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https://www.readbyqxmd.com/read/28340406/a-local-adjustment-strategy-for-the-initialization-of-dynamic-causal-modelling-to-infer-effective-connectivity-in-brain-epileptic-structures
#1
Wentao Xiang, Ahmad Karfoul, Huazhong Shu, Régine Le Bouquin Jeannès
This paper addresses the question of effective connectivity in the human cerebral cortex in the context of epilepsy. Among model based approaches to infer brain connectivity, spectral Dynamic Causal Modelling is a conventional technique for which we propose an alternative to estimate cross spectral density. The proposed strategy we investigated tackles the sub-estimation of the free energy using the well-known variational Expectation-Maximization algorithm highly sensitive to the initialization of the parameters vector by a permanent local adjustment of the initialization process...
March 7, 2017: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/28340172/repositioning-disulfiram-as-a-radiosensitizer-against-atypical-teratoid-rhabdoid-tumor
#2
Young Eun Lee, Seung Ah Choi, Pil Ae Kwack, Hak Jae Kim, Il Han Kim, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Sangjoon Chong, Sung-Hye Park, Kyung Duk Park, Do Won Hwang, Kyeung Min Joo, Seung-Ki Kim
Background.: Atypical teratoid/rhabdoid tumor (AT/RT) is one of the most common malignant brain tumors in infants. Although cancer stem cells of AT/RT express aldehyde dehydrogenase (ALDH), effective chemotherapies against AT/RT have not been established. Here, we examined radiosensitizing effects of disulfiram (DSF), an irreversible inhibitor of ALDH against AT/RT for a novel therapeutic method. Methods.: Patient-derived primary cultured AT/RT cells (SNU.AT/RT-5 and SNU...
March 17, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28339833/vdac1-is-a-molecular-target-in-glioblastoma-with-its-depletion-leading-to-reprogrammed-metabolism-and-reversed-oncogenic-properties
#3
Tasleem Arif, Yakov Kerlin, Itay Nakdimon, Daniel Benharroch, Avijit Paul, Daniela Dadon-Klein, Varda Shoshan-Barmatz
Background.: Glioblastoma (GBM), an aggressive brain tumor with frequent relapses and a high mortality, still awaits an effective treatment. Like many cancers, GBM cells acquire oncogenic properties, including metabolic reprogramming, vital for growth. As such, tumor metabolism is an emerging avenue for cancer therapy. One relevant target is the voltage-dependent anion channel 1 (VDAC1), a mitochondrial protein controlling cell energy and metabolic homeostasis. Methods...
February 28, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28339748/genotype-based-gene-signature-of-glioma-risk
#4
Yen-Tsung Huang, Yi Zhang, Zhijin Wu, Dominique S Michaud
Background.: Glioma accounts for 80% of malignant brain tumors, but its etiologic determinants remain elusive. Despite genetic susceptibility loci identified by genome-wide association study (GWAS), the agnostic approach leaves open the possibility that other susceptibility genes remain to be discovered. Here we conduct a gene-centric integrative GWAS (iGWAS) of glioma risk that combines transcriptomics and genetics. Methods.: We synthesized a brain transcriptomics dataset (n = 354), a GWAS dataset (n = 4203), and an advanced glioma tumor transcriptomic dataset (n = 483) to conduct an iGWAS...
February 22, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28339691/z-guggulsterone-produces-antidepressant-like-effects-in-mice-through-activation-of-the-bdnf-signaling-pathway
#5
Chao Huang, Wen-Feng Hu, Ji-Li Wang, Peng Wang, Yu Gong, Li-Juan Tong, Bo Jiang, Wei Zhang, Yi-Bin Qin, Zhuo Chen, Rong-Rong Yang
Background: Z-guggulsterone, an active compound extracted from the gum resin of the tree commiphora mukul, has been shown to improve animal memory deficits via activating the brain-derived neurotrophic factor (BDNF) signaling pathway. Here, we investigated the antidepressant-like effect of Z-guggulsterone in a chronic unpredictable stress (CUS) mouse model of depression. Methods: The effects of Z-guggulsterone were assessed in mice tail suspension test (TST), forced swimming test (FST)...
February 21, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28339607/gross-motor-trajectories-during-the-first-year-of-life-for-preterm-infants-with-very-low-birth-weight
#6
Yu-Han Su, Suh-Fang Jeng, Wu-Shiun Hsieh, Yu-Kang Tu, Yen-Tzu Wu, Li-Chiou Chen
Background.: Early identification of motor dysfunction in very-low-birth-weight (VLBW) preterm infants is important in order to provide early intervention. Objective.: This study was to examine the motor trajectories of VLBW preterm infants during their first year of life and to investigate the predictive ability and influencing factors of the trajectories. Design and Methods.: A total of 342 VLBW preterm infants were prospectively assessed for motor development by the Alberta Infant Motor Scales at 4, 6, 9 and 12 months and for developmental outcomes using the Bayley Scales of Infant and Toddler Development- second edition at 24 months...
February 4, 2017: Physical Therapy
https://www.readbyqxmd.com/read/28339310/investigations-of-octylglyceryl-dextran-graft-poly-lactic-acid-nanoparticles-for-peptide-delivery-to-the-brain
#7
Asme Boussahel, Daniel M Ibegbu, Rhita Lamtahri, Julie Maucotel, Julien Chuquet, Benjamin Lefranc, Jérôme Leprince, Marta Roldo, Jean-Claude Le Mével, Darek Gorecki, Eugen Barbu
AIM: Develop modified dextran nanoparticles showing potential to assist with drug permeation across the blood-brain barrier for the delivery of neuropeptides. METHODS: Nanoparticles loaded by emulsification with model macromolecular actives were characterized in terms of stability, cytotoxicity and drug-release behavior. Peptide-loaded nanoformulations were tested in an in vivo trout model and in food-deprived mice. RESULTS: Nanoformulations loaded with model peptides showed good stability and appeared nontoxic in low concentration against human brain endothelial cells...
March 24, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28335587/neuronatin-is-associated-with-anti-inflammatory-role-in-the-white-adipose-tissue
#8
Hye In Ka, Sora Han, Ae Lee Jeong, Sunyi Lee, Hyo Jeong Yong, Ariundavaa Boldbaatar, Hyun Jeong Joo, Su Jung Soh, Ji Young Park, Jong-Seok Lim, Myung Sok Lee, Young Yang
Neuronatin (NNAT) is known to regulate ion channels during brain development and plays a role in maintaining the structure of the nervous system. A previous in silico analysis showed that Nnat was overexpressed in the adipose tissue of an obese rodent model relative to the wild-type. Therefore, the aim of the present study was to investigate the function of Nnat in the adipose tissue. Because obesity is known to systemically induce low-grade inflammation, the Nnat expression level was examined in the adipose tissue obtained from C57BL/6 mice administered lipopolysaccharide (LPS)...
March 24, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28334998/spatiotemporal-mapping-of-epileptic-spikes-using-simultaneous-eeg-functional-mri
#9
Jennifer M Walz, Mangor Pedersen, Amir Omidvarnia, Mira Semmelroch, Graeme D Jackson
Epileptic spikes occur on the sub-second timescale and are known to involve not only epileptic foci but also large-scale distributed brain networks. There is likely to be a sequence of neural activity in multiple brain regions that occurs within the duration of a single spike, but standard electroencephalography-functional magnetic resonance imaging analyses, which use only the timing of the spikes to model the functional magnetic resonance imaging data, cannot determine the sequence of these activations. Our aim in this study is to temporally resolve these spatial activations to observe the spatiotemporal dynamics of the spike-related neural activity at a sub-second timescale...
February 20, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334990/insulin-resistance-and-exendin-4-treatment-for-multiple-system-atrophy
#10
Fares Bassil, Marie-Hélène Canron, Anne Vital, Erwan Bezard, Yazhou Li, Nigel H Greig, Seema Gulyani, Dimitrios Kapogiannis, Pierre-Olivier Fernagut, Wassilios G Meissner
Multiple system atrophy is a fatal sporadic adult-onset neurodegenerative disorder with no symptomatic or disease-modifying treatment available. The cytopathological hallmark of multiple system atrophy is the accumulation of α-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Impaired insulin/insulin-like growth factor-1 signalling (IGF-1) and insulin resistance (i.e. decreased insulin/IGF-1) have been reported in other neurodegenerative disorders such as Alzheimer's disease. Increasing evidence also suggests impaired insulin/IGF-1 signalling in multiple system atrophy, as corroborated by increased insulin and IGF-1 plasma concentrations in multiple system atrophy patients and reduced IGF-1 brain levels in a transgenic mouse model of multiple system atrophy...
March 14, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334978/therapeutic-window-of-dopamine-d2-3-receptor-occupancy-to-treat-psychosis-in-alzheimer-s-disease
#11
Suzanne Reeves, Emma McLachlan, Julie Bertrand, Fabrizia D Antonio, Stuart Brownings, Akshay Nair, Suki Greaves, Alan Smith, David Taylor, Joel Dunn, Paul Marsden, Robert Kessler, Robert Howard
Antipsychotic drugs, originally developed to treat schizophrenia, are used to treat psychosis, agitation and aggression in Alzheimer's disease. In the absence of dopamine D2/3 receptor occupancy data to inform antipsychotic prescribing for psychosis in Alzheimer's disease, the mechanisms underpinning antipsychotic efficacy and side effects are poorly understood. This study used a population approach to investigate the relationship between amisulpride blood concentration and central D2/3 occupancy in older people with Alzheimer's disease by combining: (i) pharmacokinetic data (280 venous samples) from a phase I single (50 mg) dose study in healthy older people (n = 20, 65-79 years); (ii) pharmacokinetic, 18F-fallypride D2/3 receptor imaging and clinical outcome data on patients with Alzheimer's disease who were prescribed amisulpride (25-75 mg daily) to treat psychosis as part of an open study (n = 28; 69-92 years; 41 blood samples, five pretreatment scans, 19 post-treatment scans); and (iii) 18F-fallypride imaging of an antipsychotic free Alzheimer's disease control group (n = 10, 78-92 years), to provide additional pretreatment data...
February 4, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334922/scn2a-deletion-improves-survival-and-brain-heart-dynamics-in-the-kcna1-null-mouse-model-of-sudden-unexpected-death-in-epilepsy-sudep
#12
Vikas Mishra, Bharat K Karumuri, Nicole M Gautier, Rui Liu, Timothy N Hutson, Stephanie L Vanhoof-Villalba, Ioannis Vlachos, Leonidas Iasemidis, Edward Glasscock
People with epilepsy have greatly increased probability of premature mortality due to sudden unexpected death in epilepsy (SUDEP). Identifying which patients are most at risk of SUDEP is hindered by a complex genetic etiology, incomplete understanding of the underlying pathophysiology, and lack of prognostic biomarkers. Here we evaluated heterozygous Scn2a gene deletion (Scn2a+/-) as a protective genetic modifier in the Kcna1 knockout mouse (Kcna1-/-) model of SUDEP, while searching for biomarkers of SUDEP risk embedded in electroencephalography (EEG) and electrocardiography (ECG) recordings...
March 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334915/salience-and-default-mode-network-dysregulation-in-chronic-cocaine-users-predict-treatment-outcome
#13
Xiujuan Geng, Yuzheng Hu, Hong Gu, Betty Jo Salmeron, Bryon Adinoff, Elliot A Stein, Yihong Yang
While chronic cocaine use is associated with abnormalities in both brain structure and function within and interactions between regions, previous studies have been limited to interrogating structure and function independently, and the detected neural differences have not been applied to independent samples to assess the clinical relevance of results. We investigated consequences of structural differences on resting-state functional connectivity in cocaine addiction and tested whether resting-state functional connectivity of the identified circuits predict relapse in an independent cohort...
February 20, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334886/glioblastoma-associated-microglia-and-macrophages-targets-for-therapies-to-improve-prognosis
#14
Candice C Poon, Susobhan Sarkar, V Wee Yong, John J P Kelly
Glioblastoma is the most common and most malignant primary adult human brain tumour. Diagnosis of glioblastoma carries a dismal prognosis. Treatment resistance and tumour recurrence are the result of both cancer cell proliferation and their interaction with the tumour microenvironment. A large proportion of the tumour microenvironment consists of an inflammatory infiltrate predominated by microglia and macrophages, which are thought to be subverted by glioblastoma cells for tumour growth. Thus, glioblastoma-associated microglia and macrophages are logical therapeutic targets...
February 4, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334882/decreased-integration-and-information-capacity-in-stroke-measured-by-whole-brain-models-of-resting-state-activity
#15
Mohit H Adhikari, Carl D Hacker, Josh S Siegel, Alessandra Griffa, Patric Hagmann, Gustavo Deco, Maurizio Corbetta
While several studies have shown that focal lesions affect the communication between structurally normal regions of the brain, and that these changes may correlate with behavioural deficits, their impact on brain's information processing capacity is currently unknown. Here we test the hypothesis that focal lesions decrease the brain's information processing capacity, of which changes in functional connectivity may be a measurable correlate. To measure processing capacity, we turned to whole brain computational modelling to estimate the integration and segregation of information in brain networks...
February 20, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334875/white-matter-changes-in-paediatric-multiple-sclerosis-and-monophasic-demyelinating-disorders
#16
Giulia Longoni, Robert A Brown, Parya MomayyezSiahkal, Colm Elliott, Sridar Narayanan, Amit Bar-Or, Ruth Ann Marrie, E Ann Yeh, Massimo Filippi, Brenda Banwell, Douglas L Arnold
Most children who experience an acquired demyelinating syndrome of the central nervous system will have a monophasic disease course, with no further clinical or radiological symptoms. A subset will be diagnosed with multiple sclerosis, a life-long disorder. Using linear mixed effects models we examined longitudinal diffusion properties of normal-appearing white matter in 505 serial scans of 132 paediatric participants with acquired demyelinating syndromes followed for a median of 4.4 years, many from first clinical presentation, and 106 scans of 80 healthy paediatric participants...
March 14, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334861/defective-signaling-through-plexin-a1-compromises-the-development-of-the-peripheral-olfactory-system-and-neuroendocrine-reproductive-axis-in-mice
#17
Séverine Marcos, Carine Monnier, Xavier Rovira Algans, Corinne Fouveaut, Nelly Pitteloud, Fabrice Ango, Catherine Dodé, Jean-Pierre Hardelin
The olfacto-genital syndrome (Kallmann syndrome) associates congenital hypogonadism due to gonadotropin-releasing hormone (GnRH) deficiency and anosmia. This is a genetically heterogeneous developmental disease with various modes of transmission, including oligogenic inheritance. Previous reports have involved defective cell signaling by semaphorin-3A in the disease pathogenesis. Here, we report that the embryonic phenotype of Plxna1-/- mutant mice lacking plexin-A1 (a major receptor of class 3 semaphorins), though not fully penetrant, resembles that of Kallmann syndrome fetuses...
March 2, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334855/slc30a9-mutation-affecting-intracellular-zinc-homeostasis-causes-a-novel-cerebro-renal-syndrome
#18
Yonatan Perez, Zamir Shorer, Keren Liani-Leibson, Pauline Chabosseau, Rotem Kadir, Michael Volodarsky, Daniel Halperin, Shiran Barber-Zucker, Hanna Shalev, Ruth Schreiber, Libe Gradstein, Evgenia Gurevich, Raz Zarivach, Guy A Rutter, Daniel Landau, Ohad S Birk
A novel autosomal recessive cerebro-renal syndrome was identified in consanguineous Bedouin kindred: neurological deterioration was evident as of early age, progressing into severe intellectual disability, profound ataxia, camptocormia and oculomotor apraxia. Brain MRI was normal. Four of the six affected individuals also had early-onset nephropathy with features of tubulo-interstitial nephritis, hypertension and tendency for hyperkalemia, though none had rapid deterioration of renal function. Genome wide linkage analysis identified an ∼18 Mb disease-associated locus on chromosome 4 (maximal logarithm of odds score 4...
February 9, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334695/how-the-embryonic-chick-brain-twists
#19
Zi Chen, Qiaohang Guo, Eric Dai, Nickolas Forsch, Larry A Taber
During early development, the tubular embryonic chick brain undergoes a combination of progressive ventral bending and rightward torsion, one of the earliest organ-level left-right asymmetry events in development. Existing evidence suggests that bending is caused by differential growth, but the mechanism for the predominantly rightward torsion of the embryonic brain tube remains poorly understood. Here, we show through a combination of in vitro experiments, a physical model of the embryonic morphology and mechanics analysis that the vitelline membrane (VM) exerts an external load on the brain that drives torsion...
November 2016: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28334401/vocal-tract-images-reveal-neural-representations-of-sensorimotor-transformation-during-speech-imitation
#20
Daniel Carey, Marc E Miquel, Bronwen G Evans, Patti Adank, Carolyn McGettigan
Imitating speech necessitates the transformation from sensory targets to vocal tract motor output, yet little is known about the representational basis of this process in the human brain. Here, we address this question by using real-time MR imaging (rtMRI) of the vocal tract and functional MRI (fMRI) of the brain in a speech imitation paradigm. Participants trained on imitating a native vowel and a similar nonnative vowel that required lip rounding. Later, participants imitated these vowels and an untrained vowel pair during separate fMRI and rtMRI runs...
March 18, 2017: Cerebral Cortex
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