Hi, I mentioned a breakthrough moment in Ayurvedic treatment regarding N3 sleep (former stage 4) which I thought was critical in other posts on the forum. I went back to an essay I posted in the blog and have pasted it below. Regarding the material I've put up on PET scans and neuroinflammation it is worth pointing out that IL-6 levels increase as a result of diminished sleep quality-this reinforces the inflammatory positive feedback loop. Happy for anybody to pick this up and run with it. 'Normal sleep patterns consist of 3 non REM phases. Each phase is characterized by specific changes in Electroencephalography (EEG) (43). There follows a period of Rapid Eye Movement (REM) sleep. The four phases in total makes up one cycle of normal sleep of approximately 90 minutes duration.(44). The phase of sleep that is most relevant to normal functioning is N3 deep sleep(45). This phase is characterized by slow, large delta waves (previously denoted as stage 4 sleep). It is concomitant with "refreshing sleep"(46). The N3 stage is considered to be of greatest physiological importance(47) because deprivation of N3 leads to physical, mental and emotional fatigue and diminished ability to perform higher level cognitive functions.(48). Lack of refreshed sleep has been shown to course neuronal degradation from the activity of free radicals (and an increase in glucocorticoids)(49). During sleep, most body systems are in a heightened anabolic state - accentuating the growth and rejuvenation of immune, nervous and muscular skeletal systems(50). Further, secretion of Growth Hormone, which is pulsatile with episodic bursts, occurs in N3 stage sleep. This is precisely the phase of sleep which is deregulated in CFS/ME(51). There is evidence that Alzheimer's disease may be the result of chronic sleep debt(52). Patients suffering from CFS/ME report refreshed sleep deprivation being the norm, suffered continuously not occasionally. Profound fatigue results(53). Warwick University studies (54) indicate lack of sleep can double the risk of death from cardiovascular disease. Direct results of sleep deprivation include memory lapse, impaired judgement, impaired immune system, risk of Type 2 diabetes developing, increased reaction time in muscle and tremor(55). Studies of sleep deprivation in CFS/ME clearly show disruption of N3 stage sleep.(56). Hence, the metabolic benefits of refreshed sleep are lost, for example increased glymphatic clearance of metabolic waste products produced by neural activity in the brain (57). Sleep combats the accumulation of free radicals in the brain, in which glial cells are restored with glucose (via activity of GH)(58). N3 stage sleep is necessary for survival. (59) Does dysregulation of N3 stage sleep implicate disruption of hypothalamic function? Sleep is highly dependent on the activity of the hypothalamus and reticular formation (RF) (60). The RF cholinergic system is linked to the hypothalamus and and has active involvement in the generation, timing and execution of sleep and the regulation of transition between the different sleep stages.(61). Projection neurons in the RF modulate EEG waves(62). The hypothalamic suprachiasmatic nucleus (brain's biological clock) controls diurnal cycles thus regulating the timing of sleep and wakefulness(63). Prostaglandins are released to generate sleep(64). Also of note is that the adrenergic system (medulla) generates wakefulness (65). If the hypothalamus is indeed damaged in its normal functioning capacity this "wakefulness" system could be compromised.'