) of the corresponding opposite region. This study consists of 2 single-blinded, randomised protocols. Forty healthy participants were recruited in the propaedeutic protocol I. Electrical pain thresholds were measured on the V1 and the greater occipital nerve (GON) dermatome bilaterally as well as on the left forearm longitudinally before and after application of topical capsaicin. Protocol II was then online preregistered, and, additionally, the ipsilateral trigeminal dermatomes V2 and V3 were tested. Greater occipital nerve stimulation increased the EPT ipsilateral at V1 after 20 minutes (P = 0.006) compared with baseline, whereas trigeminal stimulation increased the EPT at the ipsilateral (P = 0.023) as well as the contralateral GON (P = 0.001) after capsaicin application. Protocol II confirmed these results and additionally showed that GON stimulation with capsaicin increased EPTs ipsilateral at all 3 trigeminal dermatomes and that trigeminal stimulation on V1 led to an ipsilateral increase of EPTs at GON, V2, and V3. Our data suggest a strong functional interplay between the trigeminal and occipital system in humans. The fact that the stimulation of one of these dermatomes increases the EPT of the respective other nerve could be explained by segmental inhibition on the brainstem level.

Cortical hemisphere preference and brainstem ear asymmetry reflect experience-dependent functional modulation of pitch

Temporal attributes of pitch processing at cortical and subcortical levels are differentially weighted and well-coordinated. The question is whether language experience induces functional modulation of hemispheric preference complemented by brainstem ear symmetry for pitch processing. Brainstem frequency-following and cortical pitch responses were recorded concurrently from Mandarin and English participants. A Mandarin syllable with a rising pitch contour was presented to both ears with monaural stimulation. At the cortical level, left ear stimulation in the Chinese group revealed an experience-dependent response for pitch processing in the right hemisphere, consistent with a functionalaccount. The English group revealed a contralateral hemisphere preference consistent with a structuralaccount. At the brainstem level, Chinese participants showed a functional leftward ear asymmetry, whereas English were consistent with a structural account. Overall, language experience modulates both cortical hemispheric preference and brainstem ear asymmetry in a complementary manner to optimize processing of temporal attributes of pitch.

Evoked potential (EP) O-EV001. The effect of watching movies on BAEP

Introduction . Previous researches on peripheral filtering at the cochlear and brainstem levels toward auditory information by using BAEP measurement had been conducted. However, the results were still varied. This study was aimed to find out the effect of selective visual attention of watching movies towards the latency and amplitude of BAEP. Methods . This study involved 12 healthy subjects (9 males, 3 females) with right-ear dominance. The age of samples ranged from 21-52 years old, and the mean was 30.7 years. BAEP measurement was done in two conditions, eyes were closed and watching a silent action movie in 14 inches monitor with a view distance of 75 cm. Every subject was recorded two times for reproducibility using 4 Ag-Cl electrodes (Cz, Fz, A1, and A2) that were placed according to the International Electrode (10–20) Placement system. The stimulus was monoaural click-sound at the right ear with the intensity of 70 dB nHL, while noise-masking was given to the left ear. The measurements of latency and amplitude of wave I, wave V and interval peak latency of wave I-V were done. Results . This study showed that there were significant latency delay of wave I as much as. 0.068 ms or 3.81% (p = 0.006) and a decrease of amplitude as much as 0.043 µV or 26.34% (p = 0.001). But no significant different of latency and amplitude of wave V on two conditions - eyes closed and during watched movie (p > 0.05). The interval peak latency wave I-V of these two groups was not significantly different also with each value [4.022 ± 0.115 ms vs 3.989 ± 0.100 ms (p = 0.241)]. Conclusion . Selective visual attention by watching movies gave an inhibition effect toward the auditory pathway at the cochlear level, but no effect at the brainstem level.

Menthol, a bioactive constituent of Mentha, attenuates motion sickness in mice model: Involvement of dopaminergic system.

Motion sickness (MS) occurs due to contradicting vestibular and visual inputs to the brain causing nausea and vomiting. Antidopaminergic drugs being effective in reducing MS create a path for effective therapy against MS by regulating dopamine levels. We aimed to evaluate the role of the striatum and brainstem dopamine and dopamine D2 receptor (DRD2) in MS and the efficacy of menthol (MNT) to modulate dopamine and DRD2 in vitro and in vivo for possible amelioration of MS. Evaluation of efficacy of MNT to inhibit dopamine release from PC12 cells and anti-MS efficacy in BALB/c mice model was performed. Dopamine, DRD2 expression in PC12 cells, mice striatum, and brainstem were detected using HPLC-ECD, RT-PCR, and Western blot analysis, respectively. DRD2 expression increased in calcium ionophore-treated PC12 cells compared with control cells. Pretreatment with 50μg/ml menthol decreased dopamine and DRD2 expression. Similarly, dopamine and DRD2 levels in mice striatum and brainstem of MS group (rotation induced) increased significantly compared with control group NC (no rotation). Pretreatment with menthol at 50mg/kg concentration (rotation induced) showed decreased dopamine and DRD2 expression, thus indicating ameliorative effect on MS. Hence, we suggest that increased striatum and brainstem dopamine and DRD2 levels might lead to MS symptoms, and menthol could be used as a potent herbal alternative medicine for MS. PRACTICAL APPLICATIONS: Antidopaminergic drugs being effective in reducing motion sickness (MS) creates a path for effective therapy against MS by regulating dopamine levels. Increased striatum and brainstem dopamine and Dopamine D2 receptor (DRD2) levels might lead to the MS symptoms induced by rotation stimulation in mice model. Menthol showed a prophylactic effect on rotation-induced MS by reducing striatal and brainstem dopamine levels, DRD2 mRNA, and protein expression. Menthol could be used as an herbal alternative to antidopaminergics to minimize the associated adverse effects.

Effect of Listening Biographies on Frequency Following Response Responses of Vocalists, Violinists, and Non-Musicians to Indian Carnatic Music Stimuli.

Background and ObjectivesThe current study investigates pitch coding using frequency following response (FFR) among vocalists, violinists, and non-musicians for Indian Carnatic transition music stimuli and assesses whether their listening biographies strengthen their F0 neural encoding for these stimuli.Subjects and MethodsThree participant groups in the age range of 18-45 years were included in the study. The first group of participants consisted of 20 trained Carnatic vocalists, the second group consisted of 13 trained violinists, and the third group consisted of 22 non-musicians. The stimuli consisted of three Indian Carnatic raga notes (/S-R2-G3/), which was sung by a trained vocalist and played by a trained violinist. For the purposes of this study, the two transitions between the notes T1=/S-R2/ and T2=/R2-G3/ were analyzed, and FFRs were recorded binaurally at 80 dB SPL using neuroscan equipment.ResultsOverall average responses of the participants were generated. To assess the participants’ pitch tracking to the Carnatic music stimuli, stimulus to response correlation (CC), pitch strength (PS), and pitch error (PE) were measured. Results revealed that both the vocalists and violinists had better CC and PS values with lower PE values, as compared to non-musicians, for both vocal and violin T1 and T2 transition stimuli. Between the musician groups, the vocalists were found to perform superiorly to the violinists for both vocal and violin T1 and T2 transition stimuli.ConclusionsListening biographies strengthened F0 neural coding, with respect to the vocalists for vocal stimulus at the brainstem level. The violinists, on the other hand, did not show such preference.

Brainstem Dysfunction in Healthy Aging

The brainstem controls sub-cortical and cortical activity and influences the processing of incoming information. The goal of this study was to characterize age related alterations of brainstem-brain interactions during different brain states detected by dynamic analysis of task-free fMRI. 79 young (20-40 years) and 51 older adults (55-80 years) were studied. Internal brainstem structures were segmented using a new multi-contrast segmentation approach. Brain and brainstem gray matter segmentations were warped onto a population template. The ICV-corrected Jacobian determinants were converted into z-score maps and the means from 420 cortical/subcortical/brainstem rois extracted. The fMRI was preprocessed in SPM12/Conn18 and the BOLD signal from 420 cortical/subcortical/brainstem rois extracted. A dynamic task-free analysis approach based on hierarchical cluster analysis was used to identify 15 brain states that were characterized using graph analysis (strength, diversity, modularity). Kruskal-Wallis tests and Spearman correlations were used for statistical analysis. One brain state (cluster 21) occurred more often in older adults (p=0.008). It was characterized by a lower mean modular strength and brainstem-cortical strength in older adults compared to younger adults. Global age related gray matter differences were positively correlated with brain state 21’s modular strength. Furthermore, brain state 21 duration was negatively correlated with working memory (r = -0.28, p=0.002). The findings suggest an age related weakening of the within and between network synchronization at the brainstem level during brain state 21 in older adults that negatively affects cortical and subcortical synchronization and working memory performance.

Brainstem Involvement in Amyotrophic Lateral Sclerosis: A Combined Structural and Diffusion Tensor MRI Analysis.

IntroductionThe brainstem is an important component in the pathology of amyotrophic lateral sclerosis (ALS). Although neuroimaging studies have shown multiple structural changes in ALS patients, few studies have investigated structural alterations in the brainstem. Herein, we compared the brainstem structure between patients with ALS and healthy controls.MethodsA total of 33 patients with ALS and 33 healthy controls were recruited in this study. T1-weighted and diffusion tensor imaging (DTI) were acquired on a 3 Tesla magnetic resonance imaging (3T MRI) scanner. Volumetric and vertex-wised approaches were implemented to assess the differences in the brainstem’s morphological features between the two groups. An atlas-based region of interest (ROI) analysis was performed to compare the white matter integrity of the brainstem between the two groups. Additionally, a correlation analysis was used to evaluate the relationship between ALS clinical characteristics and structural features.ResultsVolumetric analyses showed no significant difference in the subregion volume of the brainstem between ALS patients and healthy controls. In the shape analyses, ALS patients had a local abnormal surface contraction in the ventral medulla oblongata and ventral pons. Compared with healthy controls, ALS patients showed significantly lower fractional anisotropy (FA) in the left corticospinal tract (CST) and bilateral frontopontine tracts (FPT) at the brainstem level, and higher radial diffusivity (RD) in bilateral CST and left FPT at the brainstem level by ROI analysis in DTI. Correlation analysis showed that disease severity was positively associated with FA in left CST and left FPT.ConclusionThese findings suggest that the brainstem in ALS suffers atrophy, and degenerative processes in the brainstem may reflect disease severity in ALS. These findings may be helpful for further understanding of potential neural mechanisms in ALS.

SŁUCHOWE POTENCJAŁY WYWOŁANE FFR U WOKALISTÓW, SKRZYPKÓW I NIEMUZYKÓW W ODPOWIEDZI NA BODŹCE W POSTACI MUZYKI KARNATYCKIEJ

BackgroundThe current study investigates pitch coding among vocalists, violinists, and non-musicians to Carnatic musical stimuli.Material and methodsThree groups of participants were included in the study: 10 trained Carnatic vocalists, 10 violinists,and 10 non-musicians. Their ages ranged from 18 to 45 years. Two types of stimuli were given: three notes of a Carnatic raga (S R2 G3) sung by a trained vocalist and three notes of a Carnatic raga (S R2 G3) played on violin by a trained violinist. Frequency following responses (FFRs) were recorded binaurally at 80 dBSPL for both stimuli using Neuroscan equipment.ResultsGrand average responses of all participants were generated. To assess a participant’s pitch tracking to the Carnatic music stimuli, stimulus-to-response correlation, pitch strength, and pitch error were calculated. Vocalists and violinists had better stimulus-to-response correlation and pitch strength values with lower pitch error values than non-musicians for both vocal and violin stimuli. Within both the vocalist and violinist groups, superior performance was noticed for the vocal stimulus compared to the violin stimulus. No such preference was evident among non-musicians.ConclusionsClassical music training dependent plasticity can be demonstrated at brainstem level itself. This holds true for both vocal and violin music, a finding not reported previously. Further a link between musical training and the FFR response can be more strongly demonstrated for vocalists than for violinists.

Aging is associated with glial senescence in the brainstem - implications for age-related sympathetic overactivity.

Accumulating evidence suggests that the sympathetic nervous system (SNS) overactivity plays a crucial role in age-related increase in the risk for cardiovascular diseases such as hypertension, myocardial infarction, stroke and heart diseases. Previous studies indicate that neuroinflammation in key brainstem regions that regulate sympathetic outflow plays a pathogenic role in aging-mediated sympathoexcitation. However, the molecular mechanisms underlying this phenomenon are not clear. While senescent cells and their secretory phenotype (SASP) have been implicated in the pathogenesis of several age-related diseases, their role in age-related neuroinflammation in the brainstem and SNS overactivity has not been investigated. To test this, we isolated brainstems from young (2-4 months) and aged (24 months) male C57BL/6J mice and assessed senescence using a combination of RNA-in situ hybridization, PCR analysis, multiplex assay and SA-β gal staining. Our results show significant increases in p16Ink4a expression, increased activity of SA-β gal and increases in SASP levels in the aged brainstem, suggesting age-induced senescence in the brainstem. Further, analysis of senescence markers in glial cells enriched fraction from fresh brainstem samples demonstrated that glial cells are more susceptible to senesce with age in the brainstem. In conclusion, our study suggests that aging induces glial senescence in the brainstem which likely causes inflammation and SNS overactivity.

Auditory brainstem response asymmetries in older adults: An exploratory study using click and speech stimuli.

BackgroundSome evidence suggests that young adults exhibit a selective laterality of auditory brainstem response (ABR) elicited with speech stimuli. Little is known about such an auditory laterality in older adults.ObjectiveThe aim of this study was to investigate possible asymmetric auditory brainstem processing between right and left ear presentation in older adults.MethodsSixty-two older adults presenting with normal hearing thresholds according to their age and who were native speakers of Quebec French participated in this study. ABR was recorded using click and a 40-ms /da/ syllable. ABR was elicited through monaural right and monaural left stimulation. Latency and amplitude for click-and speech-ABR components were compared between right and left ear presentations. In addition, for the /da/ syllable, a fast Fourier transform analysis of the sustained frequency-following response (FFR) of the vowel was performed along with stimulus-to-response and right-left ear correlation analyses.ResultsNo significant differences between right and left ear presentation were found for amplitudes and latencies of the click-ABR components. Significantly shorter latencies for right ear presentation as compared to left ear presentation were observed for onset and offset transient components (V, A and O), sustained components (D and E), and voiced transition components (C) of the speech-ABR. In addition, the spectral amplitude of the fundamental frequency (F0) was significantly larger for the left ear presentation than the right ear presentation.ConclusionsResults of this study show that older adults with normal hearing exhibit symmetric encoding for click stimuli at the brainstem level between the right and left ear presentation. However, they present with brainstem asymmetries for the encoding of selective stimulus components of the speech-ABR between the right and left ear presentation. The right ear presentation of a /da/ syllable elicited reduced neural timing for both transient and sustained components compared to the left ear. Conversely, a stronger left ear F0 encoding was observed. These findings suggest that at a preattentive, sensory stage of auditory processing, older adults lateralize speech stimuli similarly to young adults.