Children's inhibition skills are associated with their P3a latency-results from an exploratory study.

BACKGROUND: The P3a response is thought to reflect involuntary orienting to an unexpected stimulus and has been connected with set-shifting and inhibition in some studies. In our exploratory study, we investigated if the amplitude and the latency of the P3a response were associated with the performance in a modified flanker task measuring inhibition and set-shifting in 10-year-old children (N = 42). Children participated in electroencephalography (EEG) measurement with an auditory multifeature paradigm including standard, deviating, and novel sounds. In addition, they performed a separate flanker task requiring inhibition and set-shifting skills. RESULTS: The P3a latencies for deviant sounds were associated with the reaction time reflecting inhibition: the shorter the response latencies were, the faster the reaction time was. The P3a latencies for novel sounds were not linked to the reaction times reflecting either inhibition or set-shifting. In addition, the magnitude of the P3a response was not associated with the performance in the flanker task. CONCLUSIONS: Our results suggest that P3a response latency and reaction speed reflecting inhibitory skills are based on shared neural mechanism. Thus, the present study brings new insight to the field investigating the associations between behavior and its neural indices.

Improved Auditory Function Caused by Music Versus Foreign Language Training at School Age: Is There a Difference?

In adults, music and speech share many neurocognitive functions, but how do they interact in a developing brain? We compared the effects of music and foreign language training on auditory neurocognition in Chinese children aged 8-11 years. We delivered group-based training programs in music and foreign language using a randomized controlled trial. A passive control group was also included. Before and after these year-long extracurricular programs, auditory event-related potentials were recorded (n = 123 and 85 before and after the program, respectively). Through these recordings, we probed early auditory predictive brain processes. To our surprise, the language program facilitated the children's early auditory predictive brain processes significantly more than did the music program. This facilitation was most evident in pitch encoding when the experimental paradigm was musically relevant. When these processes were probed by a paradigm more focused on basic sound features, we found early predictive pitch encoding to be facilitated by music training. Thus, a foreign language program is able to foster auditory and music neurocognition, at least in tonal language speakers, in a manner comparable to that by a music program. Our results support the tight coupling of musical and linguistic brain functions also in the developing brain.

Brain oscillation recordings of the audience in a live concert-like setting.

There are only a few previous EEG studies that were conducted while the audience is listening to live music. However, in laboratory settings using music recordings, EEG frequency bands theta and alpha are connected to music improvisation and creativity. Here, we measured EEG of the audience in a concert-like setting outside the laboratory and compared the theta and alpha power evoked by partly improvised versus regularly performed familiar versus unfamiliar live classical music. To this end, partly improvised and regular versions of pieces by Bach (familiar) and Melartin (unfamiliar) were performed live by a chamber trio. EEG data from left and right frontal and central regions of interest were analysed to define theta and alpha power during each performance. After the performances, the participants rated how improvised and attractive each of the performances were. They also gave their affective ratings before and after each performance. We found that theta power was enhanced during the familiar improvised Bach piece and the unfamiliar improvised Melartin piece when compared with the performance of the same piece performed in a regular manner. Alpha power was not modulated by manner of performance or by familiarity of the piece. Listeners rated partly improvised performances of a familiar Bach and unfamiliar Melartin piece as more improvisatory and innovative than the regular performances. They also indicated more joy and less sadness after listening to the unfamiliar improvised piece of Melartin and less fearful and more enthusiastic after listening to the regular version of Melartin than before listening. Thus, according to our results, it is possible to study listeners' brain functions with EEG during live music performances outside the laboratory, with theta activity reflecting the presence of improvisation in the performances.

Faster maturation of selective attention in musically trained children and adolescents: Converging behavioral and event-related potential evidence.

Previous work suggests that musical training in childhood is associated with enhanced executive functions. However, it is unknown whether this advantage extends to selective attention-another central aspect of executive control. We recorded a well-established event-related potential (ERP) marker of distraction, the P3a, during an audio-visual task to investigate the maturation of selective attention in musically trained children and adolescents aged 10-17 years and a control group of untrained peers. The task required categorization of visual stimuli, while a sequence of standard sounds and distracting novel sounds were presented in the background. The music group outperformed the control group in the categorization task and the younger children in the music group showed a smaller P3a to the distracting novel sounds than their peers in the control group. Also, a negative response elicited by the novel sounds in the N1/MMN time range (~150-200 ms) was smaller in the music group. These results indicate that the music group was less easily distracted by the task-irrelevant sound stimulation and gated the neural processing of the novel sounds more efficiently than the control group. Furthermore, we replicated our previous finding that, relative to the control group, the musically trained children and adolescents performed faster in standardized tests for inhibition and set shifting. These results provide novel converging behavioral and electrophysiological evidence from a cross-modal paradigm for accelerated maturation of selective attention in musically trained children and adolescents and corroborate the association between musical training and enhanced inhibition and set shifting.

Intracellular signalling pathways and cytoskeletal functions converge on the psoriasis candidate gene CCHCR1 expressed at P-bodies and centrosomes.

BACKGROUND: CCHCR1 (Coiled-Coil α-Helical Rod protein 1) is a putative psoriasis candidate gene with the risk alleles CCHCR1*WWCC and *Iso3, the latter inhibiting the translation of isoform 1. CCHCR1 was recently shown to be a centrosomal protein, as well as a component of cytoplasmic processing bodies (P-bodies) that regulate mRNA turnover. The function of CCHCR1 has remained unsettled, partly because of the inconsistent findings; it has been shown to play a wide variety of roles in divergent processes, e.g., cell proliferation and steroidogenesis. Here we utilized RNA sequencing (RNAseq) using HEK293 cells overexpressing isoforms 1 or 3 (Iso1, Iso3 cells), in combination with the coding non-risk or risk (*WWCC) haplotype of CCHCR1. Our aim was to study the overall role of CCHCR1 and the effects of its variants. RESULTS: The overexpression of CCHCR1 variants in HEK293 cells resulted in cell line-specific expression profiles though several similarities were observable. Overall the Iso1 and Iso3 cells showed a clear isoform-specific clustering as two separate groups, and the Non-risk and Risk cells often exhibited opposite effects. The RNAseq supported a role for CCHCR1 in the centrosomes and P-bodies; the most highlighted pathways included regulation of cytoskeleton, adherens and tight junctions, mRNA surveillance and RNA transport. Interestingly, both the RNAseq and immunofluorescent localization revealed variant-specific differences for CCHCR1 within the P-bodies. CONCLUSIONS: CCHCR1 influenced a wide variety of signaling pathways, which could reflect its active role in the P-bodies and centrosomes that both are linked to the cytoskeleton; as a centrosomal P-body protein CCHCR1 may regulate diverse cytoskeleton-mediated functions, such as cell adhesion and -division. The present findings may explain the previous inconsistent observations about the functions of CCHCR1.

Neuroanatomical substrate of noise sensitivity.

Recent functional studies suggest that noise sensitivity, a trait describing attitudes towards noise and predicting noise annoyance, is associated with altered processing in the central auditory system. In the present work, we examined whether noise sensitivity could be related to the structural anatomy of auditory and limbic brain areas. Anatomical MR brain images of 80 subjects were parcellated with FreeSurfer to measure grey matter volume, cortical thickness, cortical area and folding index of anatomical structures in the temporal lobe and insular cortex. The grey matter volume of amygdala and hippocampus was measured as well. According to our findings, noise sensitivity is associated with the grey matter volume in the selected structures. Among those, we propose and discuss particular areas, previously linked to auditory perceptual, emotional and interoceptive processing, in which larger grey matter volume seems to be related to higher noise sensitivity.

Dance on cortex: enhanced theta synchrony in experts when watching a dance piece.

When watching performing arts, a wide and complex network of brain processes emerge. These processes can be shaped by professional expertise. When compared to laymen, dancers have enhanced processes in observation of short dance movement and listening to music. But how do the cortical processes differ in musicians and dancers when watching an audio-visual dance performance? In our study, we presented the participants long excerpts from the contemporary dance choreography of Carmen. During multimodal movement of a dancer, theta phase synchrony over the fronto-central electrodes was stronger in dancers when compared to musicians and laymen. In addition, alpha synchrony was decreased in all groups during large rapid movement when compared to nearly motionless parts of the choreography. Our results suggest an enhanced cortical communication in dancers when watching dance and, further, that this enhancement is rather related to multimodal, cognitive and emotional processes than to simple observation of dance movement.

Cognitive flexibility modulates maturation and music-training-related changes in neural sound discrimination.

Previous research has demonstrated that musicians show superior neural sound discrimination when compared to non-musicians, and that these changes emerge with accumulation of training. Our aim was to investigate whether individual differences in executive functions predict training-related changes in neural sound discrimination. We measured event-related potentials induced by sound changes coupled with tests for executive functions in musically trained and non-trained children aged 9-11 years and 13-15 years. High performance in a set-shifting task, indexing cognitive flexibility, was linked to enhanced maturation of neural sound discrimination in both musically trained and non-trained children. Specifically, well-performing musically trained children already showed large mismatch negativity (MMN) responses at a young age as well as at an older age, indicating accurate sound discrimination. In contrast, the musically trained low-performing children still showed an increase in MMN amplitude with age, suggesting that they were behind their high-performing peers in the development of sound discrimination. In the non-trained group, in turn, only the high-performing children showed evidence of an age-related increase in MMN amplitude, and the low-performing children showed a small MMN with no age-related change. These latter results suggest an advantage in MMN development also for high-performing non-trained individuals. For the P3a amplitude, there was an age-related increase only in the children who performed well in the set-shifting task, irrespective of music training, indicating enhanced attention-related processes in these children. Thus, the current study provides the first evidence that, in children, cognitive flexibility may influence age-related and training-related plasticity of neural sound discrimination.

The Nature and Nurture of Melody: A Twin Study of Musical Pitch and Rhythm Perception.

Both genetic and environmental factors are known to play a role in our ability to perceive music, but the degree to which they influence different aspects of music cognition is still unclear. We investigated the relative contribution of genetic and environmental effects on melody perception in 384 young adult twins [69 full monozygotic (MZ) twin pairs, 44 full dizygotic (DZ) twin pairs, 70 MZ twins without a co-twin, and 88 DZ twins without a co-twin]. The participants performed three online music tests requiring the detection of pitch changes in a two-melody comparison task (Scale) and key and rhythm incongruities in single-melody perception tasks (Out-of-key, Off-beat). The results showed predominantly additive genetic effects in the Scale task (58 %, 95 % CI 42-70 %), shared environmental effects in the Out-of-key task (61 %, 49-70 %), and non-shared environmental effects in the Off-beat task (82 %, 61-100 %). This highly different pattern of effects suggests that the contribution of genetic and environmental factors on music perception depends on the degree to which it calls for acquired knowledge of musical tonal and metric structures.

Gene expression analysis of skin grafts and cultured keratinocytes using synthetic RNA normalization reveals insights into differentiation and growth control.

BACKGROUND: Keratinocytes (KCs) are the most frequent cells in the epidermis, and they are often isolated and cultured in vitro to study the molecular biology of the skin. Cultured primary cells and various immortalized cells have been frequently used as skin models but their comparability to intact skin has been questioned. Moreover, when analyzing KC transcriptomes, fluctuation of polyA+ RNA content during the KCs' lifecycle has been omitted. RESULTS: We performed STRT RNA sequencing on 10 ng samples of total RNA from three different sample types: i) epidermal tissue (split-thickness skin grafts), ii) cultured primary KCs, and iii) HaCaT cell line. We observed significant variation in cellular polyA+ RNA content between tissue and cell culture samples of KCs. The use of synthetic RNAs and SAMstrt in normalization enabled comparison of gene expression levels in the highly heterogenous samples and facilitated discovery of differences between the tissue samples and cultured cells. The transcriptome analysis sensitively revealed genes involved in KC differentiation in skin grafts and cell cycle regulation related genes in cultured KCs and emphasized the fluctuation of transcription factors and non-coding RNAs associated to sample types. CONCLUSIONS: The epidermal keratinocytes derived from tissue and cell culture samples showed highly different polyA+ RNA contents. The use of SAMstrt and synthetic RNA based normalization allowed the comparison between tissue and cell culture samples and thus proved to be valuable tools for RNA-seq analysis with translational approach. Transciptomics revealed clear difference both between tissue and cell culture samples and between primary KCs and immortalized HaCaT cells.

The association of noise sensitivity with music listening, training, and aptitude.

After intensive, long-term musical training, the auditory system of a musician is specifically tuned to perceive musical sounds. We wished to find out whether a musician's auditory system also develops increased sensitivity to any sound of everyday life, experiencing them as noise. For this purpose, an online survey, including questionnaires on noise sensitivity, musical background, and listening tests for assessing musical aptitude, was administered to 197 participants in Finland and Italy. Subjective noise sensitivity (assessed with the Weinstein's Noise Sensitivity Scale) was analyzed for associations with musicianship, musical aptitude, weekly time spent listening to music, and the importance of music in each person's life (or music importance). Subjects were divided into three groups according to their musical expertise: Nonmusicians (N = 103), amateur musicians (N = 44), and professional musicians (N = 50). The results showed that noise sensitivity did not depend on musical expertise or performance on musicality tests or the amount of active (attentive) listening to music. In contrast, it was associated with daily passive listening to music, so that individuals with higher noise sensitivity spent less time in passive (background) listening to music than those with lower sensitivity to noise. Furthermore, noise-sensitive respondents rated music as less important in their life than did individuals with lower sensitivity to noise. The results demonstrate that the special sensitivity of the auditory system derived from musical training does not lead to increased irritability from unwanted sounds. However, the disposition to tolerate contingent musical backgrounds in everyday life depends on the individual's noise sensitivity.

Investigating the effects of musical training on functional brain development with a novel Melodic MMN paradigm.

Sensitivity to changes in various musical features was investigated by recording the mismatch negativity (MMN) auditory event-related potential (ERP) in musically trained and nontrained children semi-longitudinally at the ages of 9, 11, and 13 years. The responses were recorded using a novel Melodic multi-feature paradigm which allows fast (<15 min) recording of an MMN profile for changes in melody, rhythm, musical key, timbre, tuning and timing. When compared to the nontrained children, the musically trained children displayed enlarged MMNs for the melody modulations by the age 13 and for the rhythm modulations, timbre deviants and slightly mistuned tones already at the age of 11. Also, a positive mismatch response elicited by delayed tones was larger in amplitude in the musically trained than in the nontrained children at age 13. No group differences were found at the age 9 suggesting that the later enhancement of the MMN in the musically trained children resulted from training and not pre-existing difference between the groups. The current study demonstrates the applicability of the Melodic multi-feature paradigm in school-aged children and indicates that musical training enhances auditory discrimination for musically central sound dimensions in pre-adolescence.

Enhanced development of auditory change detection in musically trained school-aged children: a longitudinal event-related potential study.

Adult musicians show superior auditory discrimination skills when compared to non-musicians. The enhanced auditory skills of musicians are reflected in the augmented amplitudes of their auditory event-related potential (ERP) responses. In the current study, we investigated longitudinally the development of auditory discrimination skills in musically trained and nontrained individuals. To this end, we recorded the mismatch negativity (MMN) and P3a responses from children who play a musical instrument and age-matched children with no musical training at ages 7, 9, 11, and 13. Basic auditory processing was investigated by recording ERPs in the Multi-Feature Paradigm that included frequency, duration, intensity, location, and gap deviants. The detection of musically more relevant sound changes was examined in an oddball paradigm with major chords as standards and minor chords as deviants. The musically trained children showed larger increase in MMN and P3a amplitudes with age for the chord deviants than the control children. There was also a strong trend (p = .054) for larger increase in MMN amplitude in the musically trained children for the location deviant. As no group differences in response amplitudes were evident at the early stages of the training, our results suggest that the superior neural auditory discrimination in adult musicians is due to training and not pre-existing differences between musicians and non-musicians.

The neuroscience of music - towards ecological validity.

Studies in the neuroscience of music gained momentum in the 1990s as an integrated part of the well-controlled experimental research tradition. However, during the past two decades, these studies have moved toward more naturalistic, ecologically valid paradigms. Here, I introduce this move in three frameworks: (i) sound stimulation and empirical paradigms, (ii) study participants, and (iii) methods and contexts of data acquisition. I wish to provide a narrative historical overview of the development of the field and, in parallel, to stimulate innovative thinking to further advance the ecological validity of the studies without overlooking experimental rigor.

Optimized single-cell RNA sequencing protocol to study early genome activation in mammalian preimplantation development.

Here, we present a modification of single-cell tagged reverse transcription protocol to study gene expression on a single-cell level or with limited RNA input. We describe different enzymes for reverse transcription and cDNA amplification, modified lysis buffer, and additional clean-up steps before cDNA amplification. We also detail an optimized single-cell RNA sequencing method for handpicked single cells, or tens to hundreds of cells, as input material to study mammalian preimplantation development. For complete details on the use and execution of this protocol, please refer to Ezer et al.1.

Comprehensive characterization of the embryonic factor LEUTX.

The paired-like homeobox transcription factor LEUTX is expressed in human preimplantation embryos between the 4- and 8-cell stages, and then silenced in somatic tissues. To characterize the function of LEUTX, we performed a multiomic characterization of LEUTX using two proteomics methods and three genome-wide sequencing approaches. Our results show that LEUTX stably interacts with the EP300 and CBP histone acetyltransferases through its 9 amino acid transactivation domain (9aaTAD), as mutation of this domain abolishes the interactions. LEUTX targets genomic cis-regulatory sequences that overlap with repetitive elements, and through these elements it is suggested to regulate the expression of its downstream genes. We find LEUTX to be a transcriptional activator, upregulating several genes linked to preimplantation development as well as 8-cell-like markers, such as DPPA3 and ZNF280A. Our results support a role for LEUTX in preimplantation development as an enhancer binding protein and as a potent transcriptional activator.

Mismatch negativity-stimulation paradigms in past and in future.

Mismatch negativity (MMN) studies were initiated as part of a well-controlled experimental research tradition with the aim to identify some key principles of auditory processing and memory. During the past two decades, empirical paradigms have moved toward more ecologically valid ones while retaining rigid experimental control. In this paper, I will introduce this development of MMN stimulation paradigms starting from the paradigms used in basic science and then moving to paradigms that have been particularly relevant for studies on music learning and musical expertise. Via these historical and thematic perspectives, I wish to stimulate paradigm development further to meet the demands of naturalistic ecologically valid studies also when using MMN in the context of event-related potential technique that necessarily requires averaging across several stimulus presentations.

Music-based interventions in community settings: Navigating the tension between rigor and ecological validity.

Empirical research of community-based music interventions has advanced to investigate the individual, social, and educational implications of arts-for-wellbeing practices. Here, we present the motivations, aims, hypotheses, and implications of this complex field of inquiry. We describe examples of recent large-scale investigations to reflect on the major methodological challenges. Community-based music interventions strike a balance between the empirical rigor of clinical trials and the demands of ecological validity. We argue that this balance should be viewed as an asset rather than a mere pragmatic compromise. We also offer some perspectives on best-practice models for effectively engaging in this type of work.