Developing a music-based digital therapeutic to help manage the neuropsychiatric symptoms of dementia.

The greying of the world is leading to a rapid acceleration in both the healthcare costs and caregiver burden that are associated with dementia. There is an urgent need to develop new, easily scalable modalities of support. This perspective paper presents the theoretical background, rationale, and development plans for a music-based digital therapeutic to manage the neuropsychiatric symptoms of dementia, particularly agitation and anxiety. We begin by presenting the findings of a survey we conducted with key opinion leaders. The findings highlight the value of a music-based digital therapeutic for treating neuropsychiatric symptoms, particularly agitation and anxiety. We then consider the neural substrates of these neuropsychiatric symptoms before going on to evaluate randomized control trials on the efficacy of music-based interventions in their treatment. Finally, we present our development plans for the adaptation of an existing music-based digital therapeutic that was previously shown to be efficacious in the treatment of adult anxiety symptoms.

Absolute pitch: neurophysiological evidence for early brain activity in prefrontal cortex.

Absolute pitch (AP) is the ability to rapidly label pitch without an external reference. The speed of AP labeling may be related to faster sensory processing. We compared time needed for auditory processing in AP musicians, non-AP musicians, and nonmusicians (NM) using high-density electroencephalographic recording. Participants responded to pure tones and sung voice. Stimuli evoked a negative deflection peaking at ~100 ms (N1) post-stimulus onset, followed by a positive deflection peaking at ~200 ms (P2). N1 latency was shortest in AP, intermediate in non-AP musicians, and longest in NM. Source analyses showed decreased auditory cortex and increased frontal cortex contributions to N1 for complex tones compared with pure tones. Compared with NM, AP musicians had weaker source currents in left auditory cortex but stronger currents in left inferior frontal gyrus (IFG) during N1, and stronger currents in left IFG during P2. Compared with non-AP musicians, AP musicians exhibited stronger source currents in right insula and left IFG during N1, and stronger currents in left IFG during P2. Non-AP musicians had stronger N1 currents in right auditory cortex than nonmusicians. Currents in left IFG and left auditory cortex were correlated to response times exclusively in AP. Findings suggest a left frontotemporal network supports rapid pitch labeling in AP.

The effects of music & auditory beat stimulation on anxiety: A randomized clinical trial.

BACKGROUND AND OBJECTIVES: Music and auditory beat stimulation (ABS) in the theta frequency range (4-7 Hz) are sound-based anxiety treatments that have been independently investigated in prior studies. Here, the anxiety-reducing potential of calm music combined with theta ABS was examined in a large sample of participants. METHODS: An open-label randomized controlled trial was conducted with participants taking anxiolytics (n = 163). Participants were randomly assigned using the Qualtrics randomizer algorithm, to a single session of sound-based treatment in one of four parallel arms: combined (music & ABS; n = 39), music-alone (n = 36), ABS-alone (n = 41), or pink noise (control; n = 47). Pre- and post-intervention somatic and cognitive state anxiety measures were collected along with trait anxiety, personality measures and musical preferences. The study was completed online using a custom application. RESULTS: Based on trait anxiety scores participants were separated into moderate and high trait anxiety sub-groups. Among participants with moderate trait anxiety, we observed reductions in somatic anxiety that were greater in combined and music-alone conditions than in the pink noise condition; and reductions in cognitive state anxiety that were greater in the combined condition than in the music-alone, ABS-alone, and pink noise conditions. While we also observed reductions in somatic and cognitive state anxiety in participants with high trait anxiety, the conditions were not well differentiated. CONCLUSIONS: Sound-based treatments are effective in reducing somatic and cognitive state anxiety. For participants with moderate trait anxiety, combined conditions were most efficacious.

Vocal-motor interference eliminates the memory advantage for vocal melodies.

Spontaneous motor cortical activity during passive perception of action has been interpreted as a sensorimotor simulation of the observed action. There is currently interest in how sensorimotor simulation can support higher-up cognitive functions, such as memory, but this is relatively unexplored in the auditory domain. In the present study, we examined whether the established memory advantage for vocal melodies over non-vocal melodies is attributable to stronger sensorimotor simulation during perception of vocal relative to non-vocal action. Participants listened to 24 unfamiliar folk melodies presented in vocal or piano timbres. These were encoded during three interference conditions: whispering (vocal-motor interference), tapping (non-vocal motor interference), and no-interference. Afterwards, participants heard the original 24 melodies presented among 24 foils and judged whether melodies were old or new. A vocal-memory advantage was found in the no-interference and tapping conditions; however, the advantage was eliminated in the whispering condition. This suggests that sensorimotor simulationduring the perception of vocal melodies is responsible for the observed vocal-memory advantage.

Effects of vocal training in a musicophile with congenital amusia.

Congenital amusia is a condition in which an individual suffers from a deficit of musical pitch perception and production. Individuals suffering from congenital amusia generally tend to abstain from musical activities. Here, we present the unique case of Tim Falconer, a self-described musicophile who also suffers from congenital amusia. We describe and assess Tim's attempts to train himself out of amusia through a self-imposed 18-month program of formal vocal training and practice. We tested Tim with respect to music perception and vocal production across seven sessions including pre- and post-training assessments. We also obtained diffusion-weighted images of his brain to assess connectivity between auditory and motor planning areas via the arcuate fasciculus (AF). Tim's behavioral and brain data were compared to that of normal and amusic controls. While Tim showed temporary gains in his singing ability, he did not reach normal levels, and these gains faded when he was not engaged in regular lessons and practice. Tim did show some sustained gains with respect to the perception of musical rhythm and meter. We propose that Tim's lack of improvement in pitch perception and production tasks is due to long-standing and likely irreversible reduction in connectivity along the AF fiber tract.

Music and Memory in Alzheimer's Disease and The Potential Underlying Mechanisms.

With population aging and a projected exponential expansion of persons diagnosed with Alzheimer's disease (AD), the development of treatment and prevention programs has become a fervent area of research and discovery. A growing body of evidence suggests that music exposure can enhance memory and emotional function in persons with AD. However, there is a paucity of research that aims to identify specific underlying neural mechanisms associated with music's beneficial effects in this particular population. As such, this paper reviews existing anecdotal and empirical evidence related to the enhancing effects of music exposure on cognitive function and further provides a discussion on the potential underlying mechanisms that may explain music's beneficial effect. Specifically, this paper will outline the potential role of the dopaminergic system, the autonomic nervous system, and the default network in explaining how music may enhance memory function in persons with AD.

Dynamic Range Across Music Genres and the Perception of Dynamic Compression in Hearing-Impaired Listeners.

Dynamic range compression serves different purposes in the music and hearing-aid industries. In the music industry, it is used to make music louder and more attractive to normal-hearing listeners. In the hearing-aid industry, it is used to map the variable dynamic range of acoustic signals to the reduced dynamic range of hearing-impaired listeners. Hence, hearing-aided listeners will typically receive a dual dose of compression when listening to recorded music. The present study involved an acoustic analysis of dynamic range across a cross section of recorded music as well as a perceptual study comparing the efficacy of different compression schemes. The acoustic analysis revealed that the dynamic range of samples from popular genres, such as rock or rap, was generally smaller than the dynamic range of samples from classical genres, such as opera and orchestra. By comparison, the dynamic range of speech, based on recordings of monologues in quiet, was larger than the dynamic range of all music genres tested. The perceptual study compared the effect of the prescription rule NAL-NL2 with a semicompressive and a linear scheme. Music subjected to linear processing had the highest ratings for dynamics and quality, followed by the semicompressive and the NAL-NL2 setting. These findings advise against NAL-NL2 as a prescription rule for recorded music and recommend linear settings.

Harmonic Frequency Lowering: Effects on the Perception of Music Detail and Sound Quality.

A novel algorithm for frequency lowering in music was developed and experimentally tested in hearing-impaired listeners. Harmonic frequency lowering (HFL) combines frequency transposition and frequency compression to preserve the harmonic content of music stimuli. Listeners were asked to make judgments regarding detail and sound quality in music stimuli. Stimuli were presented under different signal processing conditions: original, low-pass filtered, HFL, and nonlinear frequency compressed. Results showed that participants reported perceiving the most detail in the HFL condition. In addition, there was no difference in sound quality across conditions.

Audio-visual facilitation of the mu rhythm.

Previous studies demonstrate that perception of action presented audio-visually facilitates greater mirror neuron system (MNS) activity in humans (Kaplan and Iacoboni in Cogn Process 8(2):103-113, 2007) and non-human primates (Keysers et al. in Exp Brain Res 153(4):628-636, 2003) than perception of action presented unimodally. In the current study, we examined whether audio-visual facilitation of the MNS can be indexed using electroencephalography (EEG) measurement of the mu rhythm. The mu rhythm is an EEG oscillation with peaks at 10 and 20 Hz that is suppressed during the execution and perception of action and is speculated to reflect activity in the premotor and inferior parietal cortices as a result of MNS activation (Pineda in Behav Brain Funct 4(1):47, 2008). Participants observed experimental stimuli unimodally (visual-alone or audio-alone) or bimodally during randomized presentations of two hands ripping a sheet of paper, and a control video depicting a box moving up and down. Audio-visual perception of action stimuli led to greater event-related desynchrony (ERD) of the 8-13 Hz mu rhythm compared to unimodal perception of the same stimuli over the C3 electrode, as well as in a left central cluster when data were examined in source space. These results are consistent with Kaplan and Iacoboni's (in Cogn Process 8(2):103-113, 2007), findings that indicate audio-visual facilitation of the MNS; our left central cluster was localized approximately 13.89 mm away from the ventral premotor cluster identified in their fMRI study, suggesting that these clusters originate from similar sources. Consistency of results in electrode space and component space support the use of ICA as a valid source localization tool.

Age-related difference in melodic pitch perception is probably mediated by temporal processing: empirical and computational evidence.

OBJECTIVE: This study was designed to examine whether age-related differences in melodic pitch perception may be mediated by temporal processing. Temporal models of pitch suggest that performance will decline as the lowest component of a complex tone increases in frequency, regardless of age. In addition, if there are age-related deficits in temporal processing in older adults, this group may have reduced performance relative to younger adults even in the most favorable conditions. DESIGN: Six younger adults and 10 older adults with clinically normal audiograms up to 8 kHz were tested in a melodic pitch perception task. In each trial, two consecutive four-note melodies were presented to the listener. Melodies were identical with the exception of one note in the second melody that was shifted in pitch. The listener was required to identify which note was shifted. All notes consisted of eight successive harmonic components, with the average lowest component manipulated to be the 4th, 8th, or 12th component of the harmonic series, with lower components being absent. RESULTS: Age-related differences in melodic pitch perception were only apparent when stimulus parameters favored temporal processing of pitch. Furthermore, modeling a loss of periodicity coding yielded an outcome consistent with the observed behavioral results. Although younger adults generally outperformed older adults, about one-quarter of the older adults performed at levels that were equivalent to those of younger adults. The only follow-up tests that were able to differentiate these exceptional older adults were tests that would be sensitive to temporal processing: fundamental frequency difference limens and 500 Hz pure-tone difference limens. In contrast, otoacoustic emissions and high-frequency pure-tone thresholds, which are more commonly associated with spectral processing deficits, were not able to differentiate older exceptional adults from older typical adults. CONCLUSION: Age-related declines in temporal processing contribute to deficits in melodic pitch perception. However, some exceptional older adults with normal audiograms preserve excellent temporal processing and continue to perform at levels that are typical of younger adults.

Tune in or tune out: age-related differences in listening to speech in music.

OBJECTIVES: To examine age-related differences in listening to speech in music. DESIGN: In the first experiment, the effect of music familiarity on word identification was compared with a standard measure of word identification in multitalker babble. The average level of the backgrounds was matched and two speech-to-background ratios were tested. In the second experiment, recognition recall was measured for background music heard during a word identification task. RESULTS: For older adults, word identification did not depend on the type of background, but for younger adults word identification was better when the background was familiar music than when it was unfamiliar music or babble. Younger listeners remembered background music better than older listeners, with the pattern of false alarms suggesting that younger listeners consciously processed the background music more than older listeners. In other words, younger listeners attempted to "tune in" the music background, but older listeners attempted to "tune out" the background. CONCLUSIONS: These findings reveal age-related differences in listening to speech in music. When older listeners are confronted with a music background they tend to focus attention on the speech foreground. In contrast, younger listeners attend to both the speech foreground and music background. When music is familiar, this strategy adopted by younger listeners seems to be beneficial to word identification.

Urgency is a non-monotonic function of pulse rate.

Magnitude estimation was used to assess the experience of urgency in pulse-train stimuli (pulsed white noise) ranging from 3.13 to 200 Hz. At low pulse rates, pulses were easily resolved. At high pulse rates, pulses fused together leading to a tonal sensation with a clear pitch level. Urgency ratings followed a nonmonotonic (polynomial) function with local maxima at 17.68 and 200 Hz. The same stimuli were also used in response time and pitch scaling experiments. Response times were negatively correlated with urgency ratings. Pitch scaling results indicated that urgency of pulse trains is mediated by the perceptual constructs of speed and pitch.