Publications

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

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

Abstract

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

Bilinguals possess the ability of expressing themselves in more than one language, and typically do so in contextually rich and dynamic settings. Theories and models have indeed long considered context factors to affect bilingual language production in many ways. However, most experimental studies in this domain have failed to fully incorporate linguistic, social, or physical context aspects, let alone combine them in the same study. Indeed, most experimental psycholinguistic research has taken place in isolated and constrained lab settings with carefully selected words or sentences, rather than under rich and naturalistic conditions. We argue that the most influential experimental paradigms in the psycholinguistic study of bilingual language production fall short of capturing the effects of context on language processing and control presupposed by prominent models. This paper therefore aims to enrich the methodological basis for investigating context aspects in current experimental paradigms and thereby move the field of bilingual language production research forward theoretically. After considering extensions of existing paradigms proposed to address context effects, we present three far-ranging innovative proposals, focusing on virtual reality, dialog situations, and multimodality in the context of bilingual language production.

Abstract

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

Abstract

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

Abstract

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

Abstract

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

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

Abstract

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

Abstract

In situated communication, reference to an entity in the shared visual context can be established using eitheranexpression that conveys precise (minimally specified) or redundant (over-specified) information. There is, however, along-lasting debate in psycholinguistics concerningwhether the latter hinders referential processing. We present evidence from an eyetrackingexperiment recordingfixations as well asthe Index of Cognitive Activity –a novel measure of cognitive workload –supporting the view that over-specifications facilitate processing. We further present originalevidence that, above and beyond the effect of specificity,referring expressions thatuniformly reduce referential entropyalso benefitprocessing

Abstract

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

Abstract

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

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

Abstract

Human language is extremely versatile, combining a limited set of signals in an unlimited number of ways. However, it is unknown whether conversational visual signals feed into the composite utterances with which speakers communicate their intentions. We assessed whether different combinations of visual signals lead to different intent interpretations of the same spoken utterance. Participants viewed a virtual avatar uttering spoken questions while producing single visual signals (i.e., head turn, head tilt, eyebrow raise) or combinations of these signals. After each video, participants classified the communicative intention behind the question. We found that composite utterances combining several visual signals conveyed different meaning compared to utterances accompanied by the single visual signals. However, responses to combinations of signals were more similar to the responses to related, rather than unrelated, individual signals, indicating a consistent influence of the individual visual signals on the whole. This study therefore provides first evidence for compositional, non-additive (i.e., Gestalt-like) perception of multimodal language.

Abstract

The natural ecology of language is conversation, with individuals taking turns speaking to communicate in a back-and-forth fashion. Language in this context involves strings of words that a listener must process while simultaneously planning their own next utterance. It would thus be highly advantageous if language users distributed information within an utterance in a way that may facilitate this processing–planning dynamic. While some studies have investigated how information is distributed at the level of single words or clauses, or in written language, little is known about how information is distributed within spoken utterances produced during naturalistic conversation. It also is not known how information distribution patterns of spoken utterances may differ across languages. We used a set of matched corpora (CallHome) containing 898 telephone conversations conducted in six different languages (Arabic, English, German, Japanese, Mandarin, and Spanish), analyzing more than 58,000 utterances, to assess whether there is evidence of distinct patterns of information distributions at the utterance level, and whether these patterns are similar or differed across the languages. We found that English, Spanish, and Mandarin typically show a back-loaded distribution, with higher information (i.e., surprisal) in the last half of utterances compared with the first half, while Arabic, German, and Japanese showed front-loaded distributions, with higher information in the first half compared with the last half. Additional analyses suggest that these patterns may be related to word order and rate of noun and verb usage. We additionally found that back-loaded languages have longer turn transition times (i.e.,time between speaker turns)

Abstract

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

Abstract

The artificial grammar learning (AGL) paradigm enables systematic investigation of the acquisition of linguistically relevant structures. It is a paradigm of interest for language processing research, interfacing with theoretical linguistics, and for comparative research on language acquisition and evolution. This chapter presents a key for understanding major variants of the paradigm. An unbiased summary of neuroimaging findings of AGL is presented, using meta-analytic methods, pointing to the crucial involvement of the bilateral frontal operculum and regions in the right lateral hemisphere. Against a background of robust posterior temporal cortex involvement in processing complex syntax, the evidence for involvement of the posterior temporal cortex in AGL is reviewed. Infant AGL studies testing for neural substrates are reviewed, covering the acquisition of adjacent and non-adjacent dependencies as well as algebraic rules. The language acquisition data suggest that comparisons of learnability of complex grammars performed with adults may now also be possible with children.

Abstract

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

Abstract

Although language depends on storage and composition, just what is stored or (de)composed remains unclear. We leveraged working memory load limitations to test for composition, hypothesizing that decomposed forms should particularly tax working memory. We focused on a well-studied paradigm, English inflectional morphology. We predicted that (compositional) regulars should be harder to maintain in working memory than (non-compositional) irregulars, using a 3-back production task. Frequency, phonology, orthography, and other potentially confounding factors were controlled for. Compared to irregulars, regulars and their accompanying −s/−ing-affixed filler items yielded more errors. Underscoring the decomposition of only regulars, regulars yielded more bare-stem (e.g., walk) and stem affixation errors (walks/walking) than irregulars, whereas irregulars yielded more past-tense-form affixation errors (broughts/tolded). In line with previous evidence that regulars can be stored under certain conditions, the regular-irregular difference held specifically for phonologically consistent (not inconsistent) regulars, in particular for both low and high frequency consistent regulars in males, but only for low frequency consistent regulars in females. Sensitivity analyses suggested the findings were robust. The study further elucidates the computation of inflected forms, and introduces a simple diagnostic for linguistic composition.

Abstract

The human brain deals with the infinite variability of speech through multiple mechanisms. Some of them rely solely on information in the speech input (i.e., signal-driven) whereas some rely on linguistic or real-world knowledge (i.e., knowledge-driven). Many signal-driven perceptual processes rely on the enhancement of acoustic differences between incoming speech sounds, producing contrastive adjustments. For instance, when an ambiguous voiceless fricative is preceded by a high fundamental frequency (f0) sentence, the fricative is perceived as having lower a spectral center of gravity (CoG). However, it is not clear whether knowledge of a talker’s typical f0 can lead to similar contrastive effects. This study investigated a possible talker f0 effect on fricative CoG perception. In the exposure phase, two groups of participants (N=16 each) heard the same talker at high or low f0 for 20 minutes. Later, in the test phase, participants rated fixed-f0 /?ɔk/ tokens as being /sɔk/ (i.e., high CoG) or /ʃɔk/ (i.e., low CoG), where /?/ represents a fricative from a 5-step /s/-/ʃ/ continuum. Surprisingly, the data revealed the opposite of our contrastive hypothesis, whereby hearing high f0 instead biased perception towards high CoG. Thus, we demonstrated that talker f0 information affects fricative CoG perception.

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

Adipose-derived stromal/stem cells (ASC) are multipotent with abilities to differentiate into multiple lineages including connective tissue and neural cells. Despite unlimited opportunity and needs for human and veterinary regenerative medicine, applications of adipose-derived stromal/stem cells are at present very limited. Furthermore, the fundamental biological factors regulating stemness in ASC and their stable differentiation into other tissue cells are not fully understood. The objective of this review was to provide an update on the current knowledge of the nature and isolation, molecular and epigenetic determinants of the potency, and applications of adipose-derived stromal/stem cells, as well as challenges and future directions. The first quarter of the review focuses on the nature of ASC, namely their definition, origin, isolation and sorting methods and multilineage differentiation potential, often with a comparison to mesenchymal stem cells of bone marrow. Due to the indisputable role of epigenetic regulation on cell identities, epigenetic modifications (DNA methylation, chromatin remodeling and microRNAs) are described broadly in stem cells but with a focus on ASC. The final sections provide insights into the current and potential applications of ASC in human and veterinary regenerative medicine.

Abstract

The task of automatic playlist continuation is generating a list of recommended tracks that can be added to an existing playlist. By suggesting appropriate tracks, i. e., songs to add to a playlist, a recommender system can increase the user engagement by making playlist creation easier, as well as extending listening beyond the end of current playlist. The ACM Recommender Systems Challenge 2018 focuses on such task. Spotify released a dataset of playlists, which includes a large number of playlists and associated track listings. Given a set of playlists from which a number of tracks have been withheld, the goal is predicting the missing tracks in those playlists. We participated in the challenge as the team Unconscious Bias and, in this paper, we present our approach. We extend adversarial autoencoders to the problem of automatic playlist continuation. We show how multiple input modalities, such as the playlist titles as well as track titles, artists and albums, can be incorporated in the playlist continuation task.

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

Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.

Abstract

In this paper we investigate acoustic differences between vowels in syllables that do or do not carry lexical stress. In doing so, we concentrated on segmental acoustic phonetic features that are conventionally assumed to differ between stressed and unstressed syllables, viz. Duration, Energy and Spectral Tilt. The speech material in this study differs from the type of material used in previous research: instead of specially constructed sentences we used phonetically rich sentences from the Dutch POLYPHONE corpus. Most of the Duration, Energy and Spectral Tilt features that we used in the investigation show statistically significant differences for the population means of stressed and unstressed vowels. However, it also appears that the distributions overlap to such an extent that automatic detection of stressed and unstressed syllables yields correct classifications of 72.6% at best. It is argued that this result is due to the large variety in the ways in which the abstract linguistic feature `lexical stress' is realized in the acoustic speech signal. Our findings suggest that a lexical stress detector has little use for a single pass decoder in an automatic speech recognition (ASR) system, but could still play a useful role as an additional knowledge source in a multi-pass decoder.

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

The syntactic structure of main and subordinate clauses is determined to a considerable extent by verb biases. For example, some English and Dutch ditransitive verbs have a preference for the prepositional object dative, whereas others are typically used with the double object dative. In this study, we compare the effect of these biases on structure selection in (S)VO and (S)OV dative clauses in the Corpus of Spoken Dutch (CGN). This comparison allowed us to make inferences about the size of the advance planning scope during spontaneous speaking: If the verb is an obligatory component of clause-level advance planning scope, as is claimed by the hypothesis of hierarchical incrementality, then biases should exert their influence on structure choices, regardless of early (VO) or late (OV) position of the verb in the clause. Conversely, if planning proceeds in a piecemeal fashion, strictly guided by lexical availability, as claimed by linear incrementality, then the verb and its associated biases can only influence structure choices in VO sentences. We tested these predictions by analyzing structure choices in the CGN, using mixed logit models. Our results support a combination of linear and hierarchical incrementality, showing a significant influence of verb bias on structure choices in VO, and a weaker (but still significant) effect in OV clauses

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

An event-related brain potentials experiment was carried out to examine the interplay of referential and structural factors during sentence processing in discourse. Subjects read (Dutch) sentences beginning like “David told the girl that … ” in short story contexts that had introduced either one or two referents for a critical singular noun phrase (“the girl”). The waveforms showed that within 280 ms after onset of the critical noun the reader had already determined whether the noun phrase had a unique referent in earlier discourse. Furthermore, this referential information was immediately used in parsing the rest of the sentence, which was briefly ambiguous between a complement clause (“ … that there would be some visitors”) and a relative clause (“ … that had been on the phone to hang up”). A consistent pattern of P600/SPS effects elicited by various subsequent disambiguations revealed that a two-referent discourse context had led the parser to initially pursue the relative-clause alternative to a larger extent than a one-referent context. Together, the results suggest that during the processing of sentences in discourse, structural and referential sources of information interact on a word-by-word basis.

Abstract

This paper reports two experiments with vowels and consonants as phoneme detection targets in real words. In the first experiment, two relatively distinct vowels were compared with two confusible stop consonants. Response times to the vowels were longer than to the consonants. Response times correlated negatively with target phoneme length. In the second, two relatively distinct vowels were compared with their corresponding semivowels. This time, the vowels were detected faster than the semivowels. We conclude that response time differences between vowels and stop consonants in this task may reflect differences between phoneme categories in the variability of tokens, both in the acoustic realisation of targets and in the' representation of targets by subjects.

Abstract

Computer simulations in an instructional context can be characterized according to four aspects (themes): simulation models, learning goals, learning processes and learner activity. The present paper provides an outline of these four themes. The main classification criterion for simulation models is quantitative vs. qualitative models. For quantitative models a further subdivision can be made by classifying the independent and dependent variables as continuous or discrete. A second criterion is whether one of the independent variables is time, thus distinguishing dynamic and static models. Qualitative models on the other hand use propositions about non-quantitative properties of a system or they describe quantitative aspects in a qualitative way. Related to the underlying model is the interaction with it. When this interaction has a normative counterpart in the real world we call it a procedure. The second theme of learning with computer simulation concerns learning goals. A learning goal is principally classified along three dimensions, which specify different aspects of the knowledge involved. The first dimension, knowledge category, indicates that a learning goal can address principles, concepts and/or facts (conceptual knowledge) or procedures (performance sequences). The second dimension, knowledge representation, captures the fact that knowledge can be represented in a more declarative (articulate, explicit), or in a more compiled (implicit) format, each one having its own advantages and drawbacks. The third dimension, knowledge scope, involves the learning goal's relation with the simulation domain; knowledge can be specific to a particular domain, or generalizable over classes of domains (generic). A more or less separate type of learning goal refers to knowledge acquisition skills that are pertinent to learning in an exploratory environment. Learning processes constitute the third theme. Learning processes are defined as cognitive actions of the learner. Learning processes can be classified using a multilevel scheme. The first (highest) of these levels gives four main categories: orientation, hypothesis generation, testing and evaluation. Examples of more specific processes are model exploration and output interpretation. The fourth theme of learning with computer simulations is learner activity. Learner activity is defined as the ‘physical’ interaction of the learner with the simulations (as opposed to the mental interaction that was described in the learning processes). Five main categories of learner activity are distinguished: defining experimental settings (variables, parameters etc.), interaction process choices (deciding a next step), collecting data, choice of data presentation and metacontrol over the simulation.

Abstract

We report a series of experiments examining the effects on word processing of insertion of an optional epenthetic vowel in word-final consonant clusters in Dutch. Such epenthesis turns film, for instance, into film. In a word-reversal task listeners treated words with and without epenthesis alike, as monosyllables, suggesting that the variant forms both activate the same canonical representation, that of a monosyllabic word without epenthesis. In both lexical decision and word spotting, response times to recognize words were significantly faster when epenthesis was present than when the word was presented in its canonical form without epenthesis. It is argued that addition of the epenthetic vowel makes the liquid consonants constituting the first member of a cluster more perceptible; a final phoneme-detection experiment confirmed that this was the case. These findings show that a transformed variant of a word, although it contacts the lexicon via the representation of the canonical form, can be more easily perceptible than that canonical form.

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

The use of computer simulations in education and training can have substantial advantages over other approaches. In comparison with alternatives such as textbooks, lectures, and tutorial courseware, a simulation-based approach offers the opportunity to learn in a relatively realistic problem-solving context, to practise task performance without stress, to systematically explore both realistic and hypothetical situations, to change the time-scale of events, and to interact with simplified versions of the process or system being simulated. However, learners are often unable to cope with the freedom offered by, and the complexity of, a simulation. As a result many of them resort to an unsystematic, unproductive mode of exploration. There is evidence that simulation-based learning can be improved if the learner is supported while working with the simulation. Constructing such an instructional environment around simulations seems to run counter to the freedom the learner is allowed to in ‘stand alone’ simulations. The present article explores instructional measures that allow for an optimal freedom for the learner. An extensive discussion of learning goals brings two main types of learning goals to the fore: conceptual knowledge and operational knowledge. A third type of learning goal refers to the knowledge acquisition (exploratory learning) process. Cognitive theory has implications for the design of instructional environments around simulations. Most of these implications are quite general, but they can also be related to the three types of learning goals. For conceptual knowledge the sequence and choice of models and problems is important, as is providing the learner with explanations and minimization of error. For operational knowledge cognitive theory recommends learning to take place in a problem solving context, the explicit tracing of the behaviour of the learner, providing immediate feedback and minimization of working memory load. For knowledge acquisition goals, it is recommended that the tutor takes the role of a model and coach, and that learning takes place together with a companion. A second source of inspiration for designing instructional environments can be found in Instructional Design Theories. Reviewing these shows that interacting with a simulation can be a part of a more comprehensive instructional strategy, in which for example also prerequisite knowledge is taught. Moreover, information present in a simulation can also be represented in a more structural or static way and these two forms of presentation provoked to perform specific learning processes and learner activities by tutor controlled variations in the simulation, and by tutor initiated prodding techniques. And finally, instructional design theories showed that complex models and procedures can be taught by starting with central and simple elements of these models and procedures and subsequently presenting more complex models and procedures. Most of the recent simulation-based intelligent tutoring systems involve troubleshooting of complex technical systems. Learners are supposed to acquire knowledge of particular system principles, of troubleshooting procedures, or of both. Commonly encountered instructional features include (a) the sequencing of increasingly complex problems to be solved, (b) the availability of a range of help information on request, (c) the presence of an expert troubleshooting module which can step in to provide criticism on learner performance, hints on the problem nature, or suggestions on how to proceed, (d) the option of having the expert module demonstrate optimal performance afterwards, and (e) the use of different ways of depicting the simulated system. A selection of findings is summarized by placing them under the four themes we think to be characteristic of learning with computer simulations (see de Jong, this volume).

Abstract

This study investigated whether the negative effect of complexity on artificial grammar learning could be compensated by adding semantics. Participants were exposed to exemplars from a simple or a complex finite state grammar presented with or without a semantic reference field. As expected, performance on a grammaticality judgment test was higher for the simple grammar than for the complex grammar. For the simple grammar, the results also showed that participants presented with a reference field and instructed to decode the meaning of each exemplar (decoding condition) did better than participants who memorized the exemplars without semantic referents (memorize condition). Contrary to expectations, however, there was no significant difference between the decoding condition and the memorize condition for the complex grammar. These findings indicated that the negative effect of complexity remained, despite the addition of semantics. To clarify how the presence of a reference field influenced the learning process, its effects on the acquisition of two types of knowledge (first- and second-order dependencies) and on participants’ awareness of their knowledge were examined. The results tentatively suggested that the reference field enhanced the learning of second-order dependencies. In addition, participants in the decoding condition realized when they had knowledge relevant to making a grammaticality judgment, whereas participants in the memorize condition demonstrated some knowledge of which they were unaware. These results are in line with the view that the reference field enhanced structure learning by making certain dependencies more salient. Moreover, our findings stress the influence of complexity on artificial grammar learning

Abstract

According to the complementary learning systems (CLS) account of word learning, novel words are rapidly acquired (learning system 1), but slowly integrated into the mental lexicon (learning system 2). This two-step learning process has been shown to apply to novel word forms. In this study, we investigated whether novel word meanings are also gradually integrated after acquisition by measuring the extent to which newly learned words were able to prime semantically related words at two different time points. In addition, we investigated whether modality at study modulates this integration process. Sixty-four adult participants studied novel words together with written or spoken definitions. These words did not prime semantically related words directly following study, but did so after a 24-hour delay. This significant increase in the magnitude of the priming effect suggests that semantic integration occurs over time. Overall, words that were studied with a written definition showed larger priming effects, suggesting greater integration for the written study modality. Although the process of integration, reflected as an increase in the priming effect over time, did not significantly differ between study modalities, words studied with a written definition showed the most prominent positive effect after a 24-hour delay. Our data suggest that semantic integration requires time, and that studying in written format benefits semantic integration more than studying in spoken format. These findings are discussed in light of the CLS theory of word learning.

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

Within the first few years of life, children acquire many of the building blocks of their native language. This not only involves knowledge about the linguistic structure of spoken language, but also knowledge about the way in which this linguistic structure surfaces in their speech input. In this chapter, we review how infants and toddlers cope with differences between speakers and accents. Within the context of milestones in early speech perception, we examine how voice and accent characteristics are integrated during language processing, looking closely at the advantages and disadvantages of speaker and accent familiarity, surface-level deviation between two utterances, variability in the input, and prior speaker exposure. We conclude that although deviation from the child’s standard can complicate speech perception early in life, young listeners can overcome these additional challenges. This suggests that early spoken language processing is flexible and adaptive to the listening situation at hand.

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

Speech requires precise motor control and rapid sequencing of highly complex vocal musculature. Despite its complexity, most people produce spoken language effortlessly. This is due to activity in distributed neuronal circuitry including cortico-striato-thalamic loops that control speech-motor output. Understanding the neuro-genetic mechanisms that encode these pathways will shed light on how humans can effortlessly and innately use spoken language and could elucidate what goes wrong in speech-language disorders.
FOXP2 was the first single gene identified to cause speech and language disorder. Individuals with FOXP2 mutations display a severe speech deficit that also includes receptive and expressive language impairments. The underlying neuro-molecular mechanisms controlled by FOXP2, which will give insight into our capacity for speech-motor control, are only beginning to be unraveled. Recently FOXP2 was found to regulate genes involved in retinoic acid signaling and to modify the cellular response to retinoic acid, a key regulator of brain development. Herein we explore the evidence that FOXP2 and retinoic acid signaling function in the same pathways. We present evidence at molecular, cellular and behavioral levels that suggest an interplay between FOXP2 and retinoic acid that may be important for fine motor control and speech-motor output.
We propose that retinoic acid signaling is an exciting new angle from which to investigate how neurogenetic mechanisms can contribute to the (spoken) language ready brain.

Abstract

Both categorization and segmentation processes play a crucial role in face perception. However, the functional relation between these subprocesses is currently unclear. The present study investigates the temporal relation between segmentation-related and category-selective responses in the brain, using electroencephalography (EEG). Surface segmentation and category content were both manipulated using texture-defined objects, including faces. This allowed us to study brain activity related to segmentation and to categorization. In the main experiment, participants viewed texture-defined objects for a duration of 800 ms. EEG results revealed that segmentation-related responses precede category-selective responses. Three additional experiments revealed that the presence and timing of categorization depends on stimulus properties and presentation duration. Photographic objects were presented for a long and short (92 ms) duration and evoked fast category-selective responses in both cases. On the other hand, presentation of texture-defined objects for a short duration only evoked segmentation-related but no category-selective responses. Category-selective responses were much slower when evoked by texture-defined than by photographic objects. We suggest that in case of categorization of objects under suboptimal conditions, such as when low-level stimulus properties are not sufficient for fast object categorization, segmentation facilitates the slower categorization process

Abstract

In two ERP experiments we investigated how and when the language comprehension system relates an incoming word to semantic representations of an unfolding local sentence and a wider discourse. In experiment 1, subjects were presented with short stories. The last sentence of these stories occasionally contained a critical word that, although acceptable in the local sentence context, was semantically anomalous with respect to the wider discourse (e.g., "Jane told the brother that he was exceptionally slow" in a discourse context where he had in fact been very quick). Relative to coherent control words (e.g., "quick"), these discourse-dependent semantic anomalies elicited a large N400 effect that began at about 200-250 ms after word onset. In experiment 2, the same sentences were presented without their original story context. Although the words that had previously been anomalous in discourse still elicited a slightly larger average N400 than the coherent words, the resulting N400 effect was much reduced, showing that the large effect observed in stories was related to the wider discourse. In the same experiment, single sentences that contained a clear local semantic anomaly elicited a standard sentence-dependent N400 effect (e.g., Kutas & Hillyard, 1980). The N400 effects elicited in discourse and in single sentences had the same time course, overall morphology, and scalp distribution. We argue that these findings are most compatible with models of language processing in which there is no fundamental distinction between the integration of a word in its local (sentence-level) and its global (discourse-level) semantic context.

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

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

We review the implications of recent ERP evidence for when and how grammatical gender agreement constrains sentence parsing. In some theories of parsing, gender is assumed to immediately and categorically block gender-incongruent phrase structure alternatives from being pursued. In other theories, the parser initially ignores gender altogether. The ERP evidence we discuss suggests an intermediate position, in which grammatical gender does not immediately block gender-incongruent phrase structures from being considered, but is used to dispose of them shortly thereafter.

Abstract

The present research investigates how consumer choice is affected by Terror Management Theory’s proposition of Mortality Salience increasing one’s cultural worldview defense and self-esteem striving. The study builds empirically upon prior theorizing by Arndt, Solomon, Kasser and Sheldon (2004). During an experiment, we manipulated Mortality Salience and measured product preferences for conspicuousness and familiarity. Participants primed with death were more likely to choose conspicuous products, corroborating previous research of mortality salience raising materialistic tendencies. In addition, participants showed a tendency to prefer familiar brands. These results are in line with the Terror Management Theory framework.

Abstract

Motor-related brain potentials were used to examine the time course of grammatical and phonological processes during noun phrase production in Dutch. In the experiments, participants named colored pictures using a no-determiner noun phrase. On half of the trials a syntactic-phonological classification task had to be performed before naming. Depending on the outcome of the classifications, a left or a right push-button response was given (go trials), or no push-button response was given (no-go trials). Lateralized readiness potentials (LRPs) were derived to test whether syntactic and phonological information affected the motor system at separate moments in time. The results showed that when syntactic information determined the response-hand decision, an LRP developed on no-go trials. However, no such effect was observed when phonological information determined response hand. On the basis of the data, it can be estimated that an additional period of at least 40 ms is needed to retrieve a word's initial phoneme once its lemma has been retrieved. These results provide evidence for the view that during speaking, grammatical processing precedes phonological processing in time.

Abstract

Based on the results of an event-related brain potentials (ERP) experiment (van Berkum, Brown, & Hagoort. 1999a, b), we have recently argued that discourse-level referential context can be taken into account extremely rapidly by the parser. Moreover, our ERP results indicated that local grammatical gender information, although available within a few hundred milliseconds from word onset, is not always used quickly enough to prevent the parser from considering a discourse-supported, but agreement-violating, syntactic analysis. In a comment on our work, Brysbaert and Mitchell (2000) have raised concerns about the methodology of our ERP experiment and have challenged our interpretation of the results. In this reply, we argue that these concerns are unwarranted and, that, in contrast to our own interpretation, the alternative explanations provided by Brysbaert and Mitchell do not account for the full pattern of ERP results.

Abstract

OBJECTIVES: Deficits in response inhibition have been associated with attention-deficit/hyperactivity disorder (ADHD). Given the role of serotonin in ADHD and impulsivity, we postulated that genetic variants within the serotonin pathway might influence response inhibition. METHODS: We measured neural activation during stop-signal task performance in adolescents with ADHD (N = 185), their unaffected siblings (N = 111), and healthy controls (N = 124), and investigated the relationship of two serotonin gene polymorphisms (the rs6296 SNP of the HTR1B gene and HTTLPR variants of the 5-HTT gene) with the neural correlates of response inhibition. RESULTS: The whole-brain analyses demonstrated large scale neural activation differences in the inferior and medial frontal and temporal/parietal regions of the response inhibition network between the different variants of both the HTR1B and 5HTT genes. Activation in these regions was significantly associated with stop-task performance, but not with ADHD diagnosis or severity. No associations were found between HTR1B and 5HTT variants and ADHD or ADHD-related neural activation. CONCLUSIONS: These results provide novel evidence that serotonin may play an important role in the neurobiology of response inhibition. Although response inhibition is strongly linked to ADHD, serotonin linked genetic variants associated with response inhibition and its neural correlates do not explain variance of the ADHD phenotype.

Abstract

Do aesthetic preferences for images of neatly organized compositions (e.g., images collected on blogs like Things Organized Neatly©) generalize across cultures? In an earlier study, focusing on stimulus and personal properties related to order and complexity, Western participants indicated their preference for one of two simultaneously presented images (100 pairs). In the current study, we compared the data of the native Dutch-speaking participants from this earlier sample (N = 356) to newly collected data from a native Chinese-speaking sample (N = 220). Overall, aesthetic preferences were quite similar across cultures. When relating preferences for each sample to ratings of order, complexity, soothingness, and fascination collected from a Western, mainly Dutch-speaking sample, the results hint at a cross-culturally consistent preference for images that Western participants rate as more ordered, but a cross-culturally diverse relation between preferences and complexity.

Abstract

thebeat is a Python package for working with temporal sequences and rhythms in the behavioral and cognitive sciences, as well as in bioacoustics. It provides functionality for creating experimental stimuli, and for visualizing and analyzing temporal data. Sequences, sounds, and experimental trials can be generated using single lines of code. thebeat contains functions for calculating common rhythmic measures, such as interval ratios, and for producing plots, such as circular histograms. thebeat saves researchers time when creating experiments, and provides the first steps in collecting widely accepted methods for use in timing research. thebeat is an open-source, on-going, and collaborative project, and can be extended for use in specialized subfields. thebeat integrates easily with the existing Python ecosystem, allowing one to combine our tested code with custom-made scripts. The package was specifically designed to be useful for both skilled and novice programmers. thebeat provides a foundation for working with temporal sequences onto which additional functionality can be built. This combination of specificity and plasticity should facilitate research in multiple research contexts and fields of study.

Abstract

Contrastive pitch accents can mark sentence elements occupying parallel roles. In “Mary kissed John, not Peter”, a pitch accent on Mary or John cues the implied syntactic role of Peter. Van der Burght, Friederici, Goucha, and Hartwigsen (2021) showed that listeners can build expectations concerning syntactic and semantic properties of upcoming words, derived from pitch accent information they heard previously. To further explore these expectations, we attempted a partial replication of the original German study in Dutch. In the experimental sentences “Yesterday, the police officer arrested the thief, not the inspector/murderer”, a pitch accent on subject or object cued the subject/object role of the ellipsis clause. Contrasting elements were additionally cued by the thematic role typicality of the nouns. Participants listened to sentences in which the ellipsis clause was omitted and selected the most plausible sentence-final noun (presented visually) via button press. Replicating the original study results, listeners based their sentence-final preference on the pitch accent information available in the sentence. However, as in the original study, individual differences between listeners were found, with some following prosodic information and others relying on a structural bias. The results complement the literature on ellipsis resolution and on interindividual variability in cue weighting.

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

An important issue in current psycholinguistics is how the time course of utterance planning affects the generation of grammatical structures. The current study investigated the influence of parallel activation of the components of complex noun phrases on the generation of subject-verb agreement. Specifically, the lexical interference account (Gillespie, M. and Pearlmutter, N. J., 2011b and Solomon, E. S. and Pearlmutter, N. J., 2004) predicts more agreement errors (i.e., attraction) for subject phrases in which the head and local noun mismatch in number (e.g., the apple next to the pears) when nouns are planned in parallel than when they are planned in sequence. We used a speeded picture description task that yielded sentences such as the apple next to the pears is red. The objects mentioned in the noun phrase were either semantically related or unrelated. To induce agreement errors, pictures sometimes mismatched in number. In order to manipulate the likelihood of parallel processing of the objects and to test the hypothesized relationship between parallel processing and the rate of agreement errors, the pictures were either placed close together or far apart. Analyses of the participants' eye movements and speech onset latencies indicated slower processing of the first object and stronger interference from the related (compared to the unrelated) second object in the close than in the far condition. Analyses of the agreement errors yielded an attraction effect, with more errors in mismatching than in matching conditions. However, the magnitude of the attraction effect did not differ across the close and far conditions. Thus, spatial proximity encouraged parallel processing of the pictures, which led to interference of the associated conceptual and/or lexical representation, but, contrary to the prediction, it did not lead to more attraction errors.

Abstract

Objective: To study the effect of vaccination-associated seizure onset on disease course and estimate the risk of subsequent seizures after infant pertussis combination and measles, mumps, and rubella (MMR) vaccinations in Dravet syndrome (DS). Methods: We retrospectively analyzed data from hospital medical files, child health clinics, and the vaccination register for children with DS and pathogenic SCN1A mutations. Seizures within 24 hours after infant whole-cell, acellular, or nonpertussis combination vaccination or within 5 to 12 days after MMR vaccination were defined as "vaccination-associated." Risks of vaccination-associated seizures for the different vaccines were analyzed in univariable and in multivariable logistic regression for pertussis combination vaccines and by a self-controlled case series analysis using parental seizure registries for MMR vaccines. Disease courses of children with and without vaccination-associated seizure onset were compared. Results: Children who had DS (n = 77) with and without vaccination-associated seizure onset (21% and 79%, respectively) differed in age at first seizure (median 3.7 vs 6.1 months, p < 0.001) but not in age at first nonvaccination-associated seizure, age at first report of developmental delay, or cognitive outcome. The risk of subsequent vaccination-associated seizures was significantly lower for acellular pertussis (9%; odds ratio 0.18, 95% confidence interval [CI] 0.05-0.71) and nonpertussis (8%; odds ratio 0.11, 95% CI 0.02-0.59) than whole-cell pertussis (37%; reference) vaccines. Self-controlled case series analysis showed an increased incidence rate ratio of seizures of 2.3 (95% CI 1.5-3.4) within the risk period of 5 to 12 days following MMR vaccination. Conclusions: Our results suggest that vaccination-associated earlier seizure onset does not alter disease course in DS, while the risk of subsequent vaccination-associated seizures is probably vaccine-specific.

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

Recent research has put forward the idea that Chinese speech production is governed by the syllable as the fundamental phonological unit. However, it may be that onset priming might be more difficult to obtain in Mandarin Chinese. Therefore, in this study, the degree of overlap between prime and target was increased from C to CV (i.e., extending beyond the phoneme) as well as whether primes and targets had an overlapping structure (CV vs. CVN). Subsyllabic priming effects were found (i.e., onset + vowel overlap but not purely onset overlap), contrasting with the claim that the syllable is the compulsory building block in the initial construction of Mandarin Chinese phonology.

Abstract

The Microsoft KINECT is a 3D sensing device originally developed for the XBOX. The Microsoft KINECT opens up many exciting new opportunities for conducting experimental research on human behavior. We investigated some of these possibilities within the field of psycholinguistics (specifically: language production) by creating software, using C#, allowing for the KINECT to be used in a typical psycholinguistic experimental setting. The results of a naming experiment using this software confirmed that the KINECT was able to measure the effects of a robust psycholinguistic variable (word frequency) on naming latencies. However, although the current version of the software is able to measure psycholinguistic variables of interest, we also discuss several points where the software can still stand to be improved. The main aim of this paper is to make the software freely available for assessment and use by the psycholinguistic community and to illustrate the KINECT as a potentially valuable tool for investigating human behavior, especially in the field of psycholinguistics.

Abstract

There is evidence from both behavior and brain activity that the way information is structured, through the use of focus, can up-regulate processing of focused constituents, likely to give prominence to the relevant aspects of the input. This is hypothesized to be universal, regardless of the different ways in which languages encode focus. In order to test this universalist hypothesis, we need to go beyond the more familiar linguistic strategies for marking focus, such as by means of intonation or specific syntactic structures (e.g., it-clefts). Therefore, in this study, we examine Makhuwa-Enahara, a Bantu language spoken in northern Mozambique, which uniquely marks focus through verbal conjugation. The participants were presented with sentences that consisted of either a semantically anomalous constituent or a semantically nonanomalous constituent. Moreover, focus on this particular constituent could be either present or absent. We observed a consistent pattern: Focused information generated a more negative N400 response than the same information in nonfocus position. This demonstrates that regardless of how focus is marked, its consequence seems to result in an upregulation of processing of information that is in focus.

Abstract

Learning new words is an increasingly common necessity in everyday life. External factors, among which music and social interaction are particularly debated, are claimed to facilitate this task. Due to their influence on the learner’s temporal behavior, these stimuli are able to drive the learner’s attention to the correct referent of new words at the correct point in time. However, do music and social interaction impact learning behavior in the same way? The current study aims to answer this question. Native German speakers (N = 80) were requested to learn new words (pseudo-words) during a contextual learning game. This learning task was performed alone with a computer or with a partner, with or without music. Results showed that music and social interaction had a different impact on the learner’s behavior: Participants tended to temporally coordinate their behavior more with a partner than with music, and in both cases more than with a computer. However, when both music and social interaction were present, this temporal coordination was hindered. These results suggest that while music and social interaction do influence participants’ learning behavior, they have a different impact. Moreover, impaired behavior when both music and a partner are present suggests that different mechanisms are employed to coordinate with the two types of stimuli. Whether one or the other approach is more efficient for word learning, however, is a question still requiring further investigation, as no differences were observed between conditions in a retrieval phase, which took place immediately after the learning session. This study contributes to the literature on word learning in adults by investigating two possible facilitating factors, and has important implications for situations such as music therapy, in which music and social interaction are present at the same time.

Abstract

The classic account of language is that language processing occurs in isolation from other cognitive systems, like perception, motor action, and emotion. The central theme of this paper is the relationship between a participant’s emotional state and language comprehension. Does emotional context affect how we process neutral words? Recent studies showed that processing of word meaning – traditionally conceived as an automatic process – is affected by emotional state. The influence of emotional state on syntactic processing is less clear. One study reported a mood-related P600 modulation, while another study did not observe an effect of mood on syntactic processing. The goals of this study were: First, to clarify whether and if so how mood affects syntactic processing. Second, to shed light on the underlying mechanisms by separating possible effects of mood from those of attention on syntactic processing. Event-related potentials (ERPs) were recorded while participants read syntactically correct or incorrect sentences. Mood (happy vs. sad) was manipulated by presenting film clips. Attention was manipulated by directing attention to syntactic features vs. physical features. The mood induction was effective. Interactions between mood, attention and syntactic correctness were obtained, showing that mood and attention modulated P600. The mood manipulation led to a reduction in P600 for sad as compared to happy mood when attention was directed at syntactic features. The attention manipulation led to a reduction in P600 when attention was directed at physical features compared to syntactic features for happy mood. From this we draw two conclusions: First, emotional state does affect syntactic processing. We propose mood-related differences in the reliance on heuristics as the underlying mechanism. Second, attention can contribute to emotion-related ERP effects in syntactic language processing. Therefore, future studies on the relation between language and emotion will have to control for effects of attention

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