Choir singing is associated with enhanced structural connectivity across the adult lifespan.

The global ageing of populations calls for effective, ecologically valid methods to support brain health across adult life. Previous evidence suggests that music can promote white matter (WM) microstructure and grey matter (GM) volume while supporting auditory and cognitive functioning and emotional well-being as well as counteracting age-related cognitive decline. Adding a social component to music training, choir singing is a popular leisure activity among older adults, but a systematic account of its potential to support healthy brain structure, especially with regard to ageing, is currently missing. The present study used quantitative anisotropy (QA)-based diffusion MRI connectometry and voxel-based morphometry to explore the relationship of lifetime choir singing experience and brain structure at the whole-brain level. Cross-sectional multiple regression analyses were carried out in a large, balanced sample (N = 95; age range 21-88) of healthy adults with varying levels of choir singing experience across the whole age range and within subgroups defined by age (young, middle-aged, and older adults). Independent of age, choir singing experience was associated with extensive increases in WM QA in commissural, association, and projection tracts across the brain. Corroborating previous work, these overlapped with language and limbic networks. Enhanced corpus callosum microstructure was associated with choir singing experience across all subgroups. In addition, choir singing experience was selectively associated with enhanced QA in the fornix in older participants. No associations between GM volume and choir singing were found. The present study offers the first systematic account of amateur-level choir singing on brain structure. While no evidence for counteracting GM atrophy was found, the present evidence of enhanced structural connectivity coheres well with age-typical structural changes. Corroborating previous behavioural studies, the present results suggest that regular choir singing holds great promise for supporting brain health across the adult life span.

When direction matters: Neural correlates of interlimb coordination of rhythm and beat.

In a previous experiment, we found evidence for a bodily hierarchy governing interlimb coordination of rhythm and beat, using five effectors: 1) Left foot, 2) Right foot, 3) Left hand, 4) Right hand and 5) Voice. The hierarchy implies that, during simultaneous rhythm and beat performance and using combinations of two of these effectors, executing the task by performing the rhythm with an effector that has a higher number than the beat effector is significantly easier than vice versa. To investigate the neural underpinnings of this proposed bodily hierarchy, we here scanned 46 professional musicians using fMRI as they performed a rhythmic pattern with one effector while keeping the beat with another. The conditions combined the voice and the right hand (V + RH), the right hand and the left hand (RH + LH), and the left hand and the right foot (LH + RF). Each effector combination was performed with and against the bodily hierarchy. Going against the bodily hierarchy increased tapping errors significantly and also increased activity in key brain areas functionally associated with top-down sensorimotor control and bottom-up feedback processing, such as the cerebellum and SMA. Conversely, going with the bodily hierarchy engaged areas functionally associated with the default mode network and regions involved in emotion processing. Theories of general brain function that hold prediction as a key principle, propose that action and perception are governed by the brain's attempt to minimise prediction error at different levels in the brain. Following this viewpoint, our results indicate that going against the hierarchy induces stronger prediction errors, while going with the hierarchy allows for a higher degree of automatization. Our results also support the notion of a bodily hierarchy in motor control that prioritizes certain conductive and supportive tapping roles in specific effector combinations.

Differential effects of ageing on the neural processing of speech and singing production.

Background: Understanding healthy brain ageing has become vital as populations are ageing rapidly and age-related brain diseases are becoming more common. In normal brain ageing, speech processing undergoes functional reorganisation involving reductions of hemispheric asymmetry and overactivation in the prefrontal regions. However, little is known about how these changes generalise to other vocal production, such as singing, and how they are affected by associated cognitive demands. Methods: The present cross-sectional fMRI study systematically maps the neural correlates of vocal production across adulthood (N=100, age 21-88 years) using a balanced 2x3 design where tasks varied in modality (speech: proverbs / singing: song phrases) and cognitive demand (repetition / completion from memory / improvisation). Results: In speech production, ageing was associated with decreased left pre- and postcentral activation across tasks and increased bilateral angular and right inferior temporal and fusiform activation in the improvisation task. In singing production, ageing was associated with increased activation in medial and bilateral prefrontal and parietal regions in the completion task, whereas other tasks showed no ageing effects. Direct comparisons between the modalities showed larger age-related activation changes in speech than singing across tasks, including a larger left-to-right shift in lateral prefrontal regions in the improvisation task. Conclusion: The present results suggest that the brains' singing network undergoes differential functional reorganisation in normal ageing compared to the speech network, particularly during a task with high executive demand. These findings are relevant for understanding the effects of ageing on vocal production as well as how singing can support communication in healthy ageing and neurological rehabilitation.

Extensive Sensorimotor Training Predetermines Central Pain Changes During the Development of Prolonged Muscle Pain.

Repetitive movements (RM) are a main risk factor for musculoskeletal pain, which is partly explained by the overloading of musculoskeletal structures. However, RM may also drive brain plasticity, leading to maladaptive changes in sensorimotor areas and altered pain processing. This study aimed to understand whether individuals performing extensive RM (musicians) exhibit altered brain processing to prolonged experimental muscle pain. Nineteen healthy musicians and 20 healthy nontrained controls attended 3 sessions (Day 1-Day 3-Day 8). In each session, event-related potentials (ERPs) to non-nociceptive superficial and nociceptive intraepidermal electrical stimulation, reaction times, electrical detection thresholds, and pressure pain thresholds (PPTs) were recorded. In all participants, prolonged muscle pain was induced by intramuscular injection of nerve growth factor (NGF) into the right first dorsal interosseous muscle at the end of Day1. Pain intensity was assessed on a numerical rating scale (NRS) and was lower in musicians compared to non-musicians (P < .007). Moreover, in musicians, the higher amount of weekly training was associated with lower NRS pain scores on Day 3 to Day 8 (P < .037). Compared with Day1, NGF reduced PPTs on Day 3 to Day 8 (P < .001) and non-nociceptive P200 and P300 ERP amplitudes on Day 8 (P < .044) in both groups. Musicians compared to controls showed secondary hyperalgesia to electrical stimulation on Day 3 to Day 8 (P < .004) and reduced nociceptive P200 ERP amplitudes on Day 8 (P < .005). Across participants, ERP components correlated with pain detection reaction times, sensitivity (PPTs and electrical detection thresholds), and severity (NRS), (all P < .043). These results show that repetitive sensorimotor training leads to brain changes in the processing of prolonged pain, biasing the cortical response to nociceptive inputs. PERSPECTIVE: Repetitive sensorimotor training may increase the responsiveness of nociceptive inputs during the development of prolonged muscle pain. These novel data highlight the role of repetitive sensorimotor practice as a source for interindividual variability in central pain processing.

Extensive sensorimotor training enhances nociceptive cortical responses in healthy individuals.

BACKGROUND: Prolonged and repeated sensorimotor training is a crucial driver for promoting use-dependent plasticity, but also a main risk factor for developing musculoskeletal pain syndromes, yet the neural underpinnings that link repetitive movements to abnormal pain processing are unknown. METHODS: Twenty healthy musicians, one of the best in vivo models to study use-dependent plasticity, and 20 healthy non-musicians were recruited. Perceptual thresholds, reaction times (RTs) and event-related potentials (ERPs) were recorded using nociceptive intra-epidermal and non-nociceptive transcutaneous electrical stimulation. RESULTS: In response to comparable stimulus intensities, musicians compared to non-musicians showed larger non-nociceptive N140 (associated with higher activation of regions within the salience network), higher nociceptive N200 ERPs (associated with higher activation of regions within the sensorimotor network) and faster RTs to both stimuli. Non-musicians showed larger non-nociceptive P200 ERP. Notably, a similar P200 component prominently emerged during nociceptive stimulation in non-musicians. Across participants, larger N140 and N200 ERPs were associated with RTs, whereas the amount of daily practice in musicians explained non-nociceptive P200 and nociceptive P300 ERPs. CONCLUSIONS: These novel findings indicate that the mechanisms by which extensive sensorimotor training promotes use-dependent plasticity in multisensory neural structures may also shape the neural signatures of nociceptive processing in healthy individuals. SIGNIFICANCE: Repetitive sensorimotor training may increase the responsiveness of nociceptive evoked potentials. These novel data highlight the importance of repetitive sensorimotor practice as a contributing factor to the interindividual variability of nociceptive-related potentials.

Neuroanatomical correlates of speech and singing production in chronic post-stroke aphasia.

A classical observation in neurology is that aphasic stroke patients with impairments in speech production can nonetheless sing the same utterances. This preserved ability suggests a distinctive neural architecture for singing that could contribute to speech recovery. However, to date, these structural correlates remain unknown. Here, we combined a multivariate lesion-symptom mapping and voxel-based morphometry approach to analyse the relationship between lesion patterns and grey matter volume and production rate in speech and singing tasks. Lesion patterns for spontaneous speech and cued repetition extended into frontal, temporal and parietal areas typically reported within the speech production network. Impairment in spontaneous singing was associated with damage to the left anterior-posterior superior and middle temporal gyri. Preservation of grey matter volume in the same regions where damage led to poor speech and singing production supported better performance in these tasks. When dividing the patients into fluent and dysfluent singers based on the singing performance from demographically matched controls, we found that the preservation of the left middle temporal gyrus was related to better spontaneous singing. These findings provide insights into the structural correlates of singing in chronic aphasia and may serve as biomarkers to predict treatment response in clinical trials using singing-based interventions for speech rehabilitation.

Imagine, Sing, Play- Combined Mental, Vocal and Physical Practice Improves Musical Performance.

Classical musicians face a high demand for flawless and expressive performance, leading to highly intensified practice activity. Whereas the advantage of using mental strategies is well documented in sports research, few studies have explored the efficacy of mental imagery and overt singing on musical instrumental learning. In this study, 50 classically trained trumpet students performed short unfamiliar pieces. Performances were recorded before and after applying four prescribed practice strategies which were (1) physical practice, (2) mental imagery, (3) overt singing with optional use of solfege, (4) a combination of 1, 2 and 3 or a control condition, no practice. Three experts independently assessed pitch and rhythm accuracy, sound quality, intonation, and musical expression in all recordings. We found higher gains in the overall performance, as well as in pitch accuracy for the physical practice, and the combined practice strategies, compared to no practice. Furthermore, only the combined strategy yielded a significant improvement in musical expression. Pitch performance improvement was positively correlated with previous solfege training and frequent use of random practice strategies. The findings highlight benefits from applying practice strategies that complement physical practice in music instrument practice in short term early stages of learning a new piece. The study may generalize to other forms of learning, involving cognitive processes and motor skills.

Functional connectivity in human auditory networks and the origins of variation in the transmission of musical systems.

Music producers, whether original composers or performers, vary in their ability to acquire and faithfully transmit music. This form of variation may serve as a mechanism for the emergence of new traits in musical systems. In this study, we aim to investigate whether individual differences in the social learning and transmission of music relate to intrinsic neural dynamics of auditory processing systems. We combined auditory and resting-state functional magnetic resonance imaging (fMRI) with an interactive laboratory model of cultural transmission, the signaling game, in an experiment with a large cohort of participants (N=51). We found that the degree of interhemispheric rs-FC within fronto-temporal auditory networks predicts-weeks after scanning-learning, transmission, and structural modification of an artificial tone system. Our study introduces neuroimaging in cultural transmission research and points to specific neural auditory processing mechanisms that constrain and drive variation in the cultural transmission and regularization of musical systems.

Experience-dependent neuroplasticity in trained musicians modulates the effects of chronic pain on insula-based networks - A resting-state fMRI study.

Recent resting-state fMRI studies associated extensive musical training with increased insula-based connectivity in large-scale networks involved in salience, emotion, and higher-order cognitive processes. Similar changes have also been found in chronic pain patients, suggesting that both types of experiences can have comparable effects on insula circuitries. Based on these observations, the current study asked the question whether, and if so in what way, different forms of experience-dependent neuroplasticity may interact. Here we assessed insula-based connectivity during fMRI resting-state between musicians and non-musicians both with and without chronic pain, and correlated the results with clinical pain duration and intensity. As expected, insula connectivity was increased in chronic pain non-musicians relative to healthy non-musicians (with cingulate cortex and supplementary motor area), yet no differences were found between chronic pain non-musicians and healthy musicians. In contrast, musicians with chronic pain showed decreased insula connectivity relative to both healthy musicians (with sensorimotor and memory regions) and chronic pain non-musicians (with the hippocampus, inferior temporal gyrus, and orbitofrontal cortex), as well as lower pain-related inferences with daily activities. Pain duration correlated positively with insula connectivity only in non-musicians, whereas pain intensity exhibited distinct relationships across groups. We conclude that although music-related sensorimotor training and chronic pain, taken in isolation, can lead to increased insula-based connectivity, their combination may lead to higher-order plasticity (metaplasticity) in chronic pain musicians, engaging brain mechanisms that can modulate the consequences of maladaptive experience-dependent neural reorganization (i.e., pain chronification).

Intermittent theta burst stimulation over right somatosensory larynx cortex enhances vocal pitch-regulation in nonsingers.

While the significance of auditory cortical regions for the development and maintenance of speech motor coordination is well established, the contribution of somatosensory brain areas to learned vocalizations such as singing is less well understood. To address these mechanisms, we applied intermittent theta burst stimulation (iTBS), a facilitatory repetitive transcranial magnetic stimulation (rTMS) protocol, over right somatosensory larynx cortex (S1) and a nonvocal dorsal S1 control area in participants without singing experience. A pitch-matching singing task was performed before and after iTBS to assess corresponding effects on vocal pitch regulation. When participants could monitor auditory feedback from their own voice during singing (Experiment I), no difference in pitch-matching performance was found between iTBS sessions. However, when auditory feedback was masked with noise (Experiment II), only larynx-S1 iTBS enhanced pitch accuracy (50-250 ms after sound onset) and pitch stability (>250 ms after sound onset until the end). Results indicate that somatosensory feedback plays a dominant role in vocal pitch regulation when acoustic feedback is masked. The acoustic changes moreover suggest that right larynx-S1 stimulation affected the preparation and involuntary regulation of vocal pitch accuracy, and that kinesthetic-proprioceptive processes play a role in the voluntary control of pitch stability in nonsingers. Together, these data provide evidence for a causal involvement of right larynx-S1 in vocal pitch regulation during singing.

Insula-based networks in professional musicians: Evidence for increased functional connectivity during resting state fMRI.

Despite considerable research on experience-dependent neuroplasticity in professional musicians, detailed understanding of an involvement of the insula is only now beginning to emerge. We investigated the effects of musical training on intrinsic insula-based connectivity in professional classical musicians relative to nonmusicians using resting-state functional MRI. Following a tripartite scheme of insula subdivisions, coactivation profiles were analyzed for the posterior, ventral anterior, and dorsal anterior insula in both hemispheres. While whole-brain connectivity across all participants confirmed previously reported patterns, between-group comparisons revealed increased insular connectivity in musicians relative to nonmusicians. Coactivated regions encompassed constituents of large-scale networks involved in salience detection (e.g., anterior and middle cingulate cortex), affective processing (e.g., orbitofrontal cortex and temporal pole), and higher order cognition (e.g., dorsolateral prefrontal cortex and the temporoparietal junction), whereas no differences were found for the reversed group contrast. Importantly, these connectivity patterns were stronger in musicians who experienced more years of musical practice, including also sensorimotor regions involved in music performance (M1 hand area, S1, A1, and SMA). We conclude that musical training triggers significant reorganization in insula-based networks, potentially facilitating high-level cognitive and affective functions associated with the fast integration of multisensory information in the context of music performance. Hum Brain Mapp 38:4834-4849, 2017. © 2017 Wiley Periodicals, Inc.

Experience-dependent modulation of right anterior insula and sensorimotor regions as a function of noise-masked auditory feedback in singers and nonsingers.

Previous studies on vocal motor production in singing suggest that the right anterior insula (AI) plays a role in experience-dependent modulation of feedback integration. Specifically, when somatosensory input was reduced via anesthesia of the vocal fold mucosa, right AI activity was down regulated in trained singers. In the current fMRI study, we examined how masking of auditory feedback affects pitch-matching accuracy and corresponding brain activity in the same participants. We found that pitch-matching accuracy was unaffected by masking in trained singers yet declined in nonsingers. The corresponding brain region with the most differential and interesting activation pattern was the right AI, which was up regulated during masking in singers but down regulated in nonsingers. Likewise, its functional connectivity with inferior parietal, frontal, and voice-relevant sensorimotor areas was increased in singers yet decreased in nonsingers. These results indicate that singers relied more on somatosensory feedback, whereas nonsingers depended more critically on auditory feedback. When comparing auditory vs somatosensory feedback involvement, the right anterior insula emerged as the only region for correcting intended vocal output by modulating what is heard or felt as a function of singing experience. We propose the right anterior insula as a key node in the brain's singing network for the integration of signals of salience across multiple sensory and cognitive domains to guide vocal behavior.

Voxel-based morphometry in opera singers: Increased gray-matter volume in right somatosensory and auditory cortices.

In contrast to instrumental musicians, professional singers do not train on a specific instrument but perfect a motor system that has already been extensively trained during speech motor development. Previous functional imaging studies suggest that experience with singing is associated with enhanced somatosensory-based vocal motor control. However, experience-dependent structural plasticity in vocal musicians has rarely been studied. We investigated voxel-based morphometry (VBM) in 27 professional classical singers and compared gray matter volume in regions of the "singing-network" to an age-matched group of 28 healthy volunteers with no special singing experience. We found right hemispheric volume increases in professional singers in ventral primary somatosensory cortex (larynx S1) and adjacent rostral supramarginal gyrus (BA40), as well as in secondary somatosensory (S2) and primary auditory cortices (A1). Moreover, we found that earlier commencement with vocal training correlated with increased gray-matter volume in S1. However, in contrast to studies with instrumental musicians, this correlation only emerged in singers who began their formal training after the age of 14years, when speech motor development has reached its first plateau. Structural data thus confirm and extend previous functional reports suggesting a pivotal role of somatosensation in vocal motor control with increased experience in singing. Results furthermore indicate a sensitive period for developing additional vocal skills after speech motor coordination has matured.

Music in Research and Rehabilitation of Disorders of Consciousness: Psychological and Neurophysiological Foundations.

According to a prevailing view, the visual system works by dissecting stimuli into primitives, whereas the auditory system processes simple and complex stimuli with their corresponding features in parallel. This makes musical stimulation particularly suitable for patients with disorders of consciousness (DoC), because the processing pathways related to complex stimulus features can be preserved even when those related to simple features are no longer available. An additional factor speaking in favor of musical stimulation in DoC is the low efficiency of visual stimulation due to prevalent maladies of vision or gaze fixation in DoC patients. Hearing disorders, in contrast, are much less frequent in DoC, which allows us to use auditory stimulation at various levels of complexity. The current paper overviews empirical data concerning the four main domains of brain functioning in DoC patients that musical stimulation can address: perception (e.g., pitch, timbre, and harmony), cognition (e.g., musical syntax and meaning), emotions, and motor functions. Music can approach basic levels of patients' self-consciousness, which may even exist when all higher-level cognitions are lost, whereas music induced emotions and rhythmic stimulation can affect the dopaminergic reward-system and activity in the motor system respectively, thus serving as a starting point for rehabilitation.

Evidence for Enhanced Interoceptive Accuracy in Professional Musicians.

Interoception is defined as the perceptual activity involved in the processing of internal bodily signals. While the ability of internal perception is considered a relatively stable trait, recent data suggest that learning to integrate multisensory information can modulate it. Making music is a uniquely rich multisensory experience that has shown to alter motor, sensory, and multimodal representations in the brain of musicians. We hypothesize that musical training also heightens interoceptive accuracy comparable to other perceptual modalities. Thirteen professional singers, twelve string players, and thirteen matched non-musicians were examined using a well-established heartbeat discrimination paradigm complemented by self-reported dispositional traits. Results revealed that both groups of musicians displayed higher interoceptive accuracy than non-musicians, whereas no differences were found between singers and string-players. Regression analyses showed that accumulated musical practice explained about 49% variation in heartbeat perception accuracy in singers but not in string-players. Psychometric data yielded a number of psychologically plausible inter-correlations in musicians related to performance anxiety. However, dispositional traits were not a confounding factor on heartbeat discrimination accuracy. Together, these data provide first evidence indicating that professional musicians show enhanced interoceptive accuracy compared to non-musicians. We argue that musical training largely accounted for this effect.

Pain sensitivity and tactile spatial acuity are altered in healthy musicians as in chronic pain patients.

Extensive training of repetitive and highly skilled movements, as it occurs in professional classical musicians, may lead to changes in tactile sensitivity and corresponding cortical reorganization of somatosensory cortices. It is also known that professional musicians frequently experience musculoskeletal pain and pain-related symptoms during their careers. The present study aimed at understanding the complex interaction between chronic pain and music training with respect to somatosensory processing. For this purpose, tactile thresholds (mechanical detection, grating orientation, two-point discrimination) and subjective ratings to thermal and pressure pain stimuli were assessed in 17 professional musicians with chronic pain, 30 pain-free musicians, 20 non-musicians with chronic pain, and 18 pain-free non-musicians. We found that pain-free musicians displayed greater touch sensitivity (i.e., lower mechanical detection thresholds), lower tactile spatial acuity (i.e., higher grating orientation thresholds) and increased pain sensitivity to pressure and heat compared to pain-free non-musicians. Moreover, we also found that musicians and non-musicians with chronic pain presented lower tactile spatial acuity and increased pain sensitivity to pressure and heat compared to pain-free non-musicians. The significant increment of pain sensitivity together with decreased spatial discrimination in pain-free musicians and the similarity of results found in chronic pain patients, suggests that the extensive training of repetitive and highly skilled movements in classical musicians could be considered as a risk factor for developing chronic pain, probably due to use-dependent plastic changes elicited in somatosensory pathways.

Experience-dependent modulation of feedback integration during singing: role of the right anterior insula.

Somatosensation plays an important role in the motor control of vocal functions, yet its neural correlate and relation to vocal learning is not well understood. We used fMRI in 17 trained singers and 12 nonsingers to study the effects of vocal-fold anesthesia on the vocal-motor singing network as a function of singing expertise. Tasks required participants to sing musical target intervals under normal conditions and after anesthesia. At the behavioral level, anesthesia altered pitch accuracy in both groups, but singers were less affected than nonsingers, indicating an experience-dependent effect of the intervention. At the neural level, this difference was accompanied by distinct patterns of decreased activation in singers (cortical and subcortical sensory and motor areas) and nonsingers (subcortical motor areas only) respectively, suggesting that anesthesia affected the higher-level voluntary (explicit) motor and sensorimotor integration network more in experienced singers, and the lower-level (implicit) subcortical motor loops in nonsingers. The right anterior insular cortex (AIC) was identified as the principal area dissociating the effect of expertise as a function of anesthesia by three separate sources of evidence. First, it responded differently to anesthesia in singers (decreased activation) and nonsingers (increased activation). Second, functional connectivity between AIC and bilateral A1, M1, and S1 was reduced in singers but augmented in nonsingers. Third, increased BOLD activity in right AIC in singers was correlated with larger pitch deviation under anesthesia. We conclude that the right AIC and sensory-motor areas play a role in experience-dependent modulation of feedback integration for vocal motor control during singing.