43 research outputs found

    The face-specific N170 component is modulated by emotional facial expression

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    BACKGROUND: According to the traditional two-stage model of face processing, the face-specific N170 event-related potential (ERP) is linked to structural encoding of face stimuli, whereas later ERP components are thought to reflect processing of facial affect. This view has recently been challenged by reports of N170 modulations by emotional facial expression. This study examines the time-course and topography of the influence of emotional expression on the N170 response to faces. METHODS: Dense-array ERPs were recorded in response to a set (n = 16) of fear and neutral faces. Stimuli were normalized on dimensions of shape, size and luminance contrast distribution. To minimize task effects related to facial or emotional processing, facial stimuli were irrelevant to a primary task of learning associative pairings between a subsequently presented visual character and a spoken word. RESULTS: N170 to faces showed a strong modulation by emotional facial expression. A split half analysis demonstrates that this effect was significant both early and late in the experiment and was therefore not associated with only the initial exposures of these stimuli, demonstrating a form of robustness against habituation. The effect of emotional modulation of the N170 to faces did not show significant interaction with the gender of the face stimulus, or hemisphere of recording sites. Subtracting the fear versus neutral topography provided a topography that itself was highly similar to the face N170. CONCLUSION: The face N170 response can be influenced by emotional expressions contained within facial stimuli. The topography of this effect is consistent with the notion that fear stimuli exaggerates the N170 response itself. This finding stands in contrast to previous models suggesting that N170 processes linked to structural analysis of faces precede analysis of emotional expression, and instead may reflect early top-down modulation from neural systems involved in rapid emotional processing

    fMR-adaptation indicates selectivity to audiovisual content congruency in distributed clusters in human superior temporal cortex

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    <p>Abstract</p> <p>Background</p> <p>Efficient multisensory integration is of vital importance for adequate interaction with the environment. In addition to basic binding cues like temporal and spatial coherence, meaningful multisensory information is also bound together by content-based associations. Many functional Magnetic Resonance Imaging (fMRI) studies propose the (posterior) superior temporal cortex (STC) as the key structure for integrating meaningful multisensory information. However, a still unanswered question is how superior temporal cortex encodes content-based associations, especially in light of inconsistent results from studies comparing brain activation to semantically matching (congruent) versus nonmatching (incongruent) multisensory inputs. Here, we used fMR-adaptation (fMR-A) in order to circumvent potential problems with standard fMRI approaches, including spatial averaging and amplitude saturation confounds. We presented repetitions of audiovisual stimuli (letter-speech sound pairs) and manipulated the associative relation between the auditory and visual inputs (congruent/incongruent pairs). We predicted that if multisensory neuronal populations exist in STC and encode audiovisual content relatedness, adaptation should be affected by the manipulated audiovisual relation.</p> <p>Results</p> <p>The results revealed an occipital-temporal network that adapted independently of the audiovisual relation. Interestingly, several smaller clusters distributed over superior temporal cortex within that network, adapted stronger to congruent than to incongruent audiovisual repetitions, indicating sensitivity to content congruency.</p> <p>Conclusions</p> <p>These results suggest that the revealed clusters contain multisensory neuronal populations that encode content relatedness by selectively responding to congruent audiovisual inputs, since unisensory neuronal populations are assumed to be insensitive to the audiovisual relation. These findings extend our previously revealed mechanism for the integration of letters and speech sounds and demonstrate that fMR-A is sensitive to multisensory congruency effects that may not be revealed in BOLD amplitude per se.</p

    The Genetic Landscape and Epidemiology of Phenylketonuria

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    Phenylketonuria (PKU), caused by variants in the phenylalanine hydroxylase (PAH) gene, is the most common autosomal-recessive Mendelian phenotype of amino acid metabolism. We estimated that globally 0.45 million individuals have PKU, with global prevalence 1:23,930 live births (range 1:4,500 [Italy]–1:125,000 [Japan]). Comparing genotypes and metabolic phenotypes from 16,092 affected subjects revealed differences in disease severity in 51 countries from 17 world regions, with the global phenotype distribution of 62% classic PKU, 22% mild PKU, and 16% mild hyperphenylalaninemia. A gradient in genotype and phenotype distribution exists across Europe, from classic PKU in the east to mild PKU in the southwest and mild hyperphenylalaninemia in the south. The c.1241A>G (p.Tyr414Cys)-associated genotype can be traced from Northern to Western Europe, from Sweden via Norway, to Denmark, to the Netherlands. The frequency of classic PKU increases from Europe (56%) via Middle East (71%) to Australia (80%). Of 758 PAH variants, c.1222C>T (p.Arg408Trp) (22.2%), c.1066−11G>A (IVS10−11G>A) (6.4%), and c.782G>A (p.Arg261Gln) (5.5%) were most common and responsible for two prevalent genotypes: p.[Arg408Trp];[Arg408Trp] (11.4%) and c.[1066−11G>A];[1066−11G>A] (2.6%). Most genotypes (73%) were compound heterozygous, 27% were homozygous, and 55% of 3,659 different genotypes occurred in only a single individual. PAH variants were scored using an allelic phenotype value and correlated with pre-treatment blood phenylalanine concentrations (n = 6,115) and tetrahydrobiopterin loading test results (n = 4,381), enabling prediction of both a genotype-based phenotype (88%) and tetrahydrobiopterin responsiveness (83%). This study shows that large genotype databases enable accurate phenotype prediction, allowing appropriate targeting of therapies to optimize clinical outcome.Fil: Hillert, Alicia. No especifĂ­ca;Fil: Anikster, Yair. No especifĂ­ca;Fil: Belanger Quintana, Amaya. No especifĂ­ca;Fil: Burlina, Alberto. No especifĂ­ca;Fil: Burton, Barbara K.. No especifĂ­ca;Fil: Carducci, Carla. No especifĂ­ca;Fil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Centro de Investigaciones EndocrinolĂłgicas "Dr. CĂ©sar Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones EndocrinolĂłgicas "Dr. CĂ©sar Bergada". FundaciĂłn de EndocrinologĂ­a Infantil. Centro de Investigaciones EndocrinolĂłgicas "Dr. CĂ©sar Bergada"; ArgentinaFil: Christodoulou, John. No especifĂ­ca;Fil: Dordevic, Maja. No especifĂ­ca;Fil: Desviat, Lourdes R.. No especifĂ­ca;Fil: Eliyahu, Aviva. No especifĂ­ca;Fil: Evers, Roeland A.F.. No especifĂ­ca;Fil: Fajkusova, Lena. No especifĂ­ca;Fil: Feillet, Francois. No especifĂ­ca;Fil: Bonfim Freitas, Pedro E.. No especifĂ­ca;Fil: Gizewska, MarĂ­a. No especifĂ­ca;Fil: Gundorova, Polina. No especifĂ­ca;Fil: Karall, Daniela. No especifĂ­ca;Fil: Kneller, Katya. No especifĂ­ca;Fil: Kutsev, Sergey I.. No especifĂ­ca;Fil: Leuzzi, Vincenzo. No especifĂ­ca;Fil: Levy, Harvey L.. No especifĂ­ca;Fil: Lichter Koneck, Uta. No especifĂ­ca;Fil: Muntau, Ania C.. No especifĂ­ca;Fil: Namour, Fares. No especifĂ­ca;Fil: Oltarzewsk, Mariusz. No especifĂ­ca;Fil: Paras, Andrea. No especifĂ­ca;Fil: Perez, BelĂ©n. No especifĂ­ca;Fil: Polak, Emil. No especifĂ­ca;Fil: Polyakov, Alexander V.. No especifĂ­ca;Fil: Porta, Francesco. No especifĂ­ca;Fil: Rohrbach, Marianne. No especifĂ­ca;Fil: Scholl BĂŒrgi, Sabine. No especifĂ­ca;Fil: SpĂ©cola, Norma. No especifĂ­ca;Fil: Stojiljkovic, Maja. No especifĂ­ca;Fil: Shen, Nan. No especifĂ­ca;Fil: Santana da Silva, Luiz C.. No especifĂ­ca;Fil: Skouma, Anastasia. No especifĂ­ca;Fil: van Spronsen, Francjan. No especifĂ­ca;Fil: Stoppioni, Vera. No especifĂ­ca;Fil: Thöny, Beat. No especifĂ­ca;Fil: Trefz, Friedrich K.. No especifĂ­ca;Fil: Vockley, Jerry. No especifĂ­ca;Fil: Yu, Youngguo. No especifĂ­ca;Fil: Zschocke, Johannes. No especifĂ­ca;Fil: Hoffmann, Georg F.. No especifĂ­ca;Fil: Garbade, Sven F.. No especifĂ­ca;Fil: Blau, Nenad. No especifĂ­ca

    The Genetic Landscape and Epidemiology of Phenylketonuria

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    Phenylketonuria (PKU), caused by variants in the phenylalanine hydroxylase (PAH) gene, is the most common autosomal-recessive Mendelian phenotype of amino acid metabolism. We estimated that globally 0.45 million individuals have PKU, with global prevalence 1:23,930 live births (range 1:4,500 [Italy]-1:125,000 [Japan]). Comparing genotypes and metabolic phenotypes from 16,092 affected subjects revealed differences in disease severity in 51 countries from 17 world regions, with the global phenotype distribution of 62% classic PKU, 22% mild PKU, and 16% mild hyperphenylalaninemia. A gradient in genotype and phenotype distribution exists across Europe, from classic PKU in the east to mild PKU in the southwest and mild hyperphenylalaninemia in the south. The c.1241A gt G (p.Tyr414Cys)-associated genotype can be traced from Northern to Western Europe, from Sweden via Norway, to Denmark, to the Netherlands. The frequency of classic PKU increases from Europe (56%) via Middle East (71%) to Australia (80%). Of 758 PAH variants, c.1222C gt T (p.Arg408Trp) (22.2%), c.1066-11G gt A (IVS10-11G gt A) (6.4%), and c.782G gt A (p.Arg261Gln) (5.5%) were most common and responsible for two prevalent genotypes: p.[Arg408Trp];[Arg408Trp] (11.4%) and c.[1066-11G gt A];[1066-11G gt A] (2.6%). Most genotypes (73%) were compound heterozygous, 27% were homozygous, and 55% of 3,659 different genotypes occurred in only a single individual. PAH variants were scored using an allelic phenotype value and correlated with pre-treatment blood phenylalanine concentrations (n = 6,115) and tetrahydrobiopterin loading test results (n = 4,381), enabling prediction of both a genotype-based phenotype (88%) and tetrahydrobiopterin responsiveness (83%). This study shows that large genotype databases enable accurate phenotype prediction, allowing appropriate targeting of therapies to optimize clinical outcome

    Deviant processing of letters and speech sounds as proximate cause of reading failure: a functional magnetic resonance imaging study of dyslexic children

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    Learning to associate auditory information of speech sounds with visual information of letters is a first and critical step for becoming a skilled reader in alphabetic languages. Nevertheless, it remains largely unknown which brain areas subserve the learning and automation of such associations. Here, we employ functional magnetic resonance imaging to study letter-speech sound integration in children with and without developmental dyslexia. The results demonstrate that dyslexic children show reduced neural integration of letters and speech sounds in the planum temporale/Heschl sulcus and the superior temporal sulcus. While cortical responses to speech sounds in fluent readers were modulated by letter-speech sound congruency with strong suppression effects for incongruent letters, no such modulation was observed in the dyslexic readers. Whole-brain analyses of unisensory visual and auditory group differences additionally revealed reduced unisensory responses to letters in the fusiform gyrus in dyslexic children, as well as reduced activity for processing speech sounds in the anterior superior temporal gyrus, planum temporale/Heschl sulcus and superior temporal sulcus. Importantly, the neural integration of letters and speech sounds in the planum temporale/Heschl sulcus and the neural response to letters in the fusiform gyrus explained almost 40% of the variance in individual reading performance. These findings indicate that an interrelated network of visual, auditory and heteromodal brain areas contributes to the skilled use of letter-speech sound associations necessary for learning to read. By extending similar findings in adults, the data furthermore argue against the notion that reduced neural integration of letters and speech sounds in dyslexia reflect the consequence of a lifetime of reading struggle. Instead, they support the view that letter-speech sound integration is an emergent property of learning to read that develops inadequately in dyslexic readers, presumably as a result of a deviant interactive specialization of neural systems for processing auditory and visual linguistic inputs

    Development of visual expertise for reading: rapid emergence of visual familiarity for an artificial script

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    Adults produce left-lateralized N170 responses to visual words relative to control stimuli, even within tasks that do not require active reading. This specialization begins in preschoolers as a right-lateralized N170 effect. We investigated whether this developmental shift reflects an early learning phenomenon, such as attaining visual familiarity with a script, by training adults in an artificial script and measuring N170 responses before and afterward. Training enhanced the N170 response, especially over the right hemisphere. This suggests N170 sensitivity to visual familiarity with a script emerges before reading becomes sufficiently automatic to drive left-lateralized effects in a shallow encoding task

    The phosphorylated pathway of serine biosynthesis links plant growth with nitrogen metabolism

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    Because it is the precursor for various essential cellular components, the amino acid serine is indispensable for every living organism. In plants, serine is synthesized by two major pathways: photorespiration and the phosphorylated pathway of serine biosynthesis (PPSB). However, the importance of these pathways in providing serine for plant development is not fully understood. In this study, we examine the relative contributions of photorespiration and PPSB to providing serine for growth and metabolism in the C3 model plant Arabidopsis thaliana. Our analyses of cell proliferation and elongation reveal that PPSB-derived serine is indispensable for plant growth and its loss cannot be compensated by photorespiratory serine biosynthesis. Using isotope labeling, we show that PPSB-deficiency impairs the synthesis of proteins and purine nucleotides in plants. Furthermore, deficiency in PPSB-mediated serine biosynthesis leads to a strong accumulation of metabolites related to nitrogen metabolism. This result corroborates N-15-isotope labeling in which we observed an increased enrichment in labeled amino acids in PPSB-deficient plants. Expression studies indicate that elevated ammonium uptake and higher glutamine synthetase/glutamine oxoglutarate aminotransferase (GS/GOGAT) activity causes this phenotype. Metabolic analyses further show that elevated nitrogen assimilation and reduced amino acid turnover into proteins and nucleotides are the most likely driving forces for changes in respiratory metabolism and amino acid catabolism in PPSB-deficient plants. Accordingly, we conclude that even though photorespiration generates high amounts of serine in plants, PPSB-derived serine is more important for plant growth and its deficiency triggers the induction of nitrogen assimilation, most likely as an amino acid starvation response
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