Impact of Active Versus Receptive Music Interventions on Psychosocial and Neurological Outcomes in People with Multiple Sclerosis: A Systematic Review

Abstract

Introduction:

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that affects nearly 1 million people in the United States and 2.9 million people worldwide. The symptoms vary substantially but can include fatigue, lower extremity weakness, cognitive dysfunction, and mood impairment. The use of music to improve cognition, mood, and movement has been studied in numerous patient populations, yet the implementation for people with MS (PwMS) is understudied. This systematic review evaluates the effect of music-based interventions implemented with PwMS.

Methods:

The search used four electronic databases: PubMed/MEDLINE, CINAHL, PsycINFO, and Web of Science from January 1, 2002 to June 30, 2024. The inclusion criteria were (1) individuals diagnosed with MS, (2) music interventions, and (3) randomized controlled trials, quasi-experimental (nonrandomized controlled trials), and mixed methods studies. Outcomes included anxiety, depression, quality of life, and cognitive and functional (gait, balance, fatigue, dexterity) impairment. The risk of bias was evaluated with the National Institutes of Health Quality Assessment Tool.

Results:

A total of 15 studies were included, representing 623 participants. Most studies were conducted in Europe (n = 9). Ten studies were randomized controlled trials, and the remaining studies were quasi-experimental (case and match controlled). Intervention lengths varied from 1 session (n = 5) to 36 sessions. Most studies used receptive music engagement; the most common application was music listening while walking. Gait parameters and physical fatigue were the most common outcomes. These studies showed improved gait outcomes in music listening and active control groups. However, participants in the music interventions had less physical fatigue with activity. Four studies evaluated active music engagement interventions. Most active interventions were one session and evaluated memory through immediate and delayed recall of words sung to a melody compared with spoken words. In total, 73% of the studies evaluating motor neurological outcomes (gait, dexterity, and balance) had significant between-group improvements. Sixty-two percent of studies evaluating nonmotor neurological outcomes (cognitive functioning, fatigue, mood, and quality of life) showed significant between-group improvements. Methodological quality was assessed as fair or good for all the studies in the review. Safety and adverse event data were reported in 6/15 studies.

Discussion:

Music-based interventions show promise in improving motor and nonmotor outcomes in PwMS. However, the effectiveness of music-based interventions remains uncertain due to inconsistencies in methodologies and outcome measurements. Gaps in the research include active music engagement interventions, the impact of learning to play an instrument on cognition, and the delivery of interventions online and at home.

Registration:

PROSPERO #CRD42022338291.

Introduction

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease characterized by progressive demyelination of the central nervous system that can lead to a variety of physical and cognitive impairments.¹ The neurodegenerative disease compromises motor, sensory, visual, and autonomic systems and can decrease the quality of life for people living with MS.^2,3 Affecting nearly 1 million people in the United States and 2.9 million people worldwide, the most common symptoms of MS include fatigue, lower extremity weakness, mood impairment, and cognitive dysfunction.^4,5 However, clinical manifestations of the disease vary greatly.³ The rates of depression in people with MS (PwMS) range from 30% to 40%, while fatigue can be present in up to 85%–95% of people.^6
–8

Cognitive dysfunction can start early in the disease course and affect up to 75% of PwMS.^7,9 The most frequently affected domains are information processing speed and episodic memory.^10
–12 Even though self-reported cognitive dysfunction in PwMS is only moderately correlated with objective measures of cognitive impairment, it negatively affects the quality of life and affects mood and fatigue.^13,14 Many cognitive rehabilitative interventions have been developed to improve cognitive symptoms. A recent Cochrane Review of 44 memory rehabilitation interventions evaluated in randomized controlled trials found that patients who received memory rehabilitation reported better memory functioning and quality of life than those who did not.¹³ Approaches to cognitive rehabilitation use restorative and compensatory strategies. Restorative cognitive rehabilitation focuses on improving and rebuilding the MS patient’s cognitive abilities, while compensatory cognitive rehabilitation solely provides management strategies.¹³

Motor dysfunction associated with MS can include symptoms of weakness, spasticity, and dysfunction in balance and coordination, resulting in decreased gait speed, walking endurance, step length, and joint motion.^15
–17 Unlike other neurological conditions, no fixed deficit or symptom profile exists. Physical rehabilitation approaches are individualized, flexible, and depend on the individual’s physical limitations. Physical therapists provide exercises to maintain and strengthen physical abilities throughout the disease course.¹⁸

The use of music to improve cognition, mood, and movement has been studied in numerous populations, including chemotherapy-induced cognitive impairment in women with breast cancer,¹⁹ memory, mood, and cognitive functioning in people with Alzheimer’s disease and dementia,²⁰ and to improve movement in people with Parkinson’s disease.²¹ Music perception, listening, and performance specifically engage in a complex cognitive system involving auditory scene analysis, attention, learning and memory, multimodal learning, emotion, and social cognition.²² In addition, neuroimaging studies have shown that during music listening, perception, and performance systems are coactivated with auditory and motor systems.²³ The connections between these two systems help music cognition create predictions and expectancies associated with music perception and listening, leading to brain patterns and associations.²³

Music interventions can include active and receptive music engagement. In music therapy literature, active engagement is commonly categorized as playing an instrument, writing music, and singing.²⁴ In contrast, receptive engagement is described as the participant is “a recipient of the music experience, as distinct from being an active music maker.”^{25; p. 15} Active and receptive music therapy interventions have improved physiological and psychological symptoms in persons with neurodegenerative diseases.²⁶ Within this review, we have categorized active music engagement as creating music by playing instruments or singing and receptive music engagement as listening to music while walking, meditating, or dancing.

The purpose of this systematic review is to examine the literature over a 22-year timeframe (2002–2024) that evaluated the effect of music-based interventions implemented with people living with MS. This timeframe was chosen because the insurgence of disease-modifying therapies that began in 2002 with the approval of Interferon-ß. Since 2002, the available treatment options, which have improved the length of life for PwMS, have increased substantially.²⁷ Understanding the current state of the science will facilitate advancements in future music-based studies for PwMS. This review will address the following questions:

What are the characteristics of music-based interventions used for PwMS?

How do music-based interventions affect motor (e.g., gait, dexterity, balance) and nonmotor neurological (e.g., cognition, fatigue, psychosocial well-being) outcomes in PwMS?

Are there unique differences in outcomes based on active versus receptive music engagement?

Materials and Methods

A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting.²⁸ The details of PRISMA are shown in Supplementary Data S1. This systematic review was registered with PROSPERO (registration number: CRD42022338291).

Selection criteria

The inclusion criteria included (1) individuals diagnosed with MS, (2) music interventions, and (3) randomized controlled trials, quasi-experimental (nonrandomized controlled trials), and mixed methods studies. Exclusion criteria included: (1) individuals with forms of clinically isolated syndrome or radiologically isolated syndrome or other neurodegenerative diseases; (2) dissertations/theses, conference abstracts, case studies, qualitative studies, or commentaries. Outcomes included anxiety, depression, quality of life, and cognitive and functional (gait, balance, fatigue, dexterity) impairment. The additional search limitations were that studies were peer-reviewed, in English, and published between January 1, 2002 and June 30, 2024.

Search strategy and information sources

The review was conducted between June 2022 and June 2024 in four electronic databases: PubMed/MEDLINE, CINAHL, PsycINFO, and Web of Science. The following key terms were used in multiple combinations: music interventions, music therapy, MS, psychosocial well-being, mood, depression, anxiety, quality of life, cognition, gait, mobility, dexterity, and balance. To minimize selection bias, the reference lists of the articles obtained were reviewed to identify additional studies for inclusion. When necessary, authors of the publications were contacted to acquire further study details. The retrieval strategies in PubMed are shown in Supplementary Data S2.

Data screening and extraction

Article screening and review occurred in several phases, with an iterative process using the Covidence software.²⁹ Duplicates were automatically removed by Covidence. In every phase, two reviewers independently coded each article. In the title and abstract review, if a discrepancy occurred or sufficient information was not available in the abstract, the article was moved to the next phase of review. The full-text review phase had three coders (C.P., J.K., A.G.) per article, and one author (C.P.) provided an audit of the final articles for inclusion. Discrepancies at this phase were discussed with the coding team and resolved. Three authors (C.P., A.G., J.K.) extracted information from the studies. The following data were extracted: study characteristics (first author, publication year, and country), methods (study design and sample size), participants’ characteristics (gender, age, MS phenotype, years since diagnosis), intervention and comparison (intervention description, music details, delivery location, intervention facilitator, intervention length), outcome measures, and research results. During extraction, the reviewers were not blinded to authors or journals.

Assessment of quality

Three authors (C.P., A.G., J.K.) independently assessed the quality of the studies included in the review using one of the National Institutes of Health (NIH) Quality Assessment Tools.³⁰ In 2013, the NIH developed a set of quality assessment tools tailored to specific study designs to review study’s internal validity. The NIH Assessment of Controlled Intervention Studies tool was used for this review.

Statistical analysis

There was considerable heterogeneity in the included studies, mainly due to differences in MS phenotypes, control treatments, and outcome measures, which made it difficult to perform a meta-analysis. Accordingly, descriptive statistics were used to describe the sample, and qualitative descriptive analysis was used to report the outcomes. All relative data were synthesized in tables.

Results

Study and participant characteristics

In total, 326 citations were reviewed (Fig. 1). After abstract review, 34 studies were retrieved for full-text review. An example of a reason a study met the eligibility criteria but was eliminated is if the analysis was of duplicate data and outcomes.³¹ After the full screening process, 15 articles were included for final review.^{32

–46} All studies were conducted in Europe (Italy = 3, Belgium = 3, Austria = 2, and Turkey = 1) or North America (United States = 5). One study had a sample from the United States and Germany. Over half of the studies (9/14) were conducted within the past 5 years. The total sample size across studies in this review was 623 (range = 10–101). Of the studies that reported MS phenotypes (n = 8), 61% of participants had relapsing-remitting disease. Table 1 provides more detail about the participant demographics. A summary of each study's purpose, design, measured outcomes, and findings can be found in Table 2. Notably, 10 of the studies were randomized controlled trials. The remaining studies were controlled trials, but allocation was not randomized.

FIG. 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Diagram.

Table 1.

Demographics

First author, date(Country)	Sample size	Sex female:Male	Age (mean years)(EG/CG)	MS phenotypeRR/SP/PP	Years since Diagnosis (Mean)
Baştürk et al, 2024⁴⁶ (Turkey)	31	17:14	EG: 48.27 ± 9.3 CG: 43.12 ± 12.55		EG: 11.20 ± 3.95CG: 15 ± 6.89
Conklyn et al., 2010³²(United States)	10	7:3	EG: 47.0 ± 10.5CG: 50.2 ± 5.5	EG: 4/0/1CG: 3/2/0	EG: 16.6 ± 10.4CG: 12.2 ± 5.8
Gatti et al., 2015³³(Italy)	19	12:7	EG: 43.3 ± 8.8CG: 48.4 ± 10.1	All SP or PP
Impellizzeri et al., 2020³⁴(Italy)	30	11:19	EG: 51.7CG: 51.3	EG: 8/4/3CG: 7/4/4	EG: 9 ± 2CG: 10 ± 3
Maggio et al., 2021³⁵(Italy)	20	14:6	EG: 45.3 ± 9.7CG: 45.3 ± 9.5	EG: 5/0/5CG: 5/0/5	EG: 17.7 ± 5.3CG: 17.7 ± 5.4
Moore et al., 2008³⁶(United States)	38	30:8	EG1: 53.3 ± 9.3EG2: 50.3 ± 10.1
Moumdjian et al., 2019(Belgium)	61	45:16	EG: 53.5 ± 10.6CG: 51.8 ± 11.4	20/4/6	17.2 ± 9.8
Moumdjian et al., 2022³⁸(Belgium)	62	37:25	EG 46.9 ± 11.6CG 48.9 ± 12.8	24/4/3	11.8 ± 9.1
Schmid et al., 2004³⁹(United States)	20	14:6	All: 29–47 (range)		11.0
Seebacher et al., 2017⁴⁰(Austria)	101	85:16	EG1: 43.8EG2: 45.4CG: 43.1
Seebacher et al., 2019⁴¹(Austria)	59	47:12	EG1: 45.3EG2: 44.5EG3: 43.3
Thaut et al., 2008⁴²(United States)	20	18:2	EG: 51.7 ± 9.3CG: 53.8 ± 11.2	RR = 20
Thaut et al., 2014⁴³(United States/Germany)	54	38:16	EG: 50.3 ± 9.3CG: 53.3 ± 10.1	RR = 54
VanGeel et al., 2020(Belgium)	17	16:1	EG1: 29–52 (range)EG2: 40–65 (range)		3–21 (range)
Young et al., 2019⁴⁵(United States)	81	66:15	EG1: 49.67EG2: 48.35CG: 47.29		EG1: 13.56EG2: 10.98CG: 13.38

EG, experimental group; CG, control group; PP, primary progressive; RR, relapsing remitting; SP, secondary progressive.

Table 2.

Music Interventions for People with Multiple Sclerosis

First author, date(Country)	Purpose/study design	Design	Control group	Outcomes	Findings
Baştürk et al, 2024⁴⁶ (Turkey)	Investigate the effects of line dancing on balance, mood, and health-related quality of life.	RCT	No intervention	Primary: BalanceDepression, AnxietyQoL	Significant between-group improvements in balance (p = 0.03), anxiety status (p = 0.02), mental composite of QoL (p = 0.03). No significant differences on physical composite of QoL and depression between groups.
Conklyn et al, 2010³² (United States)	Explore the effect of a home-based rhythmic auditory stimulation walking program on walking performance.	RCT	No intervention	Primary: Gait parametersSecondary: Spasticity, muscle strength, pain, ambulation disability, MS-related disability	Significant between-group improvements in double-support time on left (p = 0.02) and right sides (p = 0.03). No significant differences on gait parameters between groups. There were no statistically significant changes in the other outcome measures.
Gatti et al, 2015³³ (Italy)	Evaluate the impact musical keyboard playing on hand function.	RCT	Keyboard without sound	Primary: Perceived hand functional useSecondary: Hand dexterity and strength	Significant improvement in hand function in EG (p = 0.003). Both groups showed a significant improvement over time in hand dexterity.
Impellizzeri et al, 2020³⁴ (Italy)	Investigate the effect of neurological music therapy on mood, motivation, emotion status, and cognitive function.	RCT	Conventional cognitive rehabilitation	Primary: Cognitive abilities, mood, emotional components, MS QoL	The experimental group had significant improvements in cognitive function (p < .000), long-term retrieval (p = 0.007), delayed recall (p = 0.001), and on multiple subscales of motivation, emotional awareness, depression, and QoL. No between-group significance.
Maggio et al, 2021³⁵ (Italy)	Evaluate the feasibility and effect of treadmill walking with music on motor skills and mood.	Case-control feasibility study	No intervention	Primary: Motor evaluation, mood, goal attainment	The experimental group improved in pre-post comparisons in static and dynamic balance (p < 0.003), walking speed (p < 0.002), mobility (p < 0.003), and physical and mental QoL perception (p < 0.002; p < 0.001).
Moore et al, 2008³⁶ (United States)	Understand the effectiveness of using music as a mnemonic device for memory recognition.	RCT	Spoken word	Primary: Verbal learning and memory, executive functioning, and sustained attention	Correlation analysis suggests that music mnemonics may facilitate learning, but there were no significant differences between the two groups on any measure.
Moumdjian et al, 2019(Belgium)	Evaluate the effect of walking with music and metronome on perceived fatigue and gait.	Observational, case-control study	Healthy control	Primary: Auditory-motor coupling and synchronization Secondary: Perceived physical and cognitive fatigue, motivation, cadence, and stride	Participants were able to synchronize to the different tempi. Noncognitively impaired had higher synchronization with the metronome compared with music (p < 0.001). People with MS perceived significantly less physical (p < 0.0001) and cognitive fatigue (p < 0.0001) when walking to music. Cognitive impaired persons perceived lower fatigue walking to music compared with metronomes (p < 0.0001).
Moumdjian et al, 2022³⁸ (Belgium)	Investigated potential to learn and perform a cognitive sequence during an embodied task by dynamic stepping movements under three different conditions (melody, sound, and visual).	Observational, case-control study	Healthy control	Primary: Cognitive and motor performances at delayed recall Secondary: Physical/cognitive fatigue, ease of executing & remembering the sequence, effort/frustration to learn/perform the sequence	Half of participants correctly recalled the sequence in all three conditions, while 70% of healthy controls in the melody condition correctly recalled the sequence. Balance impairment predicted the speed of executing the sequence and was most apparent in the melody condition. Information processing speed predicted the speed of executing the sequence in the melody and sound conditions.
Schmid et al, 2004³⁹ (United States)	Evaluate the effect of music therapy on fatigue, QoL, and mood.	Matched Control Study	No intervention	Primary: Clinical depression, anxiety, self-acceptance, quality of life, and cognitive and functional ability	No significant difference between the two groups in any of the outcome measures. There were significant improvements for the therapy group over time in self-acceptance (p = 0.012), depression (p = 0.036), and anxiety (p = 0.013).
Seebacher et al, 2017⁴⁰ (Austria)	Investigate the effect of music motor imagery on walking, fatigue, and QoL.	RCT	Metronome-cued motor imagery or no intervention	Primary: Walking speed and distance Secondary: Walking perception, fatigue, and QoL	Rhythm-cued and music-cued MI significantly improved walking speed, distance, perception, cognitive fatigue, and QoL. Physical fatigue improved only in the music-based group.
Seebacher et al, 2019⁴¹ (Austria)	Evaluate the effects of music and verbal-cued motor imagery on walking, fatigue, and QoL.	RCT	Music-cued motor imagery or motor imagery	Primary: Walking speed and distance Secondary: Walking perception, fatigue, QoL, and sensorimotor synchronization	All three interventions significantly improved walking speed and distance. Physical, cognitive, and total fatigue and QoL significantly improved only after music- and verbally-cued MI. Synchronization improved more with music and verbal MI and music MI and worsened with just MI.
Thaut et al, 2008⁴² (United States)	To investigate whether a musical template would influence verbal learning and memory performance.	RCT	Spoken word	Primary: Learning and remembering word sequences	Differences in learning performance between verbal and musical condition for the higher word order sequences (3–7 words) were all highly significant, 3 words: t(18) = 4.32, p = 0.0004; 4 words: t(18) = 4.27, p = 0.0004; 5 words: t(18) = 4.08, p = 0.0007; 6 words: t(18) = 3.89, p = 0.001; 7 words: t(18) = 2.40, p = 0.027.
Thaut et al, 2014⁴³ (United States/Germany)	Investigate whether music improves verbal learning and memory and understand the impact on system-level brain plasticity.	RCT	Spoken word	Primary: Learning, memory, brain activity with oscillatory network synchronization	The music condition had significantly more improvement in word order memory and recall (p = 0.038) and bilateral frontal alpha learning-related synchronization (p = 0.05) than the spoken condition.
VanGeel et al, 2020(Belgium)	To investigate whether an individual choreography-based dance intervention affects fatigue, physical and cognitive capacities, and sensory function.	Controlled pilot trial	Art group (painting, music, spoken word, photography, or videography)	Primary: Motor and cognitive fatigue Secondary: Walking endurance, ability, speed, balance, strength, and manual dexterity; Sensory function; cognitive capacity, dual-task performance, QoL, leg temporal/spatial performance	There were no significant differences between the DG and AG but the within analysis for both groups showed improvements in multiple domains. Both groups had significantly less fatigue (DG p = 0.034, AG p = 0.005). The DG showed significant improvements in strength (p = 0.043), balance (p = 0.043), walking (p = 0.046), and dexterity (p = 0.018).
Young et al, 2019⁴⁵ (United States)	To understand the effect of movement-to-music (M2M) and adapted yoga on physical and psychosocial outcomes.	Three-arm RCT	Biweekly newsletters via mail that contained educational information on living with MS	Primary: Mobility and balance, walking endurance, and lower extremity functional strength Secondary: Changes in self-reported scores for fatigue and pain	The between-group improvements in mobility and balance were statistically significant (F _2,57 = 3.7; p = 0.03). M2M strength is significantly lower compared with control post-intervention (last squared means [LSM] difference [95% CI]=−1.9s [−3.3 to −0.5], p = 0.01, d = 0.7). There was a significant increase in walking distance (when accounting for patient determined disease steps scale) in the M2M group compared with the control (LSM difference [95% CI]) = 41.0m [2.2–80.0], p = 0.04, d = 0.6).

AG, art group; DG, dance group; EG, experimental group; MI, motor imagery; QoL, quality of life; RCT, randomized controlled trial.

Intervention characteristics

Many studies in this review (n = 9) implemented music interventions to improve motor neurological outcomes such as gait, strength, spasticity, balance, and motor-auditory synchronization. Furthermore, 11 studies evaluated an intervention that used receptive musical engagement, such as music listening with or without activity. The length of interventions ranged from a single session to 60 min, 3 days a week for 12 weeks. Most session lengths were unique, yet five studies delivered the music-based intervention in only one session. Most interventions were delivered in the health facility or community center (n = 11), and only three were delivered within the participant’s home. The interventions were primarily delivered by research team members (n = 9). The remaining interventions were self-administered or delivered by a music therapist. More intervention characteristics are described in Table 3.

Table 3.

Music Intervention Components

First author, date	Intervention description	Music details	Delivery location	Facilitator	Intervention length
Baştürk et al, 2024⁴⁶	Line dancing program	The selection of music was preferred by the participants among the low-tempo instrumental music list suitable for mild aerobic activity	Not indicated	Physiotherapist	60 min/day, 2 days/week × 4 weeks
Conklyn et al., 2010³²	Home-based walking program listening to music.	MP3 player: songs whose tempo was 10% above the participant’s spontaneous cadence	Home	Self	20 min/day × 2 weeks
Gatti et al., 2015³³	Musical keyboard playing	Numbered colored adhesive labels were applied to the keys to cue the participants which key to press, and with which finger. The sequence of finger movements was defined by a professional musician and displayed on a sheet in front of the participant. Forty-six exercises of growing difficulty were prepared.	Health Facility	Physiotherapist	30 min/day, 5days/week × 3 weeks
Impellizzeri et al., 2020³⁴	Cognitive rehabilitation plus Neurological Music Therapy	Two NMT techniques were used: the Associative Mood and Memory Training and the Music in Psychosocial Training and Counseling. Sessions included guided music listening, musical role-playing, expressive improvisation or singing, and composition exercises.	Health Facility	Music Therapist	60 min × 3 days/week × 8 weeks
Maggio et al., 2021³⁵	Music listening while walking on treadmill	Gait Trainer 3 has integrated rhythmic auditory stimulation using music, rhythms and visual feedback. A sound library, created by music therapists, contains different metronome sounds and music. The music/metronome can be adapted to participants’ pace and complexity potential. The visual feedback analyzes gait quality (step-length, weight bearing on each leg) on an LCD display so that participants can monitor gait pattern.	Health Facility	Physiotherapist	30 min/day, 3 days/week × 8 weeks
Moore et al., 2008³⁶	Music as mnemonic device	Participants in the experimental group heard the word lists in a song format and were asked to sing back as much of the song and words as they could remember. The song was composed and performed by an adult female and was based on the song Skip to My Lou.	Health Facility	Research team	One-time delivery
Moumdjian et al., 2019	Walking to music and metronome	Participants walked to 6 tempi in music and metronome conditions. The experimental tempi were 0%, 2%, 4%, 6%, 8%, and 10% of the participant’s preferred walking cadence.	Health Facility	Research team	One-time delivery
Moumdjian et al., 2022³⁸	Embodied Learning Protocol	Participants were presented with a sequence of seven tiles and asked to perform the sequence by stepping on the tiles. Three different feedback modalities were used: melodic, sound, and visual. For the melody, each row of tiles was mapped to a different note. Upon stepping on a tile correctly, the corresponding mapped note was heard. An incorrect tile was heard through a pitch bend of the mapped note. For sound feedback, tiles were mapped to one-single note. Upon stepping on a tile correctly, the note was heard. An incorrect step was heard through a pitch bend of the correct note. For visual feedback, a correct step was indicated by the tile lighting up in green, and an incorrect step was indicated by tile lighting up in red.	Health Facility	Research team	One-time delivery
Schmid et al., 2004³⁹	Active Music Therapy	Active Music Therapy—−3 blocks of music therapy in single sessions both active and receptive depending on preference.	Health Facility	Music Therapist	8–10 sessions over 1 year
Seebacher et al., 2017⁴⁰	Motor imagery with music or metronome rhythmic auditory cueing	The music consisted of motivating instrumental music with melodies and harmony. Rhythmic cueing for the music group was in 2/4 or 4/4 meter with every first beat or every first and third beat being emphasized. The same procedure was applied for the metronome audio mix. Four similar mixes were on one CD and changed weekly.	Home	Self	17 min/day, 6 days/week × 4 weeks
Seebacher et al., 2019⁴¹	Motor imagery with rhythmic auditory cueing	Music and verbal-cued motor imagery, music-cued motor imagery, and noncued motor imagery. The musical selection described above (Seebacher et al., 2017⁴⁰) was utilized in this intervention. There was a weekly change of the audio mix to facilitate adherence and attention.	Home	Self	17 min/day × 6 days/week × 4 weeks
Thaut et al., 2008⁴²	Musical template to facilitate word learning and memory	The Auditory Verbal Learning Test was prerecorded and recorded voice responses in soundproofed booths. A single list of 15 words was repeated in 10 trials and the participant was asked to freely recall after each trial. The sung and spoken lists were the same and sung by the same female vocalist. One-syllable words were assigned one-quarter note of a 1 sec duration, the two-syllable words were assigned one-eighth note of 0.5 sec per syllable. An originally composed melody was used so participants were not familiar with the music.	Health Facility	Research team	One-time delivery
Thaut et al., 2014⁴³	Musical template to facilitate word learning and memory	The intervention details for this study are described above (Thaut et al., 2008⁴²).	Health Facility	Research team	One-time delivery
VanGeel et al., 2020	Dance Group vs. Art Group	Participants were taught three different choreographies that increased in rhythm and difficulty. These choreographies targeted (1) proprioceptive function, stretching, abdominal muscle strength, coordination, and working memory; (2) inhibition ability; and (3) speed, coordination, and dual tasking.	Community Center	Research Team	90-min class × 2 days/week × 10 weeks
Young et al., 2019⁴⁵	Movement to Music (M2M) vs. adapted yoga	M2M incorporated multiple movement routines accompanied by music. Every routine specifically targeted a fitness component, with the movements and tempo adapted to participants’ functional level.	Fitness facility	Self	60-min session × 3 days/week × 12 weeks

CD, compact disc; LCD, liquid crystal display; NMT, neurological music therapy.

Interventions to improve motor neurological outcomes

Most motor neurological music interventions focused on improving gait.^{32,35,37,38,41,45} Within the gait-driven interventions, rhythmic auditory stimulation (RAS), allowing for entrainment between the motor rhythm (recurrent footsteps) and auditory rhythm (recurrent beats or pulses), was most evaluated. RAS was operationalized in a variety of ways. Conklyn et al.³² had participants listen to songs that had a tempo 10% above the participant’s spontaneous cadence. Maggio et al.³⁵ used a sound library created by music therapists that contained different metronome sounds and music that was adapted to the participant’s current and potential pace and then integrated the music with visual feedback to help the participant monitor their gait. Moumdjian et al.³⁸ evaluated walking to music and metronome at increasing tempos (0%, 2%, 4%, 6%, 8%, and 10% of the participant’s regular walking cadence), while Seebacher et al.^40,41 examined home-based music-cued motor imagery using motivating instrumental music with melodies and harmonies.

Other interventions targeting neurological motor outcomes were a “Movement to Music” intervention that incorporated multiple movement routines that targeted specific fitness components and were tailored to a tempo that matched the participant’s functional level,⁴⁵ a choreography-based dance therapy class implementing three different choreographies that increased in rhythm and difficulty,⁴⁴ and musical keyboard exercises to improve hand dexterity and function.³³

Interventions to improve nonmotor neurological outcomes

The nonmotor neurological interventions aimed to improve cognitive impairment, cognitive fatigue, and psychosocial well-being. Three of the five interventions in this category were delivered in a single session. The single-session interventions utilized music as a mnemonic device to improve memory outcomes on the Auditory-Verbal Learning Test. However, different approaches to this technique were examined. For example, Moore et al.³⁶ delivered the memory words to participants sung to the familiar song, “Skip to My Lou.” In comparison, Thaut et al.^42,43 had the 15 words from a memory test sung to participants in an originally composed melody that was unfamiliar to participants.

Two other studies evaluated the use of music therapy to improve cognition, mood, and quality of life. Impellizzeri et al.³⁴ used two different neurological music therapy techniques, “Associative Mood and Memory Training” and “Music in Psychosocial Training and Counseling.” Sessions included guided music listening, musical role-playing, expressive improvisation or singing, and composition exercises. Schmid et al.³⁹ implemented active music therapy, which involved participants and therapists actively engaging in music with instruments and singing. Participants also had the choice not to actively engage and instead listen to the music played by the therapist.

Interventions to improve both motor and nonmotor neurological outcomes

Two studies evaluated an intervention developed to improve both motor (gait/balance) and nonmotor (cognition/mood/quality of life) primary outcomes.^36,46 In Moumdjian et al.,³⁸ participants were asked to step on seven different tiles presented in a specific sequence. Further, three different feedback modalities (melodic, sound, and visual) were used while the participants stepped on the tiles. Once they could correctly perform the sequence three times in a row, they were given a 3-min break. After the break, participants were asked to repeat the learned sequence three times in a row. Once successful, they were shown a distractor sequence, asked to perform the distractor twice, and then asked to perform the originally learned sequence immediately and 15 min later. Baştürk et al.⁴⁶ implemented one-on-one line dancing which includes a warm-up, line dancing, cool-down, and breaks as needed, under the supervision of an experienced physiotherapist. The dance routine was designed to improve balance, posture, and gait, and was taught progressively to manage fatigue. Sessions involved practicing individual steps, and then integrating them into a complete choreography set to music. Exercise intensity was adjusted based on heart rate and participant fatigue.

Intervention outcomes

Most of the studies had small sample sizes (≤40; n = 9), which may have resulted in underpowered studies impacting the evaluation of intervention efficacy. A summary of the most common outcome measures used, and a notation of statistically significant change (improvement, deterioration, or no change) was organized by active versus receptive musical engagement and displayed in Table 4.

Table 4.

Motor and Nonmotor Neurological Outcomes

			Motor neurological outcomes					Nonmotor neurological outcomes
	Control group	Quality appraisal	Dexterity	Gait/walk	Balance	Strength	Physical functioning	Cognitive functioning	Cognitive fatigue	Physical fatigue	Mood	QoL	Depression	Anxiety
Active music engagement (singing or instrument playing)
Gatti et al., 2015³³	'AC	Good	↑^§			↑^§	↑*
Moore et al., 2008³⁶	AC	Fair						—
Thaut et al., 2008⁴²	AC	Good						↑^*
Thaut et al., 2014⁴³	AC	Fair						↑^*
Receptive Music Engagement (Music Listening With or Without Activity)
Baştürk et al., 2024⁴⁶	Yes	Good			↑^*							↑^*	—	↑^*
Conklyn et al., 2010³²	Yes	Fair		↑^*
Maggio et al., 2021³⁵	Yes	Fair		↑^§	↑^§						↑^*	↑^§	↑^§
Moumdjian et al., 2019	HC	Fair		↑^*					↑^*	↑^*
Moumdjian et al., 2022³⁸	HC	Fair		↑^*				—	↑^*	↑^*			↑^*	—
Seebacher et al., 2017⁴⁰	AC	Good		↑^*					↑^*	↑^§		↑^*
Seebacher et al., 2019⁴¹	AC	Good		↑^*					—	↑^*
VanGeel et al., 2020	AC	Fair	↑^§	↑^§	↑^§	↑^§		↑^§		↑^§		↑^§
Young et al., 2019⁴⁵	AC	Good		↑^*	↑^*					—	↑^§	↑^§
Combination
Impellizzeri et al., 2020³⁴	AC	Good						↑^§				↑^§	↑^§
Schmid et al., 2004³⁹	Yes	Fair					—	—				—	↑^§	↑^§

AC, active control; HC, healthy control.

↑Significant improvement; –No significant change; ↓Significant deterioration; *Between group improvements; §Experimental group improvements.

Motor neurological outcomes

A total of 11 studies evaluated motor neurological outcomes such as gait, dexterity, and balance.^{32,33,35,37,38,40,41,43,45,46} Eight of these 11 studies showed significant between-group improvements.^{32,33,37,38,40,41,45,46} Overall, gait was the most frequently tested (n = 8)^{32,35,37,38,40,41,45} and improved outcome (n = 6).^{32,37,38,40,41,45} A variety of gait parameters were measured including the 6-min walk test (n = 4), the timed up and go test (n = 2), the 5 times sit-to-stand test (n = 2), the timed 25 ft walk test (n = 5), the spatiotemporal gait parameters (n = 2), and auditory-motor coupling synchronization (n = 1). Other improved outcomes were dexterity,^33,44 balance,^35,44
–46 physical functioning,³³ and strength.^33,44

Receptive music listening paired with walking was the most common music application and showed the most significant gains, with six out of eight studies showing between-group improvements (gait and balance).^{32,37,38,40,41,45} The other two studies evaluating dance and movement-to-music interventions showed significant improvements in gait and balance within the groups, but no significant differences between the groups.^35,44 Overall, only 4 of the 10 studies reported effect sizes to help evaluate the potential impact and clinical effect on gait parameters. Effect sizes were given for timed up and go test (d = 0.7),⁴⁵ timed 25 ft walk test (η² ranged from 0.143 to 0.581; d = 0.59),^32,40,41 and the 6-min walk test (η² ranged from 0.112 to 0.596; d = 0.6).^40,41,45

Nonmotor neurological outcomes

Eight of the 13 studies that evaluated nonmotor neurological outcomes showed significant between-group improvements.^{35,37,38,40

–43} Overall, cognitive functioning, physical fatigue, and quality of life were the most tested outcomes. The most improved outcomes were cognitive fatigue (75%)^37,38,40 and physical fatigue (50%).^37,38,41 Quality of life was measured in seven studies; however, between-group improvements were seen in only two studies.^40,46 Similarly, cognitive function was evaluated in seven studies, yet only two studies found between-group improvements.^42,43 Only one of the five studies that evaluated the impact of interventions on depression showed improvement.³⁸ Despite the lack of statistical significance, a large effect size (d = 0.83) was observed in the post-intervention scores in one study.⁴⁶

There was heterogeneity among the instruments used to measure many of the nonmotor neurological outcomes. Specifically, five different instruments were used to measure the quality of life (MS Impact Scale, Short-Form Health Survey [SF-36], Euro-5D-3L, MS Quality of Life, and the Hamburg Quality of Life Questionnaire in MS), four instruments to measure physical fatigue (PROMIS Short-Form 8a, Modified Fatigue Impact Scale, Fatigue Severity Scale, and a visual analog rating scale), three different instruments were used to measure cognitive functioning (Brief Repeatable Battery of Neuropsychological Tests in MS, Rey’s Auditory-Verbal Learning Test, and a description of cognitive performance during an experimental task), and two instruments to measure cognitive fatigue (cognitive fatigability index taken from the Paced Auditory Serial Addition Test and a visual analog rating scale).

Active and receptive musical engagement

Six of the 14 studies evaluated at least partial active musical engagement.^{33,34,36,39,41,43} Half of the six studies evaluated using a musical instrument,^33,34,39 and the other half used singing to remember words during neuropsychological testing.^36,42,43 This form of engagement was only implemented once and occurred during the testing period. Memory improved in two of the studies.^42,43 Alternatively, the three studies that utilized partial or complete musical instrument engagement were delivered over 8–24 sessions. Only one study evaluating keyboard playing showed significant between-group improvements (physical functioning).³³

The other nine studies implemented receptive musical engagement.^{32,35,37,38,40,41,44
–46} All the interventions included physical activity such as music with movement,^40,41,45 walking,^32,35,37 dancing,^44,46 and stepping.³⁸ While two studies^37,38 implemented the intervention once, seven studies delivered multiple sessions at least 2 weeks and up to 12 weeks. Gait improved in all eight studies assessed after the intervention, with six of these studies showing significant between-group improvements.

Safety and adverse events

Six studies^{32,34,38,40,41,44} reported safety and adverse events data. No participants were harmed in the studies, and if a participant could not perform one of the tests because of safety concerns, data were not collected. Two studies reported falls. Seebacher et al. noted that one participant fell without being injured and after a short break the participant was able to repeat the test twice without falling.⁴⁰ Conklyn et al. reported that one fall occurred during the entire duration of the study, but it was not during the intervention.³²

Risk of bias and quality assessment

Using the NIH Quality Assessment Tool of Controlled Intervention Studies, 15 studies were reviewed for study quality (Table 5).³⁰ A total of 14 questions were answered to evaluate the potential for bias. Overall ratings of poor (0–4 out of 14 questions), fair (5–9 out of 14 questions), or good (10–14 out of 14 questions) were assessed. The methodological quality was assessed as fair or good for all the studies in the review. There were several strengths of the studies, including low dropout rates (n = 14), use of valid and reliable study measures (n = 15), a priori specification of outcomes and groups (n = 15), and all randomized controlled trials used intention-to-treat analysis. Limitations of the studies included small sample sizes (range = 10–40, n = 9), lack of blinding of participants and interventionists (n = 15), lack of blinding researchers to participant group assignment (n = 11), and lack of reporting sufficient sample size to detect a difference in outcomes (n = 12).

Table 5.

Quality Appraisal

Study (1st author et al, date)	Was the study described as randomized, a randomized trial, a randomized clinical trial, or an RCT?	Was the method of randomization adequate (i.e., use of randomly generated assignment)?	Was the treatment allocation concealed (so that assignments could not be predicted)?	Were study participants and providers blinded to treatment group assignment?	Were the people assessing the outcomes blinded to the participants’ group assignments?	Were the groups similar at baseline on important characteristics that could affect outcomes (e.g., demographics, risk factors, co-morbid conditions)?	Was the overall drop-out rate from the study at endpoint 20% or lower of the number allocated to treatment?	Was the differential drop-out rate (between treatment groups) at endpoint 15 percentage points or lower?	Was there high adherence to the intervention protocols for each treatment group?	Were other interventions avoided or similar in the groups (e.g., similar background treatments)?	Were outcomes assessed using valid and reliable measures, implemented consistently across all study participants?	Did the authors report that the sample size was sufficiently large to be able to detect a difference in the main outcome between groups with at least 80% power?	Were outcomes reported or subgroups analyzed prespecified (i.e., identified before analyses were conducted)?	Were all randomized participants analyzed in the group to which they were originally assigned, i.e., did they use an intention-to-treat analysis?	Summary quality
Baştürk et al., 2024⁴⁶	✓	✓	✓	✗	✓	✓	✗	✓	✓	✓	✓	✓	✓	✓	Good
Conklyn et al., 2010³²	✓	✗	✗	✗	CD	✓	✓	✓	✓	CD	✓	✓	✓	✓	Fair
Gatti et al., 2015³³	✓	✓	✓	✗	CD	✓	✓	✓	✓	CD	✓	✓	✓	✓	Good
Impellizzeri et al., 2020³⁴	✓	✓	✓	✗	✓	✓	✓	✓	✓	CD	✓	✓	✓	✓	Good
Maggio et al., 2021³⁵	✗	NA	✗	✗	CD	✓	✓	✓	✓	CD	✓	✓	✓	NA	Fair
Moore et al., 2008³⁶	✓	✓	✗	✗	CD	✓	✓	✓	✓	CD	✓	✓	✓	✓	Fair
Moumdjian et al., 2019	✗	✓	✗	✗	✗	✗	✓	✓	✓	CD	✓	✓	✓	NA	Fair
Moumdjian et al., 2022³⁸	✗	✓	✗	✗	✗	✗	✓	✓	✓	CD	✓	✓	✓	NA	Fair
Schmid et al., 2004³⁹	✗	NA	✗	✗	✗	✓	✓	✓	✓	CD	✓	✓	✓	NA	Fair
Seebacher et al., 2017⁴⁰	✓	✓	✓	✗	CD	✓	✓	✓	✓	CD	✓	✓	✓	✓	Good
Seebacher et al., 2019⁴¹	✓	✓	✓	✗	CD	✗	✓	✓	✓	CD	✓	✓	✓	✓	Good
Thaut et al., 2008⁴²	✓	✓	CD	✗	✓	✓	✓	✓	✓	CD	✓	✓	✓	✓	Good
Thaut et al., 2014⁴³	✓	✓	CD	✗	CD	✓	✓	✓	✓	CD	✓	✓	✓	✓	Fair
VanGeel et al., 2020	✗	NA	✗	✗	CD	✗	✓	✓	✓	CD	✓	✓	✓	NA	Fair
Young et al., 2019⁴⁵	✓	✓	✓	✗	✓	✓	✓	✓	✓	CD	✓	✓	✓	✓	Good

CD, cannot determine; NA, not applicable; NR, not reported.

Quality was rated poor (0–4 out of 14 questions), fair (5–9 out of 14 questions), or good (10–14 out of 14 questions).

Discussion

The purpose of this systematic review was to identify and synthesize evidence on the effectiveness of music interventions for people living with MS. Specifically, this review sought to delineate the differences between active and receptive music interventions on motor and nonmotor neurological outcomes. The review included 15 studies published over 22 years and predominantly conducted in Europe and North America. The studies varied in design, sample size, intervention type, and outcome measures, which allowed for a comprehensive evaluation of the current evidence on music interventions in MS yet limited the ability to compare the findings directly.

Over half of the interventions used receptive music engagement to improve gait parameters. Three of these studies had a healthy or active control group (i.e., adapted yoga, metronome, and noncued or verbally cued motor imagery).^37,40,41 In these studies, all groups improved gait, but the music arms were superior because physical fatigue also improved. Exercise interventions have been shown to improve physical and cognitive outcomes in PwMS.^47,48 However, participation in physical activity is lower in PwMS compared with the general population.⁴⁹ High levels of physical fatigue are a barrier affecting physical activity levels.⁵⁰ One explanation for this difference is that music is a natural motivator and provides a distraction. Further, by engaging the rhythmic auditory system, physical activity may require less perceived effort. Numerous studies have shown that listening to music can improve mood, motivation, arousal, and perceived effort.⁵¹ This finding has potentially high clinical relevance, may fill a significant gap in improving gait and physical function in PwMS, and warrants further research.

In contrast to motor outcomes, the impact of music interventions on nonmotor neurological domains varied across studies. Improvements in mood and quality of life were less consistently observed across studies, suggesting that although music interventions may influence these domains positively, the effects may vary based on intervention type and participant characteristics. Receptive and active music interventions demonstrated positive effects on cognitive functioning, albeit with varying degrees of improvement compared with active controls. Although most music intervention arms improved, there was no difference compared with the active control. Notably, these interventions were limited in frequency and duration compared with receptive music interventions. For example, Thaut et al.^42,43 used sung words compared with spoken words to improve verbal memory, but active music engagement only occurred during the testing. Clinically, these findings suggest that music interventions can potentially enhance cognitive abilities in individuals with MS, but more research is needed to examine the effect of music-based interventions on cognition.

Similar gaps exist in the research examining the use of music interventions in other neurological conditions that cause cognitive impairment.⁵² A recent scoping review found that playing a musical instrument correlated with positive cognitive abilities in older adults.⁵³ Playing a musical instrument involves intricate coordination and communication between multiple sensory systems (visual, auditory, tactile) and motor functions.^54,55 As one visually looks at notes and translates them into physical actions, they simultaneously receive feedback from the auditory system to correct specific fine motor functions or keep the current status. The ability to engage these systems and coordinate motor, sensory, and cognitive domains to create audible, logical, and accurate sound may induce new cortical pathways and rewiring, inducing neuroplasticity.²⁴ This rewiring in the brain created by repeated musical practice may create alternate pathways and structures that may help PwMS compensate for deficits caused by the demyelinating disease. Overall, a significant gap exists in examining the use of music interventions to improve cognition for PwMS. More research is needed to understand the application to daily living and the long-lasting effects on day-to-day cognitive impairment.

This systematic review identified substantial variability in intervention characteristics, including the type and duration of music interventions. Interventions ranged from simple music listening sessions to more complex activities such as learning words sung to melodies or engaging in musical instrument play. This variability highlights the versatility of music as a therapeutic tool in addressing a wide range of impairments associated with MS. However, most interventions were delivered in clinical settings rather than at home, potentially limiting accessibility for individuals with mobility challenges. Future studies should explore the feasibility and efficacy of home-based music interventions to enhance adherence and long-term engagement among patients with MS.

Limitations

Several limitations of the systematic review should be noted, including the heterogeneity of control groups and outcomes as well as small sample sizes that caused many studies to be underpowered. This variability complicates direct comparisons between studies and limits the generalizability of findings. Additionally, the review was limited to studies published in English, potentially introducing language bias, and only included published studies, which may introduce publication bias.

Conclusion

While the potential of music-based interventions in improving both motor and nonmotor outcomes in individuals with MS is promising, the evidence base is still in its early stages. The adaptability of music interventions, whether through active engagement like playing instruments or receptive engagement like listening to music, allows for personalized approaches tailored to individual patient needs and preferences. This systematic review underscores the need for larger-scale studies with rigorous methodologies to establish the efficacy, optimal delivery methods, and long-term effects of music interventions in MS. Future research should explore the impact of active music engagement on mood and cognitive function, evaluate home-based interventions, and investigate the neuroplastic effects of music-making activities. By addressing these gaps, researchers and clinicians can advance rehabilitation strategies that enhance the quality of life and functional outcomes for people living with MS.

Footnotes

Authors’ Contributions

C.P.: Conceptualization, methodology, formal analysis, and writing—original draft; J.K.: Formal analysis and writing—review and editing; A.G.: Formal analysis; A.M.S.: Writing—review and editing.

Data Availability

Data collection forms, data extracted from included studies, and data used analysis are available upon request.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This study did not receive funding.

Supplementary Material

Supplementary Data S1

Supplementary Data S2

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