Development and evaluation of a novel music-based therapeutic device for upper extremity movement training: A pre-clinical, single-arm trial.

Restoration of upper limb motor function and patient functional independence are crucial treatment targets in neurological rehabilitation. Growing evidence indicates that music-based intervention is a promising therapeutic approach for the restoration of upper extremity functional abilities in neurologic conditions such as cerebral palsy, stroke, and Parkinson's Disease. In this context, music technology may be particularly useful to increase the availability and accessibility of music-based therapy and assist therapists in the implementation and assessment of targeted therapeutic goals. In the present study, we conducted a pre-clinical, single-arm trial to evaluate a novel music-based therapeutic device (SONATA) for upper limb extremity movement training. The device consists of a graphical user interface generated by a single-board computer displayed on a 32" touchscreen with built-in speakers controlled wirelessly by a computer tablet. The system includes two operational modes that allow users to play musical melodies on a virtual keyboard or draw figures/shapes whereby every action input results in controllable sensory feedback. Four motor tasks involving hand/finger movement were performed with 21 healthy individuals (13 males, aged 26.4 ± 3.5 years) to evaluate the device's operational modes and main features. The results of the functional tests suggest that the device is a reliable system to present pre-defined sequences of audiovisual stimuli and shapes and to record response and movement data. This preliminary study also suggests that the device is feasible and adequate for use with healthy individuals. These findings open new avenues for future clinical research to further investigate the feasibility and usability of the SONATA as a tool for upper extremity motor function training in neurological rehabilitation. Directions for future clinical research are discussed.

Introduction

Effective use of the arm and hand to reach, grasp, release, and manipulate objects is often compromised in individuals with neurologic disorders such as cerebral palsy [1], stroke [2, 3], Parkinson’s Disease [4, 5], among others. Impairments of upper extremity function include reduced muscle power, sensory loss, increased muscle spasticity, and lack of motor control [1, 6–8], resulting in significant long-term functional deficits with relevant impact on patients’ activities of daily living, independence, and quality of life [9-12]. Therefore, improving upper limb functional abilities and promoting functional independence are crucial treatment targets for neurological rehabilitation.

Functional restoration of the upper extremity is thought to be achieved through a combination of neurophysiological and learning-dependent processes that involve targeted training to restore, substitute, and compensate the weakened functions [13, 14]. Frequently reported neurorehabilitation approaches for upper limb movement in cerebral palsy [15, 16], stroke [13, 17], and Parkinson’s Disease [18, 19] include standard treatment methods such as general physiotherapy (i.e., muscle strengthening and stretching), constraint-induced movement therapy and bimanual training, as well as technology-based approaches (i.e., virtual reality, games, and robot-assisted training) [20-26] and music-based interventions [27-29].

There is growing evidence that music-based interventions are a promising therapeutic approach for the restoration of upper extremity functional abilities in neurologic conditions including stroke [30, 31], cerebral palsy [32], and Parkinson’s Disease [28, 33]. For instance, there is extensive research on the effectiveness of therapeutic techniques such as Music-supported Therapy and Therapeutic Instrumental Music Performance in rehabilitating arm paresis after stroke through musical instrument playing [30, 34–40]. Similarly, active musical instrument playing (i.e., piano) also seems to improve manual dexterity and finger and hand motor function in individuals with cerebral palsy [32, 41–43]. Furthermore, consistent evidence indicates that interventions using rhythmic auditory cues or rhythmically-enhanced music are effective to increase muscle activation symmetry [44], improve range of motion and isometric strength [45], enhance spatiotemporal motor control [46], and decrease compensatory reaching movements [44].

Music-based movement rehabilitation for upper limb training is particularly interesting because playing a musical instrument provides real-time multisensory information that enhances online motor error-correction mechanisms and supplements possible perceptual deficits [47-49]. Research has also shown that the engagement of multisensory and motor networks during active music playing promotes neuroplastic changes in functional networks and structural components of the brain, which are crucial neurophysiological processes for neurologic recovery [50-53]. In addition, there is robust evidence that the use of metronome or beat-enhanced music is important to support movement training as the continuous-time reference provided by the rhythmic cues allow for movement anticipation and motor preparation, bypassing the movement timing dysfunction through the activation of alternate or spared neural pathways [33, 54]. Finally, emotional-motivational aspects of music-making also play a significant role in the rehabilitating effects of music-based intervention through music-induced changes in mood, arousal, and motivation [27, 55], with potential effects on perceived physical endurance and fatigue [30, 56].

Traditionally, music-based interventions for the rehabilitation of upper extremity generally involve the use of acoustic musical instruments such as guitar, piano, and pitched and non-pitched percussive instruments [38, 42]. However, traditional instruments can impose limitations for those with significant cognitive or physical impairments as they require more resistance to press a key or to move a string and are less adaptable to the patient’s needs. Recently, studies have acknowledged the relevance of music technology to increase the availability and accessibility of music-based therapy for patients with neurological disorders in different settings, including hospitals, communities, and home environment [57-60]. For example, the use of programmable devices can help patients to exercise independently in addition to scheduled caregiver-guided sessions, thus increasing treatment intensity [58]. Digital music and sound devices can provide enhanced auditory feedback to kinematic movement components such as velocity and acceleration, range of motion, joint angles, spatial and temporal limb trajectories, even in stages of limited physical movement capability [57]. Additionally, technology may assist therapists in the implementation of individual therapeutic goals and provide immediate assessment of measurable changes with objective outcome measures (e.g., total movement time, movement variability, force, inter-response interval).

The introduction of music technology with the use of digital musical instruments, such as keyboards and drum pads [30, 38] and, more recently, touchscreen devices (e.g. tablets) using commercially available music software [40, 61, 62], have provided novel approaches for the application of active musical instrument playing in the rehabilitation of upper extremity motor function. For instance, electronic keyboards and digital sound surfaces enable users with complex needs the possibility to play a musical instrument in an adapted form to train fine and gross movements of the paretic extremity [30, 38]. However, the therapeutic sessions are commonly provided by a therapist at a rehabilitation center or hospital, thus limiting its availability for additional and independent at-home-practice. The use of mobile tablets in music therapy has notable advantages in this regard, as they provide affordable, accessible, and portable alternatives to digital music instruments. However, there is a lack of hardware and software developed specifically for clinical practice, and the use of touchscreen devices in music therapy is often limited by resources developed for the wider consumer market [63]. Therefore, there is a clear need for the development of new technology to address this important gap in music-based neurologic rehabilitation. In light of this need, a novel music-based therapeutic device for upper extremity movement training was developed with the ultimate goal to improve upper extremity motor function, to increase independent patient engagement, to enhance treatment quality, intensity, and compliance, and to assist therapists during treatment implementation and assessment.

The objective of this study is to describe a novel music-based therapeutic device called SONATA and to conduct a pre-clinical, single-arm trial to test the device with healthy individuals. For this purpose, four motor tasks requiring finger and hand movements were implemented in a convenience sample of healthy participants to examine the system’s operational modes, which allow users to play musical melodies on a touchscreen keyboard (Tasks 1–3) or draw figures/shapes (Task 4), and to assess the reliability of the device’s main features such as the presentation of sequences of audiovisual stimuli at a pre-defined order and record response and movement data (e.g., reaction time, correct/incorrect responses, inter-response interval). Specifically, Tasks 1 to 3 are adaptations of motor sequence learning tasks that have been previously used in research and/or clinical practice [34, 38, 64, 65] and involve the presentation of melodies that vary in length, tempo, and complexity that are reproduced by the participant by pressing different keys represented by squares displayed on the device’s touchscreen. Such tasks are often implemented in active music playing therapy to train finger dexterity, range of mobility, functional hand movements, spatial-temporal control, and limb coordination [34, 37, 39, 45, 51]. In addition, training of finger movements involving tracking a target or tracing a line on a computer screen is commonly implemented in motor rehabilitation to improve spatial-temporal control and fine motor skills of the paretic hand [66-68]. However, finger tracking training is not usually implemented in music-based interventions due to limitations imposed by the structure of the majority of acoustic musical instruments. Therefore, Task 4 is an example of an exercise for spatial accuracy training of continuous motions via sonification, whereby the position and movement of the finger are captured in real-time and transformed into different sounds.

Materials and methods

The experimental procedures conformed with the Declaration of Helsinki and were approved by the Local Ethics Committee of the Faculty of Psychology and Movement Science of the Universität Hamburg. All participants were fully informed about the nature of the study and provided written informed consent to participate. The individual in this manuscript has given written informed consent (as outlined in PLOS consent form) to publish these case details (Fig 4).

Fig 4

Device in use during the evaluation procedures.

The individual in this manuscript has given written informed consent (as outlined in PLOS consent form) to publish this photograph.

Device hardware and software

The Sonification Arm Training Apparatus (SONATA) consists of a custom-made graphical user interface generated by a single-board plugged-in computer (Raspberry Pi 2 B with HiFiBerry) displayed on a 32” touchscreen (iiyama ProLite T3234MSC-B3X; visible screen size: 698.4 x 392.8 mm; resolution: 1920 x 1080 pixels, pixel spacing: 0.364 x 0.364 mm) with built-in speakers and controlled wirelessly via Wi-Fi by a battery-powered computer tablet (Acer One 10) (Fig 1). The hardware and software of the system have been designed to minimize any latency (≤ 30 ms) between user input and sound output.

Fig 1

Device’s touchscreen, graphic user interface, and controller tablet.

Device design, input and settings

The touchscreen user interface is programmed through a controller tablet to individualize the therapist’s and the patient’s work surfaces. This allows the therapist to use the controller tablet pc to program the graphic and acoustic settings for a new exercise (e.g. screen layout, sound sequences, metronome setting, drawing exercises) while the client performs a different exercise on the SONATA touchscreen interface. The number and the order of the training exercises can also be designed and saved by the therapist in the device’s memory before a training session.

The graphical interface displayed on the controller tablet allows the therapist to choose between two operational modes (keyboard and drawing) and displays two distinct functions: Input and Settings (Figs 2 and 3).

Fig 2

User interface input function for the keys mode (upper panel) and drawing mode (lower panel).

Fig 3

Settings function for the keys mode.

The Keys Mode allows the user/patient to play sound sequences on a touchscreen keyboard by pressing different keys represented by squares displayed on the device’s touchscreen. Each keypress produces a feedback sound that corresponds to a pitch. The default input window presents a 4x8 key matrix (4 rows, 8 keys per row) and each key can be tuned in ascending semitones (from left to right) or in diatonic scales either as a single pitch or as a triadic major or minor chord. To accommodate for less precise reaching motion, the key sizes can be increased and displayed in a 2x4 key matrix. In the input function, the therapist can program and save up to 9 sound sequences by pressing the ‘record’ button and then playing/pressing the sequence of keys in the required order (Fig 2). Additionally, it is possible to repeat the sequence of tones using the loop function and set the metronome tempo in beats per minute (BPM) to which the participant will synchronize their movements. Features such as the loop function and the metronome can be disabled at the discretion of the therapist according to the exercise objectives and the patient’s needs.

The settings function in the Keys Mode (Fig 3) provides additional setup options where the therapist is able to select, for instance, the volume and the instrumental timbre of the feedback sounds (e.g., piano, organ, violin, guitar, trumpet, and saxophone). The sustain function determines the duration (in seconds) that the sound remains present between key presses, and the marker function enables/disables the color-highlighting function of the visual display, where each key of the sequence changes color as it is presented. During the exercise, the predefined sequence of keys is displayed to the patient by turning blue in a cumulative order and simultaneously presenting the corresponding pitch. After the sequence is introduced, the patient then reproduces the sequence of keys in the correct order and in synchrony with the metronome tempo. The device also includes a function where the therapist can determine a temporal window around the metronome tempo in which the patient is required to press the keys. With this metronome interval function, if the keypresses occur outside of the predefined temporal interval, no auditory feedback is provided, thus encouraging the patient to maintain temporal accuracy.

In the Drawing Mode, the spatial accuracy of continuous motions is trained via sonification. The therapist can program up to 9 distinct figures or shapes that are subsequently traced by the patient using his/her finger. The default input window in the drawing mode presents an empty field into which the therapist can draw the figure/shape by touching the screen and moving the finger in the required direction (Fig 2). Along with the movement of the finger on the screen, a continuous sinusoidal tone is presented whereby the pitch is determined by the position of the finger on the screen, with lower tones presented on the lower quadrants and higher tones on the top quadrants of the screen in ascending order from left to right and from bottom to top. Additionally, a visual guide is displayed during the drawing where the yellow line serves as a template indicating the movement trajectory to be performed and the blue frame sets the interval in pixels in which the patient has to move the finger on the screen to train spatial accuracy. During the exercise, the figure is first displayed to the patient at the same velocity and trajectory that were recorded by the therapist, and then the patient reproduces the drawing at their preferred tempo. During the drawing, the patient’s finger movement also produces a sinusoidal feedback sound that changes in pitch depending on the finger’s position on the screen. It is also possible to define an area of spatial accuracy around the figure lines whereby no sound feedback is provided when the finger trajectory is outside of the predefined area.

Data output

Tasks performed on the device automatically generate quantifiable movement data that are captured and stored for further analysis. The registered information about the user’s interaction with the device during the performance of a given task can be used by therapists to assess progression through therapy as well as in empirical research.

The recorded data are stored as text files (American Standard Code for Information Interchange, ASCII) and include general information about the session (date, time, therapist), patient (ID code), and task settings such as the operational mode (keys/drawing), metronome tempo (BPM), inter-stimulus interval (i.e. the time interval between the offset of one stimulus and the onset of next stimulus (ms)), key numbers of the recorded sequence (1 to 32, from bottom left to top right), and inter-response interval (i.e. the time interval between successive keypresses (ms)). Session and patient information are included in the system at the discretion of the therapist while task-related information is derived from the exercise settings as programmed by the therapist. The Keys Mode includes analyzable data such as expected sequence key and patient response key (from 1 to 32), inter-stimulus interval, inter-response interval, and synchronization error (i.e. the phasic relationship between stimulus event and motor response). The output data provided in the Drawing Mode includes position information such as the x- and y-coordinates of the patient input (in pixels, 0 to 1880 and 0 to 1040 respectively), x- and y-coordinates of the nearest target section, and the distance between patient input and the nearest target section. From the data of the Drawing Mode, the speed of the hand/finger movement can also be derived providing a velocity profile of the drawing movement. The recorded information is stored in the controller tablet password-secured internal memory and cannot be transmitted as the device is not connected to a network.

Evaluation procedure

Participants

Functional tests were conducted with 21 healthy individuals (13 males, 8 females) recruited at the Faculty of Psychology and Movement Science at the Universität Hamburg/Germany. Participants were on average 26.4 years old (SD = 3.5, range 21–36 years), 3 of them indicated a preference for the left hand and 18 for the right hand. All participants reported normal hearing, normal or corrected to normal visual acuity, and had no ongoing musculoskeletal injuries and no neurological damage or disorders that could influence normal upper limb movement.

General procedures

Participants were seated in a regular chair in a quiet test room with the SONATA device placed on a table positioned at a comfortable distance in front of them at the wrist level (Fig 4). Stimuli presentation and data collection were implemented with the SONATA device running a built-in custom-made software. Before each task, participants received written instructions and were allowed to practice the tasks. With breaks, the session took approximately 50 minutes to be completed.

Tasks

Task 1: Serial reaction time. The Serial Reaction Time (SRT) task evaluates motor sequence learning whereby participants are required to respond as rapidly as possible to targets (auditory and/or visual stimulus) that are presented either in a repeating order (sequence blocks) or in random order (random blocks) [64, 69–71]. Findings of studies using the SRT task consistently show a decrease in reaction time in the sequence blocks in relation to the blocks where targets are presented in random order, indicating an effect of implicit motor sequence learning [64, 69–71]. Given the robustness of the results reported in SRT studies, this task was implemented to examine some of the device’s main features, such as the presentation of sequences of stimulus at a pre-defined order and the data acquisition of response information including response accuracy and reaction time.

In the present task, the stimuli consisted of visual targets (squares representing different pitches) displayed on a horizontal array of 32 locations presented on the screen (Fig 1). The visual targets were a light grey color. During each experimental trial, one target at a time was presented by turning blue while the corresponding auditory stimulus (piano tone of 1000 ms duration) was simultaneously presented. The target remained on the screen until the correct response was made. The participant’s task was to reach the preferred arm and press the button corresponding to the target as fast and as accurately as possible. Stimuli were presented at a fixed 1-second interval and were divided into separate trials. In the random (R) trials, sequences of stimuli followed an unpredicted order. The random sequences were generated using a random number generator whereby each of the keys corresponded to a number from 1 to 32, starting from the top left (D1) to bottom right (A8). In the sequence trial (S), the same sequence of 12 tones was repeated throughout the task. In total, the task consisted of 8 trials: 4 random trials and 4 repetitions of the sequence trial, following a standard block design (RSRSSRRS).

Task 2: Unimanual sensorimotor synchronization task. The ability to learn new action sequences is known to be affected by task parameters such as sequence length, rate, and complexity [72, 73], as well as by individual differences in working memory capacity [74]. It has been well-documented that this learning ability is significantly impaired in aging [75-77], stroke [78, 79], and neurologic disorders [80].

In standard Music-support Therapy protocols [34], for instance, electronic keyboard and/or drum pads are used to exercise fine and gross movements whereby patients may start playing simple sequences that vary in the number of tones, movement velocity, and limb patients are required to play, which progressively increase in difficulty. Clinical studies indicate that motor improvements can be achieved already during the first training sessions with observable changes in movement velocity, key pressure, and note accuracy [30]. Music-based exercises, such as those requiring finger dexterity using electronic keyboards [34], might be adapted to touchscreen devices [29].

Therefore, the following tasks (unimanual and bimanual sensorimotor synchronization) were implemented to test the utility of the device’s Key Mode and the reliability of the data automatically acquired by the system in tasks that are often implemented in fine motor training. This task evaluated the Keys Mode of the device, which allows the presentation of pre-defined sequences of melodies that are reproduced by the user by reaching the preferred arm to press different keys represented by squares displayed on the device’s screen. For that, participants were presented with 8 distinct pre-defined melodies composed of six to nine tones. Light grey squares representing 32 distinct pitches were displayed on the SONATA screen. During each trial, one note of the melody at the time was presented on the screen by turning blue while the corresponding auditory stimulus (piano tone) was simultaneously presented and remained on the screen cumulatively. Melodies were designed to follow different motion patterns on the screen and differed in relation to sequence length (6–9 tones) and inter-stimulus interval (slow: 66 BPM/910 ms; fast: 80 BPM/750 ms). Participants were instructed to memorize the order of each note of the melody and then reproduce the sequence in the correct order and in synchrony with the metronome using their preferred hand. Each melody was presented only once (total of 8 trials).

Task 3: Bimanual sensorimotor synchronization task. Similar to Task 2, a set of 9 pre-defined melodies composed of seven notes was presented. During each trial, one note of the melody at a time was presented on the screen by turning blue while the corresponding auditory stimulus was simultaneously displayed. Each note of the melody was presented at a fixed tempo (BPM 80/750 ms). The participants’ task was to memorize the order of each note of the melody and reproduce the sequence in the correct order and in synchrony with the metronome. Additionally, participants were instructed to reach the arm and press the target notes appearing on the left side of the screen with the left hand, whereas notes appearing on the right side had to be played with the right hand. Each melody was only presented once, totaling 9 trials.

Task 4: Finger tracking task. Hand and finger functions are often impaired in neurologic disorders such as cerebral palsy [81], stroke [82], and Parkinson’s Disease [83], with a significant impact on tasks that require fine motor control, including drawing and finger tracking [66, 84]. Movement training to enhance hypometria (i.e. lack of motor coordination where movements fail to reach the intended target), slowness of movement (bradykinesia), and weakness are important treatment targets for neurologic rehabilitation [66, 82, 84]. Training of finger movements involving tracking a target on a computer screen with reciprocal extension and flexion of movement of the index finger has been previously applied in motor rehabilitation [66-68], with results suggesting significant improvements in tracking accuracy with transfer of gains to grasp and release function [66].

This functional task was implemented to assess features of the Drawing Mode of the device including movement sonification, the presentation of different target waveforms or shapes, as well as the acquisition of movement data relating to accuracy and time for completion. In this task, participants were instructed to follow two different figures displayed on the screen. One of the figures consisted of a sine wave shape (92 cm length) while the second figure was a triangle wave shape (109 cm length) that was displayed horizontally throughout the entire screen. Participants’ task was to follow the shape displayed on the screen with the index finger of their preferred hand moving from left to right at their preferred rate using flexion-extension movements at the elbow and shoulder, repeating the task 5 times per trial. In some trials, the movement of the finger on the screen generated auditory feedback (sinusoidal tones) that changed in frequency as the finger moved upward (higher frequency) or downward (lower frequency), whereas no auditory feedback was presented in half of the trials. Figures were presented in separate blocks with counterbalanced order. Each block consisted of 8 trials; 4 trials with auditory feedback and 4 trials without auditory feedback, totaling 16 trials.

Statistical analysis

In Task 1, the main variable of interest was the mean reaction times for each condition (random and sequence trials). Absolute reaction time was evaluated across conditions with a univariate analysis of variance.

In task 2, we were interested in whether the number of errors (i.e. pressing the wrong note) would differ in relation to the sequence length (6 to 9 tones) and rate (slow and fast). To obtain the information regarding accuracy, we compared the sequence note presented with the participant’s actual response, converted in percentage. A two-way analysis of variance was performed with the percentage of correct responses as the dependent variable and sequence length (4) and rate (2) as factors. Additionally, we assessed whether participants were able to synchronize their movements with the metronome, using the mean and standard deviation of the inter-response interval (IRI).

In Task 3, participants performed the task bimanually, receiving instructions to press the target notes displayed on the left side of the screen with the left hand and the notes displayed on the right side with the right hand. We were interested in whether performing the task bimanually would affect accuracy (i.e. number of errors). The percentage of correct responses was obtained by comparing the information regarding the notes presented with the participant’s actual keypresses, while data on lateralization errors were recorded manually by the experimenter. Descriptive statistics are presented. Additionally, we also assessed whether participants were able to perform the task following the tempo set by the metronome (mean/standard deviation of IRI).

In the finger tracking task (Task 4), the variables of interest were the time needed to complete each trial and drawing accuracy. The information regarding time for completion was obtained by the sum of the time difference between two points on the screen in milliseconds (screen resolution 1920 x 1080 pixels). Drawing accuracy was computed comparing the distance between the template figure and the participant’s drawing. We were interested in whether the time for completion and drawing accuracy would be affected by the shape of the figure and the availability of auditory feedback generated by the movement of the finger on the screen. A multivariate analysis of variance was performed with time (seconds) and drawing accuracy (pixels) as the dependent variable and with auditory feedback (with and without) and figure shape (sine wave or triangle wave) as factors.

For all statistical comparisons, the significance level was set to 5% (p < 0.05). Statistical analysis was performed using SPSS 24.0 (SPSS Inc., Chicago, IL, USA). The de-identified data (S1 Dataset) and metadata (S1 File) are available as supplementary material.

Results

Task 1: Serial reaction time task

Participants performed the task with an average of 100% accuracy (SD = 1.7%), demonstrating that they were able to reach the correct target position in both conditions (random and sequential). The analysis of the mean absolute reaction time indicated that participants were significantly faster to respond in the sequential order (M = 494 ms, SD = 40 ms) than in the random order trials (M = 510 ms, SD = 55 ms; p = 0.03). These results concur with previous studies showing a decrease in reaction time during the sequence trials in relation to the random trials, which is indicative of implicit motor sequence learning [64, 69–71].

Task 2: Unimanual sensorimotor synchronization task

In this task, we were interested in whether accuracy would be affected by sequence length and presentation rate. Overall, participants performed the task with an average of 96% accuracy (SD = 10%). Nonetheless, the analysis indicated that there were significant main effects of sequence length (F(3,140) = 5.896, p = 0.001) and rate (F(1,140) = 11.036, p = 0.001) on the percentage of correct responses, but there were no significant interaction between factors (p = .607). Further comparisons with Bonferroni corrections indicated that sequences with 9 tones had significantly more errors than sequences with fewer tones (p < 0.05), and that sequences presented and performed at a faster rate had more errors than sequences at a slower tempo (p = 0.02). These results corroborate findings consistently reported in previous studies demonstrating that accuracy can be affected by task parameters such as sequence length, rate, and complexity [72, 73], which is indicative that the data recorded by the device is reliable. Analysis of the IRI showed that participants were able to synchronize their movements according to the metronome tempo, as the average IRI during the slow sequences was 897 ms (SD = 153 ms) and during the fast sequences the average IRI was 740 ms (SD = 77 ms).

Task 3: Bimanual sensorimotor synchronization task

Overall, the task was performed with an average accuracy of 85% (SD = 20%), suggesting that performing the melodic sequences with both hands resulted in an increased number of errors (i.e. pressing the wrong note). When considering lateralization errors, the average accuracy was 99% (SD = 2.8%), demonstrating that participants were able to perform the task using the correctly assigned hand. Finally, the analysis indicated that participants performed the task with an average of 791 ms inter-stimulus interval (SD = 223 ms), thus significantly slower (t(166) = 2.394, p = 0.018) than the tempo set by the metronome (BPM 80/750 ms).

Task 4: Finger tracking task

In task 4, participants had to track with their index finger distinct shapes following a template displayed on the screen. We were interested in whether the time for completion and drawing accuracy would be affected by the shape of the figure and the availability of auditory feedback generated by the finger movement on the screen. Statistical analysis indicated that there were no significant interactions or main effects of figure shape or auditory feedback condition on time and drawing accuracy. Drawing accuracy, as measured with the mean distance between the participants’ finger trace and the figure template (in pixels), did not differ significantly in the sine wave shape (M = 22.5, SE = 6.2) and triangle wave (M = 22.3, SE = 6.2, p = 0.98). When considering the effect of the availability of auditory feedback, mean drawing accuracy was not significantly different in the auditory feedback condition (M = 29.25 pixels, SE = 6.2) and with no feedback (M = 15.58 pixels, SE = 6.2, p = 0.12). Time for completion also did not differ significantly between sine wave (M = 46.6 sec, SE = 28.4 sec) and triangle wave (M = 68.9 sec, SE = 28.4 sec, p = 0.58), and between trials with auditory feedback (M = 84.6 sec, SE = 28.4 sec) and without auditory feedback (M = 30.9 sec, SE = 28.4 ms, p = 0.18).

Discussion

In this study, we describe a novel music-based therapeutic device for upper extremity movement training called SONATA and evaluate the system’s functioning and usability in a convenience sample of healthy individuals. Four motor tasks requiring finger and hand movements previously used in research and/or clinical practice [34, 38, 64–66] were adapted to test the device’s operational modes (keyboard and drawing) and main features.

Overall, the present pre-clinical trial indicates that the device’s hardware and software reliably present pre-defined sequences of audiovisual stimuli and capture and store response and movement data. For instance, the results of the functional tests concur with the findings consistently reported in previous research, indicating that the data recorded by the device is reliable. In Task 1, results indicated a decrease in reaction time in trials where targets are presented in a repeating order compared to random order, a finding that has been consistently found by studies using the Serial Reaction Time paradigm [64, 69–71]. The results of Tasks 2 and 3 concur with the notion that sequence length, rate, and complexity significantly affect the accuracy of newly learned action sequences [72, 73], as our findings indicated that sequences with more elements or presented at a faster tempo had significantly more errors than sequences with fewer tones or slower rates, and that performing melodic sequences bimanually resulted in an increased number of errors. Task 4 revealed that healthy participants’ were equally accurate in tracking different waveforms independent of movement sonification conditions [66-68].

Our results also indicate that the device is feasible and easy to use by healthy individuals. This was demonstrated given the observation that participants were able to access and complete all tasks using the tested device with minimum assistance. Participants received written instructions on how to perform the exercises and were allowed to practice each task to ensure that they understood the instructions and were able to follow the procedures. Participants indicated that they felt confident to perform the tasks after a single practice block and did not require further support during the experimental trials (e.g. verbal reminder of the instructions or demonstration on how to perform the tasks). The participant’s performance accuracy further suggests that task difficulty levels were appropriate for healthy young adults. However, we acknowledge that these exercises may be cognitively demanding for neurologic patients. Thus, task features such as sequence length, rate, and complexity might need to be adjusted when implementing similar exercises on individuals with important cognitive impairment. This observation also applies to the tasks requiring movement synchronization to a metronome, which may be difficult to perform depending on the severity of the motor and/or cognitive impairment, type of injury, or stage of the condition (acute, sub-acute, chronic). The therapist may opt to adjust the metronome tempo, use the ‘metronome interval’ function to increase the temporal window around the metronome tempo in which the patient is required to press the keys, or completely disable the metronome depending on each individual’s needs. When implementing training exercises with individuals with neurologic disorders, therapists may use rhythmic auditory cues, such as a metronome, to facilitate movement planning and execution through auditory-motor entrainment to reduce reliance on stereotypical compensatory upper extremity movements (e.g. trunk flexion, excessive shoulder abduction, circular arm movements) and provide additional manual assistance to fixate trunk position during the exercises [44, 46].

In the past years, researchers and clinicians have acknowledged the relevance of technology to open the possibility of people without music training to engage in active music playing, to facilitate access to music-based therapy in different settings, and to increase motivation and client participation, while offering professionals the opportunity to deploy more resources to meet the patient’s treatment goals [60]. However, there is a need for the development of hardware and software specifically designed for clinical practice. This pre-clinical study focused on describing and testing the functionality and usability of a device designed for upper extremity motor function rehabilitation with healthy individuals. Hence, further research is needed to examine the feasibility, ease of use, and reliability of the data acquired by the system in clinical studies with neurologic patients.

Future research

The device described and evaluated in the present study may be a potential tool for the implementation of music-based interventions in neurologic rehabilitation. All tasks administered in this study required the presentation of pre-defined sequences of audiovisual stimuli or shapes and were designed to include different sequence lengths, presentation rates, task complexities, changes in the availability of real-time auditory feedback as well as capturing distinct response and movement data. These are all aspects carefully considered in the implementation of individual therapeutic plans, thus indicating that the device may be a useful tool to assist therapists during treatment implementation and assessment of targeted therapeutic goals. To examine the feasibility of this device in a clinical context, further research is needed to evaluate therapists’ interactions with the device including usability questionnaires and a qualitative assessment of the device’s interface design, ease of use, safety, feasibility, and versatility.

In this study, we adapted tasks often used in music-based interventions to train fine motor skills using electronic keyboards [30, 34] and touchscreen devices [40], as well as finger tracking tasks implemented in motor rehabilitation that involve tracing a target on a computer screen [66]. These tasks are simplified examples (and not an exhaustive list) of the different types of training exercises that could be used in neurologic rehabilitation with the device tested here. However, adjustments may be needed to use these tasks with neurologic patients in future clinical research. For instance, our findings indicated that sequence length, presentation rate, and the number of limbs required (unimanual or bimanual) can significantly influence accuracy in motor sequence learning tasks. These results, thus, suggest that these aspects need to be thoughtfully considered by researchers and therapists when planning similar exercises with cognitively impaired patients. Participant’s cognitive function, including attention, short-term memory, and executive function, should be assessed to better guide the therapist/researcher in selecting and designing the tasks according to the individuals’ capacity. This also applies to bimanual versus unimanual training [85]. Moreover, therapeutic protocols often implement training exercises that vary in length, movement velocity and direction, and these aspects progressively increase in difficulty [30]. Here, for research purposes, we combined all these features to demonstrate the different device settings that can be programmed and incorporated in the design of training exercises. However, it must be noted that all these aspects are precisely selected in a treatment protocol upon thorough assessment so that the training is adequate to the patient’s treatment goals and objectives, providing exercises that challenge the patient but that are achievable, promoting autonomy and giving patients control over the learning experience.

Future clinical research may also benefit from the evaluation of whether the data recorded with this device in tasks involving continuous motions is accurately captured when the tasks are performed by patients with significant movement impairment, such as apraxia (i.e. a motor disorder that affects a person’s ability to execute movements when asked to), tremor and bradykinesia. The level of assistance required by patients to perform different rehabilitation exercises with this device should also be subject to examination to better define its feasibility depending on the severity of motor and/or cognitive impairment, type of injury, or stage of the condition. The level of support required to access and complete different training exercises with the SONATA will also help define guidelines for the use of this device in different clinical settings (hospitals, care homes, or self-implemented home training).

Finally, research is warranted to better investigate the potential use of interventions based on motor learning to impact cognitive and emotional domains aside from the expected motor improvements. Active music playing as a therapy is an enjoyable activity that involves complex and coordinated movements while placing a high demand on cognitive functions, such as attention, working memory, and executive function [27, 86]. It has been demonstrated that active music engagement through instrument playing promotes significant cognitive benefits to attention and verbal memory [87, 88]. Moreover, several neurologic music therapy interventions have been developed specifically for cognitive rehabilitation focusing on auditory attention and perception training, memory training, and executive function training [89-91]. Future clinical research would be of interest to test whether interventions for cognitive rehabilitation could also be implemented with the SONATA.

Clinical studies are currently in place to test the feasibility and usability of the device in upper extremity movement training. Specifically, the Keys Mode of the SONATA was used to implement a 3-week Therapeutic Instrumental Music Playing (TIMP) protocol to train patterns of reaching movements involving wrist flexion, elbow flexion/extension, shoulder flexion/abduction/adduction, and trunk rotation in chronic stroke patients. The study results supported the effectiveness and feasibility of the SONATA as a music-based device to enhance motor recovery in stroke rehabilitation [92].

Limitations

This pre-clinical trial was restricted to testing the hardware/software of a novel music-based therapeutic device with highly educated, healthy, young adults. Thus, the results of this study may not directly apply to a clinical patient population. Further research on user experience evaluation from both patients and professionals are needed to examine the feasibility, usability, and ease of use of the device in different clinical settings. The feasibility of the exercises used in this study also needs to be tested with clinical patient populations requiring neurorehabilitation, with data captured with the device being correlated with standard measures to assess the reliability, acceptability, tolerance, and adherence of treatment protocols implemented with the SONATA. Moreover, prior to the implementation of large-scale clinical trials, the device needs to undergo appropriate regulation and registration.

Conclusions

A novel music-based therapeutic device called SONATA was presented and tested in the present pre-clinical, single-arm trial. Four motor exercises requiring finger and hand movements previously used in research and/or clinical practice were adapted to test the device’s functioning and usability with healthy young adults. The results of the functional tests suggest that the device is a reliable tool to present pre-defined sequences of audiovisual stimuli and shapes and to record and store response and movement data, such as reaction time, correct/incorrect responses, inter-response interval, and movement spatial accuracy. In addition, this preliminary study suggests that the device is feasible and adequate for use with healthy individuals.

The findings presented here open new avenues for further clinical research to investigate the usability of the SONATA for the implementation of upper extremity motor function training in neurological rehabilitation. We also discussed directions for future research, which include further user’s experience evaluation from both the therapists’ and the patients’ perspectives to better understand, for instance, the level of training required to operate the device, therapists’ interaction with the system to program different training exercises as well as patient’s acceptability, tolerance, and adherence. Phase I clinical studies are also needed to examine the effects of training protocols implemented with the SONATA for upper extremity movement training with clinical populations in different clinical settings (hospital, care homes, community, homes) and direct the development of specific guidelines and training protocols.

De-identified datasets.

(PDF)

Click here for additional data file.

SONATA output variables.

(PDF)

Click here for additional data file.

(PDF)

Click here for additional data file.

9 Sep 2020

PONE-D-20-23749

Development and Evaluation of a Novel Music-Based Therapeutic Device for Upper Extremity Movement Training

PLOS ONE

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ACADEMIC EDITOR: As also one of the reviewers stated, I believe your study might be a valuable step towards adding new tools to help people with motor impairment improve their function.  In this context, I thank you in advance for your careful revision work in line with the points, comments and suggestions highlighted by our reviewers in order to make your article more clearer and more useful for interested researchers.

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Dear authors,

As also one of the reviewers stated, I believe your study might be a valuable step towards adding new tools to help people with motor impairment improve their function. In this context, I thank you in advance for your careful revision work in line with the points, comments and suggestions highlighted by our reviewers in order to make your article more clearer and more useful for everyone interested.

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Partly

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

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Reviewer #1: No

Reviewer #2: No

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situation in the text box.” However, the authors stated, “The datasets generated and/or used during the current study are not publicly available but are available from the corresponding author on reasonable request.” No description of an exceptional situation was provided.

Major Comments:

- Throughout much of the manuscript, I found myself asking, “How is the SONATA different from existing music therapy devices? What is the key innovation?” The manuscript does a good job of motivating music-based rehabilitation but does not discuss the gaps that the SONATA addresses until the end of the manuscript. An earlier, structured review of relevant devices would be useful to motivate the development of the SONATA and clarify the message of the manuscript.

- Is there a reason the grid layout was chosen as opposed to a typical keyboard layout? Were other layouts tested, and, if so, did they have any impacts on the results? I also have similar questions regarding the size and shape of the virtual keys. (e.g., Can smaller keys be used to encourage greater spatial accuracy?)

- Introduction, last paragraph: “With that in mind, a novel music-based therapeutic device for upper extremity movement training was developed to improve upper extremity motor function, to increase independent patient engagement, to enhance treatment quality, intensity, and compliance, and to assist therapists during treatment implementation and assessment.” This sentence suggests that the SONATA does these things, but they have not been validated and this study does not attempt to demonstrate them. The literature review suggests that these claims could be true for the SONATA, but the statement in its current form is misleading.

- Introduction, last paragraph: “to evaluate the feasibility of the system’s functioning for upper extremity movement training.” Given the subject set, this statement is also misleading.

- Methods, Section 2.3: “… thus assisting the therapist in assessing measurable changes in upper limb function throughout training.” This claim may need more justification. The experiment does not show that the data collected by the tasks, as they are implemented by the SONATA, correspond to changes in upper-limb function. How the therapists interact with this data (e.g., visualization, as opposed to raw data) is also important to determining if the data assists therapists. If it is too difficult to draw actionable inferences from the data, then in practice it will just be ignored.

- Discussion, second paragraph: Is performance accuracy really an appropriate measure of ease of use? How hard does a device have to be to use to elicit a significant decrease in accuracy for young, healthy subjects? It also does not account for the interface design or therapist interactions with the system. Some sort of usability questionnaire or qualitative assessment may help to better support this claim. The limitations paragraph mentions the need for additional evaluation, but this statement is too strong.

- Conclusions: “… indicate the feasibility and reliability of the device as a tool for upper extremity movement training.” This statement is too strong given the subject demographics and experimental design. More cautious language should be used.

Minor Comments:

- Methods, Section 2.1: Please include a more thorough description of the hardware. For example, is the device battery-powered or plugged in? Is the system wirelessly controlled via Wi-Fi, Bluetooth, or some other standard? If the device was designed to minimize latency between user input and sound output, what was the average latency?

- Figure 1: It would be useful to readers to visually convey the scale of the devices. From the text, I see that the SONATA is rather large (approx. 0.7 m by 0.4 m), but it appears much smaller in this figure because of the adjacent tablet. (Though Figure 4 helps with this issue to some extent.) The figure should also more clearly identify which device is the SONATA and which is the tablet to prevent potential confusion.

- Figure 2: The authors may want to consider splitting or vertically arranging this figure so that the interfaces are easier to see. In comparison, Figure 3 was much easier to see.

- Methods, line 160: “BPM” Please define abbreviations before use for clarity. Readers that are not familiar with music may not know that this means beats per minute.

- Methods, Section 2.4.1, line 224: This is admittedly a bit of a nit-pick (i.e., the statement is acceptable as-is), but neurological damage or disorders can also affect upper limb movement.

- Methods, Section 2.4.4: For clarity and readability, please avoid using variable names (e.g., “PAT_TIME”) without first defining them in English. At the minimum, a table of variable names and their descriptions could be provided and referenced before use. Avoiding the use of variable names altogether and using English instead is even more preferable.

- Results, Task 4, lines 407–410: Is ms an appropriate unit here? Reporting seconds rounded to one significant digit after the decimal would be more easily parsed by the reader and would not change the conclusions.

Spelling and Grammar: Below are a few miscellaneous items the authors may wish to address. This list is not necessarily comprehensive; the authors should do another proofreading pass.

- Introduction: “Post-stroke” is usually used as an adjective and not as a noun. The authors may want to consider saying “stroke” or “stroke survivors”.

- Introduction, line 112: “With that in mind,” The “that” is ambiguous.

- Methods, line 130: “built-in”

- Methods, line 250: “pitches”

- Methods, line 282: “composed of six to nine”

- Methods, line 294: “composed of seven”

- Methods, line 295: “at a time”

- Decimal values should have a leading zero where appropriate. (e.g., “p < 0.05” on line 360.)

Reviewer #2: You have described a tablet device designed for upper limb training and presented data collected from participants' hand and finger movements using the device who do not have upper limb impairment (normal controls).

Please add to the title 'a pre-clinical, single arm trial' I would also consider revising the title further, to specify hand and finger or fine motor training, since there is no description in the manuscript of elbow or shoulder extension/flexion, aduction/abduction, or other gross motor movements.

In the abstract you use the terms neurologic recovery and neurologic conditions, please be more specific.

Line 32, correct to 'built-in'

Line 46, Abstract, this conclusion cannot be justified. please amend to reflect your findings from pre-clinical phase, i.e. it is not known whether this would work with patients who have UL paresis or apraxia.

Line 55, just state 'Stroke'

Line 74: References 35, 37, 38, 39 are not TIMP as they do not require facilitating music for movement synchrony.

Line 82. It is not clear what you are saying here. It seems that you are referring to other research here (Rojo et al, 2011, Ripolles et al, 2015, Altenmüller et al 2009, etc), where audio-motor coupling is discussed, which you cite later. Please revise the whole literature review to make it shorter and more succint, including only the key literature relevant to UL rehab (hand, finger, fine motor) and the use of rhythm-based interventions and technology such as keyboards and touchscreen instruments.

Line 117. It needs to be completely clear what you have done thorughout the manuscript, the this is pre-clinical testing, which can only show that the hardware and software is working with normal controls.

Line 130correction 'built-in, and omit the word 'sound', just write 'speakers'

139-142 graphically and acoustically program, please re-write to explain more clearly. Do you mean that the therapist (music therapist?) programs the screen layout, metronome setting and/or drawing exercise while the patient is perfomring the exercises? Please clarify.

161: do you mean synchronise their movements? Please clarify. What if they have cognitive (attention and exec function) impairment, and find the metronome distracting, performing UL movements better without it? This needs some dsicussion later

203 Please define what this (ASCII) file is. Readers really need to know that dat collection and storage is secure and can conform to relevant policies to protect patient identity. Please clarify that your system is secure in this regard.

208 'The output files also contain timing and location information of each patient’s input.' clarify, does this mean time of the session and where it took place? If so, how are these data stored to ensure data protection?

210 'inter-stimulus interval, inter-response interval' please define

219 'Functional tests were conducted with 21 healthy individuals (12 males, 8 females) recruited at...' this amounts to 20.

228 No info here about reducing compensatory movements in people who actually have UL impairment, nor at any point later in the manuscript. This must be discussed to some degree.

268-269 youve cited MST rsearch but under the name of TIMP, this needs correcting, and here you need to reference MST to help identify what it is to the reader

288-290 why such a cognitively taxing task when the focus is on UL rehab? How is this supported as a key component for UL rehab, any literature?

308 hypometria, bradykinesia, breif definition required

309-312 thi should be in the background section

328-329 (PAT_TIME –

TICK_TIME) please define

334 SEQ_KEY and PAT_KEY please define

376 'Nonetheless, the analysis indicated that there were significant main effects of

377 sequence length' This is useful data for informing on how to adapt the software/exercises for phase 1 clinical trial. There should be some discussion of this under 'future research' or 'clinical trial planning'

379-381 Anyone working in neurorehab (occupational, physiotherapis for example) would anticipate this response and be able to set up exercises of appropriate complexity for patients, based on their assessment of cognitive function, before the session. Can you explain how this is adding to or enhancing current neurorehab provision, for example in stroke? 382-384 Needs later discussion or some acknowledgement, as patients with cognitive impairment (attention and executive function) may not be able to synch with the pulse, depending on injury or stroke type and time post onset.

387 Needs discussion in the context of how to adapt the equipment.software for clinical trials/use

395 section on finger tapping task: Obviously this needs discussion in context of clinical trials, i.e. you need to test whether the data are accurate for those with apraxia for example

419-421 please amend. feasibility and ease of use of the device are not demonstrated by participants’ performance accuracy. It is the fact that they could access and complete the exercises using this equipment (each clinical setting also needs to be taken into consideration, i.e. acute, subacute, home, carehome, etc) that demonstrates this, but only if you can describe the level of support that was required by the therapist/facilitator. Was lots of assistance required so that participants could follow the exercises? How has your trial informed on the next stage, clinical trial.

422 'we replicated the results of previous research' what research? You state this previously, in the abstract. It is not clear.

440 is cognition consistently part of the focus throughout? Please ensure you maintain focus, what is primary, secondary, i.e.you need to state from the ofset that attention, executive function (memory you mention) are important to potential patient populations being able to access these exercises, that the clnician operating and delivering must consideer these functions and that there may be benefits in these domains from patients doing these exercises, as has been found in some MST research (Grau-sanchez for example).

447-450 ' Studies have consistently demonstrated that active music playing is effective to train upper extremity movement [35-44] due to crucial elements, such as the display of real-time multisensory information [54-56] and the use of metronome or beat-enhanced music to support movement training [49,62,63], which promote neuroplasticity [39,57-61]...' The way this is written suggests that these citations (39, 57-61) involved metronome or beat synchronisation, which they didn’t so I suggest re-writing this.

454-455 ...'including the availability of features that allow for better control and documentation of the training exercises implemented in each session.' No literature is cited here that indicates this is needed and this was not a clearly stated key aim at the ofset. What data supports a claim that this equipment achieves this? Have you clearly descibed how SONATA does this? Has it been reliability checked?

458 but no correlation has been made between your data and standard assessment tools for UL function such as Fugl Meyer and ARAT? SO how do you know that this helps to achieve functional goals? PLease more clearly correlate, if possible, your data with that of MST studies where there is some correlation between tapping tasks and motor assessment outcomes.

458-459 this hasn’t been feasibiity tested though. You don't know how SONATA will perform in any setting. Please amend and state that this is a limitation of your study and/or that you need to conduct a clinical trial, most likely a feasibility study.

465 ...'transform the therapeutic process.' In the interest of not making exaggerated claims, in what context? One paper is cited hear, published in a music therapy journal. You have completed a pre-clinical testing study with normal controls, not patients. Please write in a way that does not imply that SONATA can achieve this transformation. So far, you can only use published data, primarily from MST studies.

472 Can you be clear, are you saying that studies are under way (recruiting) with clinical populations?

475 need to be specific here and say what the limitations definitely were: our study was limited to testing the software and data collection. No data were correlated with standard UL measures, which needs to be done in a formal trial.

Exercises have not been tested for feasibility of delivery with stroke or other patient populations requiring neurorehabilitation in any clinical setting. Feasibility needs to be quantified in terms of acceptability of the exercises, tolerance and adherence. Following this, if data are favourable, a pilot or definitive trial would be required with a sufficiently powered sample.

Prior to that, since the device is intended for biomedical treatment, it would need to be registered as a medical device. The latter, must be acknowledged/discussed and is not mentioned at all throughout the manuscript, can you justify why it is not mentioned? If not, plese amend.

481 '9 sequences' if you are presenting this as a potential tool to aid UL rehab, then you must discuss more about the implications. Since tolerance and adherence to treatment are central in enabling patients to achieve the required high dosage of treatment (MST = 3-4 weeks at 5 X per week) to show any clinical or statistical significance, wouldn’t 9 sequences per task fall rather short of achieving this?

487 'Upper extremity movement training' Please consider revising the manuscript to consistently state hand and finger and/or fine motor function. THink about where you want to take this research, what the next stage is. This study must support the next stage, if enough has been done here to pave the way, together with all pre-existing evidence.

488 'well known' be precise, clinically relevant. Are they well known? Where are the citations?

488 'test the feasibility, ease of use.' To a degree, but the data need to be collected alongside standard UL measures from people with UL impairment and reliability checked

492 implementation and independent patient engagement ( I assume you mean self-delivery) these are two diferent things. Please clarify and define.

The conclusion could be better written. To say that results indicate feasibility and reliability is too general, too many areas are not covered in your study. What about positioning to mitigate compensatory movements, data protection (storage and transfer of data), checking of SONATA data alongside standard UL assessment tool data, infection control of equipment in clinical settings, who would deliver the exercises, a music therapist, any clinician, what can you conclude needs to be done next based on your findings, what dosage of SONATA exercises could be delivered in a clinical setting and are there currently enough exercises, how long does it take a clinician to program each exercises for each patient and what is the impact on managing a clincal case oad, what about medical device registration for SONATA?

The study might be a useful step in the right direction (adding clinical tools to help people with UL impairment to recover function), but as the manuscript stands it is not clearly framed and needs to be amended to consistenly adhere to the main areas of focus, purpose, findings, so that it is completely clear what the implcations are for future, related research, giving some indication of if and when SONATA might become a clinical tool.

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Reviewer #1: No

Reviewer #2: Yes: Alexander Street

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27 Oct 2020

Dear Dr. Torun,

We thank you and the reviewers for the constructive feedback provided and have amended the manuscript accordingly.

The main points of revision were made in the Introduction and Discussion sections to clarify aspects relating to the motivation for the development of the device and to better discuss points raised by the reviewers regarding the study results, future research and study limitations.

We have also addressed the additional journal requirements in relation to manuscript style and amended the Funding Statement and statements regarding the role of funders and authors contributions as follows:

Financial Disclosure Statement

The author(s) received no specific funding for this work. RP and SS are affiliated to a commercial company: BeSB GmbH. The funder provided support in the form of salaries for authors RP and SS but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.

Authors Contributions

Conceptualization: MT. Data curation: NS. Formal analysis: TBJ. Investigation: NS. Methodology: NS, TBJ, SS, MT. Project administration: NS. Resources: NS. Software: RP, SS. Supervision: MT. Validation: TBJ, MT. Writing - Original Draft Preparation: NS, TBJ. Writing - Review & Editing: NS, TBJ, SS, VV, MT.

Competing Interest

TBJ and VV declare no competing interests. RP and SS are employed engineers at BeSB GmbH Berlin, and NS currently serves as unpaid consultant and informal scientific advisor for BeSB GmbH Berlin. The device presented and tested in this study is a product developed in collaboration between BeSB and MT with potential for commercialization. This commercial affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials.

As suggested, we have also amended the methods section and ethics statement of the manuscript to state that the person depicted in Figure 4 provided consent for publication. The signed informed consent is submitted with the revised manuscript.

Finally, we uploaded the minimal anonymized data set for each task administered in the study along with a description of all variables definitions as Supporting Information files.

We believe that the adjustments implemented according to the feedback received have indeed increased the overall quality of the manuscript and we hope this revised version finds your approval.

We would be glad to respond to any further questions and comments that you and the reviewers may have and look forward to hearing from you regarding our submission.

Sincerely,

Dr. Nina Schaffert

Response to Reviewer 1:

Overall comment: We greatly appreciate the constructive suggestions and have adjusted the manuscript accordingly. The revisions focused primarily on the introduction and discussion sections to clarify aspects relating to the motivation for the development of the SONATA and to better discuss points raised regarding the study results, future research and study limitations. We hope that these modifications have addressed your main suggestions and concerns. Please, see below point-by-point replies to your comments.

Reviewer #1: Data Availability: The form states, “Stating ‘data available on request from the author’ is not sufficient. If your data are only available upon request, select ‘No’ for the first question and explain your exceptional situation in the text box.” However, the authors stated, “The datasets generated and/or used during the current study are not publicly available but are available from the corresponding author on reasonable request.” No description of an exceptional situation was provided.

REPLY: The data sets are now available as supplementary material.

Major Comments:

- Throughout much of the manuscript, I found myself asking, “How is the SONATA different from existing music therapy devices? What is the key innovation?” The manuscript does a good job of motivating music-based rehabilitation but does not discuss the gaps that the SONATA addresses until the end of the manuscript. An earlier, structured review of relevant devices would be useful to motivate the development of the SONATA and clarify the message of the manuscript.

REPLY: Thank you for your suggestion. We added a new paragraph addressing some limitations of currently available devices and motivating the need for the development of the SONATA (Page 5).

- Is there a reason the grid layout was chosen as opposed to a typical keyboard layout? Were other layouts tested, and, if so, did they have any impacts on the results? I also have similar questions regarding the size and shape of the virtual keys. (e.g., Can smaller keys be used to encourage greater spatial accuracy?)

REPLY: The device was conceptualized as a touch surface for motor training in therapy/rehabilitation, hence the spatial dimensions have to allow for mapping functional reaching movements of full elbow flexion/extension and shoulder adduction/abduction that are completed by touching a targeted sound button. After piloting in hemiparetic arm rehabilitation with persons with different body composition (size, gender), a 47x78cm surface seemed most appropriate to accommodate different body shapes. A typical keyboard layout would not accommodate those functional movements.

- Introduction, last paragraph: “With that in mind, a novel music-based therapeutic device for upper extremity movement training was developed to improve upper extremity motor function, to increase independent patient engagement, to enhance treatment quality, intensity, and compliance, and to assist therapists during treatment implementation and assessment.” This sentence suggests that the SONATA does these things, but they have not been validated and this study does not attempt to demonstrate them. The literature review suggests that these claims could be true for the SONATA, but the statement in its current form is misleading.

- Introduction, last paragraph: “to evaluate the feasibility of the system’s functioning for upper extremity movement training.” Given the subject set, this statement is also misleading.

REPLY: Thank you for drawing our attention to the word choices here. We have rephrased the objectives of the study to clarify any misleading points. The sentence now reads “Therefore, the objective of this study is to describe a novel music-based therapeutic device called SONATA, and to conduct a pre-clinical, single arm trial to evaluate the device’s functioning with healthy individuals” (Page 5).

- Methods, Section 2.3: “… thus assisting the therapist in assessing measurable changes in upper limb function throughout training.” This claim may need more justification. The experiment does not show that the data collected by the tasks, as they are implemented by the SONATA, correspond to changes in upper-limb function. How the therapists interact with this data (e.g., visualization, as opposed to raw data) is also important to determining if the data assists therapists. If it is too difficult to draw actionable inferences from the data, then in practice it will just be ignored.

REPLY: Thank you for your suggestion. Indeed, we cannot relate the data collected by the current study with changes in upper limb function. We modified the sentence with a more cautious wording.

- Discussion, second paragraph: Is performance accuracy really an appropriate measure of ease of use? How hard does a device have to be to use to elicit a significant decrease in accuracy for young, healthy subjects? It also does not account for the interface design or therapist interactions with the system. Some sort of usability questionnaire or qualitative assessment may help to better support this claim. The limitations paragraph mentions the need for additional evaluation, but this statement is too strong.

REPLY: As suggested, we re-structured the discussion to clarify the main findings and better discuss aspects that need to be further addressed in future research.

- Conclusions: “… indicate the feasibility and reliability of the device as a tool for upper extremity movement training.” This statement is too strong given the subject demographics and experimental design. More cautious language should be used.

REPLY: Thank you for drawing our attention to the word choices. We have completely rephrased the conclusions.

Minor Comments:

- Methods, Section 2.1: Please include a more thorough description of the hardware. For example, is the device battery-powered or plugged in? Is the system wirelessly controlled via Wi-Fi, Bluetooth, or some other standard? If the device was designed to minimize latency between user input and sound output, what was the average latency?

REPLY: We have added the missing information to the description of the devices, as suggested.

- Figure 1: It would be useful to readers to visually convey the scale of the devices. From the text, I see that the SONATA is rather large (approx. 0.7 m by 0.4 m), but it appears much smaller in this figure because of the adjacent tablet. (Though Figure 4 helps with this issue to some extent.) The figure should also more clearly identify which device is the SONATA and which is the tablet to prevent potential confusion.

REPLY: We have modified Figure 1 and added the dimensions of the devices accordingly and labelled the devices to avoid confusion.

- Figure 2: The authors may want to consider splitting or vertically arranging this figure so that the interfaces are easier to see. In comparison, Figure 3 was much easier to see.

REPLY: As suggested, we rearranged the figure and enlarged the panels to make them easier to see.

- Methods, line 160: “BPM” Please define abbreviations before use for clarity. Readers that are not familiar with music may not know that this means beats per minute.

REPLY: Corrected.

- Methods, Section 2.4.1, line 224: This is admittedly a bit of a nit-pick (i.e., the statement is acceptable as-is), but neurological damage or disorders can also affect upper limb movement.

REPLY: Thank you for this note. We have extended the sentence and included the information.

- Methods, Section 2.4.4: For clarity and readability, please avoid using variable names (e.g., “PAT_TIME”) without first defining them in English. At the minimum, a table of variable names and their descriptions could be provided and referenced before use. Avoiding the use of variable names altogether and using English instead is even more preferable.

REPLY: Thank you for the advice. As suggested, we have added a table with the variables names, their definition, abbreviation and the unit used as supplementary material. In addition, we removed the variable names and described the variables in plain language.

- Results, Task 4, lines 407–410: Is ms an appropriate unit here? Reporting seconds rounded to one significant digit after the decimal would be more easily parsed by the reader and would not change the conclusions.

REPLY: Corrected.

Spelling and Grammar: Below are a few miscellaneous items the authors may wish to address. This list is not necessarily comprehensive; the authors should do another proofreading pass.

- Introduction: “Post-stroke” is usually used as an adjective and not as a noun. The authors may want to consider saying “stroke” or “stroke survivors”.

REPLY: Corrected.

- Introduction, line 112: “With that in mind,” The “that” is ambiguous.

REPLY: We rephrased the sentence.

- Methods, line 130: “built-in”

REPLY: Corrected

- Methods, line 250: “pitches”

REPLY: Corrected

- Methods, line 282: “composed of six to nine”

REPLY: Corrected

- Methods, line 294: “composed of seven”

REPLY: Corrected

- Methods, line 295: “at a time”

REPLY: Corrected

- Decimal values should have a leading zero where appropriate. (e.g., “p < 0.05” on line 360.)

REPLY: Corrected

---------

Response to Reviewer 2:

Overall comment: We greatly appreciate the constructive suggestions and have adjusted the manuscript accordingly. The revisions focused primarily on the introduction and discussion sections to clarify aspects relating to the motivation for the development of the SONATA and to better discuss points raised regarding the study results, future research and study limitations. We hope that these modifications have addressed your main suggestions and concerns. Please, see below point-by-point replies to your comments.

Reviewer #2: You have described a tablet device designed for upper limb training and presented data collected from participants' hand and finger movements using the device who do not have upper limb impairment (normal controls).

Please add to the title 'a pre-clinical, single arm trial'. I would also consider revising the title further, to specify hand and finger or fine motor training, since there is no description in the manuscript of elbow or shoulder extension/flexion, aduction/abduction, or other gross motor movements.

REPLY: Thank you for your suggestion. We modified the title as suggested and adjusted the manuscript to specify that this study is a pre-clinical study that used tasks that require predominantly hand/finger movements. Nevertheless, we think that with the expanded task description and the added dimensions of the device, it will be clearer that the tasks do require gross movements as well.

In the abstract you use the terms neurologic recovery and neurologic conditions, please be more specific.

REPLY: We have adjusted the abstract as suggested. The term “neurologic recovery” now reads “neurological rehabilitation”, and we added examples of neurologic conditions where upper limb function can be compromised, such as cerebral palsy, stroke and Parkinson’s Disease.

Line 32, correct to 'built-in'

REPLY: Corrected.

Line 46, Abstract, this conclusion cannot be justified. please amend to reflect your findings from pre-clinical phase, i.e. it is not known whether this would work with patients who have UL paresis or apraxia.

REPLY: Thank you for the comment. We have rephrased the description of the results and conclusion of the abstract.

Line 55, just state 'Stroke'

REPLY: Corrected

Line 74: References 35, 37, 38, 39 are not TIMP as they do not require facilitating music for movement synchrony.

REPLY: Indeed, the highlighted references relate to studies using Music-supported Therapy and not TIMP. However, both techniques use musical instrument playing (although with different protocols) to train fine and gross movements of the paretic extremity. We clarified this point in the sentence.

Line 82. It is not clear what you are saying here. It seems that you are referring to other research here (Rojo et al, 2011, Ripolles et al, 2015, Altenmüller et al 2009, etc), where audio-motor coupling is discussed, which you cite later. Please revise the whole literature review to make it shorter and more succint, including only the key literature relevant to UL rehab (hand, finger, fine motor) and the use of rhythm-based interventions and technology such as keyboards and touchscreen instruments.

REPLY: Thank you for your suggestion. We excluded the highlighted sentence and attempted to focus the literature review on studies focusing on upper limb rehabilitation.

Line 117. It needs to be completely clear what you have done throughout the manuscript, the this is pre-clinical testing, which can only show that the hardware and software is working with normal controls.

REPLY: Thank you for drawing our attention to the wording used here. We have rephrased the objectives of the study to clarify any misleading points. The sentence now reads “Therefore, the objective of this study is to describe a novel music-based therapeutic device called SONATA, and to conduct a pre-clinical, single arm trial to evaluate the device’s functioning with healthy individuals” (Page 5).

Line 130 correction 'built-in, and omit the word 'sound', just write 'speakers'

REPLY: Corrected.

139-142 graphically and acoustically program, please re-write to explain more clearly. Do you mean that the therapist (music therapist?) programs the screen layout, metronome setting and/or drawing exercise while the patient is perfomring the exercises? Please clarify.

REPLY: Yes, the therapist can program new patterns using the controller tablet while the client performs a different exercise in the SONATA touchscreen interface. We trust this clarifies the motivation for having two different interfaces.

161: do you mean synchronise their movements? Please clarify. What if they have cognitive (attention and exec function) impairment, and find the metronome distracting, performing UL movements better without it? This needs some discussion later

REPLY: Yes, the metronome function allows movement synchronization and the feature can be disabled by the therapist according to the exercise objectives or the patient’s needs. A note to clarify that the metronome can be disabled was added to clarify this point (Page 9).

203 Please define what this (ASCII) file is. Readers really need to know that data collection and storage is secure and can conform to relevant policies to protect patient identity. Please clarify that your system is secure in this regard.

REPLY: Thank you for raising the point about data protection. We have included more information on the system’s security. Specifically, the recorded data is stored in the tablet’s password-secured internal memory and cannot be transmitted as the device is not connected to a network.

208 'The output files also contain timing and location information of each patient’s input.' clarify, does this mean time of the session and where it took place? If so, how are these data stored to ensure data protection?

REPLY: Thank you for this note. We have modified the sentence to clarify that only information on movement position and timing of keypresses are stored. Our word choice was not accurate in the previous version of the manuscript.

210 'inter-stimulus interval, inter-response interval' please define

REPLY: A definition for both terms was included (Page 11)

219 'Functional tests were conducted with 21 healthy individuals (12 males, 8 females) recruited at...' this amounts to 20.

REPLY: Corrected.

228 No info here about reducing compensatory movements in people who actually have UL impairment, nor at any point later in the manuscript. This must be discussed to some degree.

REPLY: The subjects in the current study are healthy and not executing compensatory movements. With persons who will potentially use compensatory movements, 2 factors can be implemented to reduce/eliminate those movements:

- Research has shown that compensatory UE movements (trunk flexion, excessive shoulder abduction, circular arm trajectories) during reaching movements are reduced when movements are cued cyclically by auditory rhythm (Thaut et al, 2002 Neuropsychologia; Malcolm et al, 2009, Topics in Stroke Rehab). SONATA does not only produce auditory feedback at movement completion but also anticipatory rhythmic auditory movement cues. The perceptual-motor architecture of SONATA will probably provide compensatory movement reduction. This can be further tested in future research.

- Additionally, therapists or caregivers may manually assist by fixating trunk position.

268-269 youve cited MST rsearch but under the name of TIMP, this needs correcting, and here you need to reference MST to help identify what it is to the reader

REPLY: We have expanded the Introduction to make reference to both therapeutic techniques (MST and TIMP). The protocol description and references cited in this paragraph indeed refer to MST.

288-290 why such a cognitively taxing task when the focus is on UL rehab? How is this supported as a key component for UL rehab, any literature?

REPLY: Therapeutic protocols often implement tasks that vary in sequence length, movement velocity and direction, and these aspects commonly progressively increase in difficulty. For research purposes, here we combined all these features in a single task as an example of a motor training exercise that could be implemented with the SONATA. However, we acknowledge that this task requires preserved cognitive functions, thus task difficulty would need to be adjusted for patients with important cognitive function impairment.

308 hypometria, bradykinesia, breif definition required

REPLY: A definition was added for both terms (Page 16).

309-312 this should be in the background section

REPLY: Thank you for your suggestion. We briefly described each task in the Introduction section.

328-329 (PAT_TIME – TICK_TIME) please define

334 SEQ_KEY and PAT_KEY please define

REPLY: We agree that including the names of the variables as found in the data output files can be confusing. We removed the variable names and described them in plain language. In addition, we have added a table with the variables names, their definition, abbreviation as supplementary material.

376 'Nonetheless, the analysis indicated that there were significant main effects of

377 sequence length' This is useful data for informing on how to adapt the software/exercises for phase 1 clinical trial. There should be some discussion of this under 'future research' or 'clinical trial planning'

REPLY: Thank you for your suggestion. We included a new section in the Discussion to address these considerations regarding the study results and future research, as suggested.

379-381 Anyone working in neurorehab (occupational, physiotherapis for example) would anticipate this response and be able to set up exercises of appropriate complexity for patients, based on their assessment of cognitive function, before the session. Can you explain how this is adding to or enhancing current neurorehab provision, for example in stroke?

REPLY: Our primary goal with this study was to describe the device and test whether the system’s hardware and software were functioning adequately. Therefore, in our view, the fact that our results corroborate the findings consistently reported in previous research is an indication that the data recorded by the device is reliable.

382-384 Needs later discussion or some acknowledgement, as patients with cognitive impairment (attention and executive function) may not be able to synch with the pulse, depending on injury or stroke type and time post onset.

REPLY: We acknowledge that movement synchronization to a metronome may be difficult depending on the severity of the motor and/or cognitive impairment, type of injury or stage of the condition, and presented possible options that the therapist have to address this issue using the different functionalities of the device.

387 Needs discussion in the context of how to adapt the equipment.software for clinical trials/use

REPLY: We included a new section in the Discussion to address important considerations about the task settings and future research, as suggested.

395 section on finger tapping task: Obviously this needs discussion in context of clinical trials, i.e. you need to test whether the data are accurate for those with apraxia for example

REPLY: Thank you for your point. We included this point regarding our study results in the discussion section.

419-421 please amend. feasibility and ease of use of the device are not demonstrated by participants’ performance accuracy. It is the fact that they could access and complete the exercises using this equipment (each clinical setting also needs to be taken into consideration, i.e. acute, subacute, home, carehome, etc) that demonstrates this, but only if you can describe the level of support that was required by the therapist/facilitator. Was lots of assistance required so that participants could follow the exercises? How has your trial informed on the next stage, clinical trial.

REPLY: Thank you for your comment. We amended the discussion regarding the results of the study to better reflect the findings of this pre-clinical study.

422 'we replicated the results of previous research' what research? You state this previously, in the abstract. It is not clear.

REPLY: We clarified this sentence. In our humble opinion, the fact that the results of the functional tests concur with the findings consistently reported in previous research is an indication that the data recorded by the device is reliable.

440 is cognition consistently part of the focus throughout? Please ensure you maintain focus, what is primary, secondary, i.e.you need to state from the ofset that attention, executive function (memory you mention) are important to potential patient populations being able to access these exercises, that the clnician operating and delivering must consideer these functions and that there may be benefits in these domains from patients doing these exercises, as has been found in some MST research (Grau-sanchez for example).

REPLY: We have rephrased this entire paragraph to better discuss the points raised.

447-450 ' Studies have consistently demonstrated that active music playing is effective to train upper extremity movement [35-44] due to crucial elements, such as the display of real-time multisensory information [54-56] and the use of metronome or beat-enhanced music to support movement training [49,62,63], which promote neuroplasticity [39,57-61]...' The way this is written suggests that these citations (39, 57-61) involved metronome or beat synchronisation, which they didn’t so I suggest re-writing this.

REPLY: This sentence was removed from the revised version of the manuscript.

454-455 ...'including the availability of features that allow for better control and documentation of the training exercises implemented in each session.' No literature is cited here that indicates this is needed and this was not a clearly stated key aim at the ofset. What data supports a claim that this equipment achieves this? Have you clearly descibed how SONATA does this? Has it been reliability checked?

REPLY: We have completely rephrased this point.

458 but no correlation has been made between your data and standard assessment tools for UL function such as Fugl Meyer and ARAT? SO how do you know that this helps to achieve functional goals? PLease more clearly correlate, if possible, your data with that of MST studies where there is some correlation between tapping tasks and motor assessment outcomes.

REPLY: We have added the observation that our pre-clinical results were not correlated with other standard assessments as a limiting aspect of this study and a point that should be incorporated in future research.

458-459 this hasn’t been feasibiity tested though. You don't know how SONATA will perform in any setting. Please amend and state that this is a limitation of your study and/or that you need to conduct a clinical trial, most likely a feasibility study.

REPLY: Thank you for your comment. We amended the limitations to add the points suggested.

465 ...'transform the therapeutic process.' In the interest of not making exaggerated claims, in what context? One paper is cited hear, published in a music therapy journal. You have completed a pre-clinical testing study with normal controls, not patients. Please write in a way that does not imply that SONATA can achieve this transformation. So far, you can only use published data, primarily from MST studies.

REPLY: This sentence was removed.

472 Can you be clear, are you saying that studies are under way (recruiting) with clinical populations?

REPLY: We added a new section to discuss directions for future clinical research

475 need to be specific here and say what the limitations definitely were: our study was limited to testing the software and data collection. No data were correlated with standard UL measures, which needs to be done in a formal trial.

Exercises have not been tested for feasibility of delivery with stroke or other patient populations requiring neurorehabilitation in any clinical setting. Feasibility needs to be quantified in terms of acceptability of the exercises, tolerance and adherence. Following this, if data are favourable, a pilot or definitive trial would be required with a sufficiently powered sample.

Prior to that, since the device is intended for biomedical treatment, it would need to be registered as a medical device. The latter, must be acknowledged/discussed and is not mentioned at all throughout the manuscript, can you justify why it is not mentioned? If not, plese amend.

REPLY: Thank you for your constructive suggestion. We amended the section discussing the limitations of this study and included the points suggested.

481 '9 sequences' if you are presenting this as a potential tool to aid UL rehab, then you must discuss more about the implications. Since tolerance and adherence to treatment are central in enabling patients to achieve the required high dosage of treatment (MST = 3-4 weeks at 5 X per week) to show any clinical or statistical significance, wouldn’t 9 sequences per task fall rather short of achieving this?

REPLY: This paragraph was amended. Further improvements in the device hardware and software might be implemented as further user-experience evaluations are conducted.

487 'Upper extremity movement training' Please consider revising the manuscript to consistently state hand and finger and/or fine motor function. THink about where you want to take this research, what the next stage is. This study must support the next stage, if enough has been done here to pave the way, together with all pre-existing evidence.

REPLY: As suggested, we adjusted the manuscript to clarify the tasks implemented in the study.

488 'well known' be precise, clinically relevant. Are they well known? Where are the citations?

REPLY: This sentence was removed and rephrased to indicate that we adapted tasks that have been previously used in research and/or clinical practice and included the appropriate citations.

488 'test the feasibility, ease of use.' To a degree, but the data need to be collected alongside standard UL measures from people with UL impairment and reliability checked

REPLY: We rephrased our results to better reflect the findings of this pre-clinical study.

492 implementation and independent patient engagement ( I assume you mean self-delivery) these are two diferent things. Please clarify and define.

REPLY: This sentence was removed.

The conclusion could be better written. To say that results indicate feasibility and reliability is too general, too many areas are not covered in your study. What about positioning to mitigate compensatory movements, data protection (storage and transfer of data), checking of SONATA data alongside standard UL assessment tool data, infection control of equipment in clinical settings, who would deliver the exercises, a music therapist, any clinician, what can you conclude needs to be done next based on your findings, what dosage of SONATA exercises could be delivered in a clinical setting and are there currently enough exercises, how long does it take a clinician to program each exercises for each patient and what is the impact on managing a clincal case oad, what about medical device registration for SONATA?

REPLY: Thank you for your constructive feedback. We completely rewrote the conclusion section based on your suggestions.

The study might be a useful step in the right direction (adding clinical tools to help people with UL impairment to recover function), but as the manuscript stands it is not clearly framed and needs to be amended to consistenly adhere to the main areas of focus, purpose, findings, so that it is completely clear what the implcations are for future, related research, giving some indication of if and when SONATA might become a clinical tool.

REPLY: We thank the reviewer for your constructive comments and suggestions. We believe that the adjustments implemented according to your feedback have increased the overall quality of the manuscript and we hope this revised version finds your approval.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

5 Nov 2020

Development and Evaluation of a Novel Music-Based Therapeutic Device for Upper Extremity Movement Training: A Pre-Clinical, Single-Arm Trial

PONE-D-20-23749R1

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Additional Editor Comments (optional):

Thank you for correcting and editing many important issues highlighted in our major revision suggestion and making the necessary adjustments to improve the scientific quality of your article.

Sincerely.

Reviewers' comments:

9 Nov 2020

PONE-D-20-23749R1

Development and evaluation of a novel music-based therapeutic device for upper extremity movement training: a pre-clinical, single-arm trial

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