Antidiabetic properties of Capparis spinosa L. and its components

Publication date: August 2017
Source:Biomedicine & Pharmacotherapy, Volume 92
Author(s): Hamideh Vahid, Hassan Rakhshandeh, Ahmad Ghorbani
An increasing line of evidence confirmed that apart from conventional hypoglycemic drugs, diet and medicinal plants have beneficial effects on diabetes. Capparis spinosa L. (Caper) is a perennial shrub in the Capparidaceae family. It grows in different regions of the world, particularly in Asian and African countries. A wide range of biological activities such as antioxidant, anti-inflammatory, anticancer, antimicrobial, and antidiabetic effects have been reported for this plant. In this review, it is focused on beneficial effects of C. spinosa on diabetes. Several studies have showed the antihyperglycemic and hypolipidemic activities of C. spinosa. The putative mechanisms involved in the antihyperglycemic effects of C. spinosa include reducing carbohydrate absorption from the small intestine, inhibiting gluconeogenesis in the liver, enhancing glucose uptake by tissues, and beta cell protection/regeneration. This plant also ameliorates cardiovascular disorders, liver damage, and nephropathy in animal models of diabetes, which are attributed to its antioxidant phytochemicals such as phenolic compounds, flavonoids, carotenoids, tocopherols, and terpenes. Antihyperglycemic and hypolipidemic activities of C. spinose, along with its beneficial effects on diabetic complications, make it a good candidate for the management of diabetes. Well-designed clinical trials are necessary to define the advantages and disadvantages of C. spinose for diabetic patients.



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Identification and in vitro characterization of novel nanobodies against human granulocyte colony-stimulating factor receptor to provide inhibition of G-CSF function

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Hamid Bakherad, Seyed Latif Mousavi Gargari, Zargham Sepehrizadeh, Hossein Aghamollaei, Ramezan Ali Taheri, Maryam Torshabi, Mojtaba Tabatabaei Yazdi, Walead Ebrahimizadeh, Neda Setayesh
It has been shown that Granulocyte colony-stimulating factor (G-CSF) has a higher expression in malignant tumors, and anti-G-CSF therapy considerably decreases tumor growth, tumor vascularization and metastasis. Thus, blocking the signaling pathway of G-CSF could be beneficial in cancer therapy. This study is aimed at designing and producing a monoclonal nanobody that could act as an antagonist of G-CSF receptor. Nanobodies are the antigen binding fragments of camelid single-chain antibodies, also known as VHH. These fragments have exceptional properties which makes them ideal for tumor imaging and therapeutic applications. We have used our previously built nanobody phage libraries to isolate specific nanobodies to the G-CSF receptor. After a series of cross-reactivity and affinity experiments, two unique nanobodies were selected for functional analysis. Proliferation assay, real-time PCR and immunofluorescence assays were used to characterize these nanobodies. Finally, VHH26 nanobody that was able to specifically bind G-CSF receptor (G-CSF-R) on the surface of NFS60 cells and efficiently block G-CSF-R downstream signaling pathway in a dose-dependent manner was selected. This nanobody could be further developed into a valuable tool in tumor therapy and it forms a basis for additional studies in preclinical animal models.



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Corn silk maysin ameliorates obesity in vitro and in vivo via suppression of lipogenesis, differentiation, and function of adipocytes

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Chang Won Lee, Jeong Yeon Seo, Sun-Lim Kim, Jisun Lee, Ji Won Choi, Yong Il Park
Present study was aimed to investigate the potential anti-obesity effects of maysin, a major flavonoid of corn silk, in vitro and in vivo using 3T3-L1 preadipocyte cells and C57BL/6 mice. Maysin decreased the levels of intracellular lipid droplets and triglycerides (TG), and down-regulated the protein expression levels of C/EBP-β, C/EBP-α, PPAR-γ, and aP2 in 3T3-L1 preadipocyte cells, suggesting that maysin inhibits lipid accumulation and adipocyte differentiation. In addition, maysin was shown to induce the apoptotic cell death in 3T3-L1 preadipocyte cells via activation of caspase cascades and mitochondrial dysfunction, which may ultimately lead to reduction of adipose tissue mass. Furthermore, oral administration of maysin (25mg/kg body weight) decreased weight gain and epididymal fat weight in high-fat diet (HFD)-fed C57BL/6 mice. Administration of maysin also reduced serum levels of TG, total-cholesterol, LDL-cholesterol, and glucose. Taken collectively, these results suggest for the first time that the purified maysin exerts an anti-obesity effect in vitro and in vivo. These observations may support the applicability of maysin as a potent functional ingredient in health-beneficial foods or as a therapeutic agent to prevent or treat obesity.

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Editorial Board

Publication date: August 2017
Source:Biomedicine & Pharmacotherapy, Volume 92





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First case of anaphylaxis after botulinum toxin type A injection

Summary

Botulinum toxin type A (BTA) (also known as onabotulinum toxin A) injection is widely used in the field of cosmetic dermatology. Although a few adverse events related to intramuscular BTA injection have been reported, no life-threatening adverse reaction has been documented to date. We report a case of anaphylaxis induced by intramuscular BTA injection into the masseter muscles of a 35-year-old woman. She had previously received injections of the identical BTA product into the same muscles without incident. However, during the reported procedure, symptoms suggestive of angio-oedema and anaphylaxis developed about 5 min after BTA injection. Intramuscular epinephrine was used to manage the reaction. Following this, the patient was found to have an elevated total serum IgE level. We could not perform testing with BTA because of the risk of triggering another episode of anaphylaxis; however, intradermal tests using the identical sterile saline and patch test using the topical anaesthetic cream both showed negative results, thus we strongly suspect BTA as being the cause of anaphylaxis in this case.

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Fingerprint–efficacy study of the quaternary alkaloids in Corydalis yanhusuo

Publication date: Available online 21 June 2017
Source:Journal of Ethnopharmacology
Author(s): Qiuyue Li, Huanyu Guan, Xiaoming Wang, Yang He, Hong Sun, Wenting Tan, Xiaomei Luo, Meifeng Su, Yue Shi
Ethnopharmacological relevanceCorydalis yanhusuo is a well-known Chinese herbal medicine that is commonly applied as an analgesic agent in clinic using for thousands of years. Resent research showed that the quaternary ammonium alkaloids from Corydalis yanhusuo have a significant effect on myocardial ischemia. However, the corresponding anti-myocardial ischemia components that represent the efficacy of the quaternary ammonium alkaloids have not been elucidated.Aim of the studyExplore the anti-myocardial ischemia components of Corydalis yanhusuo and develop a method of quality control for Corydalis yanhusuo. Chemical fingerprints of quaternary ammonium alkaloids extracted from Corydalis yanhusuo samples from 37 different sources were identified using UPLC-Q-TOF MS. The protective effects of the 37 samples with respect to H9C2 cell hypoxia–reoxygenation were detected by MTT assays. The fingerprint–efficacy relationship between the chemical fingerprints and cardioprotection afforded by Corydalis yanhusuo was investigated using three chemometric methods.ResultsBecause of their inherent differences in chemical compositions, the protective effects to H9C2 cell hypoxia–reoxygenation were different. The results of three chemometric methods showed that the source of the Corydalis yanhusuo has an important influence on both the chemical fingerprint and efficacy. In particular, dehydrocorybulbine, 13-methyldehydrocorydalmine, dehydrocorydaline, columbamine, and palmatine appear to be the main effective components for quality control of this TCM.ConclusionThis work provides a general model of combination of UPLC and cardioprotection efficiency to study the fingerprint–efficacy relationship of Corydalis yanhusuo which can offer some references for detecting principal components of Corydalis yanhusuo on cardioprotection efficiency. Fingerprint–efficacy studies also provide a powerful method of quality control in Corydalis yanhusuo and other TCMs.

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Antrodia cinnamomea sensitizes radio-/chemo-therapy of cancer stem-like cells by modulating microRNA expression

Publication date: 31 July 2017
Source:Journal of Ethnopharmacology, Volume 207
Author(s): Yu-kai Su, Ping-Hsiao Shih, Wei-Hwa Lee, Oluwaseun Adebayo Bamodu, Alexander T.H. Wu, Chun-Chih Huang, Yew-Min Tzeng, Michael Hsiao, Chi-Tai Yeh, Chien-Min Lin
Ethnopharmacological relevanceThe discovery of many tissue-specific cancer stem cells (CSCs) continues to attract scientific attention. These CSCs are considered to be associated with chemo- and radio-resistance, and consequently, failure of conventional anticancer therapies. The recent demonstration of several microRNAs as enhancers of tumorigenicity via modulation of epithelial-mesenchymal transition and cancer stemness, makes them putative novel therapeutic target in oncology. Antrodia cinnamomea is a Chinese traditional medicine with several biological functions including anti-inflammation, antioxidant, and cancer prevention. However, the anti-CSC capability of A. Cinnamomea is not clear yet.Aim of the studyTo investigate the inhibitory effect of A. cinnamomea mycelium and extract on CSCs derived from various human cancer cell lines using our in-house therapeutics and human genome-wide miRNA screening panels.Materials and methodsA broad range of human cancer cell lines, including the acute monocytic leukemia (THP-1), glioblastoma multiforme (GBM 8401), lung carcinoma (A549), breast adenocarcinoma (MDA-MB-231), hepatoblastoma (HepG2), colorectal adenocarcinoma (SW620), and foreskin fibroblast (HS68), were exposed to A. cinnamomea in this study. CD133⁺ CSCs generated from the cell lines were characterized and isolated by flow cytometry, effect of chemo- and radiotherapy was assessed using the MTT assay, while the RT-PCR and human genome wide qRT-PCR determined the differential gene expression patterns. A comparative analysis of the anticancer effect of A. cinnamomea and Cisplatin, Taxol, or irradiation was also performed.ResultsOur results indicated that A. cinnamomea mycelium and its ethyl acetate extracts showed anti-proliferation effects against all types of CSCs, especially the lung, breast, and head and neck squamous cell carcinoma CSCs. Furthermore, CSCs treatment with A. cinnamomea combined with irradiation or chemotherapeutics demonstrated significant anti-cancer effect. We also established an association between the CSC-inhibitory effect of A. cinnamomea and significant downregulation of several microRNAs and cancer stemness expression levels in brain and breast CSCs. More importantly, higher CD133 expression is associated with poor prognosis in glioblastoma and breast cancer patients.ConclusionHerein, we demonstrate the putative role of A. cinnamomea as an effective ethnopharmacologic therapeutic agent for cancer treatment.

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A review of Acalypha indica L. (Euphorbiaceae) as traditional medicinal plant and its therapeutic potential

Publication date: Available online 21 June 2017
Source:Journal of Ethnopharmacology
Author(s): Nor Syahiran Zahidin, Syafiqah Saidin, Razauden Mohamed Zulkifli, Ida Idayu Muhamad, Harisun Ya'akob, Hadi Nur
Ethnopharmacological relevanceAcalypha indica is an herbal plant that grows in wet, temperate and tropical region, primarily along the earth's equator line. This plant is considered by most people as a weed and can easily be found in these regions. Although this plant is a weed, Acalypha indica has been acknowledged by local people as a useful source of medicine for several therapeutic treatments. They consume parts of the plant for many therapeutics purposes such as anthelmintic, anti-ulcer, bronchitis, asthma, wound healing, anti-bacterial and other applications. As this review was being conducted, most of the reports related to ethnomedicinal practices were from Asian and African regions.The aim of the reviewThe aim of this review is to summarize the current studies on ethnomedicinal practices, phytochemistry, pharmacological studies and a potential study of Acalypha indica in different locations around the world. This review updates related information regarding the potential therapeutic treatments and also discusses the toxicity issue of Acalypha indica.Materials and methodsThis review was performed through a systematic search related to Acalypha indica including the ethnomedicinal practices, phytochemistry and pharmacological studies around the world. The data was collected from online journals, magazines, and books, all of which were published in English, Malay and Indonesian. Search engine websites such as Google, Google Scholar, PubMed, Science Direct, Researchgate and other online collections were utilized in this review to obtain information.ResultsThe links between ethnomedicinal practices and scientific studies have been discussed with a fair justification. Several pharmacological properties exhibited certain potentials based on the obtained results that came from different related studies. Based on literature studies, Acalypha indica has the capability to serve as anthelmintic, anti-inflammation, anti-bacterial, anti-cancer, anti-diabetes, anti-hyperlipidemic, anti-obesity, anti-venom, hepatoprotective, hypoxia, and wound healing medicine. For the traditional practices, the authors also mentioned several benefits of consuming the raw plant and decoction.ConclusionThis review summarizes the current studies of Acalypha indica collected from many regions. This review hopefully will provide a useful and basic knowledge platform for anyone interested in gaining information regarding Acalypha indica.

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Hepatoprotective effect of Gan Kang Yaun against chronic liver injury induced by alcohol

Publication date: Available online 21 June 2017
Source:Journal of Ethnopharmacology
Author(s): Yuanheng Guo, Qingsheng Zhao, Lili Cao, Bing Zhao
Ethnopharmacological relevanceGan Kang Yuan (GKY) is a compound medicine formulated on the basis of traditional Chinese medicine (TCM). It was composed of Herba Cistanchis (Roucongrong), Radix Puerariae (Gegen), Radix Astragali (Huangqi), Fructus Schisandrae (Wuweizi) and Radix Glycyrrhizae (Gancao).AimThe purpose of this study is to research the hepatoprotective effect of GKY against liver injury induced by alcohol, and to elucidate the mechanism of hepatopretective effect.Materials and methodsHepatoprotective activity of GKY was researched both in vivo and vitro. In vitro, effect of GKY on the survival rates of HepG2 cells were assessed. In vivo research, ICR mice were oral administrated with alcohol (Er Guo-tou white spirit, 56%, 6mL/kg, once per day) for 31 days to establish liver injury model. Meanwhile, positive group or experimental groups were treated with bicyclol (300mg/kg) or GKY (200, 600, 1800 mg/kg). Serological indexes including aspartate and alanine transaminases (AST, ALT), γ-glutamyl transpeptidase (γ-GTP), total bilirubin (TBil), total cholesterol (TCHO) and serum triglyceride (STG) were estimated. Hepatic indicators including superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione (GSH), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and liver triglyceride (LTG) were analyzed. Histopathologic changes of liver tissue were observed.ResultsThe survival rates of HepG2 cell were observably promoted by GKY. Alcoholic treatment drastically altered the serum indexes and liver indicators of model animals, while these alteration were significantly ameliorated by GKY (p<0.05, 0.01 or 0.001) in experimental group. The microvesicular steatosis and necrosis in hepatic histopathology induced by alcoholic treatment also were notably attenuated by GKY administration.ConclusionsThese findings indicated that GKY possessed hepatoprotective property against liver injury induced by ethanol. GKY significantly promoted activities of relative enzymes and suppressed the contents of MDA and LTG, which might be the mechanism of hepatoprotective effect of GKY.

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Development of MPC-DPA polymeric nanoparticle systems for inhalation drug delivery applications

Publication date: 30 August 2017
Source:European Journal of Pharmaceutical Sciences, Volume 106
Author(s): Abdul Khaliq Elzhry Elyafi, Guy Standen, Steven T. Meikle, Andrew L. Lewis, Jonathan P. Salvage
Inhalation of nanoparticles for pulmonary drug delivery offers the potential to harness nanomedicine formulations of emerging therapeutics, such as curcumin, for treatment of lung cancer. Biocompatible nanoparticles composed of poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(2-(diisopropylamino)ethyl methacrylate) (MPC-DPA) have been shown to be suitable nanocarriers for drugs, whilst N-trimethyl chitosan chloride (TMC) coating of nanoparticles has been reported to further enhance their cellular delivery efficacy; the combination of the two has not been previously investigated. Development of effective systems requires the predictable, controllable, and reproducible ability to prepare nanosystems possessing particle sizes, and drug loading capacities, appropriate for successful airway travel, lung tissue penetration, and tumor suppression. Although a number of MPC-DPA based nanosystems have been described, a complete understanding of parameters controlling nanoparticle formation, size, and morphology has not been reported; in particular the effects of differing solvents phases remains unclear. In this current study a matrix of 31 solvent combinations were examined to provide novel data pertaining to the formation of MPC-DPA nanoparticles, and in doing so afforded the selection of systems with particle sizes appropriate for pulmonary delivery applications to be loaded with curcumin, and coated with TMC. This paper presents the first report of novel data detailing the successful preparation, characterisation, and optimisation of MPC-DPA nanoparticles of circa 150–180nm diameter, with low polydispersity, and a curcumin loading range of circa 2.5–115μM, tunable by preparation parameters, with and without TMC coating, and thus considered suitable candidates for inhalation drug delivery applications.

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Modeling and comparison of release profiles: Effect of the dissolution method

Publication date: 30 August 2017
Source:European Journal of Pharmaceutical Sciences, Volume 106
Author(s): Sara Cascone
During the last decades, the study of the in vitro dissolution of pharmaceuticals has been strongly encouraged by the FDA in order to determine its relationship with the in vivo bioavailability of a drug. In this work immediate and extended release formulations containing diclofenac, a BCS class II drug, were studied using different dissolution methods. The release profiles obtained in USP Apparatus II and USP Apparatus IV were evaluated and compared to determine the effect of the fluid dynamic conditions on the release. The influence of the mixing conditions (i.e. the paddle rotation speed in USP Apparatus II or the inlet flow rate in USP Apparatus IV) on the drug release were evaluated, finding that, for the extended release formulations, they do not affect significantly the release profile. An in vitro device simulating the peristaltic contractions of the stomach during the digestion was used to simulate fluid dynamics closer to the real physiology. The tablets were found to behave in a completely different way if tested in the artificial stomach.Both model-independent and model-dependent approaches were used to compare and fit the dissolution profiles, respectively. Fit factors were used as indicators of similarity of two dissolution profiles; model equations (such as zero-order, first-order, or Korsmeyer-Peppas equations) were used to fit the experimental data. With the identification of the best fitting model by the use of correlation factors and Akaike Information Criterion, the transport phenomena that determine the behavior of each formulation were identified.

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Numerosity processing in early visual cortex

Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): Michele Fornaciai, Elizabeth M. Brannon, Marty G. Woldorff, Joonkoo Park
While parietal cortex is thought to be critical for representing numerical magnitudes, we recently reported an event-related potential (ERP) study demonstrating selective neural sensitivity to numerosity over midline occipital sites very early in the time course, suggesting the involvement of early visual cortex in numerosity processing. However, which specific brain area underlies such early activation is not known. Here, we tested whether numerosity-sensitive neural signatures arise specifically from the initial stages of visual cortex, aiming to localize the generator of these signals by taking advantage of the distinctive folding pattern of early occipital cortices around the calcarine sulcus, which predicts an inversion of polarity of ERPs arising from these areas when stimuli are presented in the upper versus lower visual field. Dot arrays, including 8–32dots constructed systematically across various numerical and non-numerical visual attributes, were presented randomly in either the upper or lower visual hemifields. Our results show that neural responses at about 90ms post-stimulus were robustly sensitive to numerosity. Moreover, the peculiar pattern of polarity inversion of numerosity-sensitive activity at this stage suggested its generation primarily in V2 and V3. In contrast, numerosity-sensitive ERP activity at occipito-parietal channels later in the time course (210–230ms) did not show polarity inversion, indicating a subsequent processing stage in the dorsal stream. Overall, these results demonstrate that numerosity processing begins in one of the earliest stages of the cortical visual stream.



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Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease

Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): Anne Maass, Susan Landau, Suzanne L. Baker, Andy Horng, Samuel N. Lockhart, Renaud La Joie, Gil D. Rabinovici, William J. Jagust
The recent development of tau-specific positron emission tomography (PET) tracers enables in vivo quantification of regional tau pathology, one of the key lesions in Alzheimer's disease (AD). Tau PET imaging may become a useful biomarker for clinical diagnosis and tracking of disease progression but there is no consensus yet on how tau PET signal is best quantified. The goal of the current study was to evaluate multiple whole-brain and region-specific approaches to detect clinically relevant tau PET signal. Two independent cohorts of cognitively normal adults and amyloid-positive (Aβ⁺) patients with mild cognitive impairment (MCI) or AD-dementia underwent [¹⁸F]AV-1451 PET. Methods for tau tracer quantification included: (i) in vivo Braak staging, (ii) regional uptake in Braak composite regions, (iii) several whole-brain measures of tracer uptake, (iv) regional uptake in AD-vulnerable voxels, and (v) uptake in a priori defined regions. Receiver operating curves characterized accuracy in distinguishing Aβ^- controls from AD/MCI patients and yielded tau positivity cutoffs. Clinical relevance of tau PET measures was assessed by regressions against cognition and MR imaging measures. Key tracer uptake patterns were identified by a factor analysis and voxel-wise contrasts. Braak staging, global and region-specific tau measures yielded similar diagnostic accuracies, which differed between cohorts. While all tau measures were related to amyloid and global cognition, memory and hippocampal/entorhinal volume/thickness were associated with regional tracer retention in the medial temporal lobe. Key regions of tau accumulation included medial temporal and inferior/middle temporal regions, retrosplenial cortex, and banks of the superior temporal sulcus. Our data indicate that whole-brain tau PET measures might be adequate biomarkers to detect AD-related tau pathology. However, regional measures covering AD-vulnerable regions may increase sensitivity to early tau PET signal, atrophy and memory decline.

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Representational precision in visual cortex reveals outcome encoding and reward modulation during action preparation

Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): Henk van Steenbergen, Christopher M. Warren, Simone Kühn, Sanne de Wit, Reinout W. Wiers, Bernhard Hommel
According to ideomotor theory, goal-directed action involves the active perceptual anticipation of actions and their associated effects. We used multivariate analysis of fMRI data to test if preparation of an action promotes precision in the perceptual representation of the action. In addition, we tested how reward magnitude modulates this effect. Finally, we examined how expectation and uncertainty impact neural precision in the motor cortex. In line with our predictions, preparation of a hand or face action increased the precision of neural activation patterns in the extrastriate body area (EBA) and fusiform face area (FFA), respectively. The size of this effect of anticipation predicted individuals' efficiency at performing the prepared action. In addition, increasing reward magnitude increased the precision of perceptual representations in both EBA and FFA although this effect was limited to the group of participants that learned to associate face actions with high reward. Surprisingly, examination of representations in the hand motor cortex and face motor cortex yielded effects in the opposite direction. Our findings demonstrate that the precision of representations in visual and motor areas provides an important neural signature of the sensorimotor representations involved in goal-directed action.

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Hope and the brain: Trait hope mediates the protective role of medial orbitofrontal cortex spontaneous activity against anxiety

Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): Song Wang, Xin Xu, Ming Zhou, Taolin Chen, Xun Yang, Guangxiang Chen, Qiyong Gong
As a central research topic in the field of positive psychology, hope refers to an individual's goal-oriented expectations that include both agency thinking (i.e., the motivation to initiate and sustain actions to achieve goals) and pathway thinking (i.e., the capacity to find ways toward goals). Evidence from many previous studies has shown the role of hope in protecting against anxiety. However, little is known about the neurobiological basis of hope and the underlying mechanism that how hope reduces anxiety in the brain. Here, we employed fractional amplitude of low-frequency fluctuations (fALFF) to investigate these issues in 231 high school students using resting-state functional magnetic resonance imaging (RS-fMRI). The whole-brain correlation analyses revealed that higher trait hope was related to lower fALFF in the bilateral medial orbitofrontal cortex (mOFC), which is involved in reward-related processing, motivation production, problem solving and goal-directed behaviors. Furthermore, mediation analyses suggested that trait hope acted as a mediator in the association between mOFC spontaneous activity and anxiety. These results persisted even after adjusting for the effects of positive and negative affect. Overall, this study provides the first evidence for functional brain substrates underlying trait hope and reveals a potential mechanism that trait hope mediates the protective role of spontaneous brain activity against anxiety.



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Modulating perceptual complexity and load reveals degradation of the visual working memory network in ageing

Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): Sobanawartiny Wijeakumar, Vincent A. Magnotta, John P. Spencer
Previous neuroimaging studies have reported a posterior to anterior shift of activation in ageing (PASA). Here, we explore the nature of this shift by modulating load (1,2 or 3 items) and perceptual complexity in two variants of a visual working memory task (VWM): a 'simple' color and a 'complex' shape change detection task. Functional near-infrared spectroscopy (fNIRS) was used to record changes in activation in younger (N=24) and older adults (N=24). Older adults exhibited PASA by showing lesser activation in the posterior cortex and greater activation in the anterior cortex when compared to younger adults. Further, they showed reduced accuracy at loads 2 and 3 for the simple task and across all loads for the complex task. Activation in the posterior and anterior cortices was modulated differently for younger and older adults. In older adults, increasing load in the simple task was accompanied by decreasing activation in the posterior cortex and lack of modulation in the anterior cortex, suggesting the inability to encode and/or maintain representations without much aid from higher-order centres. In the complex task, older adults recruited verbal working memory areas in the posterior cortex, suggesting that they used adaptive strategies such as labelling the shape stimuli. This was accompanied by reduced activation in the anterior cortex reflecting the inability to exert top-down modulation to typical VWM areas in the posterior cortex to improve behavioral performance.



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Cingulo-opercular activity affects incidental memory encoding for speech in noise

Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): Kenneth I. Vaden, Susan Teubner-Rhodes, Jayne B. Ahlstrom, Judy R. Dubno, Mark A. Eckert
Correctly understood speech in difficult listening conditions is often difficult to remember. A long-standing hypothesis for this observation is that the engagement of cognitive resources to aid speech understanding can limit resources available for memory encoding. This hypothesis is consistent with evidence that speech presented in difficult conditions typically elicits greater activity throughout cingulo-opercular regions of frontal cortex that are proposed to optimize task performance through adaptive control of behavior and tonic attention. However, successful memory encoding of items for delayed recognition memory tasks is consistently associated with increased cingulo-opercular activity when perceptual difficulty is minimized. The current study used a delayed recognition memory task to test competing predictions that memory encoding for words is enhanced or limited by the engagement of cingulo-opercular activity during challenging listening conditions. An fMRI experiment was conducted with twenty healthy adult participants who performed a word identification in noise task that was immediately followed by a delayed recognition memory task. Consistent with previous findings, word identification trials in the poorer signal-to-noise ratio condition were associated with increased cingulo-opercular activity and poorer recognition memory scores on average. However, cingulo-opercular activity decreased for correctly identified words in noise that were not recognized in the delayed memory test. These results suggest that memory encoding in difficult listening conditions is poorer when elevated cingulo-opercular activity is not sustained. Although increased attention to speech when presented in difficult conditions may detract from more active forms of memory maintenance (e.g., sub-vocal rehearsal), we conclude that task performance monitoring and/or elevated tonic attention supports incidental memory encoding in challenging listening conditions.



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Post-stimulus fMRI and EEG responses: Evidence for a neuronal origin hypothesised to be inhibitory

Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): K.J. Mullinger, M.T. Cherukara, R.B. Buxton, S.T. Francis, S.D. Mayhew
Post-stimulus undershoots, negative responses following cessation of stimulation, are widely observed in functional magnetic resonance (fMRI) blood oxygenation level dependent (BOLD) data. However, the debate surrounding whether the origin of this response phase is neuronal or vascular, and whether it provides functionally relevant information, that is additional to what is contained in the primary response, means that undershoots are widely overlooked. We simultaneously recorded electroencephalography (EEG), BOLD and cerebral blood-flow (CBF) [obtained from arterial spin labelled (ASL) fMRI] fMRI responses to hemifield checkerboard stimulation to test the potential neural origin of the fMRI post-stimulus undershoot. The post-stimulus BOLD and CBF signal amplitudes in both contralateral and ipsilateral visual cortex depended on the post-stimulus power of the occipital 8–13Hz (alpha) EEG neuronal activity, such that trials with highest EEG power showed largest fMRI undershoots in contralateral visual cortex. This correlation in post-stimulus EEG-fMRI responses was not predicted by the primary response amplitude. In the contralateral visual cortex we observed a decrease in both cerebral rate of oxygen metabolism (CMRO2) and CBF during the post-stimulus phase. In addition, the coupling ratio (n) between CMRO2 and CBF was significantly lower during the positive contralateral primary response phase compared with the post-stimulus phase and we propose that this reflects an altered balance of excitatory and inhibitory neuronal activity. Together our data provide strong evidence that the post-stimulus phase of the BOLD response has a neural origin which reflects, at least partially, an uncoupling of the neuronal responses driving the primary and post-stimulus responses, explaining the uncoupling of the signals measured in the two response phases. We suggest our results are consistent with inhibitory processes driving the post-stimulus EEG and fMRI responses. We therefore propose that new methods are required to model the post-stimulus and primary responses independently, enabling separate investigation of response phases in cognitive function and neurological disease.



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Decision ambiguity is mediated by a late positive potential originating from cingulate cortex

Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): Sai Sun, Shanshan Zhen, Zhongzheng Fu, Daw-An Wu, Shinsuke Shimojo, Ralph Adolphs, Rongjun Yu, Shuo Wang
People often make decisions in the face of ambiguous information, but it remains unclear how ambiguity is represented in the brain. We used three types of ambiguous stimuli and combined EEG and fMRI to examine the neural representation of perceptual decisions under ambiguity. We identified a late positive potential, the LPP, which differentiated levels of ambiguity, and which was specifically associated with behavioral judgments about choices that were ambiguous, rather than passive perception of ambiguous stimuli. Mediation analyses together with two further control experiments confirmed that the LPP was generated only when decisions are made (not during mere perception of ambiguous stimuli), and only when those decisions involved choices on a dimension that is ambiguous. A further control experiment showed that a stronger LPP arose in the presence of ambiguous stimuli compared to when only unambiguous stimuli were present. Source modeling suggested that the LPP originated from multiple loci in cingulate cortex, a finding we further confirmed using fMRI and fMRI-guided ERP source prediction. Taken together, our findings argue for a role of an LPP originating from cingulate cortex in encoding decisions based on task-relevant perceptual ambiguity, a process that may in turn influence confidence judgment, response conflict, and error correction.



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Evolution of air pollution source contributions over one decade, derived by PM10 and PM2.5 source apportionment in two metropolitan urban areas in Greece

Publication date: September 2017
Source:Atmospheric Environment, Volume 164
Author(s): E. Diapouli, M. Manousakas, S. Vratolis, V. Vasilatou, Th Maggos, D. Saraga, Th Grigoratos, G. Argyropoulos, D. Voutsa, C. Samara, K. Eleftheriadis
Metropolitan Urban areas in Greece have been known to suffer from poor air quality, due to variety of emission sources, topography and climatic conditions favouring the accumulation of pollution. While a number of control measures have been implemented since the 1990s, resulting in reductions of atmospheric pollution and changes in emission source contributions, the financial crisis which started in 2009 has significantly altered this picture. The present study is the first effort to assess the contribution of emission sources to PM10 and PM2.5 concentration levels and their long-term variability (over 5–10 years), in the two largest metropolitan urban areas in Greece (Athens and Thessaloniki). Intensive measurement campaigns were conducted during 2011–2012 at suburban, urban background and urban traffic sites in these two cities. In addition, available datasets from previous measurements in Athens and Thessaloniki were used in order to assess the long-term variability of concentrations and sources. Chemical composition analysis of the 2011–2012 samples showed that carbonaceous matter was the most abundant component for both PM size fractions. Significant increase of carbonaceous particle concentrations and of OC/EC ratio during the cold period, especially in the residential urban background sites, pointed towards domestic heating and more particularly wood (biomass) burning as a significant source. PMF analysis further supported this finding. Biomass burning was the largest contributing source at the two urban background sites (with mean contributions for the two size fractions in the range of 24–46%). Secondary aerosol formation (sulphate, nitrate & organics) was also a major contributing source for both size fractions at the suburban and urban background sites. At the urban traffic site, vehicular traffic (exhaust and non-exhaust emissions) was the source with the highest contributions, accounting for 44% of PM10 and 37% of PM2.5, respectively. The long-term variability of emission sources in the two cities (over 5–10 years), assessed through a harmonized application of the PMF technique on recent and past year data, clearly demonstrates the effective reduction in emissions during the last decade due to control measures and technological development; however, it also reflects the effects of the financial crisis in Greece during these years, which has led to decreased economic activities and the adoption of more polluting practices by the local population in an effort to reduce living costs.

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