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.
During experiment 1, participants learn the MSL by self-initiating a 5-element finger
sequence that is presented on screen. After learning, participants will be equipped with PSG,
which includes EEG. Based on blinded randomization, they will nap for 2 hours or lie on the
bed but remain awake for a similar duration. The wake PSG will ensure that no participant in
the wake group falls asleep. Participants will then enjoy a 30-45min break to counter sleep
inertia effects, prior to being re-tested on the MSL (Retest 1). The next day, participants
will be re-assessed on the MSL for 24h retention testing (Retest 2).
During experiment 2, similar procedures will be followed as described above except that
participants will learn two new finger sequences that are auditory cued, by means of a serial
reaction time task (SRT). For the SRT, participants view a row of empty squares presented in
the middle of the screen and each time a square is highlighted the participant is instructed
to tap the finger that is spatially associated to that square as quickly and accurately as
possible, i.e. a serial reaction time task. The difference between the MSL task of experiment
1 and the SRT task of experiment 2 is therefore that during experiment 1 participants
self-initiate a sequence that is explicitly shown to them, whereas in experiment 2 the
sequence is cued. The order of sequence blocks during learning and retest as well as the
sequence selected for TMR will be randomized across participants. Performance on both
sequences will be re-assessed after the break, and again at 24h retention without auditory
cues.
The MSL and SRT tests in both experiments will be preceded by a psychomotor vigilance test as
an objective measure of the participants' vigilance on the day and include a single- and
dual-task condition.
Power calculation:
Based on the findings by Terpening et al. (2013) and Dan et al. (2015), a minimum of 16
subjects per group (NAP, WAKE) will be required according to our power analysis based on the
MSL-outcomes using β=0.20 and α=0.05 to detect a significant group difference. To account for
potential dropouts, the recruitment target is set 20% higher to ensure adequate power in our
final analysis. As such, a total of 40 PD patients and 40 healthy elderly controls will be
recruited for experiment 1 (i.e. 20 in each NAP/WAKE group). The best sample estimation at
this time for experiment 2 is based on previous TMR studies in younger adults also recruiting
16 subjects per nap/wake group (Antony et al. 2012). Therefore, we will target to recruit a
total of 20 PD and 20 healthy elderly controls for Experiment 2, again accounting for 20%
potential dropout.