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      New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation

      1 ,
      British Journal of Pharmacology
      John Wiley and Sons Inc.

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          In mammals, a central circadian clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, tunes the innate circadian physiological rhythms to the ambient 24 h light–dark cycle to invigorate and optimize the internal temporal order. The SCN‐activated, light‐inhibited production of melatonin conveys the message of darkness to the clock and induces night‐state physiological functions, for example, sleep/wake blood pressure and metabolism. Clinically meaningful effects of melatonin treatment have been demonstrated in placebo‐controlled trials in humans, particularly in disorders associated with diminished or misaligned melatonin rhythms, for example, circadian rhythm‐related sleep disorders, jet lag and shift work, insomnia in children with neurodevelopmental disorders, poor (non‐restorative) sleep quality, non‐dipping nocturnal blood pressure (nocturnal hypertension) and Alzheimer's disease (AD). The diminished production of melatonin at the very early stages of AD, the role of melatonin in the restorative value of sleep (perceived sleep quality) and its sleep‐anticipating effects resulting in attenuated activation of certain brain networks are gaining a new perspective as the role of poor sleep quality in the build‐up of β amyloid, particularly in the precuneus, is unravelled. As a result of the recently discovered relationship between circadian clock, sleep and neurodegeneration, new prospects of using melatonin for early intervention, to promote healthy physical and mental ageing, are of prime interest in view of the emerging link to the aetiology of Alzheimer's disease.

          Linked Articles

          This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc

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          Most cited references71

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          Default network activity, coupled with the frontoparietal control network, supports goal-directed cognition.

          Tasks that demand externalized attention reliably suppress default network activity while activating the dorsal attention network. These networks have an intrinsic competitive relationship; activation of one suppresses activity of the other. Consequently, many assume that default network activity is suppressed during goal-directed cognition. We challenge this assumption in an fMRI study of planning. Recent studies link default network activity with internally focused cognition, such as imagining personal future events, suggesting a role in autobiographical planning. However, it is unclear how goal-directed cognition with an internal focus is mediated by these opposing networks. A third anatomically interposed 'frontoparietal control network' might mediate planning across domains, flexibly coupling with either the default or dorsal attention network in support of internally versus externally focused goal-directed cognition, respectively. We tested this hypothesis by analyzing brain activity during autobiographical versus visuospatial planning. Autobiographical planning engaged the default network, whereas visuospatial planning engaged the dorsal attention network, consistent with the anti-correlated domains of internalized and externalized cognition. Critically, both planning tasks engaged the frontoparietal control network. Task-related activation of these three networks was anatomically consistent with independently defined resting-state functional connectivity MRI maps. Task-related functional connectivity analyses demonstrate that the default network can be involved in goal-directed cognition when its activity is coupled with the frontoparietal control network. Additionally, the frontoparietal control network may flexibly couple with the default and dorsal attention networks according to task domain, serving as a cortical mediator linking the two networks in support of goal-directed cognitive processes. Copyright 2010 Elsevier Inc. All rights reserved.
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            Decoupling of the brain's default mode network during deep sleep.

            The recent discovery of a circuit of brain regions that is highly active in the absence of overt behavior has led to a quest for revealing the possible function of this so-called default-mode network (DMN). A very recent study, finding similarities in awake humans and anesthetized primates, has suggested that DMN activity might not simply reflect ongoing conscious mentation but rather a more general form of network dynamics typical of complex systems. Here, by performing functional MRI in humans, it is shown that a natural, sleep-induced reduction of consciousness is reflected in altered correlation between DMN network components, most notably a reduced involvement of frontal cortex. This suggests that DMN may play an important role in the sustenance of conscious awareness.
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              Derivation of research diagnostic criteria for insomnia: report of an American Academy of Sleep Medicine Work Group.

              Insomnia is a highly prevalent, often debilitating, and economically burdensome form of sleep disturbance caused by various situational, medical, emotional, environmental and behavioral factors. Although several consensually-derived nosologies have described numerous insomnia phenotypes, research concerning these phenotypes has been greatly hampered by a lack of widely accepted operational research diagnostic criteria (RDC) for their definition. The lack of RDC has, in turn, led to inconsistent research findings for most phenotypes largely due to the variable definitions used for their ascertainment. Given this problem, the American Academy of Sleep Medicine (AASM) commissioned a Work Group (WG) to review the literature and identify those insomnia phenotypes that appear most valid and tenable. In addition, this WG was asked to derive standardized RDC for these phenotypes and recommend assessment procedures for their ascertainment. This report outlines the WG's findings, the insomnia RDC derived, and research assessment procedures the WG recommends for identifying study participants who meet these RDC.

                Author and article information

                Br J Pharmacol
                Br. J. Pharmacol
                British Journal of Pharmacology
                John Wiley and Sons Inc. (Hoboken )
                15 January 2018
                August 2018
                15 January 2018
                : 175
                : 16 , Themed Section: Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. Guest Editor: S C Stanford ( doiID: 10.1111/bph.v175.16 )
                : 3190-3199
                [ 1 ] Department of Neurobiology, Faculty of Life Sciences Tel‐Aviv University and Neurim Pharmaceuticals Tel Aviv Israel
                Author notes
                [*] [* ] Correspondence Nava Zisapel, Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. E‐mail: navazisapel@ 123456gmail.com
                Author information
                BPH14116 2017-BJP-0932-RCT-G.R2
                © 2018 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                : 20 July 2017
                : 13 November 2017
                : 20 November 2017
                Page count
                Figures: 3, Tables: 0, Pages: 10, Words: 5628
                Review Article
                Themed Section: Review Articles
                Custom metadata
                August 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.4 mode:remove_FC converted:24.07.2018

                Pharmacology & Pharmaceutical medicine
                Pharmacology & Pharmaceutical medicine


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