Brain Imaging and Behavioural Changes Following Cued-movement Training of Finger Sequences in Healthy Older Adults

The goal of this study is to examine changes in the brain, behavior, and personal experience when music is used to guide learning of finger movement sequences (compared to visual stimuli alone) in healthy older adults. The main research questions this study aims to answer are:

1. Is auditory-based motor training associated with increased structural integrity of brain white matter tracts (connecting auditory-motor regions) compared to motor training with visual cues only?
2. Is auditory-based motor training (as compared to visual clues only) associated with increased brain cortical thickness, and changes in brain activation while performing a task in the MRI and while at rest, in auditory and sensorimotor regions?
3. Does auditory-based motor training lead to greater motor improvement on the trained task compared to a visually cued motor training?
4. Does auditory-based motor training lead to greater improvement on thinking, movement, and self-reported wellbeing measures, compared to visual cues alone?

In an 8-week home training, participants will be randomized into either the music-cued motor learning (Experimental Group) or visually cued only condition (Control Group), participants will complete the following measures before-and-after the training is administered at week 1 and in the end of the 8-week trial:

* MRI scans (structural and functional)
* Behavioral measures (motor, cognition)
* Questionnaires administered pre-and-post training (psychosocial functioning).
* Questionnaires administered once only (personality traits, musical background)
* In between measures, participants will follow an online computer-based training at home of 20 minutes per session, 3 times per week for 8 weeks, for a total of 24 sessions constituting 8 hours of training.

Rationale: Music interventions targeting motor recovery are increasingly used in clinical settings with motorically impaired patients. In recent years, research started to demonstrate the mechanism underlying motor recovery by moving to music. While neuroimaging studies began to elucidate the neural correlates of music-based movement, most of these studies have been conducted on young adults, whereas the average age at onset of movement disorders which are the target of music therapy is in the 6th decade of life. Therefore, in this study the investigators aim to elucidate the underlying mechanisms of music-based movement in healthy older adults using a motor learning, finger sequence task to a musical rhythm. The results of the study have implications for motor learning with music in the aging person and neural plasticity in old age, and may reveal the benefit of adding music-cues to motor activities for motor, cognitive, and motivational outcomes in older adults.

Objective: The goal of the current study is to examine structural and functional neural correlates, as well as changes in behavioral and self-report measures of audiovisual music-based motor training compared to an identical motor training using visual cues only. The study focuses on white matter changes as the primary objective as the researchers are interested in connections between auditory and motor brain regions implicated in music-cued motor training. The research will examine brain activation, and changes in grey matter volume as secondary neuroimaging outcomes. Moreover, the study will also examine improvement on the trained task (outside of the MRI scanner), and changes on standardized measures of motor and cognitive function, as well as self-report measures of psychological wellbeing.

The main hypothesis is that the music-based motor training group will show greater white matter integrity of the arcuate fasciculus and greater density of cortical thickness in motor areas in the right brain hemisphere opposite to the trained left hand, as well as greater changes in brain activation while performing the task and at rest. The music group is expected to show greater improvement on the trained task, and measures of motor and cognitive function, as well as self-report measures of wellbeing (motivational, mood, and experience). As an exploratory measure, the study will assess changes in dual-task interference before and after the training as a far-transfer measure of the training, both in motor function and the underlying brain function.

Study design: In an 8-week longitudinal between-group design, participants will be randomized into two groups and will participate in pre-and-post MRI scans and behavioral measures, administered at baseline (week 1) and end of trial (week 8). The learning of an audio-visual finger movement sequence task will be compared to training on the same motor sequence with visual cues only. Participants will be assessed before and after the 8-week training on MRI and behavioral measures.

Study population: A total of 50 healthy older adults (60 years and older) will be recruited for this study and randomized into two groups of 25 participants each. Inclusion criteria are being right-handed (assessed by the Edinburgh Handedness Inventory), neurologically and physically healthy adult aged 60 or older (a previous diagnosis of a neurological/psychiatric illness that is symptom-free and for which no treatment was necessary for at least 5 years may be included), other physical health conditions that are stable (no change in diagnosis or treatment in the past 2 years may be included), having age-normal cognitive function (as assessed by a score of ≥24 on the MMSE), age appropriate normal or corrected vision and hearing ability, speaking fluent Dutch, and not currently receiving musical training. Participants should have access to a computer to complete the training at home. Participants will be recruited through various channels in the Netherlands including ageing organizations, (social) media, and study recruitment websites.

Sample Size: In a previous study with a longitudinal design using the same learning task in healthy young adults, the researchers found a medium size effect for changes in white matter tracts connecting auditory and motor regions (i.e., arcuate fasciculus) in the brain hemisphere opposite the trained hand. Therefore, it is estimated that the sample size needed to show a similar medium sized effect would be 22 per group, however, this number is increased to 25 healthy older participants per group to account for additional drop out at the analysis stage.

Intervention: Two groups will receive a similar intervention of finger sequence movement learning following visual cues with (or without) rhythmic auditory stimulation. Participants will be trained on the task at the laboratory before baseline measures. Participants will continue training at home online on a computer and keyboard for 20 minutes per session 3 times per week for 8 weeks for a total of 24 sessions. The Music group will train the finger sequence with the aid of visual cues in synchrony with a musical rhythm, while the Control group will receive the same visual stimulation with no auditory component.

Main study parameters/endpoints: The main parameter is change in white matter tracts underlying auditory-motor regions (arcuate fasciculus) in the brain hemisphere opposite the trained hand, contrasting before and after training, and between hemispheres. Secondary MRI parameters focus on cortical thickness changes in primary, premotor, and supplementary motor areas, task-related brain activation in the premotor cortex, and resting-state functional connectivity of auditory-motor regions. Motor performance on the cued motor sequence task will be assessed by measuring the accuracy of the key presses and the timing stability in synchrony with the onset of the cue. Changes in the scores of standardized motor and cognitive measures, and self-reported questionnaires on motivational and mood indices will be compared between groups and timepoints. As an exploratory outcome, the study will also assess changes in dual-task interference before and after the training both behaviorally and in terms of associated brain activity while performing the task.

Eligibility Criteria:
Inclusion Criteria:

* Right-handed (assessed by the Edinburgh Handedness Inventory),
* Neurologically and physically healthy adults (a previous diagnosis of a neurological/psychiatric illness that is symptom-free and for which no treatment was necessary for at least 5 years may be included), other physical health conditions that are stable (no change in diagnosis or medication in the past 2 years may be included)
* aged 60 or older,
* Age-normal cognitive function (as assessed by a score of ≥24 on the MMSE),
* Age appropriate normal or corrected vision and hearing ability,
* Speaking fluent Dutch,
* Not currently receiving musical training.
* Participants should have access to a computer and internet to complete the training at home.

Exclusion Criteria:

* MRI contraindications (e.g., having ferromagnetic metals, such as implants, or claustrophobia)
* Starting or currently engaged in hand training, including musical training, and for example knitting, type-writing, or other hobbies (musical activities such as dancing or singing that do not involve the hand).
* Changes in medications that may affect fMRI measures.
* Not being able to follow the training at the laboratory or at home, or not completing the practice at home despite alerts and reminders.