Showing papers by "Radboud University Nijmegen published in 2011"

FieldTrip: open source software for advanced analysis of MEG, EEG, and invasive electrophysiological data

Abstract: This paper describes FieldTrip, an open source software package that we developed for the analysis of MEG, EEG, and other electrophysiological data. The software is implemented as a MATLAB toolbox and includes a complete set of consistent and user-friendly high-level functions that allow experimental neuroscientists to analyze experimental data. It includes algorithms for simple and advanced analysis, such as time-frequency analysis using multitapers, source reconstruction using dipoles, distributed sources and beamformers, connectivity analysis, and nonparametric statistical permutation tests at the channel and source level. The implementation as toolbox allows the user to perform elaborate and structured analyses of large data sets using the MATLAB command line and batch scripting. Furthermore, users and developers can easily extend the functionality and implement new algorithms. The modular design facilitates the reuse in other software packages.

antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences

Abstract: Bacterial and fungal secondary metabolism is a rich source of novel bioactive compounds with potential pharmaceutical applications as antibiotics, anti-tumor drugs or cholesterol-lowering drugs To find new drug candidates, microbiologists are increasingly relying on sequencing genomes of a wide variety of microbes However, rapidly and reliably pinpointing all the potential gene clusters for secondary metabolites in dozens of newly sequenced genomes has been extremely challenging, due to their biochemical heterogeneity, the presence of unknown enzymes and the dispersed nature of the necessary specialized bioinformatics tools and resources Here, we present antiSMASH (antibiotics & Secondary Metabolite Analysis Shell), the first comprehensive pipeline capable of identifying biosynthetic loci covering the whole range of known secondary metabolite compound classes (polyketides, non-ribosomal peptides, terpenes, aminoglycosides, aminocoumarins, indolocarbazoles, lantibiotics, bacteriocins, nucleosides, beta-lactams, butyrolactones, siderophores, melanins and others) It aligns the identified regions at the gene cluster level to their nearest relatives from a database containing all other known gene clusters, and integrates or cross-links all previously available secondary-metabolite specific gene analysis methods in one interactive view antiSMASH is available at http://antismashsecondarymetabolitesorg

Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations

Abstract: Evidence for the etiology of autism spectrum disorders (ASDs) has consistently pointed to a strong genetic component complicated by substantial locus heterogeneity. We sequenced the exomes of 20 individuals with sporadic ASD (cases) and their parents, reasoning that these families would be enriched for de novo mutations of major effect. We identified 21 de novo mutations, 11 of which were protein altering. Protein-altering mutations were significantly enriched for changes at highly conserved residues. We identified potentially causative de novo events in 4 out of 20 probands, particularly among more severely affected individuals, in FOXP1, GRIN2B, SCN1A and LAMC3. In the FOXP1 mutation carrier, we also observed a rare inherited CNTNAP2 missense variant, and we provide functional support for a multi-hit model for disease risk. Our results show that trio-based exome sequencing is a powerful approach for identifying new candidate genes for ASDs and suggest that de novo mutations may contribute substantially to the genetic etiology of ASDs.

X-shooter, the new wide band intermediate resolution spectrograph at the ESO Very Large Telescope

Abstract: X-shooter is the first 2nd generation instrument of the ESO Very Large Telescope(VLT). It is a very efficient, single-target, intermediate-resolution spectrograph that was installed at the Cassegrain focus of UT2 in 2009. The instrument covers, in a single exposure, the spectral range from 300 to 2500 nm. It is designed to maximize the sensitivity in this spectral range through dichroic splitting in three arms with optimized optics, coatings, dispersive elements and detectors. It operates at intermediate spectral resolution (R~4,000 - 17,000, depending on wavelength and slit width) with fixed echelle spectral format (prism cross-dispersers) in the three arms. It includes a 1.8"x4" Integral Field Unit as an alternative to the 11" long slits. A dedicated data reduction package delivers fully calibrated two-dimensional and extracted spectra over the full wavelength range. We describe the main characteristics of the instrument and present its performance as measured during commissioning, science verification and the first months of science operations.

Multigroup Analysis in Partial Least Squares (PLS) Path Modeling: Alternative Methods and Empirical Results

Abstract: Purpose – Partial least squares (PLS) path modeling has become a pivotal empirical research method in international marketing. Owing to group comparisons' important role in research on international marketing, we provide researchers with recommendations on how to conduct multigroup analyses in PLS path modeling. Methodology/approach – We review available multigroup analysis methods in PLS path modeling and introduce a novel confidence set approach. A characterization of each method's strengths and limitations and a comparison of their outcomes by means of an empirical example extend the existing knowledge of multigroup analysis methods. Moreover, we provide an omnibus test of group differences (OTG), which allows testing the differences across more than two groups. Findings – The empirical comparison results suggest that Keil et al.'s (2000) parametric approach can generally be considered more liberal in terms of rendering a certain difference significant. Conversely, the novel confidence set approach and Henseler's (2007) approach are more conservative. Originality/value of paper – This study is the first to deliver an in-depth analysis and a comparison of the available procedures with which to statistically assess differences between group-specific parameters in PLS path modeling. Moreover, we offer two important methodological extensions of existing research (i.e., the confidence set approach and OTG). This contribution is particularly valuable for international marketing researchers, as it offers recommendations regarding empirical applications and paves the way for future research studies aimed at comparing the approaches' properties on the basis of simulated data.

Transient ferromagnetic-like state mediating ultrafast reversal of antiferromagnetically coupled spins

Abstract: The dynamics of spin ordering in magnetic materials is of interest for both fundamental understanding and progress in information-processing and recording technology. Radu et al. study spin dynamics in a ferrimagnetic gadolinium–iron–cobalt (GdFeCo) alloy that is optically excited at a timescale shorter than the characteristic magnetic exchange interaction between the Gd and Fe spins. Using element-specific X-ray magnetic circular dichroism spectroscopy, they show that the Gd and Fe spins switch directions at very different timescales. As a consequence, an unexpected transient ferromagnetic state emerges. These surprising observations, supported by simulations, provide a possible new concept of manipulating magnetic order on a timescale of the exchange interaction. Ferromagnetic or antiferromagnetic spin ordering is governed by the exchange interaction, the strongest force in magnetism1,2,3,4. Understanding spin dynamics in magnetic materials is an issue of crucial importance for progress in information processing and recording technology. Usually the dynamics are studied by observing the collective response of exchange-coupled spins, that is, spin resonances, after an external perturbation by a pulse of magnetic field, current or light. The periods of the corresponding resonances range from one nanosecond for ferromagnets down to one picosecond for antiferromagnets. However, virtually nothing is known about the behaviour of spins in a magnetic material after being excited on a timescale faster than that corresponding to the exchange interaction (10–100 fs), that is, in a non-adiabatic way. Here we use the element-specific technique X-ray magnetic circular dichroism to study spin reversal in GdFeCo that is optically excited on a timescale pertinent to the characteristic time of the exchange interaction between Gd and Fe spins. We unexpectedly find that the ultrafast spin reversal in this material, where spins are coupled antiferromagnetically, occurs by way of a transient ferromagnetic-like state. Following the optical excitation, the net magnetizations of the Gd and Fe sublattices rapidly collapse, switch their direction and rebuild their net magnetic moments at substantially different timescales; the net magnetic moment of the Gd sublattice is found to reverse within 1.5 picoseconds, which is substantially slower than the Fe reversal time of 300 femtoseconds. Consequently, a transient state characterized by a temporary parallel alignment of the net Gd and Fe moments emerges, despite their ground-state antiferromagnetic coupling. These surprising observations, supported by atomistic simulations, provide a concept for the possibility of manipulating magnetic order on the timescale of the exchange interaction.

Retraining Automatic Action Tendencies Changes Alcoholic Patients’ Approach Bias for Alcohol and Improves Treatment Outcome

Abstract: This study tested the effects of a new cognitive-bias modification (CBM) intervention that targeted an approach bias for alcohol in 214 alcoholic inpatients. Patients were assigned to one of two experimental conditions, in which they were explicitly or implicitly trained to make avoidance movements (pushing a joystick) in response to alcohol pictures, or to one of two control conditions, in which they received no training or sham training. Four brief sessions of experimental CBM preceded regular inpatient treatment. In the experimental conditions only, patients’ approach bias changed into an avoidance bias for alcohol. This effect generalized to untrained pictures in the task used in the CBM and to an Implicit Association Test, in which alcohol and soft-drink words were categorized with approach and avoidance words. Patients in the experimental conditions showed better treatment outcomes a year later. These findings indicate that a short intervention can change alcoholics’ automatic approach bias for alcohol and may improve treatment outcome.

Gaussian interaction profile kernels for predicting drug–target interaction

Abstract: Motivation: The in silico prediction of potential interactions between drugs and target proteins is of core importance for the identification of new drugs or novel targets for existing drugs. However, only a tiny portion of all drug–target pairs in current datasets are experimentally validated interactions. This motivates the need for developing computational methods that predict true interaction pairs with high accuracy. Results: We show that a simple machine learning method that uses the drug–target network as the only source of information is capable of predicting true interaction pairs with high accuracy. Specifically, we introduce interaction profiles of drugs (and of targets) in a network, which are binary vectors specifying the presence or absence of interaction with every target (drug) in that network. We define a kernel on these profiles, called the Gaussian Interaction Profile (GIP) kernel, and use a simple classifier, (kernel) Regularized Least Squares (RLS), for prediction drug–target interactions. We test comparatively the effectiveness of RLS with the GIP kernel on four drug–target interaction networks used in previous studies. The proposed algorithm achieves area under the precision–recall curve (AUPR) up to 92.7, significantly improving over results of state-of-the-art methods. Moreover, we show that using also kernels based on chemical and genomic information further increases accuracy, with a neat improvement on small datasets. These results substantiate the relevance of the network topology (in the form of interaction profiles) as source of information for predicting drug–target interactions. Availability: Software and Supplementary Material are available at http://cs.ru.nl/~tvanlaarhoven/drugtarget2011/. Contact:tvanlaarhoven@cs.ru.nl; elenam@cs.ru.nl Supplementary Information:Supplementary data are available at Bioinformatics online.

Molecular mechanism of anaerobic ammonium oxidation

Abstract: Two distinct microbial processes, denitrification and anaerobic ammonium oxidation (anammox), are responsible for the release of fixed nitrogen as dinitrogen gas (N(2)) to the atmosphere. Denitrification has been studied for over 100 years and its intermediates and enzymes are well known. Even though anammox is a key biogeochemical process of equal importance, its molecular mechanism is unknown, but it was proposed to proceed through hydrazine (N(2)H(4)). Here we show that N(2)H(4) is produced from the anammox substrates ammonium and nitrite and that nitric oxide (NO) is the direct precursor of N(2)H(4). We resolved the genes and proteins central to anammox metabolism and purified the key enzymes that catalyse N(2)H(4) synthesis and its oxidation to N(2). These results present a new biochemical reaction forging an N-N bond and fill a lacuna in our understanding of the biochemical synthesis of the N(2) in the atmosphere. Furthermore, they reinforce the role of nitric oxide in the evolution of the nitrogen cycle.

Fast track surgery versus conventional recovery strategies for colorectal surgery

Abstract: Background In recent years the Enhanced Recovery after Surgery (ERAS) postoperative pathway in (ileo-)colorectal surgery, aiming at improving perioperative care and decreasing postoperative complications, has become more common. Objectives We investigated the effectiveness and safety of the ERAS multimodal strategy, compared to conventional care after (ileo-)colorectal surgery. The primary research question was whether ERAS protocols lead to less morbidity and secondary whether length of stay was reduced. Search methods To answer the research question we entered search strings containing keywords like "fast track", "colorectal and surgery" and "enhanced recovery" into major databases. We also hand searched references in identified reviews concerning ERAS. Selection criteria We included published randomised clinical trials, in any language, comparing ERAS to conventional treatment in patients with (ileo-) colorectal disease requiring a resection. RCT's including at least 7 ERAS items in the ERAS group and no more than 2 in the conventional arm were included. Data collection and analysis Data of included trials were independently extracted by the reviewers. Analyses were performed using "REVMAN 5.0.22". Data were pooled and rate differences as well as weighted mean differences with their 95% confidence intervals were calculated using either fixed or random effects models, depending on heterogeneity (I2). Main results 4 RCTs were included and analysed. Methodological quality of included studies was considered low, when scored according to GRADE methodology. Total numbers of inclusion were limited. The trials included in primary analysis reported 237 patients, (119 ERAS vs 118 conventional). Baseline characteristics were comparable. The primary outcome measure, complications, showed a significant risk reduction for all complications (RR 0.50; 95% CI 0.35 to 0.72). This difference was not due to reduction in major complications. Length of hospital stay was significantly reduced in the ERAS group (MD -2.94 days; 95% CI -3.69 to -2.19), and readmission rates were equal in both groups. Other outcome parameters were unsuitable for meta-analysis, but seemed to favour ERAS. Authors' conclusions The quantity and especially quality of data are low. Analysis shows a reduction in overall complications, but major complications were not reduced. Length of stay was reduced significantly. We state that ERAS seems safe, but the quality of trials and lack of sufficient other outcome parameters do not justify implementation of ERAS as the standard of care. Within ERAS protocols included, no answer regarding the role for minimally invasive surgery (i.e. laparoscopy) was found. Furthermore, protocol compliance within ERAS programs has not been investigated, while this seems a known problem in the field. Therefore, more specific and large RCT's are needed.

A clinical perspective of IL-1β as the gatekeeper of inflammation

Abstract: An expanding spectrum of acute and chronic non-infectious inflammatory diseases is uniquely responsive to IL-1β neutralization. IL-1β-mediated diseases are often called "auto-inflammatory" and the dominant finding is the release of the active form of IL-1β driven by endogenous molecules acting on the monocyte/macrophage. IL-1β activity is tightly controlled and requires the conversion of the primary transcript, the inactive IL-1β precursor, to the active cytokine by limited proteolysis. Limited proteolysis can take place extracellularly by serine proteases, released in particular by infiltrating neutrophils or intracellularly by the cysteine protease caspase-1. Therefore, blocking IL-1β resolves inflammation regardless of how the cytokine is released from the cell or how the precursor is cleaved. Endogenous stimulants such as oxidized fatty acids and lipoproteins, high glucose concentrations, uric acid crystals, activated complement, contents of necrotic cells, and cytokines, particularly IL-1 itself, induce the synthesis of the inactive IL-1β precursor, which awaits processing to the active form. Although bursts of IL-1β precipitate acute attacks of systemic or local inflammation, IL-1β also contributes to several chronic diseases. For example, ischemic injury, such as myocardial infarction or stroke, causes acute and extensive damage, and slowly progressive inflammatory processes take place in atherosclerosis, type 2 diabetes, osteoarthritis and smoldering myeloma. Evidence for the involvement of IL-1β and the clinical results of reducing IL-1β activity in this broad spectrum of inflammatory diseases are the focus of this review.

α-Oscillations in the monkey sensorimotor network influence discrimination performance by rhythmical inhibition of neuronal spiking

Abstract: Extensive work in humans using magneto- and electroencephalography strongly suggests that decreased oscillatory α-activity (8–14 Hz) facilitates processing in a given region, whereas increased α-activity serves to actively suppress irrelevant or interfering processing. However, little work has been done to understand how α-activity is linked to neuronal firing. Here, we simultaneously recorded local field potentials and spikes from somatosensory, premotor, and motor regions while a trained monkey performed a vibrotactile discrimination task. In the local field potentials we observed strong activity in the α-band, which decreased in the sensorimotor regions during the discrimination task. This α-power decrease predicted better discrimination performance. Furthermore, the α-oscillations demonstrated a rhythmic relation with the spiking, such that firing was highest at the trough of the α-cycle. Firing rates increased with a decrease in α-power. These findings suggest that α-oscillations exercise a strong inhibitory influence on both spike timing and firing rate. Thus, the pulsed inhibition by α-oscillations plays an important functional role in the extended sensorimotor system.

STAT1 Mutations in Autosomal Dominant Chronic Mucocutaneous Candidiasis

Abstract: Background Chronic mucocutaneous candidiasis (CMC) is characterized by susceptibility to candida infection of skin, nails, and mucous membranes. Patients with recessive CMC and autoimmunity have mutations in the autoimmune regulator AIRE. The cause of autosomal dominant CMC is unknown. Methods We evaluated 14 patients from five families with autosomal dominant CMC. We incubated their peripheral-blood mononuclear cells with different combinations of stimuli to test the integrity of pathways that mediate immunity, which led to the selection of 100 genes that were most likely to contain the genetic defect. We used an array-based sequence-capture assay, followed by next-generation sequencing, to identify mutations. Results The mononuclear cells from the affected patients were characterized by poor production of interferon-γ, interleukin-17, and interleukin-22, suggesting that the defect lay within the interleukin-12 receptor and interleukin-23 receptor signaling pathways. We identified heterozygous missense m...

Inflammasome is a central player in the induction of obesity and insulin resistance

Abstract: Inflammation plays a key role in the pathogenesis of obesity. Chronic overfeeding leads to macrophage infiltration in the adipose tissue, resulting in proinflammatory cytokine production. Both microbial and endogenous danger signals trigger assembly of the intracellular innate immune sensor Nlrp3, resulting in caspase-1 activation and production of proinflammatory cytokines IL-1β and IL-18. Here, we showed that mice deficient in Nlrp3, apoptosis-associated speck-like protein, and caspase-1 were resistant to the development of high-fat diet-induced obesity, which correlated with protection from obesity-induced insulin resistance. Furthermore, hepatic triglyceride content, adipocyte size, and macrophage infiltration in adipose tissue were all reduced in mice deficient in inflammasome components. Monocyte chemoattractant protein (MCP)-1 is a key molecule that mediates macrophage infiltration. Indeed, defective inflammasome activation was associated with reduced MCP-1 production in adipose tissue. Furthermore, plasma leptin and resistin that affect energy use and insulin sensitivity were also changed by inflammasome-deficiency. Detailed metabolic and molecular phenotyping demonstrated that the inflammasome controls energy expenditure and adipogenic gene expression during chronic overfeeding. These findings reveal a critical function of the inflammasome in obesity and insulin resistance, and suggest inhibition of the inflammasome as a potential therapeutic strategy.

Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis

Abstract: Thoracic aortic aneurysms and dissections are a main feature of connective tissue disorders, such as Marfan syndrome and Loeys-Dietz syndrome. We delineated a new syndrome presenting with aneurysms, dissections and tortuosity throughout the arterial tree in association with mild craniofacial features and skeletal and cutaneous anomalies. In contrast with other aneurysm syndromes, most of these affected individuals presented with early-onset osteoarthritis. We mapped the genetic locus to chromosome 15q22.2-24.2 and show that the disease is caused by mutations in SMAD3. This gene encodes a member of the TGF-β pathway that is essential for TGF-β signal transmission. SMAD3 mutations lead to increased aortic expression of several key players in the TGF-β pathway, including SMAD3. Molecular diagnosis will allow early and reliable identification of cases and relatives at risk for major cardiovascular complications. Our findings endorse the TGF-β pathway as the primary pharmacological target for the development of new treatments for aortic aneurysms and osteoarthritis.

A large-scale evaluation of the KiVa antibullying program: grades 4-6.

Abstract: This study demonstrates the effectiveness of the KiVa antibullying program using a large sample of 8,237 youth from Grades 4-6 (10-12 years). Altogether, 78 schools were randomly assigned to intervention (39 schools, 4,207 students) and control conditions (39 schools, 4,030 students). Multilevel regression analyses revealed that after 9 months of implementation, the intervention had consistent beneficial effects on 7 of the 11 dependent variables, including self- and peer-reported victimization and self-reported bullying. The results indicate that the KiVa program is effective in reducing school bullying and victimization in Grades 4-6. Despite some evidence against school-based interventions, the results suggest that well-conceived school-based programs can reduce victimization.

EEG and MEG data analysis in SPM8.

Abstract: SPM is a free and open source software written in MATLAB (The MathWorks, Inc.). In addition to standard M/EEG preprocessing, we presently offer three main analysis tools: (i) statistical analysis of scalp-maps, time-frequency images, and volumetric 3D source reconstruction images based on the general linear model, with correction for multiple comparisons using random field theory; (ii) Bayesian M/EEG source reconstruction, including support for group studies, simultaneous EEG and MEG, and fMRI priors; (iii) dynamic causal modelling (DCM), an approach combining neural modelling with data analysis for which there are several variants dealing with evoked responses, steady state responses (power spectra and cross-spectra), induced responses, and phase coupling. SPM8 is integrated with the FieldTrip toolbox , making it possible for users to combine a variety of standard analysis methods with new schemes implemented in SPM and build custom analysis tools using powerful graphical user interface (GUI) and batching tools.

Rewiring of the Jasmonate Signaling Pathway in Arabidopsis during Insect Herbivory.

Abstract: Plant defenses against insect herbivores and necrotrophic pathogens are differentially regulated by different branches of the jasmonic acid (JA) signaling pathway. In Arabidopsis, the basic helix-loop-helix leucine zipper transcription factor (TF) MYC2 and the APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) domain TF ORA59 antagonistically control these distinct branches of the JA pathway. Feeding by larvae of the specialist insect herbivore Pieris rapae activated MYC2 transcription and stimulated expression of the MYC2-branch marker gene VSP2, while it suppressed transcription of ORA59 and the ERF-branch marker gene PDF1.2. Mutant jin1 and jar1-1 plants, which are impaired in the MYC2-branch of the JA pathway, displayed a strongly enhanced expression of both ORA59 and PDF1.2 upon herbivory, indicating that in wild-type plants the MYC2-branch is prioritized over the ERF-branch during insect feeding. Weight gain of P. rapae larvae in a no-choice setup was not significantly affected, but in a two-choice setup the larvae consistently preferred jin1 and jar1-1 plants, in which the ERF-branch was activated, over wild-type Col-0 plants, in which the MYC2-branch was induced. In MYC2- and ORA59-impaired jin1-1/RNAi-ORA59 plants this preference was lost, while in ORA59-overexpressing 35S:ORA59 plants it was gained, suggesting that the herbivores were stimulated to feed from plants that expressed the ERF-branch rather than that they were deterred by plants that expressed the MYC2-branch. The feeding preference of the P. rapae larvae could not be linked to changes in glucosinolate levels. Interestingly, application of larval oral secretion into wounded leaf tissue stimulated the ERF-branch of the JA pathway, suggesting that compounds in the oral secretion have the potential to manipulate the plant response toward the caterpillar-preferred ERF-regulated branch of the JA response. Our results suggest that by activating the MYC2-branch of the JA pathway, plants prevent stimulation of the ERF-branch by the herbivore, thereby becoming less attractive to the attacker.

Bioconjugation with strained alkenes and alkynes.

Abstract: The structural complexity of molecules isolated from biological sources has always served as an inspiration for organic chemists. Since the first synthesis of a natural product, urea, chemists have been challenged to prepare exact copies of natural structures in the laboratory. As a result, a broad repertoire of synthetic transformations has been developed over the years. It is now feasible to synthesize organic molecules of enormous complexity, and also molecules with less structural complexity but prodigious societal impact, such as nylon, TNT, polystyrene, statins, estradiol, XTC, and many more.Unfortunately, only a few chemical transformations are so mild and precise that they can be used to selectively modify biochemical structures, such as proteins or nucleic acids; these are the so-called bioconjugation strategies. Even more challenging is to apply a chemical reaction on or in living cells or whole organisms; these are the so-called bioorthogonal reactions. These fields of research are of particula...

Online video game addiction: identification of addicted adolescent gamers.

Abstract: Aims To provide empirical data-driven identification of a group of addicted online gamers. Design Repeated cross-sectional survey study, comprising a longitudinal cohort, conducted in 2008 and 2009. Setting Secondary schools in the Netherlands. Participants Two large samples of Dutch schoolchildren (aged 13-16 years). Measurements Compulsive internet use scale, weekly hours of online gaming and psychosocial variables. Findings Thisstudyconfirmstheexistenceof asmallgroupof addictedonlinegamers(3%),representingabout1.5% of all children aged 13-16 years in the Netherlands. Although these gamers report addiction-like problems, relation- ships with decreased psychosocial health were less evident. Conclusions The identification of a small group of addicted online gamers supports efforts to develop and validate questionnaire scales aimed at measuring the phenom- enon of online video game addiction. The findings contribute to the discussion on the inclusion of non-substance addictions in the proposed unified concept of 'Addiction and Related Disorders' for the DSM-V by providing indirect identification and validation of a group of suspected online video game addicts.

Stress-Related Noradrenergic Activity Prompts Large-Scale Neural Network Reconfiguration

Abstract: Acute stress shifts the brain into a state that fosters rapid defense mechanisms. Stress-related neuromodulators are thought to trigger this change by altering properties of large-scale neural populations throughout the brain. We investigated this brain-state shift in humans. During exposure to a fear-related acute stressor, responsiveness and interconnectivity within a network including cortical (frontoinsular, dorsal anterior cingulate, inferotemporal, and temporoparietal) and subcortical (amygdala, thalamus, hypothalamus, and midbrain) regions increased as a function of stress response magnitudes. β-adrenergic receptor blockade, but not cortisol synthesis inhibition, diminished this increase. Thus, our findings reveal that noradrenergic activation during acute stress results in prolonged coupling within a distributed network that integrates information exchange between regions involved in autonomic-neuroendocrine control and vigilant attentional reorienting.

Stimulation of locomotor activity following injection of dopamine into the nucleus accumbens

Abstract: Recently we have observed that bilateral injection of ergometrine into the nucleus accumbens of rats results in a strong and long-lasting enhancement of locomotor activity (Pijnenburg, Woodruff & van Rossum, 1973). This effect was antagonized by low doses of haloperidol and pimozide. The hypothesis was proposed that this enhanced locomotor activity was elicited by a stimulation of dopamine receptors in the nucleus accumbens. We now report that administration of dopamine directly into the nucleus accumbens of nialamide-pretreated rats produces a pattern of enhanced locomotor activity similar to that seen after ergometrine. Seven male Wistar rats (200-220 g) were implanted with double barrelled cannulas in each side of the nucleus accumbens (coordinates A 9.4, L 1.2 and H -0.6 according to the atlas of Konig & Klippel, 1963). These animals were used for all experiments with 5-8 days between experiments. The animals were subsequently killed and brains were sectioned to determine the position of the cannulas. For details of the experimental procedure see Pijnenburg & others (1973). Injections were made by means of a 5 pl Hamilton syringe with a 31 gauge needle. The injection volume was 0.5 pl. Dopamine HCl and (-)-noradrenaline (-)-hydrogen tartrate were dissolved in saline. Locomotor activity was measured in activity cages, equipped with photoelectric cells and recorded on a cumulative recorder. The rats were always pretreated with the monoamine oxidase inhibitor nialamide (100 mg kg-l i.p.) 18 h before administration of saline, dopamine or noradrenaline. Injection of dopamine ( 5 pg) to each side of the nucleus produced a strong enhancement of locomotor activity, which started in 5 animals within 10 min of injection and lasted for up to 4 h, reaching a peak at about 1 h returning to 0 over the next 3 h with the most rapid decline over the last 30 min. In two rats, in which the injection site was found to be at the border of the nucleus accumbens, stimulation of locomotor activity started after 20 and 30 min respectively and failed to reach the level seen in the other rats. This is probably the reason for the large variability in the results (see Table 1). Injection of noradrenaline (5.0 pg) into each side of the nucleus accumbens of the same rats produced enhanced locomotor activity in 5 of the 7 animals but this was