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

Natural fast speech differs from normal-rate speech with respect to its temporal pattern. Previous results showed that word intelligibility of heavily artificially time-compressed speech could not be improved by making its temporal pattern more similar to that of natural fast speech. This might have been due to the extrapolation of timing rules for natural fast speech to rates that are much faster than can be attained by human speakers. The present study investigates whether, at a speech rate that human speakers can attain, artificially time-compressed speech is easier to process if its timing pattern is similar to that of naturally produced fast speech. Our first experiment suggests, however, that word processing speed was slowed down, relative to linear compression. In a second experiment, word processing of artificially time-compressed speech was compared with processing of naturally produced fast speech. Even when naturally produced fast speech is perfectly intelligible, its less careful articulation, combined with the changed timing pattern, slows down processing, relative to linearly time-compressed speech. Furthermore, listeners preferred artificially time-compressed speech over naturally produced fast speech. These results suggest that linearly time-compressed speech has both a temporal and a segmental advantage over natural fast speech.

Abstract

This study investigated the encoding of syllable boundary information during speech production in Dutch. Based on Levelt's model of phonological encoding, we hypothesized segments and syllable boundaries to be encoded in an incremental way. In a selfmonitoring experiment, decisions about the syllable affiliation (first or second syllable) of a pre-specified consonant, which was the third phoneme in a word, were required (e.g., ka.No canoe vs. kaN.sel pulpit ; capital letters indicate pivotal consonants, dots mark syllable boundaries). First syllable responses were faster than second syllable responses, indicating the incremental nature of segmental encoding and syllabification during speech production planning. The results of the experiment are discussed in the context of Levelt 's model of phonological encoding.

Abstract

Three experiments are reported that examined whether stem complexity plays a role in inflecting polymorphemic words in language production. Experiment 1 showed that preparation effects for words with polymorphemic stems are larger when they are produced among words with constant inflectional structures compared to words with variable inflectional structures and simple stems. This replicates earlier findings for words with monomorphemic stems (Janssen et al., 2002). Experiments 2 and 3 showed that when inflectional structure is held constant, the preparation effects are equally large with simple and compound stems, and with compound and complex adjectival stems. These results indicate that inflectional encoding is blind to the complexity of the stem, which suggests that specific inflectional rather than generic morphological frames guide the generation of inflected forms in speaking words.

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

As people find their way through their environment, objects at navigationally relevant locations can serve as crucial landmarks. The parahippocampal gyrus has previously been shown to be involved in object and scene recognition. In the present study, we investigated the neural representation of navigationally relevant locations. Healthy human adults viewed a route through a virtual museum with objects placed at intersections (decision points) or at simple turns (non-decision points). Event-related functional magnetic resonance imaging (fMRI) data were acquired during subsequent recognition of the objects in isolation. Neural activity in the parahippocampal gyrus reflected the navigational relevance of an object's location in the museum. Parahippocampal responses were selectively increased for objects that occurred at decision points, independent of attentional demands. This increase occurred for forgotten as well as remembered objects, showing implicit retrieval of navigational information. The automatic storage of relevant object location in the parahippocampal gyrus provides a part of the neural mechanism underlying successful navigation.

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

In early Dutch learner varieties, there is no evidence of finiteness being a functional category. There is no V2nd: no correlation between inflectional morphology and movement. Initially, learners express the illocutive function of finiteness through the use of illocutive markers, with the non-use of an illocutive marker expressing the default illocutive function of assertion. Illocutive markers are functioning as adjuncts with scope over the predicate. Illocutive markers become re-analysed as functional elements.The driving force is the acquisition of the auxiliary verbs that occur with past participles. It leads to a reanalysis of illocutive markers as two separate elements: an auxiliary verb and a scope adverb. The (modal) auxiliary carries illocutive function. Lexical verb-argument structure (including the external argument) occurs within the domain of the auxiliary verb. The predicate as the focus constituent occurs within the domain of a scope adverb. This reanalysis establishes a position for the external argument within the domain of AUX. The acquisition of AUX causes the acquisition of a (hierarchical) structure with a complement as a constituent which represents an underlying verb-argument structure, a predicate as the domain of elements that are in focus, and an external (specifier) position as a landing site for elements with topic function.

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

When you compare the behavior of two different age groups which are trying to master the same sensori-motor or cognitive skill, you are likely to discover varying learning routes: different stages, different intervals between stages, or even different orderings of stages. Such heterogeneous learning trajectories may be caused by at least six different types of factors: (1) Initial state: the kinds and levels of skills the learners have available at the onset of the learning episode. (2) Learning mechanisms: rule-based, inductive, connectionist, parameter setting, and so on. (3) Input and feedback characteristics: learning stimuli, information about success and failure. (4) Information processing mechanisms: capacity limitations, attentional biases, response preferences. (5) Energetic variables: motivation, emotional reactions. (6) Final state: the fine-structure of kinds and levels of subskills at the end of the learning episode. This applies to language acquisition as well. First and second language learners probably differ on all six factors. Nevertheless, the debate between advocates and opponents of the Fundamental Difference Hypothesis concerning L1 and L2 acquisition have looked almost exclusively at the first two factors. Those who believe that L1 learners have access to Universal Grammar whereas L2 learners rely on language processing strategies, postulate different learning mechanisms (UG parameter setting in L1, more general inductive strategies in L2 learning). Pienemann opposes this view and, based on his Processability Theory, argues that L1 and L2 learners start out from different initial states: they come to the grammar learning task with different structural hypotheses (SOV versus SVO as basic word order of German).

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

Listeners cannot recognize highly reduced word forms in isolation, but they can do so when these forms are presented in context (Ernestus, Baayen, & Schreuder, 2002). This suggests that not all possible surface forms of words have equal status in the mental lexicon. The present study shows that the reduced forms are linked to the canonical representations in the mental lexicon, and that these latter representations induce reconstruction processes. Listeners restore suffixes that are partly or completely missing in reduced word forms. A series of phoneme-monitoring experiments reveals the nature of this restoration: the basis for suffix restoration is mainly phonological in nature, but orthography has an influence as well.

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

Drozd's critique of Crain & Thornton's (C&T) (1998) book Investigations in Universal Grammar (IUG) raises many issues concerning theory and experimental design within generative approaches to language acquisition. I focus here on one of the strongest theoretical claims of the Modularity Matching Model (MMM): continuity of processing. For reasons different to Drozd, I argue that the assumption is tenuous. Furthermore, I argue that the focus of the MMM and the methodological prescriptions contained in IUG are too narrow to capture language acquisition.

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

Pauses during continuous speech, particularly those that occur within clauses, are thought to reflect the planning of forthcoming verbal output. We used functional Magnetic Resonance Imaging (fMRI) to examine their neural correlates. Six volunteers were scanned while describing seven Rorschach inkblots, producing 3 min of speech per inkblot. In an event-related design, the level of blood oxygenation level dependent (BOLD) contrast during brief speech pauses (mean duration 1.3 s, SD 0.3 s) during overt speech was contrasted with that during intervening periods of articulation. We then examined activity associated with pauses that occurred within clauses and pauses that occurred between grammatical junctions. Relative to articulation during speech, pauses were associated with activation in the banks of the left superior temporal sulcus (BA 39/22), at the temporoparietal junction. Continuous speech was associated with greater activation bilaterally in the inferior frontal (BA 44/45), middle frontal (BA 8) and anterior cingulate (BA 24) gyri, the middle temporal sulcus (BA 21/22), the occipital cortex and the cerebellum. Left temporal activation was evident during pauses that occurred within clauses but not during pauses at grammatical junctions. In summary, articulation during continuous speech involved frontal, temporal and cerebellar areas, while pausing was associated with activity in the left temporal cortex, especially when this occurred within a clause. The latter finding is consistent with evidence that within-clause pauses are a correlate of speech planning and in particular lexical retrieval.

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

Nobel's legacy, or the metamorphosis of what is idealistic Ever since the first Nobel prize in literature was awarded to Prudhomme in 1901, the decisions of the Swedish Academy have been subject to criticism. What is surprising in the changing decision policy as well as in its criticism is the fact that Alfred Nobel's original intentions are hardly ever taken into account: the Nobel prize is a philanthropic prize, it is not meant to select and honour the most eminent literary work but the work with maximal benefit to human beings. What is even more surprising is the fact that no one seems to care that the donator's Last Will is regularly broken.

Abstract

In this article, we discuss the implications of the fact that adult second language learners (outside the classroom) universally develop a well-structured, efficient and simple form of language–the Basic Variety (BV). Three questions are asked as to (1) the structural properties of the BV, (2) the status of these properties and (3) why some structural properties of ‘fully fledged’ languages are more complex. First, we characterize the BV in four respects: its lexical repertoire, the principles according to which utterances are structured, and temporality and spatiality expressed. The organizational principles proposed are small in number, and interact. We analyse this interaction, describing how the BV is put to use in various complex verbal tasks, in order to establish both what its communicative potentialities are, and also those discourse contexts where the constraints come into conflict and where the variety breaks down. This latter phenomenon provides a partial answer to the third question,concerning the relative complexity of ‘fully fledged’ languages–they have devices to deal with such cases. As for the second question, it is argued firstly that the empirically established continuity of the adult acquisition process precludes any assignment of the BV to a mode of linguistic expression (e.g., ‘protolanguage’) distinct from that of ‘fully fledged’ languages and, moreover, that the organizational constraints of the BV belong to the core attributes of the human language capacity, whereas a number of complexifications not attested in the BV are less central properties of this capacity. Finally, it is shown that the notion of feature strength, as used in recent versions of Generative Grammar, allows a straightforward characterization of the BV as a special case of an I-language, in the sense of this theory. Under this perspective, the acquisition of an Ilanguage beyond the BV can essentially be described as a change in feature strength.

Abstract

During the last 25 years, second language acquisition (SLA) research hasmade considerable progress, but is still far from proving a solid basis for foreign language teaching, or from a general theory of SLA. In addition, its status within the linguistic disciplines is still very low. I argue this has not much to do with low empirical or theoretical standards in the field—in this regard, SLA research is fully competitive—but with a particular perspective on the acquisition process: SLA researches learners' utterances as deviations from a certain target, instead of genuine manifestations of underlying language capacity; it analyses them in terms of what they are not rather than what they are. For some purposes such a "target deviation perspective" makes sense, but it will not help SLA researchers to substantially and independently contribute to a deeper understanding of the structure and function of the human language faculty. Therefore, these findings will remain of limited interest to other scientists until SLA researchers consider learner varieties a normal, in fact typical, manifestation of this unique human capacity.

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

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

In various applications of forensic phonetics the question arises as to how far aural-perceptual speaker recognition performance is reliable. Therefore, it is necessary to examine the relationship between speaker recognition results and human perception/production abilities like musicality or speech sensitivity. In this study, performance in a speaker recognition experiment and a speech sensitivity test are correlated. The results show a moderately significant positive correlation between the two tasks. Generally, performance in the speaker recognition task was better than in the speech sensitivity test. Professionals in speech and singing yielded a more homogeneous correlation than non-experts. Training in speech as well as choir-singing seems to have a positive effect on performance in speaker recognition. It may be concluded, firstly, that in cases where the reliability of voice line-up results or the credibility of a testimony have to be considered, the speech sensitivity test could be a useful indicator. Secondly, the speech sensitivity test might be integrated into the canon of possible procedures for the accreditation of forensic phoneticians. Both tests may also be used in combination.

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

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

This study addresses the supralexical inferential processes underlying wellformedness judgements and latencies for a specic sublexical unit that appears in Dutch compounds, the interfix. Production studies have shown that the selection of interfixes in novel Dutch compounds and the speed of
this selection is primarily determined by the distribution of interfixes in existing compounds that share the left constituent with the target compound, i.e. the ‘‘left constituent family’’. In this paper, we consider the question whether constituent families also affect wellformedness decisions of novel as well as existing Dutch compounds in comprehension. We visually presented compounds containing interfixes that were either in line with the bias of the left constituent family or not. In the case of existing compounds, we also presented variants with replaced interfixes. As in production, the bias of the left constituent family emerged as a crucial predictor for both acceptance rates and response latencies. This result supports the hypothesis that, as in production, constituent families are (co-)activated in comprehension. We argue that this co-activation is part of a supralexical inferential process, and we discuss how our data might be interpreted within sublexical and supralexical theories of morphological processing.

Abstract

This study addresses the possibility that interfixes in multiconstituent nominal compounds in German and Dutch are functional as markers of immediate constituent structure.We report a lexical statistical survey of interfixation in the lexicons of German and Dutch which shows that all interfixes of German and one interfix of Dutch are significantly more likely to appear at the major constituent boundary than expected under chance conditions. A series of experiments provides evidence that speakers of German and Dutch are sensitive to the probabilistic cues to constituent structure provided by the interfixes. Thus, our data provide evidence that probability is part and parcel of grammatical competence.

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

Dance is an icon of human expression. Despite astounding diversity around the world’s cultures and dazzling abundance of reminiscent animal systems, the evolution of dance in the human clade remains obscure. Dance requires individuals to interactively synchronize their whole-body tempo to their partner’s, with near-perfect precision. This capacity is motorically-heavy, engaging multiple neural circuitries, but also dependent on an acute socio-emotional bond between partners. Hitherto, these factors helped explain why no dance forms were present amongst nonhuman primates. Critically, evidence for conjoined full-body rhythmic entrainment in great apes that could help reconstruct possible proto-stages of human dance is still lacking. Here, we report an endogenously-effected case of ritualized dance-like behaviour between two captive chimpanzees – synchronized bipedalism. We submitted video recordings to rigorous time-series analysis and circular statistics. We found that individual step tempo was within the genus’ range of “solo” bipedalism. Between-individual analyses, however, revealed that synchronisation between individuals was non-random, predictable, phase concordant, maintained with instantaneous centi-second precision and jointly regulated, with individuals also taking turns as “pace-makers”. No function was apparent besides the behaviour’s putative positive social affiliation. Our analyses show a first case of spontaneous whole-body entrainment between two ape peers, thus providing tentative empirical evidence for phylogenies of human dance. Human proto-dance, we argue, may have been rooted in mechanisms of social cohesion among small groups that might have granted stress-releasing benefits via gait-synchrony and mutual-touch. An external sound/musical beat may have been initially uninvolved. We discuss dance evolution as driven by ecologically-, socially- and/or culturally-imposed “captivity”.

Abstract

Chronic fatigue syndrome (CFS) is characterized by a debilitating fatigue of unknown aetiology. Patients who suffer from CFS report a variety of physical complaints as well as neuropsychological complaints. Therefore, it is conceivable that the CNS plays a role in the pathophysiology of CFS. The purpose of this study was to investigate neural correlates of CFS, and specifically whether there exists a linkage between disturbances in the motor system and CFS. We measured behavioural performance and cerebral activity using rapid event-related functional MRI in 16 CFS patients and 16 matched healthy controls while they were engaged in a motor imagery task and a control visual imagery task. CFS patients were considerably slower on performance of both tasks, but the increase in reaction time with increasing task load was similar between the groups. Both groups used largely overlapping neural resources. However, during the motor imagery task, CFS patients evoked stronger responses in visually related structures. Furthermore, there was a marked between-groups difference during erroneous performance. In both groups, dorsal anterior cingulate cortex was specifically activated during error trials. Conversely, ventral anterior cingulate cortex was active when healthy controls made an error, but remained inactive when CFS patients made an error. Our results support the notion that CFS may be associated with dysfunctional motor planning. Furthermore, the between-groups differences observed during erroneous performance point to motivational disturbances as a crucial component of CFS.

Abstract

We contrast two related hypotheses of the evolution of dance: H1: Maternal bipedal walking influenced the fetal experience of sound and associated movement patterns; H2: The human transition to bipedal gait produced more isochronous/predictable locomotion sound resulting in early music-like behavior associated with the acoustic advantages conferred by moving bipedally in pace. The cadence of walking is around 120 beats per minute, similar to the tempo of dance and music. Human walking displays long-term constancies. Dyads often subconsciously synchronize steps. The major amplitude component of the step is a distinctly produced beat. Human locomotion influences, and interacts with, emotions, and passive listening to music activates brain motor areas. Across dance-genres the footwork is most often performed in time to the musical beat. Brain development is largely shaped by early sensory experience, with hearing developed from week 18 of gestation. Newborns reacts to sounds, melodies, and rhythmic poems to which they have been exposed in utero. If the sound and vibrations produced by footfalls of a walking mother are transmitted to the fetus in coordination with the cadence of the motion, a connection between isochronous sound and rhythmical movement may be developed. Rhythmical sounds of the human mother locomotion differ substantially from that of nonhuman primates, while the maternal heartbeat heard is likely to have a similar isochronous character across primates, suggesting a relatively more influential role of footfall in the development of rhythmic/musical abilities in humans. Associations of gait, music, and dance are numerous. The apparent absence of musical and rhythmic abilities in nonhuman primates, which display little bipedal locomotion, corroborates that bipedal gait may be linked to the development of rhythmic abilities in humans. Bipedal stimuli in utero may primarily boost the ontogenetic development. The acoustical advantage hypothesis proposes a mechanism in the phylogenetic development.

Abstract

Commonly known for their ability to echolocate, bats also use a wide variety of social vocalizations to communicate with one another. However, the full vocal repertoires of relatively few bat species have been studied thus far. The present study examined the vocal repertoire of the pale spear-nosed bat, Phyllostomus discolor, in a social roosting context. Based on visual examination of spectrograms and subsequent quantitative analysis of syllables, eight distinct syllable classes were defined, and their prevalence in different behavioral contexts was examined. Four more syllable classes were observed in low numbers and are described here as well. These results show that P. discolor possesses a rich vocal repertoire, which includes vocalizations comparable to previously reported repertoires of other bat species as well as vocalizations previously undescribed. Our data provide detailed information about the temporal and spectral characteristics of syllables emitted by P. discolor, allowing for a better understanding of the communicative system and related behaviors of this species. Furthermore, this vocal repertoire will serve as a basis for future research using P. discolor as a model organism for vocal communication and vocal learning and it will allow for comparative studies between bat species.

Abstract

Prediction of upcoming words facilitates language processing. Individual differences in social experience, however, might influence prediction ability by influencing input variability and representativeness. This paper explores how individual differences in social network size influence prediction and how this influence differs across linguistic levels. In Experiment 1, participants predicted likely sentence completions from several plausible endings differing in meaning or only form (e.g. work vs. job). In Experiment 2, participants’ pupil size was measured as they listened to sentences whose ending was the dominant one or deviated from it in either meaning or form. Both experiments show that people with larger social networks are better at predicting upcoming meanings but not the form they would take. The results thus show that people with different social experience process language differently, and shed light on how social dynamics interact with the structure of the linguistic level to influence learning of linguistic patterns.

Abstract

How can one conceive of the neuronal implementation of the processing model we proposed in our target article? In his commentary (Pulvermüller 1999, reprinted here in this issue), Pulvermüller makes various proposals concerning the underlying neural mechanisms and their potential localizations in the brain. These proposals demonstrate the compatibility of our processing model and current neuroscience. We add further evidence on details of localization based on a recent meta-analysis of neuroimaging studies of word production (Indefrey & Levelt 2000). We also express some minor disagreements with respect to Pulvermüller’s interpretation of the “lemma” notion, and concerning his neural modeling of phonological code retrieval. Branigan & Pickering discuss important aspects of syntactic encoding, which was not the topic of the target article. We discuss their well-taken proposal that multiple syntactic frames for a single verb lemma are represented as independent nodes, which can be shared with other verbs, such as accounting for syntactic priming in speech production. We also discuss how, in principle, the alternative multiple-frame-multiplelemma account can be tested empirically. The available evidence does not seem to support that account.

Abstract

During the second half of the 19th century, the psychology of language was invented as a discipline for the sole purpose of explaining the evolution of spoken language. These efforts culminated in Wilhelm Wundt’s monumental Die Sprache of 1900, which outlined the psychological mechanisms involved in producing utterances and considered how these mechanisms could have evolved. Wundt assumes that articulatory movements were originally rather arbitrary concomitants of larger, meaningful expressive bodily gestures. The sounds such articulations happened to produce slowly acquired the meaning of the gesture as a whole, ultimately making the gesture superfluous. Over a century later, gestural theories of language origins still abound. I argue that such theories are unlikely and wasteful, given the biological, neurological and genetic evidence.

Abstract

The first, theoretical part of this paper sketches a framework for phonological encoding in which the speaker successively generates phonological syllables in connected speech. The final stage of this process, phonetic encoding, consists of accessing articulatory gestural scores for each of these syllables in a "mental syllabary". The second, experimental part studies various predictions derived from this theory. The main finding is a syllable frequency effect: words ending in a high-frequent syllable are named faster than words ending in a low-frequent syllable. As predicted, this syllable frequency effect is independent of and additive to the effect of word frequency on naming latency. The effect, moreover, is not due to the complexity of the word-final syllable. In the General Discussion, the syllabary model is further elaborated with respect to phonological underspecification and activation spreading. Alternative accounts of the empirical findings in terms of core syllables and demisyllables are considered.

Abstract

The purpose of this study was to relate a psycholinguistic processing model of picture naming to the dynamics of cortical activation during picture naming. The activation was recorded from eight Dutch subjects with a whole-head neuromagnetometer. The processing model, based on extensive naming latency studies, is a stage model. In preparing a picture's name, the speaker performs a chain of specific operations. They are, in this order, computing the visual percept, activating an appropriate lexical concept, selecting the target word from the mental lexicon, phonological encoding, phonetic encoding, and initiation of articulation. The time windows for each of these operations are reasonably well known and could be related to the peak activity of dipole sources in the individual magnetic response patterns. The analyses showed a clear progression over these time windows from early occipital activation, via parietal and temporal to frontal activation. The major specific findings were that (1) a region in the left posterior temporal lobe, agreeing with the location of Wernicke's area, showed prominent activation starting about 200 msec after picture onset and peaking at about 350 msec, (i.e., within the stage of phonological encoding), and (2) a consistent activation was found in the right parietal cortex, peaking at about 230 msec after picture onset, thus preceding and partly overlapping with the left temporal response. An interpretation in terms of the management of visual attention is proposed.

Abstract

The evolution of speech and language has been a returning topic in the language sciences since the so-called “cognitive revolution.”

Abstract

This commentary discusses whether abstract metrical frames are stored. For stress-assigning languages (e.g., Dutch and English), which have a dominant stress pattern, metrical frames are stored only for words that deviate from the default stress pattern. The majority of the words in these languages are produced without retrieving any independent syllabic or metrical frame.

Abstract

This paper considers the AGL literature from a psycholinguistic perspective. It first presents a taxonomy of the experimental familiarization test procedures used, which is followed by a consideration of shortcomings and potential improvements of the empirical methodology. It then turns to reconsidering the issue of grammar learning from the point of view of acquiring constraints, instead of the traditional AGL approach in terms of acquiring sets of rewrite rules. This is, in particular, a natural way of handling long‐distance dependences. The final section addresses an underdeveloped issue in the AGL literature, namely how to detect latent hierarchical structure in AGL response patterns.

Abstract

The core issue in the 19-century sources of psycholinguistics was the question, "Where does language come from?'' This genetic perspective unified the study of the ontogenesis, the phylogenesis, the microgenesis, and to some extent the neurogenesis of language. This paper makes the point that this original perspective is still a valid and attractive one. It is exemplified by a discussion of the genesis of spoken words.

Abstract

This paper confronts Kant’s (1768) view of human conceptions of space as fundamentally divided along the three planes of the human body with an empirical case study in the Mayan community of Tenejapa in southern Mexico, whose inhabitants do not use left/right distinctions to project regions in space. Tenejapans have names for the left hand and the right hand, and also a term for hand/arm in general, but they do not generalize the distinction to spatial regions -- there is no linguistic expression glossing as 'to the left' or 'on the left-hand side', for example. Tenejapans also show a remarkable indifference to incongruous counterparts. Nor is there any system of value associations with the left and the right. The Tenejapan evidence that speaks to these Kantian themes points in two directions: (a) Kant was wrong to think that the structure of spatial regions founded on the human frame, and in particular the distinctions based on left and right, are in some sense essential human intuitions; (b) Kant may have been right to think that the left/right opposition, the perception of enantiomorphs, clockwiseness, East-West dichotomies, etc., are intimately connected to an overall system of spatial conception.

Abstract

This article explores the relation between language and cognition by examining the case of "absolute" (cardinal direction) spatial description in the Australian aboriginal language Guugu Yimithirr. This kind of spatial description is incongruent with the "relative" (e.g., left/right/front/back) spatial description familiar in European languages. Building on Haviland's 1993 analysis of Guugu Yimithirr directionals in speech and gesture, a series of informal experiments were developed. It is shown that Guugu Yimithirr speakers predominantly code for nonverbal memory in "absolute" concepts congruent with their language, while a comparative sample of Dutch speakers do so in "relative" concepts. Much anecdotal evidence also supports this. The conclusion is that Whorfian effects may in fact be demonstrable in the spatial domain.

Abstract

Philosophers, psychologists, and linguists have argued that spatial conception is pivotal to cognition in general, providing a general, egocentric, and universal framework for cognition as well as metaphors for conceptualizing many other domains. But in an aboriginal community in Northern Queensland, a system of cardinal directions informs not only language, but also memory for arbitrary spatial arrays and directions. This work suggests that fundamental cognitive parameters, like the system of coding spatial locations, can vary cross-culturally, in line with the language spoken by a community. This opens up the prospect of a fruitful dialogue between anthropology and the cognitive sciences on the complex interaction between cultural and universal factors in the constitution of mind.

Abstract

The present paper discusses the benefits and challenges of token-based typology, which takes into account the frequencies of words and constructions in language use. This approach makes it possible to introduce new criteria for language classification, which would be difficult or impossible to achieve with the traditional, type-based approach. This point is illustrated by several quantitative studies of word order variation, which can be measured as entropy at different levels of granularity. I argue that this variation can be explained by general functional mechanisms and pressures, which manifest themselves in language use, such as optimization of processing (including avoidance of ambiguity) and grammaticalization of predictable units occurring in chunks. The case studies are based on multilingual corpora, which have been parsed using the Universal Dependencies annotation scheme.

Abstract

Schizophrenia is a common and complex mental disorder with neuroimaging alterations. Recent neuroanatomical pattern recognition studies attempted to distinguish individuals with schizophrenia by structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI). 1, 2 Applications of cutting-edge machine learning approaches in structural neuroimaging studies have revealed potential pathways to classification of schizophrenia based on regional gray matter volume (GMV) or density or cortical thickness. 3–5 Additionally, cortical folding may have high discriminatory value in correctly identifying symptom severity in schizophrenia. 6 Regional GMV and cortical thickness have also been combined in attempts to differentiate individuals with schizophrenia from healthy controls (HCs). 7 Applications of machine learning algorithms to diffusion imaging data analysis to predict individuals with first-episode schizophrenia (FES) have achieved encouraging accuracy. 8–10 White matter (WM) abnormalities in schizophrenia as estimated by DTI appear to be present in the early stage of the disorder, most likely reflecting the developmental stage of the sample of interest.

Abstract

Identifying data-driven biotypes of major depressive disorder (MDD) has promise for the clarification of diagnostic heterogeneity. However, few studies have focused on white-matter abnormalities for MDD subtyping. This study included 116 patients with MDD and 118 demographically-matched healthy controls assessed by diffusion tensor imaging and neurocognitive evaluation. Hierarchical clustering was applied to the major fiber tracts, in conjunction with tract-based spatial statistics, to reveal white-matter alterations associated with MDD. Clinical and neurocognitive differences were compared between identified subgroups and healthy controls. With fractional anisotropy extracted from 20 fiber tracts, cluster analysis revealed 3 subgroups based on the patterns of abnormalities. Patients in each subgroup versus healthy controls showed a stepwise pattern of white-matter alterations as follows: subgroup 1 (25.9% of patient sample), widespread white-matter disruption; subgroup 2 (43.1% of patient sample), intermediate and more localized abnormalities in aspects of the corpus callosum and left cingulate; and subgroup 3 (31.0% of patient sample), possible mild alterations, but no statistically significant tract disruption after controlling for family-wise error. The neurocognitive impairment in each subgroup accompanied the white-matter alterations: subgroup 1, deficits in sustained attention and delayed memory; subgroup 2, dysfunction in delayed memory; and subgroup 3, no significant deficits. Three subtypes of white-matter abnormality exist in individuals with major depression, those having widespread abnormalities suffering more neurocognitive impairments, which may provide evidence for parsing the heterogeneity of the disorder and help optimize type-specific treatment approaches.

Abstract

We propose that the choice between the auxiliaries hebben 'have' and zijn 'be' in Dutch is determined by a particular semantic feature of verbs. In particular we propose a feature of meaning [IEPS] for 'inferable eventual position or state' that characterizes whether the action denoted by the verb allows us to determine the eventual position or state of the verb's highest argument. It is argued that only verbs which exhibit the feature [+IEPS] or which obtain the feature compositionally in the syntax select zijn as their auxiliary. Our analysis is then compared to a number of other analyses of auxiliary selection in Dutch.

Abstract

Infants point for various motives. Classically, one such motive is declarative, to share attention and interest with adults to events. Recently, some researchers have questioned whether infants have this motivation. In the current study, an adult reacted to 12-month-olds' pointing in different ways, and infants' responses were observed. Results showed that when the adult shared attention and interest (i.e. alternated gaze and emoted), infants pointed more frequently across trials and tended to prolong each point – presumably to prolong the satisfying interaction. However, when the adult emoted to the infant alone or looked only to the event, infants pointed less across trials and repeated points more within trials – presumably in an attempt to establish joint attention. Results suggest that 12-month-olds point declaratively and understand that others have psychological states that can be directed and shared.

Abstract

Mutations of the renal-specific chloride channel (CLCN5) gene, which is located on chromosome Xp11.22, are associated with hypercalciuric nephrolithiasis (kidney stones) in the Northern European and Japanese populations. CLCN5 encodes a 746 amino acid channel (CLC-5) that has approximately 12 transmembrane domains, and heterologous expression of wild-type CLC-5 in Xenopus oocytes has yielded outwardly rectifying chloride currents that were markedly reduced or abolished by these mutations. In order to assess further the structural and functional relationships of this recently cloned chloride channel, additional CLCN5 mutations have been identified in five unrelated families with this disorder. Three of these mutations were missense (G57V, G512R and E527D), one was a nonsense (R648Stop) and one was an insertion (30:H insertion). In addition, two of the mutations (30:H insertion and E527D) were demonstrated to be de novo, and the G57V and E527D mutations were identified in families of Afro-American and Indian origin, respectively. The G57V and 30:H insertion mutations represent the first CLCN5 mutations to be identified in the N-terminus region, and the R648Stop mutation, which has been observed previously in an unrelated family, suggests that this codon may be particularly prone to mutations. Heterologous expression of the mutations resulted in a marked reduction or abolition of the chloride currents, thereby establishing their functional importance. These results help to elucidate further the structure-function relationships of this renal chloride channel.