Boosting motor learning through sleep and targeted memory reactivation in ageing and Parkinson’s disease

Project Information

TARGET SLEEP

Grant agreement ID: 838576

DOI

10.3030/838576

Project closed

EC signature date 23 July 2019

Start date 1 January 2020

End date 31 December 2021

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 166 320,00

EU contribution

€ 166 320,00

Coordinated by

KATHOLIEKE UNIVERSITEIT LEUVEN
Belgium

Periodic Reporting for period 1 - TARGET SLEEP (Boosting motor learning through sleep and targeted memory reactivation in ageing and Parkinson’s disease)

Reporting period: 2020-01-01 to 2021-12-31

Summary of the context and overall objectives of the project

Parkinson’s disease (PD) is the second most prevalent degenerative brain disease, for which there is no cure. Rehabilitation is important for people with PD, whereby motor adaptations are learned to maintain daily functioning. However, patients often present difficulty consolidating the newly learned skills into their long-term memory, which reduces the benefits of training. Interventions that enhance motor memory consolidation are therefore projected to diminish the impact of PD. Sleep facilitates consolidation in healthy adults, especially in combination with targeted memory reactivation (TMR). TMR works by adding associated auditory stimuli during learning, which are replayed during sleep to reinforce the recently formed neural connections. Importantly, consolidation during sleep may be preserved in PD, but robust findings are lacking and have not involved TMR. My objective is to address this imperative by investigating the effect of sleep on motor memory consolidation by experimentally manipulating exposure to sleep and TMR. Concretely, I will compare the effect of a 2-hour daytime nap with or without TMR to that of a wake control period in PD and healthy age-matched controls. I will use a validated motor sequence learning task and apply neuroimaging techniques to study the neurophysiology underlying consolidation. My training objectives include teaching neuroscientific topics and research leadership development. I will also implement a rigorous dissemination and communication plan to achieve optimal societal impact of my research findings. I anticipate my project to spark new sleep interventions that boost the effectiveness of rehabilitation and improve the wellbeing of our ageing population, in particular those affected by PD.

Unfortunately, the global COVID-19 pandemic has significantly delayed the progress of this project, which could therefore not achieve its final conclusions within the 2-year fellowship period (2020-2021). However, in that time the applicant was appointed as professor at the beneficiary institution (KU Leuven, Belgium) and will therefore be able to continue the project beyond the fellowship period.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In light of the difficulties imposed by COVID-19, the applicant reached 73% of the recruitment target for this project. It is anticipated that the project will reach completion by the year 2023.

Besides the main studies in the project, the applicant transferred his knowledge to the research community regarding the neural basis and treatment of complex symptoms in PD, co-supervising two doctorate (PhD) students, 8 Master theses, and co-publishing a total of eight publications in scientific journals on this topic (see list below). The main contribution to the state-of-the-art during the fellowship was achieved with regards to this additional work that, in contrast to the proposed studies as specified in the description of the action, was less affected by COVID-19 restrictions.

Scientific publications (available open-access):
1. Gilat M, D’Cruz N, Ginis P, Vandenberghe W, Nieuwboer A. Freezing of gait and levodopa. Lancet Neurology. 2021. 20(7):505-506.
2. Gilat M, Ginis P, Zoetewei D, De Vleesschauwer J, Hulzinga F, D’Cruz N, Nieuwboer A. A systematic review on exercise and training-based interventions for freezing of gait in Parkinson’s disease. NPJ Parkinson’s disease. 2021. 7(1):81.
3. Hulzinga F, de Rond V, Vandendoorent B, Gilat M, Ginis P, D’Crus N, Schlenstedt C, Nieuwboer A. Repeated gait perturbation training in Parkinson’s disease and healthy older adults: A systematic review and meta-analysis. Frontiers Human Neuroscience. 2021. 15:732648.
4. Dijkstra B, Gilat M, Cofré Lizama LE, Mancini M, Bergmans B, Verchueren SMP, Nieuwboer A. Impaired weight-shift amplitude in people with Parkinson’s disease with freezing of gait. Journal of Parkinson’s disease. 2021.11(3):1367-1380.
5. D’Cruz N, Vervoort G, Chalavi S, Dijkstra BW, Gilat M, Nieuwboer A. Thalamic morphology predicts the onset of freezing of gait in Parkinson’s disease. NPJ Parkinson’s disease. 2021. 7(1): 20.
6. Dijkstra B, Bekkers E, Gilat M, de Rond V, Hardwick R, Nieuwboer A. Functional neuroimaging of human postural control: a systematic review with meta-analysis. 2020. Neuroscience and Biobehavioral Reviews. 2020 115: 351-362.
7. Canning CG, Allen NE, Nackaerts E, Paul SS, Nieuwboer A, Gilat M*. Virtual reality in research and rehabilitation of gait and balance in Parkinson’s disease. Nature Reviews Neurology. 2020. 16(8): 409-425.
8. Gilat M, Marshall NS, Testelmans D, Buyse B, Lewis SJGL. A critical review of the pharmacological treatment of REM sleep behavior disorder in adults: Time for more and larger randomized placebo-controlled trials. Journal of Neurology. Epub since 07/01/2021.

The applicant gave the following scientific presentations to researchers and clinicians at the KU Leuven, Belgium, during the fellowship period:
Date Title
25/08/20 Sleep in Neurorehabilitation
06/12/21 Differential Diagnosis of Parkinson’s disease
17/02/20 Sleep to Move
08/12/21 Neurorehabilitation of Parkinson’s disease

The applicant presented the outcomes of the fellowship to researchers and clinicians at the following international scientific congresses:
1. 12/2021 French Society of Posture Balance and Locomotion Congress, Lille, France
2. 06/2021 Belgian Association for Sleep Science (BASS) Symposium, Leuven, Belgium
3. 11/2020 Faculty at the International Movement Disorder Society virtual congress, online.
4. 07/2020 E-Learning Module on exercise for PD, Movement Disorder Society (co-presenter), online.

For Parkinson patients, the applicant:
1) Co-authored a lay-language article on the impact of COVID19 on the mobility of people with PD in the journal 'Parkoers' of the Flemish Parkinson League (VPL);
2) Published tips on promoting good sleep during the COVID19 pandemic on the VPL website;
3) Presented tips on promoting good sleep during the World Parkinson Day online webinar hosted by the VPL;
4) Became a board-member of the multidisciplinary advisory board of the VPL.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The present project will provide much-needed insights into the remaining capabilities for neurorestoration in PD with strong potential to facilitate motor output and promote wellbeing. If proven effective during a single daytime nap, implementation in longer training paradigms will be studied next. The applicant applied for project funding to continue this work.

The project contributed towards the following European policy objectives:
i) Research & Innovation: We will adhere to principles of open-science, making our research more efficient, reliable, collaborative and transparent.
ii) Education & training: New collaborations were established between international universities. By following teaching training courses, the applicant abided to the EU mission to improve teaching quality.
iii) Public Health: The outcomes will strengthen the evidence-base for applying sleep interventions in rehabilitation for motor impairment in PD. If sleep proves potent, this may inspire people to take better care of their own sleep, thereby indirectly enforcing the EU mission to promote good health in its citizens.

Although the conclusions could not be reached during the fellowship period due to COVID19 restrictions, as a newly appointed professor at the KU Leuven the applicant will be able to keep overseeing the project beyond the fellowship period and until completion.

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