Do variants in the coding regions of FOXP2, a gene implicated in speech disorder, confer a risk for congenital amusia?

Congenital amusia is a lifelong disorder that compromises the normal development of musical abilities in 1.5-4% of the general population. There is a substantial genetic contribution to congenital amusia, and it bears similarities to neurodevelopmental disorders of language. Here, we examine the extent to which variants in the forkhead box P2 gene (FOXP2)-the first gene to be identified as causal in developmental speech deficits-are associated with the amusic trait. Using a cohort of 49 individuals with amusia, of which 27 were unrelated, the role of FOXP2 variants in amusia was evaluated. Fourteen variants were examined in the cohort. None segregated with the amusic trait among participants for whom family information was available; nor were they predicted to be deleterious to protein function. Thus, variants in FOXP2 are not likely to cause amusia. Implications for ongoing debates about the distinction between musicality and language are discussed.

Improvisation is a novel tool to study musicality.

Humans spontaneously invent songs from an early age. Here, we exploit this natural inclination to probe implicit musical knowledge in 33 untrained and poor singers (amusia). Each sang 28 long improvisations as a response to a verbal prompt or a continuation of a melodic stem. To assess the extent to which each improvisation reflects tonality, which has been proposed to be a core organizational principle of musicality and which is present within most music traditions, we developed a new algorithm that compares a sung excerpt to a probability density function representing the tonal hierarchy of Western music. The results show signatures of tonality in both nonmusicians and individuals with congenital amusia, who have notorious difficulty performing musical tasks that require explicit responses and memory. The findings are a proof of concept that improvisation can serve as a novel, even enjoyable method for systematically measuring hidden aspects of musicality across the spectrum of musical ability.

Genetic factors and shared environment contribute equally to objective singing ability.

Singing ability is a complex human skill influenced by genetic and environmental factors, the relative contributions of which remain unknown. Currently, genetically informative studies using objective measures of singing ability across a range of tasks are limited. We administered a validated online singing tool to measure performance across three everyday singing tasks in Australian twins (n = 1189) to explore the relative genetic and environmental influences on singing ability. We derived a reproducible phenotypic index for singing ability across five performance measures of pitch and interval accuracy. Using this index we found moderate heritability of singing ability (h 2 = 40.7%) with a striking, similar contribution from shared environmental factors (c 2 = 37.1%). Childhood singing in the family home and being surrounded by music early in life both significantly predicted the phenotypic index. Taken together, these findings show that singing ability is equally influenced by genetic and shared environmental factors.

Cross-Frequency Brain Network Dynamics Support Pitch Change Detection.

Processing auditory sequences involves multiple brain networks and is crucial to complex perception associated with music appreciation and speech comprehension. We used time-resolved cortical imaging in a pitch change detection task to detail the underlying nature of human brain network activity, at the rapid time scales of neurophysiology. In response to tone sequence presentation to the participants, we observed slow inter-regional signaling at the pace of tone presentations (2-4 Hz) that was directed from auditory cortex toward both inferior frontal and motor cortices. Symmetrically, motor cortex manifested directed influence onto auditory and inferior frontal cortices via bursts of faster (15-35 Hz) activity. These bursts occurred precisely at the expected latencies of each tone in a sequence. This expression of interdependency between slow/fast neurophysiological activity yielded a form of local cross-frequency phase-amplitude coupling in auditory cortex, which strength varied dynamically and peaked when pitch changes were anticipated. We clarified the mechanistic relevance of these observations in relation to behavior by including a group of individuals afflicted by congenital amusia, as a model of altered function in processing sound sequences. In amusia, we found a depression of inter-regional slow signaling toward motor and inferior frontal cortices, and a chronic overexpression of slow/fast phase-amplitude coupling in auditory cortex. These observations are compatible with a misalignment between the respective neurophysiological mechanisms of stimulus encoding and internal predictive signaling, which was absent in controls. In summary, our study provides a functional and mechanistic account of neurophysiological activity for predictive, sequential timing of auditory inputs.SIGNIFICANCE STATEMENT Auditory sequences are processed by extensive brain networks, involving multiple systems. In particular, fronto-temporal brain connections participate in the encoding of sequential auditory events, but so far, their study was limited to static depictions. This study details the nature of oscillatory brain activity involved in these inter-regional interactions in human participants. It demonstrates how directed, polyrhythmic oscillatory interactions between auditory and motor cortical regions provide a functional account for predictive timing of incoming items in an auditory sequence. In addition, we show the functional relevance of these observations in relation to behavior, with data from both normal hearing participants and a rare cohort of individuals afflicted by congenital amusia, which we considered here as a model of altered function in processing sound sequences.

The relationship between acoustic and musical pitch processing in adolescents.

Amusia is defined as a difficulty processing the tonal pitch structure of music such that an individual cannot tell the difference between notes that are in-key and out-of-key. A fine-grained pitch discrimination deficit is often observed in people with amusia. It is possible that an intervention, early in development, could mitigate amusia; however, one challenge identifying amusia early in development is that identifying in- and out-of-key notes is a metacognitive task. Given the common co-occurrence of difficulties with pitch discrimination, it would be easier to identify amusia in developing children by using a pitch change detection task. The goal of this study was to explore the behavioural and neurophysiological profiles of adolescents with poor pitch processing (Poor PP) abilities compared with those with normal pitch processing (Normal PP) abilities. Neurophysiologically, the Poor PPs exhibited a similar event-related potential (ERP) profile to adult amusics during both acoustic and musical pitch discrimination tasks. That is, early ERPs (ERAN, MMN) were similar in Poor PPs compared with Normal PPs, whereas late positivities (P300, P600) were absent in Poor PPs, but present in Normal PPs. At the same time, behavioural data revealed a double dissociation between the abilities to detect a pitch deviant in acoustic and musical context, suggesting that about a third of the children would be missed by selecting a fine-grained acoustic pitch discrimination task to identify the presence of amusia in early childhood.

The singing voice is special: Persistence of superior memory for vocal melodies despite vocal-motor distractions.

Vocal melodies sung without lyrics (la la) are remembered better than instrumental melodies. What causes the advantage? One possibility is that vocal music elicits subvocal imitation, which could promote enhanced motor representations of a melody. If this motor interpretation is correct, distracting the motor system during encoding should reduce the memory advantage for vocal over piano melodies. In Experiment 1, participants carried out movements of the mouth (i.e., chew gum) or hand (i.e., squeeze a beanbag) while listening to 24 unfamiliar folk melodies (half vocal, half piano). In a subsequent memory test, they rated the same melodies and 24 timbre-matched foils from '1-Definitely New' to '7-Definitely Old'. There was a memory advantage for vocal over piano melodies with no effect of group and no interaction. In Experiment 2, participants carried out motor activities during encoding more closely related to singing, either silently articulating (la la) or vocalizing without articulating (humming continuously). Once again, there was a significant advantage for vocal melodies with no effect or interaction of group. In Experiment 3, participants audibly whispered (la la) repeatedly during encoding. Again, the voice advantage was present and did not differ appreciably from prior research with no motor task during encoding. However, we observed that the spontaneous phase-locking of whisper rate and musical beat tended to predict enhanced memory for vocal melodies. Altogether the results challenge the notion that subvocal rehearsal of the melody drives enhanced memory for vocal melodies. Instead, the voice may enhance engagement.

What Makes Musical Prodigies?

Musical prodigies reach exceptionally high levels of achievement before adolescence. Despite longstanding interest and fascination in musical prodigies, little is known about their psychological profile. Here we assess to what extent practice, intelligence, and personality make musical prodigies a distinct category of musician. Nineteen former or current musical prodigies (aged 12-34) were compared to 35 musicians (aged 14-37) with either an early (mean age 6) or late (mean age 10) start but similar amount of musical training, and 16 non-musicians (aged 14-34). All completed a Wechsler IQ test, the Big Five Inventory, the Autism Spectrum Quotient, the Barcelona Music Reward Questionnaire, the Dispositional Flow Scale, and a detailed history of their lifetime music practice. None of the psychological traits distinguished musical prodigies from control musicians or non-musicians except their propensity to report flow during practice. The other aspects that differentiated musical prodigies from their peers were the intensity of their practice before adolescence, and the source of their motivation when they began to play. Thus practice, by itself, does not make a prodigy. The results are compatible with multifactorial models of expertise, with prodigies lying at the high end of the continuum. In summary, prodigies are expected to present brain predispositions facilitating their success in learning an instrument, which could be amplified by their early and intense practice happening at a moment when brain plasticity is heightened.

Basic timekeeping deficit in the Beat-based Form of Congenital Amusia.

Humans have the capacity to match movements' timing with the beat of music. Yet some individuals show marked difficulties. The causes of these difficulties remain to be determined. Here, we investigate to what extend a beat synchronization deficit can be traced to basic timekeeping abilities. Eight beat-impaired individuals who were unable to successfully synchronize to the beat of music were compared to matched controls in their ability to tap a self-paced regular beat, to tap to a metronome spanning a large range of tempi (225-1709 ms inter-tone onsets), and to maintain the tempi after the sounds had ceased. Whether paced by a metronome or not, beat-impaired individuals showed poorer regularity (higher variability) in tapping, with an inability to synchronize at a fast tempo (225 ms between beats) or to sustain tapping at slow tempi (above 1 sec). Yet, they showed evidence of predictive and flexible processing. We suggest that the beat impairment is due to imprecise internal timekeeping mechanism.

Influence of Background Musical Emotions on Attention in Congenital Amusia.

Congenital amusia in its most common form is a disorder characterized by a musical pitch processing deficit. Although pitch is involved in conveying emotion in music, the implications for pitch deficits on musical emotion judgements is still under debate. Relatedly, both limited and spared musical emotion recognition was reported in amusia in conditions where emotion cues were not determined by musical mode or dissonance. Additionally, assumed links between musical abilities and visuo-spatial attention processes need further investigation in congenital amusics. Hence, we here test to what extent musical emotions can influence attentional performance. Fifteen congenital amusic adults and fifteen healthy controls matched for age and education were assessed in three attentional conditions: executive control (distractor inhibition), alerting, and orienting (spatial shift) while music expressing either joy, tenderness, sadness, or tension was presented. Visual target detection was in the normal range for both accuracy and response times in the amusic relative to the control participants. Moreover, in both groups, music exposure produced facilitating effects on selective attention that appeared to be driven by the arousal dimension of musical emotional content, with faster correct target detection during joyful compared to sad music. These findings corroborate the idea that pitch processing deficits related to congenital amusia do not impede other cognitive domains, particularly visual attention. Furthermore, our study uncovers an intact influence of music and its emotional content on the attentional abilities of amusic individuals. The results highlight the domain-selectivity of the pitch disorder in congenital amusia, which largely spares the development of visual attention and affective systems.

Cross-Cultural Work in Music Cognition: Challenges, Insights, and Recommendations.

Many foundational questions in the psychology of music require cross-cultural approaches, yet the vast majority of work in the field to date has been conducted with Western participants and Western music. For cross-cultural research to thrive, it will require collaboration between people from different disciplinary backgrounds, as well as strategies for overcoming differences in assumptions, methods, and terminology. This position paper surveys the current state of the field and offers a number of concrete recommendations focused on issues involving ethics, empirical methods, and definitions of "music" and "culture."

Decoding Task-Related Functional Brain Imaging Data to Identify Developmental Disorders: The Case of Congenital Amusia.

Machine learning classification techniques are frequently applied to structural and resting-state fMRI data to identify brain-based biomarkers for developmental disorders. However, task-related fMRI has rarely been used as a diagnostic tool. Here, we used structural MRI, resting-state connectivity and task-based fMRI data to detect congenital amusia, a pitch-specific developmental disorder. All approaches discriminated amusics from controls in meaningful brain networks at similar levels of accuracy. Interestingly, the classifier outcome was specific to deficit-related neural circuits, as the group classification failed for fMRI data acquired during a verbal task for which amusics were unimpaired. Most importantly, classifier outputs of task-related fMRI data predicted individual behavioral performance on an independent pitch-based task, while this relationship was not observed for structural or resting-state data. These results suggest that task-related imaging data can potentially be used as a powerful diagnostic tool to identify developmental disorders as they allow for the prediction of symptom severity.

The effects of short-term musical training on the neural processing of speech-in-noise in older adults.

Experienced musicians outperform non-musicians in understanding speech-in-noise (SPIN). The benefits of lifelong musicianship endure into older age, where musicians experience smaller declines in their ability to understand speech in noisy environments. However, it is presently unknown whether commencing musical training in old age can also counteract age-related decline in speech perception, and whether such training induces changes in neural processing of speech. Here, we recruited older adult non-musicians and assigned them to receive a short course of piano or videogame training, or no training. Participants completed two sessions of functional Magnetic Resonance Imaging where they performed a SPIN task prior to and following training. While we found no direct benefit of musical training upon SPIN perception, an exploratory Region of Interest analysis revealed increased cortical responses to speech in left Middle Frontal and Supramarginal Gyri which correlated with changes in SPIN task performance in the group which received music training. These results suggest that short-term musical training in older adults may enhance neural encoding of speech, with the potential to reduce age-related decline in speech perception.

Poor Synchronization to Musical Beat Generalizes to Speech.

The rhythmic nature of speech may recruit entrainment mechanisms in a manner similar to music. In the current study, we tested the hypothesis that individuals who display a severe deficit in synchronizing their taps to a musical beat (called beat-deaf here) would also experience difficulties entraining to speech. The beat-deaf participants and their matched controls were required to align taps with the perceived regularity in the rhythm of naturally spoken, regularly spoken, and sung sentences. The results showed that beat-deaf individuals synchronized their taps less accurately than the control group across conditions. In addition, participants from both groups exhibited more inter-tap variability to natural speech than to regularly spoken and sung sentences. The findings support the idea that acoustic periodicity is a major factor in domain-general entrainment to both music and speech. Therefore, a beat-finding deficit may affect periodic auditory rhythms in general, not just those for music.

Musical training improves the ability to understand speech-in-noise in older adults.

It is well known that hearing abilities decline with age, and one of the most commonly reported hearing difficulties reported in older adults is a reduced ability to understand speech in noisy environments. Older adult musicians have an enhanced ability to understand speech in noise, and this has been associated with enhanced brain responses related to both speech processing and the deployment of attention; however, the causal impact of music lessons in older adults has not yet been demonstrated. To investigate whether a causal relationship exists between short-term musical training and performance on auditory tests in older adults and to determine if musical training can be used to improve hearing in older adult nonmusicians, we conducted a longitudinal training study with random assignment. A sample of older adults was randomly assigned to learn to play piano (Music), to learn to play a visuospatially demanding video game (Video), or to serve as a no-contact control (No-contact). After 6 months, the Music group improved their ability to understand a word presented in loud background noise, whereas the other 2 groups did not. This improvement was related to an increase in positive-going electrical brain activity at fronto-left electrodes 200-1000 ms after the presentation of a word in noise. Source analyses suggest that this activity was due to sources located in the left inferior frontal gyrus and other regions involved in the speech-motor system. These findings support the idea that musical training provides a causal benefit to hearing abilities. Importantly, these findings suggest that musical training could be used as a foundation to develop auditory rehabilitation programs for older adults.

Electrophysiological Responses to Emotional Facial Expressions Following a Mild Traumatic Brain Injury.

The present study aimed to measure neural information processing underlying emotional recognition from facial expressions in adults having sustained a mild traumatic brain injury (mTBI) as compared to healthy individuals. We thus measured early (N1, N170) and later (N2) event-related potential (ERP) components during presentation of fearful, neutral, and happy facial expressions in 10 adults with mTBI and 11 control participants. Findings indicated significant differences between groups, irrespective of emotional expression, in the early attentional stage (N1), which was altered in mTBI. The two groups showed similar perceptual integration of facial features (N170), with greater amplitude for fearful facial expressions in the right hemisphere. At a higher-level emotional discrimination stage (N2), both groups demonstrated preferential processing for fear as compared to happiness and neutrality. These findings suggest a reduced early selective attentional processing following mTBI, but no impact on the perceptual and higher-level cognitive processes stages. This study contributes to further improving our comprehension of attentional versus emotional recognition following a mild TBI.

Decreased risk of falls in patients attending music sessions on an acute geriatric ward: results from a retrospective cohort study.

BACKGROUND: Music has been shown to improve health and quality of life. It was suggested that music may also have an impact on gait stability and fall risk. Yet, few studies have exploited music in the hospital setting, and even less so in the geriatric population. Our objective was to examine the influence of music listening on the risk of falls by comparing the Morse Fall Scale score in patients admitted to a Geriatric Assessment Unit (GAU) who attended music listening sessions and in patients who did not attend music sessions. METHODS: This was a retrospective cohort study (mean follow-up 13.3 ± 6.8 days) which took place in a GAU, St. Mary's Hospital Center, Montreal. A total of 152 charts of participants, with a mean age of 85.7 ± 6.4 years and 88.2% female were reviewed and included. There were 61 participants exposed to the music listening sessions group and 91 in the non-exposed group matched for age, sex, cause and season of admission, and living situation. One-hour music sessions were provided to the patients by volunteer musicians. The Morse Fall Scale score upon admission and discharge as well as its variation (change from before to after exposure) were used as outcomes. Age, sex, living situation, reason for admission, season of admission, Mini Mental Status Examination score, number of therapeutic classes taken daily upon admission, use of psychoactive drugs upon admission and length of stay were used as covariates. RESULTS: The Morse Fall Scale score decreased significantly in the exposed group compared to the non-exposed group (p = 0.025) and represented a small to medium-sized effect, d = 0.395. The multiple linear regression model showed a significant association between the decrease of the Morse Fall Scale score and music exposure (B = - 17.1, p = 0.043). CONCLUSION: Participating in music listening sessions was associated with a decreased risk of falls in patients admitted to a GAU. Further controlled research is necessary to confirm these findings and to determine the mechanisms by which music listening impacts fall risk. TRIAL REGISTRATION: Clinical trial registry: ClinicalTrials.gov . Registration number: NCT03348657 (November 17th, 2017). Retrospectively registered.

Comorbidity and cognitive overlap between developmental dyslexia and congenital amusia.

This study investigated whether there is a co-occurrence between developmental dyslexia and congenital amusia in adults. First, a database of online musical tests on 18,000 participants was analysed. Self-reported dyslexic participants performed significantly lower on melodic skills than matched controls, suggesting a possible link between reading and musical disorders. In order to test this relationship more directly, we evaluated 20 participants diagnosed with dyslexia, 16 participants diagnosed with amusia, and their matched controls, with a whole battery of literacy (reading, fluency, spelling), phonological (verbal working memory, phonological awareness) and musical tests (melody, rhythm and metre perception, incidental memory). Amusia was diagnosed in six (30%) dyslexic participants and reading difficulties were found in four (25%) amusic participants. Thus, the results point to a moderate comorbidity between amusia and dyslexia. Further research will be needed to determine what factors at the neural and/or cognitive levels are responsible for this co-occurrence.

The co-occurrence of pitch and rhythm disorders in congenital amusia.

The most studied form of congenital amusia is characterized by a difficulty with detecting pitch anomalies in melodies, also referred to as pitch deafness. Here, we tested for the presence of associated deficits in rhythm processing, beat in particular, in pitch deafness. In Experiment 1, participants performed beat perception and production tasks with musical excerpts of various genres. The results show a beat finding disorder in six of the ten assessed pitch-deaf participants. In order to remove a putative interference of pitch variations with beat extraction, the same participants were tested with percussive rhythms in Experiment 2 and showed a similar impairment. Furthermore, musical pitch and beat processing abilities were correlated. These new results highlight the tight connection between melody and rhythm in music processing that can nevertheless dissociate in some individuals.

Specialized neural dynamics for verbal and tonal memory: fMRI evidence in congenital amusia.

Behavioral and neuropsychological studies have suggested that tonal and verbal short-term memory are supported by specialized neural networks. To date however, neuroimaging investigations have failed to confirm this hypothesis. In this study, we investigated the hypothesis of distinct neural resources for tonal and verbal memory by comparing typical nonmusician listeners to individuals with congenital amusia, who exhibit pitch memory impairments with preserved verbal memory. During fMRI, amusics and matched controls performed delayed-match-to-sample tasks with tones and words and perceptual control tasks with the same stimuli. For tonal maintenance, amusics showed decreased activity in the right auditory cortex, inferior frontal gyrus (IFG) and dorso-lateral-prefrontal cortex (DLPFC). Moreover, they exhibited reduced right-lateralized functional connectivity between the auditory cortex and the IFG during tonal encoding and between the IFG and the DLPFC during tonal maintenance. In contrasts, amusics showed no difference compared with the controls for verbal memory, with activation in the left IFG and left fronto-temporal connectivity. Critically, we observed a group-by-material interaction in right fronto-temporal regions: while amusics recruited these regions less strongly for tonal memory than verbal memory, control participants showed the reversed pattern (tonal > verbal). By benefitting from the rare condition of amusia, our findings suggest specialized cortical systems for tonal and verbal short-term memory in the human brain.