A Randomized Controlled Trial of Ukulele Playing Compared to Music Listening to Improve Cognition in People with Multiple Sclerosis: a Feasibility Study

Multiple sclerosis (MS) affects more than 2.8 million people worldwide. The prevalence has increased in every region worldwide since 2013, and in the United States, rates have nearly doubled. It is the main cause of nontraumatic disability in young adults in many countries. MS is a chronic neuroinflammatory and neurodegenerative disease with an unpredictable course. Varying visible and invisible symptoms occur in MS. The invisible symptoms, such as fatigue, depression, psychological distress, insomnia, and cognitive dysfunction pose a significant burden on quality of life (QoL) and workforce participation, rendering PwMS more vulnerable to mental health challenges compared to those affected by physical disability alone. Cognitive impairment occurs in 40-70%, depression in up to 50%, and fatigue can be present in up to 85-95% of PwMS. The interplay of cognitive impairment, mood, impaired sleep quality, and fatigue contributes significantly to worsened QoL. Cognitive impairment can occur in early and late phases of the disease and may include alterations in information processing, attention, executive functions and working memory. Multiple interventions have been created to address cognitive impairments such as conventional cognitive rehabilitation, computer-based programs, non-invasive brain stimulation, and neurologic music therapy. Many of these interventions have shown improvements in various domains of cognitive impairment. However, the effect of cognitive rehabilitation on psychosocial well-being in addition to cognitive symptoms is rare.

This research aims to fill a gap in cognitive rehabilitation with an innovative music training intervention for PwMS. Active music engagement interventions (i.e., instrument playing) have shown improvements in cognitive, motor, and psychosocial outcomes in other neurological conditions. However, few studies have examined the impact for PwMS. Most music intervention studies in PwMS evaluate the impact of music on fatigue, pain, mood disorders, walking, and balance. The impact of music on cognition is much less studied. Our team is currently conducting a systematic review examining the differences between active and passive music engagement in PwMS. Sixteen studies were included in the review. Only two studies examined active music making (singing or musical instrument playing), only one of those evaluated the impact on cognition (no improvement), and neither evaluated the effect on psychosocial (anxiety, depression, quality of life) outcomes. Twelve of the studies evaluated passive music engagement (music listening with or without movement); however, the primary outcome in most of these studies was neurological motor skills versus non-motor or psychosocial outcomes. One study, that used both active and passive musical engagement, examined the effect of cognitive rehabilitation plus neurological music therapy on cognitive abilities, mood, emotional components, and MS quality of life. They found significant improvements in cognitive function, motivation, emotional awareness, depression, and quality of life in the intervention that entailed cognitive rehabilitation plus neurological music therapy. However, no significant differences were found between the experimental group (cognitive rehabilitation plus neurological music therapy) and active control (cognitive rehabilitation alone).

Music listening and making is processed throughout spinal, subcortical, and cortical regions, and thus has meaningful and broad impacts on complex cognitive, affective, and sensorimotor processes. The impact of instrumental music playing on executive functioning has been demonstrated in many studies with children; however, this has not been studied in PwMS. Specific to executive function, neuroimaging studies with functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS) show an increase in neural activations the right frontal and prefrontal regions in PwMS on cognitive tests requiring lower cognitive load (e.g., 1-back) working memory tasks when compared to healthy controls and lower activation on higher cognitive load tasks (2- and 3-back). Theoretically, it is hypothesized that the neuronal damage caused by MS causes processing resources to be diminished, thus different brain areas are recruited to cope with task demands as difficulty increases. The rehabilitative effects of music in relation to other neurological disorders is linked to changes in brain neuroplasticity, which describes the adaption and cortical reorganization after training or learning a new task. This study will examine the feasibility of an online musical training intervention (MTI) for PwMS, explore the potential effect on cognitive functioning, psychosocial, and functional well-being, and explore a neuroimaging via fNIRS, a non-invasive technique, to determine if pre-intervention brain activity predicts post-intervention cognitive functioning.

The purpose of this study is to determine the feasibility of an online musical training intervention (MTI) for PwMS and explore the potential effect on cognition, psychosocial, and functional well-being compared to an active control group (music listening (ML)). The specific aims are to: 1) determine the feasibility and acceptability of delivering the MTI virtually over three months to PwMS; 2) evaluate the effect of the MTI on cognitive functioning (processing speed, working memory, cognitive flexibility, response inhibition), psychosocial (anxiety, depression, stress, quality of life, self-efficacy) and functional (insomnia) well-being compared to ML; and 3) (exploratory aim) to utilize non-invasive neuroimaging to determine if pre-intervention brain activity predicts post-intervention cognitive functioning.