Neurobiology of Sleep—Circadian Rhythms PDF

Neurobiology of Sleep—Circadian Rhythms, Sleep-Wake Cycle and I... https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2533795-dt-... Neurobiology of Sleep—Circadian Rhythms, Sleep-Wake Cycle and Insomnia Hi and welcome to Hub Bites. I...

Neurobiology of Sleep—Circadian Rhythms, Sleep-Wake Cycle and I... https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2533795-dt-... Neurobiology of Sleep—Circadian Rhythms, Sleep-Wake Cycle and Insomnia Hi and welcome to Hub Bites. I'm Sanil Rege, consultant psychiatrist from Psych Scene. Today, I'll be taking you through the neurobiology of sleep. There are two key processes involved in the neurobiology of sleep. One is the circadian process. Two, the homeostatic process. The circadian process is linked to the internal clock, which is present in all cells of the body. We have the hormone melatonin and the neuropeptide adenosine that are sleep-promoting. The circadian rhythm is very closely linked to what we call zeitgebers, which is the German term for time givers. These time givers are sensitive to our routines, sleep- wake routine, physical activity, eating. Light is a very, very important zeitgeber, and we'll see that blue light tends to be a very, very important zeitgeber, which has positive and negative consequences. The homeostatic process, on the other hand, is really the need or the pressure for sleep, and this is a function of the time since you last had an adequate sleep. So, if you haven't slept well, it's likely that the homeostatic process will kick, in forcing you to get adequate sleep. Next, let's have a look at the circadian rhythm. The circadian rhythm is closely linked to light, and when light hits the retinal ganglion cells, it's translated via the retinohypothalamic tract to the suprachiasmatic nucleus. So you can see here, from the retinal ganglion cells to the suprachiasmatic nucleus. From the suprachiasmatic nucleus, this will signal the pineal gland to turn o! melatonin production. So, during daylight, we essentially want melatonin production to cease so that we can stay awake. On the other hand, when it's dark, there is no input from the retinohypothalamic tract to the suprachiasmatic nucleus, and darkness will signal the 1 of 5 12/8/24, 4:32 PM Neurobiology of Sleep—Circadian Rhythms, Sleep-Wake Cycle and I... https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2533795-dt-... pineal gland to produce melatonin, facilitating sleep. So as it gets darker, we know that melatonin tends to increase, and it will peak in the middle of the night, and then starts going down as we come closer to daybreak. There is another important process when we think about the sleep-wake cycle, and that's known as the "ip-"op switch. The three key elements in the "ip-"op switch are orexin neurons, the locus coeruleus raphe nucleus, and the tuba miliary nucleus, the TMN, and the ventrolateral preoptic neurons are the nuclei that are situated there and I'll be calling it the VLPO. So what does orexin do? The orexin neurons can be considered to be the wakefulness neurons. They also stimulate the monoaminergic nuclei, and the monoaminergic nuclei are also wakefulness neurons. But the monoaminergic nuclei also tend to play an important part in actually ceasing or inhibiting the sleep promoting nuclei, which are the VLPO, as we'll see in a bit. And #nally, the monoaminergic nuclei also directly stimulate wakefulness. So essentially to summarize, we've got three key processes playing a part. We know that in wakefulness, orexin neurons are wakefulness neurons, they stimulate wakefulness. The monoaminergic stimulate wakefulness directly, but they will also inhibit the sleep-promoting nuclei situated in the VLPO. Now let's have a think about how sleep is promoted. The VLPO: the neurons situated there promote sleep. The VLPO neurons inhibit the monoaminergic nuclei, and the disinhibition of these VLPO nuclei will inhibit orexin, the wakefulness neurons. So to summarize what's happening here is the VLPO promotes sleep, but they also inhibit this and they inhibit the monoaminergic nuclei. And as a result of which it will promote sleep. So let's have a look at this process like this. This is the awake state, and as you can see what's happening here in the awake state, we know that orexin will be stimulating wakefulness. We know that monoaminergic nuclei will be stimulating wakefulness, but the orexin neurons will be pushing the monoaminergic nuclei to stimulate wakefulness as well. So you get a good sort of triple whammy, but on the other hand, also monoaminergic nuclei are preventing the ventrolateral preoptic or the extended ventrolateral preoptic nuclei from promoting sleep. So you get this overall awake state through the activity of these three areas, but then when it comes time to sleep, what's happening now is VLPO kicks in, and VLPO will inhibit the orexin, as you can see here. And it will inhibit the monoaminergic nuclei as well, thus promoting sleep. 2 of 5 12/8/24, 4:32 PM Neurobiology of Sleep—Circadian Rhythms, Sleep-Wake Cycle and I... https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2533795-dt-... Now earlier I mentioned that light plays an important role in the circadian rhythms. We are exposed to a range of light spectra ranging from, of course, ultraviolet, which we can't see, to the shorter wavelength, high-energy blue light. And we're surrounded by blue light. So at the moment, as I'm talking to you, looking at the computer, I'm exposed to blue light. LED lights that are energy saving are blue light. When we think about watching TV, blue light. Phones, blue light. And what blue light tends to do is... Exposure to blue light during the day is important to suppress melatonin secretion, which we know will keep us awake. But while the exposure to blue light is important for keeping the organism's wellbeing, alertness and cognitive performance during the day, chronic exposure to low intensity blue light directly before bedtime, and this is really crucial, directly before bedtime may have serious implications on sleep quality, circadian phase, and cycle durations. So blue light does have some positive e!ects, but closer to bedtime can have detrimental e!ects on sleep quality and can result in insomnia. So what you can see here is that if I just enlarge myself a bit, basically I'm wearing blue light blocking glasses here. And closer to bedtime, I'll put them on to ensure that I don't have enough exposure to blue light and thereby switching on melatonin production from the pineal gland, facilitating sleep. So let's look at what are the indicators of hyperarousal in insomnia, because one of the key aspects that actually impacts sleep is what we call hyperarousal. So when I'm seeing individuals that are referred to me with insomnia, one of the things I've got to rule out is hyperarousal. So really the top down e!ects, because sleep physicians may look at the respiratory side of things, yes, of course. Now Restless Leg Syndrome, REM sleep movement disorders, et cetera. But one of the key aspects to all of this is to see whether a lot of this is coming from the brain. So what are the indicators for hyperarousal insomnia? In the brain, this could manifest as EEG fast frequencies during sleep, and a sleep study can show that. Increased number of arousals during REM sleep, which is the rapid eye movement sleep, increased daytime sleep, onset latency, and short sleep duration. So these are indicators of hyperarousal. When we look at an EEG, for example, when we carry out a sleep study. From a systemic perspective, increased metabolic rates, increased body temperature, may indicate hyperarousal. The heart: increased heart rate and altered heart rate variability. And of course, increased activity of the pituitary-adrenal axis through high cortisol is another indicator of hyperarousal. And this is sometimes seen in individuals 3 of 5 12/8/24, 4:32 PM Neurobiology of Sleep—Circadian Rhythms, Sleep-Wake Cycle and I... https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2533795-dt-... with depression, agitated depression, where the limbic system is extremely aroused or hyperactive. The other important aspect in the pathophysiology of insomnia is to think about two key aspects. One is the arousal system, and moving sort of down is the prefrontal cortex, which is the cognitive system. Now, if you look at this whole cycle, essentially, overactivation of the arousal system, overactivation of the emotional regulatory system, ultimately ends up impacting the cognitive system. So it's really a balance between decreasing hyperarousal and strengthening the prefrontal cortex by activating or rather decreasing prefrontal hyperactivation, because prefrontal hyperactivation is associated with daytime fatigue. So often what happens is if the individual's hyperaroused or there's hyperarousal at nighttime, they'll sleep poorly. But on the other hand, what's happening is that there's prefrontal hyperactivation. So there's a double whammy, and it results in daytime fatigue as well. So as part of management of insomnia, it's important to address both the hyperarousal, and it's also important to address the cognitive fatigue that can result from it. Now, when we think about the reticular activating system, there are a range of neurotransmitters involved. So yes, we think about melatonin and adenosine, but this is a quick slide to show you that there's a lot more involved. We don't need to go through these details, but you can see that there are a range of neurotransmitters. We have orexin. We have acetylcholine. GABA plays an important role. Histamine plays an important role. We know that many antihistamines are sedating. Noradrenaline plays an important role. So excess noradrenaline, for example, due to trauma can result in nightmares or vivid dreams. And we know that acetylcholine also plays an important part. So there's a huge interplay between the various neurotransmitters when it comes to sleep. So therefore, let's have a think about what are the kind of things that can actually impact on sleep. So bring myself down here. So #rstly, it could be the misalignment of the circadian process leading to phase delays or advances, such as a prolonged sleep- onset latency. So di$culty falling asleep. Next, delayed or advanced melatonin secretion. So melatonin not being released. In that, one of the reasons could be due to excessive exposure to blue light, for example. Next, dysfunction of the homeostatic process. Homeostatic process, as you remember, 4 of 5 12/8/24, 4:32 PM Neurobiology of Sleep—Circadian Rhythms, Sleep-Wake Cycle and I... https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2533795-dt-... was linked to the pressure to fall asleep. And this is a function of the time that's passed since your last adequate sleep. Maladaptive behaviors, for example, reducing the homeostatic process. So not sleeping when you're actually feeling sleepy. Reduced GABAergic activity. So GABA potentiates sleep. GABA also reduces hyperarousal, reduces anxiety. Or orexigenic. We know that orexin is the wakefulness neurons. Over-activity of this can create issues. Over-activity in the hypothalamus, hippocampus, amygdala, and the prefrontal cortices. So if there's overactivity in the threat area of brain, that can create issues, but on the other hand, prefrontal cortex hyperactivation can result in cognitive fatigue. The hyperarousal model of insomnia, which we covered in the previous slide, which is really the increased activation of the cognitive-emotional, behavioral, and autonomous processes during waking and sleeping hours. And #nally co-morbid psychological or medical issues or genetic vulnerabilities. So some individuals are predisposed to insomnia. There are genes associated with it can exacerbate this imbalance between arousal and sleep-inducing brain activity. So I hope this has helped you get an overall perspective on the neurobiology of sleep and how this can impact on or result in sleep disturbances. So the next time round, I hope to take you through the assessment and the management of insomnia. I hope you found this useful. Take care and stay safe. Print this page 5 of 5 12/8/24, 4:32 PM