Detection of simple and pattern regularity violations occurs at different levels of the auditory hierarchy

Auditory deviance detection in humans is indexed by the mismatch negativity (MMN), a component of the auditory evoked potential (AEP) of the electroencephalogram (EEG) occurring at a latency of 100-250 ms after stimulus onset. However, by using classic oddball paradigms, differential responses to regularity violations of simple auditory features have been found at the level of the middle latency response (MLR) of the AEP occurring within the first 50 ms after stimulus (deviation) onset. These findings suggest the existence of fast deviance detection mechanisms for simple feature changes, but it is not clear whether deviance detection among more complex acoustic regularities could be observed at such early latencies. To test this, we examined the pre-attentive processing of rare stimulus repetitions in a sequence of tones alternating in frequency in both long and middle latency ranges. Additionally, we introduced occasional changes in the interaural time difference (ITD), so that a simple-feature regularity could be examined in the same paradigm. MMN was obtained for both repetition and ITD deviants, occurring at 150 ms and 100 ms after stimulus onset respectively. At the level of the MLR, a difference was observed between standards and ITD deviants at the Na component (20-30 ms after stimulus onset), for 800 Hz tones, but not for repetition deviants. These findings suggest that detection mechanisms for deviants to simple regularities, but not to more complex regularities, are already activated in the MLR range, supporting the view that the auditory deviance detection system is organized in a hierarchical manner

Normalization of Sequential Top-Down Tree-to-Word Transducers

International audienceWe study normalization of deterministic sequential top-down tree-to-word transducers (STWs), that capture the class of deterministic top-down nested-word to word transducers. We identify the subclass of earliest STWs (eSTWs) that yield normal forms when minimized. The main result of this paper is an effective normalization procedure for STWs. It consists of two stages: we first convert a given STW to an equivalent eSTW, and then, we minimize the eSTW. Keywords: formal language theory, tree automata, transformations, XML databases, XSLTExtended Version: A long version is available here.</p

Oscillatory activity in the infant brain and the representation of small numbers

Gamma-band oscillatory activity (GBA) is an established neural signature of sustained occluded object representation in infants and adults. However, it is not yet known whether the magnitude of GBA in the infant brain reflects the quantity of occluded items held in memory. To examine this, we compared GBA of 6–8 month-old infants during occlusion periods after the representation of two objects vs. that of one object. We found that maintaining a representation of two objects during occlusion resulted in significantly greater GBA relative to maintaining a single object. Further, this enhancement was located in the right occipital region, which is consistent with previous object representation research in adults and infants. We conclude that enhanced GBA reflects neural processes underlying infants’ representation of small numbers

Total and High Molecular Weight Adiponectin and Hepatocellular Carcinoma with HCV Infection

Adiponectin is shown to be inversely associated with development and progression of various cancers. We evaluated whether adiponectin level was associated with the prevalence and histological grade of hepatocellular carcinoma (HCC), and liver fibrosis in patients with hepatitis C virus (HCV) infection.A case-control study was conducted on 97 HCC patients (cases) and 97 patients (controls) matched for sex, Child-Pugh grade and platelet count in patients with HCV infection. The serum total and high molecular weight (HMW) adiponectin levels were measured by enzyme-linked immunosorbent assays and examined in their association with the prevalence of HCC. In addition, the relationship between these adiponectin levels and body mass index (BMI), progression of liver fibrosis, and histological grade of HCC was also evaluated. Liver fibrosis was assessed using the aspartate aminotransferase to platelet ratio index (APRI).There were no significant differences in the serum total and HMW adiponectin levels between cases and controls. Moreover, there were no inverse associations between serum total and HMW adiponectin levels and BMI in both cases and controls. On the other hand, serum total and HMW adiponectin levels are positively correlated with APRI in both cases (r = 0.491, P<0.001 and r = 0.485, P<0.001, respectively) and controls (r = 0.482, P<0.001 and r = 0.476, P<0.001, respectively). Interestingly, lower serum total (OR 11.76, 95% CI: 2.97–46.66 [P<0.001]) and HMW (OR 10.24, CI: 2.80–37.40 [P<0.001] adiponectin levels were independent risk factors of worse histological grade of HCC.Our results suggested that serum total and HMW adiponectin levels were predictors of liver fibrosis, but not prevalence of HCC in patients with HCV infection. Moreover, low these adiponectin levels were significantly associated with worse histological grades

Genome sequence analysis of Helicobacter pylori strains associated with gastric ulceration and gastric cancer

<p>Abstract</p> <p>Background</p> <p>Persistent colonization of the human stomach by <it>Helicobacter pylori </it>is associated with asymptomatic gastric inflammation (gastritis) and an increased risk of duodenal ulceration, gastric ulceration, and non-cardia gastric cancer. In previous studies, the genome sequences of <it>H. pylori </it>strains from patients with gastritis or duodenal ulcer disease have been analyzed. In this study, we analyzed the genome sequences of an <it>H. pylori </it>strain (98-10) isolated from a patient with gastric cancer and an <it>H. pylori </it>strain (B128) isolated from a patient with gastric ulcer disease.</p> <p>Results</p> <p>Based on multilocus sequence typing, strain 98-10 was most closely related to <it>H. pylori </it>strains of East Asian origin and strain B128 was most closely related to strains of European origin. Strain 98-10 contained multiple features characteristic of East Asian strains, including a type s1c <it>vacA </it>allele and a <it>cagA </it>allele encoding an EPIYA-D tyrosine phosphorylation motif. A core genome of 1237 genes was present in all five strains for which genome sequences were available. Among the 1237 core genes, a subset of alleles was highly divergent in the East Asian strain 98-10, encoding proteins that exhibited <90% amino acid sequence identity compared to corresponding proteins in the other four strains. Unique strain-specific genes were identified in each of the newly sequenced strains, and a set of strain-specific genes was shared among <it>H. pylori </it>strains associated with gastric cancer or premalignant gastric lesions.</p> <p>Conclusion</p> <p>These data provide insight into the diversity that exists among <it>H. pylori </it>strains from diverse clinical and geographic origins. Highly divergent alleles and strain-specific genes identified in this study may represent useful biomarkers for analyzing geographic partitioning of <it>H. pylori </it>and for identifying strains capable of inducing malignant or premalignant gastric lesions.</p

Examining the pharmacology of mismatch negativity: an electrophysiological investigation in healthy subjects

Schizophrenia is associated with impairments in pre-attentive change detection, as represented by reduced mismatch negativity (MMN) amplitudes. While most researchers believe that this reduced MMN is primarily due to the impaired glutamate (GLU) system, mediated by N-methyl-D-aspartate (NMDA) receptors, it is yet to clarify whether imbalances in other neurotransmitter systems contribute to this diminished MMN. Among the various neurotransmitter systems, whether dopamine (DA) imbalance in schizophrenia contributes to the attenuated MMN is of particular interest, because the two main neurochemical hypotheses of this disorder are the GLU and the DA hypotheses. In addition, given that the serotonin (5HT) system is also involved in the disorder, and glycine (an NMDA receptor co-agonist) has been trialled as an adjunct therapy in schizophrenia, the role of the 5HT system and the effect of glycine in MMN generation also warrant investigation. However, it is difficult to examine these issues from the clinical MMN studies due to a range of substances [drugs] misused by patients. Thus, the current thesis examined the roles of these systems in MMN generation by manipulating them in healthy volunteers, with the primary aim to determine whether acute DA manipulation modulates MMN, and the secondary aim to determine the role of the 5HT system and the effect of an NMDA agonist on MMN generation. The first experiment examined the effects from acute DA receptor stimulation on MMN, where each of 15 subjects was tested under 3 treatment conditions; placebo, 2.5mg bromocriptine (D2 receptor stimulation) and 0.1mg pergolide (D1/D2 receptor stimulation). The results showed that neither bromocriptine nor pergolide had an overall effect on MMN, suggesting that acute stimulation of D2, or D1 and D2 receptors, does not modulate MMN. The second experiment examined the effects from acutely depleting DA precursors, 5HT precursor, and all DA and 5HT precursors simultaneously on MMN, where each of 16 subjects was tested under 4 treatment conditions; balanced (no depletion), tyrosine/phenylalanine depletion (reduced DA function), tryptophan depletion (reduced 5HT function) and tyrosine/phenylalanine/tryptophan depletion (reduced both DA+5HT functions). The results showed that none of the depletion conditions had an overall effect on MMN, suggesting that acutely depleting the precursors of DA, 5HT, or both DA and 5HT systems simultaneously, do not modulate MMN. The third experiment examined the effects from an acute high-dose of glycine on MMN, where each of 16 subjects was tested under 2 treatment conditions; placebo and 0.8g/kg glycine. The results showed that high-dose glycine significantly attenuated the duration MMN amplitude measured at frontal electrodes in healthy subjects. In conclusion, while the DA agonist and monoamine depletion findings suggest that the DA and 5HT systems do not acutely play a significant role in MMN generation, acute high dose glycine resulted in MMN attenuation. This may have important ramifications for the use of chronic adjunct glycine therapy in schizophrenia, as it indicates that high dose glycine may worsen the pre-attentive change detection system of patients with relatively normal plasma glycine levels or NMDA receptor expression

A comparison of the effect of mobile phone use and alcohol consumption on driving simulation performance

Objective: The present study compared the effects of a variety of mobile phone usage conditions to different levels of alcohol intoxication on simulated driving performance and psychomotor vigilance. Methods: Twelve healthy volunteers participated in a crossover design in which each participant completed a simulated driving task on 2 days, separated by a 1-week washout period. On the mobile phone day, participants performed the simulated driving task under each of 4 conditions: no phone usage, a hands-free naturalistic conversation, a hands-free cognitively demanding conversation, and texting. On the alcohol day, participants performed the simulated driving task at four different blood alcohol concentration (BAC) levels: 0.00, 0.04, 0.07, and 0.10. Driving performance was assessed by variables including time within target speed range, time spent speeding, braking reaction time, speed deviation, and lateral lane position deviation. Results: In the BAC 0.07 and 0.10 alcohol conditions, participants spent less time in the target speed range and more time speeding and took longer to brake in the BAC 0.04, 0.07, and 0.10 than in the BAC 0.00 condition. In the mobile phone condition, participants took longer to brake in the natural hands-free conversation, cognitively demanding hands-free conversation and texting conditions and spent less time in the target speed range and more time speeding in the cognitively demanding, hands-free conversation, and texting conditions. When comparing the 2 conditions, the naturalistic conversation was comparable to the legally permissible BAC level (0.04), and the cognitively demanding and texting conversations were similar to the BAC 0.07 to 0.10 results. Conclusion: The findings of the current laboratory study suggest that very simple conversations on a mobile phone may not represent a significant driving risk (compared to legally permissible BAC levels), whereas cognitively demanding, hands-free conversation, and particularly texting represent significant risks to drivin

Editorial: Where the rubber meets the road in visual perception:High temporal-precision brain signals to top-down and bottom-up influences on perceptual resolution

Analysis of human brain responses from various neuroimaging techniques (EEG, S‐EEG, ECoG, or MEG) to visual stimuli in both the time‐ and the time‐frequency domain have provided means for researchers to understand the early stages of visual perception in humans. In the time‐domain, event‐related potentials (ERPs) have been used as neurocognitive tools to study a wide range of cognitive processing in humans, e.g. attention, vigilance, arousal, since the 1960’s (e.g. Haider et al. 1964; Spong et al. 1965; Eason et al. 1969). Importantly, the early neurophysiological studies also drew attention to the importance of carefully characterizing the visual stimulus – to account for non‐linear behavior of ERPs especially Steady State Visual Evoked Potentials (van der Tweel &amp; Lunel, 1965; van der Tweel &amp; Spekreijse, 1969)

Acute dopamine D1 and D2 receptor stimulation does not modulate mismatch negativity (MMN) in healthy human subjects

Schizophrenia is commonly associated with an impairment in pre-attentive change detection, as represented by reduced mismatch negativity (MMN), an auditory event related potential. While the neurochemical basis of MMN has been linked to the integrity of the glutamatergic system involving N-methyl-d-aspartate (NMDA) receptors, the role of the dopaminergic system and in particular, the role of D1 and D2 receptors on MMN is yet to be determined. The aim of the present project was to investigate the acute effects of dopamine D2 (bromocriptine) and D1/D2 (pergolide) receptor stimulation on the human MMN in healthy subjects. Fifteen healthy male subjects participated in a double-blind, placebo-controlled, cross-over design in which each subject was tested under three acute treatment conditions separated by a 1-week wash out period; placebo, bromocriptine (2.5 mg) and pergolide (0.1 mg). The subjects were exposed to a duration-MMN paradigm with 50 ms standard tones (91%) and 100 ms deviant tones (9%). The results showed that neither D2 receptor stimulation with bromocriptine, nor simultaneous D1 and D2 receptor stimulation with pergolide, modulated MMN. These findings suggest that acute D1 and D2 receptor stimulation does not modulate MMN. While the role of dopamine cannot be completely ruled out, the findings support the view that the aberrant MMN reported in schizophrenia may be linked primarily to glutamate dysfunction involving NMDA receptors