Publications

Abstract

So far, studies that investigated interference effects of post-learning processes on episodic memory consolidation in humans have used tasks involving only complex and meaningful information. Such tasks require reallocation of general or encoding-specific resources away from consolidation-relevant activities. The possibility that interference can be elicited using a task that heavily taxes our limited brain resources, but has low semantic and hippocampal related long-term memory processing demands, has never been tested. We address this question by investigating whether consolidation could persist in parallel with an active, encoding-irrelevant, minimally semantic task, regardless of its high resource demands for cognitive processing. We distinguish the impact of such a task on consolidation based on whether it engages resources that are: (1) general/executive, or (2) specific/overlapping with the encoding modality. Our experiments compared subsequent memory performance across two post-encoding consolidation periods: quiet wakeful rest and a cognitively demanding n-Back task. Across six different experiments (total N = 176), we carefully manipulated the design of the n-Back task to target general or specific resources engaged in the ongoing consolidation process. In contrast to previous studies that employed interference tasks involving conceptual stimuli and complex processing demands, we did not find any differences between n-Back and rest conditions on memory performance at delayed test, using both recall and recognition tests. Our results indicate that: (1) quiet, wakeful rest is not a necessary prerequisite for episodic memory consolidation; and (2) post-encoding cognitive engagement does not interfere with memory consolidation when task-performance has minimal semantic and hippocampally-based episodic memory processing demands. We discuss our findings with reference to resource and reactivation-led interference theories

Abstract

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

Abstract

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

Abstract

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

Abstract

A major challenge in second language acquisition is to build up new vocabulary. How is it possible to identify the meaning of a new word among several possible referents? Adult learners typically use contextual information, which reduces the number of possible referents a new word can have. Alternatively, a social partner may facilitate word learning by directing the learner’s attention toward the correct new word meaning. While much is known about the role of this form of ‘joint attention’ in first language acquisition, little is known about its efficacy in second language acquisition. Consequently, we introduce and validate a novel visual word learning game to evaluate how joint attention affects the contextual learning of new words in a second language. Adult learners either acquired new words in a constant or variable sentence context by playing the game with a knowledgeable partner, or by playing the game alone on a computer. Results clearly show that participants who learned new words in social interaction (i) are faster in identifying a correct new word referent in variable sentence contexts, and (ii) temporally coordinate their behavior with a social partner. Testing the learned words in a post-learning recall or recognition task showed that participants, who learned interactively, better recognized words originally learned in a variable context. While this result may suggest that interactive learning facilitates the allocation of attention to a target referent, the differences in the performance during recognition and recall call for further studies investigating the effect of social interaction on learning performance. In summary, we provide first evidence on the role joint attention in second language learning. Furthermore, the new interactive learning game offers itself to further testing in complex neuroimaging research, where the lack of appropriate experimental set-ups has so far limited the investigation of the neural basis of adult word learning in social interaction.

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

We previously discovered that mutations of the human FOXP2 gene cause a monogenic communication disorder, primarily characterized by difficulties in learning to make coordinated sequences of articulatory gestures that underlie speech. Affected people have deficits in expressive and receptive linguistic processing and display structural and/or functional abnormalities in cortical and subcortical brain regions. FOXP2 provides a unique window into neural processes involved in speech and language. In particular, its role as a transcription factor gene offers powerful functional genomic routes for dissecting critical neurogenetic mechanisms. Here, we employ chromatin immunoprecipitation coupled with promoter microarrays (ChIP-chip) to successfully identify genomic sites that are directly bound by FOXP2 protein in native chromatin of human neuron-like cells. We focus on a subset of downstream targets identified by this approach, showing that altered FOXP2 levels yield significant changes in expression in our cell-based models and that FOXP2 binds in a specific manner to consensus sites within the relevant promoters. Moreover, we demonstrate significant quantitative differences in target expression in embryonic brains of mutant mice, mediated by specific in vivo Foxp2-chromatin interactions. This work represents the first identification and in vivo verification of neural targets regulated by FOXP2. Our data indicate that FOXP2 has dual functionality, acting to either repress or activate gene expression at occupied promoters. The identified targets suggest roles in modulating synaptic plasticity, neurodevelopment, neurotransmission, and axon guidance and represent novel entry points into in vivo pathways that may be disturbed in speech and language disorders.

Abstract

Understanding the biological foundations of language is vital to gaining insight into how the capacity for language may have evolved in humans. Animal models can be exploited to learn about the biological underpinnings of shared human traits, and although no other animals display speech or language, a range of behaviors found throughout the animal kingdom are relevant to speech and spoken language. To date, such investigations have been dominated by studies of our closest primate relatives searching for shared traits, or more distantly related species that are sophisticated vocal communicators, like songbirds. Herein I make the case for turning our attention to the Chiropterans, to shed new light on the biological encoding and evolution of human language-relevant traits. Bats employ complex vocalizations to facilitate navigation as well as social interactions, and are exquisitely tuned to acoustic information. Furthermore, bats display behaviors such as vocal learning and vocal turn-taking that are directly pertinent for human spoken language. Emerging technologies are now allowing the study of bat vocal communication, from the behavioral to the neurobiological and molecular level. Although it is clear that no single animal model can reflect the complexity of human language, by comparing such findings across diverse species we can identify the shared biological mechanisms likely to have influenced the evolution of human language. Keywords

Abstract

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

Abstract

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

Abstract

This electrophysiological study asked whether the brain processes grammatical gender
violations in casual speech differently than in careful speech. Native speakers of Dutch were
presented with utterances that contained adjective-noun pairs in which the adjective was either
correctly inflected with a word-final schwa (e.g. een spannende roman “a suspenseful novel”) or
incorrectly uninflected without that schwa (een spannend roman). Consistent with previous
findings, the uninflected adjectives elicited an electrical brain response sensitive to syntactic
violations when the talker was speaking in a careful manner. When the talker was speaking in a
casual manner, this response was absent. A control condition showed electrophysiological responses
for carefully as well as casually produced utterances with semantic anomalies, showing that
listeners were able to understand the content of both types of utterance. The results suggest that
listeners take information about the speaking style of a talker into account when processing the
acoustic-phonetic information provided by the speech signal. Absent schwas in casual speech are
effectively not grammatical gender violations. These changes in syntactic processing are evidence
of contextually-driven neural flexibility.

Abstract

Three experiments investigated semantic and syntactic effects in the production of phrases in Dutch. Bilingual participants were presented with English nouns and were asked to produce an adjective + noun phrase in Dutch including the translation of the noun. In 2 experiments, the authors blocked items by either semantic category or grammatical gender. Participants performed the task slower when the target nouns were of the same semantic category than when they were from different categories and faster when the target nouns had the same gender than when they had different genders. In a final experiment, both manipulations were crossed. The authors replicated the results of the first 2 experiments, and no interaction was found. These findings suggest a feedforward flow of activation between lexico-semantic and lexico-syntactic information.

Abstract

Graded interference effects were tested in a naming task, in parallel for objects and actions. Participants named either object or action pictures presented in the context of other pictures (blocks) that were either semantically very similar, or somewhat semantically similar or semantically dissimilar. We found that naming latencies for both object and action words were modulated by the semantic similarity between the exemplars in each block, providing evidence in both domains of graded semantic effects.

Abstract

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

Abstract

Cross-linguistically, both subjects and topical information tend to be placed at the beginning of a sentence. Subjects are generally highly topical, causing both tendencies to converge on the same word order. However, subjects that lack prototypical topic properties may give rise to an incongruence between the preference to start a sentence with the subject and the preference to start a sentence with the most accessible information. We present a corpus study in which we investigate in what syntactic position (preverbal or postverbal) such low-accessible subjects are typically found in Dutch natural language. We examine the effects of both discourse accessibility (definiteness) and inherent accessibility (animacy). Our results show that definiteness and animacy interact in determining subject position in Dutch. Non-referential (bare) subjects are less likely to occur in preverbal position than definite subjects, and this tendency is reinforced when the subject is inanimate. This suggests that these two properties that make the subject less accessible together can ‘gang up’ against the subject first preference. The results support a probabilistic multifactorial account of syntactic variation.

Abstract

Autoinflammatory disorders (AID) are a heterogeneous group of diseases, characterized by an unprovoked innate immune response, resulting in recurrent or ongoing systemic inflammation and fever1-3. Inflammasomes are protein complexes with an essential role in pyroptosis and the caspase-1-mediated activation of the proinflammatory cytokines IL-1β, IL-17 and IL-18.

Abstract

We meta‐analyzed the effectiveness of incidental second language word learning from spoken input. Our sample contained 105 effect sizes from 32 primary studies employing meaning‐focused word‐learning activities with 1,964 participants with typical cognitive functioning. The random‐effects meta‐analysis yielded a mean effect size of g = 1.05, reflecting generally large vocabulary gains from spoken input in meaning‐focused activities. A meta‐regression with three substantive and two methodological predictors also revealed that adult participants outperformed children in terms of word learning and that interactive learning tasks were more effective than noninteractive ones. Furthermore, learning scores were higher when measured with recognition than with recall tests. Methodologically, the use of a no‐input control group seemed to protect against an overestimation of learning effects, evidenced by smaller effect sizes. Finally, whether a pretest–posttest design was used did not influence effect sizes. All data and the analysis script are publicly available.

Abstract

The eyebrows are used as conversational signals in face-to-face spoken interaction (Ekman, 1979). In Sign Language of the Netherlands (NGT), the eyebrows are typically furrowed in content questions, and raised in polar questions (Coerts, 1992). On the other hand, these eyebrow positions are also associated with anger and surprise, respectively, in general human communication (Ekman, 1993). This overlap in the functional load of the eyebrow positions results in a potential conflict for NGT signers when combining these functions simultaneously. In order to investigate the effect of the simultaneous realization of both functions on the eyebrow position we elicited instances of both question types with neutral affect and with various affective states. The data were coded using the Facial Action Coding System (FACS: Ekman, Friesen, & Hager, 2002) for type of brow movement as well as for intensity. FACS allows for the coding of muscle groups, which are termed Action Units (AUs) and which produce facial appearance changes. The results show that linguistic and affective functions of eyebrows may influence each other in NGT. That is, in surprised polar questions and angry content question a phonetic enhancement takes place of raising and furrowing, respectively. In the items with contrasting eyebrow movements, the grammatical and affective AUs are either blended (occur simultaneously) or they are realized sequentially. Interestingly, the absence of eyebrow raising (marked by AU 1+2) in angry polar questions, and the presence of eyebrow furrowing (realized by AU 4) in surprised content questions suggests that in general AU 4 may be phonetically stronger than AU 1 and AU 2, independent of its linguistic or affective function.

Abstract

Noticing the hole (NTH) occurs when speakers want to say something, but realise they do not know the right word(s). Such awareness of lacking knowledge supposedly facilitates the acquisition of the unknown word(s) from later input (Swain, 1993). We tested this claim by experimentally inducing NTH in a second language (L2) for some participants (experimental), but not others (control). Then, in a price comparison game, all participants were exposed to spoken L2 input containing the to-be-learned words. They were unaware of taking part in an L2 study. Post-tests showed that participants who had noticed holes in their vocabulary had indeed learned more words compared to participants who had not. This held both for the experimental group as well as those participants in the control group who later reported to have noticed holes. Thus, when we become aware of vocabulary holes, the first step to improve our vocabulary is already taken.

Abstract

In a recent series of publications (Traxler et al. J Mem Lang 39:558–592, 1998; Van Gompel et al. J Mem Lang 52:284–307, 2005; see also Van Gompel et al. (In: Kennedy, et al.(eds) Reading as a perceptual process, Oxford, Elsevier pp 621–648, 2000); Van Gompel et al. J Mem Lang 45:225–258, 2001) eye tracking data are reported showing that globally ambiguous (GA) sentences are read faster than locally ambiguous (LA) counterparts. They argue that these data rule out “constraint-based” models where syntactic and conceptual processors operate concurrently and syntactic ambiguity resolution is accomplished by competition. Such models predict the opposite pattern of reading times. However, this argument against competition is valid only in conjunction with two standard assumptions in current constraint-based models of sentence comprehension: (1) that syntactic competitions (e.g., Which is the best attachment site of the incoming constituent?) are pooled together with conceptual competitions (e.g., Which attachment site entails the most plausible meaning?), and (2) that the duration of a competition is a function of the overall (pooled) quality score obtained by each competitor. We argue that it is not necessary to abandon competition as a successful basis for explaining parsing phenomena and that the above-mentioned reading time data can be accounted for by a parallel-interactive model with conceptual and syntactic processors that do not pool their quality scores together. Within the individual linguistic modules, decision-making can very well be competition-based.

Abstract

We introduce a novel computer implementation of the Unification-Space parser (Vosse & Kempen 2000) in the form of a localist neural network whose dynamics is based on interactive activation and inhibition. The wiring of the network is determined by Performance Grammar (Kempen & Harbusch 2003), a lexicalist formalism with feature unification as binding operation. While the network is processing input word strings incrementally, the evolving shape of parse trees is represented in the form of changing patterns of activation in nodes that code for syntactic properties of words and phrases, and for the grammatical functions they fulfill. The system is capable, at least in a qualitative and rudimentary sense, of simulating several important dynamic aspects of human syntactic parsing, including garden-path phenomena and reanalysis, effects of complexity (various types of clause embeddings), fault-tolerance in case of unification failures and unknown words, and predictive parsing (expectation-based analysis, surprisal effects). English is the target language of the parser described.

Abstract

Metaphors occur frequently in literary texts. Deliberate Metaphor Theory (DMT; e.g., Steen, 2017) proposes that metaphors that serve a communicative function as metaphor are radically different from metaphors that do not have this function. We investigated differences in processing between deliberate and non-deliberate metaphors, compared to non-metaphorical words in literary reading. Using the Deliberate Metaphor Identification Procedure (Reijnierse et al., 2018), we identified metaphors in two literary stories. Then, eye-tracking was used to investigate participants’ (N = 72) reading behavior. Deliberate metaphors were read slower than non-deliberate metaphors, and both metaphor types were read slower than non-metaphorical words. Differences were controlled for several psycholinguistic variables. Differences in reading behavior were related to individual differences in reading experience and absorption and appreciation of the story. These results are in line with predictions from DMT and underline the importance of distinguishing between metaphor types in the experimental study of literary reading.

Abstract

The present study investigated the interplay between selective inhibition (the ability to suppress specific competing responses) and nonselective inhibition (the ability to suppress any inappropriate response) during single word production. To this end, we combined two well-established research paradigms: the picture-word interference task and the stop-signal task. Selective inhibition was assessed by instructing participants to name target pictures (e.g., dog) in the presence of semantically related (e.g., cat) or unrelated (e.g., window) distractor words. Nonselective inhibition was tested by occasionally presenting a visual stop-signal, indicating that participants should withhold their verbal response. The stop-signal was presented early (250 ms) aimed at interrupting the lexical selection stage, and late (325 ms) to influence the word-encoding stage of the speech production process. We found longer naming latencies for pictures with semantically related distractors than with unrelated distractors (semantic interference effect). The results further showed that, at both delays, stopping latencies (i.e., stop-signal RTs) were prolonged for naming pictures with semantically related distractors compared to pictures with unrelated distractors. Taken together, our findings suggest that selective and nonselective inhibition, at least partly, share a common inhibitory mechanism during different stages of the speech production process.

Abstract

Readers and listeners actively predict upcoming words during language processing. These predictions might serve to support the unification of incoming words into sentence context and thus rely on interactions between areas in the language network. In the current magnetoencephalography study, participants read sentences that varied in contextual constraints so that the predictability of the sentence-final words was either high or low. Before the sentence-final words, we observed stronger alpha power suppression for the highly compared with low constraining sentences in the left inferior frontal cortex, left posterior temporal region, and visual word form area. Importantly, the temporal and visual word form area alpha power correlated negatively with left frontal gamma power for the highly constraining sentences. We suggest that the correlation between alpha power decrease in temporal language areas and left prefrontal gamma power reflects the initiation of an anticipatory unification process in the language network.

Abstract

Using magnetoencephalography, the current study examined gamma activity associated with language prediction. Participants read high- and low-constraining sentences in which the final word of the sentence was either expected or unexpected. Although no consistent gamma power difference induced by the sentence-final words was found between the expected and unexpected conditions, the correlation of gamma power during the prediction and activation intervals of the sentence-final words was larger when the presented words matched with the prediction compared with when the prediction was violated or when no prediction was available. This suggests that gamma magnitude relates to the match between predicted and perceived words. Moreover, the expected words induced activity with a slower gamma frequency compared with that induced by unexpected words. Overall, the current study establishes that prediction is related to gamma power correlations and a slowing of the gamma frequency.

Abstract

The blocked cyclic naming paradigm has been increasingly employed to investigate the mechanisms underlying spoken word production. Semantic homogeneity typically elicits longer naming latencies than heterogeneity; however, it is debated whether competitive lexical selection or incremental learning underlies this effect. The current study manipulated both semantic and phonological homogeneity and used behavioural and electrophysiological measurements to provide evidence that can distinguish between the two accounts. Results show that naming latencies are longer in semantically homogeneous blocks, but shorter in phonologically homogeneous blocks, relative to heterogeneity. The semantic factor significantly modulates electrophysiological waveforms from 200 ms and the phonological factor from 350 ms after picture presentation. A positive component was demonstrated in both manipulations, possibly reflecting a task-related top-down bias in performing blocked cyclic naming. These results provide novel insights into the neural correlates of blocked cyclic naming and further contribute to the understanding of spoken word production.

Abstract

Next to propositional content, speakers distribute information in their utterances in such a way that listeners can make a distinction between new (focused) and given (non-focused) information. This is referred to as information structure. We measured event-related potentials (ERPs) to explore the role of information structure in semantic processing. Following different questions in wh-question-answer pairs (e.g. What kind of vegetable did Ming buy for cooking today? /Who bought the vegetables for cooking today?), the answer sentences (e.g., Ming bought eggplant/beef to cook today.) contained a critical word, which was either semantically appropriate (eggplant) or inappropriate (beef), and either focus or non-focus. The results showed a full N400 effect only when the critical words were in focus position. In non-focus position a strongly reduced N400 effect was observed, in line with the well-known semantic illusion effect. The results suggest that information structure facilitates semantic processing by devoting more resources to focused information.

Abstract

Neurodevelopmental disorders have a strong genetic component, but despite widespread efforts, the specific genetic factors underlying these disorders remain undefined for a large proportion of affected individuals. Given the accessibility of exome-sequencing, this problem has thus far been addressed from a protein-centric standpoint; however, protein-coding regions only make up ∼1-2% of the human genome. With the advent of whole-genome sequencing we are in the midst of a paradigm shift as it is now possible to interrogate the entire sequence of the human genome (coding and non-coding) to fill in the missing heritability of complex disorders. These new technologies bring new challenges, as the number of non-coding variants identified per individual can be overwhelming, making it prudent to focus on non-coding regions of known function, for which the effects of variation can be predicted and directly tested to assess pathogenicity. The 3’UTRome is a region of the non-coding genome that perfectly fulfils these criteria and is of high interest when searching for pathogenic variation related to complex neurodevelopmental disorders. Herein, we review the regulatory roles of the 3’UTRome as binding sites for microRNAs, RNA binding proteins or during alternative polyadenylation. We detail existing evidence that these regions contribute to neurodevelopmental disorders and outline strategies for identification and validation of novel putatively pathogenic variation in these regions. This evidence suggests that studying the 3’UTRome will lead to the identification of new risk factors, new candidate disease genes and a better understanding of the molecular mechanisms contributing to NDDs.

Abstract

Natural, spontaneous speech (and even quite careful speech) often shows extreme reduction in many speech segments, even resulting in apparent deletion of consonants. Where the flap ([(sic)]) allophone of /t/ and /d/ is expected in American English, one frequently sees an approximant-like or even vocalic pattern, rather than a clear flap. Still, the /t/ or /d/ is usually perceived, suggesting the acoustic characteristics of a reduced flap are sufficient for perception of a consonant. This paper identifies several acoustic characteristics of reduced flaps based on previous acoustic research (size of intensity dip, consonant duration, and F4 valley) and presents phonetic identification data for continua that manipulate these acoustic characteristics of reduction. The results indicate that the most obvious types of acoustic variability seen in natural flaps do affect listeners' percept of a consonant, but not sufficiently to completely account for the percept. Listeners are affected by the acoustic characteristics of consonant reduction, but they are also very skilled at evaluating variability along the acoustic dimensions that realize reduction.

Abstract

Background/Aims: Evidence from spoken word recognition suggests that for English listeners, distinguishing full versus reduced vowels is important, but discerning stress differences involving the same full vowel (as in mu- from music or museum) is not. In Dutch, in contrast, the latter distinction is important. This difference arises from the relative frequency of unstressed full vowels in the two vocabularies. The goal of this paper is to determine how this difference in the lexicon influences the perception of stressed versus unstressed vowels. Methods: All possible sequences of two segments (diphones) in Dutch and in English were presented to native listeners in gated fragments. We recorded identification performance over time throughout the speech signal. The data were here analysed specifically for patterns in perception of stressed versus unstressed vowels. Results: The data reveal significantly larger stress effects (whereby unstressed vowels are harder to identify than stressed vowels) in English than in Dutch. Both language-specific and shared patterns appear regarding which vowels show stress effects. Conclusion: We explain the larger stress effect in English as reflecting the processing demands caused by the difference in use of unstressed vowels in the lexicon. The larger stress effect in English is due to relative inexperience with processing unstressed full vowels

Abstract

This article addresses revitalization of a dormant language whose prospective speakers live in scattered geographical areas. In comparison to increasing the usage of an endangered language, revitalizing a dormant language (one with no living speakers) requires different methods to gain knowledge of the language. Language teaching for a dormant language with a scattered community presents different problems from other teaching situations. In this article, we discuss the types of tasks that must be accomplished for dormant-language revitalization, with particular focus on development of teaching materials. We also address the role of computer technologies, arguing that each use of technology should be evaluated for how effectively it increases fluency. We discuss methods for achieving semi-fluency for the first new speakers of a dormant language, and for spreading the language through the community.

Abstract

An event-related brain potential experiment was carried out to investigate on-line thematic role assignment during sentence–picture matching in patients with Broca's aphasia. Subjects were presented with a picture that was followed by an auditory sentence. The sentence either matched the picture or mismatched the visual information depicted. Sentences differed in complexity, and ranged from simple active semantically irreversible sentences to passive semantically reversible sentences. ERPs were recorded while subjects were engaged in sentence–picture matching. In addition, reaction time and accuracy were measured. Three groups of subjects were tested: Broca patients (N = 10), non-aphasic patients with a right hemisphere (RH) lesion (N = 8), and healthy aged-matched controls (N = 15). The results of this study showed that, in neurologically unimpaired individuals, thematic role assignment in the context of visual information was an immediate process. This in contrast to patients with Broca's aphasia who demonstrated no signs of on-line sensitivity to the picture–sentence mismatches. The syntactic contribution to the thematic role assignment process seemed to be diminished given the reduction and even absence of P600 effects. Nevertheless, Broca patients showed some off-line behavioral sensitivity to the sentence–picture mismatches. The long response latencies of Broca's aphasics make it likely that off-line response strategies were used.

Abstract

The establishment of a reliable model for the study of Purkinje cells in vitro is of particular importance, given their central role in cerebellar function and pathology. Recent advances in induced pluripotent stem cell (iPSC) technology offer the opportunity to generate multiple neuronal subtypes for study in vitro. However, to date, only a handful of studies have generated Purkinje cells from human pluripotent stem cells, with most of these protocols proving challenging to reproduce. Here, we describe a simplified method for the reproducible generation of Purkinje cells from human iPSCs. After 21 days of treatment with factors selected to mimic the self-inductive properties of the isthmic organiser—insulin, fibroblast growth factor 2 (FGF2), and the transforming growth factor β (TGFβ)-receptor blocker SB431542—hiPSCs could be induced to form En1-positive cerebellar progenitors at efficiencies of up to 90%. By day 35 of differentiation, subpopulations of cells representative of the two cerebellar germinal zones, the rhombic lip (Atoh1-positive) and ventricular zone (Ptf1a-positive), could be identified, with the latter giving rise to cells positive for Purkinje cell progenitor-specific markers, including Lhx5, Kirrel2, Olig2 and Skor2. Further maturation was observed following dissociation and co-culture of these cerebellar progenitors with mouse cerebellar cells, with 10% of human cells staining positive for the Purkinje cell marker calbindin by day 70 of differentiation. This protocol, which incorporates modifications designed to enhance cell survival and maturation and improve the ease of handling, should serve to make existing models more accessible, in order to enable future advances in the field.

Abstract

Previous studies have shown that spoken-language processing is inhibited by violation of obligatory regressive assimilation. Weber (2001) replicated this inhibitory effect in a phoneme-monitoring study examining regressive place assimilation of nasals, but found facilitation for violation of progressive assimilation. German listeners detected the velar fricative [x] more quickly when fricative assimilation was violated (e.g., *[bIxt] or *[blInx@n]) than when no violation occurred (e.g., [baxt] or [blu:x@n]). It was argued that a combination of two factors caused facilitation:(1) progressive assimilation creates different restrictions for the monitoring target than regressive assimilation does, and (2) the sequences violating assimilation (e.g., *[Ix]) are novel for German listeners and therefore facilitate fricative detection (novel popout). The present study tested progressive assimilation violation in non-novel sequences using the palatal fricative [C]. Stimuli either violated fricative assimilation (e.g., *[ba:C@l ]) or did not (e.g., [bi: C@l ]). This manipulation does not create novel sequences: sequences like *[a:C] can occur across word boundaries, while *[Ix] cannot. No facilitation was found. However, violation also did not significantly inhibit processing. The results confirm that facilitation depends on the combination of progressive assimilation with novelty of the sequence.

Abstract

A longstanding question in bilingualism is whether syntactic information is shared between the two language processing systems. We used an fMRI repetition suppression paradigm to investigate syntactic priming in reading comprehension in German–English late-acquisition bilinguals. In comparison to conventional subtraction analyses in bilingual experiments, repetition suppression has the advantage of being able to detect neuronal populations that are sensitive to properties that are shared by consecutive stimuli. In this study, we manipulated the syntactic structure between prime and target sentences. A sentence with a passive sentence structure in English was preceded either by a passive or by an active sentence in English or German. We looked for repetition suppression effects in left inferior frontal, left precentral and left middle temporal regions of interest. These regions were defined by a contrast of all non-target sentences in German and English versus the baseline of sentence-format consonant strings. We found decreases in activity (repetition suppression effects) in these regions of interest following the repetition of syntactic structure from the first to the second language and within the second language.
Moreover, a separate behavioural experiment using a word-by-word reading paradigm similar to the fMRI experiment showed faster reading times for primed compared to unprimed English target sentences regardless of whether they were preceded by an English or a German sentence of the same structure.
We conclude that there is interaction between the language processing systems and that at least some syntactic information is shared between a bilingual's languages with similar syntactic structures.

Abstract

Reports of an advantage of bilingualism on brain structure in young adult participants
are inconsistent. Abutalebi et al. (2012) reported more efficient monitoring of conflict during the
Flanker task in young bilinguals compared to young monolingual speakers. The present study
compared young adult (mean age = 24) Cantonese-English bilinguals in Hong Kong and young
adult monolingual speakers. We expected (a) differences in metabolites in neural tissue to result
from bilingual experience, as measured by 1H-MRS at 3T, (b) correlations between metabolic
levels and Flanker conflict and interference effects (c) different associations in bilingual and
monolingual speakers. We found evidence of metabolic differences in the ACC due to bilingualism,
specifically in metabolites Cho, Cr, Glx and NAA. However, we found no significant correlations
between metabolic levels and conflict and interference effects and no significant evidence of
differential relationships between bilingual and monolingual speakers. Furthermore, we found no
evidence of significant differences in the mean size of conflict and interference effects between
groups i.e. no bilingual advantage. Lower levels of Cho, Cr, Glx and NAA in bilingual adults
compared to monolingual adults suggest that the brains of bilinguals develop greater adaptive
control during conflict monitoring because of their extensive bilingual experience.

Abstract

Dichoptic mixtures of equiluminous components of different wavelengths were matched with a binocularly presented "monocular" mixture of appropriate chosen amounts of the same colour components. Stimuli were chosen from the region of 490-630 nm. Although satisfactory colour matches could be obtained, dichoptic mixtures differed from normal mixtures to a considerable extent. Midspectral stimuli tended to be more dominant in the dichoptic mixtures than either short or long wavelength stimuli. An attempt was made to describe the relation between monocular and dichoptic mixtures with one function containing a wavelength variable and an eye dominance parameter.

Abstract

The brain-derived neurotrophic factor (BDNF) was shown to be involved in spatial memory and spatial strategy preference. A naturally occurring single nucleotide polymorphism of the BDNF gene (Val66Met) affects activity-dependent secretion of BDNF. The current event-related fMRI study on preselected groups of ‘Met’ carriers and homozygotes of the ‘Val’ allele investigated the role of this polymorphism on encoding and retrieval in a virtual navigation task in 37 healthy volunteers. In each trial, participants navigated toward a target object. During encoding, three positional cues (columns) with directional cues (shadows) were available. During retrieval, the invisible target had to be replaced while either two objects without shadows (objects trial) or one object with a shadow (shadow trial) were available. The experiment consisted of blocks, informing participants of which trial type would be most likely to occur during retrieval. We observed no differences between genetic groups in task performance or time to complete the navigation tasks. The imaging results show that Met carriers compared to Val homozygotes activate the left hippocampus more during successful object location memory encoding. The observed effects were independent of non-significant performance differences or volumetric differences in the hippocampus. These results indicate that variations of the BDNF gene affect memory encoding during spatial navigation, suggesting that lower levels of BDNF in the hippocampus results in less efficient spatial memory processing

Abstract

Many explanations of the difficulties associated with interpreting object relative clauses appeal to the demands that object relatives make on working memory. MacDonald and Christiansen [MacDonald, M. C., & Christiansen, M. H. (2002). Reassessing working memory: Comment on Just and Carpenter (1992) and Waters and Caplan (1996). Psychological Review, 109, 35-54] pointed to variations in reading experience as a source of differences, arguing that the unique word order of object relatives makes their processing more difficult and more sensitive to the effects of previous experience than the processing of subject relatives. This hypothesis was tested in a large-scale study manipulating reading experiences of adults over several weeks. The group receiving relative clause experience increased reading speeds for object relatives more than for subject relatives, whereas a control experience group did not. The reading time data were compared to performance of a computational model given different amounts of experience. The results support claims for experience-based individual differences and an important role for statistical learning in sentence comprehension processes.

Abstract

Phonological knowledge of a language involves knowledge about which segments can be combined under what conditions. Languages vary in the quantity and quality of licensed combinations, in particular sequences of consonants, with Polish being a language with a large inventory of such combinations. The present paper reports on a two-session experiment in which Polish-speaking adult participants learned nonce words with final consonant clusters. The aim was to study the role of two factors which potentially play a role in the learning of phonotactic structures: the phonological principle of sonority (ordering sound segments within the syllable according to their inherent loudness) and the (non-) existence as a usage-based phenomenon. EEG responses in two different time windows (adversely to behavioral responses) show linguistic processing by native speakers of Polish to be sensitive to both distinctions, in spite of the fact that Polish is rich in sonority-violating clusters. In particular, a general learning effect in terms of an N400 effect was found which was demonstrated to be different for sonority-obeying clusters than for sonority-violating clusters. Furthermore, significant interactions of formedness and session, and of existence and session, demonstrate that both factors, the sonority principle and the frequency pattern, play a role in the learning process.

Abstract

Pointing gestures are recognised to be a primary manifestation of human social cognition and communicative capacity. The goal of this task is to collect empirical descriptions of pointing practices in different cultural settings.

Abstract

Although generally studied in isolation, language and action often co-occur in everyday life. Here we investigated one particular form of simultaneous language and action, namely speech and gestures that speakers use in everyday communication. In a functional magnetic resonance imaging study, we identified the neural networks involved in the integration of semantic information from speech and gestures. Verbal and/or gestural content could be integrated easily or less easily with the content of the preceding part of speech. Premotor areas involved in action observation (Brodmann area [BA] 6) were found to be specifically modulated by action information "mismatching" to a language context. Importantly, an increase in integration load of both verbal and gestural information into prior speech context activated Broca's area and adjacent cortex (BA 45/47). A classical language area, Broca's area, is not only recruited for language-internal processing but also when action observation is integrated with speech. These findings provide direct evidence that action and language processing share a high-level neural integration system.

Abstract

If motor imagery uses neural structures involved in action execution, then the neural correlates of imagining an action should differ between individuals who tend to execute the action differently. Here we report fMRI data showing that motor imagery is influenced by the way people habitually perform motor actions with their particular bodies; that is, motor imagery is ‘body-specific’ (Casasanto, 2009). During mental imagery for complex hand actions, activation of cortical areas involved in motor planning and execution was left-lateralized in right-handers but right-lateralized in left-handers. We conclude that motor imagery involves the generation of an action plan that is grounded in the participant’s motor habits, not just an abstract representation at the level of the action’s goal. People with different patterns of motor experience form correspondingly different neurocognitive representations of imagined actions.

Abstract

Several studies indicate that both posterior superior temporal sulcus/middle temporal gyrus (pSTS/MTG) and left inferior frontal gyrus (LIFG) are involved in integrating information from different modalities. Here we investigated the respective roles of these two areas in integration of action and language information. We exploited the fact that the semantic relationship between language and different forms of action (i.e. co-speech gestures and pantomimes) is radically different. Speech and co-speech gestures are always produced together, and gestures are not unambiguously understood without speech. On the contrary, pantomimes are not necessarily produced together with speech and can be easily understood without speech. We presented speech together with these two types of communicative hand actions in matching or mismatching combinations to manipulate semantic integration load. Left and right pSTS/MTG were only involved in semantic integration of speech and pantomimes. Left IFG on the other hand was involved in integration of speech and co-speech gestures as well as of speech and pantomimes. Effective connectivity analyses showed that depending upon the semantic relationship between language and action, LIFG modulates activation levels in left pSTS.

This suggests that integration in pSTS/MTG involves the matching of two input streams for which there is a relatively stable common object representation, whereas integration in LIFG is better characterized as the on-line construction of a new and unified representation of the input streams. In conclusion, pSTS/MTG and LIFG are differentially involved in multimodal integration, crucially depending upon the semantic relationship between the input streams.

Abstract

Co-speech gestures embody a form of manual action that is tightly coupled to the language system. As such, the co-occurrence of speech and co-speech gestures is an excellent example of the interplay between language and action. There are, however, other ways in which language and action can be thought of as closely related. In this paper we will give an overview of studies in cognitive neuroscience that examine the neural underpinnings of links between language and action. Topics include neurocognitive studies of motor representations of speech sounds, action-related language, sign language and co-speech gestures. It will be concluded that there is strong evidence on the interaction between speech and gestures in the brain. This interaction however shares general properties with other domains in which there is interplay between language and action.

Abstract

It has been argued that we map observed actions onto our own motor system. Here we added to this issue by investigating whether hand preference influences the neural correlates of action observation of simple, essentially meaningless hand actions. Such an influence would argue for an intricate neural coupling between action production and action observation, which goes beyond effects of motor repertoire or explicit motor training, as has been suggested before. Indeed, parts of the human motor system exhibited a close coupling between action production and action observation. Ventral premotor and inferior and superior parietal cortices showed differential activation for left- and right-handers that was similar during action production as well as during action observation. This suggests that mapping observed actions onto the observer's own motor system is a core feature of action observation - at least for actions that do not have a clear goal or meaning. Basic differences in the way we act upon the world are not only reflected in neural correlates of action production, but can also influence the brain basis of action observation.

Abstract

Background

The biological mechanisms of headache chronification are poorly understood. We aimed to identify changes in DNA methylation associated with the transformation from episodic to chronic headache.
Methods

Participants were recruited from the population-based Norwegian HUNT Study. Thirty-six female headache patients who transformed from episodic to chronic headache between baseline and follow-up 11 years later were matched against 35 controls with episodic headache. DNA methylation was quantified at 485,000 CpG sites, and changes in methylation level at these sites were compared between cases and controls by linear regression analysis. Data were analyzed in two stages (Stages 1 and 2) and in a combined meta-analysis.
Results

None of the top 20 CpG sites identified in Stage 1 replicated in Stage 2 after multiple testing correction. In the combined meta-analysis the strongest associated CpG sites were related to SH2D5 and NPTX2, two brain-expressed genes involved in the regulation of synaptic plasticity. Functional enrichment analysis pointed to processes including calcium ion binding and estrogen receptor pathways.
Conclusion

In this first genome-wide study of DNA methylation in headache chronification several potentially implicated loci and processes were identified. The study exemplifies the use of prospectively collected population cohorts to search for epigenetic mechanisms of disease

Abstract

Researchers have suggested that the vocabularies of languages are oriented towards the communicative needs of language users. Here, we provide evidence demonstrating that the higher frequency of visual words in a large variety of English corpora is reflected in greater lexical differentiation—a greater number of unique words—for the visual domain in the English lexicon. In comparison, sensory modalities that are less frequently talked about, particularly taste and smell, show less lexical differentiation. In addition, we show that even though sensory language can be expected to change across historical time and between contexts of use (e.g., spoken language versus fiction), the pattern of visual dominance is a stable property of the English language. Thus, we show that across the board, precisely those semantic domains that are more frequently talked about are also more lexically differentiated, for perceptual experiences. This correlation between type and token frequencies suggests that the sensory lexicon of English is geared towards communicative efficiency.

Abstract

It is often assumed odors are associated with hot and cold temperature, since odor processing may trigger thermal sensations, such as coolness in the case of mint. It is unknown, however, whether people make consistent temperature associations for a variety of everyday odors, and, if so, what determines them. Previous work investigating the bases of cross-modal associations suggests a number of possibilities, including universal forces (e.g., perception), as well as culture-specific forces (e.g., language and cultural beliefs). In this study, we examined odor-temperature associations in three cultures—Maniq (N = 11), Thai (N = 24), and Dutch (N = 24)—who differ with respect to their cultural preoccupation with odors, their odor lexicons, and their beliefs about the relationship of odors (and odor objects) to temperature. Participants matched 15 odors to temperature by touching cups filled with hot or cold water, and described the odors in their native language. The results showed no consistent associations among the Maniq, and only a handful of consistent associations between odor and temperature among the Thai and Dutch. The consistent associations differed across the two groups, arguing against their universality. Further analysis revealed cross-modal associations could not be explained by language, but could be the result of cultural beliefs

Abstract

Brain processing depends on the interactions between neuronal groups. Those interactions are governed by the pattern of anatomical connections and by yet unknown mechanisms that modulate the effective strength of a given connection. We found that the mutual influence among neuronal groups depends on the phase relation between rhythmic activities within the groups. Phase relations supporting interactions between the groups preceded those interactions by a few milliseconds, consistent with a mechanistic role. These effects were specific in time, frequency, and space, and we therefore propose that the pattern of synchronization flexibly determines the pattern of neuronal interactions.

Abstract

Spinocerebellar ataxia type 14 (SCA14) is a subtype of the autosomal dominant cerebellar ataxias that is characterized by slowly progressive cerebellar dysfunction and neurodegeneration. SCA14 is caused by mutations in the PRKCG gene, encoding protein kinase C gamma (PKCγ). Despite the identification of 40 distinct disease-causing mutations in PRKCG, the pathological mechanisms underlying SCA14 remain poorly understood. Here we report the molecular neuropathology of SCA14 in post-mortem cerebellum and in human patient-derived induced pluripotent stem cells (iPSCs) carrying two distinct SCA14 mutations in the C1 domain of PKCγ, H36R and H101Q. We show that endogenous expression of these mutations results in the cytoplasmic mislocalization and aggregation of PKCγ in both patient iPSCs and cerebellum. PKCγ aggregates were not efficiently targeted for degradation. Moreover, mutant PKCγ was found to be hyper-activated, resulting in increased substrate phosphorylation. Together, our findings demonstrate that a combination of both, loss-of-function and gain-of-function mechanisms are likely to underlie the pathogenesis of SCA14, caused by mutations in the C1 domain of PKCγ. Importantly, SCA14 patient iPSCs were found to accurately recapitulate pathological features observed in post-mortem SCA14 cerebellum, underscoring their potential as relevant disease models and their promise as future drug discovery tools.

Abstract

The cerebellar ataxias are a group of incurable brain disorders that are caused primarily by the progressive dysfunction and degeneration of cerebellar Purkinje cells. The lack of reliable disease models for the heterogeneous ataxias has hindered the understanding of the underlying pathogenic mechanisms as well as the development of effective therapies for these devastating diseases. Recent advances in the field of induced pluripotent stem cell (iPSC) technology offer new possibilities to better understand and potentially reverse disease pathology. Given the neurodevelopmental phenotypes observed in several types of ataxias, iPSC-based models have the potential to provide significant insights into disease progression, as well as opportunities for the development of early intervention therapies. To date, however, very few studies have successfully used iPSC-derived cells to cerebellar ataxias. In this review, we focus on recent breakthroughs in generating human iPSC-derived Purkinje cells. We also highlight the future challenges that will need to be addressed in order to fully exploit these models for the modelling of the molecular mechanisms underlying cerebellar ataxias and the development of effective therapeutics.

Abstract

Jedek is a previously unrecognized variety of the Northern Aslian subgroup of the Aslian branch of the Austroasiatic language family. It is spoken by c. 280 individuals in the resettlement area of Sungai Rual, near Jeli in Kelantan state, Peninsular Malaysia. The community originally consisted of several bands of foragers along the middle reaches of the Pergau river. Jedek’s distinct status first became known during a linguistic survey carried out in the DOBES project Tongues of the Semang (2005-2011). This paper describes the process leading up to its discovery and provides an overview of its typological characteristics.

Abstract

Electroencephalography (EEG) provides high temporal resolution cognitive information from non-invasive recordings. However, one of the common practices-using a subset of sensors in ERP analysis is hard to provide a holistic and precise dynamic results. Selecting or grouping subsets of sensors may also be subject to selection bias, multiple comparison, and further complicated by individual differences in the group-level analysis. More importantly, changes in neural generators and variations in response magnitude from the same neural sources are difficult to separate, which limit the capacity of testing different aspects of cognitive hypotheses. We introduce EasyEEG, a toolbox that includes several multivariate analysis methods to directly test cognitive hypotheses based on topographic responses that include data from all sensors. These multivariate methods can investigate effects in the dimensions of response magnitude and topographic patterns separately using data in the sensor space, therefore enable assessing neural response dynamics. The concise workflow and the modular design provide user-friendly and programmer-friendly features. Users of all levels can benefit from the open-sourced, free EasyEEG to obtain a straightforward solution for efficient processing of EEG data and a complete pipeline from raw data to final results for publication.

Abstract

Using the masked priming paradigm, we examined which phonological unit is used when naming Kanji compounds. Although the phonological unit in the Japanese language has been suggested to be the mora, Experiment 1 found no priming for mora-related Kanji prime-target pairs. In Experiment 2, significant priming was only found when Kanji pairs shared the whole sound of their initial Kanji characters. Nevertheless, when the same Kanji pairs used in Experiment 2 were transcribed into Kana, significant mora priming was observed in Experiment 3. In Experiment 4, matching the syllable structure and pitch-accent of the initial Kanji characters did not lead to mora priming, ruling out potential alternative explanations for the earlier absence of the effect. A significant mora priming effect was observed, however, when the shared initial mora constituted the whole sound of their initial Kanji characters in Experiments 5. Lastly, these results were replicated in Experiment 6. Overall, these results indicate that the phonological unit involved when naming Kanji compounds is not the mora but the whole sound of each Kanji character. We discuss how different phonological units may be involved when processing Kanji and Kana words as well as the implications for theories dealing with language production processes.

Abstract

Scene-selective regions (SSRs), including the parahippocampal place area (PPA), retrosplenial cortex (RSC), and transverse occipital sulcus (TOS), are among the most widely characterized functional regions in the human brain. However, previous studies have mostly focused on the commonality within each SSR, providing little information on different aspects of their variability. In a large group of healthy adults (N = 202), we used functional magnetic resonance imaging to investigate different aspects of topographical and functional variability within SSRs, including interindividual, interhemispheric, and sex differences. First, the PPA, RSC, and TOS were delineated manually for each individual. We then demonstrated that SSRs showed substantial interindividual variability in both spatial topography and functional selectivity. We further identified consistent interhemispheric differences in the spatial topography of all three SSRs, but distinct interhemispheric differences in scene selectivity. Moreover, we found that all three SSRs showed stronger scene selectivity in men than in women. In summary, our work thoroughly characterized the interindividual, interhemispheric, and sex variability of the SSRs and invites future work on the origin and functional significance of these variabilities. Additionally, we constructed the first probabilistic atlases for the SSRs, which provide the detailed anatomical reference for further investigations of the scene network.

Abstract

Although bilingual speakers are very good at selectively using one language rather than another, sometimes language selection errors occur. To investigate how bilinguals monitor their speech errors and control their languages in use, we recorded event-related potentials (ERPs) in unbalanced Dutch-English bilingual speakers in a cued language-switching task. We tested the conflict-based monitoring model of Nozari and colleagues by investigating the error-related negativity (ERN) and comparing the effects of the two switching directions (i.e., to the first language, L1 vs. to the second language, L2). Results show that the speakers made more language selection errors when switching from their L2 to the L1 than vice versa. In the EEG, we observed a robust ERN effect following language selection errors compared to correct responses, reflecting monitoring of speech errors. Most interestingly, the ERN effect was enlarged when the speakers were switching to their L2 (less conflict) compared to switching to the L1 (more conflict). Our findings do not support the conflict-based monitoring model. We discuss an alternative account in terms of error prediction and reinforcement learning.

Abstract

Although bilingual speakers are very good at selectively using one language rather than another, sometimes language selection errors occur. We examined the relative contribution of top-down cognitive control and bottom-up language priming to these errors. Unbalanced Dutch-English bilinguals named pictures and were cued to switch between languages under time pressure. We also manipulated the number of same-language trials before a switch (long vs. short runs). Results show that speakers made more language selection errors when switching from their second language (L2) to the first language (L1) than vice versa. Furthermore, they made more errors when switching to the L1 after a short compared to a long run of L2 trials. In the reverse switching direction (L1 to L2), run length had no effect. These findings are most compatible with an account of language selection errors that assigns a strong role to top-down processes of cognitive control.

Abstract

Genome-wide association studies using thousands to hundreds of thousands of single nucleotide polymorphism (SNP) markers and region-wide association studies using a dense panel of SNPs are already in use to identify disease susceptibility genes and to predict disease risk in individuals. Because these tasks become increasingly important, three different data sets were provided for the Genetic Analysis Workshop 15, thus allowing examination of various novel and existing data mining methods for both classification and identification of disease susceptibility genes, gene by gene or gene by environment interaction. The approach most often applied in this presentation group was random forests because of its simplicity, elegance, and robustness. It was used for prediction and for screening for interesting SNPs in a first step. The logistic tree with unbiased selection approach appeared to be an interesting alternative to efficiently select interesting SNPs. Machine learning, specifically ensemble methods, might be useful as pre-screening tools for large-scale association studies because they can be less prone to overfitting, can be less computer processor time intensive, can easily include pair-wise and higher-order interactions compared with standard statistical approaches and can also have a high capability for classification. However, improved implementations that are able to deal with hundreds of thousands of SNPs at a time are required.

Abstract

It is undisputed that presenting a rhythmic stimulus leads to a measurable brain response that follows the rhythmic structure of this stimulus. What is still debated, however, is the question whether this brain response exclusively reflects a regular repetition of evoked responses, or whether it also includes entrained oscillatory activity. Here we systematically present evidence in favor of an involvement of entrained neural oscillations in the processing of rhythmic input while critically pointing out which questions still need to be addressed before this evidence could be considered conclusive. In this context, we also explicitly discuss the potential functional role of such entrained oscillations, suggesting that these stimulus-aligned oscillations reflect, and serve as, predictive processes, an idea often only implicitly assumed in the literature.

Abstract

The Corpus NGT