Influence of sleep homeostasis and circadian rhythm on executive discriminative ability during a constant routine

Poster (2012, September)

Introduction & Objectives The human brain upholds cognitive performance throughout a waking day due to putative circadian (C) arousal signal (1) which counteracts the increase in homeostatic (H) sleep ... [more ▼]

Introduction & Objectives The human brain upholds cognitive performance throughout a waking day due to putative circadian (C) arousal signal (1) which counteracts the increase in homeostatic (H) sleep pressure associated to the deterioration in brain efficiency. When wakefulness is extended into the circadian night, maintenance of cognitive performance is jeopardized (Fig.1). Some individuals are very vulnerable to the negative effects of sleep loss and circadian misalignment, whereas others are resilient (3). These individuals differences can be readily explained within the conceptual framework of the circadian and homeostatic regulation of performance (4,5) but also by individual genetic differences and notably the PERIOD3 gene polymorphism (6). In this experiment, we investigated the consequences of sleep deprivation on cognitive performance during a working memory task (3-back). Following the signal detection theory, the ability to discriminate target from non-target stimuli is estimated by d prime (d') and criterion (cr). Here we assessed whether d' and cr were modulated by the raising sleep need and the oscillatory circadian signal. We also tested whether the individual vulnerability to sleep loss predicted by the PERIOD3 gene polymorphism influences this cognitive modulation, which is also driven by the sleep/wake regulation. Materials and Methods Population: Thirty-five right-handed healthy young volunteers aged from 19 to 26 (17 females) were recruited on the basis of their PER3 polymorphism. From a sample of about 400 screened volunteers, twelve 5/5 and twenty-three 4/4 homozygotes (matched for age, gender, chronotype, IQ, and level of education at the group level) participated in this study. Study protocol: Participants wore actigraphs for three weeks before the laboratory study. The first two weeks allowed us to determine their habitual sleep/wake schedule. During the third one, a strict sleep schedule adjusted on two possible timetables (00:00-08:00 or 01:00-09:00) was imposed in order to stagger fMRI sessions. Compliance to this schedule was again checked by wrist actigraphy and sleep diaries. The laboratory study began in the evening of day 1 and ran over 5 nights (Fig. 2). During the first 2 nights (habituation and baseline), the volunteers slept according to habitual sleep/wake schedule. Participants remained awake from the morning of day 3 for 42 hours. During this period, they remained in a semi-recumbent position, under dim light conditions (5 lux, eye level), with no information on clock time, in a constant routine protocol (CR). Saliva samples was hourly collected for melatonin analysis. Every 2 hours, volunteers received calibrated isocaloric snacks, behavioral data were collected and waking EEG recorded. During CR, behavioral measures were used to assess subjective (Karolinska Sleepiness Scale, KSS) and objective alertness (psychomotor vigilance task [PVT]). Executive functioning efficiency was assessed using the 3-back (Fig. 3) and SART tasks. During fMRI, participants performed alternating blocks of 0- and 3-back task. D’ and cr (Fig. 4) were analyzed with mixed-model analysis of variance (PROC Mixed), with main factors “session” and “genotype” (PER3 4/4 & PER3 5/5). All p-values derived from r-ANOVAs were based on Huynh-Feldt's (H-F) corrected degrees of freedom (p<0.05). Exploratory analysis assessed theoretical coefficients for the homeostatic sleep pressure (derived from a quasi-linear function) and the circadian oscillation (as a 24-hour period sine wave) were utilized in a multiple regression model to predict d’ and cr performance during the CR. Before these analyses, d’ and cr have been normalized using a z-score transformation. Results. Analyses on d’ 1. MIXED MODEL : Significant effect of sessions (F(12,385) = 17.16, p < 0.0001), but no group effect (F(1,133) = 0.00, p = 0.99) or interaction (F(12,385) = 1.51, p = 0.11). 2. REGRESSION: Significant regression (R² = 0.24, F(2,440) = 69.94, p <0.0001). The two predictors are significant (homeostat: p < 0.0001 ; circadian: p < 0.0001). Analyses on cr 1. MIXED MODEL : Significant effect of sessions (F(12,385) = 4.12, p < 0.0001), but no group effect (F(1,133) = 0.00, p = 0.99) or interaction (F(12,385) = 0.75, p = 0.71). 2. REGRESSION: Significant regression (R² = 0.04, F(2,440) = 9.35 , p = 0.0001). Only one predictor was significant (homeostat: p < 0.0001 ; circadian: p = 0.96). Conclusion These preliminary results show that both sleep homeostatic pressure and circadian factors influence executive discriminative ability during sleep loss, as assessed by signal detection theory (d’). Decision criterion (cr) appears modulated only by homeostatic sleep pressure. The difference between these two parameters could be explained by the theoretical modeling of the circadian oscillation and future analyses will incorporate individual experimentally-derived homeostatic and circadian parameters. Neither discrimination ability (d’) or criterion (cr) seem sensitive measures of individual cognitive vulnerability to sleep loss predicted by PER3 polymorphism. REFERENCES (1) Aston-Jones. Sleep Med. 2005, 6(Suppl 1), S3-7. (2) Dijk & Archer. Sleep Med. Rev. 2010, 14, 151-160.(3) Van Dongen & al. Sleep. 2004, 27, 423-433. (4) Mongrain & al. J. Sleep Res. 2006, 15, 162-166. (5) Van Dongen et al. Sleep. 2007, 30, 1129-1143. (6) Groeger & al. Sleep. 2008, 31, 1159-1167. (7) Vandewalle & al. J. Neuro. 2009, 29, 7948-7956. ACKNOWLEDGEMENTS & SPONSORS Cyclotron Research Centre (CRC) ; Belgian National Funds of Scientific Research (FNRS) ; Actions de Recherches Concertées (ARC, ULg) – Fondation Médicale Reine Elisabeth (FMRE) ; Walloon Excellence in Lifesciences and Biotechnology (WELBIO) ; Wellcome Trust ; Biotechnology and Biological Sciences Research Council (BBSRC) [less ▲]

Neural Correlates of Human Sleep and Sleep-Dependent Memory Processing

in Frank, Marcos (Ed.) Sleep and Brain Activity (2012)

Wakefulness and sleep are associated with distinct patterns of neural activity and neuromodulation. In humans, functional neuroimaging was used to characterize the related changes in regional brain ... [more ▼]

Wakefulness and sleep are associated with distinct patterns of neural activity and neuromodulation. In humans, functional neuroimaging was used to characterize the related changes in regional brain metabolism and hemodynamics. Recent data combining EEG and fMRI described the transient responses associated with spindles and slow waves, as well as the changes in functional integration during NREM sleep. It was also shown that regional brain activity during sleep is influenced by the experience acquired during the preceding waking period. These data are currently interpreted in the framework of two theories. First, the use-dependent increase in slow oscillation during NREM sleep is associated with local synaptic homeostasis. Second, reactivations of memory traces during NREM sleep would reorganize declarative memories in hippocampal-neocortical networks, a systems-level memory consolidation which can be hindered by sleep deprivation. Collectively, these data reveal the dynamical changes in brain activity during sleep which support normal human cognition. [less ▲]

Sleep, memory and the hippocampus

in Clinical Neurobiology of the Hippocampus (2012)

Functional neuroimaging of the reciprocal influences between sleep and wakefulness.

in Pflugers Archiv : European journal of physiology (2011), 463(1), 103-9

The activity patterns adopted by brain neuronal populations differ dramatically between wakefulness and sleep. However, these vigilance states are not independent and they reciprocally interact. Here, we ... [more ▼]

The activity patterns adopted by brain neuronal populations differ dramatically between wakefulness and sleep. However, these vigilance states are not independent and they reciprocally interact. Here, we provide evidence that in humans, regional brain activity during wakefulness is influenced by sleep regulation, namely by the interaction between sleep homeostasis and circadian signals. We also show that, by contrast, regional brain activity during sleep is influenced by the experience acquired during the preceding waking period. These data reveal the dynamic interactions by which the succession of vigilance states support normal brain function and human cognition. [less ▲]

Neural Correlates of Human NREM Sleep Oscillations

in Hutt, Axel (Ed.) Sleep and Anesthesia (2011)

Influence of brain-derived neurotrophic factor val66met human polymorphism on declarative memory consolidation

Poster (2010, November 15)

The Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin which in the adult brain regulates long-term potentiation. In humans, valine (val) to methionine (met) substitution in the 5’ pro-region of ... [more ▼]

The Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin which in the adult brain regulates long-term potentiation. In humans, valine (val) to methionine (met) substitution in the 5’ pro-region of the BDNF protein is associated with poorer episodic memory. Neurons transfected with met-BDNF-Green Fluorescence Protein showed lower depolarization-induced secretion, while constitutive secretion is unchanged. Here, we hypothesized that the differences in BDNF release determined by this polymorphism would influence memory consolidation and that in comparison with the val/met (=val/met or met/met), val/val individuals would show higher memory performance and different brain responses during a 16h-delayed rather than immediate retrieval session. Participants encoded a series of neutral faces in the afternoon. Retrieval sessions took place one hour after the encoding session, and in the following morning, during the acquisition of functional Magnetic Resonance Imaging (fMRI) time series with a 3 Tesla Allegra scanner. During retrieval, studied faces and new ones were presented in random order. For each stimulus, the subjects indicated whether they could retrieve the encoding episode with (“Remember”), or without details (“Know”), or if they thought the item had not been presented during encoding (“New”). A repeated-measure ANOVA on discrimination index (d’) showed significant effects of group (F(1, 27)=8.65, p=0.007, n(val/val)=14, n(val/met)=15) and session (F(1, 27)=24.64, p=0.000), although the group by session interaction was not significant (F(1, 27)=1.29, p=0.267). fMRI results showed a significant genotype (val/val > val/met) by session (delayed > immediate retrieval) by memory type (Remember > Know) interaction in the right inferior occipital gyrus (x=42, y=-78, z=0, p=0.004, Z=3.77), the left inferior parietal lobule (x=-56, y=-40, z=48, p=0.013, Z=3.43), the posterior cingulate cortex (x=14, y=-42, z=42, p=0.019, Z=3.29) and the right hippocampus (x=28, y=-22, z=-22, p=0.03, Z=3.11). Val/val individuals demonstrate higher memory performance than met-carriers but the change in memory performance between immediate and delayed retests is similar in both allelic groups. In contrast, neural correlates of recollection change between sessions differently according to genotype: responses increase significantly more in val/val than in val/met individuals in brain areas involved in the retrieval, accumulation and binding of perceptual memory details during delayed, relative to immediate retest. These data suggest that activity-dependent BDNF release promotes memory consolidation during the first post-training hours. [less ▲]

Contributions du sommeil a la consolidation mnésique

in Biologie Aujourd'hui (2010), 204(2), 139-143

Encoding Difficulty Promotes Postlearning Changes in Sleep

in Journal of Neuroscience (2006), 26(35), 8976-8982

Learning-dependent increases in sleep spindle density have been reported during nocturnal sleep immediately after the learning session. Here, we investigated experience-dependent changes in daytime sleep ... [more ▼]

Learning-dependent increases in sleep spindle density have been reported during nocturnal sleep immediately after the learning session. Here, we investigated experience-dependent changes in daytime sleep EEG activity after declarative learning of unrelated word pairs. At weekly intervals, 13 young male volunteers spent three 24 h sessions in the laboratory under carefully controlled homeostatic and circadian conditions. At approximately midday, subjects performed either one of two word-pair learning tasks or a matched nonlearning control task, in a counterbalanced order. The two learning lists differed in the level of concreteness of the words used, resulting in an easier and a more difficult associative encoding condition, as confirmed by performance at immediate cued recall. Subjects were then allowed to sleep for 4 h; afterward, delayed cued recall was tested. Compared with the control condition, sleep EEG spectral activity in the low spindle frequency range and the density of low-frequency sleep spindles (11.25–13.75 Hz) were both significantly increased in the left frontal cortex after the difficult but not after the easy encoding condition. Furthermore, we found positive correlations between theseEEG changes during sleep and changes in memory performance between pre nap and post-nap recall sessions. These results indicate that, like during nocturnal sleep, daytime sleep EEG oscillations including spindle activity are modified after declarative learning of word pairs. Furthermore, we demonstrate here that the nature of the learning material is a determinant factor for sleep-related alterations after declarative learning. [less ▲]