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Down with the Sickness: Why Do We Feel More Ill at Night?

2/9/2018

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by Rosalin Dubois
It is one of the worst times of the year - everyone, from your best friend to your professor, is getting sick. Sooner or later you probably will too, and when that time comes you’ll be struck by the same distressing experience: no matter how well you feel during the day, by the time you are ready to go to bed, you feel so miserable that you never want to leave your room again. I’ve always been told, “You’ll feel better in the morning; colds always feel worse at night!” But why is that true?

There are a few plausible explanations for this phenomenon. Some of these explanations are less scientific than others but may still be able to provide insight into why sleeping while sick can be so difficult. Consider everything that you have to distract you during the day. While you are focused on getting to class, meeting an important deadline, or even just socializing with your friends, you may pay less attention to the signals that your body is sending you that indicate you are sick. However, when you try to sleep, you have fewer distractions, and so you may notice more or these signals and feel much sicker. Additionally, when you lie down, gravity affects your body differently than when you are standing. Even just sitting up may help to clear your stuffy airways and help you to sleep better (essential for that 8:30 lecture!).

However, what if you are working late and sitting up, and still feel worse than during the day? You may be experiencing this because of the circadian rhythms of our immune system. Circadian rhythms are physical, mental, and behaviour changes that follow a daily cycle (think your “internal clock”) that tell you what time to get up in the morning. Our immune system also follows a similar pattern as researchers have found that immune response varies throughout the day. During the day, the part of the immune system called cell-mediated immunity (or just cellular immunity) is responsible for defending us from infection. This form of defence is very effective against viruses, bacteria, fungi, and other invaders. Most important to note is that we don’t typically feel the strain of this type of immunity at work.

At night, inflammation replaces cellular immunity. Inflammation is the type of immune response that we normally experience when our tissues are damaged by trauma, bacteria, heat, or other causes. When this happens, the cells that have been damaged release chemicals (including histamine and prostaglandins), which cause blood vessels to expand and allow more blood to reach the damaged area. Additionally, inflammatory mediators increase the permeability of blood vessels to defence cells that carry fluid into the tissue and cause swelling. By surrounding the damaging substance with a barrier of this released fluid, inflammation aims to isolate the invader from our tissues, and therefore prevent it from doing more damage. We experience the worst of our symptoms of being sick, like fever, increased amounts of mucus, and fatigue, when we feel the effects of swelling when our system is inflamed.

Studies over the last decade indicate that this transition between cellular immunity and inflammation occurs due to a change in the activity of a type of white blood cells called T-cells. These cells are important in cell-mediated immunity because they attack and kill antigens (foreign substances). It was determined that T-cells actually become less active against antigens during times when the body would normally be resting, especially at night.

This seems bizarre; why would the body turn off such important defenders when we need them most? A study done by a team of German researchers just last year may hold the answer to that question. In this study, researchers observed changes in the population of the lymph nodes of mice during their active times, and during their rest times. They correctly expected to see more T-cells present in the lymph nodes when they were not working and the mice were resting. However, they were surprised to find that high levels of dendritic cells were also present at this time. Dendritic cells process information about antigens and communicate this information to T-cells so that cellular immunity can effectively target this threat.
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This research seems to indicate that during the day, T-cells and dendritic cells move normally throughout the body, gathering information and dealing with threats. When T-cells randomly come into contact with dendritic cells throughout the body, they receive information so that they can adapt their immune response to better eliminate the antigens. At night, both types of cell move to the lymph nodes, and the high concentration of these cells allows for a greater likelihood of interaction. Through this interaction, the T-cells will receive the information from the dendritic cells to develop a functional immune response to this threat - meaning you could potentially heal faster! Think of it as these cells meeting up to share information on any invaders to be more effective at fighting them off! Meanwhile, the inflammatory part of immunity does its best to prevent any infection from progressing further.

At the end of the day (pun intended), it seems likely that it is a combination of these factors (distraction, position, and dynamics of the immune system) that cause us to feel worse at night. Unfortunately, there still isn’t much to do to prevent this phenomenon other than what you should already be doing to treat a cold. Get well soon, Queen’s!
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"Are You Happy?": Using Neuroimaging to Communicate

2/2/2018

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by Lauren Lin 
“Locked-in syndrome” is used to describe a medical condition in which there is complete paralysis of all voluntary muscles in the body including most facial muscles. Individuals who have locked-in syndrome are conscious, have cognitive function, and are aware of their environment, but they cannot produce movements or speak. This condition is often caused by damage to the pons, a part of the brainstem that relays information to different parts of the brain. The damage can result from strokes, infections of the brain, or bleeding. Certain disorders like Amyotrophic Lateral Sclerosis (ALS), a motor neuron disease, can also cause total motor paralysis. Many people with locked-in syndrome can communicate through moving their eyes and/or blinking, but individuals with locked-in syndrome may eventually lose their ability to move their eyes, and so communication becomes extremely difficult.

Chaudhary, Xia, Silvoni, Cohen, and Birbaumer (2017) report on the potential for brain-computer interface (BCI) to offer a way for patients with ALS who are paralyzed to communicate. BCI research may involve invasive procedures like implanting electrodes in the brain or noninvasive technologies like functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS) to record brain activity. The recorded brain activity then can be interpreted for what the user is communicating. Chaudhary et al. (2017) used fNIRS to measure the changes in blood flow by assessing oxygenated hemoglobin (O2Hb) and used electroencephalography (EEG) to measure brain waves of four patients who had no motor movement. The relative changes in oxygenated hemoglobin when patients responded to “true/yes” and “false/no” statements were significantly different from each other, and so fNIRS measurements were used to recognize whether the patient answered "yes" or "no". However, EEG measurements were not able to reliably discriminate between yes or no answers.

To train the patients to be able to answer questions using BCI, the researchers asked the patients to respond “yes” or “no” to personal statements with known answers like “Your husband’s name is Joachim” or “You were born in Berlin.” For each known statement with a clear “yes” answer, a similar statement with a clear “no” answer was also given. For example, if the statement “You were born in Berlin” was true, it could be paired with “You were born in Paris,” a false statement. The reverse was done for statements with clear “no” answers. The patients were explicitly told to think of “yes” or “no” answers but not to imagine the answer visually or auditorily so that the BCI would only be picking up on signals that correspond with “yes” or “no” sentiments rather than the look or sound of the words. The patients also received feedback on what their answer was interpreted as (e.g. “Your answer was recognized as ‘yes’”) during training.

The patients were asked a total of at least 200 sentences with known answers and 40 open questions or statements that asked about the person’s quality of life or questions of caretakers that only the patient could answer (e.g. “You have back pain.”). The four patients communicated using BCI with a correct response rate of 70% over the course of several weeks, which is above the level of chance (50%). Three of the four patients were asked open questions about their quality of life, such as “Are you happy?” and “I love to live.” These questions were asked repeatedly to ensure validity of the response. All three patients answered “yes,” which indicated an overall positive attitude towards their current situation and towards life.
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BCI seems like a promising way for patients with paralysis in almost all voluntary muscles to communicate since it does not require any motor movements. However, the interpretations of the responses are not always correct, and so it is extremely important to take precautions like asking a single question multiple times. Additionally, BCI may not be accessible in all healthcare settings since it requires both the equipment needed to measure and interpret brain signals and the training for the patient to use it. Despite these limitations, BCI still has a lot of potential to provide a way for locked-in patients to convey their thoughts who may not have been able to previously, especially when considering that one of the patients included in the study had not been able to communicate for four years. The researchers of this study are hopeful that this technology could be a stepping stone towards improving the quality of life of patients who are in a locked-in state and even write that family members all “experienced substantial relief” when they were able to communicate with the patients and that they still use the system.
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