Functional connectivity of the human hypothalamus during wakefulness and nonrapid eye movement sleep

Abstract

Animal experiments indicate that the hypothalamus plays an essential role in regulating the sleep-wake cycle. A recent neuroimaging study conducted under resting wakefulness conditions suggested the presence of a wake-promoting region and a sleep-promoting region in the human posterior hypothalamus and anterior hypothalamus, respectively, and interpreted their anticorrelated organization in resting-state functional networks as evidence for their opposing roles in sleep-wake regulation.However, whether and how the functional networks of the two hypothalamic regions reorganize according to their wake-or sleep-promoting roles during sleep are unclear. Here, we constructed functional networks of the posterior and anterior hypothalamus during wakefulness and nonrapid eye movement (NREM) sleep using simultaneous electroencephalography and functional magnetic resonance imaging data collected from 62 healthy participants. The functional networks of the posterior and anterior hypothalamus exhibited inversely correlated organizations during both wakefulness and NREM sleep. The connectivity strength of the posterior hypothalamic functional network was stronger during wakefulness than during stable sleep.From wakefulness to sleep, the anterior cingulate gyrus, paracingulate gyrus, insular cortex, and fontal operculum cortex showed decreased positive connectivity, while the precentral gyrus and postcentral gyrus showed decreased negative connectivity with the posterior hypothalamus. Additionally, the insular cortex and frontal operculum cortex showed negative connectivity during wakefulness and positive connectivity during sleep with the anterior hypothalamus, exhibiting an increasing trend. These findings provide insights into the correspondence between the functional network organizations and hypothalamic sleep-wake regulation in humans.

Sleep Neuroimaging: past research, present challenges and future directions

“…Recent works have explored functional networks across the sleep-wake cycle and subject measures of sleep impact on the functional connectivity of the DMN during NREM sleep. Jiang et al (Jiang et al, 2021) focused on hypothalamic regions, as animal and lesion studies support the observation that the posterior hypothalamus promotes wakefulness (J.-S. Lin et al, 1989), and by contrast, the anterior hypothalamus is activated explicitly during NREM sleep (J. Lin et al, 1994).…”

“…Wake-NREM Buchsbaum et al, 1989;Maquet et al, 1990;Maquet et al, 1997;Braun et al, 1997;Andersson et al, 1998Horovitz et al, 2008Picchioni et al, 2008Picchioni et al, & 2014Koike et al, 2011;Larson-Prior et al, 2009Sämann et al, 2011;Spoormaker et al, 2010Spoormaker et al, & 2012Tagliazucchi et al, 2012Tagliazucchi et al, , 2013Tagliazucchi et al, & 2014Boly et al, 2012;Lei et al, 2015;Hale et al, 2016;Davis et al, 2016;Mitra et al, 2016;Haimovici et al, 2019;Housin et al, 2019;Wilson et al, 2019;Stevner et al, 2019;Jiang et al, 2021Tagliazucchi et al, 2016 lightdeep NREM Maquet et al, 1992;Kajimura et al, 1999Koike et al, 2011Sämann et al, 2011;Spoormaker et al, 2010;Tagliazucchi et al, 2012Tagliazucchi et al, , 2013Tagliazucchi et al, & 2014Davis et al, 2016;Haimovici et al, 2019;Houldin et al, 2019;Stevner et al, 2019;Jiang et al, 2021 Wake-REM Buchsbaum et al, 1989;Maq...…”

“…Dang-Vu et al, 2011;Schabus et al, 2012;Wilf et al, 2016;Blume et al, 2018 Connectivity Horovitz et al, 2008Picchioni et al, 2008Picchioni et al, & 2014Koike et al, 2011;Larson-Prior et al, 2009Sämann et al, 2011;Spoormaker et al, 2010Spoormaker et al, & 2012Tagliazucchi et al, 2012Tagliazucchi et al, & 2013Tagliazucchi et al, & 2014Boly et al, 2012; Let et al, 2015;Hale et al, 2016; Davis et al, 2016; Mitra et al, 2016;Haimovici et al, 2017;Houldin et al, 2019;Wilson et al, 2019;Stevner et al, 2019;Jiang et al, 2021 …”

Deficient sleep, altered hypothalamic functional connectivity, depression and anxiety in cigarette smokers

“…The hypothalamus regulates the sleep-wake cycle and body clock ( Mignot et al, 2002 ; Szymusiak et al, 2007 ). Studies have characterized changes in hypothalamic resting state functional connectivities (rsFCs) in relation to sleep-wake transition ( Boes et al, 2018 ; Jiang et al, 2021 ) and to sleep deficiency and deprivation ( Ding et al, 2021 ; Krause et al, 2017 ; Qi et al, 2021 ). For instance, patients with insomnia disorder vs. healthy controls showed stronger hypothalamic rsFCs with bilateral medial frontal cortex and left pallidum and weaker rsFCs with right inferior temporal cortex ( Ding et al, 2021 ).…”

Hypothalamus volumes in adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Impact of self-reported fatigue and illness duration

“…Thus, changes to PVN circuitry may cause robust alterations to homeostasis (Rosenzweig et al, 2020) and disrupt functional integration between hypothalamic nuclei and processes relevant to ME/CFS pathophysiology. This includes interactions between the PVN and medial preoptic area, dorsomedial nucleus, lateral hypothalamus and suprachiasmatic nucleus to regulate the stress response (Gao and Sun, 2016), interactions with preoptic nuclei to initiate sleep (Jiang et al, 2021), and lateral and tuberomammillary nuclei to promote wakefulness (Ono et al, 2020). Disturbances to stress, sleep and wakefulness processes facilitated by the hypothalamus have been implicated in fatigue pathophysiology in other chronic conditions such as multiple sclerosis (Burfeind et al, 2016), but whether such relationships exist in ME/CFS have yet to be examined.…”