Role of Sleep on Motor Learning in Parkinson's Disease and Healthy Older Adults

NCT04144283 | Unknown

• 3 other identifiers: S617928385762019-J4121350-212854
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

People with Parkinson's disease (pwPD) often present difficulty consolidating newly learned skills into long-term memory. Sleep facilitates motor memory consolidation in healthy adults, especially in combination with targeted memory reactivation (TMR). TMR works by adding associated sounds during learning that are replayed during sleep and thus reinforce the recently formed neural connections. Importantly, recent work suggested that consolidation during sleep may be preserved in pwPD, but robust findings are lacking and have not involved TMR. The objective of the present study is to address this imperative question by investigating the effect of napping on motor memory consolidation by experimentally manipulating exposure to sleep and TMR for the first time. Concretely, the investigators will first compare the effect of a 2-hour nap to that of a wake control period in pwPD and healthy age-matched controls. A validated motor sequence learning task will be used to test for behavioral markers of motor learning and polysomnography with electroencephalography (EEG) will be conducted to study the neural correlates of sleep-related motor learning effects. In a second experiment, the investigators will then test the effects of adding TMR during post-learning sleep, by comparing performance on two motor sequences of which only one is reactivated during post-learning napping using auditory TMR.

Conditions

Parkinson Disease; Aging

Keywords

Parkinson's disease; Ageing; Rehabilitation; Sleep; Motor learning; Targeted Memory Reactivation

Outcome Measures

Primary Outcomes (4)

• Experiment 1 - MSL single task: Offline consolidation

  Participants perform a self-initiated MSL task by tapping a five-element finger sequence presented on screen as rapidly and accurately as possible with their non-dominant hand for 18 blocks during learning and again at each retest assessment. Each block consists of 50 key presses (ideally 10 sequences) and is followed by a rest block of 15-20 seconds without finger tapping. A two-minute rest period will be implemented after 14 blocks to further minimize the effects of fatigue on the last 4 blocks that are used to calculate the primary outcome. Performance on the MSL will be assessed using the 'Performance Index (PI)' \[PI=exp\^-(seqDur) \* exp\^-(Errors/12) \* 100\], taking both speed and accuracy into account (King et al. 2017b). After learning the MSL, participants are randomly allocated to undergo a post-learning 2-hour diurnal sleep opportunity (NAP) or 2-hour period of quiescent wakefulness (WAKE) before being reassessed on the MSL.

  Change in PI between the first 4 blocks immediately after the 2-hour NAP or WAKE intervention (Retest 1) and the last 4 blocks of learning immediately prior to the intervention.

• Experiment 1 - MSL single task: Retention

  The same MSL task as described above in Primary outcome 1 is again repeated 24-hours after Retest 1 in order to assess whether the sleep-related effects on motor memory consolidation are retained in the long-term (Retest 2).

  Change in PI between the first 4 blocks after the 24-hour retention period (Retest 2) and the last 4 blocks of Retest 1 immediately after the 2-hour NAP or WAKE intervention.

• Experiment 2, SRT single task: Offline consolidation

  Experiment 2 is similar to experiment 1, except that participants will learn two motor sequences that are visually and auditory cued by means of a serial reaction time task (SRT). After learning both sequences, participants will nap for 2-hours, but this time while one of the two auditory sequences will be replayed during NREM sleep. Performance on both sequences will be re-assessed immediately after the intervention (Retest 1), and again at 24h retention (Retest 2). The PI will be used to assess performance on the task and compared between the sequence that was replayed and the sequence that is not replayed.

  Change in PI between the first 4 blocks immediately after the nap+TMR intervention (Retest 1) and the last 4 blocks of learning immediately prior to the intervention.

• Experiment 2, SRT single task: Retention

  The same SRT task as described above in Primary outcome 3 is again repeated 24-hours after Retest 1 in order to assess whether the sleep- and TMR-related effects on motor memory consolidation are retained in the long-term.

  Change in PI between the first 4 blocks after the 24-hour retention period (Retest 2) and the last 4 blocks of Retest 1 immediately after the 2-hour NAP+TMR intervention.

Secondary Outcomes (4)

• Experiment 1 - MSL dual tasking: Offline consolidation

  Change in PI between the 4 blocks of dual tasking immediately after the 2-hour NAP or WAKE intervention (Retest 1) and the 4 blocks of dual tasking during learning prior to the intervention.

• Experiment 1 - MSL dual tasking: Retention

  Change in PI between the 4 blocks of dual tasking after the 24-hour retention period (Retest 2) and the 4 blocks of dual tasking at Retest 1 immediately after the 2-hour NAP or WAKE intervention.

• Experiment 2 - SRT dual tasking: Offline consolidation

  Difference in PI between sequences A and B assessed across the 4 blocks of dual tasking immediately after the 2-hour NAP+TMR intervention (Retest 1).

• Experiment 2 - SRT dual tasking: Retention

  Difference in PI between sequences A and B assessed across the 4 blocks of dual tasking after the 24-hour retention period (Retest 2).

Study Arms (2)

NAP

EXPERIMENTAL

The NAP group will undergo a post-learning 2-hour sleep opportunity in Experiment 1.

Behavioral: NAP

WAKE

ACTIVE COMPARATOR

The WAKE group will undergo a post-learning 2-hour period of quiescent wakefulness in Experiment 1.

Behavioral: WAKE

Interventions

NAP BEHAVIORAL

For experiment 1, the NAP group will undergo a post-learning 2-hour diurnal sleep opportunity (i.e. 'nap') without cues. For experiment 2 the NAP+TMR group will undergo a post-learning 2-hour diurnal sleep opportunity (i.e. 'nap') with auditory TMR. The learning related sounds will be presented to participants at 140% of their minimal auditory detection threshold during stage 2 and stage 3 of NREM sleep.

NAP

WAKE BEHAVIORAL

For experiment 1, the WAKE group will undergo a post-learning 2-hour period of quiescent wakefulness without cues.

WAKE

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Right handed
• Can read and understand Dutch
• Age equal or greater than 40 years
• PwPD will have a clinical diagnosis of idiopathic Parkinson's disease made by a Neurologist
• Completed written informed consent approved by the assigned medical ethical committee

You may not qualify if:

• Receiving deep brain stimulation
• Enrollment in an interventional trial for Parkinson's disease therapy
• Severe sleep apnea determined as an Apnea/Hypopnea index (AHI) \> 30 during the screening polysomnography (PSG)
• Cognitive impairment that could question the participant's ability to provide voluntary informed consent as determined by an Mini Mental State Examination score \<24
• Co-morbidities that would hamper interpretation of MSL or SRT learning, such as musculoskeletal abnormalities, as determined by a Neurologist or Physical Therapist.

Sponsors & Collaborators

• KU Leuven: lead

Study Sites (1)

UZ Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

RECRUITING

Related Publications (6)

• Nieuwboer A, Rochester L, Muncks L, Swinnen SP. Motor learning in Parkinson's disease: limitations and potential for rehabilitation. Parkinsonism Relat Disord. 2009 Dec;15 Suppl 3:S53-8. doi: 10.1016/S1353-8020(09)70781-3.

  PMID: 20083008 BACKGROUND

• King BR, Hoedlmoser K, Hirschauer F, Dolfen N, Albouy G. Sleeping on the motor engram: The multifaceted nature of sleep-related motor memory consolidation. Neurosci Biobehav Rev. 2017 Sep;80:1-22. doi: 10.1016/j.neubiorev.2017.04.026. Epub 2017 Apr 29.

  PMID: 28465166 BACKGROUND

• King BR, Saucier P, Albouy G, Fogel SM, Rumpf JJ, Klann J, Buccino G, Binkofski F, Classen J, Karni A, Doyon J. Cerebral Activation During Initial Motor Learning Forecasts Subsequent Sleep-Facilitated Memory Consolidation in Older Adults. Cereb Cortex. 2017 Feb 1;27(2):1588-1601. doi: 10.1093/cercor/bhv347.

  PMID: 26802074 BACKGROUND

• Terpening Z, Naismith S, Melehan K, Gittins C, Bolitho S, Lewis SJ. The contribution of nocturnal sleep to the consolidation of motor skill learning in healthy ageing and Parkinson's disease. J Sleep Res. 2013 Aug;22(4):398-405. doi: 10.1111/jsr.12028. Epub 2013 Feb 11.

  PMID: 23398021 BACKGROUND

• Diekelmann S, Biggel S, Rasch B, Born J. Offline consolidation of memory varies with time in slow wave sleep and can be accelerated by cuing memory reactivations. Neurobiol Learn Mem. 2012 Sep;98(2):103-11. doi: 10.1016/j.nlm.2012.07.002. Epub 2012 Jul 10.

  PMID: 22789831 BACKGROUND

• Micca L, Albouy G, King BR, D'Cruz N, Nieuwboer A, Vandenberghe W, Borzee P, Buyse B, Testelmans D, Nicolas J, Gilat M. The Effect of a Post-Learning Nap on Motor Memory Consolidation in People With Parkinson's Disease: A Randomised Controlled Trial. J Sleep Res. 2025 Sep 26:e70203. doi: 10.1111/jsr.70203. Online ahead of print.

  PMID: 41001836 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Alice Nieuwboer, PhD

  University of Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Moran Gilat, PhD

CONTACT

+3216329427; moran.gilat@kuleuven.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: For experiment 2, participants will be told that sounds may be played during the nap or wake period, without further knowledge on the anticipated effects of these sounds.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Performance on the MSL task (Experiment 1) will be compared between a group that undergoes a 2-hour post-learning NAP and a group that will undergo a 2-hour post-learning WAKE period. Participants will be randomized (1:1) to either the NAP or WAKE group. Performance on the SRT task (Experiment 2) will be compared between the sequence that was replayed during the post-learning nap using auditory TMR (replay) and the sequence that was not replayed (no-replay). The order of sequence blocks during learning and retest as well as the sequence selected for TMR will be randomized across participants. Randomization for both experiments will be done by an independent researcher who is not involved in the measurements of any of the studies using a computerized random number generation technique.

Study Record Dates

• First Submitted: October 28, 2019
• First Posted: October 30, 2019
• Study Start: November 15, 2019
• Primary Completion: September 1, 2023
• Study Completion: December 1, 2023
• Last Updated: March 9, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Upon publication of the study findings for a period of five years.
• Access Criteria: Pseudonymised data will only be shared with research projects that have obtained written approval from a Medical Ethical Committee to use the data for a specific research purpose. Requests for accessing the data should then be made to the PI of the study, Prof Nieuwboer.

Locations

BE (1)