Neurophysiological Changes Induced by Music-Supported Therapy for Recovering Upper Extremity Function after Stroke: A Case Series.

Music-supported therapy (MST) follows the best practice principles of stroke rehabilitation and has been proven to instigate meaningful enhancements in motor recovery post-stroke. The existing literature has established that the efficacy and specificity of MST relies on the reinforcement of auditory-motor functional connectivity in related brain networks. However, to date, no study has attempted to evaluate the underlying cortical network nodes that are key to the efficacy of MST post-stroke. In this case series, we evaluated changes in connectivity within the auditory-motor network and changes in upper extremity function following a 3-week intensive piano training in two stroke survivors presenting different levels of motor impairment. Connectivity was assessed pre- and post-training in the α- and the ß-bands within the auditory-motor network using magnetoencephalography while participants were passively listening to a standardized melody. Changes in manual dexterity, grip strength, movement coordination, and use of the upper extremity were also documented in both stroke survivors. After training, an increase in the clinical measures was accompanied by enhancements in connectivity between the auditory and motor network nodes for both the α- and the ß-bands, especially in the affected hemisphere. These neurophysiological changes associated with the positive effects of post-stroke MST on motor outcomes delineate a path for a larger scale clinical trial.

Coupled oscillations enable rapid temporal recalibration to audiovisual asynchrony.

The brain naturally resolves the challenge of integrating auditory and visual signals produced by the same event despite different physical propagation speeds and neural processing latencies. Temporal recalibration manifests in human perception to realign incoming signals across the senses. Recent behavioral studies show it is a fast-acting phenomenon, relying on the most recent exposure to audiovisual asynchrony. Here we show that the physiological mechanism of rapid, context-dependent recalibration builds on interdependent pre-stimulus cortical rhythms in sensory brain regions. Using magnetoencephalography, we demonstrate that individual recalibration behavior is related to subject-specific properties of fast oscillations (>35 Hz) nested within a slower alpha rhythm (8-12 Hz) in auditory cortex. We also show that the asynchrony of a previously presented audiovisual stimulus pair alters the preferred coupling phase of these fast oscillations along the alpha cycle, with a resulting phase-shift amounting to the temporal recalibration observed behaviorally. These findings suggest that cross-frequency coupled oscillations contribute to forming unified percepts across senses.

Oscillatory Entrainment of the Frequency-following Response in Auditory Cortical and Subcortical Structures.

There is much debate about the existence and function of neural oscillatory mechanisms in the auditory system. The frequency-following response (FFR) is an index of neural periodicity encoding that can provide a vehicle to study entrainment in frequency ranges relevant to speech and music processing. Criteria for entrainment include the presence of poststimulus oscillations and phase alignment between stimulus and endogenous activity. To test the hypothesis of entrainment, in experiment 1 we collected FFR data for a repeated syllable using magnetoencephalography (MEG) and electroencephalography in 20 male and female human adults. We observed significant oscillatory activity after stimulus offset in auditory cortex and subcortical auditory nuclei, consistent with entrainment. In these structures, the FFR fundamental frequency converged from a lower value over 100 ms to the stimulus frequency, consistent with phase alignment, and diverged to a lower value after offset, consistent with relaxation to a preferred frequency. In experiment 2, we tested how transitions between stimulus frequencies affected the MEG FFR to a train of tone pairs in 30 people. We found that the FFR was affected by the frequency of the preceding tone for up to 40 ms at subcortical levels, and even longer durations at cortical levels. Our results suggest that oscillatory entrainment may be an integral part of periodic sound representation throughout the auditory neuraxis. The functional role of this mechanism is unknown, but it could serve as a fine-scale temporal predictor for frequency information, enhancing stability and reducing susceptibility to degradation that could be useful in real-life noisy environments.SIGNIFICANCE STATEMENT Neural oscillations are proposed to be a ubiquitous aspect of neural function, but their contribution to auditory encoding is not clear, particularly at higher frequencies associated with pitch encoding. In a magnetoencephalography experiment, we found converging evidence that the frequency-following response has an oscillatory component according to established criteria: poststimulus resonance, progressive entrainment of the neural frequency to the stimulus frequency, and relaxation toward the original state on stimulus offset. In a second experiment, we found that the frequency and amplitude of the frequency-following response to tones are affected by preceding stimuli. These findings support the contribution of intrinsic oscillations to the encoding of sound, and raise new questions about their functional roles, possibly including stabilization and low-level predictive coding.

MEG Intersubject Phase Locking of Stimulus-Driven Activity during Naturalistic Speech Listening Correlates with Musical Training.

Musical training is associated with increased structural and functional connectivity between auditory sensory areas and higher-order brain networks involved in speech and motor processing. Whether such changed connectivity patterns facilitate the cortical propagation of speech information in musicians remains poorly understood. We here used magnetoencephalography (MEG) source imaging and a novel seed-based intersubject phase-locking approach to investigate the effects of musical training on the interregional synchronization of stimulus-driven neural responses during listening to naturalistic continuous speech presented in silence. MEG data were obtained from 20 young human subjects (both sexes) with different degrees of musical training. Our data show robust bilateral patterns of stimulus-driven interregional phase synchronization between auditory cortex and frontotemporal brain regions previously associated with speech processing. Stimulus-driven phase locking was maximal in the delta band, but was also observed in the theta and alpha bands. The individual duration of musical training was positively associated with the magnitude of stimulus-driven alpha-band phase locking between auditory cortex and parts of the dorsal and ventral auditory processing streams. These findings provide evidence for a positive relationship between musical training and the propagation of speech-related information between auditory sensory areas and higher-order processing networks, even when speech is presented in silence. We suggest that the increased synchronization of higher-order cortical regions to auditory cortex may contribute to the previously described musician advantage in processing speech in background noise.SIGNIFICANCE STATEMENT Musical training has been associated with widespread structural and functional brain plasticity. It has been suggested that these changes benefit the production and perception of music but can also translate to other domains of auditory processing, such as speech. We developed a new magnetoencephalography intersubject analysis approach to study the cortical synchronization of stimulus-driven neural responses during the perception of continuous natural speech and its relationship to individual musical training. Our results provide evidence that musical training is associated with higher synchronization of stimulus-driven activity between brain regions involved in early auditory sensory and higher-order processing. We suggest that the increased synchronized propagation of speech information may contribute to the previously described musician advantage in processing speech in background noise.

A thalamocortical pathway for fast rerouting of tactile information to occipital cortex in congenital blindness.

In congenitally blind individuals, the occipital cortex responds to various nonvisual inputs. Some animal studies raise the possibility that a subcortical pathway allows fast re-routing of tactile information to the occipital cortex, but this has not been shown in humans. Here we show using magnetoencephalography (MEG) that tactile stimulation produces occipital cortex activations, starting as early as 35 ms in congenitally blind individuals, but not in blindfolded sighted controls. Given our measured thalamic response latencies of 20 ms and a mean estimated lateral geniculate nucleus to primary visual cortex transfer time of 15 ms, we claim that this early occipital response is mediated by a direct thalamo-cortical pathway. We also observed stronger directed connectivity in the alpha band range from posterior thalamus to occipital cortex in congenitally blind participants. Our results strongly suggest the contribution of a fast thalamo-cortical pathway in the cross-modal activation of the occipital cortex in congenitally blind humans.

Musicians at the Cocktail Party: Neural Substrates of Musical Training During Selective Listening in Multispeaker Situations.

Musical training has been demonstrated to benefit speech-in-noise perception. It is however unknown whether this effect translates to selective listening in cocktail party situations, and if so what its neural basis might be. We investigated this question using magnetoencephalography-based speech envelope reconstruction and a sustained selective listening task, in which participants with varying amounts of musical training attended to 1 of 2 speech streams while detecting rare target words. Cortical frequency-following responses (FFR) and auditory working memory were additionally measured to dissociate musical training-related effects on low-level auditory processing versus higher cognitive function. Results show that the duration of musical training is associated with a reduced distracting effect of competing speech on target detection accuracy. Remarkably, more musical training was related to a robust neural tracking of both the to-be-attended and the to-be-ignored speech stream, up until late cortical processing stages. Musical training-related increases in FFR power were associated with a robust speech tracking in auditory sensory areas, whereas training-related differences in auditory working memory were linked to an increased representation of the to-be-ignored stream beyond auditory cortex. Our findings suggest that musically trained persons can use additional information about the distracting stream to limit interference by competing speech.

Motor origin of temporal predictions in auditory attention.

In behavior, action and perception are inherently interdependent. However, the actual mechanistic contributions of the motor system to sensory processing are unknown. We present neurophysiological evidence that the motor system is involved in predictive timing, a brain function that aligns temporal fluctuations of attention with the timing of events in a task-relevant stream, thus facilitating sensory selection and optimizing behavior. In a magnetoencephalography experiment involving auditory temporal attention, participants had to disentangle two streams of sound on the unique basis of endogenous temporal cues. We show that temporal predictions are encoded by interdependent delta and beta neural oscillations originating from the left sensorimotor cortex, and directed toward auditory regions. We also found that overt rhythmic movements improved the quality of temporal predictions and sharpened the temporal selection of relevant auditory information. This latter behavioral and functional benefit was associated with increased signaling of temporal predictions in right-lateralized frontoparietal associative regions. In sum, this study points at a covert form of auditory active sensing. Our results emphasize the key role of motor brain areas in providing contextual temporal information to sensory regions, driving perceptual and behavioral selection.

Pre-target neural oscillations predict variability in the detection of small pitch changes.

Pitch discrimination is important for language or music processing. Previous studies indicate that auditory perception depends on pre-target neural activity. However, so far the pre-target electrophysiological conditions which enable the detection of small pitch changes are not well studied, but might yield important insights into pitch-processing. We used magnetoencephalography (MEG) source imaging to reveal the pre-target effects of successful auditory detection of small pitch deviations from a sequence of standard tones. Participants heard a sequence of four pure tones and had to determine whether the last target tone was different or identical to the first three standard sounds. We found that successful pitch change detection could be predicted from the amplitude of theta (4-8 Hz) oscillatory activity in the right inferior frontal gyrus (IFG) as well as beta (12-30 Hz) oscillatory activity in the right auditory cortex. These findings confirm and extend evidence for the involvement of theta as well as beta-band activity in auditory perception.

Region-specific reduction of auditory sensory gating in older adults.

Aging has been associated with declines in sensory-perceptual processes. Sensory gating (SG), or repetition suppression, refers to the attenuation of neural activity in response to a second stimulus and is considered to be an automatic process to inhibit redundant sensory inputs. It is controversial whether SG deficits, as tested with an auditory paired-stimulus protocol, accompany normal aging in humans. To reconcile the debates arising from event-related potential studies, we recorded auditory neuromagnetic reactivity in 20 young and 19 elderly adult men and determined the neural activation by using minimum-norm estimate (MNE) source modeling. SG of M100 was calculated by the ratio of the response to the second stimulus over that to the first stimulus. MNE results revealed that fronto-temporo-parietal networks were implicated in the M100 SG. Compared to the younger participants, the elderly showed selectively increased SG ratios in the anterior superior temporal gyrus, anterior middle temporal gyrus, temporal pole and orbitofrontal cortex, suggesting an insufficient age-related gating to repetitive auditory stimulation. These findings also highlight the loss of frontal inhibition of the auditory cortex in normal aging.

Effects of aging on the neuromagnetic mismatch detection to speech sounds.

The ability to discriminate speech sounds is crucial for higher language functions in humans. However, it remains unclear whether physiological aging affects the functional integrity of pre-attentive phonological discrimination. The neuromagnetic cortical responses during automatic change detection of speech sounds (/ba/versus/da/) were recorded in 24 young and 21 aged male adults. We used minimum norm estimate of source reconstruction to characterize the spatiotemporal dynamics of magnetic mismatch responses (MMNm). Distributed activations to phonetic changes were identified in the temporal, frontal and parietal regions. Compared to younger participants, elderly volunteers exhibited a significant reduction of cortical responses to phonetic-MMNm, except for the left orbitofrontal cortex and anterior inferior temporal gyrus. However, among the identified regions of interest, we did not observe significant between-group differences in the hemispheric asymmetry of phonetic-MMNm. Conclusively, our results suggest an altered phonetic processing at the perceptual level during physiological aging.

Effects of aging on neuromagnetic mismatch responses to pitch changes.

Although aging-related alterations in the auditory sensory memory and involuntary change discrimination have been widely studied, it remains controversial whether the mismatch negativity (MMN) or its magnetic counterpart (MMNm) is modulated by physiological aging. This study aimed to examine the effects of aging on mismatch activity to pitch deviants by using a whole-head magnetoencephalography (MEG) together with distributed source modeling analysis. The neuromagnetic responses to oddball paradigms consisting of standards (1000 Hz, p=0.85) and deviants (1100 Hz, p=0.15) were recorded in healthy young (n=20) and aged (n=18) male adults. We used minimum norm estimate of source reconstruction to characterize the spatiotemporal neural dynamics of MMNm responses. Distributed activations to MMNm were identified in the bilateral fronto-temporo-parietal areas. Compared to younger participants, the elderly exhibited a significant reduction of cortical activation in bilateral superior temporal guri, superior temporal sulci, inferior fontal gyri, orbitofrontal cortices and right inferior parietal lobules. In conclusion, our results suggest an aging-related decline in auditory sensory memory and automatic change detection as indexed by MMNm.

rtMEG: a real-time software interface for magnetoencephalography.

To date, the majority of studies using magnetoencephalography (MEG) rely on off-line analysis of the spatiotemporal properties of brain activity. Real-time MEG feedback could potentially benefit multiple areas of basic and clinical research: brain-machine interfaces, neurofeedback rehabilitation of stroke and spinal cord injury, and new adaptive paradigm designs, among others. We have developed a software interface to stream MEG signals in real time from the 306-channel Elekta Neuromag MEG system to an external workstation. The signals can be accessed with a minimal delay (≤45 ms) when data are sampled at 1000 Hz, which is sufficient for most real-time studies. We also show here that real-time source imaging is possible by demonstrating real-time monitoring and feedback of alpha-band power fluctuations over parieto-occipital and frontal areas. The interface is made available to the academic community as an open-source resource.

Hearing faces: how the infant brain matches the face it sees with the speech it hears.

Speech is not a purely auditory signal. From around 2 months of age, infants are able to correctly match the vowel they hear with the appropriate articulating face. However, there is no behavioral evidence of integrated audiovisual perception until 4 months of age, at the earliest, when an illusory percept can be created by the fusion of the auditory stimulus and of the facial cues (McGurk effect). To understand how infants initially match the articulatory movements they see with the sounds they hear, we recorded high-density ERPs in response to auditory vowels that followed a congruent or incongruent silently articulating face in 10-week-old infants. In a first experiment, we determined that auditory-visual integration occurs during the early stages of perception as in adults. The mismatch response was similar in timing and in topography whether the preceding vowels were presented visually or aurally. In the second experiment, we studied audiovisual integration in the linguistic (vowel perception) and nonlinguistic (gender perception) domain. We observed a mismatch response for both types of change at similar latencies. Their topographies were significantly different demonstrating that cross-modal integration of these features is computed in parallel by two different networks. Indeed, brain source modeling revealed that phoneme and gender computations were lateralized toward the left and toward the right hemisphere, respectively, suggesting that each hemisphere possesses an early processing bias. We also observed repetition suppression in temporal regions and repetition enhancement in frontal regions. These results underscore how complex and structured is the human cortical organization which sustains communication from the first weeks of life on.