Significant numbers of interesting findings in both theoretical neurobiology and in more practical applications aimed at studying various brain conditions and diseases have been published this month. Choosing the most interesting articles to include in this monthly review is a highly subjective exercise. As usual, the content of this article mostly reflects my personal opinion about their significance.

On 9 June, the scientific community marked 140 years since the birth of Sir Henry Dale. Sir Dale is credited for identification of achetylcholine as a potential neurotransmitter back in 1914. The role of acetylcholine in nervous system was later confirmed by Otto Loewi, and both scientists shared the Nobel Prize for Medicine in 1936. The discovery is still considered a foundation stone for our understanding of signal transmission in nervous system.

THE BEST

Mental flexibility and the function of rare neurons

We all know that some people are flexible in their behavior and can quickly adapt to the changing environments, while others are very slow at recognizing that the rules have changed and continue sticking to the old “time-proven” norms.

Researchers have now found that this mental flexibility, or the lack of such, is not just a psychological phenomenon but is linked to the function of certain rare neurons in the brain. Cholinergic interneurons that represent only 1% of neurons in the striatum turn out to play a key role in this behavioral flexibility. The striatum is a part of the brain involved in the higher-level decision-making.

In their experiments, researchers trained rats to claim food rewards by reacting to certain external signals. After this, they destroyed cholinergic interneurons in some rats and changed the type of stimulus, leading to a better reward. Normal rats were able to quickly find out which strategy led to receiving the food. However, the animals with damaged cholinergic interneurons were unable to change their behavior and kept using the previously learned tricks for getting the rewards even though they were very ineffective. It remains to be seen how the function of cholinergic interneurons in humans correlates with individual mental flexibility.

Bad diet affects mental flexibility

Cognitive flexibility was the subject of another interesting study that analyzed the link between high-fat and high-sugar diets and mental functions.

It turned out that after just four weeks on these unhealthy diets, especially on the diet rich in sugar, the performance of experimental animals on various mental and physical tests started to decrease. Cognitive flexibility – the ability to adjust behavior to the changing circumstances – was particularly affected. Rats demonstrated serious decline in their learning abilities, as well as worsening short- and long-term memory. Scientists believe that this is a result of changes in the gut flora that take place during the expended periods of unhealthy eating. The findings confirm once again the importance of the crosstalk between the bacterial flora in the gut and our brain functions.

Genetic link between creativity and mental disorders

It is already proven that there is a link between creativity and higher risk of some mental disorders such as bipolar disorder and schizophrenia. What remained unknown until now is whether this link has any genetic component, or the connection exists due to socio-psychological reasons and environmental factors. New findings published by researchers from King’s College London have now confirmed that creativity and some mental disorders do have common genetic roots.

Scientists analyzed the genetic data from over 86,000 individuals from Iceland and found that the genes linked to schizophrenia and bipolar disorders are indeed much more common in the individuals defined as creative. It appears that creative people do have genetic predisposition to thinking differently. Combined with negative environmental factors, this predisposition can lead to the development of mental illnesses.

Sleep model in a Petri dish

Despite decades of research, sleep remains a mystery. We don’t know why we sleep or what purpose sleeping serves and very little is known about biochemical and physiological mechanisms involved in sleep. This makes a new discovery of scientists from the Washington State University particularly important.

The researchers managed to isolate and grow in the Petri dish a small group of neurons that exhibit a typical sleep and wake behavior depending on the experimental conditions. The network of cells in the mature culture displays the same EEG patterns that can be observed in the whole brain. For a long time it was believed that sleep is a whole-brain phenomenon. Now it is becoming apparent that parts of the brain and even small neuronal network can “fall asleep” independently. The discovery will help to study the genetic and biochemical aspects of the sleep in a small laboratory model without intrusions into the whole brains.

Another twist in the placebo story

The use of placebo is a mainstream approach in the clinical trials of new drug. The amazing thing is that a placebo (a fake pill filled with some innocent ingredients) often works. Although nobody knows exactly how it works, scientists believe that a simple expectation of positive effect is sufficient to achieve certain improvements. This belief, however, may not be entirely correct.

In a series of recent experiments, researchers gave placebo pills to people with various conditions and told them that the pills were fakes. Nonetheless, they still produced improvements for a seriously large number of patients. Irritable bowel syndrome, depression and migraine are some of the conditions where this effect has been demonstrated. There is no explanation to this phenomenon yet. However, new neurophysiological studies reveal neurotransmitter pathways that mediate placebo effects. There is evidence that genetic variations in these pathways can modify placebo effects in individuals.

THE WORST

It is not rare to see scientific theories to be proven wrong. However, the negative results are often informative and help to get a better picture of a problem in question.

Social phobia is caused but excess of serotonin, not its shortage

Rather unexpected results were obtained this month by researchers studying social anxiety disorder. It was generally believed that people with social phobia produce too little serotonin in the brain. Therefore, treatment involves the use of SSRIs (selective serotonin re-uptake inhibitors), which increase the amount of serotonin by inhibiting its reabsorption back into the presynaptic cells. Using a special tracer, the researchers found that the situation is exactly opposite – patients with social anxiety disorder produce excessive amounts of serotonin, and also pump back more of this neurotransmitter. The finding may have major implications for treating this condition.

Mental activity does not prevent the development of Alzheimer’s signs in brain

A number of recent studies point to the fact that keeping body and mind active may protect against the development of Alzheimer’s disease. However, novel data cast certain doubts on this emerging view. Researchers found that keeping active has no influence on the biochemical markers of Alzheimer’s, such as amyloid-beta deposit, which remains on the same level regardless of the patients activity level. However, more active people clearly performed better in the cognitive tests and had higher IQ level. It is likely that mental and physical activity triggers some compensatory mechanisms that prevent or slow down the disease manifestation, even when the underlying physiological changes take place.

Parkinson’s disease probably starts in the gut, not the brain

Like with many other neurodegenerative disorders, it is not clear why, how and when Parkinson’s disease starts. New data suggest that the disease originates not in the brain, as previously thought, but in the gut. This conclusion is based on an interesting observation of researchers from Denmark. The scientists noticed that the incidence of Parkinson’s disease is much lower among people who underwent vagotomy, a surgical treatment for ulcer that involves severing of the vagus nerve. This nerve connects the gastrointestinal tract with the brain. It is known that many Parkinson’s patients had history of gastrointestinal problems before the onset of the disease. So it appears that Parkinson’s disease initially develops in the gut and later spreads to the brain via the vagus nerve.

General anesthesia is harmful for young children’s brain

It was always suspected but now this is official: the use of surgical anesthesia in young children has a negative effect on their brain structure and mental abilities later in life. In their retrospective study of children who underwent surgery under general anesthesia before age 4, researchers from Cincinnati Children’s Hospital Medical Center reported that these children had lower IQ, diminished language comprehension and lower density of grey matter in the posterior region of the brain.

Although all these parameters still remain within the normal range, statistically they are lower than in children who didn’t experience anesthesia at this young age. The findings highlight the need to develop better approaches to surgical anesthesia for young children.

Some MRI contrast agents might be dangerous

With millions of patients getting MRI scans every year, the technique rapidly becomes one of the most commonly used diagnostic tools in the developed countries. However, new data published this month cast the shadow on the safety of the contrast agents used for the data acquisition – so-called linear-type gadolinium-based contrast agents.

It appears that repeated use of these agents in the MRI scans lead to accumulation of toxic heavy metal gadolinium in the patients’ brains. The safety concerns may have serious implication on the whole MRI industry and likely to result in substituting linear-type agents with safer and more stable macrocyclic gadolinium-based agents. The use of the latter does not lead to accumulation of gadolinium in the brain.

References

Aoki, S., Liu, A., Zucca, A., Zucca, S., & Wickens, J. (2015). Role of Striatal Cholinergic Interneurons in Set-Shifting in the Rat Journal of Neuroscience, 35 (25), 9424-9431 DOI: 10.1523/JNEUROSCI.0490-15.2015

Backeljauw, B., Holland, S., Altaye, M., & Loepke, A. (2015). Cognition and Brain Structure Following Early Childhood Surgery With Anesthesia PEDIATRICS, 136 (1) DOI: 10.1542/peds.2014-3526

Frick, A., Åhs, F., Engman, J., Jonasson, M., Alaie, I., Björkstrand, J., Frans, ?., Faria, V., Linnman, C., Appel, L., Wahlstedt, K., Lubberink, M., Fredrikson, M., & Furmark, T. (2015). Serotonin Synthesis and Reuptake in Social Anxiety Disorder JAMA Psychiatry DOI: 10.1001/jamapsychiatry.2015.0125

Gidicsin, C., Maye, J., Locascio, J., Pepin, L., Philiossaint, M., Becker, J., Younger, A., Dekhtyar, M., Schultz, A., Amariglio, R., Marshall, G., Rentz, D., Hedden, T., Sperling, R., & Johnson, K. (2015). Cognitive activity relates to cognitive performance but not to Alzheimer disease biomarkers Neurology, 85 (1), 48-55 DOI: 10.1212/WNL.0000000000001704

Hall, K., Loscalzo, J., & Kaptchuk, T. (2015). Genetics and the placebo effect: the placebome Trends in Molecular Medicine, 21 (5), 285-294 DOI: 10.1016/j.molmed.2015.02.009

Jewett, K., Taishi, P., Sengupta, P., Roy, S., Davis, C., & Krueger, J. (2015). Tumor necrosis factor enhances the sleep-like state and electrical stimulation induces a wake-like state in co-cultures of neurons and glia European Journal of Neuroscience DOI: 10.1111/ejn.12968

Magnusson, K., Hauck, L., Jeffrey, B., Elias, V., Humphrey, A., Nath, R., Perrone, A., & Bermudez, L. (2015). Relationships between diet-related changes in the gut microbiome and cognitive flexibility Neuroscience, 300, 128-140 DOI: 10.1016/j.neuroscience.2015.05.016

Power, R., Steinberg, S., Bjornsdottir, G., Rietveld, C., Abdellaoui, A., Nivard, M., Johannesson, M., Galesloot, T., Hottenga, J., Willemsen, G., Cesarini, D., Benjamin, D., Magnusson, P., Ullén, F., Tiemeier, H., Hofman, A., van Rooij, F., Walters, G., Sigurdsson, E., Thorgeirsson, T., Ingason, A., Helgason, A., Kong, A., Kiemeney, L., Koellinger, P., Boomsma, D., Gudbjartsson, D., Stefansson, H., & Stefansson, K. (2015). Polygenic risk scores for schizophrenia and bipolar disorder predict creativity Nature Neuroscience, 18 (7), 953-955 DOI: 10.1038/nn.4040

Robert, P., Lehericy, S., Grand, S., Violas, X., Fretellier, N., Idée, J., Ballet, S., & Corot, C. (2015). T1-Weighted Hypersignal in the Deep Cerebellar Nuclei After Repeated Administrations of Gadolinium-Based Contrast Agents in Healthy Rats Investigative Radiology, 50 (8), 473-480 DOI: 10.1097/RLI.0000000000000181

Svensson, E., Horváth-Puhó, E., Thomsen, R., Djurhuus, J., Pedersen, L., Borghammer, P., & Sørensen, H. (2015). Vagotomy and subsequent risk of Parkinson’s disease Annals of Neurology DOI: 10.1002/ana.24448

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