Practice Points
- Compared with traditional cognitive rehabilitation, music activities can be fun and engaging and build connections while also challenging cognitive systems. Clinicians should consider recommending music-based interventions or community-based music lessons to improve cognitive functioning.
- Tasks that are highly demanding and that progressively tax executive abilities are most successful in improving cognitive abilities, which may explain the potential benefits of music learning on cognitive functioning as opposed to the less challenging task of music listening.
Multiple sclerosis (MS) affects more than 2.8 million people worldwide.1 The prevalence has increased in all regions since 2013, and rates have nearly doubled in the United States.1 It is also one of the main causes of nontraumatic disability in young adults in many countries.2 Individuals with MS experience both visible and invisible symptoms. Invisible symptoms—including fatigue, depression, psychological distress, insomnia, and cognitive dysfunction—can substantially impair quality of life and workforce participation and increase vulnerability to mental health challenges.3,4
Cognitive impairment affects 40% to 70% of people with MS, depression occurs in up to 50%, and fatigue may affect 85% to 95%.5-7 The interplay between cognitive impairment, mood, impaired sleep quality, and fatigue contributes to diminished quality of life.8,9 Cognitive impairment can occur throughout the disease course and commonly involves slowed information processing, attention deficits, executive dysfunction, and working memory impairment,10 with processing speed and memory being the most commonly affected domains.11 Existing interventions targeting cognitive impairment include conventional cognitive rehabilitation, computer-based programs, noninvasive brain stimulation, and music therapy.12-16 Although many demonstrate benefits, most interventions rely primarily on visual or language-based exercises and may not engage multiple sensory systems simultaneously.17
Music is a complex, multidomain stimulus that activates a large-scale bilateral network of temporal, frontal, parietal, cerebellar, limbic, and paralimbic brain areas associated with multiple parallel cognitive, verbal, motor, and emotional processes.18-20 Playing a musical instrument involves intricate coordination and communication between multiple sensory systems (visual, auditory, tactile) and motor functions.18,19 As individuals read musical notes and translate them into physical actions, they simultaneously receive feedback from their auditory system. The ability to engage these systems and coordinate multiple domains may induce new cortical pathways fostering neuroplasticity.18 This rewiring in the brain created by repeated musical practice may create alternative pathways and structures to help people with MS compensate for deficits caused by the demyelinating disease.
A recent systematic review by our team examined active and receptive music interventions for people with MS.21 Most studies evaluated receptive music engagement; only 1 instrument-based intervention (keyboard) focused on hand dexterity.22 Although music listening has demonstrated psychosocial benefits, the cognitive effects of learning to play a musical instrument in people with MS remain largely unexplored.
The Therapeutic Music Capacities Model23 outlines 7 core capacities (engaging, emotional, physical, personal, synchronous, social, persuasive) of music that consistently underlie the health benefits of music for people with neurological problems. Although the model was originally designed for dementia care, it is not specific to any single diagnosis. Evidence suggests these capacities influence outcomes through mechanisms such as auditory-motor coupling, activation of the mirror neuron system, reward and motivation pathways, and neuroplasticity.24-26 Some of the proposed mechanisms of action responsible for inducing therapeutic change include priming neural networks that link music with nonmusic functions such as autobiographical memory and language, the activation of the mirror neuron system, auditory motor coupling, facilitation of motivation and reward, and neuroplasticity.25,26 Although these attributes typically occur concurrently during rehabilitative music engagement, treatment plans can be developed to emphasize individual capacities to target specific neurological symptoms.23 The model thus serves as a guide for developing music-based interventions that are evidence informed, individualized, and adaptable to various therapeutic contexts.
The purpose of this study was to evaluate the feasibility of a 12-week, online music-learning (ukulele) intervention, Music-4-MS, in people with MS and to preliminarily examine psychosocial, functional, and cognitive outcomes. We hypothesized the following: (1) Music-4-MS would be feasible to deliver and acceptable to people with MS, and (2) compared with an active control group (music listening), intervention participants would demonstrate greater improvements in anxiety, depression, self-efficacy, quality of life, fatigue, cognitive abilities, and cognitive performance.
Methods
This feasibility study was a 2-group parallel randomized experimental design (ClinicalTrials.gov ID: NCT05792176).The groups were compared quantitatively on psychosocial well-being, functional well-being, and cognitive performance (Figure 1). Feasibility was assessed quantitatively and qualitatively. The study was approved by The University of Texas at Austin Institutional Review Board (STUDY00003870).
Participants
Participants were recruited across the United States over 8 months through the National Multiple Sclerosis Society (NMSS) website and local walks, online support groups, social media, ClinicalTrials.gov registration, and word of mouth. Inclusion criteria were (1) self-reported diagnosis of MS (relapsing-remitting, secondary progressive, or primary progressive); (2) diagnosis 6 months or more before enrollment; (3) ability to read, write, and understand English; (4) access to a computer; and (5) self-reported cognitive impairment indicated by at least 5 items endorsed as “sometimes” or more often on the Perceived Deficits Questionnaire.27 Exclusion criteria included (1) another neurological condition associated with cognitive impairment, (2) MS exacerbation within the past 30 days, and (3) being a professional musician (primary source of income).
Interested participants were contacted by the research team, scheduled for a telephone call to review study information, and sent a consent form via REDCap.28 During the call, research staff reviewed the risks and benefits of participation. Written informed consent was obtained electronically. Group allocation was concealed until after baseline data collection, after which participants were randomly assigned to the intervention (Music-4-MS) or active control (music listening) group in a 1:1 ratio using block randomization to ensure equal distribution between groups.27 Research Randomizer (Social Psychology Network) generated the randomization sequence.
Intervention Program
Music-4-MS was a 12-week intervention (Table S1; all supplemental materials are available in a PDF at the end of the online article) that taught participants to play the ukulele. The intervention was informed by our prior systematic review and developed with guidance from the primary author (C.S.P.), a performing musician. The ukulele was selected because it is an inexpensive, manageable instrument that requires less hand dexterity than many stringed instruments. Participants used a concert-sized ukulele, which is slightly larger and easier for adults to manage. Each week, participants followed online instructional videos covering basic skills, such as holding, tuning, strumming, and playing chords, while practicing multiple popular songs. Participants were instructed to complete the weekly sessions and practice at least 30 minutes per day, 5 days per week (150 minutes per week). A written version of the protocol was also emailed to participants. A ukulele-trained research team member conducted weekly phone calls to answer questions, address challenges, and provide feedback on technique. To support intervention fidelity, all participants followed the same protocol and recorded their practice in a daily log.
Control Group
Participants listened to their preferred music (not predetermined) for a minimum of 30 minutes per day, 5 days a week, totaling 150 minutes per week. To support their engagement, a research team member conducted weekly phone calls to address any questions or challenges related to their music listening experience. Participants were also asked to document their daily listening activities and reflections in a log.
Data Collection
Surveys were administered using REDCap28 at 3 time points: baseline (preintervention; T1), immediately after the intervention (T2), and 1 month after the intervention (T3). Each participant received up to $100 in gift cards after data collection as a thank-you for their time. The primary outcome of the study was feasibility and acceptability. To evaluate the feasibility of Music-4-MS, we assessed recruitment (how many accept the invitation to participate in the study and recruitment time frame), retention (how many participants drop out of the study), and engagement (weekly participation in Music-4-MS). Acceptability was evaluated with semistructured interviews to evaluate participants’ perception of Music-4-MS delivery and content as well as the perceived impact. Exploratory outcome data evaluating psychosocial, functional, and cognitive well-being were also collected at T1, T2, and T3.
Measures
Background Information
Background information was collected to describe the participant demographic and disease characteristics. Participants completed the Patient-Determined Disease Steps (PDDS), a self-report measure of MS-related disability.29 The PDDS has strong reliability and validity. Scores range from 0 to 8, with higher scores indicating greater disability.
Self-Report Outcomes
Multiple Patient-Reported Outcomes Measurement Information System (PROMIS) short forms were used to measure anxiety (8 items), depression (8 items), fatigue (8 items), and cognitive abilities (8 items). The reliability and validity of the PROMIS scales have been reported for various populations, including people with MS.30,31 Higher scores indicate more of the construct. The Multiple Sclerosis Quality of Life Questionnaire measured quality of life.32 This 27-item questionnaire measures health-related quality of life in people with MS. Higher scores indicate a worse quality of life. Self-efficacy was measured with the Self-Efficacy for Managing Chronic Disease Scale (6 items),33 which had strong psychometric properties when tested in people with MS.34 Higher scores indicate greater self-efficacy.
Cognitive Performance Outcomes
Participants completed BrainCheck,35 a standardized, computerized neurocognitive testing battery assessing processing speed, visual attention (Trails A), cognitive flexibility (Trails B), attention and visuoperception (Digit Symbol Substitution), response inhibition (Stroop Color and Word), and verbal declarative learning and memory (immediate and delayed list recall). Testing required approximately 20 minutes. The first half of participants completed testing in the office using an iPad 10.2 (Apple), whereas the remaining participants completed testing remotely using their own device (desktop computer, laptop, or iPad) in a quiet room at home. BrainCheck demonstrates strong psychometric properties and sensitivity for detecting mild cognitive impairment, although it has not previously been used in people with MS.36,37 The battery provides age- and device-adjusted standard scores (mean, 100; SD, 15) for each test and a composite score, with higher scores indicating better cognitive performance.
Data Analysis
Descriptive statistics were used to describe background and feasibility data. Qualitative content analysis was used to summarize the findings from the acceptability interviews.38 This method is used most often with qualitative descriptive methodology and is appropriate when little is known about the phenomenon. The researchers allowed categories to flow from the data using inductive coding. To improve the trustworthiness of the analysis,39 4 researchers (C.S.P, J.K., R.H., S.D.) coded, analyzed, and discussed the preliminary and final coding. An audit trail of coding and decision-making was maintained throughout the analysis process. Standards for Reporting Qualitative Research guidelines were followed.40
Outcomes data were analyzed using IBM SPSS version 29.0. Before analysis, the data set was examined for missing data and violations of statistical assumptions. Descriptive statistics characterized the sample, and groups were compared at baseline on all variables. An analysis of covariance (ANCOVA) was conducted at T2 and T3 to evaluate the effects of Music-4-MS while controlling for T1 scores, with separate analyses for each outcome. Effect sizes (partial η2) were calculated for T2 and T3 differences. Because this was a feasibility study, the intentionally small sample size may have limited statistical power. The α level was set at P less than .10 to prioritize detection of potentially meaningful differences for future trials.41 Consort guidelines for randomized pilot and feasibility trials were followed.42
Results
Participants
A total of 29 people with MS completed baseline data collection and were randomly assigned to the Music-4-MS group (n = 16) or the music-listening group (n = 13). Participants had an average age of 51.7 years (range, 31-76) and had been living with MS for an average of 14.5 years. The majority were female (79.3%), were White (79.3%), and had a diagnosis of relapsing-remitting MS (69%). No statistically significant differences were observed between the groups in terms of demographic or disease-related variables (Table 1). However, more participants in the Music-4-MS group had relapsing-remitting MS (n = 14) compared with those in the music-listening group (n = 6).
Feasibility
Over 8 months, 46 people were screened for participation, 31 consented, and 29 enrolled (Figure 2). The most successful recruitment methods were in person at the local NMSS walk, the NMSS website research post, and online MS support groups. The overall dropout rate was 21%, and 5 of the 6 people who dropped out were in the Music-4-MS group. Of the 5 Music-4-MS participants who dropped out, 2 people found it too challenging, 1 person had complicating health reasons, and 2 people’s lives were too busy to participate. The person who dropped out of the control group was bored by music listening. At the end of the study, 9 Music-4-MS participants submitted daily logs. Of the participants who submitted their daily music logs, on average, participants in the intervention group played the ukulele for 165 minutes per week, 85% followed the protocol from weeks 1 to 8, and 72% adhered from weeks 9 to 12.
For the music-listening group, participants listened to music for an average of 245 minutes per week. Analysis of the weekly call field notes revealed that the most common times to listen were first thing in the morning, while driving, after work, during exercise, and before going to sleep. All but 3 participants were multitasking while listening to the audio. One additional participant listened undisturbed until approximately week 6. Participants who listened undistracted were more likely to intentionally listen to a broader variety of music. The choice of songs was often songs that the participant liked in the past and felt nostalgic about. Two participants mentioned active engagement (ie, singing or playing along with the music) while listening.
Acceptability
The 11 participants who remained in the Music-4-MS group were interviewed at the end of the study to understand protocol acceptability. Six themes emerged from the interview data (Table 2).
Emotional Resonance
Participants described positive and negative effects on their mood. On the positive side, participants had fun playing the ukulele, especially if they felt like they were “jamming,” and felt fulfillment, personal growth, engagement, pride in learning a new skill, a sense of accomplishment, and increased confidence in their skills. The negative moods expressed by some stemmed from frustration with the protocol’s speed. However, there were equal numbers of people who thought it was too fast, too slow at the beginning, or just right overall.
Navigating Challenges
Hand dexterity and fatigue were the primary physical challenges discussed. Difficulties included reduced confidence in fine motor skills, stiffness, and neuropathy. Although these symptoms were challenging for some participants, many appreciated the hand stretches and reported increased confidence in their dexterity by the end of the protocol. Cognitively, participants described a new awareness of the demands involved in learning a new skill, which some found frustrating. However, many also reported cognitive gains, noting that learning the ukulele supported cognitive function, and they enjoyed the combination of music, learning, and problem-solving.
Fostering Connection and Meaning
The intervention enhanced participants’ connection with family and friends, fostering social bonding. Some participants learned the ukulele with their children, adding fulfillment and motivation, whereas others brought their instruments on vacation and played with friends. Learning the ukulele also created new opportunities for conversation in social settings and opened space to discuss their diagnoses and daily challenges within the context of a new activity. Participants also described feeling personally connected to the music and learning new stories from friends and family through shared memories associated with the songs.
Fluctuating Motivation
The positive side of motivation was evident when participants could see their progress, and revisiting prior material sometimes helped them remain motivated. Participants also found motivation in the desire to learn and improve their MS symptoms, whereas others described a lack of motivation to practice.
Adaptive Learning Strategies
Participants employed a variety of strategies to enhance navigation of the protocol, especially as learning a new skill challenged both physical and cognitive skills. One successful strategy was establishing a routine practice schedule during the time of day when they experienced fewer MS symptoms. They also described the benefits of isolating specific aspects of learning—for instance, muting the strings and focusing solely on the physicality of the strumming hand or, when too tired to play, simply listening to the songs so that they could learn the music without the instrument and feel the music more deeply.
Future Recommendations
All participants said they would recommend this intervention to individuals with MS, particularly those seeking opportunities to enhance cognition and hand dexterity. Participant recommendations for the intervention included moving the protocol to a single platform (ie, rather than videos sourced from multiple online sites) to simplify navigation; incorporating videos to provide more opportunities for reinforcement, muscle memory development, and reminders of the basics along the way; and extending the length of the intervention. When asked about their preference for online vs in-person delivery, most participants preferred the online option due to its flexibility and accommodation of symptoms.
Exploratory Outcomes
Table 3 shows T1 mean scores, the adjusted mean scores at T2 and T3, and the ANCOVA results for each outcome measure, adjusting for baseline scores on that measure. The analysis showed that at T2, the intervention group scored significantly better than the control group on measures of anxiety (F = 3.940; P = .061) and depression (F = 3.120; P = .040). At T3, the intervention group scored significantly better than the control group on the Trails B test (F = 3.897; P = .063). The effect sizes for differences in most of the self-report outcomes were small to moderate at T2 but large for anxiety, depression, and fatigue. At T3, the effect sizes were moderate for anxiety, self-efficacy, cognitive abilities, BrainCheck composite score, Trails A, Digit Symbol Substitution, and delayed recall and were large for Trails B.
Discussion
The online music-learning intervention, Music-4-MS, aims to address a gap in cognitive rehabilitation by combining music and learning—2 modalities known to improve brain health and neuroplasticity independently. Previous research has demonstrated that music-based activities can engage neural networks across auditory, motor, emotional, and executive systems, making music a uniquely multimodal form of cognitive stimulation.43-45 Findings from this study demonstrate partial feasibility and provide preliminary evidence to suggest Music-4-MS improves psychosocial well-being and cognitive functioning. The study’s overall dropout rate was 21%; 30% of participants in the Music-4-MS group dropped out. The reason for discontinuation was unrelated to the Music-4-MS intervention; however, it is possible that the level of intervention burden increased the rate of discontinuation among individuals trying to balance busy lives. Similar feasibility challenges have been observed in other behavioral and rehabilitation interventions for people with MS, particularly those requiring sustained engagement outside structured clinical settings.46 Despite the intervention group dropout rate, adherence was strong, and participants found the intervention acceptable. Generally, they spoke positively about it and provided meaningful feedback to refine and optimize it. Participants in both groups engaged more than the required weekly amount, indicating that music-based activities may have intrinsic motivational value for individuals living with MS.
Both groups showed some improvement across several outcome measures, suggesting that music in any form can be a valuable tool for mental health and cognitive function in people with MS. Prior studies of music interventions in neurological populations similarly report improvements in mood, cognitive functioning, and quality of life following both active and receptive music interventions.47,48 In the present study, the Music-4-MS group outperformed the music-listening group on 3 cognitive measures at T2 and all cognitive measures at T3. Although most of the differences were not statistically significant, moderate effect sizes were observed at T3 for all BrainCheck measures except immediate recall. Because the structured intervention concluded at T2, these findings may reflect delayed effects of skill acquisition rather than ongoing exposure to the intervention itself.
This pattern aligns with the Therapeutic Music Capacities Model,23 which proposes that music promotes cognitive engagement and neuroplasticity by simultaneously activating multiple brain regions. Learning to play an instrument requires the integration of auditory perception, fine motor coordination, attention, and executive control, processes known to strengthen functional connectivity in the brain with repeated practice.43 The sustained cognitive improvements seen in the Music-4-MS groups were consistent with research suggesting that executive function is part of neuropsychological activities that require more time for change.49
When learning to play an instrument, there is usually an emphasis on progressively more difficult lessons. Simple songs, rhythms, or melodies are attempted before more complex ones and are played at slow tempos until familiarity allows them to be played at faster tempos. Thus, various executive and cognitive functions, such as inhibitory control and working memory, are constantly being taxed as learned patterns are built upon.50 Highly demanding tasks that progressively tax executive abilities are most successful in improving them,51 which likely explains the potential benefits of music learning on cognitive functioning, as opposed to less challenging tasks. Integrating multiple brain regions involved with musical performance and learning new information in music training may result in new gray matter and new white matter linking various brain regions.52 Although well-controlled interventions demonstrating this effect are lacking, Loui provided correlational evidence to suggest this may be the case.53
Compared with traditional cognitive rehabilitation, there are unique advantages to music-learning interventions. A challenge with many cognitive interventions that enhance cognitive abilities is that they are often discontinued,54 and interventions that cultivate ongoing commitment and social connection, such as book clubs, may not adequately pressure cognition. Music-related activities, on the other hand, tend to tax cognitive systems and have the potential to evoke pleasure. Research has shown that music-related pleasure reflects white-matter connectivity between sensory, social, and emotion-processing areas (eg, between the superior temporal gyrus, insula, and medial prefrontal cortex).47 Thus, musical experiences may reduce the extent of age-related declines and promote the maintenance of cognitive, emotional, and social functioning across the lifespan.
This study has several limitations. The small sample size limits generalizability and may have reduced statistical power to detect significant effects across all outcomes. Generalizability is further limited by the predominance of White female participants, although MS is most commonly diagnosed in this population.55 Additionally, over two-thirds of participants reported relapsing-remitting MS, providing limited insight into the feasibility of the intervention for individuals with progressive MS. Nearly 90% of participants had previously taken music lessons, suggesting possible selection bias. Participants were also not asked to abstain from music engagement outside the study; individuals who enjoy music may be more likely to participate and may regularly listen to or play music.
The cognitive testing battery was selected for its strong psychometric properties, focus on processing speed and memory, domains most affected in MS, and efficiency of administration to reduce participant burden. However, the battery has not been validated in the MS population and may have been insufficiently sensitive to detect subtle changes. Future studies should consider including a broader range of cognitive tests, more precise measures of specific cognitive processes, and additional cognitive domains. Finally, the control group was not interviewed after the intervention, limiting insight into how music listening might be intentionally prescribed as a therapeutic strategy.
Conclusions
The findings of this feasibility study provide preliminary evidence that Music-4-MS may support improvements in cognitive performance and psychosocial well-being among people with MS. These results should be interpreted within the broader context of MS care, where interventions rarely benefit all individuals equally and multiple approaches may be needed to address the diverse symptoms experienced. Learning to play an instrument may be particularly appealing and feasible for individuals with sufficient motor function, cognitive capacity, and interest in developing a musical skill, whereas more accessible forms of music engagement, such as structured music listening, may offer meaningful benefits for those with greater physical or cognitive limitations. Participants in the music-listening group also demonstrated improvements on several outcomes, suggesting that different forms of music engagement may influence well-being through distinct mechanisms. Given that many people with MS seek innovative strategies to enhance cognitive function and quality of life, active music-learning interventions may represent a promising complementary approach to existing management strategies. However, the long-term sustainability of instrument practice and the durability of cognitive benefits were not evaluated. Future research with larger samples, longer follow-up, and optimized intervention designs based on participant feedback will be important for determining the effectiveness and clinical utility of music-based interventions for people with MS.
