Generating New Musical Preferences From Multilevel Mapping of Predictions to Reward.

Much of what we know and love about music hinges on our ability to make successful predictions, which appears to be an intrinsically rewarding process. Yet the exact process by which learned predictions become pleasurable is unclear. Here we created novel melodies in an alternative scale different from any established musical culture to show how musical preference is generated de novo. Across nine studies (n = 1,185), adult participants learned to like more frequently presented items that adhered to this rapidly learned structure, suggesting that exposure and prediction errors both affected self-report liking ratings. Learning trajectories varied by music-reward sensitivity but were similar for U.S. and Chinese participants. Furthermore, functional MRI activity in auditory areas reflected prediction errors, whereas functional connectivity between auditory and medial prefrontal regions reflected both exposure and prediction errors. Collectively, results support predictive coding as a cognitive mechanism by which new musical sounds become rewarding.

Music and Brain Circuitry: Strategies for Strengthening Evidence-Based Research for Music-Based Interventions.

The neuroscience of music and music-based interventions (MBIs) is a fascinating but challenging research field. While music is a ubiquitous component of every human society, MBIs may encompass listening to music, performing music, music-based movement, undergoing music education and training, or receiving treatment from music therapists. Unraveling the brain circuits activated and influenced by MBIs may help us gain better understanding of the therapeutic and educational values of MBIs by gathering strong research evidence. However, the complexity and variety of MBIs impose unique research challenges. This article reviews the recent endeavor led by the National Institutes of Health to support evidence-based research of MBIs and their impact on health and diseases. It also highlights fundamental challenges and strategies of MBI research with emphases on the utilization of animal models, human brain imaging and stimulation technologies, behavior and motion capturing tools, and computational approaches. It concludes with suggestions of basic requirements when studying MBIs and promising future directions to further strengthen evidence-based research on MBIs in connections with brain circuitry.SIGNIFICANCE STATEMENT Music and music-based interventions (MBI) engage a wide range of brain circuits and hold promising therapeutic potentials for a variety of health conditions. Comparative studies using animal models have helped in uncovering brain circuit activities involved in rhythm perception, while human imaging, brain stimulation, and motion capture technologies have enabled neural circuit analysis underlying the effects of MBIs on motor, affective/reward, and cognitive function. Combining computational analysis, such as prediction method, with mechanistic studies in animal models and humans may unravel the complexity of MBIs and their effects on health and disease.

Functional Organization of Auditory and Reward Systems in Aging.

The intrinsic organization of functional brain networks is known to change with age, and is affected by perceptual input and task conditions. Here, we compare functional activity and connectivity during music listening and rest between younger (n = 24) and older (n = 24) adults, using whole-brain regression, seed-based connectivity, and ROI-ROI connectivity analyses. As expected, activity and connectivity of auditory and reward networks scaled with liking during music listening in both groups. Younger adults show higher within-network connectivity of auditory and reward regions as compared with older adults, both at rest and during music listening, but this age-related difference at rest was reduced during music listening, especially in individuals who self-report high musical reward. Furthermore, younger adults showed higher functional connectivity between auditory network and medial prefrontal cortex that was specific to music listening, whereas older adults showed a more globally diffuse pattern of connectivity, including higher connectivity between auditory regions and bilateral lingual and inferior frontal gyri. Finally, connectivity between auditory and reward regions was higher when listening to music selected by the participant. These results highlight the roles of aging and reward sensitivity on auditory and reward networks. Results may inform the design of music-based interventions for older adults and improve our understanding of functional network dynamics of the brain at rest and during a cognitively engaging task.

Integrating music-based interventions with Gamma-frequency stimulation: Implications for healthy ageing.

In recent years, music-based interventions (MBIs) have risen in popularity as a non-invasive, sustainable form of care for treating dementia-related disorders, such as Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD). Despite their clinical potential, evidence regarding the efficacy of MBIs on patient outcomes is mixed. Recently, a line of related research has begun to investigate the clinical impact of non-invasive Gamma-frequency (e.g., 40 Hz) sensory stimulation on dementia. Current work, using non-human-animal models of AD, suggests that non-invasive Gamma-frequency stimulation can remediate multiple pathophysiologies of dementia at the molecular, cellular and neural-systems scales, and, importantly, improve cognitive functioning. These findings suggest that the efficacy of MBIs could, in theory, be enhanced by incorporating Gamma-frequency stimulation into current MBI protocols. In the current review, we propose a novel clinical framework for non-invasively treating dementia-related disorders that combines previous MBIs with current approaches employing Gamma-frequency sensory stimulation. We theorize that combining MBIs with Gamma-frequency stimulation could increase the therapeutic power of MBIs by simultaneously targeting multiple biomarkers of dementia, restoring neural activity that underlies learning and memory (e.g., Gamma-frequency neural activity, Theta-Gamma coupling), and actively engaging auditory and reward networks in the brain to promote behavioural change.

Creativity and tradition: Music and bifocal stance theory.

We argue that music can serve as a time-sensitive lens into the interplay between instrumental and ritual stances in cultural evolution. Over various timescales, music can switch between pursuing an end goal or not, and between presenting a causal opacity that is resolvable, or not. With these fluctuations come changes in the motivational structures that drive innovation versus copying.

Toward inclusive theories of the evolution of musicality.

We compare and contrast the 60 commentaries by 109 authors on the pair of target articles by Mehr et al. and ourselves. The commentators largely reject Mehr et al.'s fundamental definition of music and their attempts to refute (1) our social bonding hypothesis, (2) byproduct hypotheses, and (3) sexual selection hypotheses for the evolution of musicality. Instead, the commentators generally support our more inclusive proposal that social bonding and credible signaling mechanisms complement one another in explaining cooperation within and competition between groups in a coevolutionary framework (albeit with some confusion regarding terminologies such as "byproduct" and "exaptation"). We discuss the proposed criticisms and extensions, with a focus on moving beyond adaptation/byproduct dichotomies and toward testing of cross-species, cross-cultural, and other empirical predictions.

Improvising at rest: Differentiating jazz and classical music training with resting state functional connectivity.

Jazz improvisation offers a model for creative cognition, as it involves the real-time creation of a novel, information-rich product. Previous research has shown that when musicians improvise, they recruit regions in the Default Mode Network (DMN) and Executive Control Network (ECN). Here, we ask whether these findings from task-fMRI studies might extend to intrinsic differences in resting state functional connectivity. We compared Improvising musicians, Classical musicians, and Minimally Musically Trained (MMT) controls in seed-based functional connectivity and network analyses in resting state functional MRI. We also examined the functional correlates of behavioral performance in musical improvisation and divergent thinking. Seed-based analysis consistently showed higher connectivity in ventral DMN (vDMN) and bilateral ECN in both groups of musically trained individuals as compared to MMT controls, with additional group differences in primary visual network. In particular, primary visual network connectivity to DMN and ECN was highest in Improvisational musicians, as was connectivity between ECN and DMN; in contrast, connectivity between vDMN and frontal pole was highest in Classical musicians. Furthermore, graph-theoretical analysis indicated heightened network measures in both musician groups, with betweenness centrality, clustering, and local efficiency showing highest levels in Classical musicians, and degrees and strengths showing highest levels in Improvisational musicians. Taken together, results suggest that heightened functional connectivity among musicians can be explained by higher within-network connectivity (more tight-knit cortical networks) in Classical musicians, as opposed to more disperse, globally-connected cortical networks in Improvisational musicians.

Music as a coevolved system for social bonding.

Why do humans make music? Theories of the evolution of musicality have focused mainly on the value of music for specific adaptive contexts such as mate selection, parental care, coalition signaling, and group cohesion. Synthesizing and extending previous proposals, we argue that social bonding is an overarching function that unifies all of these theories, and that musicality enabled social bonding at larger scales than grooming and other bonding mechanisms available in ancestral primate societies. We combine cross-disciplinary evidence from archeology, anthropology, biology, musicology, psychology, and neuroscience into a unified framework that accounts for the biological and cultural evolution of music. We argue that the evolution of musicality involves gene-culture coevolution, through which proto-musical behaviors that initially arose and spread as cultural inventions had feedback effects on biological evolution because of their impact on social bonding. We emphasize the deep links between production, perception, prediction, and social reward arising from repetition, synchronization, and harmonization of rhythms and pitches, and summarize empirical evidence for these links at the levels of brain networks, physiological mechanisms, and behaviors across cultures and across species. Finally, we address potential criticisms and make testable predictions for future research, including neurobiological bases of musicality and relationships between human music, language, animal song, and other domains. The music and social bonding hypothesis provides the most comprehensive theory to date of the biological and cultural evolution of music.

Jazz musicians reveal role of expectancy in human creativity.

Creativity has been defined as the ability to produce work that is novel, high in quality, and appropriate to an audience. While the nature of the creative process is under debate, many believe that creativity relies on real-time combinations of known neural and cognitive processes. One useful model of creativity comes from musical improvisation, such as in jazz, in which musicians spontaneously create novel sound sequences. Here we use jazz musicians to test the hypothesis that individuals with training in musical improvisation, which entails creative generation of musical ideas, might process expectancy differently. We compare jazz improvisers, non-improvising musicians, and non-musicians in the domain-general task of divergent thinking, as well as the musical task of preference ratings for chord progressions that vary in expectation while EEGs were recorded. Behavioral results showed for the first time that jazz musicians preferred unexpected chord progressions. ERP results showed that unexpected stimuli elicited larger early and mid-latency ERP responses (ERAN and P3b), followed by smaller long-latency responses (Late Positivity Potential) in jazz musicians. The amplitudes of these ERP components were significantly correlated with behavioral measures of fluency and originality on the divergent thinking task. Together, results highlight the role of expectancy in creativity.

Neural Mechanisms Underlying Musical Pitch Perception and Clinical Applications Including Developmental Dyslexia.

Music production and perception invoke a complex set of cognitive functions that rely on the integration of sensorimotor, cognitive, and emotional pathways. Pitch is a fundamental perceptual attribute of sound and a building block for both music and speech. Although the cerebral processing of pitch is not completely understood, recent advances in imaging and electrophysiology have provided insight into the functional and anatomical pathways of pitch processing. This review examines the current understanding of pitch processing and behavioral and neural variations that give rise to difficulties in pitch processing, and potential applications of music education for language processing disorders such as dyslexia.

A Dual-Stream Neuroanatomy of Singing.

Singing requires effortless and efficient use of auditory and motor systems that center around the perception and production of the human voice. Although perception and production are usually tightly coupled functions, occasional mismatches between the two systems inform us of dissociable pathways in the brain systems that enable singing. Here I review the literature on perception and production in the auditory modality, and propose a dual-stream neuroanatomical model that subserves singing. I will discuss studies surrounding the neural functions of feedforward, feedback, and efference systems that control vocal monitoring, as well as the white matter pathways that connect frontal and temporal regions that are involved in perception and production. I will also consider disruptions of the perception-production network that are evident in tone-deaf individuals and poor pitch singers. Finally, by comparing expert singers against other musicians and nonmusicians, I will evaluate the possibility that singing training might offer rehabilitation from these disruptions through neuroplasticity of the perception-production network. Taken together, the best available evidence supports a model of dorsal and ventral pathways in auditory-motor integration that enables singing and is shared with language, music, speech, and human interactions in the auditory environment.

Predictive coding in musical anhedonia: A study of groove.

Groove, or the pleasurable urge to move to music, offers unique insight into the relationship between emotion and action. The predictive coding of music model posits that groove is linked to predictions of music formed over time, with stimuli of moderate complexity rated as most pleasurable and likely to engender movement. At the same time, listeners vary in the pleasure they derive from music listening: individuals with musical anhedonia report reduced pleasure during music listening despite no impairments in music perception and no general anhedonia. Little is known about musical anhedonics' subjective experience of groove. Here we examined the relationship between groove and music reward sensitivity. Participants (n = 287) heard drum-breaks that varied in perceived complexity, and rated each for pleasure and wanting to move. Musical anhedonics (n = 13) had significantly lower ratings compared to controls (n = 13) matched on music perception abilities and general anhedonia. However, both groups demonstrated the classic inverted-U relationship between ratings of pleasure & move and stimulus complexity, with ratings peaking for intermediately complex stimuli. Across our entire sample, pleasure ratings were most strongly related with music reward sensitivity for highly complex stimuli (i.e., there was an interaction between music reward sensitivity and stimulus complexity). Finally, the sensorimotor subscale of music reward was uniquely associated with move, but not pleasure, ratings above and beyond the five other dimensions of musical reward. Results highlight the multidimensional nature of reward sensitivity and suggest that pleasure and wanting to move are driven by overlapping but separable mechanisms.

Musical anhedonia, timbre, and the rewards of music listening.

Pleasure in music has been linked to predictive coding of melodic and rhythmic patterns, subserved by connectivity between regions in the brain's auditory and reward networks. Specific musical anhedonics derive little pleasure from music and have altered auditory-reward connectivity, but no difficulties with music perception abilities and no generalized physical anhedonia. Recent research suggests that specific musical anhedonics experience pleasure in nonmusical sounds, suggesting that the implicated brain pathways may be specific to music reward. However, this work used sounds with clear real-world sources (e.g., babies laughing, crowds cheering), so positive hedonic responses could be based on the referents of these sounds rather than the sounds themselves. We presented specific musical anhedonics and matched controls with isolated short pleasing and displeasing synthesized sounds of varying timbres with no clear real-world referents. While the two groups found displeasing sounds equally displeasing, the musical anhedonics gave substantially lower pleasure ratings to the pleasing sounds, indicating that their sonic anhedonia is not limited to musical rhythms and melodies. Furthermore, across a large sample of participants, mean pleasure ratings for pleasing synthesized sounds predicted significant and similar variance in six dimensions of musical reward considered to be relatively independent, suggesting that pleasure in sonic timbres play a role in eliciting reward-related responses to music. We replicate the earlier findings of preserved pleasure ratings for semantically referential sounds in musical anhedonics and find that pleasure ratings of semantic referents, when presented without sounds, correlated with ratings for the sounds themselves. This association was stronger in musical anhedonics than in controls, suggesting the use of semantic knowledge as a compensatory mechanism for affective sound processing. Our results indicate that specific musical anhedonia is not entirely specific to melodic and rhythmic processing, and suggest that timbre merits further research as a source of pleasure in music.

Network connectivity differences in music listening among older adults following a music-based intervention.

Music-based interventions are a common feature in long-term care with clinical reports highlighting music's ability to engage individuals with complex diagnoses. While these findings are promising, normative findings from healthy controls are needed to disambiguate treatment effects unique to pathology and those seen in healthy aging. The present study examines brain network dynamics during music listening in a sample of healthy older adults before and after a music-based intervention. We found intervention effects from hidden Markov model-estimated fMRI network data. Following the intervention, participants demonstrated greater occupancy (the amount of time a network was occupied) in a temporal-mesolimbic network. We conclude that network dynamics in healthy older adults are sensitive to music-based interventions. We discuss these findings' implications for future studies with individuals with neurodegeneration.

Creative tempo: Spatiotemporal dynamics of the default mode network in improvisational musicians.

The intrinsic dynamics of human brain activity display a recurring pattern of anti-correlated activity between the default mode network (DMN), associated with internal processing and mentation, and task positive regions, associated with externally directed attention. In human functional magnetic resonance imaging (fMRI) data, this anti-correlated pattern is detectable on the infraslow timescale (<0.1 Hz) as a quasi-periodic pattern (QPP). While the DMN is implicated in creativity and musicality in traditional time-averaged functional connectivity studies, no one has yet explored how creative training may alter dynamic spatiotemporal patterns involving the DMN such as QPPs. In the present study, we compare the outputs of two QPP detection approaches, sliding window algorithm and complex principal components analysis (cPCA). We apply both methods to an existing dataset of musicians captured with resting state fMRI, grouped as either classical, improvisational, or minimally trained non-musicians. The original time-averaged functional connectivity (FC) analysis of this dataset used improvisation as a proxy for creative thinking and found that the DMN and visual networks (VIS) display higher connectivity in improvisational musicians. We expand upon this dataset's original study and find that QPP analysis detects convergent results at the group level with both methods. In improvisational musicians, dynamic functional correlation in the group-averaged QPP was found to be increased between the DMN-VIS and DMN-FPN for both the QPP algorithm and complex principal components analysis (cPCA) methods. Additionally, we found an unexpected increase in FC in the group-averaged QPP between the dorsal attention network and amygdala in improvisational musicians; this result was not reported in the original seed-based study of this dataset. The current study represents a novel application of two dynamic FC detection methods with results that replicate and expand upon previous seed-based FC findings. The results show the robustness of both the QPP phenomenon and its detection methods. This study also demonstrates the value of dynamic FC methods in reproducing seed-based findings and their promise in detecting group-wise or individual differences that may be missed by traditional seed-based resting state fMRI studies.

Pathways to seeing music: enhanced structural connectivity in colored-music synesthesia.

Synesthesia, a condition in which a stimulus in one sensory modality consistently and automatically triggers concurrent percepts in another modality, provides a window into the neural correlates of cross-modal associations. While research on grapheme-color synesthesia has provided evidence for both hyperconnectivity-hyperbinding and disinhibited feedback as potential underlying mechanisms, less research has explored the neuroanatomical basis of other forms of synesthesia. In the current study we investigated the white matter correlates of colored-music synesthesia. As these synesthetes report seeing colors upon hearing musical sounds, we hypothesized that they might show unique patterns of connectivity between visual and auditory association areas. We used diffusion tensor imaging to trace the white matter tracts in temporal and occipital lobe regions in 10 synesthetes and 10 matched non-synesthete controls. Results showed that synesthetes possessed hemispheric patterns of fractional anisotropy, an index of white matter integrity, in the inferior fronto-occipital fasciculus (IFOF), a major white matter pathway that connects visual and auditory association areas to frontal regions. Specifically, white matter integrity within the right IFOF was significantly greater in synesthetes than controls. Furthermore, white matter integrity in synesthetes was correlated with scores on audiovisual tests of the Synesthesia Battery, especially in white matter underlying the right fusiform gyrus. Our findings provide the first evidence of a white matter substrate of colored-music synesthesia, and suggest that enhanced white matter connectivity is involved in enhanced cross-modal associations.

Graph Theoretical Network Structures Underlie Age-Related Differences in the Functional Connectome During Rest and Music Listening.

Aging is associated with decreased functional connectivity within the default mode network, as well as auditory and reward systems which are involved in music listening. Understanding how music listening affects network organization of the aging brain, both globally and specific to the brain networks, will have implications for designing lifestyle interventions that tap into distinct networks in the brain. Here we apply graph-theory metrics of modularity, global efficiency, clustering coefficients, degrees, and betweenness centrality to compare younger and older adults (YA/OA, N=24 per group) in fMRI connectivity during rest and a music listening task. Results show a less modular but more globally efficient connectome in OAs, especially during music listening, resulting in main effects of group and task, as well as group-by-task interactions. ROI analyses indicated that the posterior cingulate is more centrally located than the medial prefrontal cortex in OAs. Overall, reduced modularity and increased global efficiency with age is in keeping with previously-observed functional reorganizations, and interaction effects show that age-related differences in baseline network organization are reflected in, potentially magnified by, music listening.

Age-related variability in network engagement during music listening.

Listening to music is an enjoyable behaviour that engages multiple networks of brain regions. As such, the act of music listening may offer a way to interrogate network activity, and to examine the reconfigurations of brain networks that have been observed in healthy aging. The present study is an exploratory examination of brain network dynamics during music listening in healthy older and younger adults. Network measures were extracted and analyzed together with behavioural data using a combination of hidden Markov modelling and partial least squares. We found age- and preference-related differences in fMRI data collected during music listening in healthy younger and older adults. Both age groups showed higher occupancy (the proportion of time a network was active) in a temporal-mesolimbic network while listening to self-selected music. Activity in this network was strongly positively correlated with liking and familiarity ratings in younger adults, but less so in older adults. Additionally, older adults showed a higher degree of correlation between liking and familiarity ratings consistent with past behavioural work on age-related dedifferentiation. We conclude that, while older adults do show network and behaviour patterns consistent with dedifferentiation, activity in the temporal-mesolimbic network is relatively robust to dedifferentiation. These findings may help explain how music listening remains meaningful and rewarding in old age.

Functional Organization of Auditory and Reward Systems in Aging.

The intrinsic organization of functional brain networks is known to change with age, and is affected by perceptual input and task conditions. Here, we compare functional activity and connectivity during music listening and rest between younger (N=24) and older (N=24) adults, using whole brain regression, seed-based connectivity, and ROI-ROI connectivity analyses. As expected, activity and connectivity of auditory and reward networks scaled with liking during music listening in both groups. Younger adults show higher within-network connectivity of auditory and reward regions as compared to older adults, both at rest and during music listening, but this age-related difference at rest was reduced during music listening, especially in individuals who self-report high musical reward. Furthermore, younger adults showed higher functional connectivity between auditory network and medial prefrontal cortex (mPFC) that was specific to music listening, whereas older adults showed a more globally diffuse pattern of connectivity, including higher connectivity between auditory regions and bilateral lingual and inferior frontal gyri. Finally, connectivity between auditory and reward regions was higher when listening to music selected by the participant. These results highlight the roles of aging and reward sensitivity on auditory and reward networks. Results may inform the design of music- based interventions for older adults, and improve our understanding of functional network dynamics of the brain at rest and during a cognitively engaging task.

Influence of mild cognitive impairment and body mass index on white matter integrity assessed by diffusion tensor imaging.

Mild cognitive impairment (MCI), a prodromal stage of Alzheimer's disease, is characterized by decreased memory and cognition, which are linked to degenerative changes in the brain. To assess whether white matter (WM) integrity is compromised in MCI, we collected diffusion-weighted images from 60 healthy older adults (OA) (69.16 ± 0.7) and 20 older adults with amnestic MCI (72.45 ± 1.9). WM integrity differences were examined using Tract-Based Spatial Statistics (TBSS). We hypothesized that those with MCI would have diminished WM integrity relative to OA. In a whole-brain comparison, those with MCI showed higher axial diffusivity in the splenium (SCC) and body of the corpus callosum (BCC), superior corona radiata (SCR), and the retrolenticular part of the internal capsule (RLIC) (p's < .05 TFCE-corrected). Additionally, significant between-group connectivity differences were observed using probabilistic tractography between the SCC, chosen from the TBSS results, and forceps major and minor (p-value's < .05). To further relate a physical health indicator to WM alterations, linear regression showed significant interactions between cognitive status and body mass index (BMI) on diffusivity outcome measures from probabilistic tractography (p-value-'s < .05). Additionally, we examined the association between relational memory, BMI, and WM integrity. WM integrity was positively associated with relational memory performance. These findings suggest that these regions may be more sensitive to early markers of neurodegenerative disease and health behaviors, suggesting that modifiable lifestyle factors may affect white matter integrity.