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1.
PLoS Comput Biol ; 19(6): e1011154, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37285380

RESUMEN

A musician's spontaneous rate of movement, called spontaneous motor tempo (SMT), can be measured while spontaneously playing a simple melody. Data shows that the SMT influences the musician's tempo and synchronization. In this study we present a model that captures these phenomena. We review the results from three previously-published studies: solo musical performance with a pacing metronome tempo that is different from the SMT, solo musical performance without a metronome at a tempo that is faster or slower than the SMT, and duet musical performance between musicians with matching or mismatching SMTs. These studies showed, respectively, that the asynchrony between the pacing metronome and the musician's tempo grew as a function of the difference between the metronome tempo and the musician's SMT, musicians drifted away from the initial tempo toward the SMT, and the absolute asynchronies were smaller if musicians had matching SMTs. We hypothesize that the SMT constantly acts as a pulling force affecting musical actions at a tempo different from a musician's SMT. To test our hypothesis, we developed a model consisting of a non-linear oscillator with Hebbian tempo learning and a pulling force to the model's spontaneous frequency. While the model's spontaneous frequency emulates the SMT, elastic Hebbian learning allows for frequency learning to match a stimulus' frequency. To test our hypothesis, we first fit model parameters to match the data in the first of the three studies and asked whether this same model would explain the data the remaining two studies without further tuning. Results showed that the model's dynamics allowed it to explain all three experiments with the same set of parameters. Our theory offers a dynamical-systems explanation of how an individual's SMT affects synchronization in realistic music performance settings, and the model also enables predictions about performance settings not yet tested.


Asunto(s)
Música , Elasticidad , Aprendizaje , Movimiento , Humanos
2.
J Virol ; 96(24): e0148422, 2022 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-36453885

RESUMEN

Adeno-associated virus (AAV) is a small ssDNA satellite virus of high interest (in recombinant form) as a safe and effective gene therapy vector. AAV's human cell entry receptor (AAVR) contains polycystic kidney disease (PKD) domains bound by AAV. Seeking understanding of the spectrum of interactions, goat AAVGo.1 is investigated, because its host is the species most distant from human with reciprocal cross-species cell susceptibility. The structure of AAVGo.1, solved by cryo-EM to 2.9 Å resolution, is most similar to AAV5. Through ELISA (enzyme-linked immunosorbent assay) studies, it is shown that AAVGo.1 binds to human AAVR more strongly than do AAV2 or AAV5, and that it joins AAV5 in a class that binds exclusively to PKD domain 1 (PKD1), in contrast to other AAVs that interact primarily with PKD2. The AAVGo.1 cryo-EM structure of a complex with a PKD12 fragment of AAVR at 2.4 Å resolution shows PKD1 bound with minimal change in virus structure. There are only minor conformational adaptations in AAVR, but there is a near-rigid rotation of PKD1 with maximal displacement of the receptor domain by ~1 Å compared to PKD1 bound to AAV5. AAVGo.1 joins AAV5 as the second member of an emerging class of AAVs whose mode of receptor-binding is completely different from other AAVs, typified by AAV2. IMPORTANCE Adeno-associated virus (AAV) is a small ssDNA satellite parvovirus. As a recombinant vector with a protein shell encapsidating a transgene, recombinant AAV (rAAV) is a leading delivery vehicle for gene therapy, with two FDA-approved treatments and 150 clinical trials for 30 diseases. The human entry receptor AAVR has five PKD domains. To date, all serotypes, except AAV5, have interacted primarily with the second PKD domain, PKD2. Goat is the AAV host most distant from human with cross-species cell infectivity. AAVGo.1 is similar in structure to AAV5, the two forming a class with a distinct mode of receptor-binding. Within the two classes, binding interactions are mostly conserved, giving an indication of the latitude available in modulating delivery vectors.


Asunto(s)
Dependovirus , Vectores Genéticos , Animales , Humanos , Dependovirus/metabolismo , Dependovirus/ultraestructura , Vectores Genéticos/química , Vectores Genéticos/genética , Cabras , Unión Proteica , Terapia Genética/métodos
3.
J Acoust Soc Am ; 154(6): 3799-3809, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-38109404

RESUMEN

Computational models are used to predict the performance of human listeners for carefully specified signal and noise conditions. However, there may be substantial discrepancies between the conditions under which listeners are tested and those used for model predictions. Thus, models may predict better performance than exhibited by the listeners, or they may "fail" to capture the ability of the listener to respond to subtle stimulus conditions. This study tested a computational model devised to predict a listener's ability to detect an aircraft in various soundscapes. The model and listeners processed the same sound recordings under carefully specified testing conditions. Details of signal and masker calibration were carefully matched, and the model was tested using the same adaptive tracking paradigm. Perhaps most importantly, the behavioral results were not available to the modeler before the model predictions were presented. Recordings from three different aircraft were used as the target signals. Maskers were derived from recordings obtained at nine locations ranging from very quiet rural environments to suburban and urban settings. Overall, with a few exceptions, model predictions matched the performance of the listeners very well. Discussion focuses on those differences and possible reasons for their occurrence.


Asunto(s)
Enmascaramiento Perceptual , Percepción del Habla , Humanos , Umbral Auditivo , Ruido , Aeronaves , Simulación por Computador
4.
Eur J Neurosci ; 55(11-12): 3303-3323, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-33236353

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Envejecimiento Saludable , Música , Enfermedad de Alzheimer/terapia , Animales , Encéfalo , Disfunción Cognitiva/terapia
5.
Exp Brain Res ; 240(6): 1775-1790, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35507069

RESUMEN

A consistent relationship has been found between rhythmic processing and reading skills. Impairment of the ability to entrain movements to an auditory rhythm in clinical populations with language-related deficits, such as children with developmental dyslexia, has been found in both behavioral and neural studies. In this study, we explored the relationship between rhythmic entrainment, behavioral synchronization, reading fluency, and reading comprehension in neurotypical English- and Mandarin-speaking adults. First, we examined entrainment stability by asking participants to coordinate taps with an auditory metronome in which unpredictable perturbations were introduced to disrupt entrainment. Next, we assessed behavioral synchronization by asking participants to coordinate taps with the syllables they produced while reading sentences as naturally as possible (tap to syllable task). Finally, we measured reading fluency and reading comprehension for native English and native Mandarin speakers. Stability of entrainment correlated strongly with tap to syllable task performance and with reading fluency, and both findings generalized across English and Mandarin speakers.


Asunto(s)
Dislexia , Lectura , Adulto , Niño , Humanos , Lenguaje , Movimiento
6.
Dev Sci ; 24(5): e13103, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33570778

RESUMEN

Previous work suggests that auditory-vestibular interactions, which emerge during bodily movement to music, can influence the perception of musical rhythm. In a seminal study on the ontogeny of musical rhythm, Phillips-Silver and Trainor (2005) found that bouncing infants to an unaccented rhythm influenced infants' perceptual preferences for accented rhythms that matched the rate of bouncing. In the current study, we ask whether nascent, diffuse coupling between auditory and motor systems is sufficient to bootstrap short-term Hebbian plasticity in the auditory system and explain infants' preferences for accented rhythms thought to arise from auditory-vestibular interactions. First, we specify a nonlinear, dynamical system in which two oscillatory neural networks, representing developmentally nascent auditory and motor systems, interact through weak, non-specific coupling. The auditory network was equipped with short-term Hebbian plasticity, allowing the auditory network to tune its intrinsic resonant properties. Next, we simulate the effect of vestibular input (e.g., infant bouncing) on infants' perceptual preferences for accented rhythms. We found that simultaneous auditory-vestibular training shaped the model's response to musical rhythm, enhancing vestibular-related frequencies in auditory-network activity. Moreover, simultaneous auditory-vestibular training, relative to auditory- or vestibular-only training, facilitated short-term auditory plasticity in the model, producing stronger oscillator connections in the auditory network. Finally, when tested on a musical rhythm, models which received simultaneous auditory-vestibular training, but not models that received auditory- or vestibular-only training, resonated strongly at frequencies related to their "bouncing," a finding qualitatively similar to infants' preferences for accented rhythms that matched the rate of infant bouncing.


Asunto(s)
Música , Estimulación Acústica , Percepción Auditiva , Humanos , Lactante , Movimiento
7.
Biol Cybern ; 115(1): 43-57, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33399947

RESUMEN

We study multifrequency Hebbian plasticity by analyzing phenomenological models of weakly connected neural networks. We start with an analysis of a model for single-frequency networks previously shown to learn and memorize phase differences between component oscillators. We then study a model for gradient frequency neural networks (GrFNNs) which extends the single-frequency model by introducing frequency detuning and nonlinear coupling terms for multifrequency interactions. Our analysis focuses on models of two coupled oscillators and examines the dynamics of steady-state behaviors in multiple parameter regimes available to the models. We find that the model for two distinct frequencies shares essential dynamical properties with the single-frequency model and that Hebbian learning results in stronger connections for simple frequency ratios than for complex ratios. We then compare the analysis of the two-frequency model with numerical simulations of the GrFNN model and show that Hebbian plasticity in the latter is locally dominated by a nonlinear resonance captured by the two-frequency model.


Asunto(s)
Aprendizaje , Redes Neurales de la Computación
8.
PLoS Comput Biol ; 15(10): e1007371, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31671096

RESUMEN

Dancing and playing music require people to coordinate actions with auditory rhythms. In laboratory perception-action coordination tasks, people are asked to synchronize taps with a metronome. When synchronizing with a metronome, people tend to anticipate stimulus onsets, tapping slightly before the stimulus. The anticipation tendency increases with longer stimulus periods of up to 3500ms, but is less pronounced in trained individuals like musicians compared to non-musicians. Furthermore, external factors influence the timing of tapping. These factors include the presence of auditory feedback from one's own taps, the presence of a partner performing coordinated joint tapping, and transmission latencies (TLs) between coordinating partners. Phenomena like the anticipation tendency can be explained by delay-coupled systems, which may be inherent to the sensorimotor system during perception-action coordination. Here we tested whether a dynamical systems model based on this hypothesis reproduces observed patterns of human synchronization. We simulated behavior with a model consisting of an oscillator receiving its own delayed activity as input. Three simulation experiments were conducted using previously-published behavioral data from 1) simple tapping, 2) two-person alternating beat-tapping, and 3) two-person alternating rhythm-clapping in the presence of a range of constant auditory TLs. In Experiment 1, our model replicated the larger anticipation observed for longer stimulus intervals and adjusting the amplitude of the delayed feedback reproduced the difference between musicians and non-musicians. In Experiment 2, by connecting two models we replicated the smaller anticipation observed in human joint tapping with bi-directional auditory feedback compared to joint tapping without feedback. In Experiment 3, we varied TLs between two models alternately receiving signals from one another. Results showed reciprocal lags at points of alternation, consistent with behavioral patterns. Overall, our model explains various anticipatory behaviors, and has potential to inform theories of adaptive human synchronization.


Asunto(s)
Estimulación Acústica/métodos , Percepción Auditiva/fisiología , Percepción del Tiempo/fisiología , Ciclos de Actividad , Anticipación Psicológica/fisiología , Ciencias Bioconductuales , Simulación por Computador , Retroalimentación , Retroalimentación Sensorial/fisiología , Humanos , Música , Periodicidad , Desempeño Psicomotor
9.
PLoS Genet ; 13(5): e1006769, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28493873

RESUMEN

Most biological traits and common diseases have a strong but complex genetic basis, controlled by large numbers of genetic variants with small contributions to a trait or disease risk. The effect-size of most genetic variants is not absolute and is instead dependent upon multiple factors such as the age and genetic background of an organism. In order to understand the mechanistic basis of these changes, we characterized heritable trait differences between two domesticated strains of C. elegans. We previously identified a major effect locus, caused in part by a mutation in a component of the NURF chromatin remodeling complex, that regulates reproductive output in an age-dependent manner. The effect-size of this locus changes from positive to negative over the course of an animal's reproductive lifespan. Here, we use a previously published macroscale model of the egg-laying rate in C. elegans to show that time-dependent effect-size is explained by an unequal use of sperm combined with negative feedback between sperm and ovulation rate. We validate key predictions of this model with controlled mating experiments and quantification of oogenesis and sperm use. Incorporation of this model into QTL mapping allows us to identify and partition new QTLs into specific aspects of the egg-laying process. Finally, we show how epistasis between two genetic variants is predicted by this modeling as a consequence of the unequal use of sperm. This work demonstrates how modeling of multicellular communication systems can improve our ability to predict and understand the role of genetic variation on a complex phenotype. Negative autoregulatory feedback loops, common in transcriptional regulation, could play an important role in modifying genetic architecture in other traits.


Asunto(s)
Caenorhabditis elegans/genética , Ensamble y Desensamble de Cromatina/genética , Pleiotropía Genética , Sitios de Carácter Cuantitativo/genética , Animales , Caenorhabditis elegans/crecimiento & desarrollo , Mapeo Cromosómico , Epistasis Genética , Retroalimentación Fisiológica , Gónadas/crecimiento & desarrollo , Humanos , Masculino , Mutación , Oocitos/crecimiento & desarrollo , Espermatozoides/crecimiento & desarrollo
10.
Neuroimage ; 185: 96-101, 2019 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-30336253

RESUMEN

Neural activity phase-locks to rhythm in both music and speech. However, the literature currently lacks a direct test of whether cortical tracking of comparable rhythmic structure is comparable across domains. Moreover, although musical training improves multiple aspects of music and speech perception, the relationship between musical training and cortical tracking of rhythm has not been compared directly across domains. We recorded the electroencephalograms (EEG) from 28 participants (14 female) with a range of musical training who listened to melodies and sentences with identical rhythmic structure. We compared cerebral-acoustic coherence (CACoh) between the EEG signal and single-trial stimulus envelopes (as measure of cortical entrainment) across domains and correlated years of musical training with CACoh. We hypothesized that neural activity would be comparably phase-locked across domains, and that the amount of musical training would be associated with increasingly strong phase locking in both domains. We found that participants with only a few years of musical training had a comparable cortical response to music and speech rhythm, partially supporting the hypothesis. However, the cortical response to music rhythm increased with years of musical training while the response to speech rhythm did not, leading to an overall greater cortical response to music rhythm across all participants. We suggest that task demands shaped the asymmetric cortical tracking across domains.


Asunto(s)
Corteza Cerebral/fisiología , Música , Percepción de la Altura Tonal/fisiología , Percepción del Habla/fisiología , Adulto , Mapeo Encefálico/métodos , Electroencefalografía/métodos , Femenino , Humanos , Masculino , Adulto Joven
11.
PLoS Genet ; 12(7): e1006219, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27467070

RESUMEN

Evolutionary life history theory seeks to explain how reproductive and survival traits are shaped by selection through allocations of an individual's resources to competing life functions. Although life-history traits evolve rapidly, little is known about the genetic and cellular mechanisms that control and couple these tradeoffs. Here, we find that two laboratory-adapted strains of C. elegans descended from a single common ancestor that lived in the 1950s have differences in a number of life-history traits, including reproductive timing, lifespan, dauer formation, growth rate, and offspring number. We identified a quantitative trait locus (QTL) of large effect that controls 24%-75% of the total trait variance in reproductive timing at various timepoints. Using CRISPR/Cas9-induced genome editing, we show this QTL is due in part to a 60 bp deletion in the 3' end of the nurf-1 gene, which is orthologous to the human gene encoding the BPTF component of the NURF chromatin remodeling complex. Besides reproduction, nurf-1 also regulates growth rate, lifespan, and dauer formation. The fitness consequences of this deletion are environment specific-it increases fitness in the growth conditions where it was fixed but decreases fitness in alternative laboratory growth conditions. We propose that chromatin remodeling, acting through nurf-1, is a pleiotropic regulator of life history trade-offs underlying the evolution of multiple traits across different species.


Asunto(s)
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Proteínas Cromosómicas no Histona/genética , Evolución Molecular , Selección Genética/genética , Animales , Sistemas CRISPR-Cas , Cromatina/genética , Ensamble y Desensamble de Cromatina/genética , Humanos , Fenotipo , Sitios de Carácter Cuantitativo/genética , Reproducción/genética
12.
J Neurosci ; 37(26): 6331-6341, 2017 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-28559379

RESUMEN

Most humans have a near-automatic inclination to tap, clap, or move to the beat of music. The capacity to extract a periodic beat from a complex musical segment is remarkable, as it requires abstraction from the temporal structure of the stimulus. It has been suggested that nonlinear interactions in neural networks result in cortical oscillations at the beat frequency, and that such entrained oscillations give rise to the percept of a beat or a pulse. Here we tested this neural resonance theory using MEG recordings as female and male individuals listened to 30 s sequences of complex syncopated drumbeats designed so that they contain no net energy at the pulse frequency when measured using linear analysis. We analyzed the spectrum of the neural activity while listening and compared it to the modulation spectrum of the stimuli. We found enhanced neural response in the auditory cortex at the pulse frequency. We also showed phase locking at the times of the missing pulse, even though the pulse was absent from the stimulus itself. Moreover, the strength of this pulse response correlated with individuals' speed in finding the pulse of these stimuli, as tested in a follow-up session. These findings demonstrate that neural activity at the pulse frequency in the auditory cortex is internally generated rather than stimulus-driven. The current results are both consistent with neural resonance theory and with models based on nonlinear response of the brain to rhythmic stimuli. The results thus help narrow the search for valid models of beat perception.SIGNIFICANCE STATEMENT Humans perceive music as having a regular pulse marking equally spaced points in time, within which musical notes are temporally organized. Neural resonance theory (NRT) provides a theoretical model explaining how an internal periodic representation of a pulse may emerge through nonlinear coupling between oscillating neural systems. After testing key falsifiable predictions of NRT using MEG recordings, we demonstrate the emergence of neural oscillations at the pulse frequency, which can be related to pulse perception. These findings rule out alternative explanations for neural entrainment and provide evidence linking neural synchronization to the perception of pulse, a widely debated topic in recent years.


Asunto(s)
Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Relojes Biológicos/fisiología , Sincronización Cortical/fisiología , Potenciales Evocados Auditivos/fisiología , Periodicidad , Estimulación Acústica/métodos , Potenciales de Acción/fisiología , Adulto , Señales (Psicología) , Retroalimentación Fisiológica , Femenino , Humanos , Masculino , Modelos Neurológicos , Música
13.
J Acoust Soc Am ; 136(4): EL256-62, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25324107

RESUMEN

1/f serial correlations and statistical self-similarity (fractal structure) have been measured in various dimensions of musical compositions. Musical performances also display 1/f properties in expressive tempo fluctuations, and listeners predict tempo changes when synchronizing. Here the authors show that the 1/f structure is sufficient for listeners to predict the onset times of upcoming musical events. These results reveal what information listeners use to anticipate events in complex, non-isochronous acoustic rhythms, and this will entail innovative models of temporal synchronization. This finding could improve therapies for Parkinson's and related disorders and inform deeper understanding of how endogenous neural rhythms anticipate events in complex, temporally structured communication signals.


Asunto(s)
Anticipación Psicológica , Percepción Auditiva , Señales (Psicología) , Música , Periodicidad , Estimulación Acústica , Femenino , Fractales , Humanos , Masculino , Percepción de la Altura Tonal , Espectrografía del Sonido , Factores de Tiempo
14.
Sci Adv ; 10(10): eadi2525, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38446888

RESUMEN

Why do humans spontaneously dance to music? To test the hypothesis that motor dynamics reflect predictive timing during music listening, we created melodies with varying degrees of rhythmic predictability (syncopation) and asked participants to rate their wanting-to-move (groove) experience. Degree of syncopation and groove ratings are quadratically correlated. Magnetoencephalography data showed that, while auditory regions track the rhythm of melodies, beat-related 2-hertz activity and neural dynamics at delta (1.4 hertz) and beta (20 to 30 hertz) rates in the dorsal auditory pathway code for the experience of groove. Critically, the left sensorimotor cortex coordinates these groove-related delta and beta activities. These findings align with the predictions of a neurodynamic model, suggesting that oscillatory motor engagement during music listening reflects predictive timing and is effected by interaction of neural dynamics along the dorsal auditory pathway.


Asunto(s)
Música , Humanos , Membrana Celular , Corteza Cerebral , Magnetoencefalografía
15.
J Neurosci ; 32(5): 1791-802, 2012 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-22302818

RESUMEN

Moving in synchrony with an auditory rhythm requires predictive action based on neurodynamic representation of temporal information. Although it is known that a regular auditory rhythm can facilitate rhythmic movement, the neural mechanisms underlying this phenomenon remain poorly understood. In this experiment using human magnetoencephalography, 12 young healthy adults listened passively to an isochronous auditory rhythm without producing rhythmic movement. We hypothesized that the dynamics of neuromagnetic beta-band oscillations (~20 Hz)-which are known to reflect changes in an active status of sensorimotor functions-would show modulations in both power and phase-coherence related to the rate of the auditory rhythm across both auditory and motor systems. Despite the absence of an intention to move, modulation of beta amplitude as well as changes in cortico-cortical coherence followed the tempo of sound stimulation in auditory cortices and motor-related areas including the sensorimotor cortex, inferior-frontal gyrus, supplementary motor area, and the cerebellum. The time course of beta decrease after stimulus onset was consistent regardless of the rate or regularity of the stimulus, but the time course of the following beta rebound depended on the stimulus rate only in the regular stimulus conditions such that the beta amplitude reached its maximum just before the occurrence of the next sound. Our results suggest that the time course of beta modulation provides a mechanism for maintaining predictive timing, that beta oscillations reflect functional coordination between auditory and motor systems, and that coherence in beta oscillations dynamically configure the sensorimotor networks for auditory-motor coupling.


Asunto(s)
Estimulación Acústica/métodos , Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Ritmo beta/fisiología , Magnetoencefalografía/métodos , Corteza Motora/fisiología , Adulto , Femenino , Humanos , Masculino , Periodicidad , Factores de Tiempo , Adulto Joven
16.
Front Microbiol ; 14: 1116896, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36846761

RESUMEN

Adeno-associated viruses (AAV) are among the foremost vectors for in vivo gene therapy. A number of monoclonal antibodies against several serotypes of AAV have previously been prepared. Many are neutralizing, and the predominant mechanisms have been reported as the inhibition of binding to extracellular glycan receptors or interference with some post-entry step. The identification of a protein receptor and recent structural characterization of its interactions with AAV compel reconsideration of this tenet. AAVs can be divided into two families based on which domain of the receptor is strongly bound. Neighboring domains, unseen in the high-resolution electron microscopy structures have now been located by electron tomography, pointing away from the virus. The epitopes of neutralizing antibodies, previously characterized, are now compared to the distinct protein receptor footprints of the two families of AAV. Comparative structural analysis suggests that antibody interference with protein receptor binding might be the more prevalent mechanism than interference with glycan attachment. Limited competitive binding assays give some support to the hypothesis that inhibition of binding to the protein receptor has been an overlooked mechanism of neutralization. More extensive testing is warranted.

17.
Front Comput Neurosci ; 17: 1151895, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37265781

RESUMEN

Rhythmicity permeates large parts of human experience. Humans generate various motor and brain rhythms spanning a range of frequencies. We also experience and synchronize to externally imposed rhythmicity, for example from music and song or from the 24-h light-dark cycles of the sun. In the context of music, humans have the ability to perceive, generate, and anticipate rhythmic structures, for example, "the beat." Experimental and behavioral studies offer clues about the biophysical and neural mechanisms that underlie our rhythmic abilities, and about different brain areas that are involved but many open questions remain. In this paper, we review several theoretical and computational approaches, each centered at different levels of description, that address specific aspects of musical rhythmic generation, perception, attention, perception-action coordination, and learning. We survey methods and results from applications of dynamical systems theory, neuro-mechanistic modeling, and Bayesian inference. Some frameworks rely on synchronization of intrinsic brain rhythms that span the relevant frequency range; some formulations involve real-time adaptation schemes for error-correction to align the phase and frequency of a dedicated circuit; others involve learning and dynamically adjusting expectations to make rhythm tracking predictions. Each of the approaches, while initially designed to answer specific questions, offers the possibility of being integrated into a larger framework that provides insights into our ability to perceive and generate rhythmic patterns.

18.
Front Psychol ; 13: 653696, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35282203

RESUMEN

Musical rhythm abilities-the perception of and coordinated action to the rhythmic structure of music-undergo remarkable change over human development. In the current paper, we introduce a theoretical framework for modeling the development of musical rhythm. The framework, based on Neural Resonance Theory (NRT), explains rhythm development in terms of resonance and attunement, which are formalized using a general theory that includes non-linear resonance and Hebbian plasticity. First, we review the developmental literature on musical rhythm, highlighting several developmental processes related to rhythm perception and action. Next, we offer an exposition of Neural Resonance Theory and argue that elements of the theory are consistent with dynamical, radically embodied (i.e., non-representational) and ecological approaches to cognition and development. We then discuss how dynamical models, implemented as self-organizing networks of neural oscillations with Hebbian plasticity, predict key features of music development. We conclude by illustrating how the notions of dynamical embodiment, resonance, and attunement provide a conceptual language for characterizing musical rhythm development, and, when formalized in physiologically informed dynamical models, provide a theoretical framework for generating testable empirical predictions about musical rhythm development, such as the kinds of native and non-native rhythmic structures infants and children can learn, steady-state evoked potentials to native and non-native musical rhythms, and the effects of short-term (e.g., infant bouncing, infant music classes), long-term (e.g., perceptual narrowing to musical rhythm), and very-long term (e.g., music enculturation, musical training) learning on music perception-action.

19.
Brain Sci ; 12(12)2022 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-36552136

RESUMEN

Neural entrainment to musical rhythm is thought to underlie the perception and production of music. In aging populations, the strength of neural entrainment to rhythm has been found to be attenuated, particularly during attentive listening to auditory streams. However, previous studies on neural entrainment to rhythm and aging have often employed artificial auditory rhythms or limited pieces of recorded, naturalistic music, failing to account for the diversity of rhythmic structures found in natural music. As part of larger project assessing a novel music-based intervention for healthy aging, we investigated neural entrainment to musical rhythms in the electroencephalogram (EEG) while participants listened to self-selected musical recordings across a sample of younger and older adults. We specifically measured neural entrainment to the level of musical pulse-quantified here as the phase-locking value (PLV)-after normalizing the PLVs to each musical recording's detected pulse frequency. As predicted, we observed strong neural phase-locking to musical pulse, and to the sub-harmonic and harmonic levels of musical meter. Overall, PLVs were not significantly different between older and younger adults. This preserved neural entrainment to musical pulse and rhythm could support the design of music-based interventions that aim to modulate endogenous brain activity via self-selected music for healthy cognitive aging.

20.
Elife ; 112022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-36317963

RESUMEN

Humans are social animals who engage in a variety of collective activities requiring coordinated action. Among these, music is a defining and ancient aspect of human sociality. Human social interaction has largely been addressed in dyadic paradigms, and it is yet to be determined whether the ensuing conclusions generalize to larger groups. Studied more extensively in non-human animal behavior, the presence of multiple agents engaged in the same task space creates different constraints and possibilities than in simpler dyadic interactions. We addressed whether collective dynamics play a role in human circle drumming. The task was to synchronize in a group with an initial reference pattern and then maintain synchronization after it was muted. We varied the number of drummers from solo to dyad, quartet, and octet. The observed lower variability, lack of speeding up, smoother individual dynamics, and leader-less inter-personal coordination indicated that stability increased as group size increased, a sort of temporal wisdom of crowds. We propose a hybrid continuous-discrete Kuramoto model for emergent group synchronization with a pulse-based coupling that exhibits a mean field positive feedback loop. This research suggests that collective phenomena are among the factors that play a role in social cognition.


Asunto(s)
Música , Animales , Conducta Social , Relaciones Interpersonales , Conducta Animal , Grupos de Autoayuda
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