Best and Worst of Neuroscience & Neurology – February 2015




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In February we have seen, yet again, quite a few new exciting developments in neuroscience and neurology. There were interesting findings in both theoretical neuroscience and in more practical applications aimed at studying various brain conditions and diseases.

Please do note, of course, that the choice of which articles to include in the monthly review is highly subjective. The content of this review mostly reflects my personal opinion about their significance.

On 23 February, the scientific community marked the birthday of Allan McLeod Cormack who received the Nobel Prize in Physiology and Medicine in 1979 for invention of computer-assisted tomography. Allan Cormack’s research laid theoretical foundation to this method back in the early 1960s. It would be probably worth mentioning that Cormack’s original papers on the subject initially attracted very little interest, until Godfrey Hounsfield constructed the first CT scanner in 1971 based on Cormack’s theoretical concept. Allan Cormack is rightfully considered the father of modern computer tomography. These days, the CT-based techniques are actively used by neuroscientists. In fact, a number of findings reviewed below are obtained using various CT methods.

First two articles that I include deal with more theoretical aspects of neurobiology.

For decades, neuroscientists believed that adult brains do not produce new neurons. The discovery that this is not correct challenged this major dogma of neuroscience. The role of these new neurons in behavior and cognition is still not clear, however. The article published this month in Trends in Cognitive Science presents an interesting point of view on this issue.

It is now well known that environment has a profound effect on adult brains. Stress has been shown to decrease the number of new neurons in hippocampus. On the other hand, rewarding experiences stimulated the production of new neurons in this part of the brain. The authors of the report argue that new neurons may serve as a means to fine-tune the hippocampus to the predicted environment. In particular, seeking out rewarding experiences or avoiding stressful experiences may help each individual optimize his or her own brain. Thus, it appears that newly born neurons help us to flourish in the rewarding environment.

The question what make our brain unique (thus eventually making us who we are) remains the biggest unsolved mystery in neuroscience. An article published this month in Science can certainly be viewed as a serious contribution towards finding the answer to this question.

Researchers based in Germany were comparing the genes involved in the development of human brain and brain of mouse. They identified 56 genes preferentially expressed in the human neocortex. The neocortex is the part of the brain explicitly associated with cognitive abilities, and it is significantly enlarged in primates. One of the genes, ARHGAP11B, turned out to be present only in human progenitor cells, the stem cells that divide and form other brain cells during the brain growth and development. Moreover, the scientists found that gene ARHGAP11B is unique for humans and is absent even in chimpanzees, our closest evolutionary relatives. Researchers believe that this gene has contributed to the evolutionary expansion of the human neocortex.

The following two articles are related to the studies of how we learn various skills and how we learn to interact with others.

It is intuitively obvious that younger people and people in old age have different approaches to learning. Scientists from University College London decided to put this assumption to a specific test. They enrolled two groups of participants, one aged 19-35 and another aged 60-73, and assigned them the same numeric task which would require some learning to be finished successfully. Both groups performed with similar degree of success, but utilized two completely opposite strategies. Younger people were learning by integrating different types of information, while older people advanced their learning through ignoring distracting, less important information.

The study shows that the brain works rather differently at different ages, and training can enhance different age-dependent cognitive processes. Among other things, this new insight may help to inform educationists on different age-dependent approaches to teaching.

Our social behavior inevitably requires understanding of others and the ability to anticipate their actions. In fact, this ability is a cornerstone of successful social interaction. This month, researchers from Massachusetts General Hospital-Harvard Medical School Center for Nervous System Repair announced that they had discovered key neuronal elements in the dorsal anterior cingulate cortex involved in the formation of such behavior.

Scientists taught rhesus monkeys to play a game where outcome (and consequent reward) was linked to the ability to anticipate each other’s actions. The neurons in the anterior cingulate were particularly active when an animal was trying to figure out the action of the opponent. The anticipating ability disappeared when scientists artificially disrupted the activity of neurons in anterior cingulate cortex. Researchers believe that their findings will help to pave the way for better understanding and treatment of such conditions as autism and antisocial personality disorder.

This month we witnessed large number of publications related to Parkinson’s disease. There were both positive and negative developments in this area.

Encouraging news came from Sweden: in a first-of-its-kind experiment on humans, scientists injected growth factor PDGF directly into the brains of patients suffering from Parkinson’s disease. PDGF is known to stimulate regenerative processes in the body, and researchers hoped that injections of this substance can stimulate self-repair of brain. The previous trials on animals have shown that this assumption is correct and injections can improve motor functions in mice with Parkinson’s disease.

The human trial was limited to 12 patients only and was aimed to establish the safety of the procedure. No adverse effects were observed in any of the patients during the 85-day follow-up period. The symptoms of Parkinson’s disease are caused by a gradual decrease in the production of neuromediator dopamine. The results of brain tomography before and after the injections demonstrated that the level of dopamine increased in the patients who received PDGF injections, thus indicating the reversal of pathological process. Obviously, this is very exciting news, and the trials now will be taken to the next level in several countries around Europe.

Clinical trials often result in failures. The general public is often unaware of the fact that the overwhelming majority of drug trials get terminated – for a variety of reasons – at the early stages, and the potential drugs never reach patients. A trial for a previously promising treatment for Parkinson’s disease was terminated this month.

Despite decades of research and substantial recent progress in understanding the molecular mechanisms involved, we still have no clinically available drugs capable of stopping or even slowing down the development of Parkinson’s disease. Earlier studies indicated that creatine monohydrate might be capable of slowing down the development of disease’s clinical manifestations. This prompted the National Institute of Neurological Disorders and Stroke to initiate a clinical trial to study the long-term effects of this drug.

Unfortunately, after five years of follow-up, researchers did not noticed any improvements in the patients taking creatine monohydrate compared to patients taking a placebo. The trial was terminated early due to futility.

A number of studies in the past reported the association between the use of statins (cholesterol-lowering drugs) and decreased incidence of Parkinson’s disease. The evidence to support this view, however, was rather inconsistent. New analysis of long-term data published this month revealed that statins don’t have protective effect against the disease. Moreover, in the long term they even increase the risk of this disease’s development. The authors of the report caution against promoting benefits of statins until better understanding of their influence on the body and brain is reached.

Two other publications questioned the safety and efficiency of the methods and treatments that have been used in medical practice for decades.

Millions of surgeries under total anesthesia are performed every year around the world. Anesthesia is not absolutely safe and is associated with a number of risks. It appears that one of such risks is the potential impairment of brain development in young children and babies. Several experts in the field have recently published an article highlighting their concerns.

The concerns are based on two facts. First, anesthetics do kill brain cells in young monkeys. Second, children who experienced multiple exposures to anesthesia early in life are more likely to have learning problems. Both facts do not prove conclusively the danger of anesthetic for the developing human brain, but the findings do call for caution and for further research.

Another review published this month cast the doubts on the wisdom of using anti-depressants targeting the serotonin re-uptake pathway. The theory behind using such drugs states that depression is caused by decreased levels of serotonin in the synapses. However, it is not yet possible to measure directly how serotonin is released and used in the living brain, which makes the foundation of the theory quite shaky.

The authors of the report argue that anti-depressive medications, instead of helping patients, complicate their recovery. This explains why the depressive symptoms tend to get worse in the first two weeks of taking the drugs. It appears that the drugs create obstacles for the natural mechanisms of brain recovery. Many researchers will disagree with the point of view of the authors of this report. Nonetheless, the side effects of antidepressants are well known, and more detailed look into the mechanisms of their action is warranted.

Finally, a new research paper published this month challenged one textbook view that persisted in neuroscience for many years.

The hippocampus has traditionally been thought to be critical for conscious memory but not necessary for unconscious memory processing. Unconscious memory involves things that we can do without having to think about it, such as moving around and performing simple manual tasks. Much of the knowledge about the hippocampus and how our brains organize memory comes from research on amnesia patients.

This theory of unconscious memory system was recently challenged by a new analysis of the data. Results suggest that the hippocampus plays a fundamental role in aspects of memory processing that are beyond conscious awareness. It appears that both conscious and unconscious memory systems rely upon the same neural structures but function in different physiological ways.

The studies listed above as negative developments should not necessarily be viewed as such. By exposing the wrong concepts, they provide substantial contribution to our knowledge and help to advance science.

References

Addante, R. (2015). A critical role of the human hippocampus in an electrophysiological measure of implicit memory NeuroImage, 109, 515-528 DOI: 10.1016/j.neuroimage.2014.12.069

Andrews, P., Bharwani, A., Lee, K., Fox, M., & Thomson, J. (2015). Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response Neuroscience & Biobehavioral Reviews, 51, 164-188 DOI: 10.1016/j.neubiorev.2015.01.018

Florio, M., Albert, M., Taverna, E., Namba, T., Brandl, H., Lewitus, E., Haffner, C., Sykes, A., Wong, F., Peters, J., Guhr, E., Klemroth, S., Prufer, K., Kelso, J., Naumann, R., Nusslein, I., Dahl, A., Lachmann, R., Paabo, S., & Huttner, W. (2015). Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion Science DOI: 10.1126/science.aaa1975

Haroush, K., & Williams, Z. (2015). Neuronal Prediction of Opponent’s Behavior during Cooperative Social Interchange in Primates Cell DOI: 10.1016/j.cell.2015.01.045

Kieburtz, K., Tilley, B., Elm, J., Babcock, D., Hauser, R., Ross, G., Augustine, A., Augustine, E., Aminoff, M., Bodis-Wollner, I., Boyd, J., Cambi, F., Chou, K., Christine, C., Cines, M., Dahodwala, N., Derwent, L., Dewey, R., Hawthorne, K., Houghton, D., Kamp, C., Leehey, M., Lew, M., Liang, G., Luo, S., Mari, Z., Morgan, J., Parashos, S., Pérez, A., Petrovitch, H., Rajan, S., Reichwein, S., Roth, J., Schneider, J., Shannon, K., Simon, D., Simuni, T., Singer, C., Sudarsky, L., Tanner, C., Umeh, C., Williams, K., & Wills, A. (2015). Effect of Creatine Monohydrate on Clinical Progression in Patients With Parkinson Disease JAMA, 313 (6) DOI: 10.1001/jama.2015.120

Huang, X., Alonso, A., Guo, X., Umbach, D., Lichtenstein, M., Ballantyne, C., Mailman, R., Mosley, T., & Chen, H. (2015). Statins, plasma cholesterol, and risk of Parkinson’s disease: A prospective study Movement Disorders DOI: 10.1002/mds.26152

Cappelletti, M., Pikkat, H., Upstill, E., Speekenbrink, M., & Walsh, V. (2015). Learning to Integrate versus Inhibiting Information Is Modulated by Age Journal of Neuroscience, 35 (5), 2213-2225 DOI: 10.1523/JNEUROSCI.1018-14.2015

Opendak, M., & Gould, E. (2015). Adult neurogenesis: a substrate for experience-dependent change Trends in Cognitive Sciences, 19 (3), 151-161 DOI: 10.1016/j.tics.2015.01.001

Paul, G., Zachrisson, O., Varrone, A., Almqvist, P., Jerling, M., Lind, G., Rehncrona, S., Linderoth, B., Bjartmarz, H., Shafer, L., Coffey, R., Svensson, M., Mercer, K., Forsberg, A., Halldin, C., Svenningsson, P., Widner, H., Frisén, J., Pålhagen, S., & Haegerstrand, A. (2015). Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson’s disease patients Journal of Clinical Investigation, 125 (3), 1339-1346 DOI: 10.1172/JCI79635

Rappaport, B., Suresh, S., Hertz, S., Evers, A., & Orser, B. (2015). Anesthetic Neurotoxicity — Clinical Implications of Animal Models New England Journal of Medicine, 372 (9), 796-797 DOI: 10.1056/NEJMp1414786

Image via Bangkok happiness / Shutterstock.

Viatcheslav Wlassoff, PhD

Viatcheslav Wlassoff, PhD, is a scientific and medical consultant with experience in pharmaceutical and genetic research. He has an extensive publication history on various topics related to medical sciences. He worked at several leading academic institutions around the globe (Cambridge University (UK), University of New South Wales (Australia), National Institute of Genetics (Japan). Dr. Wlassoff runs consulting service specialized on preparation of scientific publications, medical and scientific writing and editing (Scientific Biomedical Consulting Services).
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