ResearchPad - midbrain https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Direct comparison of activation maps during galvanic vestibular stimulation: A hybrid H<sub>2</sub>[<sup>15</sup> O] PET—BOLD MRI activation study]]> https://www.researchpad.co/article/elastic_article_14749 Previous unimodal PET and fMRI studies in humans revealed a reproducible vestibular brain activation pattern, but with variations in its weighting and expansiveness. Hybrid studies minimizing methodological variations at baseline conditions are rare and still lacking for task-based designs. Thus, we applied for the first time hybrid 3T PET-MRI scanning (Siemens mMR) in healthy volunteers using galvanic vestibular stimulation (GVS) in healthy volunteers in order to directly compare H215O-PET and BOLD MRI responses. List mode PET acquisition started with the injection of 750 MBq H215O simultaneously to MRI EPI sequences. Group-level statistical parametric maps were generated for GVS vs. rest contrasts of PET, MR-onset (event-related), and MR-block. All contrasts showed a similar bilateral vestibular activation pattern with remarkable proximity of activation foci. Both BOLD contrasts gave more bilateral wide-spread activation clusters than PET; no area showed contradictory signal responses. PET still confirmed the right-hemispheric lateralization of the vestibular system, whereas BOLD-onset revealed only a tendency. The reciprocal inhibitory visual-vestibular interaction concept was confirmed by PET signal decreases in primary and secondary visual cortices, and BOLD-block decreases in secondary visual areas. In conclusion, MRI activation maps contained a mixture of CBF measured using H215O-PET and additional non-CBF effects, and the activation-deactivation pattern of the BOLD-block appears to be more similar to the H215O-PET than the BOLD-onset.

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<![CDATA[640-Slice CT Measurement of Superior Orbital Fissure as Gateway for Light into the Brain: Statistical Evaluation of Area and Distance]]> https://www.researchpad.co/article/5989db4bab0ee8fa60bda3ed

Objective

Our aim was to provide normative data concerning superior orbital fissure area (SOFA), ocular skin and the substantia nigra (D-SS) and orbital fissure and the substantia nigra (D-SOF-S) distances by CT scan in adult Caucasian population

Methods

The area of the superior orbital fissure (SOF), the distance between the ocular skin and the substantia nigra and the distance between the superior orbital fissure and the substantia nigra using CT and 3D-CT images.

Results

Normative data stratified for age and gender were obtained. The data here reported show that some degree of variability in SOFA, D-SS and D-SOF-S measurements can be observed healthy Caucasian subjects. Gender stratified prediction intervals (mean +/- 2 Standard Deviations) for SOFA and D-SOF-S were 69.2 (+/-15.8) and 38.4 (+/-7.6) for male and 56.8 (+/-11.9) and 36.5 (+/-6.1) for female, respectively. Age and gender significantly impacted on D-SS values and normative data were constructed generating data stratified for these two variables. D-SS was 89.4 (+/-10.3) and 86.4 (+/-9.7) for male and female, respectively.

Conclusions

Here we provide adjunctive anatomical information on specific anatomical cerebral zones. Our data may have implications for surgeons actively committed to treat pathological conditions involving these cerebral areas. Additionally, the anatomical variability found with respect to SOF and the potential different exposure of the substanzia nigra to the bright light could play a role in Parkinson’s disease as already speculated in literature.

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<![CDATA[Functional Plasticity after Unilateral Vestibular Midbrain Infarction in Human Positron Emission Tomography]]> https://www.researchpad.co/article/5989d9e8ab0ee8fa60b6bea1

The aim of the study was to uncover mechanisms of central compensation of vestibular function at brainstem, cerebellar, and cortical levels in patients with acute unilateral midbrain infarctions presenting with an acute vestibular tone imbalance. Eight out of 17 patients with unilateral midbrain infarctions were selected on the basis of signs of a vestibular tone imbalance, e.g., graviceptive (tilts of perceived verticality) and oculomotor dysfunction (skew deviation, ocular torsion) in F18-fluordeoxyglucose (FDG)-PET at two time points: A) in the acute stage, and B) after recovery 6 months later. Lesion-behavior mapping analyses with MRI verified the exact structural lesion sites. Group subtraction analyses and comparisons with healthy controls were performed with Statistic Parametric Mapping for the PET data. A comparison of PET A of acute-stage patients with that of healthy controls showed increases in glucose metabolism in the cerebellum, motion-sensitive visual cortex areas, and inferior temporal lobe, but none in vestibular cortex areas. At the supratentorial level bilateral signal decreases dominated in the thalamus, frontal eye fields, and anterior cingulum. These decreases persisted after clinical recovery in contrast to the increases. The transient activations can be attributed to ocular motor and postural recovery (cerebellum) and sensory substitution of vestibular function for motion perception (visual cortex). The persisting deactivation in the thalamic nuclei and frontal eye fields allows alternative functional interpretations of the thalamic nuclei: either a disconnection of ascending sensory input occurs or there is a functional mismatch between expected and actual vestibular activity. Our data support the view that both thalami operate separately for each hemisphere but receive vestibular input from ipsilateral and contralateral midbrain integration centers. Normally they have gatekeeper functions for multisensory input to the cortex and automatic motor output to subserve balance and locomotion, as well as sensorimotor integration.

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<![CDATA[Surface-Based fMRI-Driven Diffusion Tractography in the Presence of Significant Brain Pathology: A Study Linking Structure and Function in Cerebral Palsy]]> https://www.researchpad.co/article/5989da2bab0ee8fa60b828a8

Diffusion MRI (dMRI) tractography analyses are difficult to perform in the presence of brain pathology. Automated methods that rely on cortical parcellation for structural connectivity studies often fail, while manually defining regions is extremely time consuming and can introduce human error. Both methods also make assumptions about structure-function relationships that may not hold after cortical reorganisation. Seeding tractography with functional-MRI (fMRI) activation is an emerging method that reduces these confounds, but inherent smoothing of fMRI signal may result in the inclusion of irrelevant pathways. This paper describes a novel fMRI-seeded dMRI-analysis pipeline based on surface-meshes that reduces these issues and utilises machine-learning to generate task specific white matter pathways, minimising the requirement for manually-drawn ROIs. We directly compared this new strategy to a standard voxelwise fMRI-dMRI approach, by investigating correlations between clinical scores and dMRI metrics of thalamocortical and corticomotor tracts in 31 children with unilateral cerebral palsy. The surface-based approach successfully processed more participants (87%) than the voxel-based approach (65%), and provided significantly more-coherent tractography. Significant correlations between dMRI metrics and five clinical scores of function were found for the more superior regions of these tracts. These significant correlations were stronger and more frequently found with the surface-based method (15/20 investigated were significant; R2 = 0.43–0.73) than the voxelwise analysis (2 sig. correlations; 0.38 & 0.49). More restricted fMRI signal, better-constrained tractography, and the novel track-classification method all appeared to contribute toward these differences.

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<![CDATA[Activin A Inhibits MPTP and LPS-Induced Increases in Inflammatory Cell Populations and Loss of Dopamine Neurons in the Mouse Midbrain In Vivo]]> https://www.researchpad.co/article/5989db4fab0ee8fa60bdb85a

Parkinson’s disease is a chronic neurodegenerative disease characterized by a significant loss of dopaminergic neurons within the substantia nigra pars compacta region and a subsequent loss of dopamine within the striatum. A promising avenue of research has been the administration of growth factors to promote the survival of remaining midbrain neurons, although the mechanism by which they provide neuroprotection is not understood. Activin A, a member of the transforming growth factor β superfamily, has been shown to be a potent anti-inflammatory following acute brain injury and has been demonstrated to play a role in the neuroprotection of midbrain neurons against MPP+-induced degeneration in vitro. We hypothesized that activin A may offer similar anti-inflammatory and neuroprotective effects in in vivo mouse models of Parkinson’s disease. We found that activin A significantly attenuated the inflammatory response induced by both MPTP and intranigral administration of lipopolysaccharide in C57BL/6 mice. We found that administration of activin A promoted survival of dopaminergic and total neuron populations in the pars compacta region both 8 days and 8 weeks after MPTP-induced degeneration. Surprisingly, no corresponding protection of striatal dopamine levels was found. Furthermore, activin A failed to protect against loss of striatal dopamine transporter expression in the striatum, suggesting the neuroprotective action of activin A may be localized to the substantia nigra. Together, these results provide the first evidence that activin A exerts potent neuroprotection and anti-inflammatory effects in the MPTP and lipopolysaccharide mouse models of Parkinson’s disease.

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<![CDATA[The Genetic Architecture of Murine Glutathione Transferases]]> https://www.researchpad.co/article/5989da66ab0ee8fa60b91f71

Glutathione S-transferase (GST) genes play a protective role against oxidative stress and may influence disease risk and drug pharmacokinetics. In this study, massive multiscalar trait profiling across a large population of mice derived from a cross between C57BL/6J (B6) and DBA2/J (D2)—the BXD family—was combined with linkage and bioinformatic analyses to characterize mechanisms controlling GST expression and to identify downstream consequences of this variation. Similar to humans, mice show a wide range in expression of GST family members. Variation in the expression of Gsta4, Gstt2, Gstz1, Gsto1, and Mgst3 is modulated by local expression QTLs (eQTLs) in several tissues. Higher expression of Gsto1 in brain and liver of BXD strains is strongly associated (P < 0.01) with inheritance of the B6 parental allele whereas higher expression of Gsta4 and Mgst3 in brain and liver, and Gstt2 and Gstz1 in brain is strongly associated with inheritance of the D2 parental allele. Allele-specific assays confirmed that expression of Gsto1, Gsta4, and Mgst3 are modulated by sequence variants within or near each gene locus. We exploited this endogenous variation to identify coexpression networks and downstream targets in mouse and human. Through a combined systems genetics approach, we provide new insight into the biological role of naturally occurring variants in GST genes.

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<![CDATA[Enhancing Beta-Catenin Activity via GSK3beta Inhibition Protects PC12 Cells against Rotenone Toxicity through Nurr1 Induction]]> https://www.researchpad.co/article/5989dacaab0ee8fa60bb3c88

Parkinson’s disease (PD) is characterized by progressive degeneration of dopaminergic (DA) neurons in the substantial nigra pars compacta. Increasing evidence showed that Wnt/β-catenin pathway and the orphan nuclear receptor Nurr1 play crucial roles in the survival and functional maintenance of DA neurons in the midbrain and GSK-3β antagonists LiCl and SB216763 were used to activate Wnt/β-catenin pathway experimentally. However, the detail mechanism underlying the neuroprotection against apoptosis on DA neuron is still unclear and the interaction between Wnt/β-catenin and Nurr1 remains undisclosed. In this study, using cell biological assay we investigated the function of Wnt/β-catenin and its crosstalk with Nurr1 on the course of PC12 cell degeneration in vitro. Our data showed that PC12 cell viability was inhibited by rotenone, but attenuated by GSK-3β antagonists LiCl or SB216763. The activity of Wnt/β-catenin pathway was deregulated on exposure of rotenone in a concentration-dependent manner. After the interference of β-catenin with siRNA, LiCl or SB216763 failed to protect PC12 cells from apoptosis by the rotenone toxicity. Our data confirmed that Wnt/β-catenin signaling activated by LiCl or SB216763 enhanced Nurr1 expression to 2.75 ± 0.55 and 4.06 ± 0.41 folds respectively compared with control detected by real-time PCR and the interaction of β-catenin with Nurr1 was identified by co-immunoprecipitate analysis. In conclusion, the data suggested that Wnt/β-catenin and Nurr1 are crucial factors in the survival of DA neurons, and the activation of Wnt/β-catenin pathway exerts protective effects on DA neurons partly by mean of a co-active pattern with Nurr1. This finding may shed a light on the potential treatment of Parkinson disease.

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<![CDATA[Dopaminergic Neurodegeneration in the Mouse Is Associated with Decrease of Viscoelasticity of Substantia Nigra Tissue]]> https://www.researchpad.co/article/5989da31ab0ee8fa60b8475c

The biomechanical properties of brain tissue are altered by histopathological changes due to neurodegenerative diseases like Parkinson's disease (PD). Such alterations can be measured by magnetic resonance elastography (MRE) as a non-invasive technique to determine viscoelastic parameters of the brain. Until now, the correlation between histopathological mechanisms and observed alterations in tissue viscoelasticity in neurodegenerative diseases is still not completely understood. Thus, the objective of this study was to evaluate (1) the validity of MRE to detect viscoelastic changes in small and specific brain regions: the substantia nigra (SN), midbrain and hippocampus in a mouse model of PD, and (2) if the induced dopaminergic neurodegeneration and inflammation in the SN is reflected by local changes in viscoelasticity. Therefore, MRE measurements of the SN, midbrain and hippocampus were performed in adult female mice before and at five time points after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin hydrochloride (MPTP) treatment specifically lesioning dopaminergic neurons in the SN. At each time point, additional mice were utilized for histological analysis of the SN. After treatment cessation, we observed opposed viscoelastic changes in the midbrain, hippocampus and SN with the midbrain showing a gradual rise and the hippocampus a distinct transient increase of viscous and elastic parameters, while viscosity and–to a lesser extent—elasticity in the SN decreased over time. The decrease in viscosity and elasticity in the SN was paralleled by a reduced number of neurons due to the MPTP-induced neurodegeneration. In conclusion, MRE is highly sensitive to detect local viscoelastic changes in specific and even small brain regions. Moreover, we confirmed that neuronal cells likely constitute the backbone of the adult brain mainly accounting for its viscoelasticity. Therefore, MRE could be established as a new potential instrument for clinical evaluation and diagnostics of neurodegenerative diseases.

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<![CDATA[Embryonic Development of the Deer Mouse, Peromyscus maniculatus]]> https://www.researchpad.co/article/5989daebab0ee8fa60bbf4f5

Deer mice, or Peromyscus maniculatus, are an emerging model system for use in biomedicine. P. maniculatus are similar in appearance to laboratory mice, Mus musculus, but are more closely related to hamsters than to Mus. The laboratory strains of Peromyscus have captured a high degree of the genetic variability observed in wild populations, and are more similar to the genetic variability observed in humans than are laboratory strains of Mus. The Peromyscus Genetic Stock Center at the University of South Carolina maintains several lines of Peromyscus harboring mutations that result in developmental defects. We present here a description of P. maniculatus development from gastrulation to late gestation to serve as a guide for researchers interested in pursuing developmental questions in Peromyscus.

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<![CDATA[Correlating Function and Imaging Measures of the Medial Longitudinal Fasciculus]]> https://www.researchpad.co/article/5989daa8ab0ee8fa60ba8321

Objective

To test the validity of diffusion tensor imaging (DTI) measures of tissue injury by examining such measures in a white matter structure with well-defined function, the medial longitudinal fasciculus (MLF). Injury to the MLF underlies internuclear ophthalmoparesis (INO).

Methods

40 MS patients with chronic INO and 15 healthy controls were examined under an IRB-approved protocol. Tissue integrity of the MLF was characterized by DTI parameters: longitudinal diffusivity (LD), transverse diffusivity (TD), mean diffusivity (MD) and fractional anisotropy (FA). Severity of INO was quantified by infrared oculography to measure versional disconjugacy index (VDI).

Results

LD was significantly lower in patients than in controls in the medulla-pons region of the MLF (p < 0.03). FA was also lower in patients in the same region (p < 0.0004). LD of the medulla-pons region correlated with VDI (R = -0.28, p < 0.05) as did FA in the midbrain section (R = 0.31, p < 0.02).

Conclusions

This study demonstrates that DTI measures of brain tissue injury can detect injury to a functionally relevant white matter pathway, and that such measures correlate with clinically accepted evaluation indices for INO. The results validate DTI as a useful imaging measure of tissue integrity.

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<![CDATA[Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain]]> https://www.researchpad.co/article/5989db5aab0ee8fa60bdf2ad

All vertebrate brains develop following a common Bauplan defined by anteroposterior (AP) and dorsoventral (DV) subdivisions, characterized by largely conserved differential expression of gene markers. However, it is still unclear how this Bauplan originated during evolution. We studied the relative expression of 48 genes with key roles in vertebrate neural patterning in a representative amphioxus embryonic stage. Unlike nonchordates, amphioxus develops its central nervous system (CNS) from a neural plate that is homologous to that of vertebrates, allowing direct topological comparisons. The resulting genoarchitectonic model revealed that the amphioxus incipient neural tube is unexpectedly complex, consisting of several AP and DV molecular partitions. Strikingly, comparison with vertebrates indicates that the vertebrate thalamus, pretectum, and midbrain domains jointly correspond to a single amphioxus region, which we termed Di-Mesencephalic primordium (DiMes). This suggests that these domains have a common developmental and evolutionary origin, as supported by functional experiments manipulating secondary organizers in zebrafish and mice.

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<![CDATA[Quantitative T1, T2, and T2* Mapping and Semi-Quantitative Neuromelanin-Sensitive Magnetic Resonance Imaging of the Human Midbrain]]> https://www.researchpad.co/article/5989dae2ab0ee8fa60bbc366

Purpose

Neuromelanin is a dark pigment granule present within certain catecholamine neurons of the human brain. Here, we aimed to clarify the relationship between contrast of neuromelanin-sensitive magnetic resonance imaging (MRI) and MR relaxation times using T1, T2, and T2* mapping of the lower midbrain.

Methods

The subjects were 14 healthy volunteers (11 men and 3 women, mean age 29.9 ± 6.9 years). Neuromelanin-sensitive MRI was acquired using an optimized T1-weighted two-dimensional (2D)-turbo spin-echo sequence. To quantitatively evaluate the relaxation time, 2D-image data for the T1, T2, and T2* maps were also acquired. The regions of interest (substantia nigra pars compacta [SNc], superior cerebellar peduncles [SCP], cerebral peduncles [CP], and midbrain tegmentum [MT]) were manually drawn on neuromelanin-sensitive MRI to measure the contrast ratio (CR) and on relaxation maps to measure the relaxation times.

Results

The CR in the SNc was significantly higher than the CRs in the SCP and CP. Compared to the SCP and CP, the SNc had significantly higher T1 relaxation times. Moreover, the SNc had significantly lower T2 and T2* relaxation times than the other three regions (SCP, CP, and MT). Correlation analyses showed no significant correlations between the CRs in the SNc, SCP, and CP and each relaxation time.

Conclusions

We demonstrated the relationship between the CR of neuromelanin-sensitive MRI and the relaxation times of quantitative maps of the human midbrain.

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<![CDATA[Speech-in-noise representation in the aging midbrain and cortex: Effects of hearing loss]]> https://www.researchpad.co/article/5c92b38bd5eed0c4843a427a

Age-related deficits in speech-in-noise understanding pose a significant problem for older adults. Despite the vast number of studies conducted to investigate the neural mechanisms responsible for these communication difficulties, the role of central auditory deficits, beyond peripheral hearing loss, remains unclear. The current study builds upon our previous work that investigated the effect of aging on normal-hearing individuals and aims to estimate the effect of peripheral hearing loss on the representation of speech in noise in two critical regions of the aging auditory pathway: the midbrain and cortex. Data from 14 hearing-impaired older adults were added to a previously published dataset of 17 normal-hearing younger adults and 15 normal-hearing older adults. The midbrain response, measured by the frequency-following response (FFR), and the cortical response, measured with the magnetoencephalography (MEG) response, were recorded from subjects listening to speech in quiet and noise conditions at four signal-to-noise ratios (SNRs): +3, 0, -3, and -6 dB sound pressure level (SPL). Both groups of older listeners showed weaker midbrain response amplitudes and overrepresentation of cortical responses compared to younger listeners. No significant differences were found between the two older groups when the midbrain and cortical measurements were analyzed independently. However, significant differences between the older groups were found when investigating the midbrain-cortex relationships; that is, only hearing-impaired older adults showed significant correlations between midbrain and cortical measurements, suggesting that hearing loss may alter reciprocal connections between lower and higher levels of the auditory pathway. The overall paucity of differences in midbrain or cortical responses between the two older groups suggests that age-related temporal processing deficits may contribute to older adults’ communication difficulties beyond what might be predicted from peripheral hearing loss alone; however, hearing loss does seem to alter the connectivity between midbrain and cortex. These results may have important ramifications for the field of audiology, as it indicates that algorithms in clinical devices, such as hearing aids, should consider age-related temporal processing deficits to maximize user benefit.

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