Towards Retention of Motor Learning in Parkinson's Disease: Understanding Sleep-related Effects of Consolidation
试验速览
- 阶段
- 不适用
- 发起方
- KU Leuven
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Experiment 1 - MSL single task: Retention
研究概览
简要总结
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.
详细描述
PwPD often fail to retain training effects via the process of motor memory consolidation, by which newly acquired skills transform intro robust and long-lasting motor memories without further practice. Compromised consolidation leads to an inevitable deterioration of daily functioning while hindering the prolonged effects of rehabilitation even in the early stages of the disease (Nieuwboer et al. 2008). Intriguingly, post-training sleep facilitates consolidation in healthy adults (King et al. 2017a) and this effect may be preserved in pwPD (Terpening, 2013). Targeted Memory Reactivation (TMR) is a technique tested in young adults, whereby auditory stimuli are added during motor learning. The learning-related sounds are then replayed during post-training non-rapid eye movement (NREM) sleep to reinforce the recently formed neural connections (Diekelmann et al. 2012). The overarching hypothesis of this project is that bouts of sleep and TMR will improve the consolidation of motor memories and markers of neuroplasticity in pwPD and older adults.
To test this, the investigators will employ a 'napping' protocol that accounts for circadian effects while allowing performance after diurnal sleep to be directly compared to that of a wake control group (King et al. 2017a). Consolidation will be defined as the change in Motor Sequence Learning (MSL) of finger tapping after a post-training period of either napping or wakefulness compared to the end of initial training. To further indicate robust consolidation, changes in performance will be assessed after a 24h retention period without further practice as well as during a dual-task as a measure of motor automaticity. A parallel group design will allow within group comparison (nap/wake) as well as between pwPD and controls. In a second study, the effects of TMR on consolidation will be compared across groups using a serial reaction time task (SRT).
The first objective (Experiment 1) is to determine whether a 2-hour nap improves the immediate consolidation, 24h retention and dual task interference of an MSL task as compared to a similar period of diurnal wakefulness in people with pwPD and healthy age-matched controls and whether the degree of performance change is different between these groups. Hypothesis 1: The investigators expect to find improved consolidation, 24h retention and reduced dual-task interference of MSL performance following a post-training nap compared to wakefulness in both groups. Possibly, improvements are less apparent in pwPD compared to controls due to their cortico-striatal impairments.
The second objective (Experiment 2) is to determine whether TMR improves immediate consolidation, 24h retention and dual task interference in pwPD and healthy older adults by comparing performance on two learned motor sequences before and after a 2-hour nap period, during which one of the two sequences is replayed using auditory TMR. Hypothesis 3: TMR during napping will improve immediate consolidation, 24h retention and dual task interference of the SRT in both healthy elderly and PD.
Participants first undergo screening, during which demographics, cognitive capacity and disease severity indexes (including dexterity tests) will be obtained prior to undergoing a diagnostic screening night with polysomnography (PSG) to assess for sleep disorder features. Participants will also complete a test battery on sleep quality scales and mood and wear an Actigraphy watch at home for at least five days and nights prior to the first experiment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
盲法说明
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.
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
结局指标
主要结局
Experiment 1 - MSL single task: Retention
时间窗: 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.
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).
Experiment 2, SRT single task: Retention
时间窗: 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.
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.
Experiment 1 - MSL single task: Offline consolidation
时间窗: 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.
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.
Experiment 2, SRT single task: Offline consolidation
时间窗: 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 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.
次要结局
- 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).)
- 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 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.)