Triggering Motor Memory Consolidation in Healthy Aging: the Effects of Complex Practice on Brain Activity During Learning of Postural Tasks
Phase: NA
Conditions: Healthy Aging
Sponsor: KU Leuven

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Study protocol - Version 3, 17/10/2022 
 
 
 
The effect of training on brain activity during postural control tasks in 
older adults 
 
 
 
 
Protocol identification number 
S62917 
 
Study type 
Interventional 
 
Principle investigator 
Prof. Alice Nieuwboer 
 
Sub-investigator 
Veerle de Rond, MSc 
 
 

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1 General information 
Sponsors:  
 
European Union’s Horizon 2020 research and innovation programme under the  
Marie Sklowdowska-Curie grant agreement No. 721577 
Research Unit: 
Neurorehabilitation Research Group, Faculty of Kinesiology and Rehabilitation 
Sciences, KU Leuven 
Principal investigator: Prof. Alice Nieuwboer 
 
 
 
Tervuursevest 101, 3001 Heverlee 
 
 
 
Tel: 016/32.91.19 
 
 
 
E-mail: alice.nieuwboer@kuleuven.be  
Sub-investigator: 
Veerle de Rond, MSc 
 
 
 
Tervuursevest 101, 3001 Heverlee 
 
 
 
Tel: 016/37.28.39 
 
 
 
E-mail: veerle.derond@kuleuven.be 
Study period:   
01/10/2020 – 01/01/2022 
 
 
2 Summary of the protocol 
2.1 Participants 
40 healthy older adults 
2.2 Study type 
Monocentric study at the faculty of Movement and Rehabilitation Sciences, observational study, academic 
study. 
2.3 Measurements 
 
Screening tests to evaluate motor and cognitive function 
 
Clinical measuring scales for the evaluation of balance 
 
Task that requires weight-shifting 
 
Measurements of cortical activity by means of functional Near-Infrared Spectroscopy (fNIRS) 
2.4 Duration experiments 
One session of ± 3.5 hours, including 25 min of training, and one session of ± 1.5u. There will be a period 
of 24 hours between both sessions. 

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2.5 Location experiments 
Faculty of Movement and Rehabilitation Sciences (KU Leuven). 
3 Background and rationale 
In 2015, about 900 million people in the world were aged 60+. By 2050, this population will increase up to 
more than 2 billion1. Older people show deficits in balance control2 and dynamic weight shifting, as more 
time is needed to perform weight-shifts and the movement becomes less fluent and accurate3. In addition, 
mediolateral weight-shift performance has been linked not only to ageing, but also to balance and falls4, 5. 
An observational study even showed that incorrect weight-shifting accounted for 41% of falls6, making it 
one of the main causes of falls in the older population. Previous work reported prevalence rates of 33% 
up to 50% of healthy older adults who fall at least once a year7, 8. Falling has serious consequences for 
quality of life and mortality9. As such, investigating potential methods to delay or reduce falling is of utmost 
importance to prevent immobility and a sedentary lifestyle in healthy ageing. 
Studying the neural basis of whole body movements is of great importance to increase our insight of gait 
and balance. The gold standard method is functional Magnetic Resonance Imaging (fMRI) during motor 
imagery of stance, which identified increased Blood Oxygenation Level Dependent (BOLD) activity in the 
brainstem, basal ganglia, cerebellum and cerebral cortex during ‘postural control’10. A major drawback of 
brain scanning is that it occurs in a supine position. In contrast, functional near-infrared spectroscopy 
(fNIRS) allows measuring brain activity while being upright, albeit at a much lower temporal and spatial 
resolution11. However, mobile fNIRS systems now permit a wider brain coverage than hitherto possible to 
examine the neural correlates of postural stability, at least at the cortical level. fNIRS has also been 
validated against fMRI12, is more resistant to head motion compared to other EEG12 and is feasible for use 
in older adults13, 14.  
Recent systematic reviews showed that postural control in older adults can be improved with training15. 
However, little is known about the ability and maintenance of re-learning to weight-shift, let alone about 
its underlying mechanism. Therefore, the primary aim of this project will address this lacuna by studying 
the effects of training in weight-shifting performance in older adults and its underlying neural imprint. As 
our previous study (unpublished) showed that adding an extra cognitive task in a so-called dual-task (DT) 
negatively affects weight-shifting performance, a secondary aim will be to test whether weight-shift 
training will enhance performance during such DT conditions. The results of this study might form a basis 
for future technology-based rehabilitation programs. 
4 Study objectives 
The effects of postural learning on cortical activity have not been identified yet in older adults. During non-
postural tasks, older adults needed greater activity and recruited more brain areas during automatization 
compared to young adults. This is suggested to be the primary reason for impaired motor automaticity 
with age16. We will use fNIRS to examine postural learning in the upright position for the first time in older 
adults. More specifically, we will investigate: 

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1. Changes in brain activity in frontal, (pre-)motor, and parietal regions associated with the 
acquisition and consolidation of weight shifting in older adults. In addition, as moving the Centre 
of Mass (CoM) deliberately also loads sensorimotor function, we will include the parietal cortex as 
region of interest. 
2. Changes in brain activity in frontal, (pre-)motor, and parietal regions associated with the 
acquisition and consolidation of weight shifting compared to no training (control group). 
3. Changes in brain activity in frontal, (pre-)motor, and parietal regions associated with the transfer 
of single-task acquisition and consolidation of weight shifting to dual-task weight shifting 
performance. 
5 Methodology of the research 
5.1 Participants 
In total, 40 subjects will be recruited aged 65+. Inclusion criterion include being able to independently 
stand upright > 5 min. Exclusion criteria are: (a) history of neurological disorders; (b) balance impairments 
(i.e. vestibular disorders); (c) cognitive impairment (Mini Mental State Exam (MMSE) < 24); (d) visual 
impairment precluding following of visual targets or colour-blindness as measured with the Ishihara test 
for color deficiency; (e) chronic musculoskeletal (e.g. osteoarthritis, osteoporosis), cardiovascular (e.g. 
hypertension, peripheral vascular disease) and respiratory (e.g. chronic obstructive pulmonary disease) 
disease, as well as diabetes related polyneuropathy.  
For this study, 40 healthy older adults will be included. Our previous fNIRS study (unpublished) revealed 
that our primary outcome, weight-shifting speed, improved from 0,0668 ± 0,0255 m/s to 0,0916 ± 0,0350 
m/s. Based on Caljouw et al.17, we expect a training effect size of 20%, resulting in a weight-shifting speed 
of 0.1094 ± 0,0418 m/s. Applying a power of 80% and alpha of 0.05 for a repeated measures ANOVA with 
a within-between interaction design (within: pre vs post: between: training vs control) we calculated a 
total sample size of 40 participants (20 per group). Considering possible data exclusion due to fNIRS 
measurements, the collected fNIRS data will be monitored during recruitment, and recruit more 
participants if necessary.  
 
5.2 Recruitment 
Heathy older adults will be recruited based on the age-criterion, i.e. 65+ years. We will announce our study 
on websites and pin boards reaching older adults (e.g. seniorama, Universiteit Derde Leeftijd, gym clubs, 
etc.). When interested, potential participants will be provided with the information folders (either via e-
mail or regular mail) to present the necessary information in writing. A follow-up conversation will follow, 
either via telephone or at the candidates’ home if preferred. During this conversation the study goals and 
protocol of the study, as described in the informed consent forms, will be explained thoroughly to make 
sure everything is clear for the possible participant and allowing him/her to ask questions and make an 
informed decision. The researchers responsible for testing will execute this recruitment process. The flyers 
and information folders can be found in the respective files.  
 

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5.3 Experimental procedure 
5.3.1 General procedures 
Design 
Participants will be randomly allocated to the training and control groups. The control group will not 
receive any form of training. Randomization will be computer-generated and blocked in groups of four to 
achieve optimal distribution in each training arm. The study will have a repeated measures design with 
two test sessions on two consecutive days. 
Motor and cognitive screening 
We will collect data on fall frequency, Mini-Balance Evaluation System (Mini-BESTest), and Falls Efficacy 
Scale. The cognitive assessment will consist of Montreal Cognitive Assessment and specific tests for 
visuospatial and attention. 
Weight-shifting task 
Before starting the weight-shifting task (WASP task), functional limits of stability (fLOS) will be assessed by 
asking the subject to move the Centre of Mass (CoM) as far as possible over its base of support (Fig. 3A) in 
eight different directions by pushing a virtual bar away from the center position. Mean CoM shifts will be 
calculated and used for personalized scaling of the WASP. Only weight-shifting in the ML direction will be 
tested and trained to avoid motion artefacts during fNIRS data collection, and because ML weight-shifting 
in particular has been linked to balance and falls4, 5. The WASP task (Fig. 3B) was developed and piloted to 
meet the requirements for balance training for older people in a PhD project under supervision of prof. S. 
Verschueren (De Vries A, 2018). Pilot data showed that the WASP is feasible for use in older adults and can 
capture fluency of motion as a learning outcome.  
Figure 1: (A) Functional limits of stability; (B) Weight shifting task in ST. Red ball is CoM; (C) WASP + serial subtraction in DT 
 

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Fig. 3B shows that the player is in the middle of an area infested by wasps. By moving the CoM (displayed 
by the red dot) towards a pre-defined 80% of the fLOS, a water stream will come on to hit the wasp. The 
number of wasps hit, weight-shifting accuracy, comprising the CoM traject and target deviation, and speed 
are used as outcomes. The WASP-ST involves hitting wasps in the ML direction by shifting weight. Fig. 3C 
illustrates the WASP-DT. Participants have to perform a serial subtraction task as the secondary task, 
whereby the red ball (representing the CoM) will change color from red to white and white to red within 
a random interval between 2-5 seconds. A starting number will appear on the screen for 1.5 sec at the 
beginning of each trial. Every time the ball changes its color, subtractions have to be made in threes. 
Subjects will indicate the correct number afterwards, so as not to disturb the fNIRS recording.   
5.3.2 Study specific procedures 
On day 1, subjects in the training group will receive the WASP-training, consisting of 10 blocks of 2.5 
minutes. Training will be adjusted to the individual fLOS targeting at least 80%. Before and after training, 
weight shifting ability will be assessed using the WASP-tests with and without serial subtractions. We will 
measure cortical activity with fNIRS during weight-shifting following recent guidelines11. We propose a 
block design distinguishing periods of quite stance from weight shifting. Participants will undergo two 
blocks offered in a fixed order: I) WASP-ST; II) WASP-DT. Each block has a duration of 4m40s, starting with 
20s quiet stance, followed by 20s weight-shifting, alternating in seven trials. This block design allows for 
the 4s-7s delay in the hemodynamic peak response by having sufficiently long periods of task exposure. 
Subjects are not allowed to speak, so as not to disturb the fNIRS signal. In the DT-condition, subjects will 
be asked to focus on the primary and secondary tasks equally. Subjects in the control group will not receive 
any form of training. Retention tests will occur on day 2 (24 hr). Also, simultaneous fNIRS measurements 
will be carried out. fNIRS was found to have adequate test-retest reliability18. Cap placement will be 
marked to facilitate accurate placement on day 2. 
5.4 Equipment 
Postural outcomes will be measured on the Computer Assisted Rehab Environment (CAREN) (Motek 
Medical BV, Amsterdam) with integrated force plates. Spherical reflective markers placed bilaterally on 
anatomical landmarks will allow 3D-kinematic analysis with 7 MX-T20 optoelectronical cameras (Vicon, 
Oxford Metrics, UK), which will be done both online with D-Flow software (Motek Medical BV, Amsterdam) 
as offline. Changes in the brain hemoglobin concentrations will be registered with a wireless 16-16 fNIRS 
system (NirXsports 2), which has the required resolution and coverage to meet the study objectives. 
Sixteen optodes per hemisphere will be placed over the prefrontal, posterior parietal and premotor, SMA 
and M1 regions with an inter-optode distance of 35 mm, placed on an EEG-cap using the 10-20/10-10/10-
5 EEG system. 
6 Statistics, data handling and data management 
6.1 Data storage 
Part of the data that are obtained on paper will be stored on paper (e.g. questionnaires, informed consent 
forms), as well as in an excel file. The data obtained by computerized measures will all be stored in the 
original digital files, and the main variables will be stored in excel data files. All digital files will be saved on 

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protected server file storages of the KU Leuven (automatic back-up). Anonymized data files will be shared 
after publications of the results and upon request with the PI. 
6.2 Data analysis and statistics 
Calculation of the CoM data will be processed using Nexus 2.4 and customized Matlab scripts. Body 
movement during postural control, comprising CoM displacement, deviation of trajectory and speed will 
be calculated. To account for motion artefacts during fNIRS measurements, we will perform visual checks 
and signal processing techniques, including filtering and noise removal. A linear mixed model will analyze 
learning effects with training group as between-subject and pre-post-retention as within subject factor.  
7 Safety 
There are no permanent risks involved for the subjects participating in this study. All experiments are 
painless and harmless for participants. A safe and existing test infrastructure will be used and experienced 
researchers will conduct the experiments. Participants will be informed about the procedure and possible 
risks of the tests before the start of the experiment. Some of the participants may feel some fatigue during 
the weight shifting trials. To prevent excessive fatigue, participants will be encouraged to take breaks as 
needed in-between all trials. The fNIRS head cap will be cleaned/washed after each participant to ensure 
appropriate adherence to infection control policies. Based on a recent PhD thesis on the development and 
validity of the WASP task [de Vries, A (PhD thesis, March 2018)] we do not anticipate that any risks will be 
involved in the use of this WASP task. 
For all subjects, a safety screening will be executed for the MRI protocol before informed consent will be 
obtained. Participants will be encouraged to ask questions about the study protocol and possible risks at 
any time of the experiment, as well as during the inclusion session. In between trials, sufficient rest periods 
will be inserted to avoid fatigue. During the MRI scan sessions, the aim is to minimize the potential 
discomfort of the participants. All subjects will be informed thoroughly about MRI technology and the 
setup in UZ Leuven Hospital. In addition, participants will be prepared for the real scanning session by 
including a practice session in a dummy MRI scanner. During the MRI scan session at the UZ Leuven 
Hospital, the researcher will be in contact (verbally) with the subject to assess his / her condition. An easily 
accessible panic button will be provided to all subjects and the function of this button will be explained in 
detail. The MRI scan sessions will be conducted by the researchers involved and will have no diagnostic 
purpose. Through the consent form, participants will be informed that the images will go through standard 
checks by a radiologist. Possible abnormalities can always be missed. If any deviations are detected, this 
will be reported to the Radiology Department of the UZ Leuven hospital, supervised by Prof. Stefan Sunaert 
and appropriate information will be delivered to the general practitioner involved. 
7.1 Adverse event reporting 
7.1.1 Definitions 
 
Adverse event (AE): any untoward medical occurrence in a patient or subject during an 
experiment, and which does not necessarily have a causal relationship with this treatment. An AE 
can be any unfavorable and unintended sign (including an abnormality on an MRI scan), symptom 
or disease temporally associated with the intervention, whether or not considered related to the 

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intervention. Any worsening (i.e., any clinically significant adverse change in the frequency or 
intensity of a pre-existing condition) should be considered an AE. 
 
Adverse Reaction (AR): any untoward and unintended responses to an investigational medicinal 
product or to an experiment and, when an investigational product is concerned, related to any 
dose administered. 
 
Serious adverse event (SAE): any untoward medical occurrence that results in any of the following: 
o Death 
o A life-threatening experience, i.e. in which the subject was at risk of death at the time of 
the event 
o In-patient hospitalization 
o A persistent or significant disability or incapacity 
o Important medical events that may be considered an SAE when, based on appropriate 
medical judgement, they may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the above outcomes 
 
Suspected Unexpected Serious Adverse Reaction (SUSAR): an adverse reaction, the nature or 
severity of which is not consistent with the information on the experiment, and, when a clinical 
trial is concerned, with the applicable product information (e.g. investigator's brochure for an 
unauthorised investigational product or the patient leaflet joined to the summary of product 
characteristics for an authorised product). 
7.1.2 Adverse events that do not require reporting 
 
Pre-existing conditions related to the symptomatology and medical treatment of Parkinson’s 
disease, e.g. tremor, rigidity, balance impairments, freezing, orthostatic hypotension, etc. 
 
Pre-planned hospitalizations, unless the condition for which the hospitalization was planned has 
worsened from the first trial-related activity after the subject has signed the informed consent 
7.1.3 Recording and reporting of adverse events 
The investigators will seek information on AEs during each patient contact after the start of the 
intervention, i.e. at the end of day 1 and on day 2, by means of a safety assessment. All events, whether 
reported by the patient or noted by the trial staff, will be recorded within a reasonable time after becoming 
aware. 
All AEs will be evaluated by an investigator as to: 
 
Seriousness: whether the AE is an SAE or SUSAR, see above for criteria 
 
Severity 
o Mild: no or transient symptoms, no interference with the subject’s daily activities 
o Moderate: marked symptoms, moderate interference with the subject’s daily activities 
o Severe: considerable interference with the subject’s daily activities, unacceptable 
 
Causality 
o None: An AE which is not related to the study-related interventions 

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o Unlikely: An AE for which an alternative explanation is more likely (e.g. concomitant 
medication(s), concomitant disease(s)), and/or the relationship in time suggests that a 
causal relationship is unlikely 
o Possible: An AE which might be due to the study-related interventions. An alternative 
explanation is inconclusive. The relationship in time is reasonable; therefore the causal 
relationship cannot be ruled out. 
o Probable: An AE which might be due to the study-related intervention. The relationship in 
time is suggestive (e.g. confirmed by dechallenge). An alternative explanation is less likely. 
o Definitely: An AE which is known as a possible adverse reaction and cannot be reasonably 
explained by an alternative explanation. The relationship in time is very suggestive (e.g. it 
is confirmed by dechallenge and rechallenge). 
After informed consent has been obtained and after initiation of study-related interventions, all AEs, ARs, 
SAEs and SUSARs causally related to a study-related intervention will be reported until 30 days after the 
last study-related intervention or until last follow-up visit (whichever occurs first). All SAEs or SUSARs will 
be reported to the treating physician and ethical committee within 24 hours of the trial staff becoming 
aware of the event. Further study participation will be discussed with the treating physician. The 
immediate report shall be followed by detailed, written reports. 
SAEs and SUSARs will be followed up until the outcome of the event and any related queries are resolved. 
Non-serious AEs and ARs will be followed up until the participants last study visit, and until all related 
queries have been resolved. 
If the investigator becomes aware of an SAE with suspected causal relationship to the study-related 
interventions after the subject has ended the trial, the investigator will report this SAE within the same 
timelines as for SAEs during the trial. 
7.1.4 Annual reporting 
The sponsor has the obligation to, once a year throughout the clinical trial (or on request), submit a 
progress report to the ethical committee containing an overview of all serious adverse reactions that 
occurred during the reporting period and taking into account all new available safety information received 
during the reporting period. 
8 Costs 
Full reimbursement of travel expenses for the people with Parkinson’s disease and age-matched controls 
(i.e. the healthy elderly) will be covered by the project. There will be no additional reimbursement. 
9 Ethics 
The protocol is submitted for review to the local Ethics Committee of KU Leuven (Commissie Medische 
Ethiek UZ Leuven, Herestraat 49, 3000 Leuven). The study will be performed in accordance with The Code 
of Ethics of the World Medical Association (Declaration of Helsinki) and the principles of GCP. Any 

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subsequent protocol amendments will be submitted to the Ethics Committee and Regulary Authorities for 
approval. 
After complete explanation of the study protocol, written informed consent will be obtained from all 
participants prior to participation in the experiment. 
The investigators will treat all information and data relating to the study confidential. If data are shared 
on the internet upon publications of the results, obligations with regard to protection of the results, 
confidentiality, security and the obligations to protect personal data will be guaranteed. Critical or 
sensitive data will be pseudonymized to ensure that re-identification by combining pseudonymized data 
with other population data is impossible. The key to the pseudonymized data will be stored on KU Leuven 
network drives, with no access from outside. 
The collection, processing and disclosure of personal data, such as patient health and medical information 
is subject to compliance with applicable personal data protection and the processing of personal data 
(Directive 95/46/EC and Belgian law of December 8, 1992 on the Protection of the Privacy in relation to 
the Processing of Personal Data). 
It is possible that pseudonomized data will be shared with other partners in the Keep Control network, to 
further improve and cross-validate algorithms. This network consists of 12 European Principal 
Investigators and fellows, respectively, all focusing on the improvement of motion-based algorithms for 
the detection and description of neurological movement disorders and age-associated movement deficits. 
Transmission of information will only be performed with encrypted data files. The cooperation partners 
are not entitled to pass on the data to third parties. Anyone with access to the data, including the 
investigator, is subject to professional secrecy during and after the project. 
10 Insurance 
In accordance with the Belgian Law relating to experiments on human persons dated May 7, 2004, Sponsor 
shall assume, even without fault, the responsibility of any damages incurred by a Study Patient and linked 
directly or indirectly to the participation to the Study, and shall provide compensation therefore through 
its insurance. 
The study is insured by KU Leuven. 
11 References 
1. 
United Nations DoEaSA, Population Division. World Population Ageing 20152015. 
2. 
Park JH, Mancini M, Carlson-Kuhta P, Nutt JG, Horak FB. Quantifying effects of age on balance and 
gait with inertial sensors in community-dwelling healthy adults. Exp Gerontol 2016;85:48-58. 
3. 
de Vries EA, Caljouw SR, Coppens MJ, Postema K, Verkerke GJ, Lamoth CJ. Differences between 
young and older adults in the control of weight shifting within the surface of support. PLoS One 
2014;9:e98494. 
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Cofre Lizama LE, Pijnappels M, Rispens SM, Reeves NP, Verschueren SM, van Dieen JH. 
Mediolateral balance and gait stability in older adults. Gait Posture 2015;42:79-84. 

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5. 
Piirtola M, Era P. Force platform measurements as predictors of falls among older people - a 
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Robinovitch SN, Feldman F, Yang Y, et al. Video capture of the circumstances of falls in elderly 
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Vitorio R, Stuart S, Rochester L, Alcock L, Pantall A. fNIRS response during walking - Artefact or 
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Noah JA, Ono Y, Nomoto Y, et al. fMRI Validation of fNIRS Measurements During a Naturalistic 
Task. J Vis Exp 2015:e52116. 
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Maidan I, Nieuwhof F, Bernad-Elazari H, et al. The Role of the Frontal Lobe in Complex Walking 
Among Patients With Parkinson's Disease and Healthy Older Adults: An fNIRS Study. Neurorehabil Neural 
Repair 2016;30:963-971. 
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Nieuwhof F, Reelick MF, Maidan I, et al. Measuring prefrontal cortical activity during dual task 
walking in patients with Parkinson's disease: feasibility of using a new portable fNIRS device. Pilot 
Feasibility Stud 2016;2:59. 
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Howe TE, Rochester L, Neil F, Skelton DA, Ballinger C. Exercise for improving balance in older 
people. Cochrane Database Syst Rev 2011:CD004963. 
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Wu T, Hallett M. The influence of normal human ageing on automatic movements. J Physiol 
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Caljouw SR, Veldkamp R, Lamoth CJ. Implicit and Explicit Learning of a Sequential Postural Weight-
Shifting Task in Young and Older Adults. Front Psychol 2016;7:733. 
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Schecklmann M, Ehlis AC, Plichta MM, Fallgatter AJ. Functional near-infrared spectroscopy: a long-
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