bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological Receptors of the Cerebral Arteries of the Goat
Authors: Urquilla Pedro R. , Marco Emilio J. , Lluch Salvador
Published: September 2008

5-Hydroxytryptamine (5-HT), norepinephrine (NE), histamine (H) and potassium (K+) chloride induce dose-dependent changes in tension of the isolated middle cerebral artery of the goat. Vasopressin produces highly variable responses followed by tachyphylaxis; angiotensin II is ineffective over a wide dose range. The order of potencies of these vasoactive agents is 5-HT > NE > H > K+. With regard to their ability to induce maximal contractile responses, the order is: H > 5-HT, K+ > NE. Lysergic acid diethylamide (LSD) antagonizes the actions of 5-HT in a manner which progresses from surmountability to unsurmountability of the blockade depending on the concentration of LSD. The blockade exerted by LSD is reversed by washing. Phentolamine and diphenhydramine competitively antagonize the actions of NE and H, respectively. The potency of phentolamine and diphenhydramine in the cerebral arteries of the goat is similar to that determined in different tissues obtained from a variety of animal species. It is concluded that the cerebral arteries of the goat possess receptors for biogenic amines, the most effective of which is 5-HT; receptors for vasoactive peptides are ill defined.
Reactivity of Aorta and Portal Vein in Germfree Rats
Authors: Altura Bella T. , Altura Burton M. , Baez Silvio
Published: September 2008

The responsiveness of conventional and germfree rat aortas and portal veins to vasoactive agents were compared in vitro. The results indicate: (1) aortas and portal veins from germfree rats exhibit an attenuated reactivity to angiotensin, vasopressin and epinephrine but not to KC1; (2) the dose-response curves for epi-nephrine and the peptides were shifted to the right concomitant with a decrease in maximum contractile tension, and (3) CaCl2 dose-response curves obtained on potassium-depolarized aorta were not different from one another, whereas those obtained on portal veins from germfree animals were shifted to the right with a concomitant decrease in maximum response. In addition, aortas and portal veins from germfree rats were found to exhibit a higher total Ca content (but not Mg or water) when compared to conventional animals.
Triglyceride Lipase Activity in Bovine Aorta
Authors: Filipovic Ivan , Rutemöller Margret , Helten Peter
Published: September 2008

The cell-free supernatant from homogenized bovine aorta hydrolyzed triglycerides, β-naphthylesters of lauric and stearic acid and Tween 20, 40 and 60. The rate of hydrolysis decreases as the acyl chain length of the substrates increases. The activity against triglycerides of short-chain fatty acids and monoacylesters could be partially separated from that of glycerol-trioleate lipase by ammonium sulfate fractionation. The activity of glycerol-trioleate lipase remained unaffected by heating for 5 min at 60 °C or by addition of bile acids, whereas the activity causing hydrolysis of triglycerides with short-chain fatty acids and monoacylesters decreases up to 60% by analogous treatment. No changes in the hydrolytic activity occurs in presence of sodium heparin. This indicates that this activity is not identical with a lipoprotein lipase.
Intrinsic Prostaglandin Release
Authors: Kalsner Stanley
Published: September 2008

Isolated coronary artery strips of the bovine heart in vitro relax in response to decreased bath oxygen tensions (from 515 mm Hg to 112, 53, and 38 mm Hg). In addition, the rate of intrinsic formation and release of prostaglandin is considerably increased under conditions of decreased PO2. The vascular relaxations under reduced PO2 are attenuated and the elevations in prostaglandin output blocked by prostaglandin synthesis inhibitors. It appears that alterations in the output of a PGE with vasodilator activity, probably E1, is a significant factor regulating the compensatory changes in tone of the coronary arteries in response to anoxic conditions.
Angiotensin Analogs: Effect of Prostaglandin Synthesis Inhibitor
Authors: Hall M.M. , Gurchinoff S. , Khosla M.C. , Khairallah P.A.
Published: September 2008

Structurally different inhibitors of prostaglandin synthesis reversed the antagonistic activity of the angiotensin II analog 1-sarcosine, 8-threonine angiotensin II. In isolated rabbit aorta, indomethacin or ETYA (eicosa 5, 8, 11, 14, tetraynoic) reversed the antagonism of the angiotensin II analog without affecting the dose response curves to angiotensin II. Both indomethacin and ETYA were able to reverse the tachyphylaxis to angiotensin II. Investigating the possibility that indomethacin could affect the binding of angiotensin II, it was found that at doses of indomethacin higher than 10–5 m, binding of tritiated angiotensin to isolated adrenal cortical cells was reduced. It is postulated that indomethacin may have more than one effect on angiotensin, possessing a concentration-dependent effect on binding and prostaglandin synthesis.
Venous Changes in Renal Hypertensive Rats: The Role of Humoral Factors
Authors: Simon Geza
Published: September 2008

In order to investigate the role of circulating humoral substances in the pathogenesis of venous changes in experimental hypertension, an attempt was made to induce venous changes in rats in parabiosis with two-kidney Goldblatt hypertensive rats. Sham-operated normotensive rats in parabiosis were used as controls. Venous pressure-volume curves were obtained in the pump perfused vascular beds of the lower body of rats by recording the femoral vein pressure rise during rapid infusion of fluid into the inferior vena cava. The water, sodium and potassium content of veins also was measured. Compared to values in normotensive control rats (n = 11), the venous pressure-volume curves of two-kidney Goldblatt hypertensive rats in parabiosis with unoperated rats (n = 13) were shifted in the direction of the pressure axis (p < 0.01), indicating decreased venous capacity. Venous pressure-volume curves in rats in parabiosis with two-kidney Goldblatt hypertensive rats (n = 13) and in rats in parabiosis with sham-operated rats (n = 10) were similar. The venous wall water, sodium and potassium content in two-kidney Goldblatt hypertensive rats (n = 8) and in their unoperated parabiotic mates (n = 8) was increased (p < 0.05) in comparison to that of sham-operated rats in parabiosis (n = 10). These experiments provide evidence for the role of circulating humoral substances in the pathogenesis of abnormal venous wall composition but not of decreased venous capacity in renal hypertensive rats.
L-Ascorbic Acid: Effects on Aortic Glycosaminoglycan 35S Incorporation in Rabbit-Induced Atherogenesis
Authors: Verlangieri Anthony J. , Stevens Jeff W.
Published: September 2008

The effects of L-ascorbic acid on 35S-incorporation into thoracic aorta glycosaminoglycans and upon aorta cholesterol levels were determined in hypercholesterolemic rabbits. No significant difference was observed in serum free or esterified cholesterol levels between animals receiving L-ascorbic acid supplementation or saline while maintained on a cholesterol diet (0.5%). A 15-fold higher serum cholesterol was observed in animals on the cholesterol diet to those animals which received a normal rabbit (Purina) diet. L-Ascorbic acid increased sulfated glycosaminoglycans concentrations in hypercholesterolemic rabbits which paralleled lower tissue free and esterified cholesterol levels. The 35S-specific activity of glycosaminoglycans in hypercholesterolemic animals receiving saline was much greater than in those animals receiving L-ascorbic acid. This suggests that L -ascorbic acid plays a role in the maintenance of adequate levels of aortic sulfated glycosaminoglycans. This then is a suggested biochemical mechanism of L-ascorbic acids interaction in the atherogenic process.
Experimental Homocystinemia, Endothelial Lesions and Thrombosis
Authors: Hladovec Josef
Published: September 2008

A single intravenous injection of homocystine led to an increase in the number of circulating endothelial cells in the blood of rats. We observed also increased permeability of the lung capillaries, platelet sequestration and activation of the venostatic thrombosis. Endothelial injury is probably the key mechanism of thrombotic and atherosclerotic complications in homocystinuria, an inborn error of the amino acid metabolism.
Effects of Inhibitors of Collagen Maturation on Hypertension in Rats
Authors: Franklin T.J. , Morris W.P. , Loveday B.E.
Published: September 2008

The effects of β-aminopropionitrile (BAPN), an inhibitor of collagen maturation, have been examined in three models of hypertension in rats. It is shown for the first time that BAPN has a rapidly developing antihypertensive action in rats with renal (one kidney-one clip) hypertension. The compound also lowered blood pressure in spontaneously hypertensive rats. In both these experiments although BAPN lowered blood pressure it did not affect the hypertension-induced hypertrophy of the aorta. BAPN suppressed the rise in blood pressure during the developing phase of deoxycorticosterone acetate-salt-induced hypertension and in this model the compound also prevented the accompanying aortic hypertrophy. However, another inhibitor of collagen synthesis and maturation, 3,4-dehydroproline, completely suppressed aortic hypertrophy but failed to prevent the rise in blood pressure in deoxycorticosterone acetate-salt hypertension. It is concluded that: (1) BAPN may have a direct antihypertensive action, and (2) inhibition of aortic hypertrophy alone cannot prevent the rise in blood pressure in the developing phase of deoxycorticosterone acetate-salt hypertension.
Functional and Non-Functional Nerve-Smooth Muscle Transmission in the Renal Arteries of the Newborn and Adult Rabbit and Guinea-Pig
Authors: Gallen D.D. , Cowen T. , Griffith S.G. , Haven A.J. , Burnstock G.
Published: September 2008

Isolated renal arteries from newborn and adult guinea-pigs failed to respond to electrical stimulation of the intramural nerves, using parameters identical to those which elicit large neurogenic contractions in renal arteries from newborn and adult rabbits. The threshold stimulation frequency was lower and responses were greater in adult compared with neonatal rabbits. Comparisons of noradrenaline EC50 values showed that guinea-pig renal arteries are significantly less sensitive to noradrenaline than rabbit vessels. Quantitative fluorescence histochemistry of the perivascular adrenergic nerves in renal arteries revealed that the density of innervation gradually declines in the guinea-pig but substantially increases in the rabbit during postnatal development. The lack of neurogenic response of the guinea-pig renal artery, despite the existence of a varicose, adrenergic nerve plexus, is discussed.
Effect of Inhibitors of Neuronal and Extraneuronal Uptake on the Accumulation and Metabolism of 3H-l-Norepinephrine in Rabbit Aorta
Authors: Levin Jerome A. , Wilson Susan E.
Published: September 2008

In the isolated adventitia of rabbit aorta, blockade of neuronal uptake decreased the accumulation and deamination of 3H-/-norepinephrine (3H-l-NE) whereas blockade of extraneuronal uptake decreased O-methylation. Thus most of the O-methylation occurs in the extraneuronal elements. In the isolated media, blockade of extraneuronal uptake decreased metabolism but not accumulation of 3H-l-NE. If NE metabolism was prevented by pretreatment with pargyline and U-0521, 3H-l-NE accumulation in the isolated media increased markedly and now inhibitors of extraneuronal uptake could decrease this accumulation of 3H-l-NE by the isolated media. Thus when MAO and COMT are intact, NE does not accumulate in the extraneuronal compartment containing these enzymes, probably because it is metabolized as fast as it enters the compartment. Since the level of 3H-l-NE in the isolated media exceeded the sorbitol space when MAO and COMT were intact, some 3H-l-NE must have accumulated in a compartment which does not contain these enzymes.
Effect of Ouabain and Alterations in Potassium Concentration on Relaxation Induced by Sodium Nitroprusside
Authors: Rapoport Robert M. , Murad Ferid
Published: September 2008

Relaxation of the rat thoracic aorta induced by sodium nitroprusside, 8-bromo-cyclic GMP and cyclic nucleotide phosphodiesterase inhibitor M & B 22,948 was inhibited by exposure to K+-free solution and ouabain in a concentration-dependent manner. Relaxation occurring with the change in potassium concentration in media from 1 to 2 to 10 mM was increased by sodium nitroprusside, 8-bromo-cyclic GMP and M & B 22,948. Thus, agents and procedures known to decrease and increase the activity of the Na+, K+-pump, and presumably alter the membrane potential, inhibited and enhanced relaxation, respectively. Exposure to 1 mM K+ solution increased the relaxation to low concentrations of sodium nitroprusside, but had no effect on relaxation induced by 8-bromo-cyclic GMP or M & B 22,948. Thus, another procedure which inhibits the Na+, K+-pump enhanced the effect of low concentrations of sodium nitroprusside on relaxation. Ouabain had no effect on sodium nitroprusside-induced accumulation of cyclic GMP. These results suggest that sodium nitroprusside may induce relaxation through cyclic GMP formation, effects on the Na+, K+-pump and/or hyper-polarization of the smooth muscle cell membrane.
Extracellular Ca2+ Dependence and Diltiazem Inhibition of Contraction in Rabbit Conduit Arteries and Mesenteric Resistance Vessels
Authors: Cauvin Cynthia , Saida Kooichi , van Breemen Cornells
Published: September 2008

The dependence of norepinephrine-(NE-) and high potassium (80 mMK) depolarization-induced contractions on extracellular versus intracellular calcium (Ca2+) pools was studied in strips of rabbit superior mesenteric artery and its branches, and in perfused mesenteric resistance vessels. 80 mM K contractions were abolished in the presence of 0 Ca2+ 2 mM EGTA in all arteries studied, whereas 10-5M NE-induced contractions and stimulated 45Ca efflux in 0 Ca2+ 2 mM EGTA decreased in a graded fashion from proximal to distal arteries. These data indicate a decreasing release of intracellular Ca2+ and an increasing dependence on extracellular Ca2+ for NE-induced contractions as one proceeds from proximal to distal arteries. This pattern was paralleled by increasing sensitivity of NE-induced contractions to inhibition by diltiazem (10-9 10-4M) from proximal to distal arteries, while inhibition of 80 mM K contractions was similar in all vessels. 45Ca influx induced by 10-5M NE in the resistance vessels, wherein the NE does not release intracellular Ca2+, is approximately 10,000-fold more sensitive to the action of diltiazem than that in the aorta. However, when the aorta is activated by 10-8 MNE, it becomes more sensitive to inhibition by diltiazem than when it is activated by 10-5 MNE. The former NE concentration does not release intracellular Ca2+ in the aorta, whereas the latter does. Thus, it appears that NE-induced 45Ca influx is most susceptible to inhibition by diltiazem when the NE has not also released intracellular Ca2+. We suggest that the release of intracellular Ca2+ by NE may make its stimulated Ca2+ influx less susceptible to inhibition by diltiazem.
In vitro Effects of the Farnesyltransferase Inhibitor Tipifarnib on Myelodysplastic Syndrome Progenitors
Authors: Kotsianidis Ioannis , Bazdiara Ioanna , Anastasiadis Athanasios , Spanoudakis Emmanouil , Pantelidou Despoina , Margaritis Dimitrios , Bourikas George , De Coster Roland , De Porre Peter , Tsatalas Costas
Published: September 2008

Background: Farnesyltransferase inhibitors (FTIs) target proteins needing prenylation for functioning. Tipifarnib (Zarnestra®), a potent and specific inhibitor of farnesyltransferase, showed considerable activity in phase I and II studies in myelodysplastic syndrome (MDS), but the optimal regimen achieving high response rates with minor myelosuppression remains to be determined. Additionally, a direct effect on purified human MDS progenitors has not yet been shown. Methods: MDS and normal CD34+ cells isolated by using immunomagnetic beads were plated for short-term cultures in semisolid media or liquid cultures for flow-cytometric assessment of apoptosis in the presence of either DMSO or various FTI concentrations. Results: Tipifarnib exerted selective in vitro toxicity against clonal MDS hematopoiesis at concentrations less than 10 nM the effect being more prominent in white cell progenitors. This action was not due to apoptosis induction as both normal and MDS progenitors displayed equivalent DiOC3 and annexin V expression up to 72 h after exposure to tipifarnib. Conclusion: The leukemic clone is more susceptible in tipifarnib than normal progenitors. Since myelosuppression represents the main obstacle in the clinical use of tipifarnib in MDS, further reduction of the currently employed dose will potentially result in a more tolerable regimen without compromising its antileukemic action.
Pancreatic Fibrosis Correlates with Exocrine Pancreatic Insufficiency after Pancreatoduodenectomy
Authors: Tran T.C.K. , van ‘t Hof G. , Kazemier G. , Hop W.C. , Pek C. , van Toorenenbergen A.W. , van Dekken H. , van Eijck C.H.J.
Published: September 2008

Background: Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Methods: Fifty-five patients who were treated for pancreatic and periampullary carcinoma and 19 patients with chronic pancreatitis were evaluated. Exocrine pancreatic function was evaluated by fecal elastase-1 test, while endocrine pancreatic function was assessed by plasma glucose level. The extent of fibrosis, duct dilation and endocrine tissue loss was examined histopathologically. Results: A strong correlation was found between pancreatic fibrosis and elastase-1 level less than 100 µg/g (p < 0.0001), reflecting severe exocrine pancreatic insufficiency. A strong correlation was found between pancreatic fibrosis and endocrine tissue loss (p < 0.0001). Neither pancreatic fibrosis nor endocrine tissue loss were correlated with the development of postoperative diabetes mellitus. Duct dilation alone was neither correlated with exocrine nor with endocrine function loss. Conclusion: The majority of patients develop severe exocrine pancreatic insufficiency after pancreatoduodenectomy. The extent of exocrine pancreatic insufficiency is strongly correlated with preoperative fibrosis. The loss of endocrine tissue does not correlate with postoperative diabetes mellitus. Preoperative dilation of the pancreatic duct per se does not predict exocrine or endocrine pancreatic insufficiency postoperatively.
Decision-making under Risk: An fMRI Study
Authors: Hewig Johannes , Straube Thomas , Trippe Ralf H. , Kretschmer Nora , Hecht Holger , Coles Michael G. H. , Miltner Wolfgang H. R.
Published: September 2008

Recent research has focused on decision-making under risk and its neural bases. Two kinds of bad decisions under risk may be defined: too risky decisions and too cautious decisions. Here we show that suboptimal decisions of both kinds lead to increased activity in the anterior cingulate cortex in a Blackjack gambling task. Moreover, this increased activity is related to the avoidance of the negatively evaluated decision under risk. These findings complement other results suggesting an important role of the dorsal anterior cingulate cortex in reward-based decision-making and conflict resolution.
Conceptual Processing in Music as Revealed by N400 Effects on Words and Musical Targets
Authors: Daltrozzo Jérôme , Schön Daniele
Published: September 2008

The cognitive processing of concepts, that is, abstract general ideas, has been mostly studied with language. However, other domains, such as music, can also convey concepts. Koelsch et al. [Koelsch, S., Kasper, E., Sammler, D., Schulze, K., Gunter, T., & Friederici, A. D. Music, language and meaning: Brain signatures of semantic processing. Nature Neuroscience, 7, 302–307, 2004] showed that 10 sec of music can influence the semantic processing of words. However, the length of the musical excerpts did not allow the authors to study the effect of words on musical targets. In this study, we decided to replicate Koelsch et al. findings using 1-sec musical excerpts (Experiment 1). This allowed us to study the reverse influence, namely, of a linguistic context on conceptual processing of musical excerpts (Experiment 2). In both experiments, we recorded behavioral and electrophysiological responses while participants were presented 50 related and 50 unrelated pairs (context/target). Experiments 1 and 2 showed a larger N400 component of the event-related brain potentials to targets following a conceptually unrelated compared to a related context. The presence of an N400 effect with musical targets suggests that music may convey concepts. The relevance of these results for the comprehension of music as a structured set of conceptual units and for the domain specificity of the mechanisms underlying N400 effects are discussed.
A Multisensory Cortical Network for Understanding Speech in Noise
Authors: Bishop Christopher W. , Miller Lee M.
Published: September 2008

In noisy environments, listeners tend to hear a speaker's voice yet struggle to understand what is said. The most effective way to improve intelligibility in such conditions is to watch the speaker's mouth movements. Here we identify the neural networks that distinguish understanding from merely hearing speech, and determine how the brain applies visual information to improve intelligibility. Using functional magnetic resonance imaging, we show that understanding speech-in-noise is supported by a network of brain areas including the left superior parietal lobule, the motor/premotor cortex, and the left anterior superior temporal sulcus (STS), a likely apex of the acoustic processing hierarchy. Multisensory integration likely improves comprehension through improved communication between the left temporal–occipital boundary, the left medial-temporal lobe, and the left STS. This demonstrates how the brain uses information from multiple modalities to improve speech comprehension in naturalistic, acoustically adverse conditions.
Mind Your Left: Spatial Bias in Subcortical Fear Processing
Authors: Siman-Tov Tali , Papo David , Gadoth Natan , Schonberg Tom , Mendelsohn Avi , Perry Daniella , Hendler Talma
Published: September 2008

Hemispheric lateralization of emotional processing has long been suggested, but its underlying neural mechanisms have not yet been defined. In this functional magnetic resonance imaging study, facial expressions were presented to 10 right-handed healthy adult females in an event-related visual half-field presentation paradigm. Differential activations to fearful versus neutral faces were observed in the amygdala, pulvinar, and superior colliculus only for faces presented in the left hemifield. Interestingly, the left hemifield advantage for fear processing was observed in both hemispheres. These results suggest a leftward bias in subcortical fear processing, consistent with the well-documented leftward bias of danger-associated behaviors in animals. The current finding highlights the importance of hemifield advantage in emotional lateralization, which might reflect the combination of hemispheric dominance and asymmetric interhemispheric information transfer.
The Role of Serotonin in Nonnormative Risky Choice: The Effects of Tryptophan Supplements on the “Reflection Effect” in Healthy Adult Volunteers
Authors: Murphy Susannah E. , Longhitano Carlo , Ayres Rachael E. , Cowen Philip J. , Harmer Catherine J. , Rogers Robert D.
Published: September 2008

Risky decision-making involves weighing good and bad outcomes against their probabilities in order to determine the relative values of candidate actions. Although human decision-making sometimes conforms to rational models of how this weighting is achieved, irrational (or nonnormative) patterns of risky choice, including shifts between risk-averse and risk-seeking choices involving equivalent-value gambles (the “reflection effect”), are frequently observed. In the present experiment, we investigated the role of serotonin in decision-making under conditions of uncertainty. Fifteen healthy adult volunteers received a treatment of 3 g per day of the serotonin precursor, tryptophan, in the form of dietary supplements over a 14-day period, whereas 15 age- and IQ-matched control volunteers received a matched placebo substance. At test, all participants completed a risky decision-making task involving a series of choices between two simultaneously presented gambles, differing in the magnitude of their possible gains, the magnitude of their possible losses, and the probabilities with which these outcomes were delivered. Tryptophan supplements were associated with alterations in the weighting of gains and small losses perhaps reflecting reduced loss-aversion, and a marked and significant diminution of the reflection effect. We conclude that serotonin activity plays a significant role in nonnormative risky decision-making under conditions of uncertainty.
The Cerebral Basis of Mapping Nonsymbolic Numerical Quantities onto Abstract Symbols: An fMRI Training Study
Authors: Lyons Ian M. , Ansari Daniel
Published: September 2008

Although significant insights into the neural basis of numerical and mathematical processing have been made, the neural processes that enable abstract symbols to become numerical remain largely unexplored in humans. In the present study, adult participants were trained to associate novel symbols with nonsymbolic numerical magnitudes (arrays of dots). Functional magnetic resonance imaging was used to examine the neural correlates of numerical comparison versus recognition of the novel symbols after each of two training stages. A left-lateralized fronto-parietal network, including the intraparietal sulcus, the precuneus, and the dorsal prefrontal cortex, was more active during numerical comparison than during perceptual recognition. In contrast, a network including bilateral temporal–occipital regions was more active during recognition than comparison. A whole-brain three-way interaction revealed that those individuals who had higher scores on a postscan numerical task (measuring their understanding of the global numerical organization of the novel symbols) exhibited increasing segregation between the two tasks in the bilateral intraparietal sulci as a function of increased training. Furthermore, whole-brain regression analysis showed that activity in the left intraparietal sulcus was systematically related to the effect of numerical distance on accuracy. These data provide converging evidence that parietal and left prefrontal cortices are involved in learning to map numerical quantities onto visual symbols. Only the parietal cortex, however, appeared systematically related to the degree to which individuals learned to associate novel symbols with their numerical referents. We conclude that the left parietal cortex, in particular, may play a central role in imbuing visual symbols with numerical meaning.
Word Semantics Is Processed Even without Attentional Effort
Authors: Relander Kristiina , Rämä Pia , Kujala Teija
Published: September 2008

We examined the attentional modulation of semantic priming and the N400 effect for spoken words. The aim was to find out how the semantics of spoken language is processed when attention is directed to another modality (passive task), to the phonetics of spoken words (phonological task), or to the semantics of spoken words (word task). Equally strong behavioral priming effects were obtained in the phonological and the word tasks. A significant N400 effect was found in all tasks. The effect was stronger in the word and the phonological tasks than in the passive task, but there was no difference in the magnitude of the effect between the phonological and the word tasks. The latency of the N400 effect did not differ between the tasks. Although the N400 effect had a centroparietal maximum in the phonological and the word tasks, it was largest at the parietal recording sites in the passive task. The effect was more pronounced at the left than right recording sites in the phonological task, but there was no laterality effect in the other tasks. The N400 effect in the passive task indicates that semantic priming occurs even when spoken words are not actively attended. However, stronger N400 effect in the phonological and the word tasks than in the passive task suggests that controlled processes modulate the N400 effect. The finding that there were no differences in the N400 effect between the phonological and the word tasks indicates that the semantics of attended spoken words is processed regardless of whether semantic processing is relevant for task performance.
Learning to Become an Expert: Reinforcement Learning and the Acquisition of Perceptual Expertise
Authors: Krigolson Olav E. , Pierce Lara J. , Holroyd Clay B. , Tanaka James W.
Published: September 2008

To elucidate the neural mechanisms underlying the development of perceptual expertise, we recorded ERPs while participants performed a categorization task. We found that as participants learned to discriminate computer generated “blob” stimuli, feedback modulated the amplitude of the error-related negativity (ERN)—an ERP component thought to reflect error evaluation within medial–frontal cortex. As participants improved at the categorization task, we also observed an increase in amplitude of an ERP component associated with object recognition (the N250). The increase in N250 amplitude preceded an increase in amplitude of an ERN component associated with internal error evaluation (the response ERN). Importantly, these electroencephalographic changes were not observed for participants who failed to improve on the categorization task. Our results suggest that the acquisition of perceptual expertise relies on interactions between the posterior perceptual system and the reinforcement learning system involving medial–frontal cortex.
Neural Systems Supporting the Control of Affective and Cognitive Conflicts
Authors: Ochsner Kevin N. , Hughes Brent , Robertson Elaine R. , Cooper Jeffrey C. , Gabrieli John D. E.
Published: September 2008

Although many studies have examined the neural bases of controlling cognitive responses, the neural systems for controlling conflicts between competing affective responses remain unclear. To address the neural correlates of affective conflict and their relationship to cognitive conflict, the present study collected whole-brain fMRI data during two versions of the Eriksen flanker task. For these tasks, participants indicated either the valence (affective task) or the semantic category (cognitive task) of a central target word while ignoring flanking words that mapped onto either the same (congruent) or a different (incongruent) response as the target. Overall, contrasts of incongruent > congruent trials showed that bilateral dorsal ACC, posterior medial frontal cortex, and dorsolateral pFC were active during both kinds of conflict, whereas rostral medial pFC and left ventrolateral pFC were differentially active during affective or cognitive conflict, respectively. Individual difference analyses showed that separate regions of rostral cingulate/ventromedial pFC and left ventrolateral pFC were positively correlated with the magnitude of response time interference. Taken together, the findings that controlling affective and cognitive conflicts depends upon both common and distinct systems have important implications for understanding the organization of control systems in general and their potential dysfunction in clinical disorders.
Seeing Sounds and Hearing Colors: An Event-related Potential Study of Auditory–Visual Synesthesia
Authors: Goller Aviva I. , Otten Leun J. , Ward Jamie
Published: September 2008

In auditory–visual synesthesia, sounds automatically elicit conscious and reliable visual experiences. It is presently unknown whether this reflects early or late processes in the brain. It is also unknown whether adult audiovisual synesthesia resembles auditory-induced visual illusions that can sometimes occur in the general population or whether it resembles the electrophysiological deflection over occipital sites that has been noted in infancy and has been likened to synesthesia. Electrical brain activity was recorded from adult synesthetes and control participants who were played brief tones and required to monitor for an infrequent auditory target. The synesthetes were instructed to attend either to the auditory or to the visual (i.e., synesthetic) dimension of the tone, whereas the controls attended to the auditory dimension alone. There were clear differences between synesthetes and controls that emerged early (100 msec after tone onset). These differences tended to lie in deflections of the auditory-evoked potential (e.g., the auditory N1, P2, and N2) rather than the presence of an additional posterior deflection. The differences occurred irrespective of what the synesthetes attended to (although attention had a late effect). The results suggest that differences between synesthetes and others occur early in time, and that synesthesia is qualitatively different from similar effects found in infants and certain auditory-induced visual illusions in adults. In addition, we report two novel cases of synesthesia in which colors elicit sounds, and vice versa.
Anticipating Conflict Facilitates Controlled Stimulus-response Selection
Authors: Correa Ángel , Rao Anling , Nobre Anna C.
Published: September 2008

Cognitive control can be triggered in reaction to previous conflict, as suggested by the finding of sequential effects in conflict tasks. Can control also be triggered proactively by presenting cues predicting conflict (“proactive control”)? We exploited the high temporal resolution of ERPs and controlled for sequential effects to ask whether proactive control based on anticipating conflict modulates neural activity related to cognitive control, as may be predicted from the conflict-monitoring model. ERPs associated with conflict detection (N2) were measured during a cued flanker task. Symbolic cues were either informative or neutral with respect to whether the target involved conflicting or congruent responses. Sequential effects were controlled by analyzing the congruency of the previous trial. The results showed that cueing conflict facilitated conflict resolution and reduced the N2 latency. Other potentials (frontal N1 and P3) were also modulated by cueing conflict. Cueing effects were most evident after congruent than after incongruent trials. This interaction between cueing and sequential effects suggests neural overlap between the control networks triggered by proactive and reactive signals. This finding clarifies why previous neuroimaging studies, in which reactive sequential effects were not controlled, have rarely found anticipatory effects upon conflict-related activity. Finally, the high temporal resolution of ERPs was critical to reveal a temporal modulation of conflict detection by proactive control. This novel finding suggests that anticipating conflict speeds up conflict detection and resolution. Recent research suggests that this anticipatory mechanism may be mediated by preactivation of ACC during the preparatory interval.
An fMRI Investigation of Spontaneous Mental State Inference for Moral Judgment
Authors: Young Liane , Saxe Rebecca
Published: September 2008

Human moral judgment depends critically on “theory of mind,” the capacity to represent the mental states of agents. Recent studies suggest that the right TPJ (RTPJ) and, to lesser extent, the left TPJ (LTPJ), the precuneus (PC), and the medial pFC (MPFC) are robustly recruited when participants read explicit statements of an agent's beliefs and then judge the moral status of the agent's action. Real-world interactions, by contrast, often require social partners to infer each other's mental states. The current study uses fMRI to probe the role of these brain regions in supporting spontaneous mental state inference in the service of moral judgment. Participants read descriptions of a protagonist's action and then either (i) “moral” facts about the action's effect on another person or (ii) “nonmoral” facts about the situation. The RTPJ, PC, and MPFC were recruited selectively for moral over nonmoral facts, suggesting that processing moral stimuli elicits spontaneous mental state inference. In a second experiment, participants read the same scenarios, but explicit statements of belief preceded the facts: Protagonists believed their actions would cause harm or not. The response in the RTPJ, PC, and LTPJ was again higher for moral facts but also distinguished between neutral and negative outcomes. Together, the results illuminate two aspects of theory of mind in moral judgment: (1) spontaneous belief inference and (2) stimulus-driven belief integration.
Distinct Hippocampal and Basal Ganglia Contributions to Probabilistic Learning and Reversal
Authors: Shohamy Daphna , Myers Catherine E. , Hopkins Ramona O. , Sage Jake , Gluck Mark A.
Published: September 2008

The hippocampus and the basal ganglia are thought to play fundamental and distinct roles in learning and memory, supporting two dissociable memory systems. Interestingly, however, the hippocampus and the basal ganglia have each, separately, been implicated as necessary for reversal learning—the ability to adaptively change a response when previously learned stimulus–outcome contingencies are reversed. Here, we compared the contribution of the hippocampus and the basal ganglia to distinct aspects of learning and reversal. Amnesic subjects with selective hippocampal damage, Parkinson subjects with disrupted basal ganglia function, and healthy controls were tested on a novel probabilistic learning and reversal paradigm. In this task, reversal can be achieved in two ways: Subjects can reverse a previously learned response, or they can select a new cue during the reversal phase, effectively “opting out” of the reversal. We found that both patient groups were intact at initial learning, but differed in their ability to reverse. Amnesic subjects failed to reverse, and continued to use the same cue and response learned before the reversal. Parkinson subjects, by contrast, opted out of the reversal by learning a new cue–outcome association. These results suggest that both the hippocampus and the basal ganglia support reversal learning, but in different ways. The basal ganglia are necessary for learning a new response when a previously learned response is no longer rewarding. The failure of the amnesic subjects to reverse their response or to learn a new cue is consistent with a more general role for the hippocampus in configural learning, and suggests it may also support the ability to respond to changes in cue–outcome contingencies.
Target Selection by the Frontal Cortex during Coordinated Saccadic and Smooth Pursuit Eye Movements
Authors: Srihasam Krishna , Bullock Daniel , Grossberg Stephen
Published: September 2008

Oculomotor tracking of moving objects is an important component of visually based cognition and planning. Such tracking is achieved by a combination of saccades and smooth-pursuit eye movements. In particular, the saccadic and smooth-pursuit systems interact to often choose the same target, and to maximize its visibility through time. How do multiple brain regions interact, including frontal cortical areas, to decide the choice of a target among several competing moving stimuli? How is target selection information that is created by a bias (e.g., electrical stimulation) transferred from one movement system to another? These saccade–pursuit interactions are clarified by a new computational neural model, which describes interactions between motion processing areas: the middle temporal area, the middle superior temporal area, the frontal pursuit area, and the dorsal lateral pontine nucleus; saccade specification, selection, and planning areas: the lateral intraparietal area, the frontal eye fields, the substantia nigra pars reticulata, and the superior colliculus; the saccadic generator in the brain stem; and the cerebellum. Model simulations explain a broad range of neuroanatomical and neurophysiological data. These results are in contrast with the simplest parallel model with no interactions between saccades and pursuit other than common-target selection and recruitment of shared motoneurons. Actual tracking episodes in primates reveal multiple systematic deviations from predictions of the simplest parallel model, which are explained by the current model.
Global Perspective of the Quasi-Biweekly Oscillation*
Authors: Kikuchi Kazuyoshi , Wang Bin
Published: September 2008

The quasi-biweekly oscillation (QBW: here defined as a 12–20-day oscillation) is one of the major systems that affect tropical and subtropical weather and seasonal mean climate. However, knowledge is limited concerning its temporal and spatial structures and dynamics, particularly in a global perspective. To advance understanding of the QBW, its life cycle is documented using a tracking method and extended EOF analysis. Both methods yield consistent results. The analyses reveal a wide variety of QBW activity in terms of initiation, movement, development, and dissipation. The convective anomalies associated with the QBW are predominant in the latitude bands between 10° and 30° in both hemispheres. The QBW modes tend to occur regionally and be associated with monsoons. Three boreal summer modes are identified in the Asia–Pacific, Central America, and subtropical South Pacific regions. Five austral summer modes are identified in the Australia–southwest Pacific, South Africa–Indian Ocean, South America–Atlantic, subtropical North Pacific, and North Atlantic–North Africa regions.

The QBW modes are classified into two categories: westward- and eastward-propagating modes. The westward mode is found in the Asia–Pacific and Central America regions during boreal summer; it originates in the tropics and dissipates in the subtropics. The behavior of the westward-propagating mode can be understood in terms of equatorial Rossby waves in the presence of monsoon mean flow and convective coupling. The eastward-propagating mode, on the other hand, connects with upstream extratropical Rossby wave trains and propagates primarily eastward and equatorward. Barotropic Rossby wave trains play an essential role in controlling initiation, development, and propagation of the eastward QBW mode in the subtropics. The results therefore suggest that not only tropical but also extratropical dynamics are required for fully understanding the behavior of the QBW systems worldwide. The new conceptual picture of QBW obtained here based on long-term observation provides valuable information on the behavior of QBW systems in a global perspective, which is important for a thorough understanding of tropical variability on a time scale between day-to-day weather and the Madden–Julian oscillation.
Evolution of a Random Directional Wave and Freak Wave Occurrence
Authors: Waseda Takuji , Kinoshita Takeshi , Tamura Hitoshi
Published: September 2008

The evolution of a random directional wave in deep water was studied in a laboratory wave tank (50 m long, 10 m wide, 5 m deep) utilizing a directional wave generator. A number of experiments were conducted, changing the various spectral parameters (wave steepness 0.05 < ɛ < 0.11, with directional spreading up to 36° and frequency bandwidth 0.2 < δk/k < 0.6). The wave evolution was studied by an array of wave wires distributed down the tank. As the spectral parameters were altered, the wave height statistics change. Without any wave directionality, the occurrence of waves exceeding twice the significant wave height (the freak wave) increases as the frequency bandwidth narrows and steepness increases, due to quasi-resonant wave–wave interaction. However, the probability of an extreme wave rapidly reduces as the directional bandwidth broadens. The effective Benjamin–Feir index (BFIeff) is introduced, extending the BFI (the relative magnitude of nonlinearity and dispersion) to incorporate the effect of directionality, and successfully parameterizes the observed occurrence of freak waves in the tank. Analysis of the high-resolution hindcast wave field of the northwest Pacific reveals that such a directionally confined wind sea with high extreme wave probability is rare and corresponds mostly to a swell–wind sea mixed condition. Therefore, extreme wave occurrence in the sea as a result of quasi-resonant wave–wave interaction is a rare event that occurs only when the wind sea directionality is extremely narrow.
Multiclass ROC Analysis
Authors: Wandishin Matthew S. , Mullen Steven J.
Published: September 2008

Receiver operating characteristic (ROC) curves have become a common analysis tool for evaluating forecast discrimination: the ability of a forecast system to distinguish between events and nonevents. As is implicit in that statement, application of the ROC curve is limited to forecasts involving only two possible outcomes, such as rain and no rain. However, many forecast scenarios exist for which there are multiple possible outcomes, such as rain, snow, and freezing rain. An extension of the ROC curve to multiclass forecast problems is explored. The full extension involves high-dimensional hypersurfaces that cannot be visualized and that present other problems. Therefore, several different approximations to the full extension are introduced using both artificial and actual forecast datasets. These approximations range from sets of simple two-class ROC curves to sets of three-dimensional ROC surfaces. No single approximation is superior for all forecast problems; thus, the specific aims in evaluating the forecast must be considered.
EU agencies: what is common and what is distinctive compared with national-level public agencies
Authors: Barbieri Dario , Ongaro Edoardo
Published: September 2008

The number and relevance of EU agencies have rapidly increased over the years: EU agencies nowadays constitute an important part of the EU institutional landscape. The article investigates the EU agencies through categories of analysis well established in studies of public management focused on the phenomenon of agencies at the country level: structural disaggregation, autonomy, and contractualization. It emerges that EU agencies are relatively homogeneous, an aspect that differentiates European agencies from the highly heterogeneous world of national-level agencies. The main features of the EU agencies are examined, the `European type' of agency is identified and defined, and the way the EU agency model differs from country-level agencies is analysed. Research agendas on the reform of the European Union might benefit from systematic investigation of EU agencies: theoretical frameworks drawn from the public management field can provide a significant contribution in this respect.

Points for practitioners EU agencies are no longer `residual' organizations: they are a significant component of the functioning of the EU system and policy networks. By investigating the features of such agencies through the conceptual lenses of public management, and through comparison with the (much more investigated) national-level agencies, the article provides an outline of EU agencies in terms of structural relations with the other EU institutions, autonomy, and modalities of steering and control. Reforms of the EU through the establishment or revamping of agencies could benefit from the systematic consideration of such features.