Melodic Intonation Therapy for aphasia: A multi-level meta-analysis of randomized controlled trials and individual participant data.

Melodic Intonation Therapy (MIT) is a prominent rehabilitation program for individuals with post-stroke aphasia. Our meta-analysis investigated the efficacy of MIT while considering quality of outcomes, experimental design, influence of spontaneous recovery, MIT protocol variant, and level of generalization. Extensive literature search identified 606 studies in major databases and trial registers; of those, 22 studies-overall 129 participants-met all eligibility criteria. Multi-level mixed- and random-effects models served to separately meta-analyze randomized controlled trial (RCT) and non-RCT data. RCT evidence on validated outcomes revealed a small-to-moderate standardized effect in noncommunicative language expression for MIT-with substantial uncertainty. Unvalidated outcomes attenuated MIT's effect size compared to validated tests. MIT's effect size was 5.7 times larger for non-RCT data compared to RCT data (g̅case report = 2.01 vs. g̅RCT = 0.35 for validated Non-Communicative Language Expression measures). Effect size for non-RCT data decreased with number of months post-stroke, suggesting confound through spontaneous recovery. Deviation from the original MIT protocol did not systematically alter benefit from treatment. Progress on validated tests arose mainly from gains in repetition tasks rather than other domains of verbal expression, such as everyday communication ability. Our results confirm the promising role of MIT in improving trained and untrained performance on unvalidated outcomes, alongside validated repetition tasks, and highlight possible limitations in promoting everyday communication ability.

GCN5 contributes to intracellular lipid accumulation in human primary cardiac stromal cells from patients affected by Arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is a genetic disease associated with sudden cardiac death and cardiac fibro-fatty replacement. Over the last years, several works have demonstrated that different epigenetic enzymes can affect not only gene expression changes in cardiac diseases but also cellular metabolism. Specifically, the histone acetyltransferase GCN5 is known to facilitate adipogenesis and modulate cardiac metabolism in heart failure. Our group previously demonstrated that human primary cardiac stromal cells (CStCs) contribute to adipogenesis in the ACM pathology. Thus, this study aims to evaluate the role of GCN5 in ACM intracellular lipid accumulation. To do so, CStCs were obtained from right ventricle biopsies of ACM patients and from samples of healthy cadaveric donors (CTR). GCN5 expression was increased both in ex vivo and in vitro ACM samples compared to CTR. When GCN5 expression was silenced or pharmacologically inhibited by the administration of MB-3, we observed a reduction in lipid accumulation and a mitigation of reactive oxygen species (ROS) production in ACM CStCs. In agreement, transcriptome analysis revealed that the presence of MB-3 modified the expression of pathways related to cellular redox balance. Altogether, our findings suggest that GCN5 inhibition reduces fat accumulation in ACM CStCs, partially by modulating intracellular redox balance pathways.

Voice modulatory cues to structure across languages and species.

Voice modulatory cues such as variations in fundamental frequency, duration and pauses are key factors for structuring vocal signals in human speech and vocal communication in other tetrapods. Voice modulation physiology is highly similar in humans and other tetrapods due to shared ancestry and shared functional pressures for efficient communication. This has led to similarly structured vocalizations across humans and other tetrapods. Nonetheless, in their details, structural characteristics may vary across species and languages. Because data concerning voice modulation in non-human tetrapod vocal production and especially perception are relatively scarce compared to human vocal production and perception, this review focuses on voice modulatory cues used for speech segmentation across human languages, highlighting comparative data where available. Cues that are used similarly across many languages may help indicate which cues may result from physiological or basic cognitive constraints, and which cues may be employed more flexibly and are shaped by cultural evolution. This suggests promising candidates for future investigation of cues to structure in non-human tetrapod vocalizations. This article is part of the theme issue 'Voice modulation: from origin and mechanism to social impact (Part I)'.

The Influence of Different Prosodic Cues on Word Segmentation.

A prerequisite for spoken language learning is segmenting continuous speech into words. Amongst many possible cues to identify word boundaries, listeners can use both transitional probabilities between syllables and various prosodic cues. However, the relative importance of these cues remains unclear, and previous experiments have not directly compared the effects of contrasting multiple prosodic cues. We used artificial language learning experiments, where native German speaking participants extracted meaningless trisyllabic "words" from a continuous speech stream, to evaluate these factors. We compared a baseline condition (statistical cues only) to five test conditions, in which word-final syllables were either (a) followed by a pause, (b) lengthened, (c) shortened, (d) changed to a lower pitch, or (e) changed to a higher pitch. To evaluate robustness and generality we used three tasks varying in difficulty. Overall, pauses and final lengthening were perceived as converging with the statistical cues and facilitated speech segmentation, with pauses helping most. Final-syllable shortening hindered baseline speech segmentation, indicating that when cues conflict, prosodic cues can override statistical cues. Surprisingly, pitch cues had little effect, suggesting that duration may be more relevant for speech segmentation than pitch in our study context. We discuss our findings with regard to the contribution to speech segmentation of language-universal boundary cues vs. language-specific stress patterns.

Scaling Laws for Phonotactic Complexity in Spoken English Language Data.

Two prominent statistical laws in language and other complex systems are Zipf's law and Heaps' law. We investigate the extent to which these two laws apply to the linguistic domain of phonotactics-that is, to sequences of sounds. We analyze phonotactic sequences with different lengths within words and across word boundaries taken from a corpus of spoken English (Buckeye). We demonstrate that the expected relationship between the two scaling laws can only be attested when boundary spanning phonotactic sequences are also taken into account. Furthermore, it is shown that Zipf's law exhibits both high goodness-of-fit and a high scaling coefficient if sequences of more than two sounds are considered. Our results support the notion that phonotactic cognition employs information about boundary spanning phonotactic sequences.

Non-native speaker pause patterns closely correspond to those of native speakers at different speech rates.

When speaking a foreign language, non-native speakers can typically be readily identified by their accents. But which aspects of the speech signal determine such accents? Speech pauses occur in all languages but may nonetheless vary in different languages with regard to their duration, number or positions in the speech stream, and therefore are one potential contributor to foreign speech production. The aim of this study was therefore to investigate whether non-native speakers pause 'with a foreign accent'. We recorded native English speakers and non-native speakers of German or Serbo-Croatian with excellent English reading out an English text at three different speech rates, and analyzed their vocal output in terms of number, duration and location of pauses. Overall, all non-native speakers were identified by native raters as having non-native accents, but native and non-native speakers made pauses that were similarly long, and had similar ratios of pause time compared to total speaking time. Furthermore, all speakers changed their pausing behavior similarly at different speech rates. The only clear difference between native and non-native speakers was that the latter made more pauses than the native speakers. Thus, overall, pause patterns contributed little to the acoustic characteristics of speakers' non-native accents, when reading aloud. Non-native pause patterns might be acquired more easily than other aspects of pronunciation because pauses are perceptually salient and producing pauses is easy. Alternatively, general cognitive processing mechanisms such as attention, planning or memory may constrain pausing behavior, allowing speakers to transfer their native pause patterns to a second language without significant deviation. We conclude that pauses make a relatively minor contribution to the acoustic characteristics of non-native accents.