Publications

Abstract

Phosphomannomutase 2 deficiency, or PMM2-CDG, is the most common congenital disorder of glycosylation and affects over 1000 patients globally. There are no approved drugs that treat the symptoms or root cause of PMM2-CDG. To identify clinically actionable compounds that boost human PMM2 enzyme function, we performed a multispecies drug repurposing screen using a novel worm model of PMM2-CDG, followed by PMM2 enzyme functional studies in PMM2-CDG patient fibroblasts. Drug repurposing candidates from this study, and drug repurposing candidates from a previously published study using yeast models of PMM2-CDG, were tested for their effect on human PMM2 enzyme activity in PMM2-CDG fibroblasts. Of the 20 repurposing candidates discovered in the worm-based phenotypic screen, 12 were plant-based polyphenols. Insights from structure-activity relationships revealed epalrestat, the only antidiabetic aldose reductase inhibitor approved for use in humans, as a first-in-class PMM2 enzyme activator. Epalrestat increased PMM2 enzymatic activity in four PMM2-CDG patient fibroblast lines with genotypes R141H/F119L, R141H/E139K, R141H/N216I and R141H/F183S. PMM2 enzyme activity gains ranged from 30% to 400% over baseline, depending on genotype. Pharmacological inhibition of aldose reductase by epalrestat may shunt glucose from the polyol pathway to glucose-1,6-bisphosphate, which is an endogenous stabilizer and coactivator of PMM2 homodimerization. Epalrestat is a safe, oral and brain penetrant drug that was approved 27 years ago in Japan to treat diabetic neuropathy in geriatric populations. We demonstrate that epalrestat is the first small molecule activator ofPMM2 enzyme activity with the potential to treat peripheral neuropathy and correct the underlying enzyme deficiency in a majority of pediatric and adult PMM2-CDG patients.

Abstract

This study investigates how listeners cope with gradient forms of deletion of word-final /t/ when recognising words in a phonological context that makes /t/-deletion viable. A corpus study confirmed a high incidence of /t/-deletion in an /st#b/ context in Dutch. A discrimination study showed that differences between released /t/, unreleased /t/ and fully deleted /t/ in this specific /st#b/ context were salient. Two on-line experiments were carried out to investigate whether lexical activation might be affected by this form variation. Even though unreleased and released variants were processed equally fast by listeners, a detailed analysis of the unreleased condition provided evidence for gradient activation. Activating a target ending in /t/ is slowest for the most reduced variant because phonological context has to be taken into account. Importantly, activation for a target with /t/ in the absence of cues for /t/ is reduced if there is a surface-matching lexical competitor.

Abstract

Research Findings: The present study compared effects of explicit instruction on and practice with the phonological form of words (form-focused instruction) versus explicit instruction on and practice with the meaning of words (meaning-focused instruction). Instruction was given via interactive storybook reading in the kindergarten classroom of children learning Dutch. We asked whether the 2 types of instruction had different effects on vocabulary development and 2 precursors of reading ability—phonological awareness and letter knowledge—and we examined effects on these measures of the ability to learn new words with minimal acoustic-phonetic differences. Learners showed similar receptive target-word vocabulary gain after both types of instruction, but learners who received form-focused vocabulary instruction showed more gain in semantic knowledge of target vocabulary, phonological awareness, and letter knowledge than learners who received meaning-focused vocabulary instruction. Level of ability to learn pairs of words with minimal acoustic-phonetic differences predicted gain in semantic knowledge of target vocabulary and in letter knowledge in the form-focused instruction group only. Practice or Policy: A focus on the form of words during instruction appears to have benefits for young children learning vocabulary.

Abstract

The influence of larynx position on vowel articulation is an important topic in understanding speech production, the present-day distribution of linguistic diversity and the evolution of speech and language in our lineage. We introduce here a realistic computer model of the vocal tract, constructed from actual human MRI data, which can learn, using machine learning techniques, to control the articulators in such a way as to produce speech sounds matching as closely as possible to a given set of target vowels. We systematically control the vertical position of the larynx and we quantify the differences between the target and produced vowels for each such position across multiple replications. We report that, indeed, larynx height does affect the accuracy of reproducing the target vowels and the distinctness of the produced vowel system, that there is a “sweet spot” of larynx positions that are optimal for vowel production, but that nevertheless, even extreme larynx positions do not result in a collapsed or heavily distorted vowel space that would make speech unintelligible. Together with other lines of evidence, our results support the view that the vowel space of human languages is influenced by our larynx position, but that other positions of the larynx may also be fully compatible with speech.

Abstract

Children's abilities to process the phonological structure of words are important predictors of their literacy development. In the current study, we examined the interrelatedness between implicit (i.e., speech decoding) and explicit (i.e., phonological awareness) phonological abilities, and especially the role therein of lexical specificity (i.e., the ability to learn to recognize spoken words based on only minimal acoustic-phonetic differences). We tested 75 Dutch monolingual and 64 Turkish–Dutch bilingual kindergartners. SEM analyses showed that speech decoding predicted lexical specificity, which in turn predicted rhyme awareness in the first language learners but phoneme awareness in the second language learners. Moreover, in the latter group there was an impact of the second language: Dutch speech decoding and lexical specificity predicted Turkish phonological awareness, which in turn predicted Dutch phonological awareness. We conclude that language-specific phonological characteristics underlie different patterns of transfer from implicit to explicit phonological abilities in first and second language learners.

Abstract

Successful navigation is facilitated by the presence of landmarks. Previous functional magnetic resonance imaging (fMRI) evidence indicated that the human parahippocampal gyrus automatically distinguishes between landmarks placed at navigationally relevant (decision points) and irrelevant locations (nondecision points). This storage of navigational relevance can provide a neural mechanism underlying successful navigation. However, an efficient wayfinding mechanism requires that important spatial information is learned quickly and maintained over time. The present study investigates whether the representation of navigational relevance is modulated by time and practice. Participants learned 2 film sequences through virtual mazes containing objects at decision and at nondecision points. One maze was shown one time, and the other maze was shown 3 times. Twenty-four hours after study, event-related fMRI data were acquired during recognition of the objects. The results showed that activity in the parahippocampal gyrus was increased for objects previously placed at decision points as compared with objects placed at nondecision points. The decision point effect was not modulated by the number of exposures to the mazes and independent of explicit memory functions. These findings suggest a persistent representation of navigationally relevant information, which is stable after only one exposure to an environment. These rapidly induced and long-lasting changes in object representation provide a basis for successful wayfinding.

Abstract

The human brain distinguishes between landmarks placed at navigationally relevant and irrelevant locations. However, to provide a successful wayfinding mechanism not only landmarks but also the routes between them need to be stored. We examined the neural representation of a memory for route direction and a memory for relevant landmarks. Healthy human adults viewed objects along a route through a virtual maze. Event-related functional magnetic resonance imaging (fMRI) data were acquired during a subsequent subliminal priming recognition task. Prime-objects either preceded or succeeded a target-object on a preciously learned route. Our results provide evidence that the parahippocampal gyri distinguish between relevant and irrelevant landmarks whereas the inferior parietal gyrus, the anterior cingulate gyrus as well as the right caudate nucleus are involved in the coding of route direction. These data show that separated memory systems store different spatial information. A memory for navigationally relevant object information and a memory for route direction exist.

Abstract

In 7 experiments the authors investigated the locus of word frequency effects in speech production. Experiment 1 demonstrated a frequency effect in picture naming that was robust over repetitions. Experiments 2, 3, and 7 excluded contributions from object identification and initiation of articulation. Experiments 4 and 5 investigated whether the effect arises in accessing the syntactic word (lemma) by using a grammatical gender decision task. Although a frequency effect was found, it dissipated under repeated access to word's gender. Experiment 6 tested whether the robust frequency effect arises in accessing the phonological form (lexeme) by having Ss translate words that produced homophones. Low-frequent homophones behaved like high-frequent controls, inheriting the accessing speed of their high-frequent homophone twins. Because homophones share the lexeme, not the lemma, this suggests a lexeme-level origin of the robust effect.

Abstract

Language processing is influenced by multiple sources of information. We examined whether the performance in simultaneous interpreting would be improved when providing two sources of information, the auditory speech as well as corresponding lip-movements, in comparison to presenting the auditory speech alone. Although there was an improvement in sentence recognition when presented with visible speech, there was no difference in performance between these two presentation conditions when bilinguals simultaneously interpreted from English to German or from English to Spanish. The reason why visual speech did not contribute to performance could be the presentation of the auditory signal without noise (Massaro, 1998). This hypothesis should be tested in the future. Furthermore, it should be investigated if an effect of visible speech can be found for other contexts, when visual information could provide cues for emotions, prosody, or syntax.

Abstract

We investigate differences of cerebral activation in 12 right-handed and left-handed participants, respectively, using a sentence-processing task. Functional MRI shows activation of left-frontal and inferior-parietal speech areas (BA 44, BA9, BA 40) in both groups, but a stronger bilateral activation in left-handers. Direct group comparison reveals a stronger activation in right-frontal cortex (BA 47, BA 6) and left cerebellum in left-handers. Laterality indices for the inferior-frontal cortex are less asymmetric in left-handers and are not related to the degree of handedness. Thus, our results show that sentence-processing induced enhanced activation involving a bilateral network in left-handed participants.

Abstract

Purpose: Factors affecting the efficacy of therapeutic monoclonal antibodies (mAb) directed to the epidermal growth factor receptor (EGFR) remain relatively unknown, especially in glioma. Experimental Design: We examined the efficacy of two EGFR-specific mAbs (mAbs 806 and 528) against U87MG-derived glioma xenografts expressing EGFR variants. Using this approach allowed us to change the form of the EGFR while keeping the genetic background constant. These variants included the de2-7 EGFR (or EGFRvIII), a constitutively active mutation of the EGFR expressed in glioma. Results: The efficacy of the mAbs correlated with EGFR number; however, the most important factor was receptor activation. Whereas U87MG xenografts expressing the de2-7 EGFR responded to therapy, those exhibiting a dead kinase de2-7 EGFR were refractory. A modified de2-7 EGFR that was kinase active but autophosphorylation deficient also responded, suggesting that these mAbs function in de2-7 EGFR–expressing xenografts by blocking transphosphorylation. Because de2-7 EGFR–expressing U87MG xenografts coexpress the wild-type EGFR, efficacy of the mAbs was also tested against NR6 xenografts that expressed the de2-7 EGFR in isolation. Whereas mAb 806 displayed antitumor activity against NR6 xenografts, mAb 528 therapy was ineffective, suggesting that mAb 528 mediates its antitumor activity by disrupting interactions between the de2-7 and wild-type EGFR. Finally, genetic disruption of Src in U87MG xenografts expressing the de2-7 EGFR dramatically enhanced mAb 806 efficacy. Conclusions: The effective use of EGFR-specific antibodies in glioma will depend on identifying tumors with activated EGFR. The combination of EGFR and Src inhibitors may be an effective strategy for the treatment of glioma.

Abstract

Children who hear large amounts of diverse speech learn language more quickly than children who do not. However, high correlations between the amount and the diversity of the input in speech samples makes it difficult to isolate the influence of each. We overcame this problem by controlling the input to a computational model so that amount of exposure to linguistic input (quantity) and the quality of that input (lexical diversity) were independently manipulated. Sublexical, lexical, and multi-word knowledge were charted across development (Study 1), showing that while input quantity may be important early in learning, lexical diversity is ultimately more crucial, a prediction confirmed against children’s data (Study 2). The model trained on a lexically diverse input also performed better on nonword repetition and sentence recall tests (Study 3) and was quicker to learn new words over time (Study 4). A language input that is rich in lexical diversity outperforms equivalent richness in quantity for learned sublexical and lexical knowledge, for well-established language tests, and for acquiring words that have never been encountered before.

Abstract

Sustained attention has previously been shown as a requirement for language production. However, this is mostly evident for difficult conditions, such as a dual-task situation. The current study provides corroborating evidence that this relationship holds even for simple picture naming. Sustained attention ability, indexed both by participants’ reaction times and individuals’ hit rate (the proportion of correctly detected targets) on a digit discrimination task, correlated with picture naming latencies. Individuals with poor sustained attention were consistently slower and their RT distributions were more positively skewed when naming pictures compared to individuals with better sustained attention. Additionally, the need to sustain attention was manipulated by changing the speed of stimulus presentation. Research has suggested that fast event rates tax sustained attention resources to a larger degree than slow event rates. However, in this study the fast event rate did not result in increased difficulty, neither for the picture naming task nor for the sustained attention task. Instead, the results point to a speed-accuracy trade-off in the sustained attention task (lower accuracy but faster responses in the fast than in the slow event rate), and to a benefit for faster rates in the picture naming task (shorter naming latencies with no difference in accuracy). Performance on both tasks was largely comparable, supporting previous findings that sustained attention is called upon during language production

Abstract

Children with specific language impairment (SLI) have problems not only with language performance but also with sustained attention, which is the ability to maintain alertness over an extended period of time. Although there is consensus that this ability is impaired with respect to processing stimuli in the auditory perceptual modality, conflicting evidence exists concerning the visual modality.
Aims

To address the outstanding issue whether the impairment in sustained attention is limited to the auditory domain, or if it is domain-general. Furthermore, to test whether children's sustained attention ability relates to their word-production skills.
Methods & Procedures

Groups of 7–9 year olds with SLI (N = 28) and typically developing (TD) children (N = 22) performed a picture-naming task and two sustained attention tasks, namely auditory and visual continuous performance tasks (CPTs).
Outcomes & Results

Children with SLI performed worse than TD children on picture naming and on both the auditory and visual CPTs. Moreover, performance on both the CPTs correlated with picture-naming latencies across developmental groups.
Conclusions & Implications

These results provide evidence for a deficit in both auditory and visual sustained attention in children with SLI. Moreover, the study indicates there is a relationship between domain-general sustained attention and picture-naming performance in both TD and language-impaired children. Future studies should establish whether this relationship is causal. If attention influences language, training of sustained attention may improve language production in children from both developmental groups.

Abstract

Theories of conversation propose that in order to have smooth transitions from one turn to the next, speakers already plan their response while listening to their interlocutor. Moreover, it has been argued that speakers align their linguistic representations (i.e. prime each other), thereby reducing the processing costs associated with concurrent listening and speaking. In two experiments, we assessed how identity and associative priming from spoken words onto picture naming were affected by a concurrent speech planning task. In a baseline (no name) condition, participants heard prime words that were identical, associatively related, or unrelated to target pictures presented two seconds after prime onset. Each prime was accompanied by a non-target picture and followed by its recorded name. The participant did not name the non-target picture. In the plan condition, the participants first named the non-target picture, instead of listening to the recording, and then the target. In Experiment 1, where the plan- and no-plan conditions were tested between participants, priming effects of equal strength were found in the plan and no-plan condition. In Experiment 2, where the two conditions were tested within participants, the identity priming effect was maintained, but the associative priming effect was only seen in the no-plan but not in the plan condition. In this experiment, participant had to decide at the onset of each trial whether or not to name the non-target picture, rendering the task more complex than in Experiment 1. These decision processes may have interfered with the processing of the primes. Thus, associative priming can take place during speech planning, but only if the cognitive load is not too high.

Abstract

Spontaneous language learning both in children learning their mother tongue and in adults learning a second language shows that language development proceeds in a stage-wise manner. Given that a developmental stage is defined as a coherent linguistic system, utterances of language learners can be accounted for in terms of what (Selinker, Larry. 1972. Interlanguage. International Review of Applied Linguistics 10. 209-231) referred to with the term Interlanguage. This paper is a study on the early interlanguage systems of children learning Dutch and German as their mother tongue. The present child learner systems, so it is claimed, are coherent lexical systems based on types of verb-argument structure that are either agentive (as in Dutch: kannie bal pakke 'cannot ball get', or German: mag nich nase putzen 'like not nose clean') or non-agentive (as in Dutch: popje valt bijna 'doll falls nearly', or in German: ente fällt 'duck falls'). At this lexical stage, functional morphology (e. g. morphological finiteness, tense), function words (e. g. auxiliary verbs, determiners) and word order variation are absent. For these typically developing children, both in Dutch and in German, it is claimed that developmental progress is driven by the acquisition of the formal properties of topicalization. It is, furthermore, argued that this feature seems to serve as the driving force in the instantiation of the functional, i. e. informational linguistic properties of the target-language system

Abstract

Objective. The aims of this study were to compare the temporomandibular joint (TMJ) retrodiscal tissue T2 relaxation times between patients with temporomandibular disorders (TMDs) and asymptomatic volunteers and to assess the diagnostic potential of this approach.
Study Design. Patients with TMD (n = 173) and asymptomatic volunteers (n = 17) were examined by using a 1.5-T magnetic resonance scanner. The imaging protocol consisted of oblique sagittal, T2-weighted, 8-echo fast spin echo sequences in the closed mouth position. Retrodiscal tissue T2 relaxation times were obtained. Additionally, disc location and reduction, disc configuration, joint effusion, osteoarthritis, and bone edema or osteonecrosis were classified using MRI scans. The T2 relaxation times of each group were statistically compared.
Results. Retrodiscal tissue T2 relaxation times were significantly longer in patient groups than in asymptomatic volunteers (P < .01). T2 relaxation times were significantly longer in all of the morphologic categories. The most important variables affecting retrodiscal tissue T2 relaxation times were disc configuration, joint effusion, and osteoarthritis.
Conclusion. Retrodiscal tissue T2 relaxation times of patients with TMD were significantly longer than those of healthy volunteers. This finding may lead to the development of a diagnostic marker to aid in the early detection of TMDs.

Abstract

Is visual reinterpretation of bistable figures (e.g., duck/rabbit figure) in visual imagery possible? Current consensus suggests that it is in principle possible because of converging evidence of quasi-pictorial functioning of visual imagery. Yet, studies that have directly tested and found evidence for reinterpretation in visual imagery, allow for the possibility that reinterpretation was already achieved during memorization of the figure(s). One study resolved this issue, providing evidence for reinterpretation in visual imagery (Mast and Kosslyn, Cognition 86:57-70, 2002). However, participants in that study performed reinterpretations with aid of visual cues. Hence, reinterpretation was not performed with mental imagery alone. Therefore, in this study we assessed the possibility of reinterpretation without visual support. We further explored the possible role of haptic cues to assess the multimodal nature of mental imagery. Fifty-three participants were consecutively presented three to be remembered bistable 2-D figures (reinterpretable when rotated 180 degrees), two of which were visually inspected and one was explored hapticly. After memorization of the figures, a visually bistable exemplar figure was presented to ensure understanding of the concept of visual bistability. During recall, 11 participants (out of 36; 30.6%) who did not spot bistability during memorization successfully performed reinterpretations when instructed to mentally rotate their visual image, but additional haptic cues during mental imagery did not inflate reinterpretation ability. This study validates previous findings that reinterpretation in visual imagery is possible.

Abstract

In two experiments, we examined the role of gesture in reinterpreting a mental image. In Experiment 1, we found that participants gestured more about a figure they had learned through manual exploration than about a figure they had learned through vision. This supports claims that gestures emerge from the activation of perception-relevant actions during mental imagery. In Experiment 2, we investigated whether such gestures have a causal role in affecting the quality of mental imagery. Participants were randomly assigned to gesture, not gesture, or engage in a manual interference task as they attempted to reinterpret a figure they had learned through manual exploration. We found that manual interference significantly impaired participants' success on the task. Taken together, these results suggest that gestures reflect mental imaginings of interactions with a mental image and that these imaginings are critically important for mental manipulation and reinterpretation of that image. However, our results suggest that enacting the imagined movements in gesture is not critically important on this particular task.

Abstract

Intergroup variation (IGV) refers to variation between different groups of the same species. While its existence in the behavioural realm has been expected and evidenced, the potential effects of IGV are rarely considered in studies that aim to shed light on the evolutionary origins of human socio-cognition, especially in our closest living relatives—the great apes. Here, by taking chimpanzees as a point of reference, we argue that (i) IGV could plausibly explain inconsistent research findings across numerous topics of inquiry (experimental/behavioural studies on chimpanzees), (ii) understanding the evolutionary origins of behaviour requires an accurate assessment of species' modes of behaving across different socio-ecological contexts, which necessitates a reliable estimation of variation across intraspecific groups, and (iii) IGV in the behavioural realm is increasingly likely to be expected owing to the progressive identification of non-human animal cultures. With these points, and by extrapolating from chimpanzees to generic guidelines, we aim to encourage researchers to explicitly consider IGV as an explanatory variable in future studies attempting to understand the socio-cognitive and evolutionary determinants of behaviour in group-living animals.

Abstract

There is evidence that the human cerebellum is involved not only in motor control but also in other cognitive functions. Several studies have shown that language-related activation is lateralized toward the right cerebellar hemisphere in most people, in accordance with leftward cerebral cortical lateralization for language and a general contralaterality of cerebral–cerebellar activations. In terms of behavior, hand use elicits asymmetrical activation in the cerebellum, while hand preference is weakly associated with language lateralization. However, it is not known how, or whether, these functional relations are reflected in anatomy. We investigated volumetric gray matter asymmetries of cerebellar lobules in an MRI data set comprising 2226 subjects. We tested these cerebellar asymmetries for associations with handedness, and for correlations with cerebral cortical anatomical asymmetries of regions important for language or hand motor control, as defined by two different automated image analysis methods and brain atlases, and supplemented with extensive visual quality control. No significant associations of cerebellar asymmetries to handedness were found. Some significant associations of cerebellar lobular asymmetries to cerebral cortical asymmetries were found, but none of these correlations were greater than 0.14, and they were mostly method-/atlas-dependent. On the basis of this large and highly powered study, we conclude that there is no overt structural manifestation of cerebellar functional lateralization and connectivity, in respect of hand motor control or language laterality

Abstract

This paper presents a theory of the syntactic aspects of human sentence production. An important characteristic of unprepared speech is that overt pronunciation of a sentence can be initiated before the speaker has completely worked out the meaning content he or she is going to express in that sentence. Apparently, the speaker is able to build up a syntactically coherent utterance out of a series of syntactic fragments each rendering a new part of the meaning content. This incremental, left-to-right mode of sentence production is the central capability of the proposed Incremental Procedural Grammar (IPG). Certain other properties of spontaneous speech, as derivable from speech errors, hesitations, self-repairs, and language pathology, are accounted for as well. The psychological plausibility thus gained by the grammar appears compatible with a satisfactory level of linguistic plausibility in that sentences receive structural descriptions which are in line with current theories of grammar. More importantly, an explanation for the existence of configurational conditions on transformations and other linguistics rules is proposed. The basic design feature of IPG which gives rise to these psychologically and linguistically desirable properties, is the “Procedures + Stack” concept. Sentences are built not by a central constructing agency which overlooks the whole process but by a team of syntactic procedures (modules) which work-in parallel-on small parts of the sentence, have only a limited overview, and whose sole communication channel is a stock. IPG covers object complement constructions, interrogatives, and word order in main and subordinate clauses. It handles unbounded dependencies, cross-serial dependencies and coordination phenomena such as gapping and conjunction reduction. It is also capable of generating self-repairs and elliptical answers to questions. IPG has been implemented as an incremental Dutch sentence generator written in LISP.

Abstract

We report a hitherto unknown statistical relationship between the corpus frequency of finite verbs and their fixed linear positions (early vs. late) in finite clauses of English, Dutch, and German. Compared to the overall frequency distribution of verb lemmas in the corpora, high-frequency finite verbs are overused in main clauses, at the expense of nonfinite verbs. This finite versus nonfinite split of high-frequency verbs is basically absent from subordinate clauses. Furthermore, this “main-clause bias” (MCB) of high-frequency verbs is more prominent in German and Dutch (SOV languages) than in English (an SVO language). We attribute the MCB and its varying effect sizes to faster accessibility of high-frequency finite verbs, which (1) increases the probability for these verbs to land in clauses mandating early verb placement, and (2) boosts the activation of clause plans that assign verbs to early linear positions (in casu: clauses with SVO as opposed to SOV order).

Abstract

In this article, we examine gaze direction in responses to polar questions using both quantitative and conversation analytic (CA) methods. The data come from a novel corpus of conversations in which participants wore eye-tracking glasses to obtain direct measures of their eye movements. The results show that while most preferred responses are produced with gaze toward the questioner, most dispreferred responses are produced with gaze aversion. We further demonstrate that gaze aversion by respondents can occasion self-repair by questioners in the transition space between turns, indicating that the relationship between gaze direction and preference is more than a mere statistical association. We conclude that gaze direction in responses to polar questions functions as a signal of response preference. Data are in American, British, and Canadian English.

Abstract

Written information is often of limited accessibility to deaf people who use sign language. The eSign project was undertaken as a response to the need for technologies enabling efficient production and distribution over the Internet of sign language content. By using an avatar-independent scripting notation for signing gestures and a client-side web browser plug-in to translate this notation into motion data for an avatar, we achieve highly efficient delivery of signing, while avoiding the inflexibility of video or motion capture. Tests with members of the deaf community have indicated that the method can provide an acceptable quality of signing.

Abstract

Speech is structured into parts by syntactic and prosodic breaks. In locally syntactic ambiguous sentences, the detection of a syntactic break necessarily follows detection of a corresponding prosodic break, making an investigation of the immediate interplay of syntactic and prosodic information impossible when studying sentences in isolation. This problem can be solved, however, by embedding sentences in a discourse context that induces the expectation of either the presence or the absence of a syntactic break right at a prosodic break. Event-related potentials (ERPs) were compared to acoustically identical sentences in these different contexts. We found in two experiments that the closure positive shift, an ERP component known to be elicited by prosodic breaks, was reduced in size when a prosodic break was aligned with a syntactic break. These results establish that the brain matches prosodic information against syntactic information immediately.

Abstract

English speakers have been shown to map abstract concepts in space, which occurs on both the vertical and horizontal dimensions. For example, words such as God are associated with up and right spatial locations, and words such as Satan with down and left. If the tendency to map concepts in space is a universal property of human cognition, then it is likely that such mappings may be at least partly culturally-specific, since many concepts are themselves language-specific and therefore cultural conventions. Here we investigated whether Mandarin speakers report spatial mapping of concepts, and how these mappings compare with English speakers (i.e. are words with the same meaning associated with the same spatial locations). Across two studies, results showed that both native English and Mandarin speakers reported spatial mapping of concepts, and that the distribution of mappings was highly similar for the two groups. Theoretical implications are discussed.

Abstract

This paper reports on two studies investigating children's and adults' processing of sentences containing ambiguity of prepositional phrase (PP) attachment. Study 1 used corpus data to investigate whether cues argued to be used by adults to resolve PP-attachment ambiguities are available in child-directed speech. Study 2 was an on-line reaction time study investigating the role of lexical and referential biases in syntactic ambiguity resolution by children and adults. Forty children (mean age 8;4) and 37 adults listened to V-NP-PP sentences containing temporary ambiguity of PP-attachment. The sentences were manipulated for (i) verb semantics, (ii) the definiteness of the object NP, and (iii) PP-attachment site. The children and adults did not differ qualitatively from each other in their resolution of the ambiguity. A verb semantics by attachment interaction suggested that different attachment analyses were pursued depending on the semantics of the verb. There was no influence of the definiteness of the object NP in either children's or adults' parsing preferences. The findings from the on-line task matched up well with the corpus data, thus identifying a role for the input in the development of parsing strategies.

Abstract

We present the results from four studies, two corpora and two experimental, which suggest that English- and German-speaking children (3;1–4;9 years) use multiple constraints to process and produce object relative clauses. Our two corpora studies show that children produce object relatives that reflect the distributional and discourse regularities of the input. Specifically, the results show that when children produce object relatives they most often do so with (a) an inanimate head noun, and (b) a pronominal relative clause subject. Our experimental findings show that children use these constraints to process and produce this construction type. Moreover, when children were required to repeat the object relatives they most often use in naturalistic speech, the subject-object asymmetry in processing of relative clauses disappeared. We also report cross-linguistic differences in children's rate of acquisition which reflect properties of the input language. Overall, our results suggest that children are sensitive to the same constraints on relative clause processing as adults.

Abstract

We investigate whether grammatical information is accessed in processing noun phrase ellipsis (NPE) and other anaphoric constructions. The first experiment used an agreement attraction paradigm to reveal that ungrammatical plural verbs following NPE with an antecedent containing a plural modifier (e.g. Derek’s key to the boxes … and Mary’s_ probably *are safe in the drawer) show similar facilitation to non-elided NPs. The second experiment used the same paradigm to examine a coordination construction without anaphoric elements, and the third examined anaphoric one. Agreement attraction was not observed in either experiment, suggesting that processing NPE is different from processing non-anaphoric coordination constructions or anaphoric one. Taken together, the results indicate that the parser is sensitive to grammatical distinctions at the ellipsis site where it prioritises and retrieves the head at the initial stage of processing and retrieves the local noun within the modifier phrase only when it is necessary in parsing NPE.

Abstract

It is well-established that allographs like the uppercase and lowercase forms of the Roman alphabet (e.g., a and A) map onto the same "abstract letter identity," orthographic representations that are independent of the visual form. Consistent with this, in the allograph match task ("Are 'a' and 'A' the same letter?"), priming by a masked letter prime is equally robust for visually dissimilar prime-target pairs (e.g., d and D) and similar pairs (e.g., c and C). However, in principle this pattern of priming is also consistent with the possibility that allograph priming is purely phonological, based on the letter name. Because different allographic forms of the same letter, by definition, share a letter name, it is impossible to rule out this possibility a priori. In the present study, we investigated the influence of shared letter names by taking advantage of the fact that Japanese is written in two distinct writing systems, syllabic kana-that has two parallel forms, hiragana and katakana-and logographic kanji. Using the allograph match task, we tested whether a kanji prime with the same pronunciation as the target kana (e.g., both pronounced /i/) produces the same amount of priming as a kana prime in the opposite kana form (e.g.,). We found that the kana primes produced substantially greater priming than the phonologically identical kanji prime. which we take as evidence that allograph priming is based on abstract kana identity, not purely phonology.

Abstract

The Japanese kana syllabary has 2 allographic forms, hiragana and katakana. As with other allographic variants like the uppercase and lowercase letters of the Roman alphabet, they show robust formindependent priming effects in the allograph match task (e.g., Kinoshita. Schubert. & Verdonschot, 2019). suggesting that they share abstract character-level representations. In direct contradiction, Perea. Nakayama, and Lupker (2017) argued that hiragana and katakana do not share character-level representations. based on their finding of reduced priming with identity prime containing a mix of hiragana and katakana (the mixed-kana prime) relative to the all-katakana identity prime in a lexical-decision task with loanword targets written in katakana. Here we sought to reconcile these seemingly contradictory claims, using mixed-kana. hiragana, and katakana primes in lexical decision. The mixed-kana prime and hiragana prime produced priming effects that are indistinguishable, and both were reduced in size relative to the priming effect produced by the katakana identity prime. Furthermore, this pattern was unchanged when the target was presented in hiragana. The findings are interpreted in terms of the assumption that the katakana format is specified in the orthographic representation of loanwords in Japanese readers. Implications of the account for the universality across writing systems is discussed.

Abstract

We report three studies (one corpus, two experimental) that investigated the acquisition of relative clauses (RCs) in Finnish-speaking children. Study 1 found that Finnish children's naturalistic exposure to RCs predominantly consists of non-subject relatives (i.e. oblique, object) which typically have inanimate head nouns. Study 2 tested children's comprehension of subject, object, and two types of oblique relatives. No difference was found in the children's performance on different structures, including a lack of previously widely reported asymmetry between subject and object relatives. However, children's comprehension was modulated by animacy of the head referent. Study 3 tested children's production of the same RC structures using sentence repetition. Again we found no subject–object asymmetry. The pattern of results suggested that distributional frequency patterns and the relative complexity of the relativizer contribute to the difficulty associated with particular RC structures.

Abstract

Pretence and creativity are often regarded as ubiquitous characteristics of childhood, yet not all education systems value or promote these attributes to the same extent. Different pedagogies and practices are evident within the UK National Curriculum, Steiner and Montessori schools. In this study, 20 children participated from each of these school systems (N = 60, aged 6;10–8;11) completing the test of creative thinking—drawing production (TCT-DP; K. K. Urban, & H. G. Jellen, 1996) and a pretend actions task (W. F. Overton & J. P. Jackson, 1973). Overall, Steiner pupils performed significantly higher on the TCT-DP than both the Montessori and National Curriculum pupils who performed similarly. Steiner pupils also performed significantly better on the pretend actions task than the Montessori pupils, but no other significant differences were found. Overall, there was also a significant positive correlation between pretence and creativity in the current sample, supporting previous research suggesting that these skills are related (e.g., A.S. Kaugars & S. W. Russ, 2009; P. Y. Mullineaux & L. F. Dilalla, 2009).

Abstract

Gestures that accompany speech are known to be tightly coupled with speech production. However little is known about the cognitive processes that underlie this link. Previous cross-linguistic research has provided preliminary evidence for online interaction between the two systems based on the systematic co-variation found between how different languages syntactically package Manner and Path information of a motion event and how gestures represent Manner and Path. Here we elaborate on this finding by testing whether speakers within the same language gesturally express Manner and Path differently according to their online choice of syntactic packaging of Manner and Path, or whether gestural expression is pre-determined by a habitual conceptual schema congruent with the linguistic typology. Typologically congruent and incongruent syntactic structures for expressing Manner and Path (i.e., in a single clause or multiple clauses) were elicited from English speakers. We found that gestural expressions were determined by the online choice of syntactic packaging rather than by a habitual conceptual schema. It is therefore concluded that speech and gesture production processes interface online at the conceptual planning phase. Implications of the findings for models of speech and gesture production are discussed

Abstract

People spontaneously produce gestures during speaking and thinking. The authors focus here on gestures that depict or indicate information related to the contents of concurrent speech or thought (i.e., representational gestures). Previous research indicates that such gestures have not only communicative functions, but also self-oriented cognitive functions. In this article, the authors propose a new theoretical framework, the gesture-for-conceptualization hypothesis, which explains the self-oriented functions of representational gestures. According to this framework, representational gestures affect cognitive processes in 4 main ways: gestures activate, manipulate, package, and explore spatio-motoric information for speaking and thinking. These four functions are shaped by gesture's ability to schematize information, that is, to focus on a small subset of available information that is potentially relevant to the task at hand. The framework is based on the assumption that gestures are generated from the same system that generates practical actions, such as object manipulation; however, gestures are distinct from practical actions in that they represent information. The framework provides a novel, parsimonious, and comprehensive account of the self-oriented functions of gestures. The authors discuss how the framework accounts for gestures that depict abstract or metaphoric content, and they consider implications for the relations between self-oriented and communicative functions of gestures

Abstract

In a Turing test, a judge decides whether their conversation partner is either a machine or human. What cues does the judge use to determine this? In particular, are presumably unique features of human language actually perceived as humanlike? Participants rated the humanness of a set of sentences that were manipulated for grammatical construction: linear right-branching or hierarchical center-embedded and their plausibility with regard to world knowledge.

We found that center-embedded sentences are perceived as less humanlike than right-branching sentences and more plausible sentences are regarded as more humanlike. However, the effect of plausibility of the sentence on perceived humanness is smaller for center-embedded sentences than for right-branching sentences.

Participants also rated a conversation with either correct or incorrect use of the context by the agent. No effect of context use was found. Also, participants rated a full transcript of either a real human or a real chatbot, and we found that chatbots were reliably perceived as less humanlike than real humans, in line with our expectation. We did, however, find individual differences between chatbots and humans.

Abstract

In a way, the entire history of linguistic thought from the Antiquity to present days is a series of variations on two key themes: 1. In a certain sense, language and cognition are the same, and 2. In a certain sense, all languages are the same. What varies is the way in which “in a certain sense” is spelled out. Interpretations oscillate between radical positions such as the idea that thinking without speaking is impossible to the idea that it is just language which vexes our cognition and hence makes it rather impossible, and similarly between the idea that all differences between natural languages are nothing but irrelevant variations in the “vox”, the “external form” to the idea that it our thought is massively shaped by the particular structural features of the language we happen to speak. It is remarkable how little agreement has been reached on these issues after more than 2500 years of discussion. This, it is argued, has mainly two reasons: (a) The entire argument is largely confined to a few lexical and morphological properties of human languages, and (b) the discussion is rarely based on empirical research on “language at work” - how do we manage to solve those many little tasks for which human languages are designed in the first place.

Abstract

The German Perfekt has two quite different temporal readings, as illustrated by the two possible continuations of the sentence Peter hat gearbeitet in i, ii, respectively: (i) Peter hat gearbeitet und ist müde. Peter has worked and is tired. (ii) Peter hat gearbeitet und wollte nicht gestört werden. Peter has worked and wanted not to be disturbed. The first reading essentially corresponds to the English present perfect; the second can take a temporal adverbial with past time reference ('yesterday at five', 'when the phone rang', and so on), and an English translation would require a past tense ('Peter worked/was working'). This article shows that the Perfekt has a uniform temporal meaning that results systematically from the interaction of its three components-finiteness marking, auxiliary and past participle-and that the two readings are the consequence of a structural ambiguity. This analysis also predicts the properties of other participle constructions, in particular the passive in German.

Abstract

Chinese has a number of particles such as le, guo, zai and zhe that add a particular aspectual value to the verb to which they are attached. There have been many characterisations of this value in the literature. In this paper, we review several existing influential accounts of these particles, including those in Li and Thompson (1981), Smith (1991), and Mangione and Li (1993). We argue that all these characterisations are intuitively plausible, but none of them is precise.We propose that these particles serve to mark which part of the sentence''s descriptive content is asserted, and that their aspectual value is a consequence of this function. We provide a simple and precise definition of the meanings of le, guo, zai and zhe in terms of the relationship between topic time and time of situation, and show the consequences of their interaction with different verb expressions within thisnew framework of interpretation.

Abstract

Language acquisition is the transition between the language faculty, with which we are born as a part of our genetic endowment, to the mastery of one or more linguistic systems. There is a plethora of findings about this process; but these findings still do not form a coherent picture of the principles which underlie this process. There are at least six reasons for this situation. First, there is an enormous variability in the conditions under which this process occurs. Second, the learning capacity does not remain constant over time. Third, the process extends over many years and is therefore hard to study. Fourth, especially the investigation of the meaning side is problem-loaded. Fifth, many skills and types of knowledge must be learned in a more or less synchronised way. And sixth, our understanding of the functioning of linguistic systems is still very limited. Nevertheless, there are a few overarching results, three of which are discussed here: (1) There are salient differences between child and adult learners: While children normally end up with perfect mastery of the language to be learned, this is hardly ever the case for adults. On the hand, it could be shown for each linguistic property examined so far, that adults are in principle able to learn it up to perfection. So, adults can learn everything perfectly well, they just don’t. (2) Within childhood, age of onset plays no essential role for ultimate attainment. (3) Children care much more for formal correctness than adults - they are just better in mimicking existing systems. It is argued that age does not affect the „construction capacity”- the capacity to build up linguistic systems - but the „copying faculty”, i.e., the faculty to imitate an existing system.

Abstract

Neurodevelopmental disorders are defined by highly heritable problems during development and brain growth. Attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), and intellectual disability (ID) are frequent neurodevelopmental disorders, with common comorbidity among them. Imaging genetics studies on the role of disease-linked genetic variants on brain structure and function have been performed to unravel the etiology of these disorders. Here, we reviewed imaging genetics literature on these disorders attempting to understand the mechanisms of individual disorders and their clinical overlap. For ADHD and ASD, we selected replicated candidate genes implicated through common genetic variants. For ID, which is mainly caused by rare variants, we included genes for relatively frequent forms of ID occurring comorbid with ADHD or ASD. We reviewed case-control studies and studies of risk variants in healthy individuals. Imaging genetics studies for ADHD were retrieved for SLC6A3/DAT1, DRD2, DRD4, NOS1, and SLC6A4/5HTT. For ASD, studies on CNTNAP2, MET, OXTR, and SLC6A4/5HTT were found. For ID, we reviewed the genes FMR1, TSC1 and TSC2, NF1, and MECP2. Alterations in brain volume, activity, and connectivity were observed. Several findings were consistent across studies, implicating, for example, SLC6A4/5HTT in brain activation and functional connectivity related to emotion regulation. However, many studies had small sample sizes, and hypothesis-based, brain region-specific studies were common. Results from available studies confirm that imaging genetics can provide insight into the link between genes, disease-related behavior, and the brain. However, the field is still in its early stages, and conclusions about shared mechanisms cannot yet be drawn.

Abstract

Starting with Ross (1970), various proposals have been made to classify elliptical coordinations and to characterize different languages according to the types of ellipses which they admit. Sanders (1977) discusses four of these proposals, shows that they are inadequate on various grounds and proposes a fifth typology whose central claim is 'evidently correct', as he states (p. 258). In the following, I shall briefly outline this typology and then show that it is inadequate, too. Since there is only one language 1 know — German — I will take all my examples from this language. Moreover, all examples will be straightforward and easy to be judged.

Abstract

In John has left London, it is clear that the event in question, John's leaving London, has occurred in the past, for example yesterday at ten. Why is it impossible, then, to make this the event time more explicit by such an adverbial, as in Yesterday at ten, John has left London? Any solution of this puzzle crucially hinges on the meaning assigned to the perfect, and the present perfect in particular. Two such solutions, a scope solution and the 'current relevance'-solution, are discussed and shown to be inadequate. A new, strictly compositional analysis of the English perfect is suggested, and it is argued that the imcompatibility of the present perfect and most past tense adverbials has neither syntactic nor semantic reasons but follows from a simple pragmatical constraint, called here the 'position-definiteness constraint'. It is the very same constraint, which also makes an utterance such as At ten, John had left at nine pragmatically odd, even if John indeed had left at nine, and hence the utterance is true.

Abstract

The interaction of action-related language processing with actual movement is an indicator of the functional role of motor cortical involvement in language understanding. This paper describes two experiments using single action verb stimuli. Motor responses were performed with the hand or the foot. To test the double dissociation of language-motor facilitation effects within subjects, Experiments 1 and 2 used a priming procedure where both hand and foot reactions had to be performed in response to different geometrical shapes, which were preceded by action verbs. In Experiment 1, the semantics of the verbs could be ignored whereas Experiment 2 included semantic decisions. Only Experiment 2 revealed a clear double dissociation in reaction times: reactions were facilitated when preceded by verbs describing actions with the matching effector. In Experiment 1, by contrast, there was an interaction between verb-response congruence and a semantic variable related to motor features of the verbs. Thus, the double dissociation paradigm of semantic motor priming was effective, corroborating the role of the motor system in action-related language processing. Importantly, this effect was body part specific.

Abstract

Neurons of the neocortex are organized into six radial layers, which have appeared at different times during evolution, with the superficial layers representing a more recent acquisition. Input to the neocortex predominantly reaches superficial layers (SL, i.e., layers (L) 2-4), while output is generated in deep layers (DL, i.e., L5-6) [1]. Intracortical connections, which bridge input and output pathways, are key components of cortical circuits because they allow the propagation and processing of information within the neocortex. Two main types of intracortically projecting neurons (ICPN) can be distinguished by their axonal features: L4 spiny stellate neurons (SSN) with short axons projecting locally within cortical columns [2, 3, 4, 5], and SL and DL long-range projection neurons, including callosally projecting neurons (CPNSL and CPNDL) [5, 6]. Here, we investigate the molecular hallmarks that distinguish SSN, CPNSL, and CPNDL and relate their transcriptional signatures with their output connectivity. Specifically, taking advantage of the presence of CPN in both SL and DL, we identify lamina-independent genetic hallmarks of a constant projection motif (i.e., interhemispheric projection). By performing unbiased transcriptomic comparisons between CPNSL, CPNDL and SSN, we provide specific molecular profiles for each of these populations and show that target identity supersedes laminar position in defining ICPN transcriptional diversity. Together, these findings reveal a projection-based organization of transcriptional programs across cortical layers, which we propose reflects conserved strategy to protect canonical circuit structure (and hence function) across a diverse range of neuroanatomies.

Abstract

An important question in predictive language processing is the extent to which prediction effects can reliably be measured on pre-nominal material (e.g. articles before nouns). Here, we present a large sample (N = 58) close replication of a study by Otten and van Berkum (2009). They report ERP modulations in relation to the predictability of nouns in sentences, measured on gender-marked Dutch articles. We used nearly identical materials, procedures, and data analysis steps. We fail to replicate the original effect, but do observe a pattern consistent with the original data. Methodological differences between our replication and the original study that could potentially have contributed to the diverging results are discussed. In addition, we discuss the suitability of Dutch gender-marked determiners as a test-case for future studies of pre-activation of lexical items.

Abstract

Spatial navigation is a crucial ability for living. Previous animal studies have shown that the S100B gene is causally related to spatial navigation performance in mice. However, the genetic factors influencing human navigation and its neural substrates remain unclear. Here, we provided the first evidence that the S100B gene modulates neural processing of navigationally relevant scenes in humans. First, with a novel protocol, we demonstrated that the spatial pattern of S100B gene expression in postmortem brains was associated with brain activation pattern for spatial navigation in general, and for scene processing in particular. Further, in a large fMRI cohort of healthy adults of Han Chinese (N = 202), we found that S100B gene polymorphisms modulated scene selectivity in the retrosplenial cortex (RSC) and parahippocampal place area. Finally, the serum levels of S100B protein mediated the association between S100B gene polymorphism and scene selectivity in the RSC. Our study takes the first step toward understanding the neurogenetic mechanism of human spatial navigation and suggests a novel approach to discover candidate genes modulating cognitive functions.

Abstract

Spatial navigation is a crucial ability for living. Previous work has revealed multiple distributed brain regions associated with human navigation. However, little is known about how these regions work together as a network (referred to as navigation network) to support flexible navigation. In a novel protocol, we combined neuroimaging meta-analysis, and functional connectivity and behavioral data from the same subjects. Briefly, we first constructed the navigation network for each participant, by combining a large-scale neuroimaging meta-analysis (with the Neurosynth) and resting-state functional magnetic resonance imaging. Then, we investigated multiple topological properties of the navigation networks, including small-worldness, modularity, and highly connected hubs. Finally, we explored the behavioral relevance of these intrinsic properties in a large sample of healthy young adults (N = 190). We found that navigation networks showed small-world and modular organization at global level. More importantly, we found that increased small-worldness and modularity of the navigation network were associated with better navigation ability. Finally, we found that the right retrosplenial complex (RSC) acted as one of the hubs in the navigation network, and that higher betweenness of this region correlated with better navigation ability, suggesting a critical role of the RSC in modulating the navigation network in human brain. Our study takes one of the first steps toward understanding the underlying organization of the navigation network. Moreover, these findings suggest the potential applications of the novel approach to investigating functionally meaningful networks in human brain and their relations to the behavioral impairments in the aging and psychiatric patients.

Abstract

Spatial navigation is a crucial ability for living. Previous studies have shown that males are better at navigation than females, but little is known about the neural basis underlying the sex differences. In this study, we investigated whether cortical scene processing in three well-established scene-selective regions was sexually different, by examining sex differences in scene selectivity and its behavioral relevance to navigation. To do this, we used functional magnetic resonance imaging (fMRI) to scan the parahippocampal place area (PPA), retrosplenial complex (RSC), and occipital place area (OPA) in a large cohort of healthy young adults viewing navigationally relevant scenes (N = 202), and correlated their neural selectivity to scenes with their self-reported navigational ability. Behaviorally, we replicated the previous finding that males were better at navigation than females. Neurally, we found that the scene selectivity in the bilateral PPA, not in the RSC or OPA, was significantly higher in males than females. Such differences could not be explained by confounding factors including brain size and fMRI data quality. Importantly, males, not females, with stronger scene selectivity in the left PPA possessed better navigational ability. This brain-behavior association could not be accounted for by non-navigational abilities (i.e., intelligence and mental rotation ability). Overall, our study provides novel empirical evidence demonstrating sex differences in the brain activity, inviting further studies on sex differences in the neural network for spatial navigation.

Abstract

Objective The aim of the study was to perform a systematic literature search and meta-analysis to reveal the most effective mouthwash for head and neck cancer patients who are experiencing radiation therapy-induced mucositis. Methods Using two electronic databases, a literature search and data interpretation were systematically performed as follows: (i) problem specification, (ii) devising of a literature search plan, (iii) literature search and retrieval of publications, and (iv) meta-analysis and data interpretation. The main problem was specified as follows: what mouthwash is effective in alleviating oral mucositis for head and neck cancer patients who are undergoing radiotherapy? Results The literature search yielded 354 titles and abstracts. After reviewing the extracted literature, 25 publications met the inclusion criteria for this study and 17 of 25 were eventually evaluated in the meta-analysis. Conclusion The results of the meta-analysis indicated that the use of a mouthwash that includes anti-inflammatory properties contributes the most to alleviating oral mucositis in patients who are undergoing radiotherapy to treat head and neck cancer.

Abstract

An important dimension of linguistic variation is formality. This study investigates the role of social distance between interlocutors. Twenty-five native Dutch speakers retold eight short films to confederates, who acted either formally or informally. Speakers were familiarized with the informal confederates, whereas the formal confederates remained strangers. Results show that the two types of interlocutors elicited different versions of the same stories. Formal interlocutors (large social distance) elicited lower articulation rates, and more nouns and prepositions, both indicators of explicit information. Speakers addressing interlocutors to whom social distance was small, however, provided more explicit information with an involved character (i.e. adjectives with subjective meanings). They also used the word and more often as a gap filler or as a way to keep the floor. Furthermore, they were more likely to laugh and to use more interjections, first-person pronouns and direct speech, which are all indicators of involvement, empathy and subjectivity.

Abstract

Does the naming of clocks always require conceptual preparation? To examine this question, speakers were presented with analog and digital clocks that had to be named in Dutch using either a relative (e.g., “quarter to four”) or an absolute (e.g., “three forty-five”) clock time expression format. Naming latencies showed evidence of conceptual preparation when speakers produced relative time expressions to analog and digital clocks, but not when they used absolute time expressions. These findings indicate that conceptual mediation is not always mandatory for telling time, but instead depends on clock time expression format, supporting a multiple-route account of Dutch clock time naming.

Abstract

In the last decade, the involvement of neural oscillatory mechanisms in speech comprehension has been increasingly investigated. Current evidence suggests that low-frequency and high-frequency neural entrainment to the acoustic dynamics of speech are linked to its analysis. One crucial question is whether acoustical processing primarily modulates neural entrainment, or whether entrainment instead reflects linguistic processing. Here, we review studies investigating the effect of linguistic manipulations on neural oscillatory activity. In light of the current findings, we argue that theta (3–8 Hz) entrainment may primarily reflect the analysis of the acoustic features of speech. In contrast, recent evidence suggests that delta (1–3 Hz) and high-frequency activity (>40 Hz) are reliable indicators of perceived linguistic representations. The interdependence between low-frequency and high-frequency neural oscillations, as well as their causal role on speech comprehension, is further discussed with regard to neurophysiological models of speech processing

Abstract

Hand preference is a conspicuous variation in human behaviour, with a worldwide proportion of around 90% of people preferring to use the right hand for many tasks, and 10% the left hand. We used the large cohort of the UK biobank (~500,000 participants) to study possible relations between early life factors and adult hand preference. The probability of being left-handed was affected by the year and location of birth, likely due to cultural effects. In addition, hand preference was affected by birthweight, being part of a multiple birth, season of birth, breastfeeding, and sex, with each effect remaining significant after accounting for all others. Analysis of genome-wide genotype data showed that left-handedness was very weakly heritable, but shared no genetic basis with birthweight. Although on average left-handers and right-handers differed for a number of early life factors, all together these factors had only a minimal predictive value for individual hand preference.

Abstract

Background

Left-right asymmetry is a fundamental organizing feature of the human brain, and neuro-psychiatric disorders such as schizophrenia sometimes involve alterations of brain asymmetry. As early as 8 weeks post conception, the majority of human fetuses move their right arms more than their left arms, but because nerve fibre tracts are still descending from the forebrain at this stage, spinal-muscular asymmetries are likely to play an important developmental role.
Methods

We used RNA sequencing to measure gene expression levels in the left and right spinal cords, and left and right hindbrains, of 18 post-mortem human embryos aged 4-8 weeks post conception. Genes showing embryonic lateralization were tested for an enrichment of signals in genome-wide association data for schizophrenia.
Results

The left side of the embryonic spinal cord was found to mature faster than the right side. Both sides transitioned from transcriptional profiles associated with cell division and proliferation at earlier stages, to neuronal differentiation and function at later stages, but the two sides were not in synchrony (p = 2.2 E-161). The hindbrain showed a left-right mirrored pattern compared to the spinal cord, consistent with the well-known crossing over of function between these two structures. Genes that showed lateralization in the embryonic spinal cord were enriched for association signals with schizophrenia (p = 4.3 E-05).
Conclusions
These are the earliest-stage left-right differences of human neural development ever reported. Disruption of the lateralised developmental programme may play a role in the genetic susceptibility to schizophrenia.

Abstract

Importance Knowing the range of symptoms seen in patients with a missense or loss-of-function variant in KCNB1 and how these symptoms correlate with the type of variant will help clinicians with diagnosis and prognosis when treating new patients. Objectives To investigate the clinical spectrum associated with KCNB1 variants and the genotype-phenotype correlations. Design, Setting, and Participants This study summarized the clinical and genetic information of patients with a presumed pathogenic variant in KCNB1.Patients were identified in research projects or during clinical testing. Information on patients from previously published articles was collected and authors contacted if feasible. All patients were seen at a clinic at one of the participating institutes because of presumed genetic disorder. They were tested in a clinical setting or included in a research project. Main Outcomes and Measures The genetic variant and its inheritance and information on the patient's symptoms and characteristics in a predefined format. All variants were identified with massive parallel sequencing and confirmed with Sanger sequencing in the patient. Absence of the variant in the parents could be confirmed with Sanger sequencing in all families except one. Results Of 26 patients (10 female, 15 male, 1 unknown; mean age at inclusion, 9.8 years; age range, 2-32 years) with developmental delay, 20 (77%) carried a missense variant in the ion channel domain of KCNB1, with a concentration of variants in region S5 to S6. Three variants that led to premature stops were located in the C-terminal and 3 in the ion channel domain. Twenty-one of 25 patients (84%) had seizures, with 9 patients (36%) starting with epileptic spasms between 3 and 18 months of age. All patients had developmental delay, with 17 (65%) experiencing severe developmental delay; 14 (82%) with severe delay had behavioral problems. The developmental delay was milder in 4 of 6 patients with stop variants and in a patient with a variant in the S2 transmembrane element rather than the S4 to S6 region. Conclusions and Relevance De novo KCNB1 missense variants in the ion channel domain and loss-of-function variants in this domain and the C-terminal likely cause neurodevelopmental disorders with or without seizures. Patients with presumed pathogenic variants in KCNB1 have a variable phenotype. However, the type and position of the variants in the protein are (imperfectly) correlated with the severity of the disorder.

Abstract

Objective:

Asymmetry is a subtle but pervasive aspect of the human brain, and it may be altered in several psychiatric conditions. MRI studies have shown subtle differences of brain anatomy between people with major depressive disorder and healthy control subjects, but few studies have specifically examined brain anatomical asymmetry in relation to this disorder, and results from those studies have remained inconclusive. At the functional level, some electroencephalography studies have indicated left fronto-cortical hypoactivity and right parietal hypoactivity in depressive disorders, so aspects of lateralized anatomy may also be affected. The authors used pooled individual-level data from data sets collected around the world to investigate differences in laterality in measures of cortical thickness, cortical surface area, and subcortical volume between individuals with major depression and healthy control subjects.
Methods:

The authors investigated differences in the laterality of thickness and surface area measures of 34 cerebral cortical regions in 2,256 individuals with major depression and 3,504 control subjects from 31 separate data sets, and they investigated volume asymmetries of eight subcortical structures in 2,540 individuals with major depression and 4,230 control subjects from 32 data sets. T1-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas. The large sample size provided 80% power to detect effects of the order of Cohen’s d=0.1.
Results:

The largest effect size (Cohen’s d) of major depression diagnosis was 0.085 for the thickness asymmetry of the superior temporal cortex, which was not significant after adjustment for multiple testing. Asymmetry measures were not significantly associated with medication use, acute compared with remitted status, first episode compared with recurrent status, or age at onset.
Conclusions:

Altered brain macro-anatomical asymmetry may be of little relevance to major depression etiology in most cases.

Abstract

Hand preference is a prominent behavioural trait linked to human brain asymmetry. A handful of genetic variants have been reported to associate with hand preference or quantitative measures related to it. Most of these reports were on the basis of limited sample sizes, by current standards for genetic analysis of complex traits. Here we performed a genome-wide association analysis of hand preference in the large, population-based UK Biobank cohort (N = 331,037). We used gene-set enrichment analysis to investigate whether genes involved in visceral asymmetry are particularly relevant to hand preference, following one previous report. We found no evidence supporting any of the previously suggested variants or genes, nor that genes involved in visceral laterality have a role in hand preference. It remains possible that some of the previously reported genes or pathways are relevant to hand preference as assessed in other ways, or else are relevant within specific disorder populations. However, some or all of the earlier findings are likely to be false positives, and none of them appear relevant to hand preference as defined categorically in the general population. Our analysis did produce a small number of novel, significant associations, including one implicating the microtubule-associated gene MAP2 in handedness.

Abstract

Previous studies of Austrian Sign Language (ÖGS) word-order variations have demonstrated the human processing system’s tendency to interpret a sentence-initial (case-) ambiguous argument as the subject of the clause (“subject preference”). The electroencephalogram study motivating the current report revealed earlier reanalysis effects for object-subject compared to subject-object sentences, in particular, before the start of the movement of the agreement marking sign. The effects were bound to time points prior to when both arguments were referenced in space and/or the transitional hand movement prior to producing the disambiguating sign. Due to the temporal proximity of these time points, it was not clear which visual cues led to disambiguation; that is, whether non-manual markings (body/shoulder/head shift towards the subject position) or the transitional hand movement resolved ambiguity. The present gating study further supports that disambiguation in ÖGS is triggered by cues occurring before the movement of the disambiguating sign. Further, the present study also confirms the presence of the subject preference in ÖGS, showing again that signers and speakers draw on similar strategies during language processing independent of language modality. Although the ultimate role of the visual cues leading to disambiguation (i.e., non-manual markings and transitional movements) requires further investigation, the present study shows that they contribute crucial information about argument structure during online processing. This finding provides strong support for granting these cues some degree of linguistic status (at least in ÖGS).

Abstract

* Kristiansen, M., Deriziotis, P. These authors contributed equally to this work.* - The mechanism of cell death in prion disease is unknown but is associated with the production of a misfolded conformer of the prion protein. We report that disease-associated prion protein specifically inhibits the proteolytic β subunits of the 26S proteasome. Using reporter substrates, fluorogenic peptides, and an activity probe for the β subunits, this inhibitory effect was demonstrated in pure 26S proteasome and three different cell lines. By challenge with recombinant prion and other amyloidogenic proteins, we demonstrate that only the prion protein in a nonnative β sheet conformation inhibits the 26S proteasome at stoichiometric concentrations. Preincubation with an antibody specific for aggregation intermediates abrogates this inhibition, consistent with an oligomeric species mediating this effect. We also present evidence for a direct relationship between prion neuropathology and impairment of the ubiquitin-proteasome system (UPS) in prion-infected UPS-reporter mice. Together, these data suggest a mechanism for intracellular neurotoxicity mediated by oligomers of misfolded prion protein.

Abstract

Only relatively recently have theories of speech production concerned themselves with the part idioms and other multi-word lexical items (MLIs) play in the processes of speech production. Two theories of speech production which attempt to account for the accessing of idioms in speech production are those of Cutting and Bock (1997) and superlemma theory (Sprenger, 2003; Sprenger, Levelt, & Kempen, 2006). Much of the data supporting theories of speech production comes either from time course experiments or from slips of the tongue (Bock & Levelt, 1994). The latter are of two kinds: experimentally induced (Baars, 1992) or naturally observed (Fromkin, 1980). Cutting and Bock use experimentally induced speech errors while Sprenger et al. use time course experiments. The missing data type that has a bearing on speech production involving MLIs is that of naturally occurring slips. In this study the impact of data taken from naturally observed slips involving English and Dutch MLIs are brought to bear on these theories. The data are taken initially from a corpus of just over 1000 naturally observed English slips involving MLIs (the Tuggy corpus). Our argument proceeds as follows. First we show that slips occur independent of whether or not there are MLIs involved. In other words, speech production proceeds in certain of its aspects as though there were no MLI present. We illustrate these slips from the Tuggy data. Second we investigate the predictions of superlemma theory. Superlemma theory (Sprenger et al., 2006) accounts for the selection of MLIs and how their properties enter processes of speech production. It predicts certain activation patterns dependent on a MLI being selected. Each such pattern might give rise to slips of the tongue. This set of predictions is tested against the Tuggy data. Each of the predicted activation patterns yields a significant number of slips. These findings are therefore compatible with a view of MLIs as single units in so far as their activation by lexical concepts goes. However, the theory also predicts that some slips are likely not to occur. We confirm that such slips are not present in the data. These findings are further corroborated by reference a second smaller dataset of slips involving Dutch MLIs (the Kempen corpus). We then use slips involving irreversible binomials to distinguish between the predictions of superlemma theory which are supported by slips involving irreversible binomials and the Cutting and Bock model's predictions for slips involving these MLIs which are not

Abstract

In this exploratory study we test the hypothesis that the retrieval from memory of proper noun Agents (PNAs) under processing pressure causes a greater proportion of such semantic arguments to be placed to the right of the initial position in a clause than would be the case if such retrieval from memory were not necessary. This effect is manifest in sports commentary. Processing pressure on sports commentators is modulated by the speed at which the sport is played and reported. Non-initial placement is also facilitated by formulae which have slots in non-initial position. It follows that the non-initial placement of PNAs is not always semantically or pragmatically motivated. This finding therefore runs counter to a strong form of the functionalist hypothesis that syntactic choices available in the systemic structure of the syntax of a language offer solely semantic or pragmatic choices. It is an open question in a weak functionalist account of language and language use how processing and communicative functions interact in general.

Abstract

Many natural auditory signals, including music and language, change periodically. The effect of such auditory rhythms on the brain is unclear however. One widely held view, dynamic attending theory, proposes that the attentional system entrains to the rhythm and increases attention at moments of rhythmic salience. In support, 2 experiments reported here show reduced response times to visual letter strings shown at auditory rhythm peaks, compared with rhythm troughs. However, we argue that an account invoking the entrainment of general attention should further predict rhythm entrainment to also influence memory for visual stimuli. In 2 pseudoword memory experiments we find evidence against this prediction. Whether a pseudoword is shown during an auditory rhythm peak or not is irrelevant for its later recognition memory in silence. Other attention manipulations, dividing attention and focusing attention, did result in a memory effect. This raises doubts about the suggested attentional nature of rhythm entrainment. We interpret our findings as support for auditory rhythm perception being based on auditory-motor entrainment, not general attention entrainment.

Abstract

It has been hypothesized that schizophrenia is characterized by overly broad automatic activity within lexico-semantic networks. We used two complementary neuroimaging techniques, Magnetoencephalography (MEG) and functional Magnetic Resonance Imaging (fMRI), in combination with a highly automatic indirect semantic priming paradigm, to spatiotemporally localize this abnormality in the brain.

Eighteen people with schizophrenia and 20 demographically-matched control participants viewed target words (“bell”) preceded by directly related (“church”), indirectly related (“priest”), or unrelated (“pants”) prime words in MEG and fMRI sessions. To minimize top-down processing, the prime was masked, the target appeared only 140ms after prime onset, and participants simply monitored for words within a particular semantic category that appeared in filler trials.

Both techniques revealed a significantly larger automatic indirect priming effect in people with schizophrenia than in control participants. MEG temporally localized this enhanced effect to the N400 time window (300-500ms) — the critical stage of accessing meaning from words. fMRI spatially localized the effect to the left temporal fusiform cortex, which plays a role in mapping of orthographic word-form on to meaning. There was no evidence of an enhanced automatic direct semantic priming effect in the schizophrenia group.

These findings provide converging neural evidence for abnormally broad highly automatic lexico-semantic activity in schizophrenia. We argue that, rather than arising from an unconstrained spread of automatic activation across semantic memory, this broader automatic lexico-semantic activity stems from looser connections between the form and meaning of words.

Abstract

This study explores the effects of informational redundancy, as carried by a word's morphological paradigmatic structure, on acoustic duration in read aloud speech. The hypothesis that the more predictable a linguistic unit is, the less salient its realization, was tested on the basis of the acoustic duration of interfixes in Dutch compounds in two datasets: One for the interfix -s- (1155 tokens) and one for the interfix -e(n)- (742 tokens). Both datasets show that the more probable the interfix is, given the compound and its constituents, the longer it is realized. These findings run counter to the predictions of information-theoretical approaches and can be resolved by the Paradigmatic Signal Enhancement Hypothesis. This hypothesis argues that whenever selection of an element from alternatives is probabilistic, the element's duration is predicted by the amount of paradigmatic support for the element: The most likely alternative in the paradigm of selection is realized longer.