Neuroanatomical Disposition, Natural Development, and Training-Induced Plasticity of the Human Auditory System from Childhood to Adulthood: A 12-Year Study in Musicians and Nonmusicians.

Auditory perception is fundamental to human development and communication. However, no long-term studies have been performed on the plasticity of the auditory system as a function of musical training from childhood to adulthood. The long-term interplay between developmental and training-induced neuroplasticity of auditory processing is still unknown. We present results from AMseL (Audio and Neuroplasticity of Musical Learning), the first longitudinal study on the development of the human auditory system from primary school age until late adolescence. This 12-year project combined neurologic and behavioral methods including structural magnetic resonance imaging (MRI), magnetoencephalography (MEG), and auditory tests. A cohort of 112 typically developing participants (51 male, 61 female), classified as "musicians" (n = 66) and "nonmusicians" (n = 46), was tested at five measurement timepoints. We found substantial, stable differences in the morphology of auditory cortex (AC) between musicians and nonmusicians even at the earliest ages, suggesting that musical aptitude is manifested in macroscopic neuroanatomical characteristics. Maturational plasticity led to a continuous increase in white matter myelination and systematic changes of the auditory evoked P1-N1-P2 complex (decreasing latencies, synchronization effects between hemispheres, and amplitude changes) regardless of musical expertise. Musicians showed substantial training-related changes at the neurofunctional level, in particular more synchronized P1 responses and bilaterally larger P2 amplitudes. Musical training had a positive influence on elementary auditory perception (frequency, tone duration, onset ramp) and pattern recognition (rhythm, subjective pitch). The observed interplay between "nature" (stable biological dispositions and natural maturation) and "nurture" (learning-induced plasticity) is integrated into a novel neurodevelopmental model of the human auditory system.Significance Statement We present results from AMseL (Audio and Neuroplasticity of Musical Learning), a 12-year longitudinal study on the development of the human auditory system from childhood to adulthood that combined structural magnetic resonance imaging (MRI), magnetoencephalography (MEG), and auditory discrimination and pattern recognition tests. A total of 66 musicians and 46 nonmusicians were tested at five timepoints. Substantial, stable differences in the morphology of auditory cortex (AC) were found between the two groups even at the earliest ages, suggesting that musical aptitude is manifested in macroscopic neuroanatomical characteristics. We also observed neuroplastic and perceptual changes with age and musical practice. This interplay between "nature" (stable biological dispositions and natural maturation) and "nurture" (learning-induced plasticity) is integrated into a novel neurodevelopmental model of the human auditory system.

The use of noninvasive brain stimulation techniques to improve reading difficulties in dyslexia: A systematic review.

Noninvasive brain stimulation (NIBS) allows to actively and noninvasively modulate brain function. Aside from inhibiting specific processes, NIBS may also enhance cognitive functions, which might be used for the prevention and intervention of learning disabilities such as dyslexia. However, despite the growing interest in modulating learning abilities, a comprehensive, up-to-date review synthesizing NIBS studies with dyslexics is missing. Here, we fill this gap and elucidate the potential of NIBS as treatment option in dyslexia. The findings of the 15 included studies suggest that repeated sessions of reading training combined with different NIBS protocols may induce long-lasting improvements of reading performance in child and adult dyslexics, opening promising avenues for future research. In particular, the "classical" reading areas seem to be most successfully modulated through NIBS, and facilitatory protocols can improve various reading-related subprocesses. Moreover, we emphasize the need to further explore the potential to modulate auditory cortex function as a preintervention and intervention approach for affected children, for example, to avoid the development of auditory and phonological difficulties at the core of dyslexia. Finally, we outline how future studies may increase our understanding of the neurobiological basis of NIBS-induced improvements in dyslexia.

Perturbation of left posterior prefrontal cortex modulates top-down processing in sentence comprehension.

Communication is an inferential process. In particular, language comprehension constantly requires top-down efforts, as often multiple interpretations are compatible with a given sentence. To assess top-down processing in the language domain, our experiment employed ambiguous sentences that allow for multiple interpretations (e.g., The client sued the murderer with the corrupt lawyer., where the corrupt lawyer could either belong to The client or the murderer). Interpretation thus depended on whether participants chunk the words of the sentence into short or long syntactic phrases. In principle, bottom-up acoustic information (i.e., the presence or absence of an intonational phrase boundary at the offset of the murderer) indicates one of the two possible interpretations. Yet, acoustic information often indicates interpretations that require words to be chunked into overly long phrases that would overburden working memory. Processing is biased against these demands, reflected in a top-down preference to chunk words into short rather than long phrases. It is often proposed, but also hotly debated, that the ability to chunk words into short phrases is subserved by the left inferior frontal gyrus (IFG). Here, we employed focal repetitive transcranial magnetic stimulation to perturb the left IFG, which resulted in a further decrease of the aptitude to tolerate long phrases, indicating the inability of the left IFG to assist the chunking of words into phrases. In contrast, the processing of auditory information was not affected. Our findings support a causal top-down role of the left inferior frontal gyrus in the chunking of words into phrases.

Investigating the neural mechanisms of transcranial direct current stimulation effects on human cognition: current issues and potential solutions.

Transcranial direct current stimulation (tDCS) has been studied extensively for its potential to enhance human cognitive functions in healthy individuals and to treat cognitive impairment in various clinical populations. However, little is known about how tDCS modulates the neural networks supporting cognition and the complex interplay with mediating factors that may explain the frequently observed variability of stimulation effects within and between studies. Moreover, research in this field has been characterized by substantial methodological variability, frequent lack of rigorous experimental control and small sample sizes, thereby limiting the generalizability of findings and translational potential of tDCS. The present manuscript aims to delineate how these important issues can be addressed within a neuroimaging context, to reveal the neural underpinnings, predictors and mediators of tDCS-induced behavioral modulation. We will focus on functional magnetic resonance imaging (fMRI), because it allows the investigation of tDCS effects with excellent spatial precision and sufficient temporal resolution across the entire brain. Moreover, high resolution structural imaging data can be acquired for precise localization of stimulation effects, verification of electrode positions on the scalp and realistic current modeling based on individual head and brain anatomy. However, the general principles outlined in this review will also be applicable to other imaging modalities. Following an introduction to the overall state-of-the-art in this field, we will discuss in more detail the underlying causes of variability in previous tDCS studies. Moreover, we will elaborate on design considerations for tDCS-fMRI studies, optimization of tDCS and imaging protocols and how to assure high-level experimental control. Two additional sections address the pressing need for more systematic investigation of tDCS effects across the healthy human lifespan and implications for tDCS studies in age-associated disease, and potential benefits of establishing large-scale, multidisciplinary consortia for more coordinated tDCS research in the future. We hope that this review will contribute to more coordinated, methodologically sound, transparent and reproducible research in this field. Ultimately, our aim is to facilitate a better understanding of the underlying mechanisms by which tDCS modulates human cognitive functions and more effective and individually tailored translational and clinical applications of this technique in the future.

Disrupted network interactions serve as a neural marker of dyslexia.

Dyslexia, a frequent learning disorder, is characterized by severe impairments in reading and writing and hypoactivation in reading regions in the left hemisphere. Despite decades of research, it remains unclear to date if observed behavioural deficits are caused by aberrant network interactions during reading and whether differences in functional activation and connectivity are directly related to reading performance. Here we provide a comprehensive characterization of reading-related brain connectivity in adults with and without dyslexia. We find disrupted functional coupling between hypoactive reading regions, especially between the left temporo-parietal and occipito-temporal cortices, and an extensive functional disruption of the right cerebellum in adults with dyslexia. Network analyses suggest that individuals with dyslexia process written stimuli via a dorsal decoding route and show stronger reading-related interaction with the right cerebellum. Moreover, increased connectivity within networks is linked to worse reading performance in dyslexia. Collectively, our results provide strong evidence for aberrant task-related connectivity as a neural marker for dyslexia that directly impacts behavioural performance. The observed differences in activation and connectivity suggest that one effective way to alleviate reading problems in dyslexia is through modulating interactions within the reading network with neurostimulation methods.

Cortical, subcortical, and cerebellar contributions to language processing: A meta-analytic review of 403 neuroimaging experiments.

Language is a key human faculty for communication and interaction that provides invaluable insight into the human mind. Previous work has dissected different linguistic operations, but the large-scale brain networks involved in language processing are still not fully uncovered. Particularly, little is known about the subdomain-specific engagement of brain areas during semantic, syntactic, phonological, and prosodic processing and the role of subcortical and cerebellar areas. Here, we present the largest coordinate-based meta-analysis of language processing including 403 experiments. Overall, language processing primarily engaged bilateral fronto-temporal cortices, with the highest activation likelihood in the left posterior inferior frontal gyrus (IFG). Whereas we could not detect any syntax-specific regions, semantics specifically engaged left posterior temporal areas (left fusiform and occipitotemporal cortex) and the left frontal pole. Phonology showed highest subdomain-specificity in bilateral auditory and left postcentral regions, whereas prosody engaged specifically the right amygdala and the right IFG. Across all subdomains and modalities, we found strong bilateral subcortical and cerebellar contributions. Especially the right cerebellum was engaged during various processes, including speech production, visual, and phonological tasks. Collectively, our results emphasize consistent recruitment and high functional modularity for general language processing in bilateral domain-specific (temporo-frontal) and domain-general (medial frontal/anterior cingulate cortex) regions but also a high specialization of different subareas for different linguistic subdomains. Our findings refine current neurobiological models of language by adding novel insight into the general sensitivity of the language network and subdomain-specific functions of different brain areas and highlighting the role of subcortical and cerebellar regions for different language operations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The role of the angular gyrus in semantic cognition: a synthesis of five functional neuroimaging studies.

Semantic knowledge is central to human cognition. The angular gyrus (AG) is widely considered a key brain region for semantic cognition. However, the role of the AG in semantic processing is controversial. Key controversies concern response polarity (activation vs. deactivation) and its relation to task difficulty, lateralization (left vs. right AG), and functional-anatomical subdivision (PGa vs. PGp subregions). Here, we combined the fMRI data of five studies on semantic processing (n = 172) and analyzed the response profiles from the same anatomical regions-of-interest for left and right PGa and PGp. We found that the AG was consistently deactivated during non-semantic conditions, whereas response polarity during semantic conditions was inconsistent. However, the AG consistently showed relative response differences between semantic and non-semantic conditions, and between different semantic conditions. A combined analysis across all studies revealed that AG responses could be best explained by separable effects of task difficulty and semantic processing demand. Task difficulty effects were stronger in PGa than PGp, regardless of hemisphere. Semantic effects were stronger in left than right AG, regardless of subregion. These results suggest that the AG is engaged in both domain-general task-difficulty-related processes and domain-specific semantic processes. In semantic processing, we propose that left AG acts as a "multimodal convergence zone" that binds different semantic features associated with the same concept, enabling efficient access to task-relevant features.

Short-term plasticity of neuro-auditory processing induced by musical active listening training.

Although there is strong evidence for the positive effects of musical training on auditory perception, processing, and training-induced neuroplasticity, there is still little knowledge on the auditory and neurophysiological short-term plasticity through listening training. In a sample of 37 adolescents (20 musicians and 17 nonmusicians) that was compared to a control group matched for age, gender, and musical experience, we conducted a 2-week active listening training (AULOS: Active IndividUalized Listening OptimizationS). Using magnetoencephalography and psychoacoustic tests, the short-term plasticity of auditory evoked fields and auditory skills were examined in a pre-post design, adapted to the individual neuro-auditory profiles. We found bilateral, but more pronounced plastic changes in the right auditory cortex. Moreover, we observed synchronization of the auditory evoked P1, N1, and P2 responses and threefold larger amplitudes of the late P2 response, similar to the reported effects of musical long-term training. Auditory skills and thresholds benefited largely from the AULOS training. Remarkably, after training, the mean thresholds improved by 12 dB for bone conduction and by 3-4 dB for air conduction. Thus, our findings indicate a strong positive influence of active listening training on neural auditory processing and perception in adolescence, when the auditory system is still developing.

Exploring the neurobiology of reading through non-invasive brain stimulation: A review.

Non-invasive brain stimulation (NIBS) has gained increasing popularity as a modulatory tool for drawing causal inferences and exploring task-specific network interactions. Yet, a comprehensive synthesis of reading-related NIBS studies is still missing. We fill this gap by synthesizing the results of 78 NIBS studies investigating the causal involvement of brain regions for reading processing, and then link these results to a neurobiological model of reading. The included studies provide evidence for a functional-anatomical double dissociation for phonology versus semantics during reading-related processes within left inferior frontal and parietal areas. Additionally, the posterior parietal cortex and the anterior temporal lobe are identified as critical regions for reading-related processes. Overall, the findings provide some evidence for a dual-stream neurobiological model of reading, in which a dorsal stream (left temporo-parietal and inferior frontal areas) processes unfamiliar words and pseudowords, and a ventral stream (left occipito-temporal and inferior frontal areas, with assistance from the angular gyrus and the anterior temporal lobe) processes known words. However, individual differences in reading abilities and strategies, as well as differences in stimulation parameters, may impact the neuromodulatory effects induced by NIBS. We emphasize the need to investigate task-specific network interactions in future studies by combining NIBS with neuroimaging.

Examining Individual Differences in Language Learning: A Neurocognitive Model of Language Aptitude.

A common practice in the cognitive neurosciences is to investigate population-typical phenomena, treating individuals as equal except for a few outliers that are usually discarded from analyses or that disappear on group-level patterns. Only a few studies to date have captured the heterogeneity of language processing across individuals as so-called "individual differences"; fewer have explicitly researched language aptitude, which designates an individual's ability for acquiring foreign languages. Existing studies show that, relative to average learners, very gifted language learners display different task-related patterns of functional activation and connectivity during linguistic tasks, and structural differences in white and grey matter morphology, and in white matter connectivity. Despite growing interest in language aptitude, there is no recent comprehensive review, nor a theoretical model to date that includes the neural level. To fill this gap, we review neuroscientific research on individual differences in language learning and language aptitude and present a first, preliminary neurocognitive model of language aptitude. We suggest that language aptitude could arise from an advantageous neurocognitive profile, which leads to high intrinsic motivation and proactive engagement in language learning activities. On the neural level, interindividual differences in the morphology of the bilateral auditory cortex constrain individual neural plasticity, as is evident in the speed and efficiency of language learning. We suggest that language learning success is further dependent upon highly efficient auditory-motor connections (speech-motor networks) and the structural characteristics of dorsal and ventral fibre tracts during language learning.

Auditory Cortex Morphology Predicts Language Learning Potential in Children and Teenagers.

In two recent studies, we identified neuroanatomical and neurofunctional markers of musical aptitude, attention deficit (hyperactivity) disorder and dyslexia in the auditory cortex (AC) of children. In a subsequent study with adults, we found evidence for neuroanatomical correlates of speech imitation ability in right Heschl's gyrus (HG), a structure comprising primary and parts of secondary AC. In the present study, we aimed to verify this previously suggested link between structural variation of right HG and language aptitude in a younger population of children and teenagers (N = 42; age range: 10-16 years), while behaviorally exploring the relationship between language aptitude, working memory, arithmetic skills and musicality. Behaviorally, scores on the language aptitude battery strongly correlated with working memory and speech imitation ability. Furthermore, we found that self- and parent-reported language aptitude and school grades were closely associated with language aptitude scores. Neuroanatomical analyses revealed a significant relationship between the occurrence of multiple HGs and high gray matter (GM) volumes in right AC and high language aptitude regardless of age, gender or musical ability. Additionally, low language aptitude was associated with the occurrence of single gyri in right AC. In accordance with previous research, we suggest that right HG might be associated with language aptitude, with a stronger gyrification and higher GM volumes being beneficial for successful auditory processing and the integration of speech-related cues.

Cognitive and Behavioural Weaknesses in Children with Reading Disorder and AD(H)D.

Working memory capacity, an essential prerequisite for language learning and the development of arithmetic skills, has been reported as deficient in children with reading disorder (RD) and attention deficit (hyperactivity) disorder (AD(H)D). However, few studies to date have explored potential associations of working memory impairments and foreign language learning, mathematical skills and school achievement in these groups, in particular in children with a comorbidity of both. In the present study, we assessed working memory, language learning, arithmetic fluency and academic achievement in children (N = 166; Mage = 14.3, range 8-18 y), including typically-developing children (n = 89), subjects with RD (n = 27), AD(H)D (n = 43), and a comorbidity (n = 15). While children with AD(H)D performed similar to typically developing children on all tasks, RD children performed weakly on various language learning and working memory tasks, with major deficits in non-word span, phonetic memory and vocabulary learning. Combining weaknesses of the two groups, children with a comorbidity further performed significantly worse on arithmetic skills, learning of sound-symbol combinations and simple digit span forward. The findings suggest a reconsideration of working memory and learning impairments in AD(H)D, while highlighting the additional weaknesses of comorbid children and pointing out severe foreign language learning difficulties in RD children.

"When Music Speaks": Auditory Cortex Morphology as a Neuroanatomical Marker of Language Aptitude and Musicality.

Recent research has shown that the morphology of certain brain regions may indeed correlate with a number of cognitive skills such as musicality or language ability. The main aim of the present study was to explore the extent to which foreign language aptitude, in particular phonetic coding ability, is influenced by the morphology of Heschl's gyrus (HG; auditory cortex), working memory capacity, and musical ability. In this study, the auditory cortices of German-speaking individuals (N = 30; 13 males/17 females; aged 20-40 years) with high and low scores in a number of language aptitude tests were compared. The subjects' language aptitude was measured by three different tests, namely a Hindi speech imitation task (phonetic coding ability), an English pronunciation assessment, and the Modern Language Aptitude Test (MLAT). Furthermore, working memory capacity and musical ability were assessed to reveal their relationship with foreign language aptitude. On the behavioral level, significant correlations were found between phonetic coding ability, English pronunciation skills, musical experience, and language aptitude as measured by the MLAT. Parts of all three tests measuring language aptitude correlated positively and significantly with each other, supporting their validity for measuring components of language aptitude. Remarkably, the number of instruments played by subjects showed significant correlations with all language aptitude measures and musicality, whereas, the number of foreign languages did not show any correlations. With regard to the neuroanatomy of auditory cortex, adults with very high scores in the Hindi testing and the musicality test (AMMA) demonstrated a clear predominance of complete posterior HG duplications in the right hemisphere. This may reignite the discussion of the importance of the right hemisphere for language processing, especially when linked or common resources are involved, such as the inter-dependency between phonetic and musical aptitude.