Publications

Abstract

Interactions between functionally specialized brain regions are crucial for normal brain function. Magnetoencephalography (MEG) and electroencephalography (EEG) are techniques suited to capture these interactions, because they provide whole head measurements of brain activity in the millisecond range. More than one sensor picks up the activity of an underlying source. This field spread severely limits the utility of connectivity measures computed directly between sensor recordings. Consequentially, neuronal interactions should be studied on the level of the reconstructed sources. This article reviews several methods that have been applied to investigate interactions between brain regions in source space. We will mainly focus on the different measures used to quantify connectivity, and on the different strategies adopted to identify regions of interest. Despite various successful accounts of MEG and EEG source connectivity, caution with respect to the interpretation of the results is still warranted. This is due to the fact that effects of field spread can never be completely abolished in source space. However, in this very exciting and developing field of research this cautionary note should not discourage researchers from further investigation into the connectivity between neuronal sources.

Abstract

This paper combines acoustic features with a high temporal and a high frequency resolution to reliably classify articulatory events of short duration, such as bursts in plosives. SVM classification experiments on TIMIT and SVArticulatory showed that articulatory-acoustic features (AFs) based on a combination of MFCCs derived from a long window of 25ms and a short window of 5ms that are both shifted with 2.5ms steps (Both) outperform standard MFCCs derived with a window of 25 ms and a shift of 10 ms (Baseline). Finally, comparison of the TIMIT and SVArticulatory results showed that for classifiers trained on data that allows for asynchronously changing AFs (SVArticulatory) the improvement from Baseline to Both is larger than for classifiers trained on data where AFs change simultaneously with the phone boundaries (TIMIT).

Abstract

Although there is good evidence that social animals show elaborate cognitive skills to deal with others, there are few reports of animals physically using social agents and their respective responses as means to an end—social tool use. In this case study, we investigated spontaneous and repeated social tool use behavior in chimpanzees (Pan troglodytes). We presented a group of chimpanzees with an apparatus, in which pushing two buttons would release juice from a distantly located fountain. Consequently, any one individual could only either push the buttons or drink from the fountain but never push and drink simultaneously. In this scenario, an adult male attempted to retrieve three other individuals and push them toward the buttons that, if pressed, released juice from the fountain. With this strategy, the social tool user increased his juice intake 10-fold. Interestingly, the strategy was stable over time, which was possibly enabled by playing with the social tools. With over 100 instances, we provide the biggest data set on social tool use recorded among nonhuman animals so far. The repeated use of other individuals as social tools may represent a complex social skill linked to Machiavellian intelligence.

Abstract

The motor theory of speech perception assumes that activation of the motor system is essential in the perception of speech. However, deficits in speech perception and comprehension do not arise from damage that is restricted to the motor cortex, few functional imaging studies reveal activity in motor cortex during speech perception, and the motor cortex is strongly activated by many different sound categories. Here, we evaluate alternative roles for the motor cortex in spoken communication and suggest a specific role in sensorimotor processing in conversation. We argue that motor-cortex activation it is essential in joint speech, particularly for the timing of turn-taking.

Abstract

Bipolar disorder (BP) is a disabling and often life-threatening disorder that affects approximately 1% of the population worldwide. To identify genetic variants that increase the risk of BP, we genotyped on the Illumina HumanHap550 Beadchip 2,076 bipolar cases and 1,676 controls of European ancestry from the National Institute of Mental Health Human Genetics Initiative Repository, and the Prechter Repository and samples collected in London, Toronto, and Dundee. We imputed SNP genotypes and tested for SNP-BP association in each sample and then performed meta-analysis across samples. The strongest association P value for this 2-study meta-analysis was 2.4 x 10(-6). We next imputed SNP genotypes and tested for SNP-BP association based on the publicly available Affymetrix 500K genotype data from the Wellcome Trust Case Control Consortium for 1,868 BP cases and a reference set of 12,831 individuals. A 3-study meta-analysis of 3,683 nonoverlapping cases and 14,507 extended controls on >2.3 M genotyped and imputed SNPs resulted in 3 chromosomal regions with association P approximately 10(-7): 1p31.1 (no known genes), 3p21 (>25 known genes), and 5q15 (MCTP1). The most strongly associated nonsynonymous SNP rs1042779 (OR = 1.19, P = 1.8 x 10(-7)) is in the ITIH1 gene on chromosome 3, with other strongly associated nonsynonymous SNPs in GNL3, NEK4, and ITIH3. Thus, these chromosomal regions harbor genes implicated in cell cycle, neurogenesis, neuroplasticity, and neurosignaling. In addition, we replicated the reported ANK3 association results for SNP rs10994336 in the nonoverlapping GSK sample (OR = 1.37, P = 0.042). Although these results are promising, analysis of additional samples will be required to confirm that variant(s) in these regions influence BP risk.

Abstract

Representations learned by deep convolutional neural networks (CNNs) for object recognition are a widely
investigated model of the processing hierarchy in the human visual system. Using functional magnetic resonance
imaging, CNN representations of visual stimuli have previously been shown to correspond to processing stages in
the ventral and dorsal streams of the visual system. Whether this correspondence between models and brain
signals also holds for activity acquired at high temporal resolution has been explored less exhaustively. Here, we
addressed this question by combining CNN-based encoding models with magnetoencephalography (MEG).
Human participants passively viewed 1,000 images of objects while MEG signals were acquired. We modelled
their high temporal resolution source-reconstructed cortical activity with CNNs, and observed a feed-forward
sweep across the visual hierarchy between 75 and 200 ms after stimulus onset. This spatiotemporal cascade
was captured by the network layer representations, where the increasingly abstract stimulus representation in the
hierarchical network model was reflected in different parts of the visual cortex, following the visual ventral
stream. We further validated the accuracy of our encoding model by decoding stimulus identity in a left-out
validation set of viewed objects, achieving state-of-the-art decoding accuracy.

Abstract

Syntactic binding refers to combining words into larger structures. Using EEG, we investigated the neural processes involved in syntactic binding. Participants were auditorily presented two-word sentences (i.e. pronoun and pseudoverb such as ‘I grush’, ‘she grushes’, for which syntactic binding can take place) and wordlists (i.e. two pseudoverbs such as ‘pob grush’, ‘pob grushes’, for which no binding occurs). Comparing these two conditions, we targeted syntactic binding while minimizing contributions of semantic binding and of other cognitive processes such as working memory. We found a converging pattern of results using two distinct analysis approaches: one approach using frequency bands as defined in previous literature, and one data-driven approach in which we looked at the entire range of frequencies between 3-30 Hz without the constraints of pre-defined frequency bands. In the syntactic binding (relative to the wordlist) condition, a power increase was observed in the alpha and beta frequency range shortly preceding the presentation of the target word that requires binding, which was maximal over frontal-central electrodes. Our interpretation is that these signatures reflect that language comprehenders expect the need for binding to occur. Following the presentation of the target word in a syntactic binding context (relative to the wordlist condition), an increase in alpha power maximal over a left lateralized cluster of frontal-temporal electrodes was observed. We suggest that this alpha increase relates to syntactic binding taking place. Taken together, our findings suggest that increases in alpha and beta power are reflections of distinct the neural processes underlying syntactic binding.

Abstract

Using kinetic contours derived from everyday objects, we investigated how motion affects object identification. In order not to be distinguishable when static, kinetic contours were made from random dot displays consisting of two regions, inside and outside the object contour. In Experiment 1, the dots were moving in only one of two regions. The objects were identified nearly equally well as soon as the dots either in the figure or in the background started to move. RTs decreased with increasing motion coherence levels and were shorter for complex, less compact objects than for simple, more compact objects. In Experiment 2, objects could be identified when the dots were moving both in the figure and in the background with speed and direction differences between the two. A linear increase in either the speed difference or the direction difference caused a linear decrease in RT for correct identification. In addition, the combination of speed and motion differences appeared to be super-additive.

Abstract

French-learning 11-month-old and English-learning 11- and 4-month-old infants were familiarized with consonant–vowel–consonant syllables in which the final consonants were dependent on whether the preceding vowel was oral or nasal. Oral and nasal vowels are present in the ambient language of all participants, but vowel nasality is phonemic (contrastive) in French and allophonic (noncontrastive) in English. After familiarization, infants heard novel syllables that either followed or violated the familiarized patterns. French-learning 11-month-olds and English-learning 4-month-olds displayed a reliable pattern of preference demonstrating learning and generalization of the patterns, while English-learning 11-month-olds oriented equally to syllables following and violating the familiarized patterns. The results are consistent with an experience-driven reduction of attention to allophonic contrasts by as early as 11 months, which influences phonotactic learning.

Abstract

This discussion note reviews responses of the linguistics profession to the grave issues of language
endangerment identified a quarter of a century ago in the journal Language by Krauss,
Hale, England, Craig, and others (Hale et al. 1992). Two and a half decades of worldwide research
not only have given us a much more accurate picture of the number, phylogeny, and typological
variety of the world’s languages, but they have also seen the development of a wide range of new
approaches, conceptual and technological, to the problem of documenting them. We review these
approaches and the manifold discoveries they have unearthed about the enormous variety of linguistic
structures. The reach of our knowledge has increased by about 15% of the world’s languages,
especially in terms of digitally archived material, with about 500 languages now
reasonably documented thanks to such major programs as DoBeS, ELDP, and DEL. But linguists
are still falling behind in the race to document the planet’s rapidly dwindling linguistic diversity,
with around 35–42% of the world’s languages still substantially undocumented, and in certain
countries (such as the US) the call by Krauss (1992) for a significant professional realignment toward
language documentation has only been heeded in a few institutions. Apart from the need for
an intensified documentarist push in the face of accelerating language loss, we argue that existing
language documentation efforts need to do much more to focus on crosslinguistically comparable
data sets, sociolinguistic context, semantics, and interpretation of text material, and on methods
for bridging the ‘transcription bottleneck’, which is creating a huge gap between the amount we
can record and the amount in our transcribed corpora.*

Abstract

This study longitudinally investigated developmental changes in the frame of reference used by children in their gestures and speech. Fifteen children, between 4 and 6 years of age, were asked once a year to describe their route home from their nursery school. When the children were 4 years old, they tended to produce gestures that directly and continuously indicated their actual route in a large gesture space. In contrast, as 6-year-olds, their gestures were segmented and did not match the actual route. Instead, at age 6, the children seemed to create a virtual space in front of themselves to symbolically describe their route. These results indicate that the use of frames of reference develops across the preschool years, shifting from an actual environmental to an abstract environmental frame of reference. Factors underlying the development of frame of reference, including verbal encoding skills and experience, are discussed.

Abstract

We examined gesture representation of motion events in narratives produced by three- and nine-year-olds, and adults. Two aspects of gestural depiction were analysed: how protagonists were depicted, and how gesture space was used. We found that older groups were more likely to express protagonists as an object that a gesturing hand held and manipulated, and less likely to express protagonists with whole-body enactment gestures. Furthermore, for older groups, gesture space increasingly became less similar to narrated space. The older groups were less likely to use large gestures or gestures in the periphery of the gesture space to represent movements that were large relative to a protagonist’s body or that took place next to a protagonist. They were also less likely to produce gestures on a physical surface (e.g. table) to represent movement on a surface in narrated events. The development of gestural depiction indicates that older speakers become less immersed in the story world and start to control and manipulate story representation from an outside perspective in a bounded and stage-like gesture space. We discuss this developmental shift in terms of increasing symbolic distancing (Werner & Kaplan, 1963).

Abstract

The article concentrates on the question of the composition, the internal ordering and the placement of clitic-clusters (C-clusters) in French and Italian, though clitic data from other languages are drawn in occasionally. The system proposed is top-down transformational, in the terms of Semantic Syntax (Seuren, Blackwell, 1996). Clitics are taken to originate in underlying structure as canonical argument terms or adverbial constituents of clauses. During the process of transformation from semantic to surface form, nonfocus, nonsubject, pronominal argument terms are assigned values for the features of animacy ([±an]), dative status ([±dat]) and reflexivity ([±refl]). On the basis of these, the rule feature cm, inducing clitic movement, is assigned or withheld. Plus-values increase, and minus-values reduce, the “semantic weight” of the clitics in question. Pronouns without the feature cm are not cliticised and stay in their canonical term position in their full phonological form. Pronouns with the feature cm are attached to the nearest verb form giving rise to clitic clusters, which accounts for the composition of well-formed C-clusters. The attachment of clitics to a cluster occurs in a fixed order, which accounts for the ordering of clitics in well-formed clusters. Branching directionality, together with a theory of complementation, accounts for the placement of C-clusters. Clitics often take on a reduced phonological form. It is argued that, in French and Italian, which are languages with a right-branching syntax and a left-branching flectional morphology, postverbal clitics, or enclitics, are part of left-branching structures and hence fit naturally into the morphology. They are best categorised as affixes. Occasionally, as in Italian glielo, dative clitics (e.g., gli) turn preceding lighter clitics (e.g., lo) into affixes, resulting in the left-branching structure glielo, where -lo is an affix. In a brief Intermezzo, instances are shown of the irregular but revealing lui-le-lui phenomenon in French, and its much less frequent analog in Italian. On these assumptions, supported by the official orthographies, the clitic systems of French and Italian largely coincide. This new analysis of the facts in question invites further reflection on the interface between syntax and morphology. The final section deals with reflexive clitics. There, the system begins to be unable to account for the observed facts. At this end, therefore, the system is allowed to remain fraying, till further research brings greater clarity.

Abstract

Ever since the category of evidentiality has been identified in the verbal grammar of certain languages, it has been assumed that evidentiality plays no role in the grammars of those languages that have not incorporated it into their verb morphology or at least their verb clusters. The present paper attempts to show that even if evidentiality is not visible in the verbal grammar of English and Dutch, it appears to be a motivating factor, both historically and synchronically, in the process whereby evidential predicates are made to play a subordinate syntactic role with regard to their embedded subject clause. This process, known as AUXILIATION (Kuteva 2001), appears to manifest itself in a variety of, often successive, grammatical processes or rules, such as Subject-to-Subject Raising (the subject of the embedded clause becomes the subject of the main verb, as in John is likely to be late), V-ING (as in The man stopped breathing), Incorporation-by-Lowering (the evidential main verb is lowered on to the V-constituent of the embedded subject clause, as in John may have left), or Incorporation-by-Raising (also known as Predicate Raising), not or hardly attested in English but dominant in Dutch. A list is provided of those English (and Dutch) predicates that induce one of the above-mentioned auxiliation rules and it is checked how many of those have an evidential meaning. This is set off against evidential predicates that do not induce an auxiliation rule. It results that, for English and Dutch, lexical evidentiality is a powerful determinant for the induction of syntactic auxiliation.

Abstract

A t(X;1)(p11.2;q21.2) has been reported in cases of papillary renal cell tumors arising in males. In this study two cell lines derived from this tumor type have been used to indicate the breakpoint region on the X chromosome. Both cell lines have the translocation in addition to other rearrangements and one is derived from the first female case to be reported with the t(X;1)(p11.2;q21.2). Fluorescence in situ hybridization (FISH) has been used to position YACs belonging to contigs in the Xp11.2 region relative to the breakpoint. When considered together with detailed mapping information from the Xp11.2 region the position of the breakpoint in both cell lines was suggested as follows: Xpter-->Xp11.23-OATL1-GATA1-WAS-TFE3-SY P-t(X;1)-DXS255-CLCN5-DXS146-OATL2- Xp11.22-->Xcen. The breakpoint was determined to lie in an uncloned region between SYP and a YAC called FTDM/1 which extends 1 Mb distal to DXS255. These results are contrary to the conclusion from previous FISH studies that the breakpoint was near the OATL2 locus, but are consistent with, and considerably refine, the position that had been established by molecular analysis.

Abstract

Since Pillsbury [1908. Attention. London: Swan Sonnenschein & Co], the issue of whether attention operates through inhibition or enhancement has been on the scientific agenda. We examined whether overcoming previous attentional inhibition or enhancement is the source of asymmetrical switch costs in spoken noun-phrase production and colour-word Stroop tasks. In Experiment 1, using bivalent stimuli, we found asymmetrical costs in response times for switching between long and short phrases and between Stroop colour naming and reading. However, in Experiment 2, using bivalent stimuli for the weaker tasks (long phrases, colour naming) and univalent stimuli for the stronger tasks (short phrases, word reading), we obtained an asymmetrical switch cost for phrase production, but a symmetrical cost for Stroop. The switch cost evidence was quantified using Bayesian statistical analyses. Our findings suggest that switching between phrase types involves inhibition, whereas switching between colour naming and reading involves enhancement. Thus, the attentional mechanism depends on the language-production task involved. The results challenge theories of task switching that assume only one attentional mechanism, inhibition or enhancement, rather than both mechanisms.

Abstract

Recently, it has been proposed that sequence learning engages a combination of modality-specific operating networks and modality-independent computational principles. In the present study, we compared the behavioural and EEG outcomes of implicit artificial grammar learning in the visual vs. auditory modality. We controlled for the influence of surface characteristics of sequences (Associative Chunk Strength), thus focusing on the strictly structural aspects of sequence learning, and we adapted the paradigms to compensate for known frailties of the visual modality compared to audition (temporal presentation, fast presentation rate). The behavioural outcomes were similar across modalities. Favouring the idea of modality-specificity, ERPs in response to grammar violations differed in topography and latency (earlier and more anterior component in the visual modality), and ERPs in response to surface features emerged only in the auditory modality. In favour of modality-independence, we observed three common functional properties in the late ERPs of the two grammars: both were free of interactions between structural and surface influences, both were more extended in a grammaticality classification test than in a preference classification test, and both correlated positively and strongly with theta event-related-synchronization during baseline testing. Our findings support the idea of modality-specificity combined with modality-independence, and suggest that memory for visual vs. auditory sequences may largely contribute to cross-modal differences.

Abstract

Studies of emotion signaling inform claims about the taxonomic structure, evolutionary origins, and physiological correlates of emotions. Emotion vocalization research has tended to focus on a limited set of emotions: anger, disgust, fear, sadness, surprise, happiness, and for the voice, also tenderness. Here, we examine how well brief vocal bursts can communicate 22 different emotions: 9 negative (Study 1) and 13 positive (Study 2), and whether prototypical vocal bursts convey emotions more reliably than heterogeneous vocal bursts (Study 3). Results show that vocal bursts communicate emotions like anger, fear, and sadness, as well as seldom-studied states like awe, compassion, interest, and embarrassment. Ancillary analyses reveal family-wise patterns of vocal burst expression. Errors in classification were more common within emotion families (e.g., ‘self-conscious,’ ‘pro-social’) than between emotion families. The three studies reported highlight the voice as a rich modality for emotion display that can inform fundamental constructs about emotion.

Abstract

Important speech cues such as lexical tone and vowel quality are perceptually contrasted to the distribution of those same cues in surrounding contexts. However, it is unclear whether preceding and following contexts have similar influences, and to what extent those influences are modulated by the auditory history of previous trials. To investigate this, Cantonese participants labeled sounds from (a) a tone continuum (mid- to high-level), presented with a context that had raised or lowered F0 values and (b) a vowel quality continuum (/u/ to /o/), where the context had raised or lowered F1 values. Contexts with high or low F0/F1 were presented in separate blocks or intermixed in 1 block. Contexts were presented following (Experiment 1) or preceding the target continuum (Experiment 2). Contrastive effects were found for both tone and vowel quality (e.g., decreased F0 values in contexts lead to more high tone target judgments and vice versa). Importantly, however, lexical tone was only influenced by F0 in immediately preceding and following contexts. Vowel quality was only influenced by the F1 in preceding contexts, but this extended to contexts from preceding trials. Contextual influences on tone and vowel quality are qualitatively different, which has important implications for understanding the mechanism of context effects in speech perception.

Abstract

Young children's visual environments are dynamic, changing moment-by-moment as children physically and visually explore spaces and objects and interact with people around them. Head-mounted eye tracking offers a unique opportunity to capture children's dynamic egocentric views and how they allocate visual attention within those views. This protocol provides guiding principles and practical recommendations for researchers using head-mounted eye trackers in both laboratory and more naturalistic settings. Head-mounted eye tracking complements other experimental methods by enhancing opportunities for data collection in more ecologically valid contexts through increased portability and freedom of head and body movements compared to screen-based eye tracking. This protocol can also be integrated with other technologies, such as motion tracking and heart-rate monitoring, to provide a high-density multimodal dataset for examining natural behavior, learning, and development than previously possible. This paper illustrates the types of data generated from head-mounted eye tracking in a study designed to investigate visual attention in one natural context for toddlers: free-flowing toy play with a parent. Successful use of this protocol will allow researchers to collect data that can be used to answer questions not only about visual attention, but also about a broad range of other perceptual, cognitive, and social skills and their development.

Abstract

Abstract In the past, several assessment reports on writing repeatedly showed that elementary school students do not develop the essential writing skills to be successful in school. In this respect, prior research has pointed to the fact that cognitive and motivational challenges are at the root of the rather basic level of elementary students' writing performance. Additionally, previous research has revealed gender and achievement-level differences in elementary students' writing. In view of providing effective writing instruction for all students to overcome writing difficulties, the present study provides more in-depth insight into (a) how cognitive and motivational challenges mediate and correlate with students' writing performance and (b) whether and how these relations vary for boys and girls and for writers of different achievement levels. In the present study, 1,577 fifth- and sixth-grade students completed questionnaires regarding their writing self-efficacy, writing motivation, and writing strategies. In addition, half of the students completed two writing tests, respectively focusing on the informational or narrative text genre. Based on multiple group structural equation modeling (MG-SEM), we put forward two models: a MG-SEM model for boys and girls and a MG-SEM model for low, average, and high achievers. The results underline the importance of studying writing models for different groups of students in order to gain more refined insight into the complex interplay between motivational and cognitive challenges related to students' writing performance.

Abstract

The present experiment tested the suggestion that human listeners may exploit durational information in speech to parse continuous utterances into words. Listeners were presented with six-syllable unpredictable utterances under noise-masking, and were required to judge between alternative word strings as to which best matched the rhythm of the masked utterances. For each utterance there were four alternative strings: (a) an exact rhythmic and word boundary match, (b) a rhythmic mismatch, and (c) two utterances with the same rhythm as the masked utterance, but different word boundary locations. Listeners were clearly able to perceive the rhythm of the masked utterances: The rhythmic mismatch was chosen significantly less often than any other alternative. Within the three rhythmically matched alternatives, the exact match was chosen significantly more often than either word boundary mismatch. Thus, listeners both perceived speech rhythm and used durational cues effectively to locate the position of word boundaries.

Abstract

The appropriate definition and scaling of the magnitude of electroencephalogram (EEG) oscillations is an underdeveloped area. The aim of this study was to optimize the analysis of resting EEG alpha magnitude, focusing on alpha peak frequency and nonlinear transformation of alpha power. A family of nonlinear transforms, Box-Cox transforms, were applied to find the transform that (a) maximized a non-disputed effect: the increase in alpha magnitude when the eyes are closed (Berger effect), and (b) made the distribution of alpha magnitude closest to normal across epochs within each participant, or across participants. The transformations were performed either at the single epoch level or at the epoch-average level. Alpha peak frequency showed large individual differences, yet good correspondence between various ways to estimate it in 2min of eyes-closed and 2min of eyes-open resting EEG data. Both alpha magnitude and the Berger effect were larger for individual alpha than for a generic (8-12Hz) alpha band. The log-transform on single epochs (a) maximized the t-value of the contrast between the eyes-open and eyes-closed conditions when tested within each participant, and (b) rendered near-normally distributed alpha power across epochs and participants, thereby making further transformation of epoch averages superfluous. The results suggest that the log-normal distribution is a fundamental property of variations in alpha power across time in the order of seconds. Moreover, effects on alpha power appear to be multiplicative rather than additive. These findings support the use of the log-transform on single epochs to achieve appropriate scaling of alpha magnitude.

Abstract

Sentence comprehension requires the retrieval of single word information from long-term memory, and the integration of this information into multiword representations. The current functional magnetic resonance imaging study explored the hypothesis that the left posterior temporal gyrus supports the retrieval of lexical-syntactic information, whereas left inferior frontal gyrus (LIFG) contributes to syntactic unification. Twenty-eight subjects read sentences and word sequences containing word-category (noun–verb) ambiguous words at critical positions. Regions contributing to the syntactic unification process should show enhanced activation for sentences compared to words, and only within sentences display a larger signal for ambiguous than unambiguous conditions. The posterior LIFG showed exactly this predicted pattern, confirming our hypothesis that LIFG contributes to syntactic unification. The left posterior middle temporal gyrus was activated more for ambiguous than unambiguous conditions (main effect over both sentences and word sequences), as predicted for regions subserving the retrieval of lexical-syntactic information from memory. We conclude that understanding language involves the dynamic interplay between left inferior frontal and left posterior temporal regions.

Abstract

Chromatin remodeling is of crucial importance during brain development. Pathogenic
alterations of several chromatin remodeling ATPases have been implicated in neurodevelopmental
disorders. We describe an index case with a de novo missense mutation in CHD3,
identified during whole genome sequencing of a cohort of children with rare speech disorders.
To gain a comprehensive view of features associated with disruption of this gene, we use a
genotype-driven approach, collecting and characterizing 35 individuals with de novo CHD3
mutations and overlapping phenotypes. Most mutations cluster within the ATPase/helicase
domain of the encoded protein. Modeling their impact on the three-dimensional structure
demonstrates disturbance of critical binding and interaction motifs. Experimental assays with
six of the identified mutations show that a subset directly affects ATPase activity, and all but
one yield alterations in chromatin remodeling. We implicate de novo CHD3 mutations in a
syndrome characterized by intellectual disability, macrocephaly, and impaired speech and
language.

Abstract

Many genetic causes of developmental delay and/or intellectual disability (DD/ID) are extremely rare, and robust discovery of these requires both large-scale DNA sequencing and data sharing. Here we describe a GeneMatcher collaboration which led to a cohort of 13 affected individuals harboring protein-altering variants, 11 of which are de novo, in MED13; the only inherited variant was transmitted to an affected child from an affected mother. All patients had intellectual disability and/or developmental delays, including speech delays or disorders. Other features that were reported in two or more patients include autism spectrum disorder, attention deficit hyperactivity disorder, optic nerve abnormalities, Duane anomaly, hypotonia, mild congenital heart abnormalities, and dysmorphisms. Six affected individuals had mutations that are predicted to truncate the MED13 protein, six had missense mutations, and one had an in-frame-deletion of one amino acid. Out of the seven non-truncating mutations, six clustered in two specific locations of the MED13 protein: an N-terminal and C-terminal region. The four N-terminal clustering mutations affect two adjacent amino acids that are known to be involved in MED13 ubiquitination and degradation, p.Thr326 and p.Pro327. MED13 is a component of the CDK8-kinase module that can reversibly bind Mediator, a multi-protein complex that is required for Polymerase II transcription initiation. Mutations in several other genes encoding subunits of Mediator have been previously shown to associate with DD/ID, including MED13L, a paralog of MED13. Thus, our findings add MED13 to the group of CDK8-kinase module-associated disease genes

Abstract

Do we mentally simulate olfactory information? We investigated mental simulation of odors and sounds in two experiments. Participants retained a word while they smelled an odor or heard a sound, then rated odor/sound intensity and recalled the word. Later odor/sound recognition was also tested, and pleasantness and familiarity judgments were collected. Word recall was slower when the sound and sound-word mismatched (e.g., bee sound with the word typhoon). Sound recognition was higher when sounds were paired with a match or near-match word (e.g., bee sound with bee or buzzer). This indicates sound-words are mentally simulated. However, using the same paradigm no memory effects were observed for odor. Instead it appears odor-words only affect lexical-semantic representations, demonstrated by higher ratings of odor intensity and pleasantness when an odor was paired with a match or near-match word (e.g., peach odor with peach or mango). These results suggest fundamental differences in how odor and sound-words are represented.

Abstract

Olfaction is often considered a vestigial sense in humans, demoted throughout evolution to make way for the dominant sense of vision. This perspective on olfaction is reflected in how we think and talk about smells in the West, with odor imagery and odor language reported to be difficult. In the present study we demonstrate odor cognition is superior in odor-color synaesthesia, where there are additional sensory connections to odor concepts. Synaesthesia is a neurological phenomenon in which input in 1 modality leads to involuntary perceptual associations. Semantic accounts of synaesthesia posit synaesthetic associations are mediated by activation of inducing concepts. Therefore, synaesthetic associations may strengthen conceptual representations. To test this idea, we ran 6 odor-color synaesthetes and 17 matched controls on a battery of tasks exploring odor and color cognition. We found synaesthetes outperformed controls on tests of both odor and color discrimination, demonstrating for the first time enhanced perception in both the inducer (odor) and concurrent (color) modality. So, not only do synaesthetes have additional perceptual experiences in comparison to controls, their primary perceptual experience is also different. Finally, synaesthetes were more consistent and accurate at naming odors. We propose synaesthetic associations to odors strengthen odor concepts, making them more differentiated (facilitating odor discrimination) and easier to link with lexical representations (facilitating odor naming). In summary, we show for the first time that both odor language and perception is enhanced in people with synaesthetic associations to odors

Abstract

Two word-by-word, self-paced reading experiments investigated the speed with which readers were sensitive to discourse-level anomalies. An account arguing for delayed sensitivity (Guzman & Klin, 2000 Guzman, A. E. and Klin, C. M. 2000. Maintaining global coherence in reading: The role of sentence boundaries.. Memory & Cognition, 28: 722–730. [PubMed], [Web of Science ®], [Google Scholar]) was contrasted with one allowing for rapid sensitivity (Myers & O'Brien, 1998 Myers, J. L. and O'Brien, E. J. 1998. Accessing the discourse representation during reading.. Discourse Processes, 26: 131–157. [Taylor & Francis Online], [Web of Science ®], [Google Scholar]). Anomalies related to spatial information (Experiment 1) and character-attribute information (Experiment 2) were examined. Both experiments found that readers displayed rapid sensitivity to the anomalous information. A reading time penalty was observed for the region of text containing the anomalous information. This finding is most compatible with an account of text processing whereby incoming words are rapidly evaluated with respect to prior context. They are not consistent with an account that argues for delayed integration. Results are discussed in light of their implications for competing models of text processing.

Abstract

The ability to represent conditional information is central to human cognition. In two self-paced reading experiments we investigated how readers process counterfactual conditionals (e.g., If Darren had been athletic, he could probably have played on the rugby team ) and indicative conditionals (e.g., If Darren is athletic, he probably plays on the rugby team ). In Experiment 1 we focused on how readers process counterfactual conditional sentences. We found that processing of the antecedent of counterfactual conditionals was rapidly constrained by prior context (i.e., knowing whether Darren was or was not athletic). A reading-time penalty was observed for the critical region of text comprising the last word of the antecedent and the first word of the consequent when the information in the antecedent did not fit with prior context. In Experiment 2 we contrasted counterfactual conditionals with indicative conditionals. For counterfactual conditionals we found the same effect on the critical region as we found in Experiment 1. In contrast, however, we found no evidence that processing of the antecedent of indicative conditionals was constrained by prior context. For indicative conditionals (but not for counterfactual conditionals), the results we report are consistent with the suppositional account of conditionals. We propose that current theories of conditionals need to be able to account for online processing differences between indicative and counterfactual conditionals

Abstract

Informal verbal interaction is the core matrix for human social life. A mechanism for coordinating this basic mode of interaction is a system of turn-taking that regulates who is to speak and when. Yet relatively little is known about how this system varies across cultures. The anthropological literature reports significant cultural differences in the timing of turn-taking in ordinary conversation. We test these claims and show that in fact there are striking universals in the underlying pattern of response latency in conversation. Using a worldwide sample of 10 languages drawn from traditional indigenous communities to major world languages, we show that all of the languages tested provide clear evidence for a general avoidance of overlapping talk and a minimization of silence between conversational turns. In addition, all of the languages show the same factors explaining within-language variation in speed of response. We do, however, find differences across the languages in the average gap between turns, within a range of 250 ms from the cross-language mean. We believe that a natural sensitivity to these tempo differences leads to a subjective perception of dramatic or even fundamental differences as offered in ethnographic reports of conversational style. Our empirical evidence suggests robust human universals in this domain, where local variations are quantitative only, pointing to a single shared infrastructure for language use with likely ethological foundations.

Abstract

This study assesses the effects of age and language exposure on VOT production in 29 simultaneous bilingual children aged 3;7 to 5;11 who speak German as a heritage language in the Netherlands. Dutch and German have a binary voicing contrast, but the contrast is implemented with different VOT values in the two languages. The results suggest that bilingual children produce ‘voiced’ plosives similarly in their two languages, and these productions are not monolingual-like in either language. Bidirectional cross-linguistic influence between Dutch and German can explain these results. Yet, the bilinguals seemingly have two autonomous categories for Dutch and German ‘voiceless’ plosives. In German, the bilinguals’ aspiration is not monolingual-like, but bilinguals with more heritage language exposure produce more target-like aspiration. Importantly, the amount of exposure to German has no effect on the majority language's ‘voiceless’ category. This implies that more heritage language exposure is associated with more language-specific voicing systems.

Abstract

Human intracranial electroencephalography (iEEG) recordings provide data with much greater spatiotemporal precision
than is possible from data obtained using scalp EEG, magnetoencephalography (MEG), or functional MRI. Until recently,
the fusion of anatomical data (MRI and computed tomography (CT) images) with electrophysiological data and their
subsequent analysis have required the use of technologically and conceptually challenging combinations of software.
Here, we describe a comprehensive protocol that enables complex raw human iEEG data to be converted into more readily
comprehensible illustrative representations. The protocol uses an open-source toolbox for electrophysiological data
analysis (FieldTrip). This allows iEEG researchers to build on a continuously growing body of scriptable and reproducible
analysis methods that, over the past decade, have been developed and used by a large research community. In this
protocol, we describe how to analyze complex iEEG datasets by providing an intuitive and rapid approach that can handle
both neuroanatomical information and large electrophysiological datasets. We provide a worked example using
an example dataset. We also explain how to automate the protocol and adjust the settings to enable analysis of
iEEG datasets with other characteristics. The protocol can be implemented by a graduate student or postdoctoral
fellow with minimal MATLAB experience and takes approximately an hour to execute, excluding the automated cortical
surface extraction.

Abstract

As participants repeatedly interact using graphical signals (as in a game of Pictionary), the signals gradually shift from being iconic (or motivated) to being symbolic (or arbitrary). The aim here is to test experimentally whether this change in the form of the signal implies a concomitant shift in the inferential mechanisms needed to understand it. The results show that, during early, iconic stages, there is more reliance on creative inferential processes associated with insight problem solving, and that the recruitment of these cognitive mechanisms decreases over time. The variation in inferential mechanism is not predicted by the sign’s visual complexity or iconicity, but by its familiarity, and by the complexity of the relevant mental representations. The discussion explores implications for pragmatics, language evolution, and iconicity research.

Abstract

Five word-spotting experiments explored the role of consonantal and vocalic phonotactic cues in the segmentation of spoken Italian. The first set of experiments tested listeners' sensitivity to phonotactic constraints cueing syllable boundaries. Participants were slower in spotting words in nonsense strings when target onsets were misaligned (e.g., lago in ri.blago) than when they were aligned (e.g., lago in rin.lago) with phonotactically determined syllabic boundaries. This effect held also for sequences that occur only word-medially (e.g., /tl/ in ri.tlago), and competition effects could not account for the disadvantage in the misaligned condition. Similarly, target detections were slower when their offsets were misaligned (e.g., cittaacute in cittaacuteu.ba) than when they were aligned (e.g., cittaacute in cittaacute.oba) with a phonotactic syllabic boundary. The second set of experiments tested listeners' sensitivity to phonotactic cues, which specifically signal lexical (and not just syllable) boundaries. Results corroborate the role of syllabic information in speech segmentation and suggest that Italian listeners make little use of additional phonotactic information that specifically cues word boundaries.

Abstract

Two cross-modal priming experiments tested whether lexical access is constrained by syllabic structure in Italian. Results extend the available Italian data on the processing of stressed syllables showing that syllabic information restricts the set of candidates to those structurally consistent with the intended word (Experiment 1). Lexical access, however, takes place as soon as possible and it is not delayed till the incoming input corresponds to the first syllable of the word. And, the initial activated set includes candidates whose syllabic structure does not match the intended word (Experiment 2). The present data challenge the early hypothesis that in Romance languages syllables are the units for lexical access during spoken word recognition. The implications of the results for our understanding of the role of syllabic information in language processing are discussed.

Abstract

We investigate the emergence of iconicity, specifically a bouba-kiki effect in miniature artificial languages under different functional constraints: when the languages are reproduced and when they are used communicatively. We ran transmission chains of (a) participant dyads who played an interactive communicative game and (b) individual participants who played a matched learning game. An analysis of the languages over six generations in an iterated learning experiment revealed that in the Communication condition, but not in the Reproduction condition, words for spiky shapes tend to be rated by naive judges as more spiky than the words for round shapes. This suggests that iconicity may not only be the outcome of innovations introduced by individuals, but, crucially, the result of interlocutor negotiation of new communicative conventions. We interpret our results as an illustration of cultural evolution by random mutation and selection (as opposed to by guided variation).

Abstract

This study examined the role of verbal short-term memory (STM) and executive function (EF) underlying semantic and syntactic interference resolution during sentence comprehension for persons with aphasia (PWA) with varying degrees of STM and EF deficits. Semantic interference was manipulated by varying the semantic plausibility of the intervening NP as subject of the verb and syntactic interference was manipulated by varying whether the NP was another subject or an object. Nine PWA were assessed on sentence reading times and on comprehension question performance. PWA showed exaggerated semantic and syntactic interference effects relative to healthy age-matched control subjects. Importantly, correlational analyses showed that while answering comprehension questions, PWA’ semantic STM capacity related to their ability to resolve semantic but not syntactic interference. In contrast, PWA’ EF abilities related to their ability to resolve syntactic but not semantic interference. Phonological STM deficits were not related to the ability to resolve either type of interference. The results for semantic STM are consistent with prior findings indicating a role for semantic but not phonological STM in sentence comprehension, specifically with regard to maintaining semantic information prior to integration. The results for syntactic interference are consistent with the recent findings suggesting that EF is critical for syntactic processing.

Abstract

Bats are unique among mammals, possessing some of the rarest mammalian adaptations, including true self-powered flight, laryngeal echolocation, exceptional longevity, unique immunity, contracted genomes, and vocal learning. They provide key ecosystem services, pollinating tropical plants, dispersing seeds, and controlling insect pest populations, thus driving healthy ecosystems. They account for more than 20% of all living mammalian diversity, and their crown-group evolutionary history dates back to the Eocene. Despite their great numbers and diversity, many species are threatened and endangered. Here we announce Bat1K, an initiative to sequence the genomes of all living bat species (n∼1,300) to chromosome-level assembly. The Bat1K genome consortium unites bat biologists (>132 members as of writing), computational scientists, conservation organizations, genome technologists, and any interested individuals committed to a better understanding of the genetic and evolutionary mechanisms that underlie the unique adaptations of bats. Our aim is to catalog the unique genetic diversity present in all living bats to better understand the molecular basis of their unique adaptations; uncover their evolutionary history; link genotype with phenotype; and ultimately better understand, promote, and conserve bats. Here we review the unique adaptations of bats and highlight how chromosome-level genome assemblies can uncover the molecular basis of these traits. We present a novel sequencing and assembly strategy and review the striking societal and scientific benefits that will result from the Bat1K initiative.

Abstract

Difficulties with pragmatic aspects of communication are universal across individuals with autism spectrum disorders (ASDs). Here we focused on an aspect of pragmatic language comprehension that is relevant to social interaction in daily life: the integration of speaker characteristics inferred from the voice with the content of a message. Using functional magnetic resonance imaging (fMRI), we examined the neural correlates of the integration of voice-based inferences about the speaker’s age, gender or social background, and sentence content in adults with ASD and matched control participants. Relative to the control group, the ASD group showed increased activation in right inferior frontal gyrus (RIFG; Brodmann area 47) for speakerincongruent sentences compared to speaker-congruent sentences. Given that both groups performed behaviourally at a similar level on a debriefing interview outside the scanner, the increased activation in RIFG for the ASD group was interpreted as being compensatory in nature. It presumably reflects spill-over processing from the language dominant left hemisphere due to higher task demands faced by the participants with ASD when integrating speaker characteristics and the content of a spoken sentence. Furthermore, only the control group showed decreased activation for speaker-incongruent relative to speaker-congruent sentences in right ventral medial prefrontal cortex (vMPFC; Brodmann area 10), including right anterior cingulate cortex (ACC; Brodmann area 24/32). Since vMPFC is involved in self-referential processing related to judgments and inferences about self and others, the absence of such a modulation in vMPFC activation in the ASD group possibly points to atypical default self-referential mental activity in ASD. Our results show that in ASD compensatory mechanisms are necessary in implicit, low-level inferential processes in spoken language understanding. This indicates that pragmatic language problems in ASD are not restricted to high-level inferential processes, but encompass the most basic aspects of pragmatic language processing.

Abstract

When interpreting a message, a listener takes into account several sources of linguistic and extralinguistic information. Here we focused on one particular form of extralinguistic information, certain speaker characteristics as conveyed by the voice. Using functional magnetic resonance imaging, we examined the neural structures involved in the unification of sentence meaning and voice-based inferences about the speaker's age, sex, or social background. We found enhanced activation in the inferior frontal gyrus bilaterally (BA 45/47) during listening to sentences whose meaning was incongruent with inferred speaker characteristics. Furthermore, our results showed an overlap in brain regions involved in unification of speaker-related information and those used for the unification of semantic and world knowledge information [inferior frontal gyrus bilaterally (BA 45/47) and left middle temporal gyrus (BA 21)]. These findings provide evidence for a shared neural unification system for linguistic and extralinguistic sources of information and extend the existing knowledge about the role of inferior frontal cortex as a crucial component for unification during language comprehension.

Abstract

Purpose: The question of how and when English-speaking children acquire auxiliaries is the subject of extensive debate. Some researchers posit the existence of innately given Universal Grammar principles to guide acquisition, although some aspects of the auxiliary system must be learned from the input. Others suggest that auxiliaries can be learned without Universal Grammar, citing evidence of piecemeal learning in their support. This study represents a unique attempt to trace the development of auxiliary syntax by using a longitudinal elicitation methodology. Method: Twelve English-speaking children participated in 3 tasks designed to elicit auxiliary BE in declaratives and yes/no and wh-questions. They completed each task 6 times in total between the ages of 2;10 (years;months) and 3;6. Results: The children’s levels of correct use of 2 forms of BE (is,are) differed according to auxiliary form and sentence structure, and these relations changed over development. An analysis of the children’s errors also revealed complex interactions between these factors. Conclusion: These data are problematic for existing accounts of auxiliary acquisition and highlight the need for researchers working within both generativist and constructivist frameworks to develop more detailed theories of acquisition that directly predict the pattern of acquisition observed.

Abstract

Establishing non-native phoneme categories can be a notoriously difficult endeavour—in both speech perception and speech production. This study asks how these two domains interact in the course of this learning process. It investigates the effect of perceptual learning and related production practice of a challenging non-native category on the perception and/or production of that category. A four-day perceptual training protocol on the British English /æ/-/ɛ/ vowel contrast was combined with either related or unrelated production practice. After feedback on perceptual categorisation of the contrast, native Dutch participants in the related production group (N = 19) pronounced the trial's correct answer, while participants in the unrelated production group (N = 19) pronounced similar but phonologically unrelated words. Comparison of pre- and post-tests showed significant improvement over the course of training in both perception and production, but no differences between the groups were found. The lack of an effect of production practice is discussed in the light of previous, competing results and models of second-language speech perception and production. This study confirms that, even in the context of related production practice, perceptual training boosts production learning.

Abstract

The way top-down and bottom-up processes interact to shape our perception and behaviour is a fundamental question and remains highly controversial. How early in a processing stream do such interactions occur, and what factors govern such interactions? The degree of abstractness of a perceptual attribute (for example, orientation versus shape in vision, or loudness versus sound identity in hearing) may determine the locus of neural processing and interaction between bottom-up and internal information. Using an imagery-perception repetition paradigm, we find that imagined speech affects subsequent auditory perception, even for a low-level attribute such as loudness. This effect is observed in early auditory responses in magnetoencephalography and electroencephalography that correlate with behavioural loudness ratings. The results suggest that the internal reconstruction of neural representations without external stimulation is flexibly regulated by task demands, and that such top-down processes can interact with bottom-up information at an early perceptual stage to modulate perception.

Abstract

Synesthesia is a rare nonpathological phenomenon where stimulation of one sense automatically provokes a secondary perception in another. Hypothesized to result from differences in cortical wiring during development, synesthetes show atypical structural and functional neural connectivity, but the underlying molecular mechanisms are unknown. The trait also appears to be more common among people with autism spectrum disorder and savant abilities. Previous linkage studies searching for shared loci of large effect size across multiple families have had limited success. To address the critical lack of candidate genes, we applied whole-exome sequencing to three families with sound–color (auditory–visual) synesthesia affecting multiple relatives across three or more generations. We identified rare genetic variants that fully cosegregate with synesthesia in each family, uncovering 37 genes of interest. Consistent with reports indicating genetic heterogeneity, no variants were shared across families. Gene ontology analyses highlighted six genes—COL4A1, ITGA2, MYO10, ROBO3, SLC9A6, and SLIT2—associated with axonogenesis and expressed during early childhood when synesthetic associations are formed. These results are consistent with neuroimaging-based hypotheses about the role of hyperconnectivity in the etiology of synesthesia and offer a potential entry point into the neurobiology that organizes our sensory experiences.

Abstract

Peak bone mass achieved in adolescence is a determinant of bone mass in later life. In order to identify genetic variants affecting bone mineral density (BMD), we performed a genome-wide association study of BMD and related traits in 1518 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). We compared results with a scan of 134 adults with high or low hip BMD. We identified associations with BMD in an area of chromosome 12 containing the Osterix (SP7) locus, a transcription factor responsible for regulating osteoblast differentiation (ALSPAC: P = 5.8 x 10(-4); Australia: P = 3.7 x 10(-4)). This region has previously shown evidence of association with adult hip and lumbar spine BMD in an Icelandic population, as well as nominal association in a UK population. A meta-analysis of these existing studies revealed strong association between SNPs in the Osterix region and adult lumbar spine BMD (P = 9.9 x 10(-11)). In light of these findings, we genotyped a further 3692 individuals from ALSPAC who had whole body BMD and confirmed the association in children as well (P = 5.4 x 10(-5)). Moreover, all SNPs were related to height in ALSPAC children, but not weight or body mass index, and when height was included as a covariate in the regression equation, the association with total body BMD was attenuated. We conclude that genetic variants in the region of Osterix are associated with BMD in children and adults probably through primary effects on growth.

Abstract

This paper explores phrase-length-related alternations in the association of tones to positions in metrical structure in two melodic constructions of Spanish. An imitation-and-completion task eliciting (a) the low–falling–rising contour and (b) the circumflex contour on intonation phrases (IPs) of one, two, and three prosodic words revealed that, although the focus structure and pragmatic context is constant across conditions, phrases containing one prosodic word differ in their nuclear (i.e. final) pitch accents and edge tones from phrases containing more than one prosodic word. For contour (a), short intonation phrases (e.g. [ Ma no lo ] IP ) were produced with a low accent followed by a high edge tone (L ∗ H% in ToBI notation), whereas longer phrases (e.g. [ El her ma no de la a m igadeMa no lo ] IP ‘Manolo’s friend’s brother’) had a low accent on the first stressed syllable, a rising accent on the last stressed syllable, and a low edge tone (L ∗ L+H ∗ L%). For contour (b), short phrases were produced with a high–rise (L+H ∗ ¡H%), whereas longer phrases were produced with an initial accentual rise followed by an upstepped rise–fall (L+H ∗ ¡H ∗ L%). These findings imply that the common practice of describing the structure of intonation contours as consisting of a constant nuclear pitch accent and following edge tone is not adequate for modeling Spanish intonation. To capture the observed melodic alternations, we argue for clearer separation between tones and metrical structure, whereby intonational tones do not necessarily have an intrinsic culminative or delimitative function (i.e. as pitch accents or as edge tones). Instead, this function results from melody-specific principles of tonal–metrical association.

Abstract

Bilingual children with reduced exposure to one or both languages may have language profiles that are
apparently similar to those of children with developmental language disorder (DLD). Children with
DLD receive enough input, but have difficulty using this input for acquisition due to processing deficits.
The present investigation aims to determine aspects of adjective production that are differentially
affected by reduced input (in bilingualism) and reduced intake (in DLD). Adjectives were elicited
from Dutch–Russian simultaneous bilinguals with limited exposure to Russian and Russian-speaking
monolinguals with andwithout DLD.Anantonymelicitation taskwas used to assess the size of adjective
vocabularies, and a degree task was employed to compare the preferences of the three groups in the
use of morphological, lexical, and syntactic degree markers. The results revealed that adjective–noun
agreement is affected to the same extent by both reduced input and reduced intake. The size of adjective
lexicons is also negatively affected by both, but more so by reduced exposure. However, production
of morphological degree markers and learning of semantic paradigms are areas of relative strength in
which bilinguals outperform monolingual children with DLD.We suggest that reduced input might be
counterbalanced by linguistic and cognitive advantages of bilingualism

Abstract

When we comprehend language, we often do this in rich settings in which we can use many cues to understand what someone is saying. However, it has traditionally been difficult to design experiments with rich three-dimensional contexts that resemble our everyday environments, while maintaining control over the linguistic and non-linguistic information that is available. Here we test the validity of combining electroencephalography (EEG) and Virtual Reality (VR) to overcome this problem. We recorded electrophysiological brain activity during language processing in a well-controlled three-dimensional virtual audiovisual environment. Participants were immersed in a virtual restaurant, while wearing EEG equipment. In the restaurant participants encountered virtual restaurant guests. Each guest was seated at a separate table with an object on it (e.g. a plate with salmon). The restaurant guest would then produce a sentence (e.g. “I just ordered this salmon.”). The noun in the spoken sentence could either match (“salmon”) or mismatch (“pasta”) with the object on the table, creating a situation in which the auditory information was either appropriate or inappropriate in the visual context. We observed a reliable N400 effect as a consequence of the mismatch. This finding validates the combined use of VR and EEG as a tool to study the neurophysiological mechanisms of everyday language comprehension in rich, ecologically valid settings.

Abstract

Narrative fiction may invite us to share the perspective of characters which are very much unlike ourselves. Inanimate objects featuring as protagonists or narrators are an extreme example of this. The way readers experience these characters was examined by means of a narrative immersion study. Participants (N = 200) judged narratives containing animate or inanimate characters in predominantly Agent or Experiencer roles. Narratives with inanimate characters were judged to be less emotionally engaging. This effect was influenced by the dominant thematic role associated with the character: inanimate Agents led to more defamiliarization compared to their animate counterparts than inanimate Experiencers. I argue for an integrated account of thematic roles and animacy in literary experience and linguistics in general.

Abstract

We show by means of a corpus study that the language used by the inanimate first person narrator in the novel Specht en zoon deviates from what we would expect on the basis of the fact that the narrator is inanimate, but at the same time also differsfrom the language of a human narrator in the novel De wijde blik on several linguistic dimensions. Whereas the human narrator is associated strongly with action verbs, preferring the Agent role, the inanimate narrator is much more limited to the Experiencer role, predominantly associated with cognition and sensory verbs. Our results show that animacy as a linguistic concept may be refined by taking into account the myriad ways in which an entity’s conceptual animacy may be expressed: we accept the conceptual animacy of the inanimate narrator despite its inability to act on its environment, showing this need not be a requirement for animacy

Abstract

Actions may be used to directly act on the world around us, or as a means of communication. Effective communication requires the addressee to recognize the act as being communicative. Humans are sensitive to ostensive communicative cues, such as direct eye gaze (Csibra & Gergely, 2009). However, there may be additional cues present in the action or gesture itself. Here we investigate features that characterize the initiation of a communicative interaction in both production and comprehension.

We asked 40 participants to perform 31 pairs of object-directed actions and representational gestures in more- or less- communicative contexts. Data were collected using motion capture technology for kinematics and video recording for eye-gaze. With these data, we focused on two issues. First, if and how actions and gestures are systematically modulated when performed in a communicative context. Second, if observers exploit such kinematic information to classify an act as communicative.

Our study showed that during production the communicative context modulates space–time dimensions of kinematics and elicits an increase in addressee-directed eye-gaze. Naïve participants detected communicative intent in actions and gestures preferentially using eye-gaze information, only utilizing kinematic information when eye-gaze was unavailable.

Our study highlights the general communicative modulation of action and gesture kinematics during production but also shows that addressees only exploit this modulation to recognize communicative intention in the absence of eye-gaze. We discuss these findings in terms of distinctive but potentially overlapping functions of addressee directed eye-gaze and kinematic modulations within the wider context of human communication and learning.

Abstract

Two artificial-language learning experiments directly compared English, French, and Dutch listeners’ use of suprasegmental cues for continuous-speech segmentation. In both experiments, listeners heard unbroken sequences of consonant-vowel syllables, composed of recurring three- and four-syllable “words.” These words were demarcated by(a) no cue other than transitional probabilities induced by their recurrence, (b) a consistent left-edge cue, or (c) a consistent right-edge cue. Experiment 1 examined a vowel lengthening cue. All three listener groups benefited from this cue in right-edge position; none benefited from it in left-edge position. Experiment 2 examined a pitch-movement cue. English listeners used this cue in left-edge position, French listeners used it in right-edge position, and Dutch listeners used it in both positions. These findings are interpreted as evidence of both language-universal and language-specific effects. Final lengthening is a language-universal effect expressing a more general (non-linguistic) mechanism. Pitch movement expresses prominence which has characteristically different placements across languages: typically at right edges in French, but at left edges in English and Dutch. Finally, stress realization in English versus Dutch encourages greater attention to suprasegmental variation by Dutch than by English listeners, allowing Dutch listeners to benefit from an informative pitch-movement cue even in an uncharacteristic position.

Abstract

Synapse development and neuronal activity represent fundamental processes for the establishment of cognitive function. Structural organization as well as signalling pathways from receptor stimulation to gene expression regulation are mediated by synaptic activity and misregulated in neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). Deleterious mutations in the PTCHD1 (Patched domain containing 1) gene have been described in male patients with X-linked ID and/or ASD. The structure of PTCHD1 protein is similar to the Patched (PTCH1) receptor; however, the cellular mechanisms and pathways associated with PTCHD1 in the developing brain are poorly determined. Here we show that PTCHD1 displays a C-terminal PDZ-binding motif that binds to the postsynaptic proteins PSD95 and SAP102. We also report that PTCHD1 is unable to rescue the canonical sonic hedgehog (SHH) pathway in cells depleted of PTCH1, suggesting that both proteins are involved in distinct cellular signalling pathways. We find that Ptchd1 deficiency in male mice (Ptchd1−/y) induces global changes in synaptic gene expression, affects the expression of the immediate-early expression genes Egr1 and Npas4 and finally impairs excitatory synaptic structure and neuronal excitatory activity in the hippocampus, leading to cognitive dysfunction, motor disabilities and hyperactivity. Thus our results support that PTCHD1 deficiency induces a neurodevelopmental disorder causing excitatory synaptic dysfunction.

Abstract

Perceptual and sensorimotor timing skills can be thoroughly assessed with the Battery for the Assessment of Auditory Sensorimotor and Timing Abilities (BAASTA). The battery has been used for testing rhythmic skills in healthy adults and patient populations (e.g., with Parkinson disease), showing sensitivity to timing and rhythm deficits. Here we assessed the test-retest reliability of the BAASTA in 20 healthy adults. Participants were tested twice with the BAASTA, implemented on a tablet interface, with a 2-week interval. They completed 4 perceptual tasks, namely, duration discrimination, anisochrony detection with tones and music, and the Beat Alignment Test (BAT). Moreover, they completed motor tasks via finger tapping, including unpaced and paced tapping with tones and music, synchronization-continuation, and adaptive tapping to a sequence with a tempo change. Despite high variability among individuals, the results showed good test-retest reliability in most tasks. A slight but significant improvement from test to retest was found in tapping with music, which may reflect a learning effect. In general, the BAASTA was found a reliable tool for evaluating timing and rhythm skills.

Abstract

How does the brain respond to statements that clash with a person's value system? We recorded event-related brain potentials while respondents from contrasting political-ethical backgrounds completed an attitude survey on drugs, medical ethics, social conduct, and other issues. Our results show that value-based disagreement is unlocked by language extremely rapidly, within 200 to 250 ms after the first word that indicates a clash with the reader's value system (e.g., "I think euthanasia is an acceptable/unacceptable…"). Furthermore, strong disagreement rapidly influences the ongoing analysis of meaning, which indicates that even very early processes in language comprehension are sensitive to a person's value system. Our results testify to rapid reciprocal links between neural systems for language and for valuation.

Abstract

Learning new vocabulary from context typically requires multiple encounters during which word meaning can be retrieved from memory or inferred from context. We compared the effect of memory retrieval and context inferences on short‐ and long‐term retention in three experiments. Participants studied novel words and then practiced the words either in an uninformative context that required the retrieval of word meaning from memory (“I need the funguo”) or in an informative context from which word meaning could be inferred (“I want to unlock the door: I need the funguo”). The informative context facilitated word comprehension during practice. However, later recall of word form and meaning and word recognition in a new context were better after successful retrieval practice and retrieval practice with feedback than after context‐inference practice. These findings suggest benefits of retrieval during contextualized vocabulary learning whereby the uninformative context enhanced word retention by triggering memory retrieval.

Abstract

An essential phenomenon in the development towards syntactic maturity after early childhood is the increasing use of so-called sentence-combining transformations. Especially by using subordination, complex sentences are produced. The research reported here is an attempt to arrive at a more adequate characterization and explanation. Our starting point was an analysis of 280 texts written by Dutch-speaking pupils of the two highest grades of the primary school and the four lowest grades of three different types of secondary education. It was examined whether systematic shifts in the use of certain groups of so-called function words could be traced. We concluded that the development of the syntactic formulating ability can be characterized as an increase in connectivity: the use of all kinds of function words which explicitly mark logico-semantic relations between propositions. This development starts by inserting special adverbs and coordinating conjunctions resulting in various types of coordination. In a later stage, the syntactic patterning of the sentence is affected as well (various types of subordination). The increase in sentence complexity is only one aspect of the entire development. An explanation for the increase in connectivity is offered based upon a distinction between narrative and expository language use. The latter, but not the former, is characterized by frequent occurrence of connectives. The development in syntactic formulating ability includes a high level of skill in expository language use. Speed of development is determined by intensity of training, e.g. in scholastic and occupational settings.

Abstract

Heterozygous mutations of the Forkhead-box protein 2 (FOXP2) gene in humans cause childhood apraxia of speech. Loss of Foxp2 in mice is known to affect striatal development and impair motor skills. However, it is unknown if striatal excitatory/inhibitory balance is affected during development and if the imbalance persists into adulthood. We investigated the effect of reduced Foxp2 expression, via a loss-of-function mutation, on striatal medium spiny neurons (MSNs). Our data show that heterozygous loss of Foxp2 decreases excitatory (AMPA receptor-mediated) and increases inhibitory (GABA receptor-mediated) currents in D1 dopamine receptor positive MSNs of juvenile and adult mice. Furthermore, reduced Foxp2 expression increases GAD67 expression, leading to both increased presynaptic content and release of GABA. Finally, pharmacological blockade of inhibitory activity in vivo partially rescues motor skill learning deficits in heterozygous Foxp2 mice. Our results suggest a novel role for Foxp2 in the regulation of striatal direct pathway activity through managing inhibitory drive.

Abstract

Interpersonal discourse particles (DPs), such as Dutch inderdaad (≈‘indeed’) and eigenlijk (≈‘actually’) are highly frequent in everyday conversational interaction. Despite extensive theoretical descriptions of their polyfunctionality, little is known about how they are used by language comprehenders. In two visual world eye-tracking experiments involving an online dialogue completion task, we asked to what extent inderdaad, confirming an inferred expectation, and eigenlijk, contrasting with an inferred expectation, influence real-time understanding of dialogues. Answers in the dialogues contained a DP or a control adverb, and a critical discourse referent was replaced by a beep; participants chose the most likely dialogue completion by clicking on one of four referents in a display. Results show that listeners make rapid and fine-grained situation-specific inferences about the use of DPs, modulating their expectations about how the dialogue will unfold. Findings further specify and constrain theories about the conversation-managing function and polyfunctionality of DPs.

Abstract

In the recent literature, the effects of noninvasive neurostimulation on cognitive functioning appear to lack consistency and replicability. We propose that such effects may be concealed unless dedicated, sensitive, and process-specific dependent measures are used. The expression and subsequent suppression of response capture are often studied using conflict tasks. Response-time distribution analyses have been argued to provide specific measures of the susceptibility to make fast impulsive response errors, as well as the proficiency of the selective suppression of these impulses. These measures of response capture and response inhibition are particularly sensitive to experimental manipulations and clinical deficiencies that are typically obfuscated in commonly used overall performance analyses. Recent work using structural and functional imaging techniques links these behavioral outcome measures to the integrity of frontostriatal networks. These studies suggest that the presupplementary motor area (pre-SMA) is linked to the susceptibility to response capture whereas the right inferior frontal cortex (rIFC) is associated with the selective suppression of action impulses. Here, we used repetitive transcranial magnetic stimulation (rTMS) to test the causal involvement of these two cortical areas in response capture and inhibition in the Simon task. Disruption of rIFC function specifically impaired selective suppression of conflicting action tendencies, whereas the anticipated increase of fast impulsive errors after perturbing pre-SMA function was not confirmed. These results provide a proof of principle of the notion that the selection of appropriate dependent measures is perhaps crucial to establish the effects of neurostimulation on specific cognitive functions.

Abstract

Social information use is a pivotal characteristic of the human species. Avoiding the cost of individual exploration, social learning confers substantial fitness benefits under a wide variety of environmental conditions, especially when the process is governed by biases toward relative superiority (e.g., experts, the majority). Here, we examine the development of social information use in children aged 4–14 years (n = 605) across seven societies in a standardised social learning task. We measured two key aspects of social information use: general reliance on social information and majority preference. We show that the extent to which children rely on social information depends on children’s cultural background. The extent of children’s majority preference also varies cross-culturally, but in contrast to social information use, the ontogeny of majority preference follows a U-shaped trajectory across all societies. Our results demonstrate both cultural continuity and diversity in the realm of human social learning.

Abstract

Meermalen is getracht om syntactische formuleenuuirdigheid direct en objectief te meten aan de hand van gesproken of geschreven teksten. Uitgangspunt hierbij vormde in de regel de syntactische complexiteit van de geproduceerde taaluitingen. Dit heeft echter niet geleid tot een plausibele, duidelijk omschreven en praktisch bruikbare index. N.a.v. een kritische bespreking van de notie complexiteit wordt in dit artikel als nieuw criterium voorgesteld de connectiviteit van de taaluitingen; de expliciete aanduiding van logiscli-scmantische relaties tussen proposities. Connectiviteit is gemakkelijk scoorbaar aan de hand van functiewoorden die verschillende vormen van nevenschikkend en onderschikkend zinsverband markeren. Deze nieuwe index ondetrangt de kritiek die op complexiteit gegeven kon worden, blijkt duidelijk te discrimineren tussen groepen leerlingen die van elkaar verschillen naar leeftijd en opleidingsniveau, en sluit aan bij recente taalpsychologische en sociolinguïstische theorie. Tot besluit worden enige onderwijskundige implicaties aangegeven.

Abstract

Reactive and proactive subtypes of aggression have been recognized to help parse etiological heterogeneity of this complex phenotype. With a heritability of about 50%, genetic factors play a role in the development of aggressive behavior. Imaging studies implicate brain structures related to social behavior in aggression etiology, most notably the amygdala and striatum. This study aimed to gain more insight into the pathways from genetic risk factors for aggression to aggression phenotypes. To this end, we conducted genome-wide gene-based cross-trait meta-analyses of aggression with the volumes of amygdala, nucleus accumbens and caudate nucleus to identify genes influencing both aggression and aggression-related brain volumes. We used data of large-scale genome-wide association studies (GWAS) of: (a) aggressive behavior in children and adolescents (EAGLE, N = 18,988); and (b) Magnetic Resonance Imaging (MRI)-based volume measures of aggression-relevant subcortical brain regions (ENIGMA2, N = 13,171). Second, the identified genes were further investigated in a sample of healthy adults (mean age (SD) = 25.28 (4.62) years; 43% male) who had genome-wide genotyping data and questionnaire data on aggression subtypes available (Brain Imaging Genetics, BIG, N = 501) to study their effect on reactive and proactive subtypes of aggression. Our meta-analysis identified two genes, MECOM and AVPR1A, significantly associated with both aggression risk and nucleus accumbens (MECOM) and amygdala (AVPR1A) brain volume. Subsequent in-depth analysis of these genes in healthy adults (BIG), including sex as an interaction term in the model, revealed no significant subtype-specific gene-wide associations. Using cross-trait meta-analysis of brain measures and psychiatric phenotypes, this study generated new hypotheses about specific links between genes, the brain and behavior. Results indicate that MECOM and AVPR1A may exert an effect on aggression through mechanisms involving nucleus accumbens and amygdala volumes, respectively.

Abstract

Understanding intraspecific variation in sociality is essential for characterizing the flexibility and evolution of social systems, yet its study in nonhuman animals is rare. Here, we investigated whether chimpanzees exhibit population-level differences in sociality that cannot be easily explained by differences in genetics or ecology. We compared social proximity and grooming tendencies across four semiwild populations of chimpanzees living in the same ecological environment over three consecutive years, using both linear mixed models and social network analysis. Results indicated temporally stable, population-level differences in dyadic-level sociality. Moreover, group cohesion measures capturing network characteristics beyond dyadic interactions (clustering, modularity, and social differentiation) showed population-level differences consistent with the dyadic indices. Subsequently, we explored whether the observed intraspecific variation in sociality could be attributed to cultural processes by ruling out alternative sources of variation including the influences of ecology, genetics, and differences in population demographics. We conclude that substantial variation in social behavior exists across neighboring populations of chimpanzees and that this variation is in part shaped by cultural processes.

Abstract

Mixed languages are said to be the result of a process of intertwining (e.g. Bakker & Muysken 1995, Bakker 1997), a regular process in which the grammar of one language is combined with the lexicon of another. However, the outcome of this process differs from language pair to language pair. As far as morphosyntax is concerned, people have discussed these different outcomes and the reasons for them extensively, e.g. Bakker 1997 for Michif, Mous 2003 for Ma’a, Muysken 1997a for Media Lengua and 1997b for Callahuaya. The issue of phonology, however, has not generated a large debate. This paper compares the phonological systems of the mixed languages Media Lengua, Callahuaya, Mednyj Aleut, and Michif. It will be argued that the outcome of the process of intertwining, as far as phonology is concerned, is at least partly determined by the extent to which unmixed phonological domains exist.

Abstract

In natural conversations, words are generally shorter and they often lack segments. It is unclear to what extent such durational and segmental reductions affect word recognition. The present study investigates to what extent reduction in the initial syllable hinders word comprehension, which types of segments listeners mostly rely on, and whether listeners use word duration as a cue in word recognition. We conducted three experiments in Dutch, in which we adapted the gating paradigm to study the comprehension of spontaneously uttered conversational speech by aligning the gates with the edges of consonant clusters or vowels. Participants heard the context and some segmental and/or durational information from reduced target words with unstressed initial syllables. The initial syllable varied in its degree of reduction, and in half of the stimuli the vowel was not clearly present. Participants gave too short answers if they were only provided with durational information from the target words, which shows that listeners are unaware of the reductions that can occur in spontaneous speech. More importantly, listeners required fewer segments to recognize target words if the vowel in the initial syllable was absent. This result strongly suggests that this vowel hardly plays a role in word comprehension, and that its presence may even delay this process. More important are the consonants and the stressed vowel.

Abstract

Insight in the developmental trajectory of the neuroanatomical reading correlates is important to understand related cognitive processes and disorders. In adults, a dual pathway model has been suggested encompassing a dorsal phonological and a ventral orthographic white matter system. This dichotomy seems not present in pre-readers, and the specific role of ventral white matter in reading remains unclear. Therefore, the present longitudinal study investigated the relation between ventral white matter and cognitive processes underlying reading in children with a broad range of reading skills (n = 61). Ventral pathways of the reading network were manually traced using diffusion tractography: the inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF) and uncinate fasciculus (UF). Pathways were examined pre-reading (5–6 years) and after two years of reading acquisition (7–8 years). Dimension reduction for the cognitive measures resulted in one component for pre-reading cognitive measures and a separate phonological and orthographic component for the early reading measures. Regression analyses revealed a relation between the pre-reading cognitive component and bilateral IFOF and left ILF. Interestingly, exclusively the left IFOF was related to the orthographic component, whereas none of the pathways was related to the phonological component. Hence, the left IFOF seems to serve as the lexical reading route, already in the earliest reading stages.

Abstract

Learning often occurs in communicative and collaborative settings, yet almost all research into the neural basis of memory relies on participants encoding and retrieving information on their own. We investigated whether learning linguistic labels in a collaborative context at least partly relies on cognitively and neurally distinct representations, as compared to learning in an individual context. Healthy human participants learned labels for sets of abstract shapes in three different tasks. They came up with labels with another person in a collaborative communication task (collaborative condition), by themselves (individual condition), or were given pre-determined unrelated labels to learn by themselves (arbitrary condition). Immediately after learning, participants retrieved and produced the labels aloud during a communicative task in the MRI scanner. The fMRI results show that the retrieval of collaboratively generated labels as compared to individually learned labels engages brain regions involved in understanding others (mentalizing or theory of mind) and autobiographical memory, including the medial prefrontal cortex, the right temporoparietal junction and the precuneus. This study is the first to show that collaboration during encoding affects the neural networks involved in retrieval.

Abstract

During a post-encoding delay period, the ongoing consolidation of recently acquired memories can suffer interference if the delay period involves encoding of new memories, or sensory stimulation tasks. Interestingly, two recent independent studies suggest that (i) autobiographical thinking also interferes markedly with ongoing consolidation of recently learned wordlist material, while (ii) a 2-Back task might not interfere with ongoing consolidation, possibly due to the suppression of autobiographical thinking. In this study, we directly compare these conditions against a quiet wakeful rest baseline to test whether the promotion (via familiar sound-cues) or suppression (via a 2-Back task) of autobiographical thinking during the post-encoding delay period can affect consolidation of studied wordlists in a negative or a positive way, respectively. Our results successfully replicate previous studies and show a significant interference effect (as compared to the rest condition) when learning is followed by familiar sound-cues that promote autobiographical thinking, whereas no interference effect is observed when learning is followed by the 2-Back task. Results from a post-experimental experience-sampling questionnaire further show significant differences in the degree of autobiographical thinking reported during the three post-encoding periods: highest in the presence of sound-cues and lowest during the 2-Back task. In conclusion, our results suggest that varying levels of autobiographical thought during the post-encoding period may modulate episodic memory consolidation.

Abstract

Despite considerable research interest, it is still an open issue as to how morphologically complex words such as “car+s” are represented and processed in the brain. We studied the neural correlates of the processing of inflected nouns in the morphologically rich Finnish language. Previous behavioral studies in Finnish have yielded a robust inflectional processing cost, i.e., inflected words are harder to recognize than otherwise matched morphologically simple words. Theoretically this effect could stem either from decomposition of inflected words into a stem and a suffix at input level and/or from subsequent recombination at the semantic–syntactic level to arrive at an interpretation of the word. To shed light on this issue, we used magnetoencephalography to reveal the time course and localization of neural effects of morphological structure and frequency of written words. Ten subjects silently read high- and low-frequency Finnish words in inflected and monomorphemic form. Morphological complexity was accompanied by stronger and longerlasting activation of the left superior temporal cortex from 200 ms onwards. Earlier effects of morphology were not found, supporting the view that the well-established behavioral processing cost for inflected words stems from the semantic–syntactic level rather than from early decomposition. Since the effect of morphology was detected throughout the range of word frequencies employed, the majority of inflected Finnish words appears to be represented in decomposed form and only very high-frequency inflected words may acquire full-form representations.

Abstract

In English, Dutch, and other European languages, it is well established that the fundamental phonological unit in word production is the phoneme; in contrast, recent studies have shown that in Chinese it is the (atonal) syllable and in Japanese the mora. The present study investigated whether this cross-language variation in the size of the unit of word production is due to the type of script used in the language (i.e., alphabetic, morphosyllabic, or moraic). Capitalizing on the multiscriptal nature of Japanese, and using the Stroop color naming task, we show that the overlap in the initial mora between the color name and the written distractor facilitates color naming independent of script type. These results confirm the mora as the phonological unit of word production in Japanese, and establish the Stroop color naming task as a useful task for investigating the fundamental (or "proximate") phonological unit used in speech production.

Abstract

This study investigates the acquisition of post-verbal (temporal) adverbials and post-verbal negation in L2 Dutch. It is based on previous findings for L2 French that post-verbal negation poses less of a problem for L2 learners than post-verbal adverbial placement (Hawkins, Towell, Bazergui, Second Language Research 9: 189-233, 1993; Herschensohn, Minimally raising the verb issue: 325-336, Cascadilla Press, 1998). The current data show that, at first sight, Moroccan and Turkish learners of Dutch also have fewer problems with post-verbal negation than with post-verbal adverbials. However, when a distinction is made between different types of adverbials, it seems that this holds for adverbials of position such as 'today' but not for adverbials of contrast such as 'again'. To account for this difference, it is argued that different types of adverbial occupy different positions in the L2 data for reasons of scope marking. Moreover, the placement of adverbials such as 'again' interacts with the acquisition of finiteness marking (resulting in post-verbal placement), while there is no such interaction between adverbials such as 'today' and finiteness marking.

Abstract

TANK-binding kinase 1 (TBK1) loss-of-function (LoF) mutations are known to cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), often combined with memory deficits early in the disease course. We performed targeted resequencing of TBK1 in 1253 early onset Alzheimer's disease (EOAD) patients from 8 European countries to investigate whether pathogenic TBK1 mutations are enriched among patients with clinical diagnosis of EOAD. Variant frequencies were compared against 2117 origin-matched controls. We identified only 1 LoF mutation (p.Thr79del) in a patient clinically diagnosed with Alzheimer's disease and a positive family history of ALS. We did not observe enrichment of rare variants in EOAD patients compared to controls, nor of rare variants affecting NFκB induction. Of 3 common coding variants, rs7486100 showed evidence of association (OR 1.46 [95% CI 1.13–1.9]; p-value 0.01). Homozygous carriers of the risk allele showed reduced expression of TBK1 (p-value 0.03). Our findings are not indicative of a significant role for TBK1 mutations in EOAD. The association between common variants in TBK1, disease risk and reduced TBK1 expression warrants follow-up in FTD/ALS cohorts. © 2017 The Author(s)

Abstract

Over 25 genes are known to affect the risk of developing Alzheimer disease (AD), the most common neurodegenerative dementia. However, mechanistic insights and improved disease management remains limited, due to difficulties in determining the functional consequences of genetic associations. Transcriptomics is increasingly being used to corroborate or enhance interpretation of genetic discoveries. These approaches, which include second and third generation sequencing, single-cell sequencing, and bioinformatics, reveal allele-specific events connecting AD risk genes to expression profiles, and provide converging evidence of pathophysiological pathways underlying AD. Simultaneously, they highlight brain region- and cell-type-specific expression patterns, and alternative splicing events that affect the straightforward relation between a genetic variant and AD, re-emphasizing the need for an integrated approach of genetics and transcriptomics in understanding AD. © 2018 The Authors

Abstract

Neurodevelopmental disorders that disturb speech and language are highly heritable. Isolation of the underlying genetic risk factors has been hampered by complexity of the phenotype and potentially large number of contributing genes. One exception is the identification of rare heterozygous mutations of the FOXP2 gene in a monogenic syndrome characterised by impaired sequencing of articulatory gestures, disrupting speech (developmental verbal dyspraxia, DVD), as well as multiple deficits in expressive and receptive language. The protein encoded by FOXP2 belongs to a divergent subgroup of forkhead-box transcription factors, with a distinctive DNA-binding domain and motifs that mediate hetero- and homodimerisation. FOXP1, the most closely related member of this subgroup, can directly interact with FOXP2 and is co-expressed in neural structures relevant to speech and language disorders. Moreover, investigations of songbird orthologues indicate that combinatorial actions of the two proteins may play important roles in vocal learning, leading to the suggestion that human FOXP1 should be considered a strong candidate for involvement in DVD. Thus, in this study, we screened the entire coding region of FOXP1 (exons and flanking intronic sequence) for nucleotide changes in a panel of probands used earlier to detect novel mutations in FOXP2. A non-synonymous coding change was identified in a single proband, yielding a proline-to-alanine change (P215A). However, this was also found in a random control sample. Analyses of non-coding SNP changes did not find any correlation with affection status. We conclude that FOXP1 mutations are unlikely to represent a major cause of DVD.

Abstract

Childhood syndromes disturbing language development are common and display high degrees of heritability. In most cases, the underlying genetic architecture is likely to be complex, involving multiple chromosomal loci and substantial heterogeneity, which makes it difficult to track down the crucial genomic risk factors. Investigation of rare Mendelian phenotypes offers a complementary route for unravelling key neurogenetic pathways. The value of this approach is illustrated by the discovery that heterozygous FOXP2 (where FOX is forkhead box) mutations cause an unusual monogenic disorder, characterized by problems with articulating speech along with deficits in expressive and receptive language. FOXP2 encodes a regulatory protein, belonging to the forkhead box family of transcription factors, known to play important roles in modulating gene expression in development and disease. Functional genetics using human neuronal models suggest that the different FOXP2 isoforms generated by alternative splicing have distinct properties and may act to regulate each other's activity. Such investigations have also analysed the missense and nonsense mutations found in cases of speech and language disorder, showing that they alter intracellular localization, DNA binding and transactivation capacity of the mutated proteins. Moreover, in the brains of mutant mice, aetiological mutations have been found to disrupt the synaptic plasticity of Foxp2-expressing circuitry. Finally, although mutations of FOXP2 itself are rare, the downstream networks which it regulates in the brain appear to be broadly implicated in typical forms of language impairment. Thus, through ongoing identification of regulated targets and interacting co-factors, this gene is providing the first molecular entry points into neural mechanisms that go awry in language-related disorders

Abstract

This study examines the influence of orthography on the processing of reduced word forms. For this purpose, we compared the impact of phonological variation with the impact of spelling-sound consistency on the processing of words that may be produced with or without the vowel schwa. Participants learnt novel French words in which the vowel schwa was present or absent in the first syllable. In Experiment 1, the words were consistently produced without schwa or produced in a variable manner (i.e., sometimes produced with and sometimes produced without schwa). In Experiment 2, words were always produced in a consistent manner, but an orthographic exposure phase was included in which words that were produced without schwa were either spelled with or without the letter . Results from naming and eye-tracking tasks suggest that both phonological variation and spelling-sound consistency influence the processing of spoken novel words. However, the influence of phonological variation outweighs the effect of spelling-sound consistency. Our findings therefore suggest that the influence of orthography on the processing of reduced word forms is relatively small.

Abstract

How do we individuate body parts? Here, we investigated the effect of body segmentation between hand and arm in tactile and visual perception. In a first experiment, we showed that two tactile stimuli felt farther away when they were applied across the wrist than when they were applied within a single body part (palm or forearm), indicating a “category boundary effect”. In the following experiments, we excluded two hypotheses, which attributed tactile segmentation to other, nontactile factors. In Experiment 2, we showed that the boundary effect does not arise from motor cues. The effect was reduced during a motor task involving flexion and extension movements of the wrist joint. Action brings body parts together into functional units, instead of pulling them apart. In Experiments 3 and 4, we showed that the effect does not arise from perceptual cues of visual discontinuities. We did not find any segmentation effect for the visual percept of the body in Experiment 3, nor for a neutral shape in Experiment 4. We suggest that the mental representation of the body is structured in categorical body parts delineated by joints, and that this categorical representation modulates tactile spatial perception.