Musical and electrical stimulation as intervention in disorder of consciousness (DOC) patients: A randomised cross-over trial.

BACKGROUND: Disorders of consciousness (DOC), i.e., unresponsive wakefulness syndrome (UWS) or vegetative state (VS) and minimally conscious state (MCS), are conditions that can arise from severe brain injury, inducing widespread functional changes. Given the damaging implications resulting from these conditions, there is an increasing need for rehabilitation treatments aimed at enhancing the level of consciousness, the quality of life, and creating new recovery perspectives for the patients. Music may represent an additional rehabilitative tool in contexts where cognition and language are severely compromised, such as among DOC patients. A further type of rehabilitation strategies for DOC patients consists of Non-Invasive Brain Stimulation techniques (NIBS), including transcranial electrical stimulation (tES), affecting neural excitability and promoting brain plasticity. OBJECTIVE: We here propose a novel rehabilitation protocol for DOC patients that combines music-based intervention and NIBS in neurological patients. The main objectives are (i) to assess the residual neuroplastic processes in DOC patients exposed to music, (ii) to determine the putative neural modulation and the clinical outcome in DOC patients of non-pharmacological strategies, i.e., tES(control condition), and music stimulation, and (iii) to evaluate the putative positive impact of this intervention on caregiver's burden and psychological distress. METHODS: This is a randomised cross-over trial in which a total of 30 participants will be randomly allocated to one of three different combinations of conditions: (i) Music only, (ii) tES only (control condition), (iii) Music + tES. The music intervention will consist of listening to an individually tailored playlist including familiar and self-relevant music together with fixed songs; concerning NIBS, tES will be applied for 20 minutes every day, 5 times a week, for two weeks. After these stimulations two weeks of placebo treatments will follow, with sham stimulation combined with noise for other two weeks. The primary outcomes will be clinical, i.e., based on the differences in the scores obtained on the neuropsychological tests, such as Coma Recovery Scale-Revised, and neurophysiological measures as EEG, collected pre-intervention, post-intervention and post-placebo. DISCUSSION: This study proposes a novel rehabilitation protocol for patients with DOC including a combined intervention of music and NIBS. Considering the need for rigorous longitudinal randomised controlled trials for people with severe brain injury disease, the results of this study will be highly informative for highlighting and implementing the putative beneficial role of music and NIBS in rehabilitation treatments. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05706831, registered on January 30, 2023.

Making sense of music: Insights from neurophysiology and connectivity analyses in naturalistic listening conditions.

According to the latest frameworks, auditory perception and memory involve the constant prediction of future sound events by the brain, based on the continuous extraction of feature regularities from the environment. The neural hierarchical mechanisms for predictive processes in perception and memory for sounds are typically studied in relation to simple acoustic features in isolated sounds or sound patterns inserted in highly certain contexts. Such studies have identified reliable prediction formation and error signals, e.g., the N100 or the mismatch negativity (MMN) evoked responses. In real life, though, individuals often face situations in which uncertainty prevails and where making sense of sounds becomes a hard challenge. In music, not only deviations from predictions are masterly set up by composers to induce emotions but sometimes the sheer uncertainty of sound scenes is exploited for aesthetic purposes, especially in compositional styles such as Western atonal classical music. In very recent magnetoencephalography (MEG) and electroencephalography (EEG) studies, experimental and technical advances in stimulation paradigms and analysis approaches have permitted the identification of prediction-error responses from highly uncertain, atonal contexts and the extraction of prediction-related responses from real, continuous music. Moreover, functional connectivity analyses revealed the emergence of cortico-hippocampal interactions during the formation of auditory memories for more predictable vs. less predictable patterns. These findings contribute to understanding the general brain mechanisms that enable us to predict even highly uncertain sound environments and to possibly make sense of and appreciate even atonal music.

Aesthetics and predictive processing: grounds and prospects of a fruitful encounter.

In the last few years, a remarkable convergence of interests and results has emerged between scholars interested in the arts and aesthetics from a variety of perspectives and cognitive scientists studying the mind and brain within the predictive processing (PP) framework. This convergence has so far proven fruitful for both sides: while PP is increasingly adopted as a framework for understanding aesthetic phenomena, the arts and aesthetics, examined under the lens of PP, are starting to be seen as important windows into our mental functioning. The result is a vast and fast-growing research programme that promises to deliver important insights into our aesthetic encounters as well as a wide range of psychological phenomena of general interest. Here, we present this developing research programme, describing its grounds and highlighting its prospects. We start by clarifying how the study of the arts and aesthetics encounters the PP picture of mental functioning (§1). We then go on to outline the prospects of this encounter for the fields involved: philosophy and history of art (§2), psychology of aesthetics and neuroaesthetics (§3) and psychology and neuroscience more generally (§4). The upshot is an ambitious but well-defined framework within which aesthetics and cognitive science can partner up to illuminate crucial aspects of the human mind. This article is part of the theme issue 'Art, aesthetics and predictive processing: theoretical and empirical perspectives'.

The impact of crossmodal predictions on the neural processing of aesthetic stimuli.

Neuroaesthetic research has focused on neural predictive processes involved in the encounter with art stimuli or the related evaluative judgements, and it has been mainly conducted unimodally. Here, with electroencephalography, magnetoencephalography and an affective priming protocol, we investigated whether and how the neural responses to non-representational aesthetic stimuli are top-down modulated by affective representational (i.e. semantically meaningful) predictions between audition and vision. Also, the neural chronometry of affect processing of these aesthetic stimuli was investigated. We hypothesized that the early affective components of crossmodal aesthetic responses are dependent on the affective and representational predictions formed in another sensory modality resulting in differentiated brain responses, and that audition and vision indicate different processing latencies for affect. The target stimuli were aesthetic visual patterns and musical chords, and they were preceded by a prime from the opposing sensory modality. We found that early auditory-cortex responses to chords were more affected by valence than the corresponding visual-cortex ones. Furthermore, the assessments of visual targets were more facilitated by affective congruency of crossmodal primes than the acoustic targets. These results indicate, first, that the brain uses early affective information for predictively guiding aesthetic responses; second, that an affective transfer of information takes place crossmodally, mainly from audition to vision, impacting the aesthetic assessment. This article is part of the theme issue 'Art, aesthetics and predictive processing: theoretical and empirical perspectives'.

Age differences in central auditory system responses to naturalistic music.

Aging influences the central auditory system leading to difficulties in the decoding and understanding of overlapping sound signals, such as speech in noise or polyphonic music. Studies on central auditory system evoked responses (ERs) have found in older compared to young listeners increased amplitudes (less inhibition) of the P1 and N1 and decreased amplitudes of the P2, mismatch negativity (MMN), and P3a responses. While preceding research has focused on simplified auditory stimuli, we here tested whether the previously observed age-related differences could be replicated with sounds embedded in medium and highly naturalistic musical contexts. Older (age 55-77 years) and younger adults (age 21-31 years) listened to medium naturalistic (synthesized melody) and highly naturalistic (studio recording of a music piece) stimuli. For the medium naturalistic music, the age group differences on the P1, N1, P2, MMN, and P3a amplitudes were all replicated. The age group differences, however, appeared reduced with the highly compared to the medium naturalistic music. The finding of lower P2 amplitude in older than young was replicated for slow event rates (0.3-2.9 Hz) in the highly naturalistic music. Moreover, the ER latencies suggested a gradual slowing of the auditory processing time course for highly compared to medium naturalistic stimuli irrespective of age. These results support that age-related differences on ERs can partly be observed with naturalistic stimuli. This opens new avenues for including naturalistic stimuli in the investigation of age-related central auditory system disorders.

Worlds apart? Testing the cultural distance hypothesis in music perception of Chinese and Western listeners.

According to the cultural distance hypothesis (CDH), individuals learn culture-specific statistical structures in music as internal stylistic models and use these models in predictive processing of music, with musical structures closer to their home culture being easier to predict. This cultural distance effect may be affected by domain-specific (musical ability) and domain-general individual characteristics (openness, implicit cultural bias). To test the CDH and its modulation by individual characteristics, we recruited Chinese and Western adults to categorize stylistically ambiguous and unambiguous Chinese and Western melodies by cultural origin. Categorization performance was better for unambiguous (low CD) than ambiguous melodies (high CD), and for in-culture melodies regardless of ambiguity for both groups, providing evidence for CDH. Musical ability, but not other traits, correlated positively with melody categorization, suggesting that musical ability refines internal stylistic models. Therefore, both cultures show musical enculturation in their home culture with a modulatory effect of individual musical ability.

Mismatch negativity as a marker of music perception in individual cochlear implant users: A spike density component analysis study.

OBJECTIVE: Ninety percent of cochlear implant (CI) users are interested in improving their music perception. However, only few objective behavioral and neurophysiological tests have been developed for tracing the development of music discrimination skills in CI users. In this study, we aimed to obtain an accurate individual mismatch negativity (MMN) marker that could predict behavioral auditory discrimination thresholds. METHODS: We measured the individual MMN response to four magnitudes of deviations in four different musical features (intensity, pitch, timbre, and rhythm) in a rare sample of experienced CI users and a control sample of normally hearing participants. We applied a recently developed spike density component analysis (SCA), which can suppress confounding alpha waves, and contrasted it with previously proposed methods. RESULTS: Statistically detected individual MMN predicted attentive sound discrimination ability with high accuracy: for CI users 89.2% (278/312 cases) and for controls 90.5% (384/424 cases). As expected, MMN was detected for fewer CI users when the sound deviants were of smaller magnitude. CONCLUSIONS: The findings support the use of MMN responses in individual CI users as a diagnostic tool for testing music perception. SIGNIFICANCE: For CI users, the new SCA method provided more accurate and replicable diagnostic detections than preceding state-of-the-art.

Adapting to the Sound of Music - Development of Music Discrimination Skills in Recently Implanted CI Users.

Cochlear implants (CIs) are optimized for speech perception but poor in conveying musical sound features such as pitch, melody, and timbre. Here, we investigated the early development of discrimination of musical sound features after cochlear implantation. Nine recently implanted CI users (CIre) were tested shortly after switch-on (T1) and approximately 3 months later (T2), using a musical multifeature mismatch negativity (MMN) paradigm, presenting four deviant features (intensity, pitch, timbre, and rhythm), and a three-alternative forced-choice behavioral test. For reference, groups of experienced CI users (CIex; n = 13) and normally hearing (NH) controls (n = 14) underwent the same tests once. We found significant improvement in CIre's neural discrimination of pitch and timbre as marked by increased MMN amplitudes. This was not reflected in the behavioral results. Behaviorally, CIre scored well above chance level at both time points for all features except intensity, but significantly below NH controls for all features except rhythm. Both CI groups scored significantly below NH in behavioral pitch discrimination. No significant difference was found in MMN amplitude between CIex and NH. The results indicate that development of musical discrimination can be detected neurophysiologically early after switch-on. However, to fully take advantage of the sparse information from the implant, a prolonged adaptation period may be required. Behavioral discrimination accuracy was notably high already shortly after implant switch-on, although well below that of NH listeners. This study provides new insight into the early development of music-discrimination abilities in CI users and may have clinical and therapeutic relevance.

High-fidelity transmission of auditory symbolic material is associated with reduced right-left neuroanatomical asymmetry between primary auditory regions.

The intergenerational stability of auditory symbolic systems, such as music, is thought to rely on brain processes that allow the faithful transmission of complex sounds. Little is known about the functional and structural aspects of the human brain which support this ability, with a few studies pointing to the bilateral organization of auditory networks as a putative neural substrate. Here, we further tested this hypothesis by examining the role of left-right neuroanatomical asymmetries between auditory cortices. We collected neuroanatomical images from a large sample of participants (nonmusicians) and analyzed them with Freesurfer's surface-based morphometry method. Weeks after scanning, the same individuals participated in a laboratory experiment that simulated music transmission: the signaling games. We found that high accuracy in the intergenerational transmission of an artificial tone system was associated with reduced rightward asymmetry of cortical thickness in Heschl's sulcus. Our study suggests that the high-fidelity copying of melodic material may rely on the extent to which computational neuronal resources are distributed across hemispheres. Our data further support the role of interhemispheric brain organization in the cultural transmission and evolution of auditory symbolic systems.

The early adolescent brain on music: Analysis of functional dynamics reveals engagement of orbitofrontal cortex reward system.

Music listening plays a pivotal role for children and adolescents, yet it remains unclear how music modulates brain activity at the level of functional networks in this young population. Analysing the dynamics of brain networks occurring and dissolving over time in response to music can provide a better understanding of the neural underpinning of music listening. We collected functional magnetic resonance imaging (fMRI) data from 17 preadolescents aged 10-11 years while listening to two similar music pieces separated by periods without music. We subsequently tracked the occurrence of functional brain networks over the recording time using a recent method that detects recurrent patterns of phase-locking in the fMRI signals: the leading eigenvector dynamics analysis (LEiDA). The probabilities of occurrence and switching profiles of different functional networks were compared between periods of music and no music. Our results showed significantly increased occurrence of a specific functional network during the two music pieces compared to no music, involving the medial orbitofrontal and ventromedial prefrontal cortices-a brain subsystem associated to reward processing. Moreover, the higher the musical reward sensitivity of the preadolescents, the more this network was preceded by a pattern involving the insula. Our findings highlight the involvement of a brain subsystem associated with hedonic and emotional processing during music listening in the early adolescent brain. These results offer novel insight into the neural underpinnings of musical reward in early adolescence, improving our understanding of the important role and the potential benefits of music at this delicate age.

Consonance and dissonance perception. A critical review of the historical sources, multidisciplinary findings, and main hypotheses.

Revealed more than two millennia ago by Pythagoras, consonance and dissonance (C/D) are foundational concepts in music theory, perception, and aesthetics. The search for the biological, acoustical, and cultural factors that affect C/D perception has resulted in descriptive accounts inspired by arithmetic, musicological, psychoacoustical or neurobiological frameworks without reaching a consensus. Here, we review the key historical sources and modern multidisciplinary findings on C/D and integrate them into three main hypotheses: the vocal similarity hypothesis (VSH), the psychocultural hypothesis (PH), and the sensorimotor hypothesis (SH). By illustrating the hypotheses-related findings, we highlight their major conceptual, methodological, and terminological shortcomings. Trying to provide a unitary framework for C/D understanding, we put together multidisciplinary research on human and animal vocalizations, which converges to suggest that auditory roughness is associated with distress/danger and, therefore, elicits defensive behavioral reactions and neural responses that indicate aversion. We therefore stress the primacy of vocality and roughness as key factors in the explanation of C/D phenomenon, and we explore the (neuro)biological underpinnings of the attraction-aversion mechanisms that are triggered by C/D stimuli. Based on the reviewed evidence, while the aversive nature of dissonance appears as solidly rooted in the multidisciplinary findings, the attractive nature of consonance remains a somewhat speculative claim that needs further investigation. Finally, we outline future directions for empirical research in C/D, especially regarding cross-modal and cross-cultural approaches.

Magnetoencephalography recordings reveal the spatiotemporal dynamics of recognition memory for complex versus simple auditory sequences.

Auditory recognition is a crucial cognitive process that relies on the organization of single elements over time. However, little is known about the spatiotemporal dynamics underlying the conscious recognition of auditory sequences varying in complexity. To study this, we asked 71 participants to learn and recognize simple tonal musical sequences and matched complex atonal sequences while their brain activity was recorded using magnetoencephalography (MEG). Results reveal qualitative changes in neural activity dependent on stimulus complexity: recognition of tonal sequences engages hippocampal and cingulate areas, whereas recognition of atonal sequences mainly activates the auditory processing network. Our findings reveal the involvement of a cortico-subcortical brain network for auditory recognition and support the idea that stimulus complexity qualitatively alters the neural pathways of recognition memory.

Learning to play a musical instrument in the middle school is associated with superior audiovisual working memory and fluid intelligence: A cross-sectional behavioral study.

Music training, in all its forms, is known to have an impact on behavior both in childhood and even in aging. In the delicate life period of transition from childhood to adulthood, music training might have a special role for behavioral and cognitive maturation. Among the several kinds of music training programs implemented in the educational communities, we focused on instrumental training incorporated in the public middle school curriculum in Italy that includes both individual, group and collective (orchestral) lessons several times a week. At three middle schools, we tested 285 preadolescent children (aged 10-14 years) with a test and questionnaire battery including adaptive tests for visuo-spatial working memory skills (with the Jack and Jill test), fluid intelligence (with a matrix reasoning test) and music-related perceptual and memory abilities (with listening tests). Of these children, 163 belonged to a music curriculum within the school and 122 to a standard curriculum. Significant differences between students of the music and standard curricula were found in both perceptual and cognitive domains, even when controlling for pre-existing individual differences in musical sophistication. The music children attending the third and last grade of middle school had better performance and showed the largest advantage compared to the control group on both audiovisual working memory and fluid intelligence. Furthermore, some gender differences were found for several tests and across groups in favor of females. The present results indicate that learning to play a musical instrument as part of the middle school curriculum represents a resource for preadolescent education. Even though the current evidence is not sufficient to establish the causality of the found effects, it can still guide future research evaluation with longitudinal data.

I know what i like when i see it: Likability is distinct from pleasantness since early stages of multimodal emotion evaluation.

Liking and pleasantness are common concepts in psychological emotion theories and in everyday language related to emotions. Despite obvious similarities between the terms, several empirical and theoretical notions support the idea that pleasantness and liking are cognitively different phenomena, becoming most evident in the context of emotion regulation and art enjoyment. In this study it was investigated whether liking and pleasantness indicate behaviourally measurable differences, not only in the long timespan of emotion regulation, but already within the initial affective responses to visual and auditory stimuli. A cross-modal affective priming protocol was used to assess whether there is a behavioural difference in the response time when providing an affective rating to a liking or pleasantness task. It was hypothesized that the pleasantness task would be faster as it is known to rely on rapid feature detection. Furthermore, an affective priming effect was expected to take place across the sensory modalities and the presentative and non-presentative stimuli. A linear mixed effect analysis indicated a significant priming effect as well as an interaction effect between the auditory and visual sensory modalities and the affective rating tasks of liking and pleasantness: While liking was rated fastest across modalities, it was significantly faster in vision compared to audition. No significant modality dependent differences between the pleasantness ratings were detected. The results demonstrate that liking and pleasantness rating scales refer to separate processes already within the short time scale of one to two seconds. Furthermore, the affective priming effect indicates that an affective information transfer takes place across modalities and the types of stimuli applied. Unlike hypothesized, liking rating took place faster across the modalities. This is interpreted to support emotion theoretical notions where liking and disliking are crucial properties of emotion perception and homeostatic self-referential information, possibly overriding pleasantness-related feature analysis. Conclusively, the findings provide empirical evidence for a conceptual delineation of common affective processes.

Genetic polymorphisms in COMT and BDNF influence synchronization dynamics of human neuronal oscillations.

Neuronal oscillations, their inter-areal synchronization, and scale-free dynamics constitute fundamental mechanisms for cognition by regulating communication in neuronal networks. These oscillatory dynamics have large inter-individual variability that is partly heritable. We hypothesized that this variability could be partially explained by genetic polymorphisms in neuromodulatory genes. We recorded resting-state magnetoencephalography (MEG) from 82 healthy participants and investigated whether oscillation dynamics were influenced by genetic polymorphisms in catechol-O-methyltransferase (COMT) Val158Met and brain-derived neurotrophic factor (BDNF) Val66Met. Both COMT and BDNF polymorphisms influenced local oscillation amplitudes and their long-range temporal correlations (LRTCs), while only BDNF polymorphism affected the strength of large-scale synchronization. Our findings demonstrate that COMT and BDNF genetic polymorphisms contribute to inter-individual variability in neuronal oscillation dynamics. Comparison of these results to computational modeling of near-critical synchronization dynamics further suggested that COMT and BDNF polymorphisms influenced local oscillations by modulating the excitation-inhibition balance according to the brain criticality framework.

Atonal Music as a Model for Investigating Exploratory Behavior.

Atonal music is often characterized by low predictability stemming from the absence of tonal or metrical hierarchies. In contrast, Western tonal music exhibits intrinsic predictability due to its hierarchical structure and therefore, offers a directly accessible predictive model to the listener. In consequence, a specific challenge of atonal music is that listeners must generate a variety of new predictive models. Listeners must not only refrain from applying available tonal models to the heard music, but they must also search for statistical regularities and build new rules that may be related to musical properties other than pitch, such as timbre or dynamics. In this article, we propose that the generation of such new predictive models and the aesthetic experience of atonal music are characterized by internal states related to exploration. This is a behavior well characterized in behavioral neuroscience as fulfilling an innate drive to reduce uncertainty but which has received little attention in empirical music research. We support our proposal with emerging evidence that the hedonic value is associated with the recognition of patterns in low-predictability sound sequences and that atonal music elicits distinct behavioral responses in listeners. We end by outlining new research avenues that might both deepen our understanding of the aesthetic experience of atonal music in particular, and reveal core qualities of the aesthetic experience in general.

A systematic review on resting state functional connectivity in patients with neurodegenerative disease and hallucinations.

Hallucinations are a complex and multidimensional phenomenon which can differ based on the involved pathology, typology and sensory modality. Hallucinations are common in patients with neurodegenerative diseases. Recent sparse evidence from resting state functional magnetic resonance imaging (rs-fMRI) studies has identified altered functional connectivity in those patients within several brain networks, such as the default mode, attentional and sensory ones, without, however, providing an organized picture of the mechanisms involved. This systematic review, following PRISMA guidelines, aims at critically analyzing the current literature on the brain networks associated with the phenomenon of hallucinations in patients with neurodegenerative diseases. Ten rs-fMRI studies fulfilled our selection criteria. All these studies focused on synucleinopathies, and most of them focused on visual hallucinations and were characterized by a heterogeneous methodology. Thus, instead of offering a definite picture of the mechanisms underlying hallucinations in neurodegeneration, this systematic review encourages further research especially concerning tauopathies. Notwithstanding, the findings overall suggest a disruption in the top-down (associated with memory intrusion and difficulty of inhibition) and in the bottom-up processes (associated with the sensory areas involved in the hallucinations). Further investigations are needed in order to disentangle the brain mechanisms involved in hallucinations and to overcome possible limitations characterizing the current literature.

An ALE meta-analytic review of musical expertise.

Through long-term training, music experts acquire complex and specialized sensorimotor skills, which are paralleled by continuous neuro-anatomical and -functional adaptations. The underlying neuroplasticity mechanisms have been extensively explored in decades of research in music, cognitive, and translational neuroscience. However, the absence of a comprehensive review and quantitative meta-analysis prevents the plethora of variegated findings to ultimately converge into a unified picture of the neuroanatomy of musical expertise. Here, we performed a comprehensive neuroimaging meta-analysis of publications investigating neuro-anatomical and -functional differences between musicians (M) and non-musicians (NM). Eighty-four studies were included in the qualitative synthesis. From these, 58 publications were included in coordinate-based meta-analyses using the anatomic/activation likelihood estimation (ALE) method. This comprehensive approach delivers a coherent cortico-subcortical network encompassing sensorimotor and limbic regions bilaterally. Particularly, M exhibited higher volume/activity in auditory, sensorimotor, interoceptive, and limbic brain areas and lower volume/activity in parietal areas as opposed to NM. Notably, we reveal topographical (dis-)similarities between the identified functional and anatomical networks and characterize their link to various cognitive functions by means of meta-analytic connectivity modelling. Overall, we effectively synthesized decades of research in the field and provide a consistent and controversies-free picture of the neuroanatomy of musical expertise.

Enhanced mismatch negativity in harmonic compared with inharmonic sounds.

Many natural sounds have frequency spectra composed of integer multiples of a fundamental frequency. This property, known as harmonicity, plays an important role in auditory information processing. However, the extent to which harmonicity influences the processing of sound features beyond pitch is still unclear. This is interesting because harmonic sounds have lower information entropy than inharmonic sounds. According to predictive processing accounts of perception, this property could produce more salient neural responses due to the brain's weighting of sensory signals according to their uncertainty. In the present study, we used electroencephalography to investigate brain responses to harmonic and inharmonic sounds commonly occurring in music: Piano tones and hi-hat cymbal sounds. In a multifeature oddball paradigm, we measured mismatch negativity (MMN) and P3a responses to timbre, intensity, and location deviants in listeners with and without congenital amusia-an impairment of pitch processing. As hypothesized, we observed larger amplitudes and earlier latencies (for both MMN and P3a) in harmonic compared with inharmonic sounds. These harmonicity effects were modulated by sound feature. Moreover, the difference in P3a latency between harmonic and inharmonic sounds was larger for controls than amusics. We propose an explanation of these results based on predictive coding and discuss the relationship between harmonicity, information entropy, and precision weighting of prediction errors.