Healthy Human Brain Research Articles

The Effect of the 5-HT4 Agonist, Prucalopride, on a Functional Magnetic Resonance Imaging Faces Task in the Healthy Human Brain.

Depression is a common and often recurrent illness with significant negative impact on a global scale. Current antidepressants are ineffective for up to one third of people with depression, many of whom experience persistent symptomatology. 5-HT4 receptor agonists show promise in both animal models of depression and cognitive deficit. We therefore studied the effect of the 5-HT4 partial agonist prucalopride (1 mg daily for 6 days) on the neural processing of emotional faces in 43 healthy participants using a randomised placebo-controlled design. Participants receiving prucalopride were more accurate at identifying the gender of emotional faces. In whole brain analyses, prucalopride was also associated with reduced activation in a network of regions corresponding to the default mode network. However, there was no evidence that prucalopride treatment produced a positive bias in the neural processing of emotional faces. Our study provides further support for a pro-cognitive effect of 5-HT4 receptor agonism in humans. While our current behavioural and neural investigations do not suggest an antidepressant-like profile of prucalopride in humans, it will be important to study a wider dose range in future studies.

Viewing neurovascular coupling through the lens of combined EEG-fNIRS: A systematic review of current methods.

Neurovascular coupling is a key physiological mechanism that occurs in the healthy human brain, and understanding this process has implications for understanding the aging and neuropsychiatric populations. Combined electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) has emerged as a promising, noninvasive tool for probing neurovascular interactions in humans. However, the utility of this approach critically depends on the methodological quality used for multimodal integration. Despite a growing number of combined EEG-fNIRS applications reported in recent years, the methodological rigor of past studies remains unclear, limiting the accurate interpretation of reported findings and hindering the translational application of this multimodal approach. To fill this knowledge gap, we critically evaluated various methodological aspects of previous combined EEG-fNIRS studies performed in healthy individuals. A literature search was conducted using PubMed and PsycINFO on June 28, 2021. Studies involving concurrent EEG and fNIRS measurements in awake and healthy individuals were selected. After screening and eligibility assessment, 96 studies were included in the methodological evaluation. Specifically, we critically reviewed various aspects of participant sampling, experimental design, signal acquisition, data preprocessing, outcome selection, data analysis, and results presentation reported in these studies. Altogether, we identified several notable strengths and limitations of the existing EEG-fNIRS literature. In light of these limitations and the features of combined EEG-fNIRS, recommendations are made to improve and standardize research practices to facilitate the use of combined EEG-fNIRS when studying healthy neurovascular coupling processes and alterations in neurovascular coupling among various populations.

The effect of external stimulation on functional networks in the aging healthy human brain.

Understanding the brain changes occurring during aging can provide new insights for developing treatments that alleviate or reverse cognitive decline. Neurostimulation techniques have emerged as potential treatments for brain disorders and to improve cognitive functions. Nevertheless, given the ethical restrictions of neurostimulation approaches, in silico perturbation protocols based on causal whole-brain models are fundamental to gaining a mechanistic understanding of brain dynamics. Furthermore, this strategy could serve to identify neurophysiological biomarkers differentiating between age groups through an exhaustive exploration of the global effect of all possible local perturbations. Here, we used a resting-state fMRI dataset divided into middle-aged (N =310, <65 years) and older adults (N =310, $\geq $65) to characterize brain states in each group as a probabilistic metastable substate (PMS) space. We showed that the older group exhibited a reduced capability to access a metastable substate that overlaps with the rich club. Then, we fitted the PMS to a whole-brain model and applied in silico stimulations in each node to force transitions from the brain states of the older- to the middle-aged group. We found that the precuneus was the best stimulation target. Overall, these findings could have important implications for designing neurostimulation interventions for reversing the effects of aging on whole-brain dynamics.

Gene expression associated with human brain activations in facial expression recognition.

Previous studies identified some genetic loci of emotion, but few focused on human emotion-related gene expression. In this study, the facial expression recognition (FER) task-based high-resolution fMRI data of 203 subjects in the Human Connectome Project (HCP) and expression data of the six healthy human postmortem brain tissues in theAllen Human Brain Atlas (AHBA) were used to conduct a transcriptome-neuroimaging spatial association analysis. Finally, 371 genes were identified to be significantly associated with FER-related brain activations. Enrichment analyses revealed that FER-related genes were mainly expressed in the brain, especially neurons, and might be related to cell junction organization, synaptic functions, and nervous system development regulation, indicating that FER was a complex polygenetic biological process involving multiple pathways. Moreover, these genes exhibited higher enrichment for psychiatric diseases with heavy emotion impairments. This study provided new insight into understanding the FER-related biological mechanisms and might be helpful to explore treatment methods for emotion-related psychiatric disorders.

Tailored magnetic resonance fingerprinting for simultaneous non-synthetic and quantitative imaging: A repeatability study.

The goals of this study include: (a) generating tailored magnetic resonance fingerprinting (TMRF) based non-synthetic imaging; (b) assessing the repeatability of TMRF and deep learning-based mapping of in vitro ISMRM/NIST phantom and in vivo brain data of healthy human subjects. We have acquired qualitative images obtained from the vendor-supplied gold standard (GS), MRF (synthetic), and TMRF (non-synthetic) on one representative healthy human brain. We also acquired 30 datasets on the ISMRM/NIST phantom for the in vitro repeatability study on a GE Discovery 3T MR750w scanner using the TMRF sequence. We compared T1 and T2 maps generated from 30 ISMRM/NIST phantom datasets to the spin-echo (SE) based GS method as part of the in vitro repeatability study. R-squared coefficient of determination in a simple linear regression and Bland-Altman analysis were computed for 30 datasets of ISMRM/NIST phantom to assess the accuracy of in vitro quantitative TMRF data. The repeatability of T1 and T2 estimates by TMRF was evaluated by calculating the standard deviation (SD) divided by the average of 30 datasets for each sphere, respectively. We acquired 10 volunteers for the in vivo repeatability study on the same scanner using the same TMRF sequence. These volunteers were imaged five times with two runs per repetition, resulting in 100 in vivo datasets. Five contrasts, T1 and T2 maps of 10 human volunteers acquired over five repetitions, were evaluated in the in vivo repeatability study. We computed the intraclass correlation coefficient (ICC) of the signal-to-noise ratio (SNR), signal intensities, T1 and T2 relaxation times in white matter (WM), and gray matter (GM). The synthetic images generated from MRF show partial volume and flow artifacts compared to non-synthetic images obtained from TMRF images and the GS. In vitro studies show that TMRF estimates have less than 5% variations except sphere 14 in the T2 array (6.36%). TMRF and SE relaxometry measurements were strongly correlated; R2 values were 0.9958 and 0.9789 for T1 and T2 estimates, respectively. Based on the ICC values, SNR, mean intensity values, and relaxation times of WM and GM for the in vivo studies were consistent. T1 and T2 values of WM and GM were similar to previously published values. The mean ± SD of T1 and T2 for WM for ten subjects and five repeats are 992 ± 41ms and 99 ± 6ms, while the corresponding values for T1 and T2 for GM are 1598 ± 73ms and 152 ± 14ms. TMRF and deep learning-based reconstruction produce repeatable, non-synthetic multi-contrast images, and parametric maps simultaneously.

Cortical thickness systematically varies with curvature and depth in healthy human brains.

Cortical thickness varies throughout the cortex in a systematic way. However, it is challenging to investigate the patterns of cortical thickness due to the intricate geometry of the cortex. The cortex has a folded nature both in radial and tangential directions which forms not only gyri and sulci but also tangential folds and intersections. In this article, cortical curvature and depth are used to characterize the spatial distribution of the cortical thickness with much higher resolution than conventional regional atlases. To do this, a computational pipeline was developed that is capable of calculating a variety of quantitative measures such as surface area, cortical thickness, curvature (mean curvature, Gaussian curvature, shape index, intrinsic curvature index, and folding index), and sulcal depth. By analyzing 501 neurotypical adult human subjects from the ABIDE‐I dataset, we show that cortex has a very organized structure and cortical thickness is strongly correlated with local shape. Our results indicate that cortical thickness consistently increases along the gyral–sulcal spectrum from concave to convex shape, encompassing the saddle shape along the way. Additionally, tangential folds influence cortical thickness in a similar way as gyral and sulcal folds; outer folds are consistently thicker than inner.

One-week escitalopram intake alters the excitation-inhibition balance in the healthy female brain.

Neural health relies on cortical excitation–inhibition balance (EIB). Previous research suggests a link between increased cortical excitation and neuroplasticity induced by selective serotonin reuptake inhibitors (SSRIs). Whether there are modulations of EIB following SSRI‐administration in the healthy human brain, however, remains unclear. Thus, in a randomized double‐blind study, we administered a clinically relevant dose of 20 mg escitalopram for 7 days (time when steady state is achieved) in 59 healthy women (28 escitalopram, 31 placebo) on oral contraceptives. We acquired resting‐state electroencephalography data at baseline, after a single dose, and at steady state. We assessed 1/f slope of the power spectrum as a marker of EIB, compared individual trajectories of 1/f slope changes contrasting single dose and 1‐week drug intake, and tested the relationship of escitalopram plasma levels and cortical excitatory and inhibitory balance shifts. Escitalopram‐intake was associated with decreased 1/f slope, indicating an EIB shift in favor of excitation. Furthermore, 1/f slope at baseline and after a single dose of escitalopram was associated with 1/f slope at steady state. Higher plasma escitalopram levels at a single dose were associated with better maintenance of these EIB changes throughout the drug administration week. These findings demonstrate the potential for 1/f slope to predict individual cortical responsivity to SSRIs and widen the lens through which we map the human brain by testing an interventional psychopharmacological design in a clearly defined endocrinological state.

Cellular and Molecular Targets for Non-Invasive, Non-Pharmacological Therapeutic/Rehabilitative Interventions in Acute Ischemic Stroke.

BACKGROUND: Cerebral circulation delivers the blood flow to the brain through a dedicated network of sanguine vessels. A healthy human brain can regulate cerebral blood flow (CBF) according to any physiological or pathological challenges. The brain is protected by its self-regulatory mechanisms, which are dependent on neuronal and support cellular populations, including endothelial ones, as well as metabolic, and even myogenic factors. OBJECTIVES: Accumulating data suggest that “non-pharmacological” approaches might provide new opportunities for stroke therapy, such as electro-/acupuncture, hyperbaric oxygen therapy, hypothermia/cooling, photobiomodulation, therapeutic gases, transcranial direct current stimulations, or transcranial magnetic stimulations. We reviewed the recent data on the mechanisms and clinical implications of these non-pharmaceutical treatments. METHODS: To present the state-of-the-art for currently available non-invasive, non-pharmacological-related interventions in acute ischemic stroke, we accomplished this synthetic and systematic literature review based on the Preferred Reporting Items for Systematic Principles Reviews and Meta-Analyses (PRISMA). RESULTS: The initial number of obtained articles was 313. After fulfilling the five steps in the filtering/selection methodology, 54 fully eligible papers were selected for synthetic review. We enhanced our documentation with other bibliographic resources connected to our subject, identified in the literature within a non-standardized search, to fill the knowledge gaps. Fifteen clinical trials were also identified. DISCUSSION: Non-invasive, non-pharmacological therapeutic/rehabilitative interventions for acute ischemic stroke are mainly holistic therapies. Therefore, most of them are not yet routinely used in clinical practice, despite some possible beneficial effects, which have yet to be supplementarily proven in more related studies. Moreover, few of the identified clinical trials are already completed and most do not have final results. CONCLUSIONS: This review synthesizes the current findings on acute ischemic stroke therapeutic/rehabilitative interventions, described as non-invasive and non-pharmacological.

Identification of Prognostic Biomarkers for Glioblastoma Based on Transcriptome and Proteome Association Analysis.

Objective:Glioblastoma multiforme (GBM) is the most malignant primary brain tumor in adults. This study aimed to identify significant prognostic biomarkers related to GBM.Methods:We collected 3 GBM and 3 healthy human brain samples for transcriptome and proteomic sequencing analysis. Differentially expressed genes (DEGs) between GBM and control samples were identified using the edge R package in R. Functional enrichment analyses, prediction of long noncoding RNA target genes, and protein-protein interaction network analyses were performed. Subsequently, transcriptomic and proteomic association analyses, validation using The Cancer Genome Atlas (TCGA) database, and survival and prognostic analyses were conducted. Then the hub genes directly related to GBM were screened. Finally, the expression of key genes was verified by quantitative polymerase chain reaction (qPCR).Results:Totally, 1140 transcripts and 503 proteins were significantly up- or down-regulated. A total of 25 genes were upregulated and 62 were downregulated at both the transcriptome and proteome levels. Results from TCGA database showed that 84 of these 87 genes matched with transcriptome sequencing results. A Cox regression analysis suggested that Fibronectin 1(FN1) was a prognostic risk factor. The qPCR results showed that FN1 was significantly upregulated in GBM samples.Conclusions: FN1 may play a role in GBM progression through ECM-receptor interaction and PI3K-Akt signaling pathways. FN1 may be considered as a prognostic biomarkers related to GBM.

Anisotropic mechanical properties in the healthy human brain estimated with multi-excitation transversely isotropic MR elastography

Magnetic resonance elastography (MRE) is an MRI technique for imaging the mechanical properties of brain in vivo, and has shown differences in properties between neuroanatomical regions and sensitivity to aging, neurological disorders, and normal brain function. Past MRE studies investigating these properties have typically assumed the brain is mechanically isotropic, though the aligned fibers of white matter suggest an anisotropic material model should be considered for more accurate parameter estimation. Here we used a transversely isotropic, nonlinear inversion algorithm (TI-NLI) and multi-excitation MRE to estimate the anisotropic material parameters of individual white matter tracts in healthy young adults. We found significant differences between individual tracts for three recovered anisotropic parameters: substrate shear stiffness, μ (range: 2.57 – 3.02 kPa), shear anisotropy, φ (range: -0.026 – 0.164), and tensile anisotropy, ζ (range: 0.559 – 1.049). Additionally, we demonstrated the repeatability of these parameter estimates in terms of lower variability of repeated measures in a single subject relative to variability in our sample population. Further, we observed significant differences in anisotropic mechanical properties between segments of the corpus callosum (genu, body, and splenium), which is expected based on differences in axonal microstructure. This study shows the ability of MRE with TI-NLI to estimate anisotropic mechanical properties of white matter and presents reference properties for tracts throughout the healthy brain. Statement of significanceIn this study we use magnetic resonance elastography to determine the mechanical properties of white matter, which can be useful in characterizing neurological conditions such as multiple sclerosis and traumatic brain injury. However, due to its fibrous nature, accurate estimation of mechanical properties of white matter requires an anisotropic material model. In this work, we use a transversely isotropic inversion algorithm with data from multi-excitation MRE to determine the anisotropic mechanical properties of white matter in a healthy young population based upon an anisotropic material model. We display the ability of MRE to capture structural differences between different white matter tracts and sub-regions of these tracts, which are expected to reflect differences such as average axon thickness and myelin density. This robust estimation of white matter anisotropic properties in a young, healthy population provides an avenue for future studies to implement these methods to examine brain development, aging, and pathology.

Electrical Phenotyping of Human Brain Tissues: An Automated System for Tumor Delineation

Precise surgical excision of brain tumors depends on the surgeon&#x2019;s ability to accurately differentiate tumors from healthy brain tissues. We have developed an automated system integrated with biochips, an actuation unit, and electronics to measure the electrical resistivity of ex vivo human brain tissues for differentiating normal and tumor. The electrical resistivity of fresh (n &#x003D; 48), formalin-fixed for one week (n &#x003D; 48), and long-term (six months) formalin-fixed (n &#x003D; 27) healthy human brain samples from different anatomical regions and tumor samples (glioma n &#x003D; 6; fresh, formalin-fixed for one week, and formalin-fixed for six months) were measured using the automated system. The resistivity of glioma (22.4 &#x00B1; <inline-formula> <tex-math notation="LaTeX">$1.6~\Omega$ </tex-math></inline-formula>.cm) was significantly lesser than the normal region (98.6 &#x00B1; <inline-formula> <tex-math notation="LaTeX">$1.4~\Omega$ </tex-math></inline-formula>.cm) for fresh tissue samples (p &#x003D; 5e-8). The trend of lower resistivity of glioma compared to normal was preserved after one week and six months of formalin fixation. We also report the effects of heterogeneity of normal brain tissue and formalin-fixation on the electrical properties of tissues. White matter regions were found to have higher resistivity compared to grey matter regions. The heterogeneity associated with grey matter regions was lower than the white matter regions. Formalin-fixation was observed to increase the magnitude of resistivity measured while retaining the observed trend across the different regions of the brain and tumors. The study shows that the electrical resistivity could potentially be used as an additional biomarker for delineating normal from the tumor.

Identification of HnRNPC as a novel Tau exon 10 splicing factor using RNA antisense purification mass spectrometry

ABSTRACT Alternative splicing in Tau exon 10 generates 3 R- and 4 R-Tau proteoforms, which have equal abundance in healthy adult human brain. Aberrant alternative splicing in Tau exon 10 leads to distortion of the balanced 3 R- and 4 R-Tau expression levels, which is a causal factor to trigger toxic Tau aggregation, neuron dysfunction and patient death in a group of neurodegenerative diseases known as tauopathies. Hence, identification of regulators upstream of the Tau exon 10 splicing events are crucial to understanding pathogenic mechanisms driving tauopathies. In this study, we used RNA Antisense Purification with Mass Spectrometry (RAP-MS) analysis to identify RNA-binding proteins (RBPs) that interact with the Tau pre-mRNA near exon 10. Among the newly identified RBP candidates, we show that knockdown of hnRNPC induces Tau exon 10 skipping whereas overexpression of hnRNPC promotes Tau exon 10 inclusion. In addition, we show that hnRNPC interacts with the poly-uridine (U-tract) sequences in introns 9 and 10 of Tau pre-mRNA. Mutation of these U-tract motifs abolished binding of hnRNPC with Tau pre-mRNA fragment and blocked its impact on Tau exon 10 inclusion. These findings indicate that hnRNPC binds and utilizes these U-tract motifs located in introns 9 and 10 of Tau pre-mRNA to promote Tau exon 10 inclusion. Intriguingly, high hnRNPC expression level is associated with progressive supranuclear palsy (PSP), a sporadic tauopathy with pathological accumulation of Tau species that contain exon 10, which suggests a putative therapeutic role of hnRNPC for PSP treatment.

40 Hz Light Flicker Alters Human Brain Electroencephalography Microstates and Complexity Implicated in Brain Diseases.

Previous studies showed that entrainment of light flicker at low gamma frequencies provided neuroprotection in mouse models of Alzheimer’s disease (AD) and stroke. The current study was set to explore the feasibility of using 40 Hz light flicker for human brain stimulation for future development as a tool for brain disease treatment. The effect of 40 Hz low gamma frequency light on a cohort of healthy human brains was examined using 64 channel electroencephalography (EEG), followed by microstate analyses. A random frequency light flicker was used as a negative control treatment. Light flicker at 40 Hz significantly increased the corresponding band power in the O1, Oz, and O3 electrodes covering the occipital areas of both sides of the brain, indicating potent entrainment with 40 Hz light flicker in the visual cortex area. Importantly, the 40 Hz light flicker significantly altered microstate coverage, transition duration, and the Lempel-Ziv complexity (LZC) compared to the rest state. Microstate metrics are known to change in the brains of Alzheimer’s disease, schizophrenia, and stroke patients. The current study laid the foundation for the future development of 40 Hz light flicker as therapeutics for brain diseases.

Energy metabolism measured by 31P magnetic resonance spectroscopy in the healthy human brain

Background and purposePhosphorous magnetic resonance spectroscopy (31P-MRS) allows a non-invasive analysis of phosphorus-containing compounds in vivo. The present study investigated the influence of brain region, hemisphere, age, sex and brain volume on 31P-MRS metabolites in healthy adults. Materials and methodsSupratentorial brain 31P-MRS spectra of 125 prospectively recruited healthy volunteers (64 female, 61 male) aged 20 to 85 years (mean: 49.4 ± 16.9 years) were examined with a 3D-31P-MRS sequence at 3T, and the compounds phosphocreatine (PCr), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were measured. From this data, the metabolite ratios PCr/ATP, Pi/ATP and PCr/Pi were calculated for different brain regions. In addition, volumes of gray matter, white matter and cerebrospinal fluid were determined. ResultsFor all metabolite ratios significant regional differences and in several regions sex differences were found. In some brain regions and for some metabolites hemispheric differences were detected. In addition, changes with aging were found, which differed between women and men. ConclusionsThe present results indicate that 31P-MRS metabolism varies throughout the brain, with age and between sexes, and therefore have important practical implications for the design and the interpretation of future 31P-MRS studies under physiological conditions and in patients with various cerebral diseases.

Imaging transcriptomics: Convergent cellular, transcriptomic, and molecular neuroimaging signatures in the healthy adult human brain.

The integration of transcriptomic and neuroimaging data, "imaging transcriptomics," has recently emerged to generate hypotheses about potential biological pathways underlying regional variability in neuroimaging features. However, the validity of this approach is yet to be examined in depth. Here, we sought to bridge this gap by performing transcriptomic decoding of the regional distribution of well-known molecular markers spanning different elements of the biology of the healthy human brain. Imaging transcriptomics identifies biological and cell pathways that are consistent with the known biology of a wide range of molecular neuroimaging markers. The extent to which it can capture patterns of gene expression that align well with elements of the biology of the neuroinflammatory axis, at least in healthy controls without a proinflammatory challenge, is inconclusive. Imaging transcriptomics might constitute an interesting approach to improve our understanding of the biological pathways underlying regional variability in a wide range of neuroimaging phenotypes.

The Role of the Human Brain Neuron-Glia-Synapse Composition in Forming Resting-State Functional Connectivity Networks.

While significant progress has been achieved in studying resting-state functional networks in a healthy human brain and in a wide range of clinical conditions, many questions related to their relationship to the brain’s cellular constituents remain. Here, we use quantitative Gradient-Recalled Echo (qGRE) MRI for mapping the human brain cellular composition and BOLD (blood–oxygen level-dependent) MRI to explore how the brain cellular constituents relate to resting-state functional networks. Results show that the BOLD signal-defined synchrony of connections between cellular circuits in network-defined individual functional units is mainly associated with the regional neuronal density, while the between-functional units’ connectivity strength is also influenced by the glia and synaptic components of brain tissue cellular constituents. These mechanisms lead to a rather broad distribution of resting-state functional network properties. Visual networks with the highest neuronal density (but lowest density of glial cells and synapses) exhibit the strongest coherence of the BOLD signal as well as the strongest intra-network connectivity. The Default Mode Network (DMN) is positioned near the opposite part of the spectrum with relatively low coherence of the BOLD signal but with a remarkably balanced cellular contents, enabling DMN to have a prominent role in the overall organization of the brain and hierarchy of functional networks.

The relationship between plasma free fatty acids, cognitive function and structural integrity of the brain in middle-aged healthy humans

Background: The cerebral composition of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) is believed to influence cognitive function and structural damage of the aging brain. However, existing data is inconsistent.Materials and Methods: This retrospective study explored the association between free plasma PUFA concentrations, cognitive function and brain structure atrophy in a well-characterized community-dwelling cohort of elderly individuals without stroke and dementia. Ten different fatty acids were analyzed in stored plasma samples from 391 non-demented elderly individuals by gas chromatography mass spectrometry. Neuropsychiatric tests capturing memory, executive function and visuopractical skills were performed in all participants. Brain atrophy was assessed by MRI in a subset of 167 individuals.Results: Higher plasma concentrations of free ω-6 PUFAs (p = 0.042), and, in particular, linoleic acid (p = 0.01), were significantly associated with lower executive function. No significant association existed between ω-3 PUFA concentrations and cognitive functioning. The volume of the frontal lobes was inversely associated with ω-6 PUFAs, whereas ω-3 PUFAs were positively related with temporal lobe volumes. All associations did not withstand correction for multiple comparisons.Conclusions: Our study suggests subtle effects of PUFA imbalances on cognition and brain structure. Yet the observed associations are weak and unlikely to be of clinical relevance. The brain regions that seem to be most sensitive to imbalances of ω-3 and ω-6 PUFAs are the frontal and temporal lobes.

Vestibular System Eletrophysiology: An Analysis of the Relationship between Hearing and Movement.

Introduction Knowledge about the positive effects that music and dance bring, in its various forms, to the healthy human brain, is important not only in the context of basic neuroscience but may also strongly affect practices in neurorehabilitation. Objective To verify the relationship between hearing and movement and, specifically, to analyze the interference of professional dance practice and formal musical training in the magnitude of the vestibule-cervical and vestibular reflexes. Method The sample consisted of 92 subjects, aged between 18 and 35 years old, 31 professional musicians, 31 ballet dancers, and 30 control subjects. Only subjects with normal hearing sensitivity were included. Cervical vestibular evoked myogenic potential (cVEMP) was recorded in the sternocleidomastoid muscle, and ocular vestibular evoked myogenic potential (oVEMP) was recorded in the lower oblique muscle of the eye, using tone-bursts (500Hz). Analysis of variance (ANOVA) or Kruskall-Wallis tests were performed. Results The cVEMP presented earlier and higher amplitude waves when recorded in the group of dancers, with a significant difference between all tested groups for latency and amplitude of the N23 wave; the comparison was restricted between dancers and control groups, with no difference between ballet dancers and musicians. The N1 wave of the oVEMP presented lower latencies in dancers than in musicians and controls ( p = 0.001). No significant differences were found between the groups for the P1 wave. Conclusion Greater magnitudes of vestibule-cervical reflex responses and faster vestibule-ocular reflex responses were observed in dancers. Dance practice provides greater development of the vestibular system, but musical training also contributes to the magnitude of these responses.

Upregulation of miR-144-3p expression attenuates glioma cell viability and invasion by targeting BCL6.

Glioma remains to be an aggressive type of cancer with poor prognosis irrespective of the type of standard treatment applied. Therefore, identification of accurate early diagnostic methods and therapeutic strategies for glioma is imperative for the treatment of this disease. The expression of a number of miRNAs in glioma have been reported to be associated with the regulation of tumorigenic progression, cancer cell proliferation, metastasis, invasion, angiogenesis and drug resistance. The aim of the present study was to assess the function of the microRNA (miR/miRNA)-144-3p/BCL6 axis in glioma. Reverse transcription-quantitative PCR was used to measure miR-144-3p and BCL6 expression. Western blotting was used for measuring BCL6 expression. Luciferase reporter assay was used to assess the association between miR-144-3p and BCL6 and a tumor xenograft model was established for assess tumor growth. The data demonstrated that miR-144-3p was decreased whereas BCL6 expression was increased in glioma tissues compared with those in healthy human brain tissues, where miR-144-3p suppressed BCL6 expression by targeting the 3'-UTR sequence of BCL6. miR-144-3p overexpression alleviated proliferation and invasion in U251 cells whereas transfection with the BCL6-overexpressing plasmid rescued the suppressive effects of miR-144-3p upregulation on the proliferation and invasion of U251 cells. In addition, miR-144-3p overexpression and BCL6 downregulation inhibited tumor progression in a mouse tumor xenograft model. The present findings suggest that miR-144-3p and BCL6 may serve to be indicator of proliferation and invasion for patients with glioma. Furthermore, BCL6 may serve an important role in the miR-144-3p-mediated regulation of proliferation and invasion of glioma cells, where the miR-144-3p/BCL6 axis can be used to target patients with glioma therapeutically.

Culturing astrocytes on substrates that mimic brain tumors promotes enhanced mechanical forces

Astrocytes are essential to brain homeostasis and their dysfunction can have devastating consequences on human quality of life. Such deleterious effects are generally due in part to changes that occur at the cellular level, which may be biochemical or biomechanical in nature. One biomechanical change that can occur is a change in tissue stiffness. Brain tumors are generally associated with increased brain tissue stiffness, but the impact increased tissue stiffness has on astrocyte biomechanical behavior is poorly understood. Therefore, in this study we cultured human astrocytes on flexible substrates with stiffness that mimicked the healthy human brain (1 kPa), meningioma (4 kPa), and glioma (11 kPa) and investigated astrocyte biomechanical behavior by measuring cell-substrate tractions, strain energies, cell-cell intercellular stresses, and cellular velocities. In general, tractions, intercellular stresses, and strain energy was observed to increase as a function of increased substrate stiffness, while cell velocities were observed to decrease with increased substrate stiffness. We believe this study will be of great importance to the fields of brain pathology and brain physiology.