The goal of this clinical trial is to systematically investigate two prominent factors in teenagers' daily life: Caffeine and sleep restriction (SR) and their combined influence on sleep, cognition, and behavior in healthy adolescents. The main questions it aims to answer are: The effects of caffeine under conditions of SR and SE: * on sleep pressure and sleep continuity. * on BOLD activity differences in reward related areas during a reward task (monetary incentive delay task) and on reaction times (behavioral aspect) in the same task. * on BOLD activity differences during a risk taking task (wheel of fortune task) and on risky decision-making (behavioral aspect) in the same task. Participants will be either in the SR or SE condition (between-subject). The protocol consists of 2x of approximately one week in which a participant will receive caffeine or placebo (within-subject) at the last two evenings. The experiment consists of an ambulatory and a laboratory phase: * The ambulatory phase consists of 5 nights, including 3 stabilization nights (8h sleep opportunity) prior to 2 nights consisting of either SR with 6h sleep opportunity or SE with 9.5h sleep opportunity. Participants will wear an actiwatch and fill out sleep diaries during this period. * The laboratory phase will be the 6th evening, night and morning of the protocol and will be spent in our lab. Participants will do the following: * treatment (caffeine vs. placebo) intake * saliva sampling * drug screening * cognitive tests, including risk-taking and reward task * filling in questionnaires (sleep diary, sleep quality, sleepiness, mood, expectancy) * waking and sleep with EEG The next day, participants will undergo an fMRI scan, including the following: * resting-state scan * structural scan * arterial spin labeling scan * reward task scan * risk-taking task scan Around the scan, participants will fill out/undergo: * saliva sampling * questionnaires (reward task, mood, sleepiness, expectancy)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
54
2mg/kg, once before night 6 and once before the scan (either on week 1 or 2, alternating with placebo)
Centre for Chronobiology
Basel, Switzerland
RECRUITINGNighttime Sleep SWA
Sleep at night will be quantified by polysomnographic recordings. Data will be scored epoch by epoch according to standard criteria to assign sleep stages. Spectral analysis will be performed by applying fast Fourier transformation. The key marker of sleep pressure will be slow wave activity (SWA) during NREM sleep (i.e., stage 2+3) defined as EEG power density between 0.75-4.5 Hz. To specify potential effects on SWA more precisely the investigators will additionally conduct separate analyses within this band and with separate (0.5 Hz) bins. To characterize the effects of the experimental manipulation on sleep more comprehensively, the investigators will also conduct analyses on different time bins within one night (e.g. time bin of the first 5 hours of sleep), and on different sleep stages (including wakefulness and latency to sleep), and bands other than SWA. If our resources allow, the investigators will also explore the effects of our experimental manipulation on slow wave energy.
Time frame: Laboratory night week 1
Nighttime Sleep SWA
Sleep at night will be quantified by polysomnographic recordings. Data will be scored epoch by epoch according to standard criteria to assign sleep stages. Spectral analysis will be performed by applying fast Fourier transformation. The key marker of sleep pressure will be slow wave activity (SWA) during NREM sleep (i.e., stage 2+3) defined as EEG power density between 0.75-4.5 Hz. To specify potential effects on SWA more precisely the investigators will additionally conduct separate analyses within this band and with separate (0.5 Hz) bins. To characterize the effects of the experimental manipulation on sleep more comprehensively, the investigators will also conduct analyses on different time bins within one night (e.g. time bin of the first 5 hours of sleep), and on different sleep stages (including wakefulness and latency to sleep), and bands other than SWA. If our resources allow, the investigators will also explore the effects of our experimental manipulation on slow wave energy.
Time frame: Laboratory night week 2
BOLD activity during reward processing
BOLD activity will be measured with a 3T MRT scanner. Brain responses will be modeled in an event-related design using a GLM for each subject at each voxel/trial. Regressors of no interest include motion parameters \& amount of gain or loss. At a within-subject level, the investigators contrast BOLD activity in caffeine vs placebo conditions (\& vice versa). The investigators focus on BOLD activity differences in reward-related regions between anticipation of reward vs neutral events. At the random effects level, the investigators test for the effects of SR vs SE (\& vice versa) and the interaction with caffeine vs placebo. The investigators report whole-brain results. Corrections for multiple comparisons will be made accordingly. The investigators measure RTs to expected rewards, losses, and neutral trials. Task difficulty is individually adapted throughout the task.
Time frame: fMRI session week 1
BOLD activity during reward processing
BOLD activity will be measured with a 3T MRT scanner. Brain responses will be modeled in an event-related design using a GLM for each subject at each voxel/trial. Regressors of no interest include motion parameters \& amount of gain or loss. At a within-subject level, the investigators contrast BOLD activity in caffeine vs placebo conditions (\& vice versa). The investigators focus on BOLD activity differences in reward-related regions between anticipation of reward vs neutral events. At the random effects level, the investigators test for the effects of SR vs SE (\& vice versa) and the interaction with caffeine vs placebo. The investigators report whole-brain results. Corrections for multiple comparisons will be made accordingly. The investigators measure RTs to expected rewards, losses, and neutral trials. Task difficulty is individually adapted throughout the task.
Time frame: fMRI session week 2
BOLD activity during risk-decision making (RDM)
BOLD activity/brain responses will be measured as above. Regressors of no interest additionally include risk probability, indicated amount of gain \& difference in expected value between safe and risky option. At within-subject level, the investigators contrast BOLD activity in caffeine vs placebo conditions (\&vice versa). If number of events is sufficient, the investigators focus on BOLD activity differences in regions related to RDM between safe/risky choices. At the random effects level, the investigators test for effects of SR vs SE (\&vice versa) \& the interaction with caffeine vs placebo. The investigators report whole-brain results Connectivity analyses to characterize brain activity underlying RDM are planned.
Time frame: fMRI session week 1
BOLD activity during risk-decision making (RDM)
BOLD activity/brain responses will be measured as above. Regressors of no interest additionally include risk probability, indicated amount of gain \& difference in expected value between safe and risky option. At within-subject level, the investigators contrast BOLD activity in caffeine vs placebo conditions (\&vice versa). If number of events is sufficient, the investigators focus on BOLD activity differences in regions related to RDM between safe/risky choices. At the random effects level, the investigators test for effects of SR vs SE (\&vice versa) \& the interaction with caffeine vs placebo. The investigators report whole-brain results Connectivity analyses to characterize brain activity underlying RDM are planned.
Time frame: fMRI session week 2
Resting state(rs) functional connectivity (FC)
Rs-FC will be ascertained via BOLD measured with MRI in a 3T Siemens scanner (Prisma; Siemens AG, Erlangen, Germany) using a 24-channel head coil. The standard three-dimensional magnetization-prepared rapid acquisition (MPRAGE) sequence with gradient echo (1x1x1mm, TR=2000ms, TI= 1000ms, TE=3.37ms, FA=8°) will obtain T1-weighted images to depict morphological aspects of the brain. To depict BOLD activity during resting T2\*-weighted echo-planar image (EPI) sequences (TR = 2000, TE = 35ms, FOV = 216mm, voxel size = 2.4 mm3, matrix size 90\*90, 50 slices) will be performed twice for 6-minutes. Foam and inflatable pads will be used to reduce head motion. Participants will be required to have eyes open and stare at a fixation cross to provide greater reliability of within-network connections and reduce experimental variability. Heart rate and respiration will be recorded by Siemens MRI scanner installed hardware.
Time frame: fMRI session week 1; fMRI session week 2
BOLD activity during reward feedback
BOLD activity will be measured with a 3T MRT scanner. Brain responses will first be modeled in an event-related design using a GLM for each subject at each voxel and each trial. Regressors of no interest include motion parameters and indicated amount of gain or loss (high vs low) and the type of feedback. At a within-subject level, the investigators contrast BOLD activity in caffeine vs placebo (and vice versa). The investigators focus on differences in reward-related regions between feedback of successful reward trials vs successful neutral trials. The investigators may run analyses contrasting feedback of successful reward trials vs feedback of neutral trials. At the 2nd (random effects) level, the investigators test for effects of SR vs SE (and vice versa) and interaction with caffeine vs placebo. The investigators correct for multiple comparisons within reward-related regions. The investigators report whole-brain results, corrected for whole brain multiple comparisons.
Time frame: fMRI session week 1; fMRI session week 2
Vigilance
Vigilance performance will be quantified by mean 1/RT for all reaction times in the Psychometric Vigilance Task. The investigators may also report the number of lapses (trials with RT \> 500ms) if meaningful and may explore the effects of our experimental manipulation on other typical outcome variables of the PVT.
Time frame: Laboratory evening (3 times) and morning (1 time SE & 2 times SR) week 1; Laboratory evening (3 times) and morning (1 time SE & 2 times SR) week 2
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Working Memory
Working Memory will be quantified by RT, number of n-back reached, and accuracy (number of missings, number of hits) in an adaptive n-back task. The n-back task is a computer-based task to assess working memory performance. The participant is presented with a sequence of stimuli and must indicate when the current stimulus matches the one from n steps earlier in the sequence. The investigators will use an adaptive n-back version where the n steps adapt to individual performance
Time frame: LaboratoryLaboratory evening (1 time) and morning (1 time) week 1; Laboratory evening (1 time) and morning (1 time) week 2
Inihibition
Inhibition performance will be quantified by the number of commission and omission errors in a go/nogo task. The investigators will also report RTs. The participants will be asked to press a button in response to visually presented stimuli, but to avoid responding to a rarer nontarget.
Time frame: Laboratory evening (2 times) and morning (1 time SE & 2 times SR) week 1; Laboratory evening (2 times) and morning (1 time SE & 2 times SR) week 2
Subjective Sleepiness
Subjective sleepiness will be quantified by the Karolinska Sleepiness Scale (KSS). This is a 9-point scale (1 = extremely, alert, 3 = alert, 5 = neither alert nor sleepy, 7 = sleepy - but no difficulty remaining awake, and 9 = extremely sleepy - fighting sleep) which the participants are asked to fill in.
Time frame: Laboratory evening (7 times) and morning (2 times SE & 4 times SR ) week 1; Laboratory evening (7 times) and morning (2 times SE & 4 times SR ) week 2
Circadian timing (DLMO)
The investigators will measure melatonin levels in saliva samples using biochemical analysis. The investigators will report melatonin levels and melatonin suppression. Dim-light melatonin onset (DLMO) will be the indicator for the onset of the biological night and quantified using the hockey-stick method.
Time frame: laboratory phase week 1 (9 samples SE & 11 samples SR) & fMRI Session week 1 (3 samples) ;laboratory phase week 2 (9 samples SE & 11 samples SR) & fMRI Session week 2 (3 samples)
Objective Sleepiness
The investigators will quantify sleepiness objectively via EEG delta and theta activity (ranges \~0.5-8 Hz) in a 3-minute Waking-EEG where participants will be asked to stare at a fixation cross or during task performance.
Time frame: Laboratory evening (3 times) and morning (1 time SE & 2 times SR) week 1; Laboratory evening (2 times) and morning (1 time) week 2
Subjective Sleep Quality
To measure subjective sleep quality, the investigators use the Leeds Sleep Evaluation Questionnaire (LSEQ) administered in the morning after wake-up. The questionnaire results in values on the four dimensions: Getting to Sleep, Quality of Sleep, Awake Following Sleep, and Behaviour Following Wakening.
Time frame: Laboratory morning week 1 (1 time); Laboratory morning (1 time) week 2