Predictive uncertainty in auditory sequence processing

Copyright © 2014 Hansen and Pearce. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

Distinctive growth requirements and gene expression patterns distinguish progenitor B cells from pre-B cells.

Long-term bone marrow cultures have been useful in determining gene expression patterns in pre-B cells and in the identification of cytokines such as interleukin 7 (IL-7). We have developed a culture system to selectively grow populations of B lineage restricted progenitors (pro-B cells) from murine bone marrow. Pro-B cells do not grow in response to IL-7, Steel locus factor (SLF), or a combination of the two. c-kit, the SLF receptor, and the IL-7 receptor are both expressed by pro-B cells, indicating that the lack of response is not simply due to the absence of receptors. Furthermore, SLF is not necessary for the growth of pro-B cells since they could be expanded on a stromal line derived from Steel mice that produces no SLF. IL-7 responsiveness in pre-B cells is associated with an increase in n-myc expression and is correlated with immunoglobulin (Ig) gene rearrangements. Although members of the ets family of transcription factors and the Pim-1 kinase are expressed by pro-B cells, n-myc is not expressed. Pro-B cells maintain Ig genes in the germline configuration, which is correlated with a low level of recombination activating genes 1 and 2 (Rag-1 and 2) mRNA expression, but high expression of sterile mu and terminal deoxynucleotidyl transferase. Pro-B cells are unable to grow separated from the stromal layer by a porous membrane, indicating that stromal contact is required for growth. These results suggest that pro-B cells are dependent on alternative growth signals derived from bone marrow stroma and can be distinguished from pre-B cells by specific patterns of gene expression

Deletion within the Src homology domain 3 of Bruton's tyrosine kinase resulting in X-linked agammaglobulinemia (XLA).

The gene responsible for X-linked agammaglobulinemia (XLA) has been recently identified to code for a cytoplasmic tyrosine kinase (Bruton's agammaglobulinemia tyrosine kinase, BTK), required for normal B cell development. BTK, like many other cytoplasmic tyrosine kinases, contains Src homology domains (SH2 and SH3), and catalytic kinase domain. SH3 domains are important for the targeting of signaling molecules to specific subcellular locations. We have identified a family with XLA whose affected members have a point mutation (g-->a) at the 5' splice site of intron 8, resulting in the skipping of coding exon 8 and loss of 21 amino acids forming the COOH-terminal portion of the BTK SH3 domain. The study of three generations within this kinship, using restriction fragment length polymorphism and DNA analysis, allowed identification of the mutant X chromosome responsible for XLA and the carrier status in this family. BTK mRNA was present in normal amounts in Epstein-Barr virus-induced B lymphoblastoid cell lines established from affected family members. Although the SH3 deletion did not alter BTK protein stability and kinase activity of the truncated BTK protein was normal, the affected patients nevertheless have a severe B cell defect characteristic for XLA. The mutant protein was modeled using the normal BTK SH3 domain. The deletion results in loss of two COOH-terminal beta strands containing several residues critical for the formation of the putative SH3 ligand-binding pocket. We predict that, as a result, one or more crucial SH3 binding proteins fail to interact with BTK, interrupting the cytoplasmic signal transduction process required for B cell differentiation

Children retain implicitly learned phonological sequences better than adults: A longitudinal study

This is the peer reviewed version of the following article: Eleonore H. M. Smalle, Mike P. A. Page, Wouter Duyck, Martin Edwards, and Arnaud Szmalec, 'Children retain implicitly learned phonological sequences better than adults: a longitudinal study', Developmental Science, December 2017, which has been published in final form at DOI: 10.1111/desc.12634. Under embargo until 17 December 2018. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Whereas adults often rely on explicit memory, children appear to excel in implicit memory, which plays an important role in the acquisition of various cognitive skills, such as those involved in language. The current study aimed to test the assertion of an age-dependent shift in implicit versus explicit learning within a theoretical framework that explains the link between implicit sequence memory and word-form acquisition, using the Hebb repetition paradigm. We conducted a one-year, multiple-session longitudinal study in which we presented auditory sequences of syllables, co-presented with pictures of aliens, for immediate serial recall by a group of children (8–9 years) and by an adult group. The repetition of one Hebb sequence was explicitly announced, while the repetition of another Hebb sequence was unannounced and, therefore, implicit. Despite their overall inferior recall performance, the children showed better offline retention of the implicit Hebb sequence, compared with adults who showed a significant decrement across the delays. Adults had gained more explicit knowledge of the implicit sequence than children, but this could not explain the age-dependent decline in the delayed memory for it. There was no significant age-effect for delayed memory of the explicit Hebb sequence, with both age groups showing retention. Overall performance by adults was positively correlated with measures of post-learning awareness. Performance by children was positively correlated with vocabulary knowledge. We conclude that children outperform adults in the retention over time of implicitly learned phonological sequences that will gradually consolidate into novel word-forms. The findings are discussed in the light of maturational differences for implicit versus explicit memory systems that also play a role in language acquisition. A video abstract of this article can be viewed at: https://youtu.be/G5nOfJB72t4.Peer reviewedFinal Accepted Versio

Explaining semantic short-term memory deficits:evidence for the critical role of semantic control

Patients with apparently selective short-term memory (STM) deficits for semantic information have played an important role in developing multi-store theories of STM and challenge the idea that verbal STM is supported by maintaining activation in the language system. We propose that semantic STM deficits are not as selective as previously thought and can occur as a result of mild disruption to semantic control processes, i.e., mechanisms that bias semantic processing towards task-relevant aspects of knowledge and away from irrelevant information. We tested three semantic STM patients with tasks that tapped four aspects of semantic control: (i) resolving ambiguity between word meanings, (ii) sensitivity to cues, (iii) ignoring irrelevant information and (iv) detecting weak semantic associations. All were impaired in conditions requiring more semantic control, irrespective of the STM demands of the task, suggesting a mild, but task-general, deficit in regulating semantic knowledge. This mild deficit has a disproportionate effect on STM tasks because they have high intrinsic control demands: in STM tasks, control is required to keep information active when it is no longer available in the environment and to manage competition between items held in memory simultaneously. By re-interpreting the core deficit in semantic STM patients in this way, we are able to explain their apparently selective impairment without the need for a specialised STM store. Instead, we argue that semantic STM patients occupy the mildest end of spectrum of semantic control disorders

Hierarchical Processing in Seven-Month-Old Infants

Hierarchical structures are crucial to many aspects of cognitive processing and especially for language. However, there still is little experimental support for the ability of infants to learn such structures. Here, we show that, with structures simple enough to be processed by various animals, seven-month-old infants seem to learn hierarchical relations. Infants were presented with an artificial language composed of “sentences” made of three-syllable “words.” The syllables within words conformed to repetition patterns based on syllable tokens involving either adjacent repetitions (e.g., dubaba) or nonadjacent repetitions (e.g., dubadu). Importantly, the sequence of word structures in each sentence conformed to repetition patterns based on word types (e.g., aba-abb-abb). Infants learned this repetition pattern of repetition patterns and thus likely a hierarchical pattern based on repetitions, but only when the repeated word structure was based on adjacent repetitions. While our results leave open the question of which exact sentence-level pattern infants learned, they suggest that infants embedded the word-level patterns into a higher-level pattern and thus seemed to acquire a hierarchically embedded pattern

Infant Rule Learning: Advantage Language, or Advantage Speech?

<div><p>Infants appear to learn abstract rule-like regularities (e.g., <em>la la da</em> follows an AAB pattern) more easily from speech than from a variety of other auditory and visual stimuli (Marcus et al., 2007). We test if that facilitation reflects a specialization to learn from speech alone, or from modality-independent communicative stimuli more generally, by measuring 7.5-month-old infants’ ability to learn abstract rules from sign language-like gestures. Whereas infants appear to easily learn many different rules from speech, we found that with sign-like stimuli, and under circumstances comparable to those of Marcus et al. (1999), hearing infants were able to learn an ABB rule, but not an AAB rule. This is consistent with results of studies that demonstrate lower levels of infant rule learning from a variety of other non-speech stimuli, and we discuss implications for accounts of speech-facilitation.</p> </div

Across space and time: infants learn from backward and forward visual statistics

within temporal and spatial visual streams. Two groups of 8-month-old infants were familiarized with an artificial grammar of shapes, comprised of backward and forward base pairs (i.e., two shapes linked by strong backward or forward transitional probability) and part-pairs (i.e., two shapes with weak transitional probabilities in both directions). One group viewed the continuous visual stream as a temporal sequence, while the other group viewed the same stream as a spatial array. Following familiarization, infants looked longer at test trials containing part- pairs than base pairs, though they had appeared with equal frequency during familiarization. This pattern of looking time was evident for both forward and backward pairs, in both the temporal and spatial conditions. Further, differences in looking time to part-pairs that were consistent or inconsistent with the predictive direction of the base pairs (forward or backward) indicated that infants were indeed sensitive to direction when presented with temporal sequences, but not when presented with spatial arrays. These results suggest that visual statistical learning is flexible in infancy and depends on the nature of visual input

Overnight consolidation aids the transfer of statistical knowledge from the medial temporal lobe to the striatum

Sleep is important for abstraction of the underlying principles (or gist) which bind together conceptually related stimuli, but little is known about the neural correlates of this process. Here, we investigate this issue using overnight sleep monitoring and functional magnetic resonance imaging (fMRI). Participants were exposed to a statistically structured sequence of auditory tones then tested immediately for recognition of short sequences which conformed to the learned statistical pattern. Subsequently, after consolidation over either 30min or 24h, they performed a delayed test session in which brain activity was monitored with fMRI. Behaviorally, there was greater improvement across 24h than across 30min, and this was predicted by the amount of slow wave sleep (SWS) obtained. Functionally, we observed weaker parahippocampal responses and stronger striatal responses after sleep. Like the behavioral result, these differences in functional response were predicted by the amount of SWS obtained. Furthermore, connectivity between striatum and parahippocampus was weaker after sleep, whereas connectivity between putamen and planum temporale was stronger. Taken together, these findings suggest that abstraction is associated with a gradual shift from the hippocampal to the striatal memory system and that this may be mediated by SWS

Modality effects in implicit artificial grammar learning: An EEG study

Recently, it has been proposed that sequence learning engages a combination of modality-specific operating networks and modality-independent computational principles. In the present study, we compared the behavioural and EEG outcomes of implicit artificial grammar learning in the visual vs. auditory modality. We controlled for the influence of surface characteristics of sequences (Associative Chunk Strength), thus focusing on the strictly structural aspects of sequence learning, and we adapted the paradigms to compensate for known frailties of the visual modality compared to audition (temporal presentation, fast presentation rate). The behavioural outcomes were similar across modalities. Favouring the idea of modality-specificity, ERPs in response to grammar violations differed in topography and latency (earlier and more anterior component in the visual modality), and ERPs in response to surface features emerged only in the auditory modality. In favour of modality-independence, we observed three common functional properties in the late ERPs of the two grammars: both were free of interactions between structural and surface influences, both were more extended in a grammaticality classification test than in a preference classification test, and both correlated positively and strongly with theta event-related-synchronization during baseline testing. Our findings support the idea of modality-specificity combined with modality-independence, and suggest that memory for visual vs. auditory sequences may largely contribute to cross-modal differences. (C) 2018 Elsevier B.V. All rights reserved.Max Planck Institute for Psycholinguistics; Donders Institute for Brain, Cognition and Behaviour; Fundacao para a Ciencia e Tecnologia [PTDC/PSI-PC0/110734/2009, UID/BIM/04773/2013, CBMR 1334, PEst-OE/EQB/1A0023/2013, UM/PSI/00050/2013