To err is autonomic: error-related brain potentials, ANS activity, and post-error compensatory behavior

A two-component event-related brain potential consisting of an error-related negativity (ERN/Ne) and positivity (Pe) has been associated with response monitoring and error detection. Both the ERN and Pe have been source-localized to the anterior cingulate cortex (ACC)--a frontal structure implicated in both cognitive and affective processing, as well as autonomic nervous system (ANS) modulation. The current study sought to examine the relationships among the ERN, the Pe, two autonomic measures, and behavior. Electroencephalogram (EEG), heart rate (HR), and skin conductance (SC) were recorded while subjects performed a two-choice reaction-time task. In addition to the characteristic ERN-Pe complex, errors were associated with larger SCRs and greater HR deceleration. The ERN correlated with the number of errors, but was unrelated to ANS activity and compensatory behavior. Pe, on the other hand, was correlated significantly with SCR, and both SCR and Pe were significantly correlated with post-error slowing.     

Immunogenicity and safety of the new intradermal influenza vaccine in adults and elderly: A randomized phase 1/2 clinical trial

BackgroundRecent clinical evidence indicates that an intradermal (ID) delivery of vaccines confers superior immunogenicity as compared to a standard intramusclular or subcutaneous (SC) delivery.MethodsIn this exploratory study, 600 healthy adults were randomized to 6 study groups with subgroups of young adults (20–64 years old) and older adults (65 years and older). The subjects were either injected by a novel ID injection system with a single dose of 6, 9, or 15 μg HA or two doses (21 days apart) of 15 μg HA per strain or injected by an SC injection method with a single or two doses (21 days apart) of 15 μg HA per strain. Immunogenicity was assessed using hemagglutination inhibition (HAI) titer and microneutralization titer on Days 0, 10, 21, and 42. Solicited and unsolicited adverse events were recorded for 7 and 21 days post-vaccination, respectively.ResultsIn both young adults and older adults groups, the geometric titer (GMT) ratios of HAI in the ID 15 μg HA group were higher than those in the SC 15 μg HA group on both Day 10 and Day 21, while those in the ID 6 and ID 9 μg HA groups were comparable with those in the SC 15 μg HA group. The kinetics of GMTs of HAI suggested that the ID vaccine has the potential to induce the prompt immune response, which is rather hampered in older adults as seen in the SC vaccine groups. The injection-site AEs were generally mild and transient, and did not occur in a dose or dosage-dependent manner.ConclusionsThe results of this study clearly suggest that the immunologic profile of the ID vaccine is better than that of the SC vaccine, while the safety profile of the ID vaccine is similar to that of the SC vaccine. In this exploratory study with almost 100 subjects per each group, single or two-dose administration of the ID vaccine containing 15 μg HA was suggested to be an appropriate regimen in order to prevent influenza and to reduce the associated disease burden.Trial registrationJAPIC Clinical Trials Information (JapicCTI-132096).     

Components in the P300: Don’t forget the Novelty P3!

This study investigated stimulus-response patterns of temporal principal components analysis (PCA)–derived event-related potential (ERP) components in a classical auditory habituation paradigm with long interstimulus intervals. The skin conductance response (SCR) was included as the “gold standard” model of the Orienting Reflex. Thirty participants were presented with a single series of 10 identical 60 dB tones, followed by a change trial at a different frequency. Single-trial, electrooculography-corrected ERPs were submitted to temporal PCA. The main focus was on the components expected in the P300/Late Positive Complex (LPC), and their electromagnetic tomography–derived cortical sources. Nine components were identified between 90 and 470 ms poststimulus (in temporal order): three N1 subcomponents, P2, four LPC components, and a negative Slow Wave (SW). The expected order of P3a, P3b, Novelty P3 (nP3), and positive Slow Wave (+SW) in the LPC was confirmed. SCR demonstrated strong exponential decay and recovery. P3b and nP3 each showed exponential decrement over trials, but only nP3 showed recovery at the change trial. Novelty effects failed to reach significance for the other LPC components, and were not apparent in non-LPC components. Frontal lobe activity in Brodmann areas 6, 8, and 9 was common to P3a, P3b, nP3, and +SW, consistent with the functional integration of these components in the LPC. Individual components had specific sources, although some sources overlapped between components or were reactivated later in the LPC. These data provide a fresh perspective on the components of the LPC and their cortical sources, and offer a processing model for the P300 in a habituation task, potentially generalizable to other paradigms.     

Ultrastructural defects in stereocilia and tectorial membrane in aging mouse and human cochleae

The aging cochlea is subjected to a number of pathological changes to play a role in the onset of age-related hearing loss (ARHL). Although ARHL has often been thought of as the result of the loss of hair cells, it is in fact a disorder with a complex etiology, arising from the changes to both the organ of Corti and its supporting structures. In this study, we examine two aging pathologies that have not been studied in detail despite their apparent prevalence; the fusion, elongation, and engulfment of cochlear inner hair cell stereocilia, and the changes that occur to the tectorial membrane (TM), a structure overlying the organ of Corti that modulates its physical properties in response to sound. Our work demonstrates that similar pathological changes occur in these two structures in the aging cochleae of both mice and humans, examines the ultrastructural changes that underlie stereocilial fusion, and identifies the lost TM components that lead to changes in membrane structure. We place these changes into the context of the wider pathology of the aging cochlea, and identify how they may be important in particular for understanding the more subtle hearing pathologies that precede auditory threshold loss in ARHL.     

Invertebrate immune diversity

The arms race between hosts and pathogens (and other non-self) drives the molecular diversification of immune response genes in the host. Over long periods of evolutionary time, many different defense strategies have been employed by a wide variety of invertebrates. We review here penaeidins and crustins in crustaceans, the allorecognition system encoded by fuhc, fester and Uncle fester in a colonial tunicate, Dscam and PGRPs in arthropods, FREPs in snails, VCBPs in protochordates, and the Sp185/333 system in the purple sea urchin. Comparisons among immune systems, including those reviewed here have not identified an immune specific regulatory “genetic toolkit”, however, repeatedly identified sequences (or “building materials” on which the tools act) are present in a broad range of immune systems. These include a Toll/TLR system, a primitive complement system, an LPS binding protein, and a RAG core/Transib element. Repeatedly identified domains and motifs that function in immune proteins include NACHT, LRR, Ig, death, TIR, lectin domains, and a thioester motif. In addition, there are repeatedly identified mechanisms (or “construction methods”) that generate sequence diversity in genes with immune function. These include genomic instability, duplications and/or deletions of sequences and the generation of clusters of similar genes or exons that appear as families, gene recombination, gene conversion, retrotransposition, alternative splicing, multiple alleles for single copy genes, and RNA editing. These commonly employed “materials and methods” for building and maintaining an effective immune system that might have been part of that ancestral system appear now as a fragmented and likely incomplete set, likely due to the rapid evolutionary change (or loss) of host genes that are under pressure to keep pace with pathogen diversity.     

The effect of musical experience on emotional self‐reports and psychophysiological responses to dissonance

To study the influence of musical education on emotional reactions to dissonance, we examined self‐reports and physiological responses to dissonant and consonant musical excerpts in listeners with low (LE: n=15) and high (HE: n=13) musical experience. The results show that dissonance induces more unpleasant feelings and stronger physiological responses in HE than in LE participants, suggesting that musical education reinforces aversion to dissonance. Skin conductance (SCR) and electromyographic (EMG) signals were analyzed according to a defense cascade model, which takes into account two successive time windows corresponding to orienting and defense responses. These analyses suggest that musical experience can influence the defense response to dissonance and demonstrate a powerful role of musical experience not only in autonomic but also in expressive responses to music.     

Localization of Knops system antigens in the long homologous repeats of complement receptor 1

BACKGROUND: The Sl(a) (Knops system) located on complement receptor 1 (CR1) has been associated with malarial rosetting, a process associated with severe malarial infections. Moreover, the long homologous repeats (LHRs) B and C of CR1 were implicated in rosette formation. As a step toward mapping the location of Knops system antigens, truncated CR1 proteins have been expressed and their ability to inhibit antibodies to the high-incidence Knops system antigens was assessed. STUDY DESIGN AND METHODS: Individual LHRs (A, B, C, and D) of CR1 of the common CR1*1 (F) allotype were expressed as secreted forms in 293T cells. Their abilities to specifically neutralize Knops system antibodies were tested by both hemagglutination and flow cytometry. RESULTS: Three examples of anti-Kn(a) (n = 6) were almost completely inhibited by LHR-C and three by LHR-D. Two examples of anti-McC(a) (n = 2) and seven examples of anti-Sl(a) (n = 8) were inhibited by LHR-D. Both examples of anti-Yk(a) (n = 2) were partially inhibited by LHR-D. CONCLUSION: The high-incidence Knops system antigens reside within LHR-D and to a lesser extent within LHR-C. Because of the role of Sl(a) antigen in malaria rosetting, these results indicate that LHR-D may represent an additional malaria interaction region in CR1.