Biology subjects

Landolt, H.-P.

Publications and source records attributed to Landolt, H.-P..

14 recordsLinked to original sources

bioRxiv2026

Sleep-dependent modulation of thalamic brain temperature estimates in humans

Mammalian thermal physiology is geared towards dissipating heat during sleep. Brain temperature typically decreases during non-rapid-eye-movement (NREM) sleep in all mammalian species measured to date, yet non-invasive confirmation in healthy humans is lacking: the only available human study used invasive recordings in epileptic patients without a wake control condition. Magnetic resonance spectroscopy (MRS) enables brain temperature mapping non-invasively, using the temperature-sensitive chemical shift of water relative to N-Acetyl-Aspartate as an internal reference. First, we validated that with metabolite cycling (MC), a MRS approach that enables the simultaneous acquisition of metabolite and water information without conventional water suppression, can be used to determine estimates of brain temperature in an ex vivo sheep head. Next, we determined that by using a temporal resolution of ~4 minutes, we obtained high-quality spectra without losing excessive temporal resolution. We then re-analyzed an existing set of MRS data (acquired with the MC sequence) of the thalamus in young adults (n=9) who slept in the evening for up to 2 hours in the scanner, to assess sleep-evoked changes in estimates of brain temperature. Of the nine participants, five participants took part in the subsequent wake-only experiment, allowing to control for the potential impact of circadian time and body posture on estimates of brain temperature. Sleep-wake states were quantified with standard polysomnography, confirming that the participants managed to sleep in the scanner. On average, they spent 39.4+/-15.7 min in N2 sleep, 24.8+/-18.1 min in N3 sleep, 10.0+/-4.9 min in N1 sleep, and 37.0+/-19.6 min awake. Estimates of brain temperature were correlated across the sleep and wake-only experiment within the same participant (R^2=0.29, P<0.0001). When participants entered NREM sleep, estimates of brain temperature decreased by 0.2 degrees Celcius. Moreover, the deeper NREM sleep, the more pronounced the decrease in estimates of brain temperature (P=0.014). These data suggest that an evening nap consisting of NREM sleep decreases thalamic temperature. Considering the profound impact temperature can have on brain functioning, these brain temperature changes could be a pathway through which sleep impacts the brain.

neuroscience↗

bioRxiv2025

Application of Down-Phase Targeted Auditory Stimulation During Sleep in a Home Setting: A Feasibility Study Across Seven Consecutive Nights

IntroductionSleep deprivation, also known as "wake therapy", has long been recognized as a powerful antidepressant. Phase-targeted auditory stimulation (PTAS) has been suggested as an auspicious non-invasive nocturnal substitute for sleep deprivation. Down-PTAS with stimuli presentation during the down-phase of slow waves, in particular, may have therapeutic potential to improve mood by selectively reducing slow-wave activity (SWA). With down-PTAS being more nuanced than sleep deprivation, its effects presumably develop over multiple nights, thus necessitating transfer from sleep laboratory to home settings. Therefore, in this study, we investigated the technical feasibility, tolerability, and potential risks associated with a wearable device employed for down-PTAS in an unsupervised home setting. MethodsWe recorded frontal EEG using the MHSL Sleepband Version 3 (MHSL-SB) in five healthy participants (23.8 {+/-} 0.8 years, three women) over seven consecutive nights with (STIM) and without (SHAM) tone application at their homes. Tones were delivered shortly before the negative peak of slow waves during N2/N3 sleep, using alternating 10-s ON-OFF windows. Sleep staging followed American Academy of Sleep Medicine (AASM) guidelines. Of the 67 available sleep recordings, we excluded three due to parameter adjustments and another six for technical issues, leaving 58 sleep recordings (29 SHAM, 29 STIM) for further analyses. Low SWA (0.5-2 Hz, lSWA) was computed across the entire night, ON-OFF windows, and sleep cycles. Time-frequency analyses were performed time-locked to stimulus onset. We computed linear mixed effect models with condition (STIM vs. SHAM) as a fixed effect and random participant intercepts. ResultsData quality was sufficient for analyses in 87% of the available sleep recordings, with an average of over 1500 correctly delivered stimuli per recording. Down-PTAS did not affect sleep architecture, but it reduced lSWA primarily during the first sleep cycle when sleep pressure and lSWA were highest, and particularly in OFF windows. Additionally, stimulation elicited a K-complex-like auditory evoked response, aligning with previous laboratory findings. ConclusionOur results demonstrate the successful implementation of down-PTAS in a home setting, confirming its feasibility for long-term, unsupervised use. The K-complex-like auditory evoked response may mask potential reductions in lSWA during ON windows, posing a scientific analytical challenge. Taken together, future clinical research should now assess the effects of down-PTAS in depressed patients, in whom reducing lSWA may partly mimic sleep deprivation.

neuroscience↗

bioRxiv2023

Repeated Caffeine Intake Suppresses Cerebral Grey Matter Responses to Chronic Sleep Restriction in an A1 Adenosine Receptor-Dependent Manner.

Evidence has shown that both sleep loss and daily caffeine intake can induce changes in grey matter (GM). Caffeine is frequently used to combat sleepiness and impaired performance caused by insufficient sleep. It is unclear 1) whether daily use of caffeine could prevent or exacerbate the GM alterations induced by chronic sleep restriction, and 2) whether the potential impact on GM plasticity depends on individual differences in the availability of adenosine receptors, which are involved in mediating effects of caffeine on sleep and waking function. In this double-blind, randomized, controlled study, 36 healthy adults (aged 28.9 {+/-} 5.2 y/o; 15 females; habitual daily caffeine intake < 450 mg; 29 homozygous C/C allele carriers of the A2A adenosine receptor (A2AR) gene variant rs5751876 of ADORA2A) underwent a 9-day laboratory visit consisting of one adaption day, 2 baseline days (BL), 5-day sleep restriction (CSR, 5 h time-in-bed), and a recovery day (REC) after an 8-h sleep opportunity. Nineteen participants received 300 mg caffeine in coffee through the 5 days of CSR (CAFF group), while 17 matched participants received decaffeinated coffee (DECAF group). We measured the GM morphology on the 2nd BL Day, 5th CSR Day, and REC Day. Moreover, we used [18F]-CPFPX PET to quantify the baseline availability of A1 adenosine receptors (A1R) and their relation to GM plasticity. The voxel-wise multimodal whole-brain analysis on T1-weighted images controlled for variances of cerebral blood flow indicated a significant interaction between caffeine and CSR in four brain regions: 1) right temporal-occipital region, 2) right thalamus, 3) left dorsolateral, and 4) dorsomedial prefrontal region. The post-hoc analyses indicated increased GM intensity in the DECAF group in all four regions but decreased GM in the thalamus as well as dorsolateral and dorsomedial prefrontal regions in the CAFF group after sleep restriction. Furthermore, lower baseline subcortical A1R availability predicted larger reduction in the CAFF group after CSR of all brain regions except for the caffeine-associated thalamic reduction. In conclusion, our data suggest an adaptive upregulation in GM after 5-day CSR, while concomitant use of caffeine instead leads to a GM reduction. The lack of consistent association with individual A1R availability may suggest that CSR and caffeine affect GM plasticity predominantly by a different mechanism. Future studies on the role of adenosine A2A receptors (ADORA2A) in CSR-induced GM plasticity are warranted.

neuroscience↗

bioRxiv2023

A genetic variation in the adenosine A2A receptor gene contributes to variability in oscillatory alpha power in wake and sleep EEG and A1 adenosine receptor availability in the human brain

The EEG alpha rhythm (8-13 Hz) is one of the most salient human brain activity rhythms. Spectral power in the alpha range in wakefulness and sleep varies among individuals based on genetical predisposition, yet knowledge about the underlying genes is scarce. The EEG alpha oscillations are related to cerebral energy metabolism and modulated by the level of attention and vigilance. The neuromodulator adenosine is directly linked to energy metabolism as product of adenosine tri-phosphate (ATP) breakdown and acts as a sleep promoting molecule by activitating A1 and A2A adenosine receptors. We quantified EEG oscillatory alpha power in wakefulness and sleep, as well as A1 adenosine receptor availability by positron emission tomography with 18F-CPFPX, in a large sample of healthy volunteers carrying different alleles of gene variant rs5751876 of ADORA2A encoding A2A adenosine receptors. Oscillatory alpha power was higher in homozygous C-allele carriers (n = 27, 11 females) compared to heterozygous and homozygous carriers of the T-allele (n(C/T) = 23, n(T/T) = 5, 13 females) (F(18,37) = 2.35, p = 0.014, Wilks {Lambda} = 0.467). Across considered brain regions an effect of ADORA2A genotype on A1 adenosine receptor binding potential was found (F(18,40) = 2.62, p = 0.006, Wilks {Lambda} = 0.459) and after correction for multiple testing this effect was shown to be significant for circumscribed occipital region of calcarine fissures. A correlation between individual differences in oscillatory alpha power and adenosine receptor availability was found for the subgroup of female participants only. In conclusion: a genetic variation in the adenosinergic system affects individual alpha power, although a direct modulatory effect via the A1AR has been demonstrated for females only.

neuroscience↗

bioRxiv2023

Theta and alpha EEG oscillations reflect sleep need -- except during the wake maintenance zone

Increasing time spent awake results in accumulated sleep need, a process known as sleep homeostasis. Sleep homeostasis combines with a 24 h circadian rhythm to determine when and for how long we sleep. Both sleep homeostasis and the circadian rhythm substantially affect spectral power of the wake electroencephalogram (EEG), but not in ways predicted by current models. Specifically, these models hypothesize that time spent awake increases neuronal synaptic strength, which increases synchronization and should therefore increase oscillatory activity. However, the dominant wake EEG oscillations, measured as theta (4-8 Hz) and alpha power (8-12 Hz), do not follow the predicted buildup in homeostatic sleep pressure with time awake. This is due to a limitation of spectral power analysis, which does not distinguish between changes in the amplitude of oscillations from changes in the quantity of oscillations present in the signal. We wished to determine whether the amplitudes of EEG oscillations would specifically reflect homeostatic sleep pressure, independently from changes in quantity. We collected data from 18 young healthy adults during a 4-h sleep / 24-h extended wake paradigm. We indeed found that theta and alpha oscillation amplitudes reflect homeostatic sleep pressure, increasing along a saturating exponential function with time awake. Instead, theta quantities increased linearly with time awake, and alpha quantities decreased. Notably, theta and alpha amplitudes temporarily decreased during the wake maintenance zone (WMZ), a 3-4 h time window just before bedtime when it is difficult to fall asleep. Using pupillometry, we also found that mean pupil diameter increased during this window, while variance decreased. These results suggest that the WMZ is dependent on an alerting signal from the ascending arousal system. The WMZ therefore counteracts the observed build-up in homeostatic sleep pressure reflected in EEG amplitudes by temporarily desynchronizing cortical activity.

neuroscience↗

bioRxiv2021

Time to recover from daily caffeine intake.

Caffeine elicits widespread effects in the central nervous system and is the most frequently consumed psychostimulant worldwide. First evidence indicates that, during daily intake, the elimination of caffeine may slow down and the primary metabolite, paraxanthine, may accumulate. The neural impact of such adaptions is virtually unexplored. In this report, we leveraged the data of a laboratory study with N= 20 participants and three within-subject conditions: caffeine (150 mg caffeine x 3/day x 10 days), placebo (150 mg mannitol x 3/day x 10 days), and withdrawal (caffeine x 9 days, afterwards placebo x 1 day). Using liquid chromatography-mass spectrometry coupled with tandem mass spectrometry, we determined the course of salivary caffeine and paraxanthine, measured regularly at day 10. We assessed grey matter (GM) intensity and cerebral blood flow (CBF) in the withdrawal condition as compared to their changes in caffeine in our previous report. The results indicate high remaining levels of paraxanthine and of caffeine carried overnight during daily intake, and the levels of paraxanthine remained higher than in placebo during withdrawal. After 36 h of withdrawal, the previously reported caffeine-induced GM reduction was partially mitigated, while CBF was elevated compared to placebo. Our findings unveil that conventional daily caffeine intake does not provide sufficient time to clear up psychoactive compounds and restore cerebral responses, even after 36 hours of abstinence. They also suggest investigating consequences of a paraxanthine accumulation during daily caffeine intake.

pharmacology and toxicology↗

bioRxiv2021

Working Memory Performance after Daily Caffeine Intake: Compromised Performance and Reduced Hippocampal Activity.

Neuroprotective effects of caffeine have been frequently reported in the context of disease and cognitive dysfunction as well as in epidemiological studies in humans. However, evidence on caffeine effects on neural and memory functions during daily intake in a healthy cognitive state remains scarce. This randomized double-blind placebo-controlled crossover study investigated working memory functions by N-back tasks and functional magnetic resonance imaging (fMRI) after daily caffeine intake compared to a placebo baseline and to acute caffeine withdrawal in 20 young healthy volunteers. Each volunteer was given 3 times 150 mg caffeine for 10 days in the daily caffeine condition, 3 times 150 mg mannitol for 10 days in the placebo condition, and 9-day caffeine plus 1-day mannitol in the acute withdrawal condition. During the 10th day, participants performed 4 N-back sessions (two loads each: 0- and 3-back) under controlled laboratory conditions. During the 4th session of N-Back (i.e. at 5.5 h, 36.5 h and > 10 days after the last caffeine intake in the caffeine, withdrawal, and placebo condition, respectively) we assessed blood-oxygen-level-dependent (BOLD) activity. During the entire 10th day, in 0-back tasks, we observed longer reaction times (RTs) in the withdrawal compared to the placebo (Cohens d = 0.7) and caffeine condition (Cohens d = 0.6), but no significant effects of conditions on error rates. In contrast, in 3-back tasks (controlled for 0-back), the RTs in the caffeine condition were longer compared to placebo (Cohens d = 0.6) and withdrawal (Cohens d = 0.5). Error rates were higher during both caffeine and withdrawal conditions compared to placebo (Cohens d of both contrasts = 0.4). Whole-brain analyses on fMRI data did not reveal significant condition-dependent differences in activities between task loads. Across task loads, however, we observed a reduced hippocampal activation (Cohens d = -1.3) during the caffeine condition compared to placebo, while no significant difference in brain activities between withdrawal and placebo conditions. Taken together, the worse working memory function and the hippocampal hypoactivation implicate a potential detrimental effect of daily caffeine intake on neurocognitive functions of healthy adults. Moreover, they echo the hippocampal volumetric reduction reported previously in the same volunteers. Lastly, acute withdrawal from daily caffeine intake impairs both low-order cognitive processes and working memory performance. Taking earlier studies on acute caffeine effects into account, our findings indicate that daily caffeine intake elicits a dynamic change in cerebral activities during the course of repeated consumption, with unknown consequences in the long run.

neuroscience↗

bioRxiv2020

Regular caffeine intake attenuates REM sleep promotion and sleep quality in healthy men

Acute caffeine intake can attenuate homeostatic sleep pressure and worsen sleep quality. Besides, caffeine intake - particularly in high doses and close to bedtime - may also affect circadian-regulated REM sleep promotion, an important determinant of subjective sleep quality. However, it is not known whether such changes persist under chronic caffeine consumption during daytime. Twenty male caffeine consumers (26.4 {+/-} 4 years old, habitual caffeine intake 478.1 {+/-} 102.8 mg/day) participated in a double-blind crossover study. Each volunteer completed a caffeine (3 x 150 mg caffeine daily), a withdrawal (3 x 150 mg caffeine for eight days then placebo), and a placebo condition. After ten days of controlled intake and a fixed sleep-wake cycle, we recorded 8 h of electroencephalography starting 5 h after habitual bedtime (i.e., start on average at 04:22 am which is around the peak of circadian REM sleep promotion). A 60 min evening nap preceded each sleep episode and reduced high sleep pressure levels. While total sleep time and sleep architecture did not significantly differ between the three conditions, REM latency was longer after daily caffeine intake compared to both placebo and withdrawal. Moreover, the accumulation of REM sleep proportion was slower, and volunteers reported more difficulties at awakening after sleep and feeling more tired upon wake-up in the caffeine condition compared to placebo. Our data indicate that besides acute also regular daytime caffeine intake affects REM sleep regulation in men. We have evidence that regular caffeine intake during daytime weakens circadian sleep promotion when compared to placebo. Moreover, the observed caffeine-induced deterioration in the quality of awakening may suggest a potential motive to reinstate caffeine intake after sleep.

neuroscience↗

bioRxiv2020

The impact of daily caffeine intake on nighttime sleep: signs of overnight withdrawal?

Acute caffeine intake can delay sleep initiation and reduce sleep intensity, particularly when consumed in the evening. However, it is not clear whether these sleep disturbances disappear when caffeine is continuously consumed during daytime, which is common for most coffee drinkers. To address this question, we investigated the sleep of twenty male young habitual caffeine consumers during a double-blind, randomized, crossover study including three 10-day conditions: caffeine (3 x 150 mg caffeine daily), withdrawal (3 x 150 mg caffeine for eight days, then switch to placebo), and placebo (3 x placebo daily). After nine days of continuous treatment, electroencephalographically (EEG)-derived sleep structure and intensity were recorded during a scheduled 8-h nighttime sleep episode starting 8 (caffeine condition) and 15 h (withdrawal condition) after the last caffeine intake. Upon scheduled wake up time, subjective sleep quality and caffeine withdrawal symptoms were assessed. Unexpectedly, neither polysomnography-derived total sleep time, sleep latency, sleep architecture, nor subjective sleep quality differed among placebo, caffeine, and withdrawal conditions. Nevertheless, EEG power density in the sigma frequencies (12-16 Hz) during non-rapid eye movement (NREM) sleep was reduced in both caffeine and withdrawal conditions when compared to placebo. These results indicate that daily caffeine intake in the morning and afternoon hours does not strongly impair nighttime sleep structure or subjective sleep quality in healthy good sleepers who regularly consume caffeine. The reduced EEG power density in the sigma range might represent early signs of overnight withdrawal from the continuous presence of the stimulant during the day. Statement of SignificanceCaffeine consumption is highly prevalent worldwide and has been repeatedly shown to acutely disrupt sleep, particularly when consumed after several days of abstinence or close to bedtime. However, commonly, caffeine is consumed daily and during daytime. Our well-controlled laboratory study revealed that this common pattern of intake affects nighttime sleep differently: While slow-wave sleep duration or slow-wave activity were rather similar compared to placebo, caffeine intake surprisingly reduced EEG power density in the sigma frequencies. In the light of earlier studies, this might present early signs of caffeine withdrawal which occurs due to overnight caffeine abstinence. The present findings provide novel insights into the impact of daily presence and nightly abstinence of caffeine on nighttime sleep in regular consumers.

neuroscience↗

bioRxiv2019

Haplotype of the astrocytic water channel AQP4 modulates slow wave energy in human NREM sleep

Cerebrospinal fluid (CSF) flow through the brain parenchyma is facilitated by the astrocytic water channel aquaporin 4 (AQP4). Homeostatically regulated electroencephalographic (EEG) slow waves are a hallmark of deep non-rapid-eye-movement (NREM) sleep and have been implicated in the regulation of parenchymal CSF flow and brain clearance. The human AQP4 gene harbors several single nucleotide polymorphisms (SNPs) associated with AQP4 expression, brain-water homeostasis and neurodegenerative diseases. To date, their role in sleep-wake regulation is unknown. To investigate whether functional variants in AQP4 modulate human sleep, nocturnal EEG-recordings and cognitive performance were investigated in 123 healthy participants genotyped for a common eight-SNP AQP4-haplotype. We show that this AQP4-haplotype is associated with distinct modulations of NREM slow wave energy, strongest in early sleep and mirrored by changes in sleepiness and reaction times during extended wakefulness. The study provides the first human evidence for a link between AQP4, deep NREM sleep and cognitive consequences of prolonged wakefulness.

neuroscience↗

bioRxiv2019

Caffeine-induced Plasticity of Grey Matter Volume in Healthy Brains: A placebo-controlled multimodal within-subject study

Disturbed sleep homeostatic states have been found to alter neuronal homeostasis and reduce grey matter (GM) volume. Caffeine intake that interferes with sleep homeostasis through antagonizing adenosine receptors can impair hippocampal synaptic strength, neurogenesis, as well as memory and learning in rats. In this study, reduced medial temporal GM volume was observed after daily caffeine intake in humans (3 x 150 mg x 10 days compared to 10-day placebo administration). The potential bias from reduced cerebral blood flow was controlled, and the GM reduction was independent of the change in sleep pressure. A decrease in working memory during daily caffeine intake was observed, albeit no association with the magnitude of GM changes. The findings indicate that daily caffeine intake might induce rapid cerebral plasticity and be detrimental for higher order cognitive performance in the long run. They may call into question whether the neuroprotective effects of caffeine found in acute or low dose administration in animals are generalizable onto the daily usage in humans.

neuroscience↗

bioRxiv2019

Reassessing the validity of slow-wave dynamics as a proxy for NREM sleep homeostasis

Sleep-wake driven changes in NREM sleep (NREMS) EEG delta ({delta}: [~]0.75-4.5Hz) power are widely used as proxy for a sleep homeostatic process. We noted frequency increases in {delta}-waves in sleep-deprived (SD) mice, prompting us to re-evaluate how slow-wave characteristics relate to prior sleep-wake history. We discovered two types of {delta}-waves; one responding to SD with high initial power and fast, discontinuous decay ({delta}2: [~]2.5-3.5Hz) and another unrelated to time-spent-awake with slow, linear decays ({delta}1: [~]0.75-1.75Hz). Human experiments confirmed this {delta}-band heterogeneity. Similar to SD, silencing of centromedial thalamus neurons boosted {delta}2-waves, specifically. {delta}2-dynamics paralleled that of temperature, muscle tone, heart-rate, and neuronal UP/DOWN state lengths, all reverting to characteristic NREMS levels within the first recovery hour. Thus, prolonged waking seems to necessitate a physiological recalibration before typical NREMS can be reinstated. These short-lasting {delta}2-dynamics challenge accepted models of sleep regulation and function based on the merged {delta}-band as sleep-need proxy.

neuroscience↗

bioRxiv2019

Caffeine-dependent changes of sleep-wake regulation: evidence for adaptation after repeated intake

To enhance wakefulness, daily consumption of caffeine in the morning and afternoon is highly common. However, it is unknown whether such a regular intake pattern affects timing and quality of wakefulness, as regulated by an interplay of circadian and sleep-homeostatic mechanisms. Thus, we investigated the effects of daily caffeine intake and its withdrawal on circadian rhythms and wake-promotion in 20 male young habitual caffeine consumers. We applied a double-blind, within-subject design with a caffeine (150 mg, 3 x daily), a placebo, and a withdrawal condition each lasting ten days. Starting on day nine of treatment, salivary melatonin and cortisol, evening nap sleep, as well as sleepiness and vigilance performance throughout day and night were quantified during 43 h under controlled laboratory conditions. Neither the time course of melatonin (i.e., onset, amplitude, or area under the curve) nor the time course of cortisol were significantly affected by caffeine intake or its withdrawal. During withdrawal, however, volunteers reported increased sleepiness, showed more attentional lapses, as well as polysomnography-derived markers of elevated sleep propensity in the late evening compared to both, placebo and caffeine conditions. Thus, the typical timing of habitual caffeine intake in humans may not necessarily shift circadian phase nor lead to clear-cut benefits in alertness. The time-of-day independent effects of caffeine withdrawal suggest an adaptation to the substance, presumably in the homeostatic aspect of sleep-wake regulation.

neuroscience↗

bioRxiv2018

Dynamic changes in cerebral and peripheral markers of glutamatergic signaling across the human sleep-wake cycle

Both sleep and glutamatergic signaling in the brain are tightly controlled and homeostatically regulated. Sleep homeostasis is reliably reflected by predictable changes in brain electrical activity in waking and sleep, yet the underlying molecular mechanisms remain elusive. Current hypotheses posit that recovery sleep following prolonged waking restores efficient functioning of the brain, for example by keeping glutamatergic signaling in a homeostatic range. We recently provided evidence in humans and mice that metabotropic glutamate receptors of subtype-5 (mGluR5) contribute to the brains coping mechanisms with sleep deprivation. Here we combined in 31 healthy men, proton magnetic resonance spectroscopy to measure the levels of glutamate (Glu), GLX (glutamate-to-glutamine ratio) and GABA ({gamma}-amino-butyric-acid) in basal ganglia (BG) and dorsolateral prefrontal cortex, simultaneous positron emission tomography to quantify mGluR5 availability with the novel radioligand, [18F]PSS232, and quantification in blood plasma of the mGluR5-regulated proteins, fragile-X mental retardation protein (FMRP) and brain-derived neurotrophic factor (BDNF). All measurements were conducted at the same circadian time in baseline, following sleep deprivation and after recovery sleep. We found that Glu and GLX in BG (pall < 0.01), but not in prefrontal cortex, and the plasma concentration of FMRP (p < 0.02), were increased after sleep loss and tended to normalize following recovery sleep (pall < 0.1). Furthermore, a night without sleep enhanced whole-brain and striatal mGluR5 availability and was normalized by recovery sleep (pall < 0.05). By contrast, other brain metabolites and plasma BDNF levels were not altered. The findings demonstrate convergent changes in distinct markers of glutamatergic signaling across prolonged wakefulness and recovery sleep in humans. They warrant further studies to elucidate the underlying mechanisms that link the homeostatic regulation of sleep and glutamatergic system activity in health and disease.\n\nOne-sentence summarySleep-dependent recovery of wakefulness-induced changes in, cerebral glutamatergic signaling\n\nMajor subject areaNeuroscience; Human Biology & Medicine

neuroscience↗