Publications

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

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

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

In sentences like “the mouse that chased the cat was hungry”, the syntactically correct interpretation (the mouse chases the cat) is contradicted by semantic and pragmatic knowledge. Previous research has shown that L1 speakers sometimes base sentence interpretation on this type of knowledge (so-called “shallow” or “good-enough” processing). We made use of both behavioural and ERP measurements to investigate whether L2 learners differ from native speakers in the extent to which they engage in “shallow” syntactic processing. German learners of Dutch as well as Dutch native speakers read sentences containing relative clauses (as in the example above) for which the plausible thematic roles were or were not reversed, and made plausibility judgments. The results show that behaviourally, L2 learners had more difficulties than native speakers to discriminate plausible from implausible sentences. In the ERPs, we replicated the previously reported finding of a “semantic P600” for semantic reversal anomalies in native speakers, probably reflecting the effort to resolve the syntax-semantics conflict. In L2 learners, though, this P600 was largely attenuated and surfaced only in those trials that were judged correctly for plausibility. These results generally point at a more prevalent, but not exclusive occurrence of shallow syntactic processing in L2 learners.

Abstract

Semantic unification during sentence comprehension has been associated with amplitude change of the N400 in event-related potential (ERP) studies, and activation in the left inferior frontal gyrus (IFG) in functional magnetic resonance imaging (fMRI) studies. However, the specificity of this activation to semantic unification remains unknown. To more closely examine the brain processes involved in semantic unification, we employed simultaneous EEG-fMRI to time-lock the semantic unification related N400 change, and integrated trial-by-trial variation in both N400 and BOLD change beyond the condition-level BOLD change difference measured in traditional fMRI analyses. Participants read sentences in which semantic unification load was parametrically manipulated by varying cloze probability. Separately, ERP and fMRI results replicated previous findings, in that semantic unification load parametrically modulated the amplitude of N400 and cortical activation. Integrated EEG-fMRI analyses revealed a different pattern in which functional activity in the left IFG and bilateral supramarginal gyrus (SMG) was associated with N400 amplitude, with the left IFG activation and bilateral SMG activation being selective to the condition-level and trial-level of semantic unification load, respectively. By employing the EEG-fMRI integrated analyses, this study among the first sheds light on how to integrate trial-level variation in language comprehension.

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

Swedish morphemes are classified as prosodically specified or prosodically unspecified, depending on lexical or phonological stress, respectively. Here, we investigate the allomorphy of the suffix -(i)sk, which indicates the distinction between lexical and phonological stress; if attached to a lexically stressed morpheme, it takes a non-syllabic form (-sk), whereas if attached to a phonologically stressed morpheme, an epenthetic vowel is inserted (-isk). Using mismatch negativity (MMN), we explored the neural processing of this allomorphy across lexically stressed and phonologically stressed morphemes. In an oddball paradigm, participants were occasionally presented with congruent and incongruent derivations, created by the suffix -(i)sk, within the repetitive presentation of their monomorphemic stems. The results indicated that the congruent derivation of the lexically stressed stem elicited a larger MMN than the incongruent sequences of the same stem and the derivational suffix, whereas after the phonologically stressed stem a non-significant tendency towards an opposite pattern was observed. We argue that the significant MMN response to the congruent derivation in the lexical stress condition is in line with lexical MMN, indicating a holistic processing of the sequence of lexically stressed stem and derivational suffix. The enhanced MMN response to the incongruent derivation in the phonological stress condition, on the other hand, is suggested to reflect combinatorial processing of the sequence of phonologically stressed stem and derivational suffix. These findings bring a new aspect to the dual-system approach to neural processing of morphologically complex words, namely the specification of word stress.

Abstract

Speakers remember their own utterances better than those of their interlocutors, suggesting that language production is beneficial to memory. This may be partly explained by a generation effect: The act of generating a word is known to lead to a memory advantage (Slamecka & Graf, 1978). In earlier work, we showed a generation effect for recognition of images (Zormpa, Brehm, Hoedemaker, & Meyer, 2019). Here, we tested whether the recognition of their names would also benefit from name generation. Testing whether picture naming improves memory for words was our primary aim, as it serves to clarify whether the representations affected by generation are visual or conceptual/lexical. A secondary aim was to assess the influence of processing time on memory. Fifty-one participants named pictures in three conditions: after hearing the picture name (identity condition), backward speech, or an unrelated word. A day later, recognition memory was tested in a yes/no task. Memory in the backward speech and unrelated conditions, which required generation, was superior to memory in the identity condition, which did not require generation. The time taken by participants for naming was a good predictor of memory, such that words that took longer to be retrieved were remembered better. Importantly, that was the case only when generation was required: In the no-generation (identity) condition, processing time was not related to recognition memory performance. This work has shown that generation affects conceptual/lexical representations, making an important contribution to the understanding of the relationship between memory and language.

Abstract

The production effect (better memory for words read aloud than words read silently) and the picture superiority effect (better memory for pictures than words) both improve item memory in a picture naming task (Fawcett, J. M., Quinlan, C. K., & Taylor, T. L. (2012). Interplay of the production and picture superiority effects: A signal detection analysis. Memory (Hove, England), 20(7), 655–666. doi:10.1080/09658211.2012.693510). Because picture naming requires coming up with an appropriate label, the generation effect (better memory for generated than read words) may contribute to the latter effect. In two forced-choice memory experiments, we tested the role of generation in a picture naming task on later recognition memory. In Experiment 1, participants named pictures silently or aloud with the correct name or an unreadable label superimposed. We observed a generation effect, a production effect, and an interaction between the two. In Experiment 2, unreliable labels were included to ensure full picture processing in all conditions. In this experiment, we observed a production and a generation effect but no interaction, implying the effects are dissociable. This research demonstrates the separable roles of generation and production in picture naming and their impact on memory. As such, it informs the link between memory and language production and has implications for memory asymmetries between language production and comprehension.