Neurophysiological origin of human brain asymmetry for speech and language.

The physiological basis of human cerebral asymmetry for language remains mysterious. We have used simultaneous physiological and anatomical measurements to investigate the issue. Concentrating on neural oscillatory activity in speech-specific frequency bands and exploring interactions between gestural (motor) and auditory-evoked activity, we find, in the absence of language-related processing, that left auditory, somatosensory, articulatory motor, and inferior parietal cortices show specific, lateralized, speech-related physiological properties. With the addition of ecologically valid audiovisual stimulation, activity in auditory cortex synchronizes with left-dominant input from the motor cortex at frequencies corresponding to syllabic, but not phonemic, speech rhythms. Our results support theories of language lateralization that posit a major role for intrinsic, hardwired perceptuomotor processing in syllabic parsing and are compatible both with the evolutionary view that speech arose from a combination of syllable-sized vocalizations and meaningful hand gestures and with developmental observations suggesting phonemic analysis is a developmentally acquired process.

The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain.

Maturation of the arenavirus GP precursor (GPC) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P), yielding a tripartite complex comprised of a stable signal peptide (SSP), the receptor-binding GP1, and the fusion-active transmembrane GP2. Here we investigated the roles of SKI-1/S1P processing and SSP in the biosynthesis of the recombinant GP ectodomains of lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV). When expressed in mammalian cells, the LCMV and LASV GP ectodomains underwent processing by SKI-1/S1P, followed by dissociation of GP1 from GP2. The GP2 ectodomain spontaneously formed trimers as revealed by chemical cross-linking. The endogenous SSP, known to be crucial for maturation and transport of full-length arenavirus GPC was dispensable for processing and secretion of the soluble GP ectodomain, suggesting a specific role of SSP in the stable prefusion conformation and transport of full-length GPC.

A glutathione precursor, N-acetyl-cysteine, modulates mismatch negativity generation in schizophrenia patients

Schizophrenia patients exhibit deficits in low-level processing, including pitch discrimination. This deficiency manifests in auditory evoked potentials (AEPs) as an impaired mismatch negativity (MMN), an electrophysiological response to infrequent target stimuli interspersed among frequent standard stimuli that typically peaks ~100ms post-stimulus onset. NMDA receptor antagonists have been shown to block MMN generation in both animals and humans, and NMDA dysfunction has been linked to the underlying pathophysiology of schizophrenia. A parallel line of evidence indicates that glutathione (GSH) regulation is perturbed in schizophrenia patients at the gene, protein and functional levels (Tosic et al., 2006). This GSH dysregulation leads to NMDA receptors' hypofunction through interaction with their redox site (Steullet et al., 2006). The present study aimed to modulate GSH levels in schizophrenia patients and assessed the effects of such a modulation on MMN generation mechanisms. N-acetyl-cysteine (NAC), a GSH precursor, was administered to schizophrenia patients, using a double-blind cross-over protocol. One group received NAC (2g/day) for 60 days and then placebo for another 60 days, and vice-versa for the second group. AEPs from patients were recorded at the onset of the protocol, at the point of cross-over, and at the end of the study. Participants were instructed to manually respond to target stimuli (2kHz pure tones occurring 20% of the time among 1kHz pure tones). Analyses of AEPs recorded at protocol onset indicated that patients (n=11) were significantly impaired in generating the MMN relative to age-matched controls (n=11). Specifically, the global field power (GFP), an index of AEP magnitude, was measured over the 70- 155ms post-stimulus interval and submitted to an analysis of variance (ANOVA). There was a significant interaction between population and stimulus frequency, indicating impaired MMN generation in patients at protocol onset. Analyses of AEPs recorded during administration of NAC (n=7) versus placebo (n=7) revealed the efficacy of this GSH precursor in modulating MMN generation mechanisms. ANOVA of GFP over the 70- 155ms post-stimulus interval, using stimulus frequency and treatment as within-participants variables, revealed a significant interaction and indicated that NAC can ameliorate MMN generation. We discuss these results in terms of potential therapeutic strategies for schizophrenia.

Perceptual and semantic contributions to repetition priming of environmental sounds.

Repetition of environmental sounds, like their visual counterparts, can facilitate behavior and modulate neural responses, exemplifying plasticity in how auditory objects are represented or accessed. It remains controversial whether such repetition priming/suppression involves solely plasticity based on acoustic features and/or also access to semantic features. To evaluate contributions of physical and semantic features in eliciting repetition-induced plasticity, the present functional magnetic resonance imaging (fMRI) study repeated either identical or different exemplars of the initially presented object; reasoning that identical exemplars share both physical and semantic features, whereas different exemplars share only semantic features. Participants performed a living/man-made categorization task while being scanned at 3T. Repeated stimuli of both types significantly facilitated reaction times versus initial presentations, demonstrating perceptual and semantic repetition priming. There was also repetition suppression of fMRI activity within overlapping temporal, premotor, and prefrontal regions of the auditory "what" pathway. Importantly, the magnitude of suppression effects was equivalent for both physically identical and semantically related exemplars. That the degree of repetition suppression was irrespective of whether or not both perceptual and semantic information was repeated is suggestive of a degree of acoustically independent semantic analysis in how object representations are maintained and retrieved.

Characterization of the enzyme involved in the processing of big endothelin-1 in human lung epithelial cells.

Biosynthesis of active endothelin-1 (ET-1) implies an enzymatic processing of the inactive precursor Big ET-1 (1-39) into the mature, 21 amino acid peptide. The aim of this study was to characterize in airway and alveolar epithelial cells the enzymes responsible for this activation. BEAS-2B and A549 cells, which both produce ET-1, were studied in vitro as models for bronchiolar and alveolar cells, respectively. Both cell lines were able to convert exogenously added Big ET-1 (0.1 microM) into ET-1, suggesting a cell surface or an extracellular processing. The conversion was inhibited by phosphoramidon in both cell lines with an IC50 approximately 1 microM, but not by thiorphan, a specific inhibitor of neutral endopeptidase 24.11 (NEP). The endogenous production of serum-stimulated BEAS-2B and A549 cells was not inhibited by thiorphan, and phosphoramidon showed inhibition only at high concentration (>100 microM). Western blotting following electrophoresis in reducing conditions demonstrated a protein of MR 110 corresponding to the ECE-1 monomer in both BEAS-2B and A549 cells, as well as in whole lung extracts. By RT-PCR we revealed the mRNA encoding for the ECE-1b and/or -1c subtype, but not ECE-1a, in both cell lines. We conclude that BEAS-2B and A549 cells are able to process either endogenous or exogenous Big ET-1 by ECE-1 and that isoforms 1b and 1c could be involved in this processing with no significant role of NEP.

Iowa Biodiesel and Ethanol Processing Plants, July 1, 2008

Iowa Grain Facilities Map

Where sound position influences sound object representations: a 7-T fMRI study.

Evidence from human and non-human primate studies supports a dual-pathway model of audition, with partially segregated cortical networks for sound recognition and sound localisation, referred to as the What and Where processing streams. In normal subjects, these two networks overlap partially on the supra-temporal plane, suggesting that some early-stage auditory areas are involved in processing of either auditory feature alone or of both. Using high-resolution 7-T fMRI we have investigated the influence of positional information on sound object representations by comparing activation patterns to environmental sounds lateralised to the right or left ear. While unilaterally presented sounds induced bilateral activation, small clusters in specific non-primary auditory areas were significantly more activated by contra-laterally presented stimuli. Comparison of these data with histologically identified non-primary auditory areas suggests that the coding of sound objects within early-stage auditory areas lateral and posterior to primary auditory cortex AI is modulated by the position of the sound, while that within anterior areas is not.

Effects of feed processing on the apparent ileal digestibility of amino acids in pig diets containing wheat bran or wheat middlings

Selostus: Prosessoinnin vaikutus vehnän sivutuotteita sisältävien rehuseosten aminohappojen ohutsuolisulavuuteen sioilla

Multisensory Integration and Perceptual Enhancement

We perceive our environment through multiple sensory channels. Nonetheless, research has traditionally focused on the investigation of sensory processing within single modalities. Thus, investigating how our brain integrates multisensory information is of crucial importance for understanding how organisms cope with a constantly changing and dynamic environment. During my thesis I have investigated how multisensory events impact our perception and brain responses, either when auditory-visual stimuli were presented simultaneously or how multisensory events at one point in time impact later unisensory processing. In "Looming signals reveal synergistic principles of multisensory integration" (Cappe, Thelen et al., 2012) we investigated the neuronal substrates involved in motion detection in depth under multisensory vs. unisensory conditions. We have shown that congruent auditory-visual looming (i.e. approaching) signals are preferentially integrated by the brain. Further, we show that early effects under these conditions are relevant for behavior, effectively speeding up responses to these combined stimulus presentations. In "Electrical neuroimaging of memory discrimination based on single-trial multisensory learning" (Thelen et al., 2012), we investigated the behavioral impact of single encounters with meaningless auditory-visual object parings upon subsequent visual object recognition. In addition to showing that these encounters lead to impaired recognition accuracy upon repeated visual presentations, we have shown that the brain discriminates images as soon as ~100ms post-stimulus onset according to the initial encounter context. In "Single-trial multisensory memories affect later visual and auditory object recognition" (Thelen et al., in review) we have addressed whether auditory object recognition is affected by single-trial multisensory memories, and whether recognition accuracy of sounds was similarly affected by the initial encounter context as visual objects. We found that this is in fact the case. We propose that a common underlying brain network is differentially involved during encoding and retrieval of images and sounds based on our behavioral findings. - Nous percevons l'environnement qui nous entoure à l'aide de plusieurs organes sensoriels. Antérieurement, la recherche sur la perception s'est focalisée sur l'étude des systèmes sensoriels indépendamment les uns des autres. Cependant, l'étude des processus cérébraux qui soutiennent l'intégration de l'information multisensorielle est d'une importance cruciale pour comprendre comment notre cerveau travail en réponse à un monde dynamique en perpétuel changement. Pendant ma thèse, j'ai ainsi étudié comment des événements multisensoriels impactent notre perception immédiate et/ou ultérieure et comment ils sont traités par notre cerveau. Dans l'étude " Looming signals reveal synergistic principles of multisensory integration" (Cappe, Thelen et al., 2012), nous nous sommes intéressés aux processus neuronaux impliqués dans la détection de mouvements à l'aide de l'utilisation de stimuli audio-visuels seuls ou combinés. Nos résultats ont montré que notre cerveau intègre de manière préférentielle des stimuli audio-visuels combinés s'approchant de l'observateur. De plus, nous avons montré que des effets précoces, observés au niveau de la réponse cérébrale, influencent notre comportement, en accélérant la détection de ces stimuli. Dans l'étude "Electrical neuroimaging of memory discrimination based on single-trial multisensory learning" (Thelen et al., 2012), nous nous sommes intéressés à l'impact qu'a la présentation d'un stimulus audio-visuel sur l'exactitude de reconnaissance d'une image. Nous avons étudié comment la présentation d'une combinaison audio-visuelle sans signification, impacte, au niveau comportementale et cérébral, sur la reconnaissance ultérieure de l'image. Les résultats ont montré que l'exactitude de la reconnaissance d'images, présentées dans le passé, avec un son sans signification, est inférieure à celle obtenue dans le cas d'images présentées seules. De plus, notre cerveau différencie ces deux types de stimuli très tôt dans le traitement d'images. Dans l'étude "Single-trial multisensory memories affect later visual and auditory object recognition" (Thelen et al., in review), nous nous sommes posés la question si l'exactitude de ia reconnaissance de sons était affectée de manière semblable par la présentation d'événements multisensoriels passés. Ceci a été vérifié par nos résultats. Nous avons proposé que cette similitude puisse être expliquée par le recrutement différentiel d'un réseau neuronal commun.

Accurate memory for object location by individuals with intellectual disability: Absolute spatial tagging instead of configural processing?

Using head-mounted eye tracker material, we assessed spatial recognition abilities (e.g., reaction to object permutation, removal or replacement with a new object) in participants with intellectual disabilities. The "Intellectual Disabilities (ID)" group (n=40) obtained a score totalling a 93.7% success rate, whereas the "Normal Control" group (n=40) scored 55.6% and took longer to fix their attention on the displaced object. The participants with an intellectual disability thus had a more accurate perception of spatial changes than controls. Interestingly, the ID participants were more reactive to object displacement than to removal of the object. In the specific test of novelty detection, however, the scores were similar, the two groups approaching 100% detection. Analysis of the strategies expressed by the ID group revealed that they engaged in more systematic object checking and were more sensitive than the control group to changes in the structure of the environment. Indeed, during the familiarisation phase, the "ID" group explored the collection of objects more slowly, and fixed their gaze for a longer time upon a significantly lower number of fixation points during visual sweeping.

Spatio-temporal Brain Dynamics Mediating Post-error Behavioral Adjustments.

Optimal behavior relies on flexible adaptation to environmental requirements, notably based on the detection of errors. The impact of error detection on subsequent behavior typically manifests as a slowing down of RTs following errors. Precisely how errors impact the processing of subsequent stimuli and in turn shape behavior remains unresolved. To address these questions, we used an auditory spatial go/no-go task where continual feedback informed participants of whether they were too slow. We contrasted auditory-evoked potentials to left-lateralized go and right no-go stimuli as a function of performance on the preceding go stimuli, generating a 2 × 2 design with "preceding performance" (fast hit [FH], slow hit [SH]) and stimulus type (go, no-go) as within-subject factors. SH trials yielded SH trials on the following trials more often than did FHs, supporting our assumption that SHs engaged effects similar to errors. Electrophysiologically, auditory-evoked potentials modulated topographically as a function of preceding performance 80-110 msec poststimulus onset and then as a function of stimulus type at 110-140 msec, indicative of changes in the underlying brain networks. Source estimations revealed a stronger activity of prefrontal regions to stimuli after successful than error trials, followed by a stronger response of parietal areas to the no-go than go stimuli. We interpret these results in terms of a shift from a fast automatic to a slow controlled form of inhibitory control induced by the detection of errors, manifesting during low-level integration of task-relevant features of subsequent stimuli, which in turn influences response speed.

Involvement of Dab1 in APP processing and [beta]-amyloid deposition in sporadic Creutzfeldt-Jakob patients.

Alzheimer"s disease and prion pathologies (e.g., Creutzfeldt-Jakob disease) display profound neural lesions associated with aberrant protein processing and extracellular amyloid deposits. For APP processing, emerging data suggest that the adaptor protein Dab1 plays a relevant role in regulating its intracellular trafficking and secretase-mediated proteolysis. Although some data have been presented, a putative relationship between human prion diseases and Dab1/APP interactions is lacking. Therefore, we have studied the putative relation between Dab1, APP processing and Aβ deposition, targets in sCJD cases. Our biochemical results categorized two groups of sCJD cases, which also correlated with PrPsc types 1 and 2 respectively. One group, with PrPsc type 1 showed increased Dab1 phosphorylation, and lower βCTF production with an absence of Aβ deposition. The second sCJD group, which carried PrPsc type 2, showed lower levels of Dab1 phosphorylation and βCTF production, similar to control cases. Relevant Aβ deposition in the second sCJD group was measured. Thus, a direct correlation between Dab1 phosphorylation, Aβ deposition and PrPsc type in human sCJD is presented for the first time.

One minute of grief: Emotional processing in short-term dynamic psychotherapy for adjustment disorder.

OBJECTIVE: Depth of emotional processing has shown to be related to outcome across approaches to psychotherapy. Moreover, a specific emotional sequence has been postulated and tested in several studies on experiential psychotherapy (Pascual-Leone & Greenberg, 2007). This process-outcome study aims at reproducing the sequential model of emotional processing in psychodynamic psychotherapy for adjustment disorder and linking these variables with ultimate therapeutic outcome. METHOD: In this study, 32 patients underwent short-term dynamic psychotherapy. On the basis of reliable clinical change statistics, a subgroup (n = 16) presented with good outcome and another subgroup (n = 16) had a poor outcome in the end of treatment. The strongest alliance session of each case was rated using the observer-rated system Classification of Affective Meaning States. Reliability coefficients for the measure were excellent (κ = .82). RESULTS: Using 1 min as the fine-grained unit of analysis, results showed that the experience of fundamentally adaptive grief was more common in the in-session process of patients with good outcome, compared with those with poor outcomes (χ2 = 6.56, p = .01, d = 1.23). This variable alone predicted 19% of the change in depressive symptoms as measured by the Beck Depression Inventory at the end of treatment. Moreover, sequences of the original model were supported and related to outcome. CONCLUSIONS: These results are discussed within the framework of the sequential model of emotional processing and its possible relevance for psychodynamic psychotherapy. (PsycINFO Database Record (c) 2015 APA, all rights reserved).