The pathophysiology of major depressive disorder (MDD) includes both affective and cognitive dysf... more The pathophysiology of major depressive disorder (MDD) includes both affective and cognitive dysfunctions. We aimed to clarify how regions regulating affective processing interact with those involved in attention, and how such interaction impacts perceptual processing within sensory cortices. Based on previous work showing that top-down influences from attention can determine the processing of external inputs within early sensory cortices, we tested with functional magnetic resonance imaging (fMRI) whether MDD alters attentional ("top-down") effects on the neural filtering of irrelevant, nonemotional visual stimuli. The present fMRI study was conducted in 14 nonmedicated patients with a first episode of unipolar MDD and 14 matched controls. During scanning, subjects performed two tasks imposing two different levels of attentional load at fixation (easy or difficult), while irrelevant colored stimuli were presented in the periphery. Analyses of fMRI data revealed that MDD patients show (1) an abnormal filtering of irrelevant information in visual cortex, (2) an altered functional connectivity between frontoparietal networks and visual cortices, and (3) a hyperactivity in subgenual cingulate/ medial orbitofrontal cortex that was modulated by attentional load. These results demonstrate that biological abnormalities contribute to the cognitive deficits seen in major depression, and clarify how neural networks implicated in mood regulation influence executive control and perceptual processes. These findings not only improve our understanding of the pathophysiological mechanisms underlying cognitive dysfunctions in MDD, but also shed new light on the interaction between cognition and mood regulation.
Background: While cognitive-behavioral therapy for insomnia constitutes the first-line treatment ... more Background: While cognitive-behavioral therapy for insomnia constitutes the first-line treatment for chronic insomnia, only few reports have investigated how sleep architecture relates to response to this treatment. In this pilot study, we aimed at determining whether sleep spindle density at pre-treatment predicts treatment response to cognitive behavioral therapy for insomnia. Methods: Twenty-four participants with chronic primary insomnia took part in a 6-week cognitive behavioral therapy for insomnia performed in groups of 4 to 6 participants. Treatment response was assessed using the Pittsburgh Sleep Quality Index and the Insomnia Severity Index measured at pre-and post-treatment and at 3-and 12-months follow-up assessments. Secondary outcome measures were extracted from sleep diaries over seven days and one overnight polysomnography, obtained at pre-and post-treatment. Spindle density during stages N2-N3 sleep was extracted from polysomnography at pre-treatment. Hierarchical linear modeling analysis assessed whether sleep spindle density predicted response to cognitive behavioral therapy. Results: After adjusting for age, sex and education level, lower spindle density at pre-treatment predicted poorer response over the 12-months follow-up, as reflected by smaller reduction in Pittsburgh Sleep Quality Index over time. Reduced spindle density also predicted lower improvements in sleep diary sleep efficiency and wake after sleep onset immediately after treatment. There were no significant associations between spindle density and changes in the Insomnia Severity Index or polysomnography variables over time. These preliminary results suggest that inter-individual differences in sleep spindle density in insomnia may represent an endogenous biomarker predicting responsiveness to cognitive behavioral therapy. Insomnia with altered spindle activity might constitute an insomnia
medRxiv (Cold Spring Harbor Laboratory), Mar 10, 2023
Rationale: Among individuals with obstructive sleep apnea, about 38% will present with comorbid c... more Rationale: Among individuals with obstructive sleep apnea, about 38% will present with comorbid chronic insomnia. Comorbid chronic insomnia and obstructive sleep apnea (COMISA) is associated with poorer daytime functioning and increased morbidity compared to either disorder alone. The treatment of insomnia among individuals with COMISA is suboptimal. : To assess the effects of an exercise-training intervention alone as well as a combined cognitive behavioral therapy and exercise training on insomnia symptoms in individuals with COMISA. Methods: In a pilot randomized-controlled trial, 19 individuals with COMISA were allocated to one of two arms, each comprising of 2 phases of 8 weeks. The first phase examined the effects of exercise training versus relaxation training on insomnia severity and cardiorespiratory fitness. The second phase compared changes in Insomnia Severity Index (ISI) following exercise training alone (EX) or combined Cognitive Behavioural Therapy for Insomnia and exercise training (CBTi-EX). Self-reported insomnia severity, objective sleep parameters during overnight polysomnography, and cardiopulmonary fitness were collected at baseline, 8 and 16 weeks. Results: Exercise training increased VO2peak and reduced insomnia severity (Hedges' g = 0.82) when compared to relaxation training. Moreover, combined CBTi and exercise training yielded a larger improvement in insomnia severity (Hedges' g =1.48) than exercise training alone (EX). We observed no change in objective sleep measures in both groups. Conclusions: Exercise training leads to moderate improvements in insomnia severity in individuals with COMISA. Combining exercise training with CBTi leads to larger reductions in insomnia symptoms, with effect sizes similar to the effects of CBTi alone in other populations with chronic insomnia.
Brain imaging studies have provided key insights into the neural causes, consequences and correla... more Brain imaging studies have provided key insights into the neural causes, consequences and correlates of sleep disorders. During normal sleep, functional neuroimaging data revealed specific changes in regional brain activity correlated with electroencephalographic sleep oscillations. Neuroimaging studies in insomnia support the global hyperarousal hypothesis, by showing decreased inhibition during the transition from wakefulness to sleep. In narcoleptic patients, both functional and structural abnormalities were found in the hypothalamus, supporting a hypocretinergic dysfunction, whereas altered limbic responses may relate to emotional dysregulation contributing to the onset of cataplectic episodes. In idiopathic hypersomnia, recent neuroimaging data suggest the presence of incomplete sleep-wake transitions in relationship with the severity of excessive daytime sleepiness. Lastly, functional and structural neuroimaging studies of rapid-eye-movement sleep behavior disorder converged on pontine abnormalities, as well as presynaptic dopamine dysfunction related to the development of synucleinopathy.
Functional brain imaging has been used in humans to noninvasively investigate the neural mechanis... more Functional brain imaging has been used in humans to noninvasively investigate the neural mechanisms underlying the generation of sleep stages. On the one hand, REM sleep has been associated with the activation of the pons, thalamus, limbic areas, and temporo-occipital cortices, and the deactivation of prefrontal areas, in line with theories of REM sleep generation and dreaming properties. On the other hand, during non-REM (NREM) sleep, decreases in brain activity have been consistently found in the brainstem, thalamus, and in several cortical areas including the medial prefrontal cortex (MPFC), in agreement with a homeostatic need for brain energy recovery. Benefiting from a better temporal resolution, more recent studies have characterized the brain activations related to phasic events within specific sleep stages. In particular, they have demonstrated that NREM sleep oscillations (spindles and slow waves) are indeed associated with increases in brain activity in specific subcortical and cortical areas involved in the generation or modulation of these waves. These data highlight that, even during NREM sleep, brain activity is increased, yet regionally specific and transient. Besides refining the understanding of sleep mechanisms, functional brain imaging has also advanced the description of the functional properties of sleep. For instance, it has been shown that the sleeping brain is still able to process external information and even detect the pertinence of its content. The relationship between sleep and memory has also been refined using neuroimaging, demonstrating post-learning reactivation during sleep, as well as the reorganization of memory representation on the systems level, sometimes with long-lasting effects on subsequent memory performance. Further imaging studies should focus on clarifying the role of specific sleep patterns for the processing of external stimuli, as well as the consolidation of freshly encoded information during sleep.
Recent studies in sleep and dreaming have described an activation of emotional and reward systems... more Recent studies in sleep and dreaming have described an activation of emotional and reward systems, as well as the processing of internal information during these states. Specifically, increased activity in the amygdala and across mesolimbic dopaminergic regions during REM sleep is likely to promote the consolidation of memory traces with high emotional/motivational value. Moreover, coordinated hippocampal-striatal replay during NREM sleep may contribute to the selective strengthening of memories for important events. In this review, we suggest that, via the activation of emotional/motivational circuits, sleep and dreaming may offer a neurobehavioral substrate for the offline reprocessing of emotions, associative learning, and exploratory behaviors, resulting in improved memory organization, waking emotion regulation, social skills, and creativity. Dysregulation of such motivational/emotional processes due to sleep disturbances (e.g., insomnia, sleep deprivation) would predispose to reward-related disorders, such as mood disorders, increased risk-taking and compulsive behaviors, and may have major health implications, especially in vulnerable populations.
Rejection of the pulse related artefact (PRA) from electroencephalographic (EEG) time series reco... more Rejection of the pulse related artefact (PRA) from electroencephalographic (EEG) time series recorded simultaneously with fMRI data is difficult, particularly during NREM sleep because of the similarities between sleep slow waves and PRA, in both temporal and frequency domains and the need to work with non-averaged data. Here we introduce an algorithm based on constrained independent component analysis (cICA) for PRA removal. This method has several advantages: (1) automatic detection of the components corresponding to the PRA; (2) stability of the solution and (3) computational treatability. Using multichannel EEG recordings obtained in a 3 T MR scanner, with and without concomitant fMRI acquisition, we provide evidence for the sensitivity and specificity of the method in rejecting PRA in various sleep and waking conditions.
medRxiv (Cold Spring Harbor Laboratory), Jul 27, 2023
Rationale: Sleep state misperception (SSM) represents the discrepancy between objectively recorde... more Rationale: Sleep state misperception (SSM) represents the discrepancy between objectively recorded and subjectively perceived measures of sleep, including sleep onset latency (SOL), sleep duration (TST) and wake duration (WASO). The severity of SSM is higher in insomnia disorder (INS) compared to other populations. SSM is typically assessed in-lab during one night with polysomnographic (PSG) recording or at-home with actigraphy recordings over multiple days, both complemented by subjective sleep reports. Both methods of data collection have their specific strengths and weaknesses, and provide sleep measures that may differ, especially in individuals with sleep disorders. The extent to which the methods and environment of data collection impact measures of sleep misperception remains unclear. This study aimed at providing a comprehensive assessment of SSM in INS and good sleepers (GS) by comparing recordings performed for one night in-lab (PSG and night review) and during several nights at-home (actigraphy and sleep diaries). Methods: Fifty-seven INS and 29 GS wore an actigraphy device and filled a sleep diary for two weeks athome. They subsequently completed a PSG recording and filled a night review the next morning in-lab. Sleep perception index (subjective/objective × 100; in %) of SOL, WASO and TST were computed and compared between methods and groups. Results: We found that GS and INS exhibit opposite patterns of sleep misperception. GS displayed a tendency to overestimate TST and WASO but correctly perceived SOL. The degree of misperception was similar across methods within the GS group. In contrast, INS underestimated their TST and overestimated their SOL both in-lab and at-home, yet the severity of misperception (i.e., degree of mismatch) of SOL was larger at-home than in-lab. Finally, INS overestimated WASO only in-lab while correctly perceiving it at-home. While only the degree of TST misperception was stable across methods in INS, misperception of SOL and WASO were dependent on the method used. Conclusions: We found that GS and INS exhibit opposite patterns and severity of sleep misperception. While the degree of misperception in GS was similar across methods, we found that only sleep duration misperception was reliably detected by both in-lab and at-home methods in INS. Our results highlight that, when assessing sleep misperception in individuals with insomnia disorder, the method of data collection should be carefully considered in relation to the main sleep outcomes of interest.
The idea that sleep might be involved in brain plasticity has been investigated for many years th... more The idea that sleep might be involved in brain plasticity has been investigated for many years through a large number of animal and human studies, but evidence remains fragmentary. Large amounts of sleep in early life suggest that sleep may play a role in brain maturation. In particular, the influence of sleep in developing the visual system has been highlighted. The current data suggest that both Rapid Eye Movement (REM) and non-REM sleep states would be important for brain development. Such findings stress the need for optimal paediatric sleep management. In the adult brain, the role of sleep in learning and memory is emphasized by studies at behavioural, systems, cellular and molecular levels. First, sleep amounts are reported to increase following a learning task and sleep deprivation impairs task acquisition and consolidation. At the systems level, neurophysiological studies suggest possible mechanisms for the consolidation of memory traces. These imply both thalamocortical and hippocampo-neocortical networks. Similarly, neuroimaging techniques demonstrated the experiencedependent changes in cerebral activity during sleep. Finally, recent works show the modulation during sleep of cerebral protein synthesis and expression of genes involved in neuronal plasticity.
Sleep disorders have been the subject of a number of positron emission tomography and single-phot... more Sleep disorders have been the subject of a number of positron emission tomography and single-photon emission computed tomography studies. Narcoleptic patients displayed decreased hypothalamic and thalamic perfusion during resting wakefulness, which may be related to hypocretinergic deficiency and altered vigilance. In restless legs syndrome and periodic limb movements, hypoactivity in pre- and postsynaptic dopaminergic transmission in the striatum and substantia nigra may underlie compulsive limb movements. Sleepwalking showed specific brain perfusion changes during slow wave sleep and wakefulness, possibly indicative of a dissociated state. Rapid eye movement sleep behavior disorder patients showed changes in blood flow in the pons, frontal lobes, striatum, and hippocampus, linking this disorder to later onset of Parkinson’s disease. Localized brain metabolism increases during non-rapid eye movement sleep in insomnia and depression are in line with the “hyperarousal” hypothesis underlying sleep disturbances in these patients. Even with these insights, radioisotope imaging in sleep medicine is still in its infancy. Further research should aim to increase sample sizes, provide adequate control groups, and acquire additional timepoints for imaging, for instance, before, during, and after the onset of symptoms.
During the past few decades, the development of functional neuroimaging techniques has provided a... more During the past few decades, the development of functional neuroimaging techniques has provided an important tool for noninvasive investigation in humans, allowing us to detect variations in cerebral blood flow or metabolism, notably throughout the sleep–wake cycle. Up to now, positron emission tomography (PET) has been the most commonly used technique during normal human sleep. PET studies showed that the brain activity during sleep is segregated at the regional level within specific cortical and subcortical areas in relation to the sleep stage, sleep physiological events, and previous waking activity. These results lend support to physiological theories of sleep based on animal data but also introduce original concepts about the neurobiological mechanisms of sleep, dreams, and memory in humans.
A growing number of studies support the hypothesis that sleep participates in the off-line proces... more A growing number of studies support the hypothesis that sleep participates in the off-line processing of recent memories. However, many determinants and outcomes of memory reprocessing during sleep remain to be identified. This review provides a summary description of the main behavioural, neurophysiological and hemodynamic features of sleep, with a special emphasis on sleep mechanisms deemed potentially important to support sleep-related brain plasticity and memory consolidation: PGO-waves, spindles and hippocampal rhythms. Next are presented brain imaging studies having demonstrated the reexpression and modulation of learning-related cerebral activity during posttraining sleep in humans. As a whole, functional neuroimaging results nowadays suggest that learning-dependent modulations in cerebral activity during human sleep reflect the offline processing of recent memory traces, which eventually leads to the plastic changes underlying the subsequent improvement in performance.
Characterized by dream-enactment motor manifestations arising from rapid eye movement (REM) sleep... more Characterized by dream-enactment motor manifestations arising from rapid eye movement (REM) sleep, REM sleep behavior disorder (RBD) is frequently encountered in Parkinson's disease (PD). Yet the specific neurostructural changes associated with RBD in PD patients remain to be revealed by neuroimaging. Here we identified such neurostructural alterations by comparing large samples of magnetic resonance imaging (MRI) scans in 69 PD patients with probable RBD, 240 patients without RBD and 138 healthy controls, using deformation-based morphometry (p < 0.05 corrected for multiple comparisons). All data were extracted from the Parkinson's Progression Markers Initiative. PD patients with probable RBD showed smaller volumes than patients without RBD and than healthy controls in the pontomesencephalic tegmentum, medullary reticular formation, hypothalamus, thalamus, putamen, amygdala and anterior cingulate cortex. These results demonstrate that RBD is associated with a prominent loss of volume in the pontomesencephalic tegmentum, where cholinergic, GABAergic and glutamatergic neurons are located and implicated in the promotion of REM sleep and muscle atonia. It is additionally associated with more widespread atrophy in other subcortical and cortical regions whose loss also likely contributes to the altered regulation of sleep-wake states and motor activity underlying RBD in PD patients. RBD is characterized by episodes of dream-enactment behaviors, during which abnormal motor activity during REM sleep often results in dramatic movements such as punching, flailing or jumping out of the bed 1 . It has been suggested that RBD results from an alteration of brainstem neural systems controlling motor inhibition during REM sleep 2,3 . Lesions in the brainstem, particularly involving the mesencephalic, pontine or medullary reticular formation (RF), were originally shown in animal models to produce REM sleep without atonia and acting out dreams 4-7 . In humans, neuropathological studies of small series of RBD patients have revealed loss of neurons in the region of the pontomesencephalic tegmentum (PMT) 8 . To generalize these findings, neuroimaging studies have compared regional brain volumes between subjects with idiopathic RBD (i.e., in the absence of any other neurological disorder) and subjects without. Studies of 12 to 26 idiopathic RBD patients demonstrated subtle structural alterations (indexed by MRI diffusion parameters) in regions compatible with the PMT and RF 9,10 , and the presence of altered regional brain volumes in these areas was reported in one study 11 but not in two others , which questions the consistency of pontine neuronal loss in idiopathic RBD. Beyond these studies of 'idiopathic' RBD, recent studies have focused on RBD in presence of neurodegenerative disorders. Indeed, there is increasing evidence that RBD is associated with α -synucleinopathies such as PD, dementia with Lewy bodies and multiple system atrophy. The prevalence of RBD in the general population is approximately 0.5%, 13 while this prevalence increases noticeably in PD (37 to 47%) . In fact, RBD is considered as an early symptom of α -synucleinopathies 17 . Yet not all patients with these syndromes are affected by RBD.
Background Recorded and live online physical exercise (PE) interventions are known to provide hea... more Background Recorded and live online physical exercise (PE) interventions are known to provide health benefits. However, the effects of prioritizing the number of live or recorded sessions remain unclear. Aims To explore which recorded-live sessions ratio leads to the best implementation and benefits in older adults. Methods Forty-six community-dwelling adults (> 60y.o.) were randomized into two groups completing a 12-week online PE intervention. Each group had a different ratio of live-recorded online sessions as follows: Live-Recorded-Live sessions (LRL; n = 22) vs. Recorded-Live-Recorded sessions (RLR; n = 24). Results Drop-out rates did not reach significance (LRL:14% vs. RLR: 29%, p = 0.20), and adherence was similar (> 85%) between groups. Both groups reported similar levels of satisfaction (> 70%), enjoyment (> 75%), and perceived exertion (> 60%). Both groups increased physical health and functional capacities, with greater improvements in muscle power (LRL:
Background Periods of prolonged lockdown increase the risk of physical inactivity, which can cont... more Background Periods of prolonged lockdown increase the risk of physical inactivity, which can contribute to physical decline among older adults. Online technology could be an innovative solution to promote physical activity (PA) habits in this context. The goal of this study was to examine and compare the acceptability, feasibility, and potential benefits of 2 modalities of web-based PA interventions in older adults during the coronavirus disease 2019 lockdown. Methods Eighty-three nonphysically active community-dwelling older adults (aged 60 and older) were randomized to a 12-week web-based PA intervention delivered either in a live group (LG; n = 38) or a recorded group (RG; n = 45). Acceptability, feasibility as well as functional capacities, physical performance, quality of life, and PA level were assessed pre and postintervention. Results There were fewer dropouts in the LG than RG (LG: 16% vs RG: 46%). However, adherence rate (LG: 89%; RG: 81%), level of satisfaction (LG: 77% v...
The pathophysiology of major depressive disorder (MDD) includes both affective and cognitive dysf... more The pathophysiology of major depressive disorder (MDD) includes both affective and cognitive dysfunctions. We aimed to clarify how regions regulating affective processing interact with those involved in attention, and how such interaction impacts perceptual processing within sensory cortices. Based on previous work showing that top-down influences from attention can determine the processing of external inputs within early sensory cortices, we tested with functional magnetic resonance imaging (fMRI) whether MDD alters attentional ("top-down") effects on the neural filtering of irrelevant, nonemotional visual stimuli. The present fMRI study was conducted in 14 nonmedicated patients with a first episode of unipolar MDD and 14 matched controls. During scanning, subjects performed two tasks imposing two different levels of attentional load at fixation (easy or difficult), while irrelevant colored stimuli were presented in the periphery. Analyses of fMRI data revealed that MDD patients show (1) an abnormal filtering of irrelevant information in visual cortex, (2) an altered functional connectivity between frontoparietal networks and visual cortices, and (3) a hyperactivity in subgenual cingulate/ medial orbitofrontal cortex that was modulated by attentional load. These results demonstrate that biological abnormalities contribute to the cognitive deficits seen in major depression, and clarify how neural networks implicated in mood regulation influence executive control and perceptual processes. These findings not only improve our understanding of the pathophysiological mechanisms underlying cognitive dysfunctions in MDD, but also shed new light on the interaction between cognition and mood regulation.
Background: While cognitive-behavioral therapy for insomnia constitutes the first-line treatment ... more Background: While cognitive-behavioral therapy for insomnia constitutes the first-line treatment for chronic insomnia, only few reports have investigated how sleep architecture relates to response to this treatment. In this pilot study, we aimed at determining whether sleep spindle density at pre-treatment predicts treatment response to cognitive behavioral therapy for insomnia. Methods: Twenty-four participants with chronic primary insomnia took part in a 6-week cognitive behavioral therapy for insomnia performed in groups of 4 to 6 participants. Treatment response was assessed using the Pittsburgh Sleep Quality Index and the Insomnia Severity Index measured at pre-and post-treatment and at 3-and 12-months follow-up assessments. Secondary outcome measures were extracted from sleep diaries over seven days and one overnight polysomnography, obtained at pre-and post-treatment. Spindle density during stages N2-N3 sleep was extracted from polysomnography at pre-treatment. Hierarchical linear modeling analysis assessed whether sleep spindle density predicted response to cognitive behavioral therapy. Results: After adjusting for age, sex and education level, lower spindle density at pre-treatment predicted poorer response over the 12-months follow-up, as reflected by smaller reduction in Pittsburgh Sleep Quality Index over time. Reduced spindle density also predicted lower improvements in sleep diary sleep efficiency and wake after sleep onset immediately after treatment. There were no significant associations between spindle density and changes in the Insomnia Severity Index or polysomnography variables over time. These preliminary results suggest that inter-individual differences in sleep spindle density in insomnia may represent an endogenous biomarker predicting responsiveness to cognitive behavioral therapy. Insomnia with altered spindle activity might constitute an insomnia
medRxiv (Cold Spring Harbor Laboratory), Mar 10, 2023
Rationale: Among individuals with obstructive sleep apnea, about 38% will present with comorbid c... more Rationale: Among individuals with obstructive sleep apnea, about 38% will present with comorbid chronic insomnia. Comorbid chronic insomnia and obstructive sleep apnea (COMISA) is associated with poorer daytime functioning and increased morbidity compared to either disorder alone. The treatment of insomnia among individuals with COMISA is suboptimal. : To assess the effects of an exercise-training intervention alone as well as a combined cognitive behavioral therapy and exercise training on insomnia symptoms in individuals with COMISA. Methods: In a pilot randomized-controlled trial, 19 individuals with COMISA were allocated to one of two arms, each comprising of 2 phases of 8 weeks. The first phase examined the effects of exercise training versus relaxation training on insomnia severity and cardiorespiratory fitness. The second phase compared changes in Insomnia Severity Index (ISI) following exercise training alone (EX) or combined Cognitive Behavioural Therapy for Insomnia and exercise training (CBTi-EX). Self-reported insomnia severity, objective sleep parameters during overnight polysomnography, and cardiopulmonary fitness were collected at baseline, 8 and 16 weeks. Results: Exercise training increased VO2peak and reduced insomnia severity (Hedges' g = 0.82) when compared to relaxation training. Moreover, combined CBTi and exercise training yielded a larger improvement in insomnia severity (Hedges' g =1.48) than exercise training alone (EX). We observed no change in objective sleep measures in both groups. Conclusions: Exercise training leads to moderate improvements in insomnia severity in individuals with COMISA. Combining exercise training with CBTi leads to larger reductions in insomnia symptoms, with effect sizes similar to the effects of CBTi alone in other populations with chronic insomnia.
Brain imaging studies have provided key insights into the neural causes, consequences and correla... more Brain imaging studies have provided key insights into the neural causes, consequences and correlates of sleep disorders. During normal sleep, functional neuroimaging data revealed specific changes in regional brain activity correlated with electroencephalographic sleep oscillations. Neuroimaging studies in insomnia support the global hyperarousal hypothesis, by showing decreased inhibition during the transition from wakefulness to sleep. In narcoleptic patients, both functional and structural abnormalities were found in the hypothalamus, supporting a hypocretinergic dysfunction, whereas altered limbic responses may relate to emotional dysregulation contributing to the onset of cataplectic episodes. In idiopathic hypersomnia, recent neuroimaging data suggest the presence of incomplete sleep-wake transitions in relationship with the severity of excessive daytime sleepiness. Lastly, functional and structural neuroimaging studies of rapid-eye-movement sleep behavior disorder converged on pontine abnormalities, as well as presynaptic dopamine dysfunction related to the development of synucleinopathy.
Functional brain imaging has been used in humans to noninvasively investigate the neural mechanis... more Functional brain imaging has been used in humans to noninvasively investigate the neural mechanisms underlying the generation of sleep stages. On the one hand, REM sleep has been associated with the activation of the pons, thalamus, limbic areas, and temporo-occipital cortices, and the deactivation of prefrontal areas, in line with theories of REM sleep generation and dreaming properties. On the other hand, during non-REM (NREM) sleep, decreases in brain activity have been consistently found in the brainstem, thalamus, and in several cortical areas including the medial prefrontal cortex (MPFC), in agreement with a homeostatic need for brain energy recovery. Benefiting from a better temporal resolution, more recent studies have characterized the brain activations related to phasic events within specific sleep stages. In particular, they have demonstrated that NREM sleep oscillations (spindles and slow waves) are indeed associated with increases in brain activity in specific subcortical and cortical areas involved in the generation or modulation of these waves. These data highlight that, even during NREM sleep, brain activity is increased, yet regionally specific and transient. Besides refining the understanding of sleep mechanisms, functional brain imaging has also advanced the description of the functional properties of sleep. For instance, it has been shown that the sleeping brain is still able to process external information and even detect the pertinence of its content. The relationship between sleep and memory has also been refined using neuroimaging, demonstrating post-learning reactivation during sleep, as well as the reorganization of memory representation on the systems level, sometimes with long-lasting effects on subsequent memory performance. Further imaging studies should focus on clarifying the role of specific sleep patterns for the processing of external stimuli, as well as the consolidation of freshly encoded information during sleep.
Recent studies in sleep and dreaming have described an activation of emotional and reward systems... more Recent studies in sleep and dreaming have described an activation of emotional and reward systems, as well as the processing of internal information during these states. Specifically, increased activity in the amygdala and across mesolimbic dopaminergic regions during REM sleep is likely to promote the consolidation of memory traces with high emotional/motivational value. Moreover, coordinated hippocampal-striatal replay during NREM sleep may contribute to the selective strengthening of memories for important events. In this review, we suggest that, via the activation of emotional/motivational circuits, sleep and dreaming may offer a neurobehavioral substrate for the offline reprocessing of emotions, associative learning, and exploratory behaviors, resulting in improved memory organization, waking emotion regulation, social skills, and creativity. Dysregulation of such motivational/emotional processes due to sleep disturbances (e.g., insomnia, sleep deprivation) would predispose to reward-related disorders, such as mood disorders, increased risk-taking and compulsive behaviors, and may have major health implications, especially in vulnerable populations.
Rejection of the pulse related artefact (PRA) from electroencephalographic (EEG) time series reco... more Rejection of the pulse related artefact (PRA) from electroencephalographic (EEG) time series recorded simultaneously with fMRI data is difficult, particularly during NREM sleep because of the similarities between sleep slow waves and PRA, in both temporal and frequency domains and the need to work with non-averaged data. Here we introduce an algorithm based on constrained independent component analysis (cICA) for PRA removal. This method has several advantages: (1) automatic detection of the components corresponding to the PRA; (2) stability of the solution and (3) computational treatability. Using multichannel EEG recordings obtained in a 3 T MR scanner, with and without concomitant fMRI acquisition, we provide evidence for the sensitivity and specificity of the method in rejecting PRA in various sleep and waking conditions.
medRxiv (Cold Spring Harbor Laboratory), Jul 27, 2023
Rationale: Sleep state misperception (SSM) represents the discrepancy between objectively recorde... more Rationale: Sleep state misperception (SSM) represents the discrepancy between objectively recorded and subjectively perceived measures of sleep, including sleep onset latency (SOL), sleep duration (TST) and wake duration (WASO). The severity of SSM is higher in insomnia disorder (INS) compared to other populations. SSM is typically assessed in-lab during one night with polysomnographic (PSG) recording or at-home with actigraphy recordings over multiple days, both complemented by subjective sleep reports. Both methods of data collection have their specific strengths and weaknesses, and provide sleep measures that may differ, especially in individuals with sleep disorders. The extent to which the methods and environment of data collection impact measures of sleep misperception remains unclear. This study aimed at providing a comprehensive assessment of SSM in INS and good sleepers (GS) by comparing recordings performed for one night in-lab (PSG and night review) and during several nights at-home (actigraphy and sleep diaries). Methods: Fifty-seven INS and 29 GS wore an actigraphy device and filled a sleep diary for two weeks athome. They subsequently completed a PSG recording and filled a night review the next morning in-lab. Sleep perception index (subjective/objective × 100; in %) of SOL, WASO and TST were computed and compared between methods and groups. Results: We found that GS and INS exhibit opposite patterns of sleep misperception. GS displayed a tendency to overestimate TST and WASO but correctly perceived SOL. The degree of misperception was similar across methods within the GS group. In contrast, INS underestimated their TST and overestimated their SOL both in-lab and at-home, yet the severity of misperception (i.e., degree of mismatch) of SOL was larger at-home than in-lab. Finally, INS overestimated WASO only in-lab while correctly perceiving it at-home. While only the degree of TST misperception was stable across methods in INS, misperception of SOL and WASO were dependent on the method used. Conclusions: We found that GS and INS exhibit opposite patterns and severity of sleep misperception. While the degree of misperception in GS was similar across methods, we found that only sleep duration misperception was reliably detected by both in-lab and at-home methods in INS. Our results highlight that, when assessing sleep misperception in individuals with insomnia disorder, the method of data collection should be carefully considered in relation to the main sleep outcomes of interest.
The idea that sleep might be involved in brain plasticity has been investigated for many years th... more The idea that sleep might be involved in brain plasticity has been investigated for many years through a large number of animal and human studies, but evidence remains fragmentary. Large amounts of sleep in early life suggest that sleep may play a role in brain maturation. In particular, the influence of sleep in developing the visual system has been highlighted. The current data suggest that both Rapid Eye Movement (REM) and non-REM sleep states would be important for brain development. Such findings stress the need for optimal paediatric sleep management. In the adult brain, the role of sleep in learning and memory is emphasized by studies at behavioural, systems, cellular and molecular levels. First, sleep amounts are reported to increase following a learning task and sleep deprivation impairs task acquisition and consolidation. At the systems level, neurophysiological studies suggest possible mechanisms for the consolidation of memory traces. These imply both thalamocortical and hippocampo-neocortical networks. Similarly, neuroimaging techniques demonstrated the experiencedependent changes in cerebral activity during sleep. Finally, recent works show the modulation during sleep of cerebral protein synthesis and expression of genes involved in neuronal plasticity.
Sleep disorders have been the subject of a number of positron emission tomography and single-phot... more Sleep disorders have been the subject of a number of positron emission tomography and single-photon emission computed tomography studies. Narcoleptic patients displayed decreased hypothalamic and thalamic perfusion during resting wakefulness, which may be related to hypocretinergic deficiency and altered vigilance. In restless legs syndrome and periodic limb movements, hypoactivity in pre- and postsynaptic dopaminergic transmission in the striatum and substantia nigra may underlie compulsive limb movements. Sleepwalking showed specific brain perfusion changes during slow wave sleep and wakefulness, possibly indicative of a dissociated state. Rapid eye movement sleep behavior disorder patients showed changes in blood flow in the pons, frontal lobes, striatum, and hippocampus, linking this disorder to later onset of Parkinson’s disease. Localized brain metabolism increases during non-rapid eye movement sleep in insomnia and depression are in line with the “hyperarousal” hypothesis underlying sleep disturbances in these patients. Even with these insights, radioisotope imaging in sleep medicine is still in its infancy. Further research should aim to increase sample sizes, provide adequate control groups, and acquire additional timepoints for imaging, for instance, before, during, and after the onset of symptoms.
During the past few decades, the development of functional neuroimaging techniques has provided a... more During the past few decades, the development of functional neuroimaging techniques has provided an important tool for noninvasive investigation in humans, allowing us to detect variations in cerebral blood flow or metabolism, notably throughout the sleep–wake cycle. Up to now, positron emission tomography (PET) has been the most commonly used technique during normal human sleep. PET studies showed that the brain activity during sleep is segregated at the regional level within specific cortical and subcortical areas in relation to the sleep stage, sleep physiological events, and previous waking activity. These results lend support to physiological theories of sleep based on animal data but also introduce original concepts about the neurobiological mechanisms of sleep, dreams, and memory in humans.
A growing number of studies support the hypothesis that sleep participates in the off-line proces... more A growing number of studies support the hypothesis that sleep participates in the off-line processing of recent memories. However, many determinants and outcomes of memory reprocessing during sleep remain to be identified. This review provides a summary description of the main behavioural, neurophysiological and hemodynamic features of sleep, with a special emphasis on sleep mechanisms deemed potentially important to support sleep-related brain plasticity and memory consolidation: PGO-waves, spindles and hippocampal rhythms. Next are presented brain imaging studies having demonstrated the reexpression and modulation of learning-related cerebral activity during posttraining sleep in humans. As a whole, functional neuroimaging results nowadays suggest that learning-dependent modulations in cerebral activity during human sleep reflect the offline processing of recent memory traces, which eventually leads to the plastic changes underlying the subsequent improvement in performance.
Characterized by dream-enactment motor manifestations arising from rapid eye movement (REM) sleep... more Characterized by dream-enactment motor manifestations arising from rapid eye movement (REM) sleep, REM sleep behavior disorder (RBD) is frequently encountered in Parkinson's disease (PD). Yet the specific neurostructural changes associated with RBD in PD patients remain to be revealed by neuroimaging. Here we identified such neurostructural alterations by comparing large samples of magnetic resonance imaging (MRI) scans in 69 PD patients with probable RBD, 240 patients without RBD and 138 healthy controls, using deformation-based morphometry (p < 0.05 corrected for multiple comparisons). All data were extracted from the Parkinson's Progression Markers Initiative. PD patients with probable RBD showed smaller volumes than patients without RBD and than healthy controls in the pontomesencephalic tegmentum, medullary reticular formation, hypothalamus, thalamus, putamen, amygdala and anterior cingulate cortex. These results demonstrate that RBD is associated with a prominent loss of volume in the pontomesencephalic tegmentum, where cholinergic, GABAergic and glutamatergic neurons are located and implicated in the promotion of REM sleep and muscle atonia. It is additionally associated with more widespread atrophy in other subcortical and cortical regions whose loss also likely contributes to the altered regulation of sleep-wake states and motor activity underlying RBD in PD patients. RBD is characterized by episodes of dream-enactment behaviors, during which abnormal motor activity during REM sleep often results in dramatic movements such as punching, flailing or jumping out of the bed 1 . It has been suggested that RBD results from an alteration of brainstem neural systems controlling motor inhibition during REM sleep 2,3 . Lesions in the brainstem, particularly involving the mesencephalic, pontine or medullary reticular formation (RF), were originally shown in animal models to produce REM sleep without atonia and acting out dreams 4-7 . In humans, neuropathological studies of small series of RBD patients have revealed loss of neurons in the region of the pontomesencephalic tegmentum (PMT) 8 . To generalize these findings, neuroimaging studies have compared regional brain volumes between subjects with idiopathic RBD (i.e., in the absence of any other neurological disorder) and subjects without. Studies of 12 to 26 idiopathic RBD patients demonstrated subtle structural alterations (indexed by MRI diffusion parameters) in regions compatible with the PMT and RF 9,10 , and the presence of altered regional brain volumes in these areas was reported in one study 11 but not in two others , which questions the consistency of pontine neuronal loss in idiopathic RBD. Beyond these studies of 'idiopathic' RBD, recent studies have focused on RBD in presence of neurodegenerative disorders. Indeed, there is increasing evidence that RBD is associated with α -synucleinopathies such as PD, dementia with Lewy bodies and multiple system atrophy. The prevalence of RBD in the general population is approximately 0.5%, 13 while this prevalence increases noticeably in PD (37 to 47%) . In fact, RBD is considered as an early symptom of α -synucleinopathies 17 . Yet not all patients with these syndromes are affected by RBD.
Background Recorded and live online physical exercise (PE) interventions are known to provide hea... more Background Recorded and live online physical exercise (PE) interventions are known to provide health benefits. However, the effects of prioritizing the number of live or recorded sessions remain unclear. Aims To explore which recorded-live sessions ratio leads to the best implementation and benefits in older adults. Methods Forty-six community-dwelling adults (> 60y.o.) were randomized into two groups completing a 12-week online PE intervention. Each group had a different ratio of live-recorded online sessions as follows: Live-Recorded-Live sessions (LRL; n = 22) vs. Recorded-Live-Recorded sessions (RLR; n = 24). Results Drop-out rates did not reach significance (LRL:14% vs. RLR: 29%, p = 0.20), and adherence was similar (> 85%) between groups. Both groups reported similar levels of satisfaction (> 70%), enjoyment (> 75%), and perceived exertion (> 60%). Both groups increased physical health and functional capacities, with greater improvements in muscle power (LRL:
Background Periods of prolonged lockdown increase the risk of physical inactivity, which can cont... more Background Periods of prolonged lockdown increase the risk of physical inactivity, which can contribute to physical decline among older adults. Online technology could be an innovative solution to promote physical activity (PA) habits in this context. The goal of this study was to examine and compare the acceptability, feasibility, and potential benefits of 2 modalities of web-based PA interventions in older adults during the coronavirus disease 2019 lockdown. Methods Eighty-three nonphysically active community-dwelling older adults (aged 60 and older) were randomized to a 12-week web-based PA intervention delivered either in a live group (LG; n = 38) or a recorded group (RG; n = 45). Acceptability, feasibility as well as functional capacities, physical performance, quality of life, and PA level were assessed pre and postintervention. Results There were fewer dropouts in the LG than RG (LG: 16% vs RG: 46%). However, adherence rate (LG: 89%; RG: 81%), level of satisfaction (LG: 77% v...
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