Publications

Abstract

Cerebellar ataxias are progressive neurodegenerative disorders characterized by atrophy of the cerebellum leading to motor dysfunction, balance problems, and limb and gait ataxia. These include among others, the dominantly inherited spinocerebellar ataxias, recessive cerebellar ataxias such as Friedreich's ataxia, and X-linked cerebellar ataxias. Since all cerebellar ataxias display considerable overlap in their disease phenotypes, common pathological pathways must underlie the selective cerebellar neurodegeneration. Therefore, it is important to identify the molecular mechanisms and routes to neurodegeneration that cause cerebellar ataxia. In this review, we discuss the use of functional genomic approaches including whole-exome sequencing, genome-wide gene expression profiling, miRNA profiling, epigenetic profiling, and genetic modifier screens to reveal the underlying pathogenesis of various cerebellar ataxias. These approaches have resulted in the identification of many disease genes, modifier genes, and biomarkers correlating with specific stages of the disease. This article is part of a Special Issue entitled: From Genome to Function.

Abstract

The effect of literacy on phonological processing has been described in terms of a virus that “infects all speech processing” (Frith, 1998). Empirical data has established that literacy leads to changes to the way in which phonological information is processed. Harm & Seidenberg (1999) demonstrated that a connectionist network trained to map between English orthographic and phonological representations display’s more componential phonological processing than a network trained only to stably represent the phonological forms of words. Within this study we use a similar model yet manipulate the transparency of orthographic-to-phonological mappings. We observe that networks trained on a transparent orthography are better at restoring phonetic features and phonemes. However, networks trained on non-transparent orthographies are more likely to restore corrupted phonological segments with legal, coarser linguistic units (e.g. onset, coda). Our study therefore provides an explicit description of how differences in orthographic transparency can lead to varying strains and symptoms of the ‘literacy virus’.

Abstract

When processing language, the cognitive system has access to information from a range of modalities (e.g. auditory, visual) to support language processing. Language mediated visual attention studies have shown sensitivity of the listener to phonological, visual, and semantic similarity when processing a word. In a computational model of language mediated visual attention, that models spoken word processing as the parallel integration of information from phonological, semantic and visual processing streams, we simulate such effects of competition within modalities. Our simulations raised untested predictions about stronger and earlier effects of visual and semantic similarity compared to phonological similarity around the rhyme of the word. Two visual world studies confirmed these predictions. The model and behavioral studies suggest that, during spoken word comprehension, multimodal information can be recruited rapidly to constrain lexical selection to the extent that phonological rhyme information may exert little influence on this process.

Abstract

Multimodal integration is a central characteristic of human cognition. However our understanding of the interaction between modalities and its influence on behaviour is still in its infancy. This paper examines the value of the Hub & Spoke framework (Plaut, 2002; Rogers et al., 2004; Dilkina et al., 2008; 2010) as a tool for exploring multimodal interaction in cognition. We present a Hub and Spoke model of language–vision information interaction and report the model’s ability to replicate a range of phonological, visual and semantic similarity word-level effects reported in the Visual World Paradigm (Cooper, 1974; Tanenhaus et al, 1995). The model provides an explicit connection between the percepts of language and the distribution of eye gaze and demonstrates the scope of the Hub-and-Spoke architectural framework by modelling new aspects of multimodal cognition.

Abstract

Learning to read and write requires an individual to connect additional orthographic representations to pre-existing mappings between phonological and semantic representations of words. Past empirical results suggest that the process of learning to read and write (at least in alphabetic languages) elicits changes in the language processing system, by either increasing the cognitive efficiency of mapping between representations associated with a word, or by changing the granularity of phonological processing of spoken language, or through a combination of both. Behavioural effects of literacy have typically been assessed in offline explicit tasks that have addressed only phonological processing. However, a recent eye tracking study compared high and low literate participants on effects of phonology and semantics in processing measured implicitly using eye movements. High literates’ eye movements were more affected by phonological overlap in online speech than low literates, with only subtle differences observed in semantics. We determined whether these effects were due to cognitive efficiency and/or granularity of speech processing in a multimodal model of speech processing – the amodal shared resource model (ASR, Smith, Monaghan, & Huettig, 2013). We found that cognitive efficiency in the model had only a marginal effect on semantic processing and did not affect performance for phonological processing, whereas fine-grained versus coarse-grained phonological representations in the model simulated the high/low literacy effects on phonological processing, suggesting that literacy has a focused effect in changing the grain-size of phonological mappings.

Abstract

Blindsight refers to the observation of residual visual abilities in the hemianopic field of patients without a functional V1. Given the within- and between-subject variability in the preserved abilities and the phenomenal experience of blindsight patients, the fine-grained description of the phenomenon is still debated. Here we tested a patient with established “perceptual” and “attentional” blindsight (c.f. Danckert and Rossetti, 2005). Using a pointing paradigm patient MS, who suffers from a complete left homonymous hemianopia, showed clear above chance manual localisation of ‘unseen’ targets. In addition, target presentations in his blind field led MS, on occasion, to spontaneous responses towards his sighted field. Structural and functional magnetic resonance imaging was conducted to evaluate the magnitude of V1 damage. Results revealed the presence of a calcarine sulcus in both hemispheres, yet his right V1 is reduced, structurally disconnected and shows no fMRI response to visual stimuli. Thus, visual stimulation of his blind field can lead to “action blindsight” and spontaneous antipointing, in absence of a functional right V1. With respect to the antipointing, we suggest that MS may have registered the stimulation and subsequently presumes it must have been in his intact half field.

Abstract

Previous research [9] suggests that Dutch learners of (British) English are not able to express sarcasm prosodically in their L2. The present study investigates whether explicit training on the prosodic markers of sarcasm in English can improve learners’ realisation of sarcasm. Sarcastic speech was elicited in short simulated telephone conversations between Dutch advanced learners of English and a native British English-speaking ‘friend’ in two sessions, fourteen days apart. Between the two sessions, participants were trained by means of (1) a presentation, (2) directed independent practice, and (3) evaluation of participants’ production and individual feedback in small groups. L1 British English-speaking raters subsequently evaluated the degree of sarcastic sounding in the participants’ responses on a five-point scale. It was found that significantly higher sarcasm ratings were given to L2 learners’ production obtained after the training than that obtained before the training; explicit training on prosody has a positive effect on learners’ production of sarcasm.

Abstract

POU3F3, also referred to as Brain-1, is a well-known transcription factor involved in the development of the central nervous system, but it has not previously been associated with a neurodevelopmental disorder. Here, we report the identification of 19 individuals with heterozygous POU3F3 disruptions, most of which are de novo variants. All individuals had developmental delays and/or intellectual disability and impairments in speech and language skills. Thirteen individuals had characteristic low-set, prominent, and/or cupped ears. Brain abnormalities were observed in seven of eleven MRI reports. POU3F3 is an intronless gene, insensitive to nonsense-mediated decay, and 13 individuals carried protein-truncating variants. All truncating variants that we tested in cellular models led to aberrant subcellular localization of the encoded protein. Luciferase assays demonstrated negative effects of these alleles on transcriptional activation of a reporter with a FOXP2-derived binding motif. In addition to the loss-of-function variants, five individuals had missense variants that clustered at specific positions within the functional domains, and one small in-frame deletion was identified. Two missense variants showed reduced transactivation capacity in our assays, whereas one variant displayed gain-of-function effects, suggesting a distinct pathophysiological mechanism. In bioluminescence resonance energy transfer (BRET) interaction assays, all the truncated POU3F3 versions that we tested had significantly impaired dimerization capacities, whereas all missense variants showed unaffected dimerization with wild-type POU3F3. Taken together, our identification and functional cell-based analyses of pathogenic variants in POU3F3, coupled with a clinical characterization, implicate disruptions of this gene in a characteristic neurodevelopmental disorder.

Abstract

The anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC) are involved in conflict detection and
conflict resolution, respectively. Here, we investigate how lifelong bilingualism induces neuroplasticity to these structures by
employing a novel analysis of behavioural performance. We correlated grey matter volume (GMV) in seniors reported by
Abutalebi et al. (2015) with behavioral Flanker task performance fitted using the diffusion model (Ratcliff, 1978). As
predicted, we observed significant correlations between GMV in the DLPFC and Flanker performance. However, for
monolinguals the non-decision time parameter was significantly correlated with GMV in the left DLPFC, whereas for
bilinguals the correlation was significant in the right DLPFC. We also found a significant correlation between age and GMV
in left DLPFC and the non-decision time parameter for the conflict effect for monolinguals only.
We submit that this is due to cumulative demands on cognitive control over a lifetime of bilingual language processing

Abstract

In language comprehension, a variety of contextual cues act in unison to render upcoming words more or less predictable. As a sentence unfolds, we use prior context (sentential constraints) to predict what the next words might be. Additionally, in a conversation, we can predict upcoming sounds through observing the mouth movements of a speaker (visual constraints). In electrophysiological studies, effects of visual constraints have typically been observed early in language processing, while effects of sentential constraints have typically been observed later. We hypothesized that the visual and the sentential constraints might feed into the same predictive process such that effects of sentential constraints might also be detectable early in language processing through modulations of the early effects of visual salience. We presented participants with audiovisual speech while recording their brain activity with magnetoencephalography. Participants saw videos of a person saying sentences where the last word was either sententially constrained or not, and began with a salient or non-salient mouth movement. We found that sentential constraints indeed exerted an early (N1) influence on language processing. Sentential modulations of the N1 visual predictability effect were visible in brain areas associated with semantic processing, and were differently expressed in the two hemispheres. In the left hemisphere, visual and sentential constraints jointly suppressed the auditory evoked field, while the right hemisphere was sensitive to visual constraints only in the absence of strong sentential constraints. These results suggest that sentential and visual constraints can jointly influence even very early stages of audiovisual speech comprehension.

Abstract

Humans have a strong proclivity for structuring and patterning stimuli: Whether in space or time, we tend to mentally order stimuli in our environment and organize them into units with specific types of relationships. A crucial prerequisite for such organization is the cognitive ability to discern and process regularities among multiple stimuli. To investigate the evolutionary roots of this cognitive capacity, we tested chimpanzees—which, along with bonobos, are our closest living relatives—for simple, variable distance dependency processing in visual patterns. We trained chimpanzees to identify pairs of shapes either linked by an arbitrary learned association (arbitrary associative dependency) or a shared feature (same shape, feature-based dependency), and to recognize strings where items related to either of these ways occupied the first (leftmost) and the last (rightmost) item of the stimulus. We then probed the degree to which subjects generalized this pattern to new colors, shapes, and numbers of interspersed items. We found that chimpanzees can learn and generalize both types of dependency rules, indicating that the ability to encode both feature-based and arbitrary associative regularities over variable distances in the visual domain is not a human prerogative. Our results strongly suggest that these core components of human structural processing were already present in our last common ancestor with chimpanzees.

Abstract

Flexibly adapting social behavior to social and environmental challenges helps to alleviate glucocorticoid (GC) levels, which may have positive fitness implications for an individual. For primates, the predominant social behavior is grooming. Giving grooming to others is particularly efficient in terms of GC mitigation. However, grooming is confined by certain limitations such as time constraints or restricted access to other group members. For instance, dominance hierarchies may impact grooming partner availability in primate societies. Consequently specific grooming patterns emerge. In despotic species focusing grooming activity on preferred social partners significantly ameliorates GC levels in females of all ranks. In this study we investigated grooming patterns and GC management in Barbary macaques, a comparably relaxed species. We monitored changes in grooming behavior and cortisol (C) for females of different ranks. Our results show that the C‐amelioration associated with different grooming patterns had a gradual connection with dominance hierarchy: while higher‐ranking individuals showed lowest urinary C measures when they focused their grooming on selected partners within their social network, lower‐ranking individuals expressed lowest C levels when dispersing their grooming activity evenly across their social partners. We argue that the relatively relaxed social style of Barbary macaque societies allows individuals to flexibly adapt grooming patterns, which is associated with rank‐specific GC management. Am. J. Primatol. 77:688–700, 2015

Abstract

The auditory scene is a mental representation of individual sounds extracted from the summed sound waveform reaching the ears of the listeners. Musical contexts represent particularly complex cases of auditory scenes. In such a scenario, melody may be seen as the main object moving on a background represented by the accompaniment. Both melody and accompaniment vary in time according to harmonic rules, forming a typical texture with melody in the most prominent, salient voice. In the present sparse acquisition functional magnetic resonance imaging study, we investigated the interplay between melody and accompaniment in trained pianists, by observing the activation responses elicited by processing: (1) melody placed in the upper and lower texture voices, leading to, respectively, a higher and lower auditory salience; (2) harmonic violations occurring in either the melody, the accompaniment, or both. The results indicated that the neural activation elicited by the processing of polyphonic compositions in expert musicians depends upon the upper versus lower position of the melodic line in the texture, and showed an overall greater activation for the harmonic processing of melody over accompaniment. Both these two predominant effects were characterized by the involvement of the posterior cingulate cortex and precuneus, among other associative brain regions. We discuss the prominent role of the posterior medial cortex in the processing of melodic and harmonic information in the auditory stream, and propose to frame this processing in relation to the cognitive construction of complex multimodal sensory imagery scenes.

Abstract

Aims/hypothesis Several forkhead box (FOX) transcription factor family members have important roles in controlling pancreatic cell fates and maintaining beta cell mass and function, including FOXA1, FOXA2 and FOXM1. In this study we have examined the importance of FOXP1, FOXP2 and FOXP4 of the FOXP subfamily in islet cell development and function. Methods Mice harbouring floxed alleles for Foxp1, Foxp2 and Foxp4 were crossed with pan-endocrine Pax6-Cre transgenic mice to generate single and compound Foxp mutant mice. Mice were monitored for changes in glucose tolerance by IPGTT, serum insulin and glucagon levels by radioimmunoassay, and endocrine cell development and proliferation by immunohistochemistry. Gene expression and glucose-stimulated hormone secretion experiments were performed with isolated islets. Results Only the triple-compound Foxp1/2/4 conditional knockout (cKO) mutant had an overt islet phenotype, manifested physiologically by hypoglycaemia and hypoglucagonaemia. This resulted from the reduction in glucagon-secreting alpha cell mass and function. The proliferation of alpha cells was profoundly reduced in Foxp1/2/4 cKO islets through the effects on mediators of replication (i.e. decreased Ccna2, Ccnb1 and Ccnd2 activators, and increased Cdkn1a inhibitor). Adult islet Foxp1/2/4 cKO beta cells secrete insulin normally while the remaining alpha cells have impaired glucagon secretion. Conclusions/interpretation Collectively, these findings reveal an important role for the FOXP1, 2, and 4 proteins in governing postnatal alpha cell expansion and function.

Abstract

E-Prime® is the leading software suite by Psychology Software Tools for designing and running Psychology lab experiments. The E-Primer is the perfect accompanying guide: It provides all the necessary knowledge to make E-Prime accessible to everyone. You can learn the tools of Psychological science by following the E-Primer through a series of entertaining, step-by-step recipes that recreate classic experiments. The updated E-Primer expands its proven combination of simple explanations, interesting tutorials and fun exercises, and makes even the novice student quickly confident to create their dream experiment.

Abstract

E-Prime, the software suite by Psychology Software Tools, is used for designing, developing and running custom psychological experiments. Aimed at students and researchers alike, this book provides a much needed, down-to-earth introduction into a wide range of experiments that can be set up using E-Prime. Many tutorials are provided to teach the reader how to develop experiments typical for the broad fields of psychological and cognitive science. Apart from explaining the basic structure of E-Prime and describing how it fits into daily scientific practice, this book also offers an introduction into programming using E-Prime’s own E-Basic language. The authors guide the readers step-by-step through the software, from an elementary to an advanced level, enabling them to benefit from the enormous possibilities for experimental design offered by E-Prime.

Abstract

Odors are often difficult to identify and name, which leaves them vulnerable to the influence of language. The present study tests the boundaries of the effect of language on odor cognition by examining the effect of grammatical gender. We presented participants with male and female fragrances paired with descriptions of masculine or feminine grammatical gender. In Experiment 1 we found that memory for fragrances was enhanced when the grammatical gender of a fragrance description matched the gender of the fragrance. In Experiment 2 we found memory for fragrances was affected by both grammatical gender and gender associations in fragrance descriptions – recognition memory for odors was higher when the gender was incongruent. In sum, we demonstrated that even subtle aspects of language can affect odor cognition.

Abstract

Metaphor allows us to think and talk about one thing in terms of another, ratcheting up our cognitive and expressive capacity. It gives us concrete terms for abstract phenomena, for example, ideas become things we can grasp or let go of. Perceptual experience—characterised as physical and relatively concrete—should be an ideal source domain in metaphor, and a less likely target. But is this the case across diverse languages? And are some sensory modalities perhaps more concrete than others? This volume presents critical new data on perception metaphors from over 40 languages, including many which are under-studied. Aside from the wealth of data from diverse languages—modern and historical; spoken and signed—a variety of methods (e.g., natural language corpora, experimental) and theoretical approaches are brought together. This collection highlights how perception metaphor can offer both a bedrock of common experience and a source of continuing innovation in human communication

Abstract

OBJECTIVE: Genome-wide association studies (GWAS) of BMI are mostly undertaken under the assumption that "kg/m(2) " is an index of weight fully adjusted for height, but in general this is not true. The aim here was to assess the contribution of common genetic variation to a adjusted version of that phenotype which appropriately accounts for covariation in height in children. METHODS: A GWAS of height-adjusted BMI (BMI[x] = weight/height(x) ), calculated to be uncorrelated with height, in 5809 participants (mean age 9.9 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC) was performed. RESULTS: GWAS based on BMI[x] yielded marked differences in genomewide results profile. SNPs in ADCY3 (adenylate cyclase 3) were associated at genome-wide significance level (rs11676272 (0.28 kg/m(3.1) change per allele G (0.19, 0.38), P = 6 × 10(-9) ). In contrast, they showed marginal evidence of association with conventional BMI [rs11676272 (0.25 kg/m(2) (0.15, 0.35), P = 6 × 10(-7) )]. Results were replicated in an independent sample, the Generation R study. CONCLUSIONS: Analysis of BMI[x] showed differences to that of conventional BMI. The association signal at ADCY3 appeared to be driven by a missense variant and it was strongly correlated with expression of this gene. Our work highlights the importance of well understood phenotype use (and the danger of convention) in characterising genetic contributions to complex traits.

Abstract

While a training model of cognitive intervention targets the improvement of particular skills through instruction and practice, an engagement model is based on the idea that being embedded in an intellectually and socially complex environment can impact cognition, perhaps even broadly, without explicit instruction. We contrasted these 2 models of cognitive enrichment by randomly assigning healthy older adults to a home-based inductive reasoning training program, a team-based competitive program in creative problem solving, or a wait-list control. As predicted, those in the training condition showed selective improvement in inductive reasoning. Those in the engagement condition, on the other hand, showed selective improvement in divergent thinking, a key ability exercised in creative problem solving. On average, then, both groups appeared to show ability-specific effects. However, moderators of change differed somewhat for those in the engagement and training interventions. Generally, those who started either intervention with a more positive cognitive profile showed more cognitive growth, suggesting that cognitive resources enabled individuals to take advantage of environmental enrichment. Only in the engagement condition did initial levels of openness and social network size moderate intervention effects on cognition, suggesting that comfort with novelty and an ability to manage social resources may be additional factors contributing to the capacity to take advantage of the environmental complexity associated with engagement. Collectively, these findings suggest that training and engagement models may offer alternative routes to cognitive resilience in late life

Abstract

Bilingual children are often exposed to non-native speech through their parents. Yet, little is known about the relation between bilingual preschoolers’ speech production and their speech input. The present study investigated the production of voice onset time (VOT) by Dutch-German bilingual preschoolers and their sequential bilingual mothers. The findings reveal an association between maternal VOT and bilingual children’s VOT in the heritage language German as well as in the majority language Dutch. By contrast, no input-production association was observed in the VOT production of monolingual German-speaking children and monolingual Dutch-speaking children. The results of this study provide the first empirical evidence that non-native and attrited maternal speech contributes to the often-observed linguistic differences between bilingual children and their monolingual peers.

Abstract

How can we understand each other during communicative interactions? An influential suggestion holds that communicators are primed by each other’s behaviors, with associative mechanisms automatically coordinating the production of communicative signals and the comprehension of their meanings. An alternative suggestion posits that mutual understanding requires shared conceptualizations of a signal’s use, i.e., “conceptual pacts” that are abstracted away from specific experiences. Both accounts predict coherent neural dynamics across communicators, aligned either to the occurrence of a signal or to the dynamics of conceptual pacts. Using coherence spectral-density analysis of cerebral activity simultaneously measured in pairs of communicators, this study shows that establishing mutual understanding of novel signals synchronizes cerebral dynamics across communicators’ right temporal lobes. This interpersonal cerebral coherence occurred only within pairs with a shared communicative history, and at temporal scales independent from signals’ occurrences. These findings favor the notion that meaning emerges from shared conceptualizations of a signal’s use.

Abstract

Despite the ambiguity inherent in human communication, people are remarkably efficient in establishing mutual understanding. Studying how people communicate in novel settings provides a window into the mechanisms supporting the human competence to rapidly generate and understand novel shared symbols, a fundamental property of human communication. Previous work indicates that the right posterior superior temporal sulcus (pSTS) is involved when people understand the intended meaning of novel communicative actions. Here, we set out to test whether normal functioning of this cerebral structure is required for understanding novel communicative actions using inhibitory low-frequency repetitive transcranial magnetic stimulation (rTMS). A factorial experimental design contrasted two tightly matched stimulation sites (right pSTS vs. left MT+, i.e. a contiguous homotopic task-relevant region) and tasks (a communicative task vs. a visual tracking task that used the same sequences of stimuli). Overall task performance was not affected by rTMS, whereas changes in task performance over time were disrupted according to TMS site and task combinations. Namely, rTMS over pSTS led to a diminished ability to improve action understanding on the basis of recent communicative history, while rTMS over MT+ perturbed improvement in visual tracking over trials. These findings qualify the contributions of the right pSTS to human communicative abilities, showing that this region might be necessary for incorporating previous knowledge, accumulated during interactions with a communicative partner, to constrain the inferential process that leads to action understanding.

Abstract

Developmental studies show that it takes longer for
children learning spoken languages to acquire viewpointdependent
spatial relations (e.g., left-right, front-behind),
compared to ones that are not viewpoint-dependent (e.g.,
in, on, under). The current study investigates how
children learn to express viewpoint-dependent relations
in a sign language where depicted spatial relations can be
communicated in an analogue manner in the space in
front of the body or by using body-anchored signs (e.g.,
tapping the right and left hand/arm to mean left and
right). Our results indicate that the visual-spatial
modality might have a facilitating effect on learning to
express these spatial relations (especially in encoding of
left-right) in a sign language (i.e., Turkish Sign
Language) compared to a spoken language (i.e.,
Turkish).

Abstract

There exists a clear association between animacy and the grammatical function of transitive subject. The grammar of some languages require the transitive subject to be high in animacy, or at least higher than the object. A similar animacy preference has been observed in processing studies in languages without such a categorical animacy effect. This animacy preference has been mainly established in structures in which either one or both arguments are provided before the verb. Our goal was to establish (i) whether this preference can already be observed before any argument is provided, and (ii) whether this preference is mediated by verbal information. To this end we exploited the V2 property of Dutch which allows the verb to precede its arguments. Using a visual-world eye-tracking paradigm we presented participants with V2 structures with either an auxiliary (e.g. Gisteren heeft X … ‘Yesterday, X has …’) or a lexical main verb (e.g. Gisteren motiveerde X … ‘Yesterday, X motivated …’) and we measured looks to the animate referent. The results indicate that the animacy preference can already be observed before arguments are presented and that the selectional restrictions of the verb mediate this bias, but do not override it completely.

Abstract

We investigate how the lexical nature of weak definites influences the phenomenon of direct object scrambling in Dutch. Earlier experiments have indicated that weak definites are more resistant to scrambling than strong definites. We examine how the notion of weak definiteness used in this experimental work can be reduced to lexical connectedness. We explore four different ways of quantifying the relation between a direct object and the verb. Our results show that predictability of a verb given the object (verb cloze probability) provides the best fit to the weak/strong distinction used in the earlier experiments

Abstract

General knowledge acquisition entails the extraction of statistical regularities from the environment. At high levels of complexity, this may involve the extraction, and consolidation, of associative regularities across event memories. The underlying neural mechanisms would likely involve a hippocampo-neocortical dialog, as proposed previously for system-level consolidation. To test these hypotheses, we assessed possible differences in consolidation between associative memories containing cross-episodic regularities and unique associative memories. Subjects learned face–location associations, half of which responded to complex regularities regarding the combination of facial features and locations, whereas the other half did not. Importantly, regularities could only be extracted over hippocampus-encoded, associative aspects of the items. Memory was assessed both immediately after encoding and 48 h later, under fMRI acquisition. Our results suggest that processes related to system-level reorganization occur preferentially for regular associations across episodes. Moreover, the build-up of general knowledge regarding regular associations appears to involve the coordinated activity of the hippocampus and mediofrontal regions. The putative cross-talk between these two regions might support a mechanism for regularity extraction. These findings suggest that the consolidation of cross-episodic regularities may be a key mechanism underlying general knowledge acquisition.

Abstract

To investigate the neural underpinnings of word decoding, and how it changes as a function of repeated exposure, we trained Dutch participants repeatedly over the course of a month of training to articulate a set of novel disyllabic input strings written in Greek script to avoid the use of familiar orthographic representations. The syllables in the input were phonotactically legal combinations but non-existent in the Dutch language, allowing us to assess their role in novel word decoding. Not only trained disyllabic pseudowords were tested but also pseudowords with recombined patterns of syllables to uncover the emergence of syllabic representations. We showed that with extensive training, articulation became faster and more accurate for the trained pseudowords. On the neural level, the initial stage of decoding was reflected by increased activity in visual attention areas of occipito-temporal and occipito-parietal cortices, and in motor coordination areas of the precentral gyrus and the inferior frontal gyrus. After one month of training, memory representations for holistic information (whole word unit) were established in areas encompassing the angular gyrus, the precuneus and the middle temporal gyrus. Syllabic representations also emerged through repeated training of disyllabic pseudowords, such that reading recombined syllables of the trained pseudowords showed similar brain activation to trained pseudowords and were articulated faster than novel combinations of letter strings used in the trained pseudowords.

Abstract

Memory representations of words are thought to undergo changes with consolidation: Episodic memories of novel words are transformed into lexical representations that interact with other words in the mental dictionary. Behavioral studies have shown that this lexical integration process is enhanced when there is more time for consolidation. Neuroimaging studies have further revealed that novel word representations are initially represented in a hippocampally-centered system, whereas left posterior middle temporal cortex activation increases with lexicalization. In this study, we measured behavioral and brain responses to newly-learned words in children. Two groups of Dutch children, aged between 8-10 and 14-16 years, were trained on 30 novel Japanese words depicting novel concepts. Children were tested on word-forms, word-meanings, and the novel words’ influence on existing word processing immediately after training, and again after a week. In line with the adult findings, hippocampal involvement decreased with time. Lexical integration, however, was not observed immediately or after a week, neither behaviorally nor neurally. It appears that time alone is not always sufficient for lexical integration to occur. We suggest that other factors (e.g., the novelty of the concepts and familiarity with the language the words are derived from) might also influence the integration process.

Abstract

The aim of the present study was to examine whether repetition of radicals during training of Chinese characters leads to better word acquisition performance in beginning learners of Chinese as a foreign language. Thirty Dutch university students were trained on 36 Chinese one-character words for their pronunciations and meanings. They were also exposed to the specifics of the radicals, that is, for phonetic radicals, the associated pronunciation was explained, and for semantic radicals the associated categorical meanings were explained. Results showed that repeated exposure to phonetic and semantic radicals through character pronunciation and meaning trainings indeed induced better understanding of those radicals that were shared among different characters. Furthermore, characters in the training set that shared phonetic radicals were pronounced better than those that did not. Repetition of semantic radicals across different characters, however, hindered the learning of exact meanings. Students generally confused the meanings of other characters that shared the semantic radical. The study shows that in the initial stage of learning, overlapping information of the shared radicals are effectively learned. Acquisition of the specifics of individual characters, however, requires more training.

Abstract

The complementary learning systems account of declarative memory suggests two distinct memory networks, a fast-mapping, episodic system involving the hippocampus, and a slower semantic memory system distributed across the neocortex in which new information is gradually integrated with existing representations. In this study, we investigated the extent to which these two networks are involved in the integration of novel words into the lexicon after extensive learning, and how the involvement of these networks changes after 24 hours. In particular, we explored whether having richer information at encoding influences the lexicalization trajectory. We trained participants with two sets of novel words, one where exposure was only to the words’ phonological forms (the form-only condition), and one where pictures of unfamiliar objects were associated with the words’ phonological forms (the picture-associated condition). A behavioral measure of lexical competition (indexing lexicalization) indicated stronger competition effects for the form-only words. Imaging (fMRI) results revealed greater involvement of phonological lexical processing areas immediately after training in the form-only condition, suggesting tight connections were formed between novel words and existing lexical entries already at encoding. Retrieval of picture-associated novel words involved the episodic/hippocampal memory system more extensively. Although lexicalization was weaker in the picture-associated condition, overall memory strength was greater when tested after a 24 hours’ delay, probably due to the availability of both episodic and lexical memory networks to aid retrieval. It appears that, during lexicalization of a novel word, the relative involvement of different memory networks differs according to the richness of the information about that word available at encoding.

Abstract

Not unlike the tonal system in Chinese, Japanese habitually attaches pitch accents to the production of words. However, in contrast to Chinese, few homophonic word-pairs are really distinguished by pitch accents (Shibata & Shibata, 1990). This predicts that pitch accent plays a small role in lexical selection for Japanese language comprehension. The present study investigated whether native Japanese speakers necessarily use pitch accent in the processing of accent-contrasted homophonic pairs (e.g., ame [LH] for 'candy' and ame [HI] for 'rain') measuring electroencephalographic (EEG) potentials. Electrophysiological evidence (i.e., N400) was obtained when a word was semantically incorrect for a given context but not for incorrectly accented homophones. This suggests that pitch accent indeed plays a minor role when understanding Japanese. (C) 2013 Elsevier Ltd. All rights reserved.

Abstract

Attraction interference in language comprehension and production may be as a result of common or different processes. In the present paper, we investigate attraction interference during language comprehension, focusing on the contexts in which interference arises and the time-course of these effects. Using evidence from event-related brain potentials (ERPs) and sentence judgment times, we show that agreement attraction in comprehension is best explained as morphosyntactic interference during memory retrieval. This stands in contrast to attraction as a message-level process involving the representation of the subject NP's number features, which is a strong contributor to attraction in production. We thus argue that the cognitive antecedents of agreement attraction in comprehension are non-identical with those of attraction in production, and moreover, that attraction in comprehension is primarily a consequence of similarity-based interference in cue-based memory retrieval processes. We suggest that mechanisms responsible for attraction during language comprehension are a subset of those involved in language production.

Abstract

The rates of overspecification of color, pattern, and size are compared, to investigate how salience and absoluteness contribute to the production of overspecification. Color and pattern are absolute and salient attributes, whereas size is relative and less salient. Additionally, a tendency toward consistent responses is assessed. Using a within-participants design, we find similar rates of color and pattern overspecification, which are both higher than the rate of size overspecification. Using a between-participants design, however, we find similar rates of pattern and size overspecification, which are both lower than the rate of color overspecification. This indicates that although many speakers are more likely to include color than pattern (probably because color is more salient), they may also treat pattern like color due to a tendency toward consistency. We find no increase in size overspecification when the salience of size is increased, suggesting that speakers are more likely to include absolute than relative attributes. However, we do find an increase in size overspecification when mentioning the attributes is triggered, which again shows that speakers tend to refer in a consistent manner, and that there are circumstances in which even size overspecification is frequently produced.

Abstract

Although visual imagery is argued to be an essential component of autobiographical memory, there have been surprisingly few studies on autobiographical memory processes in blind individuals, who have had no or limited visual input. The purpose of the present study was to investigate how blindness affects retrieval and phenomenology of autobiographical memories. We asked 48 congenital/early blind and 48 sighted participants to recall autobiographical memories in response to six cue words, and to fill out the Autobiographical Memory Questionnaire measuring a number of variables including imagery, belief and recollective experience associated with each memory. Blind participants retrieved fewer memories and reported higher auditory imagery at retrieval than sighted participants. Moreover, within the blind group, participants with total blindness reported higher auditory imagery than those with some light perception. Blind participants also assigned higher importance, belief and recollection ratings to their memories than sighted participants. Importantly, these group differences remained the same for recent as well as childhood memories.

Abstract

The neural processing of speech leads to specific patterns in the brain which can be measured as, e.g., EEG signals. When properly aligned with the speech input and averaged over many tokens, the Event Related Potential (ERP) signal is able to differentiate specific contrasts between speech signals. Well-known effects relate to the difference between expected and unexpected words, in particular in the N400, while effects in N100 and P200 are related to attention and acoustic onset effects. Most EEG studies deal with the amplitude of EEG signals over time, sidestepping the effect of phase and phase synchronization. This paper investigates the relation between phase in the EEG signals measured in an auditory lexical decision task by Dutch participants listening to full and reduced English word forms. We show that phase synchronization takes place across stimulus conditions, and that the so-called circular variance is narrowly related to the type of contrast between stimuli.

Abstract

This paper addresses the question how to compare reaction times computed by a computational model of speech comprehension with observed reaction times by participants. The question is based on the observation that reaction time sequences substantially differ per participant, which raises the issue of how exactly the model is to be assessed. Part of the variation in reaction time sequences is caused by the so-called local speed: the current reaction time correlates to some extent with a number of previous reaction times, due to slowly varying variations in attention, fatigue etc. This paper proposes a method, based on time series analysis, to filter the observed reaction times in order to separate the local speed effects. Results show that after such filtering the between-participant correlations increase as well as the average correlation between participant and model increases. The presented technique provides insights into relevant aspects that are to be taken into account when comparing reaction time sequences

Abstract

This paper presents DIANA, a new computational model of human speech processing. It is the first model that simulates the complete processing chain from the on-line processing of an acoustic signal to the execution of a response, including reaction times. Moreover it assumes minimal modularity. DIANA consists of three components. The activation component computes a probabilistic match between the input acoustic signal and representations in DIANA’s lexicon, resulting in a list of word hypotheses changing over time as the input unfolds. The decision component operates on this list and selects a word as soon as sufficient evidence is available. Finally, the execution component accounts for the time to execute a behavioral action. We show that DIANA well simulates the average participant in a word recognition experiment.

Abstract

DIANA is an end-to-end computational model of speech processing, which takes as input the speech signal, and provides as output the orthographic transcription of the stimulus, a word/non-word judgment and the associated estimated reaction time. So far, the model has only been tested for Dutch. In this paper, we extend DIANA such that it can also process North American English. The model is tested by having it simulate human participants in a large scale North American English lexical decision experiment. The simulations show that DIANA can adequately approximate the reaction times of an average participant (r = 0.45). In addition, they indicate that DIANA does not yet adequately model the cognitive processes that take place after stimulus offset.

Abstract

Temporal cues can be used to selectively attend to relevant information during abundant sensory stimulation. However, such cues differ vastly in the accuracy of their temporal estimates, ranging from very predictable to very unpredictable. When cues are strongly predictable, attention may facilitate selective processing by aligning relevant incoming information to high neuronal excitability phases of ongoing low-frequency oscillations. However, top-down effects on ongoing oscillations when temporal cues have some predictability, but also contain temporal uncertainties, are unknown. Here, we experimentally created such a situation of mixed predictability and uncertainty: A target could occur within a limited time window after cue but was always unpredictable in exact timing. Crucially to assess top-down effects in such a mixed situation, we manipulated target probability. High target likelihood, compared with low likelihood, enhanced delta oscillations more strongly as measured by evoked power and intertrial coherence. Moreover, delta phase modulated detection rates for probable targets. The delta frequency range corresponds with half-a-period to the target occurrence window and therefore suggests that low-frequency phase reset is engaged to produce a long window of high excitability when event timing is uncertain within a restricted temporal window.

Abstract

The brain is inherently proactive, constantly predicting the when (moment) and what (content) of future input in order to optimize information processing. Previous research on such predictions has mainly studied the “when” or “what” domain separately, missing to investigate the potential integration of both types of predictive information. In the absence of such integration, temporal cues are assumed to enhance any upcoming content at the predicted moment in time (general temporal predictor). However, if the when and what prediction domain were integrated, a much more flexible neural mechanism may be proposed in which temporal-feature interactions would allow for the creation of multiple concurrent time-content predictions (parallel time-content predictor). Here, we used a temporal association paradigm in two experiments in which sound identity was systematically paired with a specific time delay after the offset of a rhythmic visual input stream. In Experiment 1, we revealed that participants associated the time delay of presentation with the identity of the sound. In Experiment 2, we unexpectedly found that the strength of this temporal association was negatively related to the EEG steady-state evoked responses (SSVEP) in preceding trials, showing that after high neuronal responses participants responded inconsistent with the time-content associations, similar to adaptation mechanisms. In this experiment, time-content associations were only present for low SSVEP responses in previous trials. These results tentatively show that it is possible to represent multiple time-content paired predictions in parallel, however, future research is needed to investigate this interaction further.

Abstract

The role of oscillatory phase for perceptual and cognitive processes is being increasingly acknowledged. To date, little is known about the direct role of phase in categorical perception. Here we show in two separate experiments that the identification of ambiguous syllables that can either be perceived as / da/ or / ga/ is biased by the underlying oscillatory phase as measured with EEG and sensory entrainment to rhythmic stimuli. The measured phase difference in which perception is biased toward / da/ or / ga/ exactly matched the different temporal onset delays in natural audiovisual speech between mouth movements and speech sounds, which last 80 ms longer for / ga/ than for / da/. These results indicate the functional relationship between prestimulus phase and syllable identification, and signify that the origin of this phase relationship could lie in exposure and subsequent learning of unique audiovisual temporal onset differences.

Abstract

Temporal structure in the environment often has predictive value for anticipating the occurrence of forthcoming events. In this study we investigated the influence of two types of predictive temporal information on the perception of near-threshold auditory stimuli: 1) intrinsic temporal rhythmicity within an auditory stimulus stream and 2) temporally-predictive visual cues. We hypothesized that combining predictive temporal information within- and across-modality should decrease the threshold at which sounds are detected, beyond the advantage provided by each information source alone. Two experiments were conducted in which participants had to detect tones in noise. Tones were presented in either rhythmic or random sequences and were preceded by a temporally predictive visual signal in half of the trials. We show that detection intensities are lower for rhythmic (vs. random) and audiovisual (vs. auditory-only) presentation, independent from response bias, and that this effect is even greater for rhythmic audiovisual presentation. These results suggest that both types of temporal information are used to optimally process sounds that occur at expected points in time (resulting in enhanced detection), and that multiple temporal cues are combined to improve temporal estimates. Our findings underscore the flexibility and proactivity of the perceptual system which uses within- and across-modality temporal cues to anticipate upcoming events and process them optimally. (C) 2014 Elsevier Ltd. All rights reserved.

Abstract

In everyday life, people see, describe and remember motion events. We tested whether the type of motion event information (path or manner) encoded in speech and gesture predicts which information is remembered and if this varies across speakers of typologically different languages. We focus on intransitive motion events (e.g., a woman running to a tree) that are described differently in speech and co-speech gesture across languages, based on how these languages typologically encode manner and path information (Kita & Özyürek, 2003; Talmy, 1985). Speakers of Dutch (n = 19) and Turkish (n = 22) watched and described motion events. With a surprise (i.e. unexpected) recognition memory task, memory for manner and path components of these events was measured. Neither Dutch nor Turkish speakers’ memory for manner went above chance levels. However, we found a positive relation between path speech and path change detection: participants who described the path during encoding were more accurate at detecting changes to the path of an event during the memory task. In addition, the relation between path speech and path memory changed with native language: for Dutch speakers encoding path in speech was related to improved path memory, but for Turkish speakers no such relation existed. For both languages, co-speech gesture did not predict memory speakers. We discuss the implications of these findings for our understanding of the relations between speech, gesture, type of encoding in language and memory.

Abstract

Apraxia of Speech (AOS) is a motor speech disorder whose precise nature is still poorly understood. A recent behavioural experiment featuring a noise masking paradigm suggests that AOS reflects a disruption of feedforward control, whereas feedback control is spared and plays a more prominent role in achieving and maintaining segmental contrasts [10]. In the present study, we set out to validate the interpretation of AOS as a feedforward impairment by means of a series of computational simulations with the DIVA model [6, 7] mimicking the behavioural experiment. Simulation results showed a larger reduction in vowel spacing and a smaller vowel dispersion in the masking condition compared to the no-masking condition for the simulated feedforward deficit, whereas the other groups showed an opposite pattern. These results mimic the patterns observed in the human data, corroborating the notion that AOS can be conceptualized as a deficit in feedforward control

Abstract

Gesture is an important precursor of children’s early language development, for example, in the transition to multiword speech and as a predictor of later language abilities. However, it is unclear whether gestural input can influence children’s comprehension of complex grammatical constructions. In Study 1, 3- (M = 3 years 5 months) and 4-year-old (M = 4 years 6 months) children witnessed 2-participant actions described using the infrequent object-cleft-construction (OCC; It was the dog that the cat chased). Half saw an experimenter accompanying her descriptions with gestures representing the 2 participants and indicating the direction of action; the remaining children did not witness gesture. Children who witnessed gestures showed better comprehension of the OCC than those who did not witness gestures, both in and beyond the immediate physical context, but this benefit was restricted to the oldest 4-year-olds. In Study 2, a further group of older 4-year-old children (M = 4 years 7 months) witnessed the same 2-participant actions described by an experimenter and accompanied by gestures, but the gesture represented only the 2 participants and not the direction of the action. Again, a benefit of gesture was observed on subsequent comprehension of the OCC. We interpret these findings as demonstrating that representational cospeech gestures can help children comprehend complex linguistic structures by highlighting the roles played by the participants in the event.

Abstract

Our understanding of the functioning of the brain is primarily based on an average model of the brain's functional organisation, and any deviation from the standard is considered as random noise or a pathological appearance. Studying pathologies has, however, greatly contributed to our understanding of brain functions. For instance, the study of naturally-occurring or surgically-induced brain lesions revealed that language is predominantly lateralised to the left hemisphere while perception/action and emotion are commonly lateralised to the right hemisphere. The lateralisation of function was subsequently replicated by task-related functional neuroimaging in the healthy population. Despite its high significance and reproducibility, this pattern of lateralisation of function is true for most, but not all participants. Bilateral and flipped representations of classically lateralised functions have been reported during development and in the healthy adult population for language, perception/action and emotion. Understanding these different functional representations at an individual level is crucial to improve the sophistication of our models and account for the variance in developmental trajectories, cognitive performance differences and clinical recovery. With the availability of in vivo neuroimaging, it has become feasible to study large numbers of participants and reliably characterise individual differences, also referred to as phenotypes. Yet, we are at the beginning of inter-individual variability modelling, and new theories of brain function will have to account for these differences across participants.

Abstract

To test the hypothesis that thalamic midline nuclei play a transient role in memory consolidation, we reanalyzed a prospective functional MRI study, contrasting recent and progressively more remote memory retrieval. We revealed a transient thalamic connectivity increase with the hippocampus, the medial prefrontal cortex (mPFC), and a parahippocampal area, which decreased with time. In turn, mPFC-parahippocampal connectivity increased progressively. These findings support a model in which thalamic midline nuclei serve as a hub linking hippocampus, mPFC, and posterior representational areas during memory retrieval at an early (2 h) stage of consolidation, extending classical systems consolidation models by attributing a transient role to midline thalamic nuclei.

Abstract

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA’s first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way

Abstract

Infants expect people to direct actions toward objects, and they respond to actions directed to themselves, but do they have expectations about actions directed to third parties? In two experiments, we used eye tracking to investigate 1- and 2-year-olds’ expectations about communicative actions addressed to a third party. Experiment 1 presented infants with videos where an adult (the Emitter) either uttered a sentence or produced non-speech sounds. The Emitter was either face-to-face with another adult (the Recipient) or the two were back-to-back. The Recipient did not respond to any of the sounds. We found that 2-, but not 1-year-olds looked quicker and longer at the Recipient following speech than non-speech, suggesting that they expected her to respond to speech. These effects were specific to the face-to-face context. Experiment 2 presented 1-year-olds with similar face-to-face exchanges but modified to engage infants and minimize task demands. The infants looked quicker to the Recipient following speech than non-speech, suggesting that they expected a response to speech. The study suggests that by 1 year of age infants expect communicative actions to be directed at a third-party listener.

Abstract

We investigated 14-month-old infants’ expectations toward a third party addressee of communicative gestures and an instrumental action. Infants’ eye movements were tracked as they observed a person (the Gesturer) point, direct a palm-up request gesture, or reach toward an object, and another person (the Addressee) respond by grasping it. Infants’ looking patterns indicate that when the Gesturer pointed or used the palm-up request, infants anticipated that the Addressee would give the object to the Gesturer, suggesting that they ascribed a motive of request to the gestures. In contrast, when the Gesturer reached for the object, and in a control condition where no action took place, the infants did not anticipate the Addressee’s response. The results demonstrate that infants’ recognition of communicative gestures extends to others’ interactions, and that infants can anticipate how third-party addressees will respond to others’ gestures.

Abstract

Germline mutations in PTEN, which encodes a widely expressed phosphatase, was mapped to 10q23 and identified as the susceptibility gene for Cowden syndrome, characterized by macrocephaly and high risks of breast, thyroid, and other cancers. The phenotypic spectrum of PTEN mutations expanded to include autism with macrocephaly only 10 years ago. Neurological studies of patients with PTEN-associated autism spectrum disorder (ASD) show increases in cortical white matter and a distinctive cognitive profile, including delayed language development with poor working memory and processing speed. Once a germline PTEN mutation is found, and a diagnosis of phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome made, the clinical outlook broadens to include higher lifetime risks for multiple cancers, beginning in childhood with thyroid cancer. First described as a tumor suppressor, PTEN is a major negative regulator of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) signaling pathway—controlling growth, protein synthesis, and proliferation. This canonical function combines with less well-understood mechanisms to influence synaptic plasticity and neuronal cytoarchitecture. Several excellent mouse models of Pten loss or dysfunction link these neural functions to autism-like behavioral abnormalities, such as altered sociability, repetitive behaviors, and phenotypes like anxiety that are often associated with ASD in humans. These models also show the promise of mTOR inhibitors as therapeutic agents capable of reversing phenotypes ranging from overgrowth to low social behavior. Based on these findings, therapeutic options for patients with PTEN hamartoma tumor syndrome and ASD are coming into view, even as new discoveries in PTEN biology add complexity to our understanding of this master regulator.

Abstract

PTEN Hamartoma Tumor Syndrome (PHTS) is an autosomal-dominant genetic condition underlying a subset of autism spectrum disorder (ASD) with macrocephaly. Caused by germline mutations in PTEN, PHTS also causes increased risks of multiple cancers via dysregulation of the PI3K and MAPK signaling pathways. Conditional knockout models have shown that neural Pten regulates social behavior, proliferation and cell size. Although much is known about how the intracellular localization of PTEN regulates signaling in cancer cell lines, we know little of how PTEN localization influences normal brain physiology and behavior. To address this, we generated a germline knock-in mouse model of cytoplasm-predominant Pten and characterized its behavioral and cellular phenotypes. The homozygous Ptenm3m4 mice have decreased total Pten levels including a specific drop in nuclear Pten and exhibit region-specific increases in brain weight. The Ptenm3m4 model displays sex-specific increases in social motivation, poor balance and normal recognition memory—a profile reminiscent of some individuals with high functioning ASD. The cytoplasm-predominant protein caused cellular hypertrophy limited to the soma and led to increased NG2 cell proliferation and accumulation of glia. The animals also exhibit significant astrogliosis and microglial activation, indicating a neuroinflammatory phenotype. At the signaling level, Ptenm3m4 mice show brain region-specific differences in Akt activation. These results demonstrate that differing alterations to the same autism-linked gene can cause distinct behavioral profiles. The Ptenm3m4 model is the first murine model of inappropriately elevated social motivation in the context of normal cognition and may expand the range of autism-related behaviors replicated in animal models.

Abstract

Synaesthesia is a neurological phenomenon affecting perception, where triggering stimuli (e.g. letters and numbers) elicit unusual secondary sensory experiences (e.g. colours). Family-based studies point to a role for genetic factors in the development of this trait. However, the contributions of common genomic variation to synaesthesia have not yet been investigated. Here, we present the SynGenes cohort, the largest genotyped collection of unrelated people with grapheme–colour synaesthesia (n = 723). Synaesthesia has been associated with a range of other neuropsychological traits, including enhanced memory and mental imagery, as well as greater sensory sensitivity. Motivated by the prior literature on putative trait overlaps, we investigated polygenic scores derived from published genome-wide scans of schizophrenia and autism spectrum disorder (ASD), comparing our SynGenes cohort to 2181 non-synaesthetic controls. We found a very slight association between schizophrenia polygenic scores and synaesthesia (Nagelkerke's R2 = 0.0047, empirical p = 0.0027) and no significant association for scores related to ASD (Nagelkerke's R2 = 0.00092, empirical p = 0.54) or body mass index (R2 = 0.00058, empirical p = 0.60), included as a negative control. As sample sizes for studying common genomic variation continue to increase, genetic investigations of the kind reported here may yield novel insights into the shared biology between synaesthesia and other traits, to complement findings from neuropsychology and brain imaging.

Abstract

The neural response to a stimulus is influenced by endogenous factors such as expectation and attention. Current research suggests that expectation and attention exert their effects in opposite directions, where expectation decreases neural activity in sensory areas, while attention increases it. However, expectation and attention are usually studied either in isolation or confounded with each other. A recent study suggests that expectation and attention may act jointly on sensory processing, by increasing the neural response to expected events when they are attended, but decreasing it when they are unattended. Here we test this hypothesis in an auditory temporal cueing paradigm using magnetoencephalography in humans. In our study participants attended to, or away from, tones that could arrive at expected or unexpected moments. We found a decrease in auditory beta band synchrony to expected (versus unexpected) tones if they were unattended, but no difference if they were attended. Modulations in beta power were already evident prior to the expected onset times of the tones. These findings suggest that expectation and attention jointly modulate sensory processing.

Abstract

In 3 experiments, we investigated whether intonational phrase structure can be primed. In all experiments, participants listened to sentences in which the presence and location of intonational phrase boundaries were manipulated such that the recording included either no intonational phrase boundaries, a boundary in a structurally dispreferred location, a boundary in a preferred location, or boundaries in both locations. In Experiment 1, participants repeated the sentences to test whether they would reproduce the prosodic structure they had just heard. Experiments 2 and 3 used a prime–target paradigm to evaluate whether the intonational phrase structure heard in the prime sentence might influence that of a novel target sentence. Experiment 1 showed that participants did repeat back sentences that they had just heard with the original intonational phrase structure, yet Experiments 2 and 3 found that exposure to intonational phrase boundaries on prime trials did not influence how a novel target sentence was prosodically phrased. These results suggest that speakers may retain the intonational phrasing of a sentence, but this effect is not long-lived and does not generalize across unrelated sentences. Furthermore, these findings provide no evidence that intonational phrase structure is formulated during a planning stage that is separate from other sources of linguistic information.

Abstract

In this study, we investigate the timing of pre-answer inbreaths in order to shed light on the time course of response planning and execution in conversational turn-taking. Using acoustic and inductive plethysmography recordings of seven dyadic conversations in Dutch, we show that pre-answer inbreaths in conversation typically begin briefly after the end of questions. We also show that the presence of a pre-answer inbreath usually co-occurs with substantially delayed answers, with a modal latency of 576 ms vs. 100 ms for answers not preceded by an inbreath. Based on previously reported minimal latencies for internal intercostal activation and the production of speech sounds, we propose that vocal responses, either in the form of a pre-utterance inbreath or of speech proper when an inbreath is not produced, are typically launched in reaction to information present in the last portion of the interlocutor’s turn. We also show that short responses are usually made on residual breath, while longer responses are more often preceded by an inbreath. This relation of inbreaths to answer length suggests that by the time an inbreath is launched, typically during the last few hundred milliseconds of the question, the length of the answer is often prepared to some extent. Together, our findings are consistent with a two-stage model of response planning in conversational turn-taking: early planning of content often carried out in overlap with the incoming turn, and late launching of articulation based on the identification of turn-final cues

Abstract

Tone languages are often reported to make use of utterancelevel intonation as well as of lexical tone. We test the alternative hypotheses that a) the coexistence of lexical tone and utterance-level intonation in tone languages results in a diminished functional load for intonation, and b) that lexical tone and intonation can coexist in tone languages without undermining each other’s functional load in a substantial way. In order to do this, we collected data from two large typological databases, and performed mixed-effects and phylogenetic regression analyses controlling for genealogical and areal factors to estimate the probability of a language exhibiting grammatical devices for encoding polar questions given its status as a tonal or an intonation-only language. Our analyses indicate that, while both tone and intonational languages tend to develop grammatical devices for marking polar questions above chance level, tone languages do this at a significantly higher frequency, with estimated probabilities ranging between 0.88 and .98. This statistical bias provides cross-linguistic empirical support to the view that the use of tonal features to mark lexical contrasts leads to a diminished functional load for utterance-level intonation.

Abstract

This article describes how the tonal elements of two common Spanish intonation contours –the falling statement and the low-rising-falling request– align with the segmental string in broad-focus utterances differing in number of prosodic words. Using an imitation-and-completion task, we show that (i) the last stressed syllable of the utterance, traditionally viewed as carrying the ‘nuclear’ accent, associates with either a high or a low tonal element depending on phrase length (ii) that certain tonal elements can be realized or omitted depending on the availability of specific metrical positions in their intonational phrase, and (iii) that the high tonal element of the request contour associates with either a stressed syllable or an intonational phrase edge depending on phrase length. On the basis of these facts, and in contrast to previous descriptions of Spanish intonation relying on obligatory and constant nuclear contours (e.g., L* L% for all neutral statements), we argue for a less constrained intonational morphology involving tonal units linked to the segmental string via contour-specific principles.

Abstract

We investigate the extent to which French polar questions and continuation statements, two types of utterances with similar morphosyntactic and intonational forms but different pragmatic functions, can be distinguished in conversational data based on phonetic and visual bodily information. We show that the two utterance types can be distinguished well over chance level by automatic classification models including several phonetic and visual cues. We also show that a considerable amount of relevant phonetic and visual information is present before the last portion of the utterances, potentially assisting early speech act recognition by addressees. These findings indicate that bottom-up phonetic and visual cues may play an important role during the production and recognition of speech acts alongside top-down contextual information.

Abstract

We investigate the realization and discrimination of lexical stress contrasts in pitch-unaccented words in phrase-medial position in Spanish, a context in which intonational pitch accents are frequently absent. Results from production and perception experiments show that in this context durational and intensity cues to stress are produced by speakers and used by listeners above chance level. However, due to substantial amounts of phonetic overlap between stress categories in production, and of numerous errors in the identification of stress categories in perception, we suggest that, in the absence of intonational cues, Spanish speakers engaged in online language use must rely on contextual information in order to distinguish stress contrasts.

Abstract

Neuregulin 1 (NRG1) and v-erb-a erythroblastic leukemia viral oncogene homolog 4 (ErbB4) have been extensively studied in schizophrenia susceptibility because of their pivotal role in key neurodevelopmental processes. One of the reasons for the inconsistencies in results could be the fact that the phenotype investigated has mostly the diagnosis of schizophrenia per se, which is widely heterogeneous, both clinically and biologically. In the present study we tested, in a large cohort of 461 schizophrenia patients recruited in Scotland, whether several SNPs in NRG1 and/or ErbB4 are associated with schizophrenia symptom dimensions as evaluated by the Positive and Negative Syndrome Scale (PANSS). We then followed up nominally significant results in a second cohort of 439 schizophrenia subjects recruited in Germany. Using linear regression, we observed two different groups of polymorphisms in NRG1 gene: one showing a nominal association with higher scores of the PANSS positive dimension and the other one with higher scores of the PANSS negative dimension. Regarding ErbB4, a small cluster located in the 5' end of the gene was detected, showing nominal association mainly with negative, general and total dimensions of the PANSS. These findings suggest that some regions of NRG1 and ErbB4 are functionally involved in biological processes that underlie some of the phenotypic manifestations of schizophrenia. Because of the lack of significant association after correction for multiple testing, our analyses should be considered as exploratory and hypothesis generating for future studies.

Abstract

Violations of the maxims of Quantity occur when utterances provide more (over-specified) or less (under-specified) information than strictly required for referent identification. While behavioural datasuggest that under-specified expressions lead to comprehension difficulty and communicative failure, there is no consensus as to whether over-specified expressions are also detrimental to comprehension. In this study we shed light on this debate, providing neurophysiological evidence supporting the view that extra information facilitates comprehension. We further present novel evidence that referential failure due to under-specification is qualitatively different from explicit cases of referential failure, when no matching referential candidate is available in the context.

Abstract

Contrary to the Gricean maxims of quantity (Grice, in: Cole, Morgan (eds) Syntax and semantics: speech acts, vol III, pp 41–58, Academic Press, New York, 1975), it has been repeatedly shown that speakers often include redundant information in their utterances (over-specifications). Previous research on referential communication has long debated whether this redundancy is the result of speaker-internal or addressee-oriented processes, while it is also unclear whether referential redundancy hinders or facilitates comprehension. We present an information-theoretic explanation for the use of over-specification in visually-situated communication, which quantifies the amount of uncertainty regarding the referent as entropy (Shannon in Bell Syst Tech J 5:10, https://doi.org/10.1002/j.1538-7305.1948.tb01338.x, 1948). Examining both the comprehension and production of over-specifications, we present evidence that (a) listeners’ processing is facilitated by the use of redundancy as well as by a greater reduction of uncertainty early on in the utterance, and (b) that at least for some speakers, listeners’ processing concerns influence their encoding of over-specifications: Speakers were more likely to use redundant adjectives when these adjectives reduced entropy to a higher degree than adjectives necessary for target identification.

Abstract

Purpose: To determine clinical phenotypes, evolution and genetic background of a large family with a combination of two unusual forms of reflex epilepsies. Method: Phenotyping was performed in eighteen family members (10 F, 8 M) including standardized EEG recordings with intermittent photic stimulation (IPS). Genetic analyses (linkage scans, Whole Exome Sequencing (WES) and Functional studies) were performed using photoparoxysmal EEG responses (PPRs) as affection status. Results: The proband suffered from speaking induced jaw-jerks and increasing limb jerks evoked by flickering sunlight since about 50 years of age. Three of her family members had the same phenotype. Generalized PPRs were found in seven members (six above 50 years of age) with myoclonus during the PPR. Evolution was typical: Sensitivity to lights with migraine-like complaints around adolescence, followed by jerks evoked by lights and spontaneously with dropping of objects, and strong increase of light sensitivity and onset of talking induced jaw jerks around 50 years. Linkage analysis showed suggestive evidence for linkage to four genomic regions. All photosensitive family members shared a heterozygous R129C mutation in the SCNM1 gene that regulates splicing of voltage gated ion channels. Mutation screening of 134 unrelated PPR patients and 95 healthy controls, did not replicate these findings. Conclusion: This family presents a combination of two rare reflex epilepsies. Genetic analysis favors four genomic regions and points to a shared SCNM1 mutation that was not replicated in a general cohort of photosensitive subjects. Further genetic studies in families with similar combination of features are warranted. (C) 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Abstract

Measuring the quality of metadata is only possible by assessing the quality of the underlying schema and the metadata instance. We propose some factors that are measurable automatically for metadata according to the CMD framework, taking into account the variability of schemas that can be defined in this framework. The factors include among others the number of elements, the (re-)use of reusable components, the number of filled in elements. The resulting score can serve as an indicator of the overall quality of the CMD instance, used for feedback to metadata providers or to provide an overview of the overall quality of metadata within a reposi-tory. The score is independent of specific schemas and generalizable. An overall assessment of harvested metadata is provided in form of statistical summaries and the distribution, based on a corpus of harvested metadata. The score is implemented in XQuery and can be used in tools, editors and repositories

Abstract

Objective: Patients with Parkinson's disease (PD) often suffer from impairments in executive functions, such as working memory deficits. It is widely held that dopamine depletion in the striatum contributes to these impairments through decreased activity and connectivity between task-related brain networks. We investigated this hypothesis by studying task-related network activity and connectivity within a sample of de novo patients with PD, versus healthy controls, during a visuospatial working memory task. Methods: Sixteen de novo PD patients and 35 matched healthy controls performed a visuospatial n-back task while we measured their behavioral performance and neural activity using functional magnetic resonance imaging. We constructed regions-of-interest in the bilateral inferior parietal cortex (IPC), bilateral dorsolateral prefrontal cortex (DLPFC), and bilateral caudate nucleus to investigate group differences in task-related activity. We studied network connectivity by assessing the functional connectivity of the bilateral DLPFC and by assessing effective connectivity within the frontoparietal and the frontostriatal networks. Results: PD patients, compared with controls, showed trend-significantly decreased task accuracy, significantly increased task-related activity in the left DLPFC and a trend-significant increase in activity of the right DLPFC, left caudate nucleus, and left IPC. Furthermore, we found reduced functional connectivity of the DLPFC with other task-related regions, such as the inferior and superior frontal gyri, in the PD group, and group differences in effective connectivity within the frontoparietal network. Interpretation: These findings suggest that the increase in working memory-related brain activity in PD patients is compensatory to maintain behavioral performance in the presence of network deficits. Hum Brain Mapp 36:1554-1566, 2015. (c) 2015 Wiley Periodicals, Inc.

Abstract

Action, gesture, and sign represent unique aspects of human communication that use form and movement to convey meaning. Researchers typically use manual coding of video data to characterize naturalistic, meaningful movements at various levels of description, but the availability of markerless motion-tracking technology allows for quantification of the kinematic features of gestures or any meaningful human movement. We present a novel protocol for extracting a set of kinematic features from movements recorded with Microsoft Kinect. Our protocol captures spatial and temporal features, such as height, velocity, submovements/strokes, and holds. This approach is based on studies of communicative actions and gestures and attempts to capture features that are consistently implicated as important kinematic aspects of communication. We provide open-source code for the protocol, a description of how the features are calculated, a validation of these features as quantified by our protocol versus manual coders, and a discussion of how the protocol can be applied. The protocol effectively quantifies kinematic features that are important in the production (e.g., characterizing different contexts) as well as the comprehension (e.g., used by addressees to understand intent and semantics) of manual acts. The protocol can also be integrated with qualitative analysis, allowing fast and objective demarcation of movement units, providing accurate coding even of complex movements. This can be useful to clinicians, as well as to researchers studying multimodal communication or human–robot interactions. By making this protocol available, we hope to provide a tool that can be applied to understanding meaningful movement characteristics in human communication.

Abstract

Background Rapid automatised naming (RAN) and rapid alternating stimulus (RAS) are reliable predictors of reading disability. The underlying biology of reading disability is poorly understood. However, the high correlation among RAN, RAS and reading could be attributable to shared genetic factors that contribute to common biological mechanisms.

Objective To identify shared genetic factors that contribute to RAN and RAS performance using a multivariate approach.

Methods We conducted a multivariate genome-wide association analysis of RAN Objects, RAN Letters and RAS Letters/Numbers in a sample of 1331 Hispanic American and African–American youth. Follow-up neuroimaging genetic analysis of cortical regions associated with reading ability in an independent sample and epigenetic examination of extant data predicting tissue-specific functionality in the brain were also conducted.

Results Genome-wide significant effects were observed at rs1555839 (p=4.03×10−8) and replicated in an independent sample of 318 children of European ancestry. Epigenetic analysis and chromatin state models of the implicated 70 kb region of 10q23.31 support active transcription of the gene RNLS in the brain, which encodes a catecholamine metabolising protein. Chromatin contact maps of adult hippocampal tissue indicate a potential enhancer–promoter interaction regulating RNLS expression. Neuroimaging genetic analysis in an independent, multiethnic sample (n=690) showed that rs1555839 is associated with structural variation in the right inferior parietal lobule.

Conclusion This study provides support for a novel trait locus at chromosome 10q23.31 and proposes a potential gene–brain–behaviour relationship for targeted future functional analysis to understand underlying biological mechanisms for reading disability.

Abstract

The current study investigated the comprehension of subject and object relative clauses (RCs) in bilingual Mandarin-English children (N = 55, Mage = 7;5, SD = 1;8) and language-matched monolingual Mandarin-speaking children (N = 59, Mage = 5;4, SD = 0;7). The children completed a referent selection task that tested their comprehension of subject and object RCs, and standardised assessments of vocabulary knowledge. Results showed a very similar pattern of responding in both groups. In comparison to past studies of Cantonese, the bilingual and monolingual children both showed a significant subject-over-object RC advantage. An error analysis suggested that the children’s difficulty with object RCs reflected the tendency to interpret the sentential subject as the head noun. A subsequent corpus analysis suggested that children’s difficulty with object RCs may be in part due to distributional information favouring subject RC analyses. Individual differences analyses suggested cross-linguistic transfer from English to Mandarin in the bilingual children at the individual but not the group level, with the results indicating that comparative English-dominance makes children vulnerable to error

Abstract

We present the concept of a community-augmented meta-analysis (CAMA), a simple yet novel tool that significantly facilitates the accumulation and evaluation of previous studies within a specific scientific field. A CAMA is a combination of a meta-analysis and an open repository. Like a meta-analysis, it is centered around a psychologically relevant topic and includes methodological details and standardized effect sizes. As in a repository, data do not remain undisclosed and static after publication but can be used and extended by the research community, as anyone can download all information and can add new data via simple forms. Based on our experiences with building three CAMAs, we illustrate the concept and explain how CAMAs can facilitate improving our research practices via the integration of past research, the accumulation of knowledge, and the documentation of file-drawer studies

Abstract

Numerous studies have revealed an asymmetry tied to the perception of coronal place of articulation: participants accept a labial mispronunciation of a coronal target, but not vice versa. Whether or not this asymmetry is based on language-general properties or arises from language-specific experience has been a matter of debate. The current study suggests a bias of the first type by documenting an early, cross-linguistic asymmetry related to coronal place of articulation. Japanese and Dutch 4- and 6-month-old infants showed evidence of discrimination if they were habituated to a labial and then tested on a coronal sequence, but not vice versa. This finding has important implications for both phonological theories and infant speech perception research

Abstract

Although the majority of evidence on perceptual narrowing in speech sounds is based on consonants, most models of infant speech perception generalize these findings to vowels, assuming that vowel perception improves for vowel sounds that are present in the infant's native language within the first year of life, and deteriorates for non-native vowel sounds over the same period of time. The present meta-analysis contributes to assessing to what extent these descriptions are accurate in the first comprehensive quantitative meta-analysis of perceptual narrowing in infant vowel discrimination, including results from behavioral, electrophysiological, and neuroimaging methods applied to infants 0–14 months of age. An analysis of effect sizes for native and non-native vowel discrimination over the first year of life revealed that they changed with age in opposite directions, being significant by about 6 months of age

Abstract

Japanese infant-directed speech (IDS) and adult-directed speech (ADS) were compared on their segmental distributions and consonant-vowel association patterns. Consistent with findings in other languages, a higher ratio of segments that are generally produced early was found in IDS compared to ADS: more labial consonants and low-central vowels, but fewer fricatives. Consonant-vowel associations also favored the early-produced labial-central, coronal-front, coronal-central, and dorsal-back patterns. On the other hand, clear language-specific patterns included a higher frequency of dorsals, affricates, geminates and moraic nasals in IDS. These segments are frequent in adult Japanese, but not in the early productions or the IDS of other studied languages. In combination with previous results, the current study suggests that both fine-tuning (an increased use of early-produced segments) and highlighting (an increased use of language-specifically relevant segments) might modify IDS on segmental level.

Abstract

Listeners resolve ambiguity in speech by consulting context. Extensive research on this issue has largely relied on continua of sounds constructed to vary incrementally between two phonemic endpoints. In this study we presented listeners instead with phonetic ambiguity of a kind with which they have natural experience: varying degrees of word-final /t/-reduction. In two experiments, Dutch listeners decided whether or not the verb in a sentence such as Maar zij ren(t) soms ‘But she sometimes run(s)’ ended in /t/. In Dutch, presence versus absence of final /t/ distinguishes third- from first-person singular present-tense verbs. Acoustic evidence for /t/ varied from clear to absent, and immediately preceding phonetic context was consistent with more versus less likely deletion of /t/. In both experiments, listeners reported more /t/s in sentences in which /t/ would be syntactically correct. In Experiment 1, the disambiguating syntactic information preceded the target verb, as above, while in Experiment 2, it followed the verb. The syntactic bias was greater for fast than for slow responses in Experiment 1, but no such difference appeared in Experiment 2. We conclude that syntactic information does not directly influence pre-lexical processing, but is called upon in making phoneme decisions.

Abstract

This study compares how Dutch and German, two closely related languages, signal a shift from a negative to a positive polarity in two contexts, when contrasting the polarity relative to a different topic situation (In my picture the man washes the car following after In my picture the man does not wash the car, henceforth polarity contrast) and when correcting the polarity of a proposition (The man washes the car following after The man does not wash the car, henceforth polarity correction). Production data show that in both contexts German speakers produced Verum focus (i.e., a high-falling pitch accent on the finite verb), while Dutch speakers mostly used the accented affirmative particle wel. This shows that even lexically and syntactically close languages behave differently when it comes to signalling certain pragmatic functions. Furthermore, we found that in polarity correction contexts, both affirmative particles and Verum focus were realized with stronger prosodic prominence. This difference was found in both languages and might be due to a secondary (syntagmatic) effect of the information structure of the utterance (absence or presence of a contrastive topic).

Abstract

There is increasing evidence that long-lasting morphologic and
functional consequences can be present in the human visual system
after repetitive mild traumatic brain injury (r-mTBI). The exact lo-
cation and extent of the damage in this condition are not well un-
derstood. Using a recently developed mouse model of r-mTBI, we
assessed the effects on the retina and optic nerve using histology and
immunohistochemistry, electroretinography (ERG), and spectral-
domain optical coherence tomography (SD-OCT) at 10 and 13 weeks
after injury. Control mice received repetitive anesthesia alone (r-sham).
We observed decreased optic nerve diameters and increased cellularity
and areas of demyelination in optic nerves in r-mTBI versus r-sham
mice. There were concomitant areas of decreased cellularity in the
retinal ganglion cell layer and approximately 67% decrease in brain-
specific homeobox/POU domain protein 3AYpositive retinal ganglion
cells in retinal flat mounts. Furthermore, SD-OCT demonstrated a de-
tectable thinning of the inner retina; ERG demonstrated a decrease in
the amplitude of the photopic negative response without any change in
a- or b-wave amplitude or timing. Thus, the ERG and SD-OCT data
correlated well with changes detected by morphometric, histologic,
and immunohistochemical methods, thereby supporting the use of
these noninvasive methods in the assessment of visual function and
morphology in clinical cases of mTBI.

Abstract

A commonly held assumption in cognitive neuroscience is that, because measures of human brain function are closer to underlying biology than distal indices of behavior/cognition, they hold more promise for uncovering genetic pathways. Supporting this view is an influential fMRI-based study of sentence reading/listening by Pinel et al. (2012), who reported that common DNA variants in specific candidate genes were associated with altered neural activation in language-related regions of healthy individuals that carried them. In particular, different single-nucleotide polymorphisms (SNPs) of FOXP2 correlated with variation in task-based activation in left inferior frontal and precentral gyri, whereas a SNP at the KIAA0319/TTRAP/THEM2 locus was associated with variable functional asymmetry of the superior temporal sulcus. Here, we directly test each claim using a closely matched neuroimaging genetics approach in independent cohorts comprising 427 participants, four times larger than the original study of 94 participants. Despite demonstrating power to detect associations with substantially smaller effect sizes than those of the original report, we do not replicate any of the reported associations. Moreover, formal Bayesian analyses reveal substantial to strong evidence in support of the null hypothesis (no effect). We highlight key aspects of the original investigation, common to functional neuroimaging genetics studies, which could have yielded elevated false-positive rates. Genetic accounts of individual differences in cognitive functional neuroimaging are likely to be as complex as behavioral/cognitive tests, involving many common genetic variants, each of tiny effect. Reliable identification of true biological signals requires large sample sizes, power calculations, and validation in independent cohorts with equivalent paradigms.

SIGNIFICANCE STATEMENT A pervasive idea in neuroscience is that neuroimaging-based measures of brain function, being closer to underlying neurobiology, are more amenable for uncovering links to genetics. This is a core assumption of prominent studies that associate common DNA variants with altered activations in task-based fMRI, despite using samples (10–100 people) that lack power for detecting the tiny effect sizes typical of genetically complex traits. Here, we test central findings from one of the most influential prior studies. Using matching paradigms and substantially larger samples, coupled to power calculations and formal Bayesian statistics, our data strongly refute the original findings. We demonstrate that neuroimaging genetics with task-based fMRI should be subject to the same rigorous standards as studies of other complex traits.

Abstract

The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.

Abstract

This study investigates whether a clear distinction can be made between the prosody of continuation statements and polar questions in conversational French, which are both typically produced with final rising intonation. We show that the two utterance types can be distinguished over chance level by several pitch, duration, and intensity cues. However, given the substantial amount of phonetic overlap and the nature of the observed differences between the two utterance types (i.e. overall F0 scaling, final intensity drop and degree of final lengthening), we propose that variability in the phonetic detail of intonation rises in French is due to the effects of interactional factors (e.g. turn-taking context, type of speech act) rather than to the existence of two distinct rising intonation contour types in this language.

Abstract

Speech prosody, the variation in sentence melody and rhythm, plays a crucial role in sentence comprehension. Specifically, changes in intonational pitch along a sentence can affect our understanding of who did what to whom. To date, it remains unclear how the brain processes this particular use of intonation and which brain regions are involved. In particular, one central matter of debate concerns the lateralisation of intonation processing. To study the role of intonation in sentence comprehension, we designed a functional MRI experiment in which participants listened to spoken sentences. Critically, the interpretation of these sentences depended on either intonational or grammatical cues. Our results
showed stronger functional activity in the left inferior frontal gyrus (IFG) when the intonational cue was crucial for sentence comprehension compared to when it was not. When instead a grammatical cue was crucial for sentence comprehension, we found involvement of an overlapping region in the left IFG, as well as in a posterior temporal
region. A further analysis revealed that the lateralisation of intonation processing depends on its role in syntactic processing: activity in the IFG was lateralised to the left hemisphere when intonation was the only source of information to comprehend the sentence. In contrast, activity in the IFG was right-lateralised when intonation did not contribute to sentence comprehension. Together, these results emphasise the key role of the left IFG in sentence comprehension, showing the importance of this region when intonation
establishes sentence structure. Furthermore, our results provide evidence for the theory
that the lateralisation of prosodic processing is modulated by its linguistic role.

Abstract

In synaesthetes specific sensory stimuli (e.g., black letters) elicit additional experiences (e.g. colour). Synaesthesia is highly prevalent among individuals with autism spectrum disorder but the mechanisms of this co-occurrence are not clear. We hypothesized autism and synaesthesia share atypical sensory sensitivity and perception. We assessed autistic traits, sensory sensitivity, and visual perception in two synaesthete populations. In Study 1, synaesthetes (N=79, of different types) scored higher than non-synaesthetes (N=76) on the Attention-to-detail and Social skills subscales of the Autism Spectrum Quotient indexing autistic traits, and on the Glasgow Sensory Questionnaire indexing sensory hypersensitivity and hyposensitivity which frequently occur in autism. Synaesthetes performed two local/global visual tasks because individuals with autism typically show a bias toward detail processing. In synaesthetes, elevated motion coherence thresholds suggested reduced global motion perception and higher accuracy on an embedded figures task suggested enhanced local perception. In Study 2 sequence-space synaesthetes (N=18) completed the same tasks. Questionnaire and embedded figures results qualitatively resembled Study 1 results but no significant group differences with non-synaesthetes (N=20) were obtained. Unexpectedly, sequence-space synaesthetes had reduced motion coherence thresholds. Altogether, our studies suggest atypical sensory sensitivity and a bias towards detail processing are shared features of synaesthesia and autism spectrum disorder.