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Introduction: Metabotropic glutamate receptor 5 (mGluR5) that regulates glutamatergic neurotransmission contributes to pathophysiology of epilepsy. In this study, we monitored the changes of mGluR5 in vivo using [11C]ABP688 PET during the epileptogenesis in a pilocarpine-induced epilepsy rat model. Methods: In vivo mGluR5 images were acquired using [11C]ABP688 microPET/CT in pilocarpine-induced chronic epilepsy rat models and controls. We also acquired microPET/CT at acute, subacute as well as chronic periods after status epilepticus. Non-displaceable binding potential (BPND) of [11C]ABP688 was calculated using simplified reference tissue model in a voxel-based manner. mGluR5 BPND of the rat brains of epilepsy models and controls were compared. Results: Status epilepticus developed after pilocarpine administration and was followed by recurrent spontaneous seizures for more than 3 weeks. In chronic epilepsy rat model, BPND in hippocampus and amygdala was reduced on a voxel-based analysis. Temporal changes of mGluR5 BPND was also found. In acute period after status epilepticus, mGluR5 BPND was reduced in the whole brain. BPND of caudate-putamen was restored in subacute period, while BPND of the rest of the brain was still lower. In chronic period, global BPND was normalized except in hippocampus and amygdala. Conclusions: In vivo imaging of mGluR5 using [11C]ABP688 microPET/CT could successfully reveal the regional changes of mGluR5 binding potential of the rat brain in a pilocarpine-induced epilepsy model. The temporal and spatial changes in mGluR5 availability suggest [11C]ABP688 PET imaging in epilepsy provide abnormal glutamatergic network during epileptogenesis. [ABSTRACT FROM AUTHOR]

The brain network is usually constructed by estimating the connectivity matrix and thresholding it at an arbitrary level. The problem with this standard method is that we do not have any generally accepted criteria for determining a proper threshold. Thus, we propose a novel multiscale framework that models all brain networks generated over every possible threshold. Our approach is based on persistent homology and its various representations such as the Rips filtration, barcodes, and dendrograms. This new persistent homological framework enables us to quantify various persistent topological features at different scales in a coherent manner. The barcode is used to quantify and visualize the evolutionary changes of topological features such as the Betti numbers over different scales. By incorporating additional geometric information to the barcode, we obtain a single linkage dendrogram that shows the overall evolution of the network. The difference between the two networks is then measured by the Gromov–Hausdorff distance over the dendrograms. As an illustration, we modeled and differentiated the FDG-PET based functional brain networks of 24 attention-deficit hyperactivity disorder children, 26 autism spectrum disorder children, and 11 pediatric control subjects. [ABSTRACT FROM PUBLISHER]

Partial correlation is a useful connectivity measure for brain networks, especially, when it is needed to remove the confounding effects in highly correlated networks. Since it is difficult to estimate the exact partial correlation under the small-n large-p situation, a sparseness constraint is generally introduced. In this paper, we consider the sparse linear regression model with a l1-norm penalty, also known as the least absolute shrinkage and selection operator (LASSO), for estimating sparse brain connectivity. LASSO is a well-known decoding algorithm in the compressed sensing (CS). The CS theory states that LASSO can reconstruct the exact sparse signal even from a small set of noisy measurements. We briefly show that the penalized linear regression for partial correlation estimation is related to CS. It opens a new possibility that the proposed framework can be used for a sparse brain network recovery. As an illustration, we construct sparse brain networks of 97 regions of interest (ROIs) obtained from FDG-PET imaging data for the autism spectrum disorder (ASD) children and the pediatric control (PedCon) subjects. As validation, we check the network reproducibilities by leave-one-out cross validation and compare the clustered structures derived from the brain networks of ASD and PedCon. [ABSTRACT FROM AUTHOR]

Abstract: In congenitally deaf children, chronological age is generally accepted as a critical factor that affects successful rehabilitation following cochlear implantation (CI). However, a wide variance among patients is known to exist regardless of the age at CI [Sarant, J.Z., Blamey, P.J., Dowell, R.C., Clark, G.M., Gibson, W.P., 2001. Variation in speech perception scores among children with cochlear implants. Ear Hear. 22, 18–28]. In a previous study, we reported that prelingually deaf children in the age range 5–7 years at implantation showed greatest outcome variability [Oh S.H., Kim C.S., Kang E.J., Lee D.S., Lee H.J., Chang S.O., Ahn S.H., Hwang C.H., Park H.J., Koo J.W., 2003. Speech perception after cochlear implantation over a 4-year time period. Acta Otolaryngol. 123, 148–153]. Eleven children who underwent CI between the age of 5 and 7 1/2 years were subdivided into a good (above 65%: GOOD) and a poor (below 45%: POOR) group based on the performance in a speech perception test given 2 years after CI. The preoperative 18F-FDG-PET (F-18 fluorodeoxyglucose positron emission tomography) images were compared between the two groups in order to examine if regional glucose metabolic difference preexisted before the CI surgery. In the GOOD group, metabolic activity was greater in diverse fronto-parietal regions compared to the POOR group. In the POOR group, the regions related to the ventral visual pathway showed greater metabolic activity relative to the GOOD group. These findings suggest that the deaf children who had developed greater executive and visuospatial functions subserved by the prefrontal and parietal cortices might be successful in auditory language learning after CI. On the contrary, greater dependency on the visual function subserved by the occipito-temporal region due to auditory deprivation may interfere with acquisition of auditory language after CI. [Copyright &y& Elsevier]

Extracellular vesicles (EVs) have drawn attention as promising therapeutic agents whose characteristics resemble their parent cells. However, their practical utility is limited by low EV yields. Cell culture under fluidic flow to enhance EV secretion has been proposed to address this challenge. However, the precise mechanism of increased EV production in response to flow conditions has not been studied thoroughly. We investigated the mechanism of higher release of EVs from mesenchymal stem cells under flow conditions, focusing on the correlation between intracellular calcium ions and EV production. Shear stress was applied to cells through shaking cultures, and stimulated cells showed increased EV production. Results suggested that the stimulation of EV secretion was promoted by an increasing intracellular concentration of calcium ions, primarily due to their transport through calcium ion channels in the plasma membrane, which was induced by shear stress. Furthermore, we confirmed that the essential characteristics of the EVs released under shear stress remained intact by analyzing individual EVs and assessing their regeneration efficacy in a model of kidney injury in vitro . Unveiling the reason for the high production of EVs under shear stress is expected to contribute to the development of EV-application research by increasing the reliability of EV utilization.

Community and rich-club detection are a well-known method to extract functionally specialized subnetwork in brain connectivity analysis. They find densely connected subregions with large modularity or high degree in brain connectivity studies. However, densely connected nodes are not the only representation of network shape. In this study, we propose a new method to extract abnormal holes, which are another representation of network shape. While densely connected component characterizes network's efficiency, abnormal holes characterize inefficiency. The proposed method differs from the existing hole detection in two respects. One is to use Hodge Laplacian to obtain a harmonic hole in the linear combination of edges, rather than a subset of edges. The other is to use the kernel density estimation of persistence diagram of random networks to determine the significance of a hole, rather than using the persistence of a hole. We applied the proposed method to find the abnormality of metabolic connectivity in the FDG PET data of ADNI. We found that, as AD severely progressed, the brain network had more abnormal holes. The localized holes showed how inefficient the structure of brain network became as the disease progressed.

Background: Ginseng is a popular traditional herbal medicine in north-eastern Asia. It has been used for human health for over thousands of years. With the rise in global temperature, the production of Korean ginseng (Panax ginseng C.A.Meyer) in Korea have migrated from mid to northern parts of the Korean peninsula to escape from the various higher temperature related stresses. Under the high ambient temperature, vegetative growth was accelerated, which resulted in early flowering. This precocious phase change led to yield loss. Despite of its importance as a traditional medicine, biological mechanisms of ginseng has not been well studied and even the genome sequence of ginseng is yet to be determined due to its complex genome structure. Thus, it is challenging to investigate the molecular biology mechanisms at the transcript level., Results: To investigate how ginseng responds to the high ambient temperature environment, we performed high throughput RNA sequencing and implemented a bioinformatics pipeline for the integrated analysis of small-RNA and mRNA-seq data without a reference genome. By performing reverse transcriptase (RT) PCR and sanger sequencing of transcripts that were assembled using our pipeline, we validated that their sequences were expressed in our samples. Furthermore, to investigate the interaction between genes and non-coding small RNAs and their regulation status under the high ambient temperature, we identified potential gene regulatory miRNAs. As a result, 100,672 contigs with significant expression level were identified and 6 known, 214 conserved and 60 potential novel miRNAs were predicted to be expressed under the high ambient temperature., Conclusion: Collectively, we have found that development, flowering and temperature responsive genes were induced under high ambient temperature, whereas photosynthesis related genes were repressed. Functional miRNAs were down-regulated under the high ambient temperature. Among them are miR156 and miR396 that target flowering (SPL6/9) and growth regulating genes (GRF) respectively.

This study aims to evaluate the clinical validity of [ 18 F]THK5351 positron emission tomography (PET) for the assessment of disease progression and symptoms in Alzheimer's disease (AD). Fifty-one patients with AD dementia, 30 patients with amnestic mild cognitive impairment (aMCI), and 43 controls with normal cognition (NC) were included. All subjects underwent [ 18 F]THK5351 PET, 3.0-T magnetic resonance imaging, and detailed neuropsychological tests. Regions of interest and voxel-based statistical analyses were performed. In patients with AD dementia, [ 18 F]THK5351 retention was greater in most association cortices as well as the limbic area compared to NC or aMCI participants. Patients with aMCI also showed higher THK5351 retention in those areas compared to NC. [ 18 F]THK5351 retention significantly correlated with neuropsychological test results. Negative correlations between [ 18 F]THK5351 and [ 18 F] fluorodeoxyglucose were observed in AD dementia and aMCI groups. Mirror images of [ 18 F]THK5351 retention and glucose hypometabolism in [ 18 F] fluorodeoxyglucose were noticeable in the focal variants of AD. [ 18 F]THK5351 PET reflects disease severity and symptoms in AD. Our results suggest [ 18 F]THK5351 is reflective of tau-related AD pathology., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Finding underlying relationships among multiple imaging modalities in a coherent fashion is one of the challenging problems in multimodal analysis. In this study, we propose a novel approach based on multidimensional persistence. In the extension of the previous threshold-free method of persistent homology, we visualize and discriminate the topological change of integrated brain networks by varying not only threshold but also mixing ratio between two different imaging modalities. The multidimensional persistence is implemented by a new bimodal integration method called 1D projection. When the mixing ratio is predefined, it constructs an integrated edge weight matrix by projecting two different connectivity information onto the one dimensional shared space. We applied the proposed methods to PET and MRI data from 23 attention deficit hyperactivity disorder (ADHD) children, 21 autism spectrum disorder (ASD), and 10 pediatric control subjects. From the results, we found that the brain networks of ASD, ADHD children and controls differ, with ASD and ADHD showing asymmetrical changes of connected structures between metabolic and morphological connectivities. The difference of connected structure between ASD and the controls was mainly observed in the metabolic connectivity. However, ADHD showed the maximum difference when two connectivity information were integrated with the ratio 0.6. These results provide a multidimensional homological understanding of disease-related PET and MRI networks that disclose the network association with ASD and ADHD. Hum Brain Mapp 38:1387-1402, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

The aim of this report was to investigate the clinical outcome of deep brain stimulation (DBS) for autism spectrum disorder (ASD) and the functional and structural changes in the brain after DBS. We present a 14-year-old boy with ASD and self-injurious behavior (SIB) refractory with medical and behavioral therapy. He was treated by bilateral nucleus accumbens (NAc) DBS. Remarkable clinical improvement was observed following NAc DBS. Brain fluorodeoxyglucose-positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) volumetric studies revealed that the metabolism in the prefrontal and the frontal cortex as well as the occipital cortex was markedly decreased in association with the decreased cortical volumes in those areas 2 years after NAc DBS. The therapeutic potential of NAc DBS is suggested for the clinical improvement of patients with ASD and SIB with structural and functional changes after DBS.

The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases. Inhibition of high mobility group box 1 (HMGB1) and restoration of endothelial integrity are emerging as an attractive therapeutic strategies in the management of severe sepsis or septic shock. Here, we examined the effects of methylthiouracil (MTU), used as antithyroid drug, by monitoring the effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1, and on the modulation of HMGB1-mediated inflammatory responses. The anti-inflammatory activities of MTU were determined by measuring permeability, leukocyte adhesion and migration, and the activation of pro-inflammatory proteins in HMGB1-activated HUVECs and mice. MTU inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses in human endothelial cells. MTU also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with MTU reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury. Our results indicate that MTUs could be candidate therapeutic agents for various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Unlabelled: Inaccuracy in MR image-based attenuation correction (MR-AC) leads to errors in quantification and the misinterpretation of lesions in brain PET/MRI studies. To resolve this problem, we proposed an improved ultrashort echo time MR-AC method that was based on a multiphase level-set algorithm with main magnetic field (B0) inhomogeneity correction. We also assessed the feasibility of this level-set-based MR-AC method (MR-AC(level)), compared with CT-AC and MR-AC provided by the manufacturer of the PET/MRI scanner (MR-AC(mMR))., Methods: Ten healthy volunteers and 20 Parkinson disease patients underwent(18)F-FDG and(18)F-fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane ((18)F-FP-CIT) PET scans, respectively, using both PET/MRI and PET/CT scanners. The level-set-based segmentation algorithm automatically delimited air, bone, and soft tissue from the ultrashort echo time MR images. For the comparison, MR-AC maps were coregistered to reference CT. PET sinogram data obtained from PET/CT studies were then reconstructed using the CT-AC, MR-AC(mMR), and MR-AC(level) maps. The accuracies of SUV, SUVr (SUV and its ratio to the cerebellum), and specific-to-nonspecific binding ratios obtained using MR-AC(level) and MR-AC(mMR) were compared with CT-AC using region-of-interest- and voxel-based analyses., Results: There was remarkable improvement in the segmentation of air cavities and bones and the quantitative accuracy of PET measurement using the level set. Although the striatal and cerebellar activities in (18)F-FP-CIT PET and frontal activity in (18)F-FDG PET were significantly underestimated by the MR-AC(mMR), the MR-AC(level) provided PET images almost equivalent to the CT-AC images. PET quantification error was reduced by a factor of 3 using MR-AC(level) (SUV error < 10% in MR-AC(level) and < 30% in MR-AC(mMR) [version VB18P], and < 5% in MR-AC(level) and < 15% in MR-AC(mMR) [VB20P])., Conclusion: The results of this study indicate that our new multiphase level-set-based MR-AC method improves the quantitative accuracy of brain PET in PET/MRI studies., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

The expression of secretory group IIA phospholipase A2 (sPLA2-IIA) is enhanced by development of inflammatory disorders. In this study, sPLA2-IIA expression was induced in the lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells and mice to evaluate the effect of polyozellin. Polyozellin, a major constituent of a Korea edible mushroom Polyozellus multiplex, has been known to exhibit the biological activities such as anti-oxidative and anti-inflammatory effects. Polyozellin remarkably suppressed the LPS-mediated protein expression and activity of sPLA2-IIA via inhibition of phosphorylation of cytosolic phospholipase A2 and extracellular signal-regulated kinase 1/2. These results demonstrated that polyozellin might play an important role in the modulation of sPLA2-IIA expression and activity in response to the inflammatory diseases.

Aim and Objective: Two structurally related flavonoids found in Cyclopia subternata, namely vicenin-2 and scolymoside, were examined for its effects on inflammatory responses by monitoring the effects of vicenin-2 and scolymoside on lipopolysaccharide (LPS)-mediated vascular inflammatory responses., Methods: The anti-inflammatory activities of vicenin-2 and scolymoside were determined by measuring permeability,monocytes adhesion and migration, and activation of pro-inflammatory proteins in LPS-activated HUVECs and mice., Results: We found that post-treatment of each compound inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of human neutrophils to human endothelial cells. Each compound induced potent inhibition of phorbol-12-myristate 13-acetate (PMA) and LPS-induced endothelial cell protein C receptor (EPCR)shedding. It also suppressed LPS-induced hyperpermeability and leukocytes migration in vivo. Furthermore,each compound suppressed the production of tumor necrosis factor-α (TNF-α) or Interleukin (IL)-6 and the activation of nuclear factor-κB (NF-κB) or extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, posttreatment with each compound resulted in reduced LPS-induced lethal endotoxemia., Conclusion: Vicenin-2 and scolymoside possess anti-inflammatory functions by inhibiting hyperpermeability,expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.

Drug repositioning refers to the development of existing drugs for new indications. These drugs may have (I) failed to show efficacy in late stage clinical trials without safety issues; (II) stalled in the development for commercial reasons; (III) passed the point of patent expiry; or (IV) are being explored in new geographic markets. Over the past decade, pressure on the pharmaceutical industry caused by the 'innovation gap' owing to rising development costs and stagnant product output have become major reasons for the growing interest in drug repositioning. Companies that offer a variety of broad platforms for identifying new indications have emerged; some have been successful in building their own pipelines of candidates with reduced risks and timelines associated with further clinical development. The business models and platforms offered by these companies will be validated if they are able to generate positive proof-of-concept clinical data for their repositioned compounds. This review describes the strategy of biomarker-guided repositioning of chemotherapeutic drugs for inflammation therapy, considering the repositioning of methylthiouracil (MTU), an antithyroid drug, as a potential anti-inflammatory reagent., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

While deafness-induced plasticity has been investigated in the visual and auditory domains, not much is known about language processing in audiovisual multimodal environments for patients with restored hearing via cochlear implant (CI) devices. Here, we examined the effect of agreeing or conflicting visual inputs on auditory processing in deaf patients equipped with degraded artificial hearing. Ten post-lingually deafened CI users with good performance, along with matched control subjects, underwent H 2 (15) O-positron emission tomography scans while carrying out a behavioral task requiring the extraction of speech information from unimodal auditory stimuli, bimodal audiovisual congruent stimuli, and incongruent stimuli. Regardless of congruency, the control subjects demonstrated activation of the auditory and visual sensory cortices, as well as the superior temporal sulcus, the classical multisensory integration area, indicating a bottom-up multisensory processing strategy. Compared to CI users, the control subjects exhibited activation of the right ventral premotor-supramarginal pathway. In contrast, CI users activated primarily the visual cortices more in the congruent audiovisual condition than in the null condition. In addition, compared to controls, CI users displayed an activation focus in the right amygdala for congruent audiovisual stimuli. The most notable difference between the two groups was an activation focus in the left inferior frontal gyrus in CI users confronted with incongruent audiovisual stimuli, suggesting top-down cognitive modulation for audiovisual conflict. Correlation analysis revealed that good speech performance was positively correlated with right amygdala activity for the congruent condition, but negatively correlated with bilateral visual cortices regardless of congruency. Taken together these results suggest that for multimodal inputs, cochlear implant users are more vision-reliant when processing congruent stimuli and are disturbed more by visual distractors when confronted with incongruent audiovisual stimuli. To cope with this multimodal conflict, CI users activate the left inferior frontal gyrus to adopt a top-down cognitive modulation pathway, whereas normal hearing individuals primarily adopt a bottom-up strategy.

Temporal lobe epilepsy is associated with dysfunctional brain networks. Here we investigated metabolic connectivity in the pilocarpine-induced epilepsy rat model and applied a new multiscale framework to the analysis of metabolic networks of small-animal brains. [(18)F]fluorodeoxyglucose PET was acquired in pilocarpine-induced chronic epilepsy rats and controls to yield interregional metabolic correlation by inter-subject manner. When interregional correlation of epilepsy rats and controls was compared directly, the epilepsy rats showed reduced connectivity involving the left amygdala and left entorhinal cortex. When regional graph properties were calculated to characterize abnormal nodes in the epileptic brain network, the epilepsy rats showed reduced nodal and local efficiencies in the left amygdala. Then, a new multiscale framework, persistent brain network homology, was used to examine metabolic connectivity with a threshold-free approach and the difference between two networks was analyzed using single linkage distances (SLDs) of all pairwise nodes. We found a tendency for longer SLDs between the left insula/left amygdala and bilateral cortical/subcortical structures in the epilepsy rats. Persistent brain network homology analysis as well as interregional correlation study implied the abnormal left limbic-paralimbic-neocortical network in the pilocarpine-induced epilepsy rat models. In conclusion, we found a globally disrupted network in the epileptic brain in rats, particularly in the limbic and paralimbic structures by direct comparison, graph properties and multiscale network analysis. These results demonstrate that the multiscale and threshold-free network analysis can be used to find the network abnormality in small-animal brains as a preclinical research., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Prolonged deprivation of auditory input can change brain networks in pre- and postlingual deaf adults by brain-wide reorganization. To investigate morphological changes in these brains voxel-based morphometry, voxel-wise correlation with the primary auditory cortex, and whole brain network analyses using morphological covariance were performed in eight prelingual deaf, eleven postlingual deaf, and eleven hearing adults. Network characteristics based on graph theory and network filtration based on persistent homology were examined. Gray matter density in the primary auditor cortex was preserved in prelingual deafness, while it tended to decrease in postlingual deafness. Unlike postlingual, prelingual deafness showed increased bilateral temporal connectivity of the primary auditory cortex compared to the hearing adults. Of the graph theory-based characteristics, clustering coefficient, betweenness centrality, and nodal efficiency all increased in prelingual deafness, while all the parameters of postlingual deafness were similar to the hearing adults. Patterns of connected components changing during network filtration were different between prelingual deafness and hearing adults according to the barcode, dendrogram, and single linkage matrix representations, while these were the same in postlingual deafness. Nodes in fronto-limbic and left temporal components were closely coupled, and nodes in the temporo-parietal component were loosely coupled, in prelingual deafness. Patterns of connected components changing in postlingual deafness were the same as hearing adults. We propose that the preserved density of auditory cortex associated with increased connectivity in prelingual deafness, and closer coupling between certain brain areas, represent distinctive reorganization of auditory and related cortices compared with hearing or postlingual deaf adults. The differential network reorganization in the prelingual deaf adults could be related to the absence of auditory speech experience., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In our daily lives, we are confronted with a large amount of information. Because only a small fraction can be encoded in long-term memory, the brain must rely on powerful mechanisms to filter out irrelevant information. To understand the neuronal mechanisms underlying the gating of information into long-term memory, we employed a paradigm where the encoding was directed by a "Remember" or a "No-Remember" cue. We found that posterior alpha activity increased prior to the "No-Remember" stimuli, whereas it decreased prior to the "Remember" stimuli. The sources were localized in the parietal cortex included in the dorsal attention network. Subjects with a larger cue-modulation of the alpha activity had better memory for the to-be-remembered items. Interestingly, alpha activity reflecting successful inhibition following the "No-Remember" cue was observed in the frontal midline structures suggesting preparatory inhibition was mediated by anterior parts of the dorsal attention network. During the presentation of the memory items, there was more gamma activity for the "Remember" compared to the "No-Remember" items in the same regions. Importantly, the anticipatory alpha power during cue predicted the gamma power during item. Our findings suggest that top-down controlled alpha activity reflects attentional inhibition of sensory processing in the dorsal attention network, which then finally gates information to long-term memory. This gating is achieved by inhibiting the processing of visual information reflected by neuronal synchronization in the gamma band. In conclusion, the functional architecture revealed by region-specific changes in the alpha activity reflects attentional modulation which has consequences for long-term memory encoding., (Copyright © 2014 Wiley Periodicals, Inc.)

The difference between networks has been often assessed by the difference of global topological measures such as the clustering coefficient, degree distribution and modularity. In this paper, we introduce a new framework for measuring the network difference using the Gromov-Hausdorff (GH) distance, which is often used in shape analysis. In order to apply the GH distance, we define the shape of the brain network by piecing together the patches of locally connected nearest neighbors using the graph filtration. The shape of the network is then transformed to an algebraic form called the single linkage matrix. The single linkage matrix is subsequently used in measuring network differences using the GH distance. As an illustration, we apply the proposed framework to compare the FDG-PET based functional brain networks out of 24 attention deficit hyperactivity disorder (ADHD) children, 26 autism spectrum disorder (ASD) children and 11 pediatric control subjects.

Background: Neurobiologic studies have suggested that dysregulation of central noradrenergic systems may be involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD), and it has been hypothesized that genetic changes in the norepinephrine pathways might contribute to dysfunction of the prefrontal cortex circuits in ADHD. We previously reported decreased cerebral blood flow in the right lateral prefrontal cortex and both orbitofrontal cortices in children with ADHD. Genetic investigations have shown that the alpha-2A-adrenergic receptor gene (ADRA2A) is associated with ADHD. Our aim was to examine whether the presence of a risk allele of the ADRA2A MspI polymorphism is associated with differences in regional cerebral blood flow in boys with ADHD., Methods: We recruited 21 Korean boys with ADHD (mean age 9.9, standard deviation [SD] 2.7 yr) and 11 age- and sex-matched controls (mean age 10.6 [SD 2.1] yr). Each participant underwent technetium-99m-hexamethylpropylene amine oxime ((99m)Tc-HMPAO) single-photon emission computed tomography. We performed image analyses with voxe-wise t statistics using SPM2., Results: We found regional hypoperfusion in the prefrontal regions, including the right orbitofrontal and right medial gyri, and the bilateral putamen and cerebellum in boys with ADHD relative to controls (p < 0.0005, uncorrected for multiple comparisons). Boys with ADHD who carried the C allele (n = 13) at the ADRA2A MspI polymorphism had reduced perfusion in the bilateral orbitofrontal regions compared with those without the C allele (n = 8) (p < 0.0005, uncorrected for multiple comparisons)., Limitations: This study was limited by the small sample size, and we did not obtain genetic data from the controls., Conclusion: Our findings suggest that regional differences in cerebral perfusion in the orbitofrontal cortex represent an intermediate neuroimaging phenotype associated with the ADRA2A MspI polymorphism; these data support the validity of the noradrenergic hypothesis regarding the pathophysiology of ADHD.

Purpose: To investigate the clinical application of a stereotactic body radiation therapy (SBRT) boost in locally advanced pancreatic cancer patients with a focus on local efficacy and toxicity., Methods and Materials: We retrospectively reviewed 30 patients with locally advanced and nonmetastatic pancreatic cancer who had been treated between 2004 and 2006. Follow-up duration ranged from 4 to 41 months (median, 14.5 months). A total dose of 40 Gy was delivered in 20 fractions using a conventional three-field technique, and then a single fraction of 14, 15, 16, or 17 Gy SBRT was administered as a boost without a break. Twenty-one patients received chemotherapy. Overall and local progression-free survival were calculated and prognostic factors were evaluated., Results: One-year overall survival and local progression-free survival rates were 60.0% and 70.2%, respectively. One patient (3%) developed Grade 4 toxicity. Carbohydrate antigen 19-9 response was found to be an independent prognostic factor for survival., Conclusions: Our findings indicate that a SBRT boost provides a safe means of increasing radiation dose. Based on the results of this study, we recommend that a well controlled Phase II study be conducted on locally advanced pancreatic cancer.

Purpose: Regionally connected areas of the resting brain can be detected by fluorodeoxyglucose-positron emission tomography (FDG-PET). Voxel-wise metabolic connectivity was examined, and normative data were established by performing interregional correlation analysis on statistical parametric mapping of FDG-PET data., Materials and Methods: Characteristics of seed volumes of interest (VOIs) as functional brain units were represented by their locations, sizes, and the independent methods of their determination. Seed brain areas were identified as population-based gyral VOIs (n = 70) or as population-based cytoarchitectonic Brodmann areas (BA; n = 28). FDG uptakes in these areas were used as independent variables in a general linear model to search for voxels correlated with average seed VOI counts. Positive correlations were searched in entire brain areas., Results: In normal adults, one third of gyral VOIs yielded correlations that were confined to themselves, but in the others, correlated voxels extended to adjacent areas and/or contralateral homologous regions. In tens of these latter areas with extensive connectivity, correlated voxels were found across midline, and asymmetry was observed in the patterns of connectivity of left and right homologous seed VOIs. Most of the available BAs yielded correlations reaching contralateral homologous regions and/or neighboring areas. Extents of metabolic connectivity were not found to be related to seed VOI size or to the methods used to define seed VOIs., Conclusions: These findings indicate that patterns of metabolic connectivity of functional brain units depend on their regional locations. We propose that interregional correlation analysis of FDG-PET data offers a means of examining voxel-wise regional metabolic connectivity of the resting human brain.

Purpose: The aim of this study was to establish the procedures for 3D voxel-based statistical analysis of 2-deoxy-2-[(18)F]fluoro-D-glucose-positron emission tomography (FDG-PET) images of a cat's brain obtained using a small animal-dedicated PET system and to assess the utility of this approach in investigating the cerebral glucose metabolism in an animal model of cortical deafness., Procedures: This study compared several different strategies for the spatial processing of PET data acquired twice from eight cats before and after inducing deafness in terms of the comparability of the statistical analysis results to the established pattern of the cerebral glucose metabolic changes in the deaf animals., Results: The accuracy of the spatial preprocessing procedures and the statistical significance of the comparison were improved by removing the background activities outside the brain regions. The use of the spatial normalization parameters obtained from the mean image of the realigned data set for individual data also helped improve the statistical significance of the paired t testing. It was also found that an adjustment of the registration options was also important for increasing the precision of the realignment., Conclusions: A method for voxel-based analysis of the PET data of a cat's brain was optimized. The results demonstrated the high localization accuracy and specificity of this method, which is expected to be useful for examining the brain PET data of medium-sized animals such as cats.

Many forms of long-lasting behavioral and synaptic plasticity require the synthesis of new proteins. For example, long-term potentiation (LTP) that endures for more than an hour requires both transcription and translation. The signal-transduction mechanisms that couple synaptic events to protein translational machinery during long-lasting synaptic plasticity, however, are not well understood. One signaling pathway that is stimulated by growth factors and results in the translation of specific mRNAs includes the rapamycin-sensitive kinase mammalian target of rapamycin (mTOR, also known as FRAP and RAFT-1). Several components of this translational signaling pathway, including mTOR, eukaryotic initiation factor-4E-binding proteins 1 and 2, and eukaryotic initiation factor-4E, are present in the rat hippocampus as shown by Western blot analysis, and these proteins are detected in the cell bodies and dendrites in the hippocampal slices by immunostaining studies. In cultured hippocampal neurons, these proteins are present in dendrites and are often found near the presynaptic protein, synapsin I. At synaptic sites, their distribution completely overlaps with a postsynaptic protein, PSD-95. These observations suggest the postsynaptic localization of these proteins. Disruption of mTOR signaling by rapamycin results in a reduction of late-phase LTP expression induced by high-frequency stimulation; the early phase of LTP is unaffected. Rapamycin also blocks the synaptic potentiation induced by brain-derived neurotrophic factor in hippocampal slices. These results demonstrate an essential role for rapamycin-sensitive signaling in the expression of two forms of synaptic plasticity that require new protein synthesis. The localization of this translational signaling pathway at postsynaptic sites may provide a mechanism that controls local protein synthesis at potentiated synapses.