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Open research questions in Sleep and Wakefulness Research

546 gap statements mined from Sleep and Wakefulness Research papers in our 7.9M-paper local library, which holds 2,620 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • Although further research is required to understand the mental health implications of this specific intervention, there appear to be therapeutic benefits not only in influencing NREM consolidation but also in modulating REM sleep, with potential benefits for emotional integration [5,30 ]. Little is known about sleep disorders in FND.

    At-home limbic-targeted transcranial electrical stimulation during sleep: a feasibility study in healthy adults · 2026 · DOI

  • Although the core pathological mechanisms of AD have been extensively studied, the modulatory factors driving its progression remain incompletely understood.

    Sleep Disturbance Correlates with Cognitive Impairment Partly via Plasma p-Tau217: ADNI Cross-Sectional Evidence and P301L Mouse Mechanistic Observations · 2026 · DOI

  • However, the specific molecular targets underlying these effects remain unclear. The above findings are consistent with previous studies, confirming that the SD model established in this study is reliable and suitable for further investigation of pharmacological intervention mechanisms.

    Glycosides of Cistanche improve cognitive dysfunction in sleep-deprived model rats by activating the SIRT1/PGC-1α/Nrf2 signaling pathway · 2026 · DOI

  • The AcAc/BHB ratio may provide complementary information about ketone interconversion and metabolic redox state, although its relationship to brain ketone exposure and sleep physiology remains to be established.

    Ketones and Sleep: A Narrative Review of Mechanisms, Preclinical Models, and Human Evidence · 2026 · DOI

  • The need to rule out the effects of electrode impedance on power.

    Progressive decline in EEG low frequency spectral power during overnight sleep · 2026 · DOI

  • While the neuroprotective benefits of long-term exercise are well-established, the therapeutic efficacy of short-term exercise intervention initiated during established chronic SD remains poorly understood.

    Short-Term Exercise Ameliorates Cognitive Deficits and Upregulates the Hippocampal BDNF Pathway in Rats with Chronic Sleep Deprivation · 2026 · DOI

  • The paper identifies the need for further validation of techniques such as transcranial alternating current stimulation and pharmacological approaches. The study of dream experience also raises technical challenges, such as the development of methods to link dream experience to neurobiological processes.

    Are Dreams Manipulable? Toward a Neurophysiological Framework for Dream Modifiability · 2026 · DOI

  • This receptor, while being the most abundantly expressed cholinergic receptor in hippocampus and neocortex, is only one of several other muscarinic and nicotinic acetylcholine receptor types, which are not explored in this model. As such, there are multiple consolidation-relevant aspects of sleep that our model does not account for.

    Cholinergic modulation of neural networks supports sequential and complementary roles for NREM and REM states in memory consolidation · 2025 · DOI

  • Future research should focus on determining the specific time course during which glucocorticoids change from a proinflammatory to an anti-inflammatory function under stress, as well as the impact on inflammation in organs during ASF. However, the relationship of ASF with the pro-inflammatory effect of GCs is not well established.

    Effect of glucocorticoid blockade on inflammatory responses to acute sleep fragmentation in male mice · 2024 · DOI

  • Future research is needed to explore further the role of HCRT antagonism in maternal motivation and its impact on postpartum care.

    Dual hypocretin receptor antagonists enhance sleep and nursing behavior in lactating rats · 2026 · DOI

  • Further studies on the relationship between sleep and insight should therefore continue to evaluate different tasks, for instance one that is neither mathematical nor perceptual.

    N2 sleep promotes the occurrence of ‘aha’ moments in a perceptual insight task · 2025 · DOI

  • In order to take these findings closer to clinical applications, we would certainly need to increase our sample size to see if the results could be replicated.

    Morphological characteristics of cerebellum, pons and thalamus in Reccurent isolated sleep paralysis – A pilot study · 2024 · DOI

  • Finally, an important limitation of this study is that it was conducted exclusively in male rats.

    Early-life GABA-A receptor blockade with bicuculline attenuates anxiety-like behaviors and cognitive deficits induced by 24-hr sleep deprivation in adult male rats · 2026 · DOI

  • Further, stimulants are used as adjunct therapy in depression despite limited evidence.

    Redefining hypersomnia disorders in the context of psychiatry · 2026 · DOI

  • Future research should explore receptor-specific roles, optimal timing of intervention, and biomarkers predictive of treatment response.

    A Scoping Review of Orexin Antagonists in Post-Traumatic Stress Disorder: Modulating Sleep, Stress, and Fear Circuits · 2026 · DOI

  • Insomnia is a highly prevalent and burdensome sleep disorder whose pathophysiology remains incompletely understood.

    Glial Control of Insomnia: Astrocyte–Microglia Interactions in Stress, Hyperarousal and Sleep Dysregulation · 2026 · DOI

  • In this context, the contribution of the pathology to the observed slowing before surgery, and its relevance to consciousness remain open questions.

    Hemispherotomy leads to persistent sleep-like slow waves in the isolated cortex of awake humans · 2025 · DOI

  • Further genetic testing in this breed is warranted to identify carriers and prevent the further spread of this condition.

    Familial Narcolepsy in Dogo Argentino Dogs Is Caused by a Tandem Duplication Mutation in HCRTR2 · 2025 · DOI

  • Whilst candidate brainstem structures for sleep atonia have been identified in animal studies, the precise mechanisms underpinning RBD in humans remain unclear.

    Lesion network mapping of REM Sleep Behaviour Disorder · 2025 · DOI

  • Insufficient sleep's impact on cognitive and emotional function is well-documented, but its effects on social functioning remain understudied.

    Subclinically Depressed Individuals Showed Less Trust after a Night of Sleep Deprivation · 2025 · DOI

  • Future research should explore sleep-related interventions targeting the psychosocial dysfunctions of individuals with depression.

    Subclinically Depressed Individuals Showed Less Trust after a Night of Sleep Deprivation · 2025 · DOI

  • How this temporal organisation emerges in infancy, and whether prematurity or early sensorimotor experience shapes it, remains unclear.

    Characterising sleep spindle emergence in infancy: Effects of prematurity and early locomotor intervention · 2026 · DOI

  • Further evaluation of the changes between early and late impedances, - Investigation of the relation between a dynamic change in EEG power and health…

    Progressive decline in EEG low frequency spectral power during overnight sleep · 2026 · DOI

  • Further validation of approaches to modify dream cognition, - Investigation of the neural basis of dream emotion, - Exploration of the potential applications of dream manipulability in clinical…

    Are Dreams Manipulable? Toward a Neurophysiological Framework for Dream Modifiability · 2026 · DOI

  • Further research into the specific contributions of cannabinoid receptors in diverse sleep disorders and the development of cannabinoid receptor-selective compounds hold the potential to revolutionize treatment strategies, providing much-needed relief…

    Sleep, Glial Function, and the Endocannabinoid System: Implications for Neuroinflammation and Sleep Disorders · 2024 · DOI

Most-cited papers in Sleep and Wakefulness Research

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Open questions raised by papers listed on this page include: (1) Although the core pathological mechanisms of AD have been extensively studied, the modulatory factors driving its progression remain incompletely understood (“Sleep Disturbance Correlates with Cognitive Impairment Partly via Plasma…”, 2026); (2) The specific molecular targets underlying these effects remain unclear (“Glycosides of Cistanche improve cognitive dysfunction in sleep-deprived model…”, 2026); (3) The AcAc/BHB ratio may provide complementary information about ketone interconversion and metabolic redox state, although its relationship to brain ketone exposure and sleep physiology remains to be established (“Ketones and Sleep: A Narrative Review of Mechanisms, Preclinical Models, and…”, 2026); (4) While the neuroprotective benefits of long-term exercise are well-established, the therapeutic efficacy of short-term exercise intervention initiated during established chronic SD remains poorly understood (“Short-Term Exercise Ameliorates Cognitive Deficits and Upregulates the…”, 2026); (5) Future research is needed to explore further the role of HCRT antagonism in maternal motivation and its impact on postpartum care (“Dual hypocretin receptor antagonists enhance sleep and nursing behavior in…”, 2026). 546 gap statements have been mined from Sleep and Wakefulness Research papers in our 7.9M-paper local library, which holds 2,620 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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