insomnia | Finding Neuron

Why “sleep”?

Posted on October 27, 2015 by Iasmina Hornoiu

In a previous article, we talked a bit about narcolepsy as one of the very intriguing sleep disorders. It was perhaps easy to understand why people suffering from narcolepsy could have a pretty hard time performing several normal tasks; however, most of us would probably relate less to narcolepsy. But something which almost everyone can agree to have experienced regularly, in one way or another, is sleep. In comparison with disorders associated with it or derived from its impairments, sleep itself might not seem so interesting. We all do it and we can’t deny how much we enjoy it and long for it after it stops. Yet, there is much more to sleep than we think.

Sleep is very important for the normal functioning of any being. For animals as well as for humans, sleep helps in energy conservation, body restoration, predator avoidance and learning aid. Different animals have different sleep-wake cycles, from nocturnal animals (like rodents), which sleep during the day and are active at night, and animals which sleep with only half of the brain (like dolphins), all the way to diurnal animals, like humans. Although humans are advised to sleep approximately 8 hours per night, some people sleep very little (around 2-3 hours/night) and still function perfectly fine. An example of such a situation is presented in the textbook of Rosenzweig et al. (pg. 389).

But what triggers sleep and how is it regulated?

Most of us are certainly able to recall a dream the next morning and the memory of that dream is usually accompanied by feelings and emotions we sometimes do not even experience in real life. We are often under the impression that our dream has lasted the whole night. In fact, there are two stages of sleep, one of which is associated with the formation of dreams. These stages, known as non-REM sleep and REM sleep, succeed each other in cycles lasting approximately 90 minutes. Just to define the terms, REM means rapid eye movement and represents the part of sleep with the most increased brain activity. Interestingly, during REM the brain seems to consume more oxygen than during arousal!

Normally, when we fall asleep we slip into the non-REM stage or the slow-wave sleep (SWL). This, in turn, is divided into four other stages: from light sleep to very deep sleep. During this phase, the brain is said to be truly resting and the body appears to repair its tissues. No dreams can be seen! The movement of the body is reduced, but not because the muscles are incapable of moving; it’s the brain which does not send signals to the body to move! One interesting feature of non-REM sleep is sleep-walking. This peculiar behaviour some people show while asleep usually takes place during the fourth (last) part of the non-REM sleep, when the person is the deepest sleep. This is the reason why it is very difficult to wake a sleepwalker up.

In turn, REM sleep (which starts after a 30-minute non-REM period) is the “active” part of our sleep. This time, the brain sends commands to the body, but the body seems to be in an almost complete state of atonia (immobility). The heart rate and breathing become irregular and the brain is not resting. In fact, our dreams happen during this time and more importantly, our long-lasting memories are thought to be integrated and consolidated.

When it comes to sleep regulation, many neuroendocrine systems and brain functions play a role. The circadian (or sleep-wake cycle), which is controlled primarily by the suprachiasmatic nuclei, in the hypothalamus, need special attention. For the purpose of this article, I won’t focus on the circadian clock now, but I will come back to this in a future article. The autonomic nervous system and parts of the brain such as the brainstem, the limbic system, especially the amygdala, and the forebrain modulate different aspects and stages of sleep. Amygdala, which I mentioned in a previous article about emotions and decision-making, is a brain region involved in the emotions such as fear. It also appears to be very active during REM-sleep and may account for the awful nightmares we often experience.

Many cognitive functions, such as intelligence, performance and emotions are associated with disrupted non-REM as well as REM sleep. To be more specific, REM-sleep loss appears to be associated with increased anxiety and stress and loss of emotional neutrality – this means that a person deprived of REM-sleep is more likely to react negatively to neutral emotional stimuli than in normal conditions. The explanations vary, but most of the studies agree that impaired REM sleep triggers increased release of noradrenaline, hyperactivity of amygdala and decreased function of prefrontal cortex (which tells “stop!” to the amygdala when it goes crazy). At the same time, people deprived of non-REM sleep could experience depression, due to deficiency in another neurotransmitter, this time an inhibitory one, called GABA (gamma-aminobutyric acid). Other problems linked to sleep deprivation are attention deficits, working memory impairments and usually affected divergent thinking (creative, innovative thinking).

Aging people seem to sleep less and this deprivation is also associated with conditions like Alzheimer’s. Moreover, sleep deprivation can kill you! Sustained sleep loss can cause low immune system and drop in body’s temperature, which can make bacterial infections fatal. Another consequence of sleep loss is increased metabolic rate, which leads to weight loss and eventually death. Don’t think this could be a good idea for a diet! More like for “die”!!! Having said that, most people should try their best to get enough hours of sleep.

I hope this article convinced you of the importance of sleep and as usual, any questions or comments are welcome 🙂

Further information:

Article 1 – about REM-sleep and emotional discrimination

Article 2 – about non-REM sleep and GABA

Article 3 – about how sleep loss affects behaviour and emotions

Article 4 – a review on many articles about the link between sleep deprivation and emotional reactivity and perception

Bear et al., 2006. Neuroscience – Exploring the Brain. s.l.:Lippincott Williams & Wilknins

Rosenzweig et al., 2010. Biological Psychology – An Introduction to Behavioural, Cognitive and Clinical Neuroscience. 6th edition. Sinauer Associates Inc.,U.S., pg. 380-401

Both images by Gabriel Velichkova

Narcolepsy

Posted on September 21, 2015 by Iasmina Hornoiu

Can you think of any situation when, let’s say, you were talking to someone and suddenly that person would glance at you with boredom and their eyes seemed to slowly close as if they were on the verge of nodding off? This sort of situations can be very annoying and it would be a lie to say that you didn’t feel mad or at least slightly pissed off when they happened. You probably either ignored them or chose a more aggressive approach, in order to ‘wake’ them up.

But what if instead of just a very rude or uneducated person you would have to deal with someone who suffers from narcolepsy? Not only the person you would supposedly talk to is actually asleep, but waking them up is very likely to trigger unwanted behaviours.

As odd as it sounds, there are people in this world who can fall asleep instantaneously, without any previous warning, in the middle of doing anything ranging from reading and talking to cooking and driving. These people are called ‘narcoleptics’.

So what is narcolepsy?

Narcolepsy or the so-called syndrome of excessive sleepiness is a chronic neurological disorder that affects less than one percent of the population, therefore it is considered a relatively rare disease. Due to the multiple causes that lead to this disorder, narcolepsy has been considered either an autoimmune or a neurodegenerative disease. Often it is hard to be identified and wrong diagnosis is given, such as epilepsy (because cataplexy could resemble epileptic seizures) or schizophrenia (due to visual and sometimes auditory hallucinations).

Symptoms

The most common symptoms of narcolepsy are: sleep disturbance, cataplexy (muscle weakness), excessive daytime sleepiness, sleep paralysis, hypnagogic hallucinations and abnormal rapid eye movement (REM) – in narcoleptics REM occurs extremely fast (within a few minutes), whereas normally it should manifest after one hour and a half. Nevertheless, patients who suffer from narcolepsy have also experienced increased appetite, automatic behaviour, sleep apnoea and memory problems (this is not due to cortical dysfunction, but to impaired attention).

Except for cataplexy, sleep paralysis and hypnogogic hallucinations, reduced attention and disorientation after waking from daytime naps are also common. Moreover, patients could suffer from aggressive behaviour, with temper outburst and irritability especially if woken up and they might also deny their condition.

Interestingly enough, despite the fact that narcoleptics have trouble with being awake during the day, they would often experience insomnia during the night. Their sleep deficiency can be accentuated by some forms of medical treatment.

Causes

It has been demonstrated that many factors are involved in the initiation and development of narcolepsy; these range from genetic factors, including the human leukocyte antigen DQ and DR (HLA-DQ and -DR) genes and polymorphism of certain type of genes (for instance tumour necrosis factor alpha or monoamine oxidase genes, both located on chromosome 6) to environmental factors (head trauma and various infections, such as the infection with Streptococcus pyogenes). HLA genes code for the HLA complex called antigens, proteins with an essential role in the immune functions and usually associated with autoimmune diseases.

In addition, latest discoveries have shown a decrease in levels of hypocretin-1 and -2 (also known as orexin-A and-B) in the cerebrospinal fluid and hypothalamus could account for the trigger of narcolepsy. Deficiencies of this neuropeptide might produce changes in monoamine oxidases, enzymes with an important role in the degradation of amine neurotransmitters, such as serotonin and dopamine. Low levels of dopamine dramatically influence the development of some psychiatric and neurodegenerative disorders (ADHD and Parkinson’s disease, respectively) including narcolepsy.

Treatment

Given the fact that the decrease of hypocretin tone plays an important role in the production of narcolepsy, an efficient solution would involve the increase in the concentration of these peptides. One way of achieving this is by intracerebroventricular administration of hypocretin-1 peptide, which appears to reduce the frequency of cataplexy and stimulate arousal in mice. Another even more efficient and less invasive method is represented by the intranasal administration, hence the neuropeptides being directly delivered to the central nervous system.

Serotonin was also discovered to have significant role in wakefulness and REM regulation, hence decrease levels of serotonin (5-HT) might induce narcolepsy. Therefore, medicines that could increase the levels of serotonin in narcoleptic humans might be a solution for this disease.

Most of the patients diagnosed with narcolepsy are recommended pharmaceutical treatments, which usually consist of the intake of certain doses of stimulants. Nevertheless, taking into consideration the side effects of these drugs and the limited adherence of the patients to the medications, alternative methods have been discovered. One of them is represented by behavioural and psychological approaches, for instance regularly scheduled naps during the day and daily exercises (but avoidance of activities that increase body temperature).

Since treatment involving cognitive stimulants is the most wide-spread, a lot of drugs are used in order to cure narcolepsy. A very common example is represented by amphetamines (such as Ritalin), which are known to increase levels of dopamine in the brain, reduce daytime sleepiness and inhibit the monoamine oxidases. Also Mazindol, Modafil and Selegiline are used as treatment for narcolepsy, as they reduce cataplexy and inhibit the monoamine oxidases. The amino acid L-tyrosine stimulates the production of noradrenaline and dopamine, therefore it also represents a solution (although more tests of its effects are required).

Some very important drawbacks that should be considered when using pharmaceutical stimulants in treating narcolepsy, and any disorder that affects the nervous system in general, are the possible adverse effects and the chances of dependence, abuse and tolerance. Although serious addiction problems haven’t been registered, high dosages increase the risk. According to some studies, 30-40% of narcoleptic patients using medicines have developed tolerance, therefore 1-2 days per week of no medication is recommended.

The most common adverse effects of the psychostimulants are headaches, insomnia, anorexia, irritability, heart palpitation. Patients must acknowledge that these drugs cannot be taken as brain enhancers and they must also be aware of the side effects and possible risk of addiction before deciding to undergo a medicine-based treatment.

I hope you enjoyed reading this article 🙂 It is actually highly based on an essay I had to write in my first year of university and therefore I am going to add the literature I used at the time in order to gather information.