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.

Multivariate Concavity Amplitude Index (MCAI) for characterizing Heschl's gyrus shape.

Heschl's gyrus (HG), which includes primary auditory cortex, is highly variable in its shape (i.e. gyrification patterns), between hemispheres and across individuals. Differences in HG shape have been observed in the context of phonetic learning skill and expertise, and of professional musicianship, among others. Two of the most common configurations of HG include single HG, where a single transverse temporal gyrus is present, and common stem duplications (CSD), where a sulcus intermedius (SI) arises from the lateral aspect of HG. Here we describe a new toolbox, called 'Multivariate Concavity Amplitude Index' (MCAI), which automatically assesses the shape of HG. MCAI works on the output of TASH, our first toolbox which automatically segments HG, and computes continuous indices of concavity, which arise when sulci are present, along the outer perimeter of an inflated representation of HG, in a directional manner. Thus, MCAI provides a multivariate measure of shape, which is reproducible and sensitive to small variations in shape. We applied MCAI to structural magnetic resonance imaging (MRI) data of N=181 participants, including professional and amateur musicians and from non-musicians. Former studies have shown large variations in HG shape in the former groups. We validated MCAI by showing high correlations between the dominant (i.e. highest) lateral concavity values and continuous visual assessments of the degree of lateral gyrification of the first gyrus. As an application of MCAI, we also replicated previous visually obtained findings showing a higher likelihood of bilateral CSDs in musicians. MCAI opens a wide range of applications in evaluating HG shape in the context of individual differences, expertise, disorder and genetics.

Temporal hierarchy of cortical responses reflects core-belt-parabelt organization of auditory cortex in musicians.

Human auditory cortex (AC) organization resembles the core-belt-parabelt organization in nonhuman primates. Previous studies assessed mostly spatial characteristics; however, temporal aspects were little considered so far. We employed co-registration of functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in musicians with and without absolute pitch (AP) to achieve spatial and temporal segregation of human auditory responses. First, individual fMRI activations induced by complex harmonic tones were consistently identified in four distinct regions-of-interest within AC, namely in medial Heschl's gyrus (HG), lateral HG, anterior superior temporal gyrus (STG), and planum temporale (PT). Second, we analyzed the temporal dynamics of individual MEG responses at the location of corresponding fMRI activations. In the AP group, the auditory evoked P2 onset occurred ~25 ms earlier in the right as compared with the left PT and ~15 ms earlier in the right as compared with the left anterior STG. This effect was consistent at the individual level and correlated with AP proficiency. Based on the combined application of MEG and fMRI measurements, we were able for the first time to demonstrate a characteristic temporal hierarchy ("chronotopy") of human auditory regions in relation to specific auditory abilities, reflecting the prediction for serial processing from nonhuman studies.

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.

Singing Mandarin? What Short-Term Memory Capacity, Basic Auditory Skills, and Musical and Singing Abilities Reveal About Learning Mandarin.

Learning Mandarin has become increasingly important in the Western world but is rather difficult to be learnt by speakers of non-tone languages. Since tone language learning requires very precise tonal ability, we set out to test whether musical skills, musical status, singing ability, singing behavior during childhood, basic auditory skills, and short-term memory ability contribute to individual differences in Mandarin performance. Therefore, we developed Mandarin tone discrimination and pronunciation tasks to assess individual differences in adult participants' (N = 109) tone language ability. Results revealed that short-term memory capacity, singing ability, pitch perception preferences, and tone frequency (high vs. low tones) were the most important predictors, which explained individual differences in the Mandarin performances of our participants. Therefore, it can be concluded that training of basic auditory skills, musical training including singing should be integrated in the educational setting for speakers of non-tone languages who learn tone languages such as Mandarin.

Examining Individual Differences in Singing, Musical and Tone Language Ability in Adolescents and Young Adults with Dyslexia.

In recent years, evidence has been provided that individuals with dyslexia show alterations in the anatomy and function of the auditory cortex. Dyslexia is considered to be a learning disability that affects the development of music and language capacity. We set out to test adolescents and young adults with dyslexia and controls (N = 52) for their neurophysiological differences by investigating the auditory evoked P1-N1-P2 complex. In addition, we assessed their ability in Mandarin, in singing, their musical talent and their individual differences in elementary auditory skills. A discriminant analysis of magnetencephalography (MEG) revealed that individuals with dyslexia showed prolonged latencies in P1, N1, and P2 responses. A correlational analysis between MEG and behavioral variables revealed that Mandarin syllable tone recognition, singing ability and musical aptitude (AMMA) correlated with P1, N1, and P2 latencies, respectively, while Mandarin pronunciation was only associated with N1 latency. The main findings of this study indicate that the earlier P1, N1, and P2 latencies, the better is the singing, the musical aptitude, and the ability to link Mandarin syllable tones to their corresponding syllables. We suggest that this study provides additional evidence that dyslexia can be understood as an auditory and sensory processing deficit.

Musicianship-Related Structural and Functional Cortical Features Are Preserved in Elderly Musicians.

Background: Professional musicians are a model population for exploring basic auditory function, sensorimotor and multisensory integration, and training-induced neuroplasticity. The brain of musicians exhibits distinct structural and functional cortical features; however, little is known about how these features evolve during aging. This multiparametric study aimed to examine the functional and structural neural correlates of lifelong musical practice in elderly professional musicians. Methods: Sixteen young musicians, 16 elderly musicians (age >70), and 15 elderly non-musicians participated in the study. We assessed gray matter metrics at the whole-brain and region of interest (ROI) levels using high-resolution magnetic resonance imaging (MRI) with the Freesurfer automatic segmentation and reconstruction pipeline. We used BrainVoyager semiautomated segmentation to explore individual auditory cortex morphotypes. Furthermore, we evaluated functional blood oxygenation level-dependent (BOLD) activations in auditory and non-auditory regions by functional MRI (fMRI) with an attentive tone-listening task. Finally, we performed discriminant function analyses based on structural and functional ROIs. Results: A general reduction of gray matter metrics distinguished the elderly from the young subjects at the whole-brain level, corresponding to widespread natural brain atrophy. Age- and musicianship-dependent structural correlations revealed group-specific differences in several clusters including superior, middle, and inferior frontal as well as perirolandic areas. In addition, the elderly musicians exhibited increased gyrification of auditory cortex like the young musicians. During fMRI, the elderly non-musicians activated predominantly auditory regions, whereas the elderly musicians co-activated a much broader network of auditory association areas, primary and secondary motor areas, and prefrontal and parietal regions like, albeit weaker, the young musicians. Also, group-specific age- and musicianship-dependent functional correlations were observed in the frontal and parietal regions. Moreover, discriminant function analysis could separate groups with high accuracy based on a set of specific structural and functional, mainly temporal and occipital, ROIs. Conclusion: In conclusion, despite naturally occurring senescence, the elderly musicians maintained musicianship-specific structural and functional cortical features. The identified structural and functional brain regions, discriminating elderly musicians from non-musicians, might be of relevance for the aging musicians' brain. To what extent lifelong musical activity may have a neuroprotective impact needs to be addressed further in larger longitudinal studies.

A Discriminative Characterization of Heschl's Gyrus Morphology using Spectral Graph Features.

Heschl's Gyrus (HG), which hosts the primary auditory cortex, exhibits large variability not only in size but also in its gyrification patterns, within (i.e., between hemispheres) and between individuals. Conventional structural measures such as volume, surface area and thickness do not capture the full morphological complexity of HG, in particular, with regards to its shape. We present a method for characterizing the morphology of HG in terms of Laplacian eigenmodes of surface-based and volume-based graph representations of its structure, and derive a set of spectral graph features that can be used to discriminate HG subtypes. We applied this method to a dataset of 177 adults previously shown to display considerable variability in the shape of their HG, including data from amateur and professional musicians, as well as non-musicians. Results show the superiority of the proposed spectral graph features over conventional ones in differentiating HG subtypes, in particular, single HG versus Common Stem Duplications (CSDs). We anticipate the proposed shape features to be found beneficial in the domains of language, music and associated pathologies, in which variability of HG morphology has previously been established.

TASH: Toolbox for the Automated Segmentation of Heschl's gyrus.

Auditory cortex volume and shape differences have been observed in the context of phonetic learning, musicianship and dyslexia. Heschl's gyrus, which includes primary auditory cortex, displays large anatomical variability across individuals and hemispheres. Given this variability, manual labelling is the gold standard for segmenting HG, but is time consuming and error prone. Our novel toolbox, called 'Toolbox for the Automated Segmentation of HG' or TASH, automatically segments HG in brain structural MRI data, and extracts measures including its volume, surface area and cortical thickness. TASH builds upon FreeSurfer, which provides an initial segmentation of auditory regions, and implements further steps to perform finer auditory cortex delineation. We validate TASH by showing significant relationships between HG volumes obtained using manual labelling and using TASH, in three independent datasets acquired on different scanners and field strengths, and by showing good qualitative segmentation. We also present two applications of TASH, demonstrating replication and extension of previously published findings of relationships between HG volumes and (a) phonetic learning, and (b) musicianship. In sum, TASH effectively segments HG in a fully automated and reproducible manner, opening up a wide range of applications in the domains of expertise, disease, genetics and brain plasticity.

Reduced cortical thickness in Heschl's gyrus as an in vivo marker for human primary auditory cortex.

The primary auditory cortex (PAC) is located in the region of Heschl's gyrus (HG), as confirmed by histological, cytoarchitectonical, and neurofunctional studies. Applying cortical thickness (CTH) analysis based on high-resolution magnetic resonance imaging (MRI) and magnetoencephalography (MEG) in 60 primary school children and 60 adults, we investigated the CTH distribution of left and right auditory cortex (AC) and primary auditory source activity at the group and individual level. Both groups showed contoured regions of reduced auditory cortex (redAC) along the mediolateral extension of HG, illustrating large inter-individual variability with respect to shape, localization, and lateralization. In the right hemisphere, redAC localized more within the medial portion of HG, extending typically across HG duplications. In the left hemisphere, redAC was distributed significantly more laterally, reaching toward the anterolateral portion of HG. In both hemispheres, redAC was found to be significantly thinner (mean CTH of 2.34 mm) as compared to surrounding areas (2.99 mm). This effect was more dominant in the right hemisphere rather than in the left one. Moreover, localization of the primary component of auditory evoked activity (P1), as measured by MEG in response to complex harmonic sounds, strictly co-localized with redAC. This structure-function link was found consistently at the group and individual level, suggesting PAC to be represented by areas of reduced cortex in HG. Thus, we propose reduced CTH as an in vivo marker for identifying shape and localization of PAC in the individual brain.

Structured Reporting in Neuroradiology: Intracranial Tumors.

PURPOSE: The aim of this pilot study was to assess the clinical feasibility, diagnostic yield, advantages, and disadvantages of structured reporting for routine MRI-reading in patients with primary diagnosis of intracranial tumors as compared to traditional neuroradiological free text reporting. METHODS: A structured MRI reporting template was developed covering pathological, anatomical, and functional aspects in an itemized fashion. Retrospectively, 60 consecutive patients with first diagnosis of an intracranial tumor were selected from the radiology information system/PACS system. Structured reporting was performed by a senior neuroradiologist, blinded to clinical and radiological data. Reporting times were measured per patient. The diagnostic content was compared to free text reporting which was independently performed on the same MRI exams by two other neuroradiologists. The comparisons were categorized per item as: "congruent," "partially congruent," "incongruent," or "not mentioned in free-style report." RESULTS: Tumor-related items: congruent findings were found for all items (17/17) with congruence rates ranging between 98 and 39% per item. Four items achieved congruence rates ≥90%, 5 items >80%, and 9 items ≥70%. Partially congruent findings were found for all items in up to 50% per item. Incongruent findings were present in 7/17 items in up to 5% per item. Free text reports did not mention 12 of 17 items (range 7-43% per item). Non-tumor-related items, including brain atrophy, microangiopathy, vascular pathologies, and various extracranial pathologies, which were not mentioned in free-text reports between 18 and 85% per item. Mean reporting time for structured reporting was 7:49 min (3:12-17:06 min). CONCLUSION: First results showed that expert structured reporting ensured reliable detection of all relevant brain pathologies along with reproducible documentation of all predefined diagnostic items, which was not always the case for free text reporting. A mean reporting time of 8 min per patient seems clinically feasible.

Prevalence and function of Heschl's gyrus morphotypes in musicians.

Morphological variations of the first transverse Heschl's gyrus (HG) in the human auditory cortex (AC) are common, yet little is known about their functional implication. We investigated individual morphology and function of HG variations in the AC of 41 musicians, using structural and functional magnetic resonance imaging (fMRI) as well as magnetoencephalography (MEG). Four main morphotypes of HG were (i) single HG, (ii) common stem duplication (CSD), (iii) complete posterior duplication (CPD), and (iv) multiple duplications (MD). The vast majority of musicians (90%) exhibited HG multiplications (type ii-iv) in either one (39%) or both (51%) hemispheres. In 27% of musicians, MD with up to four gyri were found. To probe the functional contribution of HG multiplications to auditory processing we performed fMRI and MEG with auditory stimulation using analogous instrumental tone paradigms. Both methods pointed to the recruitment of all parts of HG during auditory stimulation, including multiplications if present. FMRI activations extended with the degree of HG gyrification. MEG source waveform patterns were distinct for the different types of HG: (i) hemispheres with single HG and (ii) CSD exhibited dominant N1 responses, whereas hemispheres with (iii) CPD and (iv) MD exhibited dominant P1 responses. N1 dipole amplitudes correlated with the localization of the first complete Heschl's sulcus (cHS), designating the most posterior anatomical border of HG. P2 amplitudes were significantly higher in professional as compared to amateur musicians. The results suggest that HG multiplications occur much more frequently in musicians than in the general population and constitute a functional unit with HG.

Neural Biomarkers for Dyslexia, ADHD, and ADD in the Auditory Cortex of Children.

Dyslexia, attention deficit hyperactivity disorder (ADHD), and attention deficit disorder (ADD) show distinct clinical profiles that may include auditory and language-related impairments. Currently, an objective brain-based diagnosis of these developmental disorders is still unavailable. We investigated the neuro-auditory systems of dyslexic, ADHD, ADD, and age-matched control children (N = 147) using neuroimaging, magnetencephalography and psychoacoustics. All disorder subgroups exhibited an oversized left planum temporale and an abnormal interhemispheric asynchrony (10-40 ms) of the primary auditory evoked P1-response. Considering right auditory cortex morphology, bilateral P1 source waveform shapes, and auditory performance, the three disorder subgroups could be reliably differentiated with outstanding accuracies of 89-98%. We therefore for the first time provide differential biomarkers for a brain-based diagnosis of dyslexia, ADHD, and ADD. The method allowed not only allowed for clear discrimination between two subtypes of attentional disorders (ADHD and ADD), a topic controversially discussed for decades in the scientific community, but also revealed the potential for objectively identifying comorbid cases. Noteworthy, in children playing a musical instrument, after three and a half years of training the observed interhemispheric asynchronies were reduced by about 2/3, thus suggesting a strong beneficial influence of music experience on brain development. These findings might have far-reaching implications for both research and practice and enable a profound understanding of the brain-related etiology, diagnosis, and musically based therapy of common auditory-related developmental disorders and learning disabilities.