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.

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.

Anhedonia to music and mu-opioids: Evidence from the administration of naltrexone.

Music's universality and its ability to deeply affect emotions suggest an evolutionary origin. Previous investigators have found that naltrexone (NTX), a µ-opioid antagonist, may induce reversible anhedonia, attenuating both positive and negative emotions. The neurochemical basis of musical experience is not well-understood, and the NTX-induced anhedonia hypothesis has not been tested with music. Accordingly, we administered NTX or placebo on two different days in a double-blind crossover study, and assessed participants' responses to music using both psychophysiological (objective) and behavioral (subjective) measures. We found that both positive and negative emotions were attenuated. We conclude that endogenous opioids are critical to experiencing both positive and negative emotions in music, and that music uses the same reward pathways as food, drug and sexual pleasure. Our findings add to the growing body of evidence for the evolutionary biological substrates of music.

Parallelized cytoindentation using convex micropatterned surfaces.

Here we present a high-throughput, parallelized cytoindentor for local compression of live cells. The cytoindentor uses convex lens-induced confinement (CLiC) to indent micrometer-sized areas in single cells and/or populations of cells with submicron precision. This is accomplished using micropatterned poly(dimethylsiloxane) (PDMS) films that are adhered to a convex lens to create arrays of extrusions referred to here as "posts." These posts caused local deformation of subcellular regions without any evidence of cell lysis upon CLiC indentation. Our micropost arrays were also functionalized with glycoproteins, such as fibronectin, to both pull and compress cells under customized confinement geometries. Measurements of Chinese hamster ovary (CHO-K1) cell migration trajectories and oxidative stress showed that the CLiC device did not damage or significantly stress the cells. Our novel tool opens a new area of investigation for visualizing mechanobiology and mechanochemistry within living cells, and the high-throughput nature of the technique will streamline investigations as current tools for mechanically probing material properties and molecular dynamics within cells, such as traditional cytoindentors and atomic force microscopy (AFM), are typically restricted to single-cell manipulation.

Efficacy of Pt-modified TiO(2) nanoparticles in cardiac cells.

BACKGROUND: The application of TiO(2) nanoparticles promises to revolutionize cardiac imaging and targeted medical treatment. METHODS: A novel type of platinum-modified TiO(2) (Pt-TiO(2)) nanoparticle was synthesized and characterized. Commercially available P25 TiO(2) nanoparticles were used for comparison. Cellular toxicity and its mechanisms were evaluated by analyzing nanoparticle uptake, oxidative stress and mitochondrial membrane potential in rat cardiac (H9c2) cells. RESULTS: There was greater cellular uptake of Pt-TiO(2). Furthermore, Pt-TiO(2) caused a greater increase in oxidative stress and greater decrease in mitochondrial membrane potential. These data suggest that Pt modification of TiO(2) nanoparticles rendered them more cytotoxic than their commercial counterparts at lower, more physiologically relevant concentrations. CONCLUSION: Despite the functional advantages of Pt modification, which results in increased uptake at a lower concentration, the corresponding increase in cardiotoxic effect indicates that a thoughtful, cautious approach to cardiac nanotechnologies is required.