Prestimulus default mode activity influences depth of processing and recognition in an emotional memory task

Low self-referential thoughts are associated with better concentration, which leads to deeper encoding and increases learning and subsequent retrieval. There is evidence that being engaged in externally rather than internally focused tasks is related to low neural activity in the default mode network (DMN) promoting open mind and the deep elaboration of new information. Thus, reduced DMN activity should lead to enhanced concentration, comprehensive stimulus evaluation including emotional categorization, deeper stimulus processing, and better long-term retention over one whole week. In this fMRI study, we investigated brain activation preceding and during incidental encoding of emotional pictures and on subsequent recognition performance. During fMRI, 24 subjects were exposed to 80 pictures of different emotional valence and subsequently asked to complete an online recognition task one week later. Results indicate that neural activity within the medial temporal lobes during encoding predicts subsequent memory performance. Moreover, a low activity of the default mode network preceding incidental encoding leads to slightly better recognition performance independent of the emotional perception of a picture. The findings indicate that the suppression of internally-oriented thoughts leads to a more comprehensive and thorough evaluation of a stimulus and its emotional valence. Reduced activation of the DMN prior to stimulus onset is associated with deeper encoding and enhanced consolidation and retrieval performance even one week later. Even small prestimulus lapses of attention influence consolidation and subsequent recognition performance. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.

Lipid remodelling of glycosylphosphatidylinositol (GPI) glycoconjugates in procyclic-form trypanosomes: biosynthesis and processing of GPIs revisited

The African trypanosome, Trypanosoma brucei, has been used as a model to study the biosynthesis of GPI (glycosylphosphatidylinositol) anchors. In mammalian (bloodstream)-form parasites, diacyl-type GPI precursors are remodelled in their lipid moieties before attachment to variant surface glycoproteins. In contrast, the GPI precursors of insect (procyclic)-form parasites, consisting of lyso-(acyl)PI (inositol-acylated acyl-lyso-phosphatidylinositol) species, remain unaltered before protein attachment. By using a combination of metabolic labelling, cell-free assays and complementary MS analyses, we show in the present study that GPI-anchored glycoconjugates in T. congolense procyclic forms initially receive tri-acylated GPI precursors, which are subsequently de-acylated either at the glycerol backbone or on the inositol ring. Chemical and enzymatic treatments of [3H]myristate-labelled lipids in combination with ESI-MS/MS (electrospray ionization-tandem MS) and MALDI-QIT-TOF-MS3 (matrix-assisted laser-desorption ionization-quadrupole ion trap-time-of-flight MS) analyses indicate that the structure of the lipid moieties of steady-state GPI lipids from T. congolense procyclic forms consist of a mixture of lyso-(acyl)PI, diacyl-PI and diacyl-(acyl)PI species. Interestingly, some of these species are myristoylated at the sn-2 position. To our knowledge, this is the first demonstration of lipid remodelling at the level of protein- or polysaccharide-linked GPI anchors in procyclic-form trypanosomes.

Impaired performance on the rapid visual information processing task (RVIP) could be an endophenotype of schizophrenia

The aim of the present study was to investigate whether healthy first-degree relatives of schizophrenia patients show reduced sensitivity performance, higher intra-individual variability (IIV) in reaction time (RT), and a steeper decline in sensitivity over time in a sustained attention task. Healthy first-degree relatives of schizophrenia patients (n=23) and healthy control subjects (n=46) without a family history of schizophrenia performed a demanding version of the Rapid Visual Information Processing task (RVIP). RTs, hits, false alarms, and the sensitivity index A' were assessed. The relatives were significantly less sensitive, tended to have higher IIV in RT, but sustained the impaired level of sensitivity over time. Impaired performance on the RVIP is a possible endophenotype for schizophrenia. Higher IIV in RT, apparently caused by impaired context representations, might result in fluctuations in control and lead to more frequent attentional lapses.

Lack of cathelicidin processing in Papillon-Lefèvre syndrome patients reveals essential role of LL-37 in periodontal homeostasis.

BACKGROUND Loss-of-function point mutations in the cathepsin C gene are the underlying genetic event in patients with Papillon-Lefèvre syndrome (PLS). PLS neutrophils lack serine protease activity essential for cathelicidin LL-37 generation from hCAP18 precursor. AIM We hypothesized that a local deficiency of LL-37 in the infected periodontium is mainly responsible for one of the clinical hallmark of PLS: severe periodontitis already in early childhood. METHODS To confirm this effect, we compared the level of neutrophil-derived enzymes and antimicrobial peptides in gingival crevicular fluid (GCF) and saliva from PLS, aggressive and chronic periodontitis patients. RESULTS Although neutrophil numbers in GCF were present at the same level in all periodontitis groups, LL-37 was totally absent in GCF from PLS patients despite the large amounts of its precursor, hCAP18. The absence of LL-37 in PLS patients coincided with the deficiency of both cathepsin C and protease 3 activities. The presence of other neutrophilic anti-microbial peptides in GCF from PLS patients, such as alpha-defensins, were comparable to that found in chronic periodontitis. In PLS microbial analysis revealed a high prevalence of Aggregatibacter actinomycetemcomitans infection. Most strains were susceptible to killing by LL-37. CONCLUSIONS Collectively, these findings imply that the lack of protease 3 activation by dysfunctional cathepsin C in PLS patients leads to the deficit of antimicrobial and immunomodulatory functions of LL-37 in the gingiva, allowing for infection with A. actinomycetemcomitans and the development of severe periodontal disease.

Stress free configuration of the human eye

Numerical simulations of eye globes often rely on topographies that have been measured in vivo using devices such as the Pentacam or OCT. The topographies, which represent the form of the already stressed eye under the existing intraocular pressure, introduce approximations in the analysis. The accuracy of the simulations could be improved if either the stress state of the eye under the effect of intraocular pressure is determined, or the stress-free form of the eye estimated prior to conducting the analysis. This study reviews earlier attempts to address this problem and assesses the performance of an iterative technique proposed by Pandolfi and Holzapfel [1], which is both simple to implement and promises high accuracy in estimating the eye's stress-free form. A parametric study has been conducted and demonstrated reliance of the error level on the level of flexibility of the eye model, especially in the cornea region. However, in all cases considered 3-4 analysis iterations were sufficient to produce a stress-free form with average errors in node location <10(-6)mm and a maximal error <10(-4)mm. This error level, which is similar to what has been achieved with other methods and orders of magnitude lower than the accuracy of current clinical topography systems, justifies the use of the technique as a pre-processing step in ocular numerical simulations.

Individual and population level effects of partner notification for Chlamydia trachomatis

Partner notification (PN or contact tracing) is an important aspect of treating bacterial sexually transmitted infections (STIs), such as Chlamydia trachomatis. It facilitates the identification of new infected cases that can be treated through individual case management. PN also acts indirectly by limiting onward transmission in the general population. However, the impact of PN, both at the level of individuals and the population, remains unclear. Since it is difficult to study the effects of PN empirically, mathematical and computational models are useful tools for investigating its potential as a public health intervention. To this end, we developed an individual-based modeling framework called Rstisim. It allows the implementation of different models of STI transmission with various levels of complexity and the reconstruction of the complete dynamic sexual partnership network over any time period. A key feature of this framework is that we can trace an individual's partnership history in detail and investigate the outcome of different PN strategies for C. trachomatis. For individual case management, the results suggest that notifying three or more partners from the preceding 18 months yields substantial numbers of new cases. In contrast, the successful treatment of current partners is most important for preventing re-infection of index cases and reducing further transmission of C. trachomatis at the population level. The findings of this study demonstrate the difference between individual and population level outcomes of public health interventions for STIs.

Developmental changes of BOLD signal correlations with global human EEG power and synchronization during working memory

In humans, theta band (5-7 Hz) power typically increases when performing cognitively demanding working memory (WM) tasks, and simultaneous EEG-fMRI recordings have revealed an inverse relationship between theta power and the BOLD (blood oxygen level dependent) signal in the default mode network during WM. However, synchronization also plays a fundamental role in cognitive processing, and the level of theta and higher frequency band synchronization is modulated during WM. Yet, little is known about the link between BOLD, EEG power, and EEG synchronization during WM, and how these measures develop with human brain maturation or relate to behavioral changes. We examined EEG-BOLD signal correlations from 18 young adults and 15 school-aged children for age-dependent effects during a load-modulated Sternberg WM task. Frontal load (in-)dependent EEG theta power was significantly enhanced in children compared to adults, while adults showed stronger fMRI load effects. Children demonstrated a stronger negative correlation between global theta power and the BOLD signal in the default mode network relative to adults. Therefore, we conclude that theta power mediates the suppression of a task-irrelevant network. We further conclude that children suppress this network even more than adults, probably from an increased level of task-preparedness to compensate for not fully mature cognitive functions, reflected in lower response accuracy and increased reaction time. In contrast to power, correlations between instantaneous theta global field synchronization and the BOLD signal were exclusively positive in both age groups but only significant in adults in the frontal-parietal and posterior cingulate cortices. Furthermore, theta synchronization was weaker in children and was--in contrast to EEG power--positively correlated with response accuracy in both age groups. In summary we conclude that theta EEG-BOLD signal correlations differ between spectral power and synchronization and that these opposite correlations with different distributions undergo similar and significant neuronal developments with brain maturation.

Increased sensitivity in mapping task demand in visuospatial processing using reaction-time-dependent hemodynamic response predictors in rapid event-related fMRI

Searching for the neural correlates of visuospatial processing using functional magnetic resonance imaging (fMRI) is usually done in an event-related framework of cognitive subtraction, applying a paradigm comprising visuospatial cognitive components and a corresponding control task. Besides methodological caveats of the cognitive subtraction approach, the standard general linear model with fixed hemodynamic response predictors bears the risk of being underspecified. It does not take into account the variability of the blood oxygen level-dependent signal response due to variable task demand and performance on the level of each single trial. This underspecification may result in reduced sensitivity regarding the identification of task-related brain regions. In a rapid event-related fMRI study, we used an extended general linear model including single-trial reaction-time-dependent hemodynamic response predictors for the analysis of an angle discrimination task. In addition to the already known regions in superior and inferior parietal lobule, mapping the reaction-time-dependent hemodynamic response predictor revealed a more specific network including task demand-dependent regions not being detectable using the cognitive subtraction method, such as bilateral caudate nucleus and insula, right inferior frontal gyrus and left precentral gyrus.

Perception of causality in schizophrenia spectrum disorder

Patients with schizophrenia spectrum disorders often maintain deviating views on cause-effect relationships, especially when positive and disorganization symptoms are manifest. Altered perceived causality is prominent in delusional ideation, in ideas of reference, and in the mentalizing ability (theory of mind [ToM]) of patients. Perceiving causal relationships may be understood either as higher order cognitive reasoning or as low-level information processing. In the present study, perception of causality was investigated as a low-level, preattentional capability similar to gestalt-like perceptual organization. Thirty-one patients (24 men and 7 women with mean age 27.7 years) and the same number of healthy control subjects matched to patients with respect to age and sex were tested. A visual paradigm was used in which 2 identical discs move, from opposite sides of a monitor, steadily toward and then past one another. Their coincidence generates an ambiguous, bistable percept (discs either "stream through" or "bounce off" one another). The bouncing perception, ie, perceived causality, is enhanced when auditory stimuli are presented at the time of coincidence. Psychopathology was measured using the Positive and Negative Syndrome Scale. It was found that positive symptoms were strongly associated with increased perceived causality and disorganization with attenuated perceived causality. Patients in general were not significantly different from controls, but symptom subgroups showed specifically altered perceived causality. Perceived causality as a basic preattentional process may contribute to higher order cognitive alterations and ToM deficiencies. It is suggested that cognitive remediation therapy should address both increased and reduced perception of causality.

An EEG approach to the neurodevelopmental hypothesis of schizophrenia studying schizophrenics, normal controls and adolescents

Based on an integrative brain model which focuses on memory-driven and EEG state-dependent information processing for the organisation of behaviour, we used the developmental changes of the awake EEG to further investigate the hypothesis that neurodevelopmental abnormalities (deviations in organisation and reorganisation of cortico-cortical connectivity during development) are involved in the pathogenesis of schizophrenia. First-episode, neuroleptic-naive schizophrenics and their matched controls and three age groups of normal adolescents were studied (total: 70 subjects). 19-channel EEG delta-theta, alpha and beta spectral band centroid frequencies during resting (baseline) and after verbal stimuli were used as measure of the level of attained complexity and momentary excitability of the neuronal network (working memory). Schizophrenics compared with all control groups showed lower delta-theta activity centroids and higher alpha and beta activity centroids. Reactivity centroids (centroid after stimulus minus centroid during resting) were used as measure of update of working memory. Schizophrenics showed partial similarities in delta-theta and beta reactivity centroids with the 11-year olds and in alpha reactivity centroids with the 13-year olds. Within the framework of our model, the results suggest multifactorially elicited imbalances in the level of excitability of neuronal networks in schizophrenia, resulting in network activation at dissociated complexity levels, partially regressed and partially prematurely developed. It is hypothesised that activation of age- and/or state-inadequate representations for coping with realities becomes manifest as productive schizophrenic symptoms. Thus, the results support some aspects of the neurodevelopmental hypothesis.

Effects of butorphanol on the withdrawal reflex using threshold, suprathreshold and repeated subthreshold electrical stimuli in conscious horses

OBJECTIVE: To assess the effects of a single intravenous dose of butorphanol (0.1 mg kg(-1)) on the nociceptive withdrawal reflex (NWR) using threshold, suprathreshold and repeated subthreshold electrical stimuli in conscious horses. STUDY DESIGN: 'Unblinded', prospective experimental study. ANIMALS: Ten adult horses, five geldings and five mares, mean body mass 517 kg (range 487-569 kg). METHODS: The NWR was elicited using single transcutaneous electrical stimulation of the palmar digital nerve. Repeated stimulations were applied to evoke temporal summation. Surface electromyography was performed to record and quantify the responses of the common digital extensor muscle to stimulation and behavioural reactions were scored. Before butorphanol administration and at fixed time points up to 2 hours after injection, baseline threshold intensities for NWR and temporal summation were defined and single suprathreshold stimulations applied. Friedman repeated-measures analysis of variance on ranks and Wilcoxon signed-rank test were used with the Student-Newman-Keul's method applied post-hoc. The level of significance (alpha) was set at 0.05. RESULTS: Butorphanol did not modify either the thresholds for NWR and temporal summation or the reaction scores, but the difference between suprathreshold and threshold reflex amplitudes was reduced when single stimulation was applied. Upon repeated stimulation after butorphanol administration, a significant decrease in the relative amplitude was calculated for both the 30-80 and the 80-200 millisecond intervals after each stimulus, and for the whole post-stimulation interval in the right thoracic limb. In the left thoracic limb a decrease in the relative amplitude was found only in the 30-80 millisecond epoch. CONCLUSION: Butorphanol at 0.1 mg kg(-1) has no direct action on spinal Adelta nociceptive activity but may have some supraspinal effects that reduce the gain of the nociceptive system. CLINICAL RELEVANCE: Butorphanol has minimal effect on sharp immediate Adelta-mediated pain but may alter spinal processing and decrease the delayed sensations of pain.

The influence of colour on oculomotor behaviour during image perception

The aim of this study was to investigate how oculomotor behaviour depends on the availability of colour information in pictorial stimuli. Forty study participants viewed complex images in colour or grey-scale, while their eye movements were recorded. We found two major effects of colour. First, although colour increases the complexity of an image, fixations on colour images were shorter than on their grey-scale versions. This suggests that colour enhances discriminability and thus affects low-level perceptual processing. Second, colour decreases the similarity of spatial fixation patterns between participants. The role of colour on visual attention seems to be more important than previously assumed, in theoretical as well as methodological terms.

Comparison of music perception in bilateral and unilateral cochlear implant users and normal-hearing subjects

Music plays an important role in the daily life of cochlear implant (CI) users, but electrical hearing and speech processing pose challenges for enjoying music. Studies of unilateral CI (UCI) users' music perception have found that these subjects have little difficulty recognizing tempo and rhythm but great difficulty with pitch, interval and melody. The present study is an initial step towards understanding music perception in bilateral CI (BCI) users. The Munich Music Questionnaire was used to investigate music listening habits and enjoyment in 23 BCI users compared to 2 control groups: 23 UCI users and 23 normal-hearing (NH) listeners. Bilateral users appeared to have a number of advantages over unilateral users, though their enjoyment of music did not reach the level of NH listeners.

Nitric oxide induces cell death in canine cruciate ligament cells by activation of tyrosine kinase and reactive oxygen species

BACKGROUND: There is increasing evidence suggesting that development of progressive canine cranial cruciate ligament (CCL) rupture involves a gradual degeneration of the CCL itself, initiated by a combination of factors, ranging from mechanical to biochemical. To date, knowledge is lacking to what extent cruciate disease results from abnormal biomechanics on a normal ligament or contrary how far preliminary alterations of the ligament due to biochemical factors provoke abnormal biomechanics. This study is focused on nitric oxide (NO), one of the potential biochemical factors. The NO-donor sodium nitroprusside (SNP) has been used to study NO-dependent cell death in canine cranial and caudal cruciate ligament cells and to characterize signaling mechanisms during NO-stimulation. RESULTS: Sodium nitroprusside increased apoptotic cell death dose- and time-dependently in cruciate ligamentocytes. Cells from the CCL were more susceptible to apoptosis than CaCL cells. Caspase-3 processing in response to SNP was not detected. Testing major upstream and signal transducing pathways, NO-induced cruciate ligament cell death seemed to be mediated on different levels. Specific inhibition of tyrosine kinase significantly decreased SNP-induced cell death. Mitogen activated protein kinase ERK1 and 2 are activated upon NO and provide anti-apoptotic signals whereas p38 kinase and protein kinase C are not involved. Moreover, data showed that the inhibition reactive oxygen species (ROS) significantly reduced the level of cruciate ligament cell death. CONCLUSIONS: Our data support the hypothesis that canine cruciate ligamentocytes, independently from their origin (CCL or CaCL) follow crucial signaling pathways involved in NO-induced cell death. However, the difference on susceptibility upon NO-mediated apoptosis seems to be dependent on other pathways than on these tested in the present study. In both, CCL and CaCL, the activation of the tyrosine kinase and the generation of ROS reveal important signaling pathways. In perspective, new efforts to prevent the development and progression of cruciate disease may include strategies aimed at reducing ROS.

Does single use of an autologous transfusion system in TKA reduce the need for allogenic blood?: a prospective randomized trial

BACKGROUND Mechanical autotransfusion systems for washed shed blood (WSB) were introduced to reduce the need for postoperative allogenic blood transfusions (ABTs). Although some authors have postulated decreased requirements for ABT by using autologous retransfusion devices, other trials, mostly evaluating retransfusion devices for unwashed shed blood (USB), verified a small or no benefit in reducing the need for postoperative ABT. Because of these contradictory findings it is still unclear whether autologous retransfusion systems for WSB can reduce transfusion requirements. QUESTIONS/PURPOSES We therefore asked whether one such autologous transfusion system for WSB can reduce the requirements for postoperative ABT. METHODS In a prospective, randomized, controlled study, we enrolled 151 patients undergoing TKA. In Group A (n=76 patients), the autotransfusion system was used for a total of 6 hours (intraoperatively and postoperatively) and the WSB was retransfused after processing. In Control Group B (n=75 patients), a regular drain without suction was used. We used signs of anemia and/or a hemoglobin value less than 8 g/dL as indications for transfusion. If necessary, we administered one or two units of allogenic blood. RESULTS Twenty-three patients (33%) in Group A, who received an average of 283 mL (range, 160-406 mL) of salvaged blood, needed a mean of 2.1 units of allogenic blood, compared with 23 patients (33%) in Control Group B who needed a mean of 2.1 units of allogenic blood. CONCLUSIONS We found the use of an autotransfusion system did not reduce the rate of postoperative ABTs. LEVEL OF EVIDENCE Level II, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.