Brain Blogger » Neuroscience & Neurology Health and Science Blog Covering Brain Topics Sun, 21 Jun 2015 22:00:34 +0000 en-US hourly 1 The Role of Serotonin and Glutamine in Aggression Sat, 20 Jun 2015 14:00:33 +0000 A few years ago, a quote by the Dalai Lama went viral. According to the Tibetan spiritual leader, if every kid in the world is taught to meditate starting today, the world will be able to wipe out violence in one generation. It is not surprising why this saying got liked, clicked, tweeted, shared, and commented on millions of times. With mindless violence escalating by the day, most amongst us are trying to find answers within ourselves and from around us.

Scientists too, are on the hunt to find what causes some people to be aggressive. Some in the scientific community believe that aggression has neurological roots. In particular, scientists implicate the neurotransmitters serotonin and glutamine.

Serotonin: The happy hormone and its role in tempering aggression

Several studies have proved that neurotransmitters can heavily influence behavioral traits in individuals. In particular, imbalances in the levels of neurotransmitters can trigger impulsive negative behaviors. So it is no surprise that scientists are now toying with the idea that neurotransmitters may have a role to play in raising or lowering aggression levels in individuals.

They are particularly interested in the role of serotonin, the “happy hormone” that is known to influence our moods, anxiety levels, impulse-control abilities, and thinking powers. When present in optimal amounts in the body, this substance gives us loads of positive energy and will power.

Researchers believe that just as the right level of serotonin keeps us sunny and cheerful, its imbalance can trigger negative emotions and disruptive behavior. There have been several studies to investigate the role of serotonin imbalance in triggering impulsive aggressive behavior. According to one study, serotonin deficiency or inadequate functioning of the neurotransmitter can make a person impulsively aggressive. Scientists believe that serotonergic dysfunction also makes the dopamine system go awry. These dual developments can trigger co-morbid psychotic disorders that, in turn, make the individual more prone to aggression.

Another study points to the link between certain variations in the serotonin transporter (5-HTT) gene and persistent, pervasive aggression in children. These variations cause the serotonin system to dysfunction triggering aggressive behavior in the child. According to the scientists who conducted this study, children who display persistently aggressive behavior tend to develop anti-social tendencies when they grow up. Impulsive aggression is a common manifestation of anti-social behavioral trends.

Glutamine and aggression

Glutamic acid is an amino acid that is converted to glutamine. Glutamine also gets reconverted to glutamic acid. Glutamic acid is also a precursor to GABA, a critical neurotransmitter that plays an integral role in regulating emotions.

The glutamate neurotransmitter helps support the central nervous system. The proper functioning of this transmitter is critical to keep away depression, enhance mood, and increase mental alertness. A recent study, however, suggests that glutamate may also have a role to play in triggering aggressive behavior in individuals.

In this study conducted on laboratory mice, it was found that injecting glutamate in the brains of the animals raised their levels of aggression towards other mice when provoked. The degree of aggression displayed was proportional to the dosage of the glutamate. What is more, scientists also discovered that the mice brains released more glutamate when they displayed aggressive behavior.

The results may not seem very surprising because excess glutamate in the body has been positively linked to anxiety, mood swings, hyperactivity, and confusion that may trigger aggression in some individuals.

In another study carried out on two groups of children, one with autism and the other healthy, it was discovered that the autistic children had higher levels of glutamate but decreased glutamine in their systems compared to their healthier peers. These were the two most significant genetic-level differences between the autistic and healthy children.

Aggression is a common characteristic of autism. The above findings have prompted researchers to explore clinical treatment methods that target the levels of glutamate and glutamine to control aggression in autistic children.

Aggression and mental isorders

Persistent and pervasive aggressive tendencies that have genetic roots increase the chances of individuals developing co-morbid mental disorders like schizophrenia and depression. Abnormal functioning of the glutamate/GABA-glutamine cycle can trigger mental disorders by hampering the normal neural signaling process.

GABA is a neurotransmitter that acts as a sort of natural tranquilizer in the brain. It lulls activity in the limbic system that is responsible for triggering emotions like anxiety and panic. Mental disorders can occur when the glutamate/GABA ratio gets skewed. Because aggression may also be triggered by an imbalance in the glutamate/GABA-glutamine cycle, aggression control is critical to reduce the chances of an individual developing mental illness.

Genetically-induced aggression points to neurotransmitter deficiencies. Neurotransmitter deficiencies can also manifest in other ways like an individual developing behavioral disorders, ADHD, and chronic and debilitating stress and anxiety. So it is imperative that researchers try to understand the roots of aggression to gain greater insights into several other mental diseases.

Aggression has its roots in several different neural regions. The various neurotransmitters interact with one another in diverse ways to trigger, exaggerate, or temper aggressive tendencies in individuals. However, the role of serotonin and glutamine seems to be more critical than others.

The above-mentioned findings on the role of serotonin and glutamine in triggering impulsive aggressive behavior present promising avenues for finding ways to manage aggression in individuals. Successful clinical and therapeutic intervention (like administering drugs, or deep brain stimulation) will have positive repercussions for diverse groups of people.

Autistic children can develop greater social skills. Criminal offenders may get a shot at reclaiming their lives by learning to manage their aggressive natures. Many other men and women can hope they can curb their aggressive streaks and lead more peaceful and productive personal and professional lives. Knowing more about the neurobiological roots of aggression and aggression control can help many people gain back control of their lives, relationships, and careers.


Beitchman, J., Baldassarra, L., Mik, H., De Luca, V., King, N., Bender, D., Ehtesham, S., & Kennedy, J. (2006). Serotonin Transporter Polymorphisms and Persistent, Pervasive Childhood Aggression American Journal of Psychiatry, 163 (6), 1103-1105 DOI: 10.1176/ajp.2006.163.6.1103

Ghanizadeh, A. (2013). Increased Glutamate and Homocysteine and Decreased Glutamine Levels in Autism: A Review and Strategies for Future Studies of Amino Acids in Autism Disease Markers, 35, 281-286 DOI: 10.1155/2013/536521

Love, T., Stohler, C., & Zubieta, J. (2009). Positron Emission Tomography Measures of Endogenous Opioid Neurotransmission and Impulsiveness Traits in Humans Archives of General Psychiatry, 66 (10) DOI: 10.1001/archgenpsychiatry.2009.134

Morrison TR, & Melloni RH Jr (2014). The role of serotonin, vasopressin, and serotonin/vasopressin interactions in aggressive behavior. Current topics in behavioral neurosciences, 17, 189-228 PMID: 24496652

Seo, D., Patrick, C., & Kennealy, P. (2008). Role of serotonin and dopamine system interactions in the neurobiology of impulsive aggression and its comorbidity with other clinical disorders Aggression and Violent Behavior, 13 (5), 383-395 DOI: 10.1016/j.avb.2008.06.003

Takahashi, A., Lee, R., Iwasato, T., Itohara, S., Arima, H., Bettler, B., Miczek, K., & Koide, T. (2015). Glutamate Input in the Dorsal Raphe Nucleus As a Determinant of Escalated Aggression in Male Mice Journal of Neuroscience, 35 (16), 6452-6463 DOI: 10.1523/JNEUROSCI.2450-14.2015

Zhao, C., & Gammie, S. (2014). Glutamate, GABA, and glutamine are synchronously upregulated in the mouse lateral septum during the postpartum period Brain Research, 1591, 53-62 DOI: 10.1016/j.brainres.2014.10.023

Image via Catalin Petolea / Shutterstock.

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Best and Worst of Neuroscience and Neurology – May 2015 Thu, 18 Jun 2015 14:00:32 +0000 The month of May saw many interesting developments, both in fundamental neuroscience and neurology and in practical aspects of dealing with brain-related diseases and disorders. The selection below outlines some of my favorite publications.

On May 28, the scientific community marked the birthday of Stanley Prusiner, the receiver of the 1997 Nobel Prize in Medicine and Physiology. Back in 1982, Dr Prusiner, who now heads the Institute for Neurodegenerative Diseases at UCSF, discovered and described prions, a new class of infectious agents composed exclusively of self-replicating protein.

Initially viewed mostly as a scientific curiosity, prions turned out to play key role in the development and progression of neurodegenerative diseases such as Alzheimer’s disease, Huntington’s disease, Parkinsonism and mad cow disease. Clear understanding of the role prions are playing in the mechanisms of these diseases gives, for the first time, a real hope of finding drugs to manage and treat these conditions.


Another twist in the Alzheimer’s story

In recent years, the science of neurodegenerative disorders has witnessed quite a few unexpected discoveries. Yet another twist in the studies of Alzheimer’s disease was revealed in the latest issue of Brain journal. It was always assumed that the onset of the disease is caused by the overproduction of certain toxic peptides. Novel data demonstrate, however, that it is the deficiency in the removal of toxic products, amyloid-beta specifically, rather than their increased production, which is causing the first clinical signs of the disease. This information will help in developing more specific targeting pharmaceutical approaches for prevention and slowing down the onset of the symptoms in the patients at risk.

New biomaterial helps in neuronal transplantation

Without doubt, the brain is the most complex organ of human body. No wonder we still have very few approaches to treat brain disorders and injuries. But progress does take place. Stem cell transplantation is viewed by many people as a highly promising technique that can help in treating various disorders and injuries, including brain damage. There are, however, several major technical issues that should be addressed before stem cell transplantation can actually succeed. Stem cells are not particularly easy to integrate into a tissue, and there is a challenge in keeping them alive at a new place.

This month, Canadian scientists have reported very promising results from their experiments with “hydrogel”, a new material that keeps transplanted stem cells bound together and boosts their healing properties. In experiments on rats, the researchers demonstrated that the use of hydrogel helps to partially reverse blindness and help in recovery from stroke. Hydrogel certainly looks like a very promising biomaterial for therapies aimed to repair nerve damage.

Obese teens easily targeted by junk food adverts

Rather unexpected findings were published this month in the journal Cerebral Cortex. We are all aware that TV commercials can be quite persuasive, but it appears that junk food adverts have particularly high appeal to obese teenagers.

By monitoring the brain activity of participants watching TV programs that included various advertisements, the scientists found that junk food adverts directly, and disproportionally, activate the regions of the brain controlling pleasure and taste in these groups. The findings point to a potential mechanism behind the formation of unhealthy eating habits.

Having a bigger brain IS a survival benefit

Evolutionary biologists always assumed that bigger brain size is associated with more adaptable behaviour and thus brings survival benefits to a species. As it turns out, this concept was never actually tested experimentally.

Scientists from Austria have helped to fill this knowledge gap in a relatively simple but revealing experiment with guppy fish. They selected two groups of fish with brains differing in size by 12% and then released them in a semi-natural stream with predators, pike cichlids. Half a year later, significantly more large-brained female guppy fish survived compared with their smaller-brained counterparts. Surprisingly, larger-brained males did not show better survival rate. Researchers believe that this difference was caused by the fact that the males of this species are very brightly coloured and thus are more easily spotted by predators.

Seeing without eyes?

Another fascinating finding came from the field of zoology this month. Scientists studying the ability of octopi skin to change color found that the skin of these animals is also sensitive to light. It contains opsins, the same light-sensitive chemicals that are found in eyes. Although the octopus cannot make the picture of its surroundings by the skin alone, it certainly can sense the brightness of the light and its changes. Unusually, this sensing and the consequent skin response occur without the input of nervous system in the processing of information.


Scientific theories and hypotheses often turn out to be wrong. There is a lot to learn from mistakes.

DNA of neurons constantly gets re-written

We always believed that the genes we inherit from our parents are fixed and unchangeable for life. Well, this is not exactly correct. Genes, and their activity, can be substantially modulated via methylation, a form of chemical modification, of DNA bases.

New data suggest that this DNA modifying activity is particularly intense in neurons, higher than anywhere else in the body. Changes in DNA methylation level influences the activity of certain genes and leads to changes in the level of activity of neurons, particularly when it comes to inter-neuronal signalling and communication. The process appears to be crucial for the normal brain functioning. Scientists also believe that problems with this DNA “re-writing” process may be linked to some brain disorders.

DNA methylation and drug addiction

Molecular mechanisms behind drug addiction have been the focus of intense research for many years, but it appears that new data published this month may point to a major flaw in our understanding of the problem. These new findings also deal with the methylation of genes in brain cells.

Researchers studying cocaine addiction in rat models found that the drug withdrawal symptoms are linked to the epigenetic changes in DNA. Specifically, certain genes get methylated following drug withdrawal, and these changes become particularly pronounced only after a long period (a month) without the drug. Apparently, the addicted personality is formed not during the drug use, but upon quitting. Providing rats with methylation inhibitors after long period without the drug substantially reduced the drug seeking behaviour. If these findings are proven correct for humans, a major review of strategies for treating drug addiction will be needed. In the view of novel data, the current treatment approaches appear to worsen withdrawal symptoms rather than help fight the addiction effectively.

Brain connectivity influences success in quitting smoking

Smokers demonstrate all the classical symptoms of drug addiction. Despite the availability of various aids to quit smoking, leaving the habit behind appears to be remarkably hard for many people. New findings suggest that people who do succeed might have rather specific brain connections that help them to overcome addiction. Brain MRI studies show that successful quitters have better synchrony between the insula and the somatosensory cortex. The former part of the brain is responsible for cravings while the latter one coordinates our senses of touch and motor control. The findings indicate that traditional approaches often fail simply because they do not address the key issue of brain connectivity.

Two other articles published this month question some of our long-held views on brain functions.

Brain actively transports essential fats

The brain contains lots of fats critical to its function. It was always believed that these fats are produced by the brain cells themselves. However, two articles published this month in Nature Genetics prove this wrong. Researchers have demonstrated that blood-circulating lysophosphatidylcholines (LPCs) composed of essential fatty acids like omega-3 get actively transported into the brain cells. Various brain abnormalities like intellectual disabilities and microcephaly can be developed when these transportation mechanisms are affected. The findings might help to pave the way for better targeting brain nutrition, particularly in babies, mothers, and elderly individuals at risk of neurodegenerative disorders.

Oxytocin: not as lovely as it seems

Oxytocin is often praised as a love hormone responsible for maternal, romantic and social bonding. However, more probing investigations with the use of intranasal oxytocin administration show some interesting similarities between the effect of oxytocin and alcohol. Like alcohol, oxytocin can affect our sense of fear and make us to take rather risky actions which would normally avoided. This darker side of the “love hormone” needs to be further studied.


Addicott, M., Sweitzer, M., Froeliger, B., Rose, J., & McClernon, F. (2015). Increased Functional Connectivity in an Insula-Based Network is Associated with Improved Smoking Cessation Outcomes Neuropsychopharmacology DOI: 10.1038/npp.2015.114

Alakbarzade, V., Hameed, A., Quek, D., Chioza, B., Baple, E., Cazenave-Gassiot, A., Nguyen, L., Wenk, M., Ahmad, A., Sreekantan-Nair, A., Weedon, M., Rich, P., Patton, M., Warner, T., Silver, D., & Crosby, A. (2015). A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome Nature Genetics DOI: 10.1038/ng.3313

Ballios, B., Cooke, M., Donaldson, L., Coles, B., Morshead, C., van der Kooy, D., & Shoichet, M. (2015). A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation Stem Cell Reports, 4 (6), 1031-1045 DOI: 10.1016/j.stemcr.2015.04.008

Guemez-Gamboa, A., Nguyen, L., Yang, H., Zaki, M., Kara, M., Ben-Omran, T., Akizu, N., Rosti, R., Rosti, B., Scott, E., Schroth, J., Copeland, B., Vaux, K., Cazenave-Gassiot, A., Quek, D., Wong, B., Tan, B., Wenk, M., Gunel, M., Gabriel, S., Chi, N., Silver, D., & Gleeson, J. (2015). Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome Nature Genetics DOI: 10.1038/ng.3311

Kotrschal, A., Buechel, S., Zala, S., Corral, A., Penn, D., & Kolm, N. (2015). Brain size affects female but not male survival under predation threat Ecology Letters DOI: 10.1111/ele.12441

Krohn, M., Bracke, A., Avchalumov, Y., Schumacher, T., Hofrichter, J., Paarmann, K., Frohlich, C., Lange, C., Bruning, T., von Bohlen und Halbach, O., & Pahnke, J. (2015). Accumulation of murine amyloid-  mimics early Alzheimer’s disease Brain DOI: 10.1093/brain/awv137

Massart, R., Barnea, R., Dikshtein, Y., Suderman, M., Meir, O., Hallett, M., Kennedy, P., Nestler, E., Szyf, M., & Yadid, G. (2015). Role of DNA Methylation in the Nucleus Accumbens in Incubation of Cocaine Craving Journal of Neuroscience, 35 (21), 8042-8058 DOI: 10.1523/JNEUROSCI.3053-14.2015

Mitchell, I., Gillespie, S., & Abu-Akel, A. (2015). Similar effects of intranasal oxytocin administration and acute alcohol consumption on socio-cognitions, emotions and behaviour: Implications for the mechanisms of action Neuroscience & Biobehavioral Reviews, 55, 98-106 DOI: 10.1016/j.neubiorev.2015.04.018

Ramirez, M., & Oakley, T. (2015). Eye-independent, light-activated chromatophore expansion (LACE) and expression of phototransduction genes in the skin of Octopus bimaculoides Journal of Experimental Biology, 218 (10), 1513-1520 DOI: 10.1242/jeb.110908

Rapuano, K., Huckins, J., Sargent, J., Heatherton, T., & Kelley, W. (2015). Individual Differences in Reward and Somatosensory-Motor Brain Regions Correlate with Adiposity in Adolescents Cerebral Cortex DOI: 10.1093/cercor/bhv097

Yu, H., Su, Y., Shin, J., Zhong, C., Guo, J., Weng, Y., Gao, F., Geschwind, D., Coppola, G., Ming, G., & Song, H. (2015). Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair Nature Neuroscience, 18 (6), 836-843 DOI: 10.1038/nn.4008

Image via xrender / Shutterstock.

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Is Your Brain Male or Female? Sat, 06 Jun 2015 14:00:36 +0000 In his book The Essential Difference: Male And Female Brains And The Truth About Autism, Simon Baron-Cohen opens with a phrase capable of causing infinite controversy: “The female brain is predominantly hard-wired for empathy. The male brain is hard-wired for understanding and building systems.”

When I first became interested in gender differentation in the brain, after reading about prairie voles and how oxytocin made them more nurturing as parents (in Steven Johnson´s book Mind Wide Open), I started commenting on new findings about the female brain with friends and acquaintances. The response I got was usually rather skeptical. This was especially the case when I tried to bring the subject up with women.

Apparently, after fighting for equal rights for centuries, many women were reluctant to acknowledge significant differences between the male and female brain. The popularization of neuroscience, aided by advances in the research, have conquered only a fraction of that skepticism. But the truth is that none of it is justified.

Vasopressin and Empathy

Structural differences between the male and female brain, most prominently connectivity between the hemispheres, are well known, while many aspects about the way each one of them works are still a mystery.

A recent study focusing on the synthesis of neuropeptides vasopressin (VP) and oxytocin (OT), which are involved in a large number of social behaviors including mate bonding and parental care, concluded that VP and OT systems frequently mediate sex differences in such behaviors.

Another study from earlier this year found that intranasal VP, yet not oxytocin, altered empathic behavior in both men and women. VP systems in male and female brains have shown many differences across different species of rodents, yet the way these differences affect VP release in the brain is still unknown. At any rate, in spite all the uncharted territory, it would seem that when Baron-Cohen attributed empathy to females, he was not too far from the truth.

Creativity in the Male and Female Brain

One of the things scientists observe most frequently when doing fMRIs of the female and male brain executing the same activities is that different areas of the brain tend to “light up.” While one sex seldom outperforms the other, the way men and women solve a problem, recall certain types of memories, or engage in creative processes appears to be quite different.

During a study focusing on creative processes, such as creative conceptual expansion and general divergent thinking, men and women showed indistinguishable performance levels across the different tasks proposed. However, fMRIs revealed profound strategic differences between the genders. For example, while in men, brain areas related to semantic cognition, rule learning, and decision making were primarily engaged during conceptual expansion, in women there was higher activity in regions associated with speech processing and social perception.

Oxytocin and Parenting

More popular than differences in empathic behavior and creativity strategies, oxytocin is the unquestioned star when it comes to making a name for itself in pop culture. Oxytocin is connected with nurturing and caring behaviors towards offspring. Research has shown that besides playing a key role in childbirth and early mother-child bonding, oxytocin release, alongside dopamine release, may also result from rewarding interactions with infants. It has actually been observed that fathers who spend time with their kids may stimulate the oxytocin-dopamine reward system in their brains.

In fact, evidence points to the possibility to “rewire” the male brain to accommodate parenting styles similar to those associated with females. For example, in one study, a vole from a species that is not nurturing with offspring was placed among a group of nurturing voles. The result was that regardless of its neurological predisposition to be less nurturing, the vole learnt from the individuals around it and became a nurturing parent.

When Babies Cry

The question is, if males can acquire characteristics associated with the female brain, why is gender differentiation in the brain still such a big deal?

Well, there is still more functional differentiation to go. Several studies have analyzed the reactions of both mothers and fathers to the crying of their infants. Scans have revealed a greater activation of amygdala and basal ganglia in brand new mothers compared with fathers, which is consistent with mothers being more preoccupied than fathers in these circumstances. Responses to baby stimuli have also been linked to OT pathways, as mothers who give birth through vaginal birth, which stimulates oxytocin release, show greater brain activity in response to the cries of their own babies versus other babies.

Arguably, parenting styles and how they originate in brain function may be the most salient aspect of male-female differentiation in the brain. However, much of the evidence in these respect points to fathers simply being slower learners. For example, when it comes to baby cry stimuli, it may take fathers between 6 to 18 months to match the level of brain activation shown by mothers, but they eventually get there.

The Extreme Male Brain

With as many champions as detractors, Baron-Cohen is still a top expert in the field. His theory of the extreme male brain may be the culprit of the passions his work never fails to excite. Basically, he proposes that the autistic brain is the “full-on” male brain, namely, zero empathy, all systemization.

In a study published earlier this year, Baron-Cohen and his colleagues presented new evidence for the extreme male brain theory in the shape of hemodynamic response measurements during second-order false-belief task and coherent story task performances. Since the measurements revealed “sex difference in the neural basis of Theory of Mind (a cognitive component of empathy) and pragmatic language,” the researchers concluded that this was in line with the extreme male brain hypothesis; a conclusion that seems slightly far-fetched. While the findings do not disprove the extreme male brain theory, they seem to contribute not much more than a grain of sand in the building of a giant castle.

What About the Gay Brain?

An interesting question that surfaces whenever the male and female brain are discussed is what happens with the gay brain? In other words, do homosexual women have a brain more akin to men´s and vice versa?

A research team tried to answer this question by studying functional cerebral lateralization for the processing of facial emotions. The sample comprised 30 heterosexual males, 30 heterosexual females and 40 gay males. Results revealed that while men were right-lateralized when viewing female faces, homosexual men were as left-lateralized as women during the same activity. Thus, researchers concluded that “gay men are feminized in some aspects of functional cerebral lateralization for facial emotion.”

Perhaps the future of male-female brain differentiations studies lies in the understanding of brain formation and development. A study from Beijing University, which appeared in Acta Radiologica earlier this year, attempts to draw conclusions from studying the brains of 400 young adults. The authors observed significant topographical differences between the sexes, including gray matter volume and cortical thickness, both larger in females, and posed a question neuroscientists will bust their own brains – whether male or female – trying to answer in the years to come: Does the difference in the topological architecture represent underlying behavioral and cognitive differences between genders?

As with many areas of neuroscience, when it comes to gender differentiation in the brain, experts today seem to have many more questions than answers, but this is precisely what makes the field so exciting.

Meanwhile, common people continue to devour books about the male and the female brain, in the hopes of understanding the other sex better, a pursuit as likely to be crowned with success anytime soon as the full understanding of the brain itself.


Abraham A, Thybusch K, Pieritz K, & Hermann C (2014). Gender differences in creative thinking: behavioral and fMRI findings. Brain imaging and behavior, 8 (1), 39-51 PMID: 23807175

Dumais KM, & Veenema AH (2015). Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior. Frontiers in neuroendocrinology PMID: 25951955

Frank CK, Baron-Cohen S, & Ganzel BL (2015). Sex differences in the neural basis of false-belief and pragmatic language comprehension. NeuroImage, 105, 300-11 PMID: 25264229

Hu Y, Xu Q, Shen J, Li K, Zhu H, Zhang Z, & Lu G (2015). Small-worldness and gender differences of large scale brain metabolic covariance networks in young adults: a FDG PET study of 400 subjects. Acta radiologica (Stockholm, Sweden : 1987), 56 (2), 204-13 PMID: 24763919

Nakstad, P. (2015). Gender differences in the human brain Acta Radiologica, 56 (2), 131-132 DOI: 10.1177/0284185114562993

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Swain, J., Kim, P., Spicer, J., Ho, S., Dayton, C., Elmadih, A., & Abel, K. (2014). Approaching the biology of human parental attachment: Brain imaging, oxytocin and coordinated assessments of mothers and fathers Brain Research, 1580, 78-101 DOI: 10.1016/j.brainres.2014.03.007

Image via Andrey Arkusha / Shutterstock.

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The Multiple Faces of “Love Hormone” Oxytocin Thu, 04 Jun 2015 14:00:45 +0000 Oxytocin acquired the title of “love hormone” when it was discovered that it influenced parental — especially the connection between mother and child — and romantic bonding. But now researchers have discovered that it also influences social communications, the dynamics of in- and out-group relationships, and social stress. Scientists also believe that abnormal functioning of the oxytocin neural pathway may aggravate the symptoms of communications and social skills disorders associated with mental diseases like autism and schizophrenia.

New Insights into Oxytocin’s Role in Maternal Behavior

Scientists knew that oxytocin had a role to play in strengthening the bond between mother and child. But now they have found out that oxytocin also affects neural signals in the brain of the mother and influences her social responses.

In an experiment conducted on laboratory mice with pups, scientists discovered that when the little ones were separated from their mums, they produced ultrasonic SOS calls. The mother mouse picked up these signals to locate her pups. The mother mice responded similarly — started looking for their pups — when the scientists played the pup distress calls on speakers.

The scientists investigated how oxytocin is involved in this behavior.

The left auditory cortex of the brain receives the sound signals. This part of the brain has a large number of oxytocin receptors. The hormone levels increased in the mother mice when they heard the distress calls of their pups. Oxytocin not only made the mother mice respond to their pups but also inhibited her brain’s ability to process other social signals.

In the above experiment, it was also found that female mice without pups did not respond to distress calls made by pups of other mice. But when they were injected with oxytocin, they responded to the distress calls by rushing to search for and rescue the pups even though those were not their own.

This newly-discovered role of oxytocin is, however, not surprising. After all, babies are helpless and unable to defend themselves if they are separated from their mums. So it seems natural that nature intended oxytocin to exert influence on mothers in this way.

Oxytocin and Our Responses to Social Stimuli

The oxytocin system is critical to the expression of three basic social bonds — parental, filial, and romantic. According to one study, the levels of oxytocin remain more or less stable in individuals over extended periods of time and go on to play crucial role in the expression of other types of social attachment behavior later in their lives.

Scientists also believe that oxytocin interacts with neural, physical, and mental factors to develop unique expressions of social cognition and empathy in humans. For instance, scientists have discovered that the quality of early-life parental care tends to influence the way children form attachments in adulthood.

In 2005, an interesting study was conducted on two groups of children. The kids in one group were raised by their biological parents. The children in the other group were adopted, but they had been raised in orphanages where they were deprived of the typical care-giving environment that the children of the other group were raised in. The oxyotcin levels in the children from both groups were monitored when they were in contact with their mothers—biological or adopted. It was found that the children who were raised by their biological parents showed an increase in oxytocin levels while levels in the other group of children remained constant. So it is evident that early-life social experience influences the way individuals form relationships later on in their lives.

The above findings led scientists to explore the connection between oxytocin and social disorders that develop during childhood, like autism spectrum disorders. And, to their surprise, they also found out that oxytocin plays a role in managing the symptoms of certain mental illnesses like schizophrenia.

Oxytocin and Mental Illnesses

The “love hormone” oxytocin floods us with feel-good vibes. It has another beneficial face too.

According to a recent study, intranasal administration of oxytocin can improve the ability of schizophrenia patients to recognize negative emotions, like fear, in other people. It was found during the study that schizophrenia patients whose baseline performance was below median level showed greater improvement when they were administered oxytocin compared to patients who were more capable.

These findings have already unleashed a slew of research into the various aspects that need to be considered before administering oxytocin for therapeutic purposes to patients suffering from mental illnesses. For instance, one study suggests that the efficacy of intranasal administration of oxytocin is dependent on gender, hormonal and genetic profiles, and attachment history. Other scientists have investigated the effects of different doses of oxytocin on patients.

These studies are crucial for finding out how long the effects of oxytocin stays in laboratory patients because elevated levels of oxytocin can also trigger anxiety.

The Adverse Effects of Oxytocin

The “love hormone” oxytocin has been found to have a disturbing effect as well when present in more-than-normal amounts in the human body. For instance, it was shown that oxytocin also influences the memory. In an experiment conducted on laboratory mice, it was found that under conditions of social stress oxytocin fires the lateral septum region of the mouse brain, a region that intensifies memories. This means that oxytocin turns a stressful experience into a long-standing painful memory that can trigger anxiety and fear every time an individual confronts similar stressors in future. Chronic anxiety and fear can also lead to depression.

In another study, it was found that women who reported less-than-satisfactory quality of relationships with their partners and longer periods of time in their lives spent without romantic attachments had more oxytocin and the stress hormone cortisol than women who enjoyed more satisfying relationships.

These findings seem crucial considering that scientists are also toying with the idea of using oxytocin to manage the anxiety symptoms. It is evident that oxytocin is not only associated with good and happy feelings.

The discovery of new faces of oxytocin presents intriguing avenues for further study. These studies should help scientists and psychiatrists better understand and accurately analyze why we behave the way we do in specific social situations and with other human beings.


Feldman, R. (2012). Oxytocin and social affiliation in humans Hormones and Behavior, 61 (3), 380-391 DOI: 10.1016/j.yhbeh.2012.01.008

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Fries, A., Ziegler, T., Kurian, J., Jacoris, S., & Pollak, S. (2005). From The Cover: Early experience in humans is associated with changes in neuropeptides critical for regulating social behavior Proceedings of the National Academy of Sciences, 102 (47), 17237-17240 DOI: 10.1073/pnas.0504767102

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Taylor, S., Gonzaga, G., Klein, L., Hu, P., Greendale, G., & Seeman, T. (2006). Relation of Oxytocin to Psychological Stress Responses and Hypothalamic-Pituitary-Adrenocortical Axis Activity in Older Women Psychosomatic Medicine, 68 (2), 238-245 DOI: 10.1097/01.psy.0000203242.95990.74

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Image via Svetlana Fedoseyeva / Shutterstock.

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Flab is Fine – The Advantages of Being Overweight Sun, 31 May 2015 16:18:33 +0000 Yes, you read right. Flab is not always bad. Scientists have discovered that being a little overweight comes with quite a few benefits.

According to several studies, the much-maligned fat cells, the ones that many people jog, sprint, swim, and walk to melt away, boost our energy levels. These fat cells crosstalk with the brain, as was discovered in experiments on laboratory mice. Scientists also indicate that the presence of an optimum number of fat cells in the body enhances longevity and keeps away several age-related symptoms and disorders.

Fat Cells and the Brain

Although the common man continues to treat fat as bad, and fat cells as things to get rid of, scientists have been working with fat cells for several years to uncover their physiological roles and relevance. In an earlier experiment carried out on lab mice, it was found that the hormone leptin produced by fat cells carries information about the amount of energy stored in these tissues in the abdominal region to the central nervous system. Leptin, or the “satiety” hormone, stimulates the brain to trigger signals that suppress the need for taking food. So there is compelling evidence that fat cells in the body communicate with the brain and influence the latter’s actions.

Another study indicates that the hypothalamus region of the brain communicates with adipose or fat tissues and regulates various metabolic processes. According to the findings of this study, the mammalian hypothalamus houses a pacemaker of sorts that monitors and regulates various core biological processes like eating, metabolism of food, and the sleep/wake cycle. This is a 24-hour clock that also influences physical activity and energy levels in individuals.

There are several components like proteins BMAL1 and CLOCK that regulate the 24-hour clock and keep it ticking and working the way it should. BMAL1 and CLOCK are also present within fat cells. In the above-mentioned study carried out on laboratory mice, it was found that animals with mutant varieties of BMAL1 and CLOCK had wayward circadian clock rhythms. These animals also exhibited several metabolic disorders that developed when the normal functionality of the ß cells in the pancreas was hampered.

These landmark studies shed critical insights into the pathogenesis of metabolic diseases like type 2 diabetes. The findings from the above-mentioned studies also led scientists to think that having a bit of fat is not that bad, after all. Scientists believe that human beings can benefit significantly from having a body mass index that skims the lower end of the range that is usually considered to be overweight. We need fat to survive!

Fat: Its Effect on the Hypothalamus and Pancreas

According to recent studies, fat cells communicate with the hypothalamus. This region of the brain is responsible for aging, longevity, and maintaining the energy levels of the body. Additionally, the hypothalamus regulates heart rate, blood pressure, hunger, thirst, and the sleep/wake cycle.

The presence of fat cells optimized the functions of the hypothalamus leading to greater energy levels in individuals. The main player in this development is an enzyme nicotinamide phosphoribosyltransferase (NAMPT) produced by fat tissues. NAMPT is involved in production of NAD, one of the energetic substances in the cell that is responsible for maintaining optimal cellular functionality. The scientists discovered that adipose tissues typically produce large quantities of NAMPT and some of it end up in the bloodstream and gets transported to the brain.

In the course of this study, scientists discovered that when there was a lack of the NAMPT enzyme in the fat cells, there was also a considerable drop in the energy levels within the adipose tissues. Although other major organs and muscles of the body remained unaffected by the change in the levels of this enzyme, the hypothalamus exhibited a similar drop in energy levels.

There were also other developments when the amount of this enzyme dropped inside the fat cells and the hypothalamus. An increase in the energy levels of the hypothalamic cells also enhances the functionality of the SIRT1 protein. This protein has been linked to longevity in mice.

These findings should also interest people living with diabetes. Fat cells produce NAMPT, and NAMPT generates nicotinamide mononucleotide that stimulates pancreatic beta cells to churn out more insulin. Although pancreatic cells themselves produce NAMPT, the amount is not adequate. So the pancreas has to depend on the fat cells to supplement its production. So the fat cells also communicate with the pancreas to regulate the production of NAMPT.

However, researchers sound a note of warning. Obesity has been conclusively linked with the development of type 2 diabetes. It is evident that there is a limit up to which the NAMPT enzyme can go on enhancing the functionality of the pancreas. Once this limit is reached, the beneficial effects of NAMPT are negated.

It is evident that a certain amount of fat is necessary for the body to not only maintain its core physiological functions but also for its survival.

How Much Fat is Good?

The findings of the above-mentioned studies will surely interest weight-watchers, and it is natural for them to wonder how much fat is good for the body. Scientists do not yet have an exact answer to this question. They are, however, quick to warn that their findings should in no way be interpreted as a license to go on a binge-eating spree, cancel the gym membership, or stop going for the morning jog around the park. Being on either end of the underweight-morbidly obese spectrum is bad for you.

So here’s the lesson. If you were trying to lose weight, keep at it. But don’t resort to fad diets, starvation, and obsessive exercising to attain an unhealthy body weight. Being a little overweight has long-term benefits. And it is not really surprising that this phenomenon, like many other processes in the body, is linked to the way our brain functions.


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Image via Poznyakov / Shutterstock.

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Genetic Basis to ALS – Interview with Robert Baloh of Cedars-Sinai Fri, 22 May 2015 12:00:27 +0000 Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with no real disease-modifying therapy. Only until recently did we attribute a small portion of individuals with ALS with a genetic basis. Research from Robert Baloh, MD, PhD, Director of Neuromuscular Medicine at Cedars-Sinai, and colleagues at Washington University in St. Louis, discovered the much larger role of genetics in ALS. Here, I interview Baloh on his findings.

Shaheen Lakhan: Can you provide us with an overview of ALS?

Dr. Robert Baloh's lab with Staff at Cedars-Sinai Medical CenterRobert Baloh: ALS, amyotrophic lateral sclerosis, is a neuromuscular disorder: It attacks nerve cells in the brain, brainstem and spinal cord that control muscles. The timing and sequence of progression is unpredictable, but it often begins in the arms or legs and eventually affects the breathing muscles in the chest.

ALS is often considered a very rare disease, but it probably is about as common as other neurodegenerative diseases, such as Parkinson’s disease. The reason ALS seems rare is that few patients survive long – people generally live only three to five years after onset – so unlike other disorders, there is not a growing number of patients living with the disease.

The disorder often is called Lou Gehrig’s disease after the New York Yankees’ first baseman who died of ALS in 1941. Even today, no significant disease-slowing treatments have been found, but we are able to offer therapies that improve patient quality of life. In recent years, there has been a surge in research to find the underlying genetic, molecular and cellular changes that cause the disease. With those discoveries, we expect to begin developing effective interventions.

Research funding increased dramatically when the ALS Ice Bucket Challenge brought much greater attention to finding cures for ALS.

SL: Is ALS inheritable?

RB: Yes, some cases are. Until very recently, we believed that about 10 percent of ALS cases had a genetic origin – there was a family history of the disease. The remaining 90 percent or so were considered “sporadic.”

SL: What is the difference between sporadic and familial ALS?

RB: ALS occurs when one or more changes in certain genes take place. A case is considered familial if a newly diagnosed patient has a previous family history of the disease, but if a new patient is the first family member diagnosed, the case is called sporadic – occurring without a previous genetic explanation.

SL: What has your research group found?

RB: Our study, which involved researchers from Cedars-Sinai and Washington University in St. Louis, found that family history may play a much larger role than previously believed – accounting for more than one-third of all ALS cases rather than only one-tenth. Examining DNA from 391 patients with ALS, we looked at 17 genes already known to be associated with the disease. We found many new or very rare mutations in ALS genes in people with no family history of the disease, suggesting that these supposedly “sporadic” cases may actually have a familial background.

We also found that patients who had mutations in two or more of these ALS genes had disease onset about 10 years earlier than those with defects in only one gene. Often, ALS is caused by well-known defects in single genes, but recent studies suggested that some cases might be brought on by the simultaneous occurrence of two or more “lesser” genetic defects. In theory, each mutation alone might not cause disease, but in combination they exceed the threshold for disease development. Not only does our study support that possibility, it shows that multiple defects can influence the way the disease manifests in individuals – striking 10 years earlier.

SL: What are the potential clinical implications of your research?

RB: We think we are entering a new phase of ALS research and treatment in which we will be able to analyze a patient’s entire genetic makeup and deliver gene-specific therapies to correct detected defects. We recently conducted a disease-in-a-dish study with cells from patients with defects in a gene that commonly causes ALS. Using small segments of genetic material to target the defects, we showed that this type of gene therapy can improve neurons from patients with the disease.

In addition, with the discovery of new and rare genetic mutations in ALS, we may be able to identify at-risk patients earlier because we can follow families previously unknown to have a genetic basis.

SL: Any closing remarks for our Brain Blogger readers?

RB: In our study, we used new technology that quickly and efficiently determines the organizational structure of large numbers of genes, but we focused only on 17 genes already known to be associated with ALS. Even though we identified the involvement of many new and rare mutations in ALS development, the majority of cases are caused by factors we do not yet understand. Therefore, more research using similar technology may help us discover other genes that influence ALS risk, providing more targets for future therapy.


Cady J, Allred P, Bali T, Pestronk A, Goate A, Miller TM, Mitra RD, Ravits J, Harms MB, & Baloh RH (2015). Amyotrophic lateral sclerosis onset is influenced by the burden of rare variants in known amyotrophic lateral sclerosis genes. Annals of neurology, 77 (1), 100-13 PMID: 25382069

Image via Gio.tto / Shutterstock.

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Decoding the Neural Pathway from Psychopathy to Serial Murder Mon, 18 May 2015 12:00:38 +0000 News stories of serial killings are, unfortunately, common. And almost always, there is no apparent motive behind the bloodbath. It makes you wonder if the serial killer is wired differently from the rest of us. What makes a person kill another human being in cold blood? Is it in the genes, or do dysfunctional and abusive families breed serial killers? Is there an “urge to kill” that serial killers cannot resist?

In his book The Criminal Man, published back in 1911, Cesare Lombroso argued that a significant proportion of all criminals are characterized by distinctive physical and anatomical features and these people are, therefore, born to be criminals.

The theory of Lombroso was based, in a significant degree, on the results of his medical and anatomical examinations of criminals. However, his observations were mostly descriptive and were not supported by any statistical data and proper population analysis. Later researchers who addressed this question (for instance, Goring in his The English convict: a statistical study, 1913) found no evidences in support of Lombroso’s conclusions. The statistical data, however, did not put the matter at rest, and various researchers were revisiting the idea of hereditary predisposition to criminality in the course of 20th century.

The question of “nature or nurture” in regards to the excessive level of cruelty in some individuals still have no clear answer. However, scientists have found that, contrary to popular belief, not all serial killers have abusive childhoods. Also, most serial killers exhibit the neurological traits of criminal psychopathy and have different brain chemistry than individuals who show no psychopathic tendencies.

Inside the Brain of a Criminal Psychopath

Many researchers believe that most serial killers show one or more singular traits of psychopathy, such as a tendency to manipulate others, superficial charm, abnormal egocentricity, and lack of empathy that shows up as guiltlessness. Most of them also exhibit anti-social traits like impulsive behavior and aggression. However, not all psychopaths go on to become serial killers.

Several studies have established the neurological roots of anti-social tendencies, violent behavior, and psychopathy.

According to one study, psychopaths show impaired connectivity between the ventromedial prefrontal cortex (vmPFC) and the amygdala and also between the vmPFC and the medial parietal cortex and reduced white matter in the right uncinate fasciculus that connects the vmPFC with the anterior temporal lobe. Incidentally, the amygdala processes negative stimuli while the vmPFC interprets the signals sent by the amygdala. The circuitry in the vmPFC region has been found to be associated with personal moral judgment.

In a study on patients with lesions in this region of their brains, it was found that these individuals tend to view personal moral violations as more acceptable than the subjects with healthy brains. The former group also tends to be bothered less by personal moral dilemmas. This indicates that the vmPFC region plays a crucial role in triggering inward-looking and reflective emotional reactions that influence moral choices. When the neural circuitry in this region is faulty, the individual does not feel any bothersome negative emotion when faced with negative stimulus. This probably explains why serial killers remain aloof to the cries of distress by or the sight of pain in their victims and also the lack of guilt at their doings.

In this context, it must be clarified that the above-mentioned impairment in the psychopath’s brain does not render him incapable of distinguishing between right and wrong. Research has uncovered that psychopaths understand what is right and what is not; they are just not bothered by the consequences that may arise from behaving inappropriately.

Few years ago, one study has uncovered a genetic basis for the impaired neural circuitry in the vmPFC region. According to this study, the presence of a particular variation of the monoamine oxidase A gene leads to a reduction in the mass of the vmPFC and amygdala regions. So it seems that genetics also has a role to play in determining whether a person will go on to kill another one when provoked or merely utter a few cuss words.

Age and Criminal Psychopathy

The role of the vmPFC in triggering psychopathic behavior and a propensity to kill has also thrown up an interesting discussion in the legal community. The vmPFC continues to mature till the age of 25. This indicates that juvenile offenders actually have little control over how their brains make them act. So it is no surprise that a survey in Britain found that more violent crimes are committed by individuals aged between 16 and 24 years than by all the people in other age groups taken together. In countries where the death penalty is prevalent, there is a debate whether lawmakers and judges should consider neuroscientific evidence before delivering death sentence in particular cases.

Co-Morbidity of Psychopathy and Other Mental Illnesses

Several scientists also associate mental conditions like Borderline Personality Disorder (BPD) and schizophrenia with serial killing. Their belief is based on numerous worldwide findings that a high percentage of prisoners convicted of committing violent crimes suffer from some sort of a mental illness. Some other surveys show that head injuries and birth complications that result in neurological damage are common amongst death-row convicts.

According to one study, there is a high level of co-occurrence of schizophrenia and psychopathy in forensic patients. Schizophrenic patients and those with high psychopathic scores exhibited low amygdala arousal when they were shown fearful faces. This means that these individuals cannot recognize fear in others and respond compassionately.

Scientists also see a connection between psychopathic symptoms and BPD. Persons afflicted with BPD are emotionally unstable and are prone to anxiety and impulsive aggression. What is more, those suffering from BPD are believed to have low or no empathy, a quality that lets a person be considerate and compassionate to the pain of others. On the other hand, psychopaths are known to be pathologically egocentric that makes them insensitive to the needs and pain of others. Scientists believe that BPD and psychopathy have common neural bases.

These findings raise new debates within the legal and medical circles. Many believe that this bank of neurological evidence should be taken into consideration before delivering punishment to serial killers. Counselors, psychologists, and therapists in institutions where violent criminals are lodged should also be made aware of findings like the co-morbidity of psychopathy and certain mental illnesses, so they can devise the most effective therapy that optimizes the chances of rehabilitation of serial killers and other violent offenders.

Because the propensity to go on a killing spree springs from psychopathy, an established and well-researched mental condition, both society and the legal machinery should take into account the neurological findings before judging legally or morally.


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Image via Igor Stevanovic / Shutterstock.

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Nicotine and Nicotinic Receptors in Disease and Therapy Sat, 16 May 2015 12:00:04 +0000 Everyone knows that smoking is a terribly harmful habit. But this is not about smoking, this is about nicotine and nicotinic receptors.

Nicotine has numerous effects: it decreases the appetite, it improves mood and has some anti-depressant properties, it increases heart rate and blood pressure and it stimulates memory, alertness, and focus, for example. The addictive nature of nicotine relies on its stimulant actions and on the activation of reward pathways, inducing feelings of pleasure.

Dopamine is the key neurotransmitter in this circuitry and nicotine is known to increase the levels of dopamine in reward pathways. Nicotine’s pharmacokinetic properties also potentiate its abuse potential: smoking delivers nicotine to the brain within 10 seconds of inhalation but its acute effects dissipate quickly, along with the feelings of reward, which causes the continued smoking to maintain the drug’s pleasurable effects and prevent withdrawal.

Nicotine acts on the cholinergic system; it is a nicotinic acetylcholine receptor agonist, hence the name of these receptors. The endogenous agonist of nicotinic receptors is acetylcholine, the main neurotransmitter of the parasympathetic nervous system (part of the autonomic nervous system). Nicotinic receptors are widely distributed throughout the nervous system and participate in a variety of physiological responses, including anxiety, pain processing, feeding behavior and cognitive functions. Dysfunctions of neuronal nicotinic receptors have been associated with many neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, as well as autism spectrum disorders and schizophrenia.

Cholinergic deficits are observed in early stages of Alzheimer’s disease and it is thought to be associated with Alzheimer’s cognitive symptoms such as memory loss, confusion, and impaired thinking and reasoning. Brain regions associated with attention, spatial and episodic memory are those where the biggest cholinergic losses are observed in early Alzheimer’s disease. Therefore, due to its ability to increase cholinergic activity via nicotinic receptors, nicotine and nicotine analogs have been considered as possible therapeutic tools for Alzheimer’s; importantly, they could be helpful at early stages of the disease, which would be the best therapeutic strategy for Alzheimer’s.

Cholinergic dysfunction also may contribute to the neurotransmitter imbalance underlying Parkinson’s disease. Studies reveal that cholinergic and dopaminergic systems work together to fine tune the control of motor and cognitive functions that become impaired in Parkinson’s disease. Activation of certain subtypes of nicotinic receptors can stimulate anti-inflammatory signaling pathways and promote neuronal survival. The activation of these receptors can potentially prevent neuroinflammation and promote neuronal survival in the brain regions affected by Parkinson’s disease. Nicotinic receptors subunits have thus been proposed as therapeutic targets against Parkinson’s disease.

Interestingly, many epidemiological studies have shown that tobacco users have a lower incidence or severity of PD, with an estimated 40% decrease of risk of developing Parkinson’s disease for smokers when compared to never smokers. It has also been shown that smoking may prevent motor complications in Parkinson’s disease patients. Obviously, this is not due to cigarette smoking, but to nicotine intake.

Abnormalities in the cholinergic system have also been linked to autism. The study of adult post-mortem autistic brains has shown a marked decrease in the expression of different nicotinic receptor subunits in the cerebral cortex, with the reduced expression of some of these subunits being a major feature of the neurochemical pathology of autism. Due to this loss of cholinergic activity in the autistic brain, nicotinic receptor ligands may restore or at least improve cholinergic transmission, thereby compensating such loss and, hopefully, significant decreasing cognitive changes associated with autism.

Schizophrenia has been genetically linked to dysfunction in the hippocampal cholinergic system. Interestingly, schizophrenia patients exhibit a much higher prevalence for smoking than the general population. This has been regarded as a form of self-medication and nicotine intake actually appears to improve or normalize some of the cognitive and sensory deficits. However, due to the adverse health effects of smoking, an alternative approach to action on nicotine receptors would obviously be desirable. Partial nicotinic agonists have in fact shown cognitive improvements in schizophrenic patients.

Nicotine is intuitively associated to smoking, but as a drug per se, it may actually have interesting therapeutic applications that are worth pursuing.


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Image via Aleksminyayalo1 / Shutterstock.

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Homosexuality in the Brain Thu, 14 May 2015 12:00:13 +0000 From an evolutionary point of view, homosexuality is rather difficult to explain. Any genetic trait that reduces the chances of producing the offspring usually gets eliminated very quickly in populations. Nonetheless, homosexuality appears to persist in humans throughout the history of our species. There are multiple hypotheses attempting to explain this phenomenon but no hard proofs confirming any of them.

Many scientists believe that sexual orientation is determined by peculiarities in the structure of the brain. Although at present time we cannot say what makes people gay, we can study their brain to see how their sexual orientation is reflected in the way it functions.

The Masculine and the Feminine Brain

Gender identity, which is the feeling of being like a man or a woman, influences various aspects of human behavior. These include choice of toys as a child and gender-specific cognitive, motor, and personality characteristics. Gender identity also has a role to play in determining sexuality. And all these developments are triggered by testosterone. Male and female fetuses vary in the level of this sex hormone.

According to one study, the human brain can show “masculine” or “feminine” traits, irrespective of physical sexual characteristics. When the fetus develops, gender identity and the sexual differentiation of the genitals may develop independently of one another. The former takes place during the second half of pregnancy while the latter starts much earlier, within the first 8 weeks of gestation. Incidentally, incongruent development in these two regions usually leads to transsexuality.

Sexual Orientation is in the Brain

Several other studies indicate that sexual orientation — heterosexuality, bisexuality, and homosexuality — is determined by peculiarities of the brain structure and differences in brain chemistry. Cultural or societal factors, upbringing, moral leanings, and educational attainments do not determine sexual orientation as greatly as neural mechanisms do. In fact, scientists have identified several areas of the brain that they believe determine sexuality in an individual. These areas include the hypothalamus and the amygdala. Inter-hemispheric neural connectivity has also been found to contribute significantly to sexual orientation.

A landmark study by Savic and Lindström indicates that there are cerebral differences in homosexual and heterosexual individuals. There are differences in brain anatomy, activities, and neurological connections. Brain scan images of the subjects who participated in this study show that the brains of homosexual individuals exhibit similar structure and functionality as that of heterosexual individuals of the opposite gender.

According to the study, lesbians and straight men have similar brain structures and functionalities while gay men and straight women share neural characteristics. For instance, MRI findings prove that the right hemispheres of the brains of the lesbians and heterosexual men have slightly greater volumes than their left hemispheres. But the left and right hemispheres of gay men and heterosexual women are symmetrical.

Another study on the brains of male-to-female (MTF) transsexual individuals, men, and women found that the volumes of gray matter across the different regions of the brains of MTF transsexuals are more or less similar to that in the brains of the men. However, the MTF transsexuals exhibited slightly greater volume of gray matter in the right putamen region of their brains compared to the men in the study. MTF transsexual individuals may have the same physical sexual characteristics as men, but they report feeling like women. This study bolsters the claims of the Savic-Lindström study that brain structure and functionality play a significant role in determining gender identity.

According to the findings of the Savic-Lindström study, the number of neural connections also varied between hetero- and homosexual subjects. For instance, gay men and straight women showed greater neural connectivity in the cingulate cortex and contralateral amygdala regions than straight men and lesbians respectively. On the other hand, straight men and lesbian women exhibited significantly more neural connections in the frontal lobe cortex and the parietal cortex regions compared to gay men and straight women respectively.

Incidentally, the Savic-Lindström study is the first to establish that differences in neural connections can influence sexual orientation. The objective of the study was also to establish that sexual orientation is largely determined by factors that are congenital.

Neurological Underpinnings of Sexual Attraction

Neurological differences determine human behavior to a large extent. So it is likely that the neural differences in hetero- and homosexual individuals influence their sexual preferences as well. Hetero- and homosexual women have different responses to specific odors, particularly those emitted by 4,16-androstadien-3-one (AND), which is a testosterone-derivative that is found primarily in male sweat, and estra-1,3,5(10),16-tetraen-3-ol (EST), which is an estrogen-like substance that is found in the urine of women. These substances are believed to be similar in nature and function to pheromones that are emitted by individual members of a species to elicit specific responses, sexual in many cases, from members of the same species.

The above study was conducted on straight men, gay men, and straight women. It was found that homosexual men and heterosexual women displayed similar brain activation patterns when they inhaled the AND chemical. The hypothalamic area of their brains were activated when they inhaled AND. In contrast, the straight women exhibited activity only in the olfactory region of their brains when they were exposed to the EST chemical. The hypothalamus is known to be active in processing sexual signals while the olfactory region only processes smells. During the same study, the subjects were exposed to commonly-occurring smells, and it was found that their brains had similar responses.

So, are people born gay or lesbian? Scientists hesitate to provide a conclusive answer.

A slew of studies indicate that neurological factors greatly influence sexual orientation. The functionalities of regions in the brain like the amygdala and the hypothalamus have been proven to be determined genetically and are influenced by hormones. Developments in these regions kick in even before an individual learns cognitive skills or is exposed to environmental and educational settings. But scientists still do not negate the role of environmental factors.


Bao, A., & Swaab, D. (2011). Sexual differentiation of the human brain: Relation to gender identity, sexual orientation and neuropsychiatric disorders Frontiers in Neuroendocrinology, 32 (2), 214-226 DOI: 10.1016/j.yfrne.2011.02.007

Hines, M. (2010). Sex-related variation in human behavior and the brain Trends in Cognitive Sciences, 14 (10), 448-456 DOI: 10.1016/j.tics.2010.07.005

Luders, E., Sánchez, F., Gaser, C., Toga, A., Narr, K., Hamilton, L., & Vilain, E. (2009). Regional gray matter variation in male-to-female transsexualism NeuroImage, 46 (4), 904-907 DOI: 10.1016/j.neuroimage.2009.03.048

Nugent, B., Wright, C., Shetty, A., Hodes, G., Lenz, K., Mahurkar, A., Russo, S., Devine, S., & McCarthy, M. (2015). Brain feminization requires active repression of masculinization via DNA methylation Nature Neuroscience, 18 (5), 690-697 DOI: 10.1038/nn.3988

Savic, I., Berglund, H., & Lindstrom, P. (2005). Brain response to putative pheromones in homosexual men Proceedings of the National Academy of Sciences, 102 (20), 7356-7361 DOI: 10.1073/pnas.0407998102

Savic I, & Lindström P (2008). PET and MRI show differences in cerebral asymmetry and functional connectivity between homo- and heterosexual subjects. Proceedings of the National Academy of Sciences of the United States of America, 105 (27), 9403-8 PMID: 18559854

Swaab, D. (2007). Sexual differentiation of the brain and behavior Best Practice & Research Clinical Endocrinology & Metabolism, 21 (3), 431-444 DOI: 10.1016/j.beem.2007.04.003

Swaab, D. (2008). Sexual orientation and its basis in brain structure and function Proceedings of the National Academy of Sciences, 105 (30), 10273-10274 DOI: 10.1073/pnas.0805542105

Image via EpicStockMedia / Shutterstock.

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Debunking the Myths of Marijuana Withdrawal “Syndrome” Wed, 13 May 2015 12:00:49 +0000 “Reefer Madness” ideology has yet to be quashed, where well-to-do, model students take one fateful puff and they are severely hooked, avoiding Trainspotting-esque withdrawal symptoms and instead spiral into a marijuana-laced world of paranoia, aggression, academic failure and mental illness. To the contrary, there are pro-marijuana myths, where marijuana could never be addictive and is a benign, happy little drug that can do absolutely no harm. As such, marijuana withdrawal syndrome is still considered by some to be just about as real as leprechauns, unicorns and the Easter bunny!

Back in reality, becoming addicted to cannabis is a real phenomenon. If you can get addicted to sausages (you can!) why not the green stuff? Putting it simply, addictions are compulsive behaviors that we continue to do despite the negative consequences.

Relatedly, marijuana withdrawal is real and is a diagnostic indicator of marijuana addiction. As with experiencing withdrawal from any addiction, there are physiological and psychological consequences that are unpleasant enough to encourage continued use for some users that are trying to quit.

As stated in a 2015 review in Clinical Pharmacology and Therapeutics:

“Chronic cannabis users typically experience unpleasant withdrawal symptoms when use is discontinued. These symptoms are much less severe than those associated with withdrawal from chronic opioid or depressant use, but aversive enough to encourage continued cannabis use and interfere with cessation attempts in some individuals.”

That being said, there is a load of uneducated nonsense perpetuated about marijuana addiction and withdrawal. Even today, major newspapers — like The Telegraph and The Daily Mail in the UK — have used blatant lies as front-page headlines, such as:

“Cannabis as Addictive as Heroin”

This shameless tabloid hysteria is continuing the misunderstanding of marijuana addiction and withdrawal, keeping us in the fiction and ideology-fueled dark ages. In reality, both of the mythical extremes — pot being super addictive and life destroying, or a totally innocent health giving and withdrawal-free substance — are just that, they are all smoke and mirrors, they are simply polar extreme modern day myths. The reality of marijuana addiction and withdrawal is somewhere in between.

Despite many gung-ho nay and yaysayers wasting their breath with the same old over opinionated claptrap, some real, tangible and clinical evidence is mounting that, if it can be heard over the nonsensical rabble, may be policy, life and society changing. Here are the latest, up-to-the-minute scientific facts on marijuana withdrawal syndrome (which we should note, as always, are susceptible to change and development).

Marijuana Addiction and Withdrawal: The Facts

Literally all scientific means of assessing the risk of taking a drug of abuse, from margin of exposure to expert panel ranking methods, are largely in agreement with one another. They place weed and its infamous active ingredient, THC, at the bottom of a very long list of addictive substances, where alcohol, heroin, crack cocaine and metamfetamine, and the seemingly benign and legal staple cigarettes and its active ingredient, nicotine, generally take the spotlight.

As published in the journal, Drug and Alcohol Dependence:

“The cumulative probability estimate of transition to dependence was 67.5% for nicotine users, 22.7% for alcohol users, 20.9% for cocaine users and 8.9% for cannabis users.”

This means that 9% of people who use marijuana are estimated to become dependent on it. As with all drugs, this value increases to ~16% for those who start smoking pot as teens, which is far less than for other drugs (e.g. 50-75% for cigarettes). Moreover, the chance of getting hooked if you smoke it for the first time after age 25 is practically nil, as described by Professor of Psychiatry, J. Michael Bostwick, M.D. in a paper published in Mayo Clinic Proceedings:

“The risk for new-onset dependence is essentially zero after the age of 25 years, whereas cocaine dependence continues to accrue until the age of 45 years. Likewise, the average age at first alcohol use is the same as for marijuana, but alcohol users will keep on making the transition from social use to dependence for decades after first use.”

With this in mind, the overwhelming majority of adults that smoke a little pot once in a while will not become addicted and thus never be at risk of experiencing withdrawal symptoms that promote relapse and spur addiction. However, as with every psychoactive drug, for more vulnerable users, such as those with chronic stress management problems, mental illness or a genetic predisposition to addiction, the chance of becoming addicted and experiencing withdrawal is undoubtedly greater.

So yes, marijuana withdrawal syndrome is real (it ain’t no Santa Claus, that’s for sure). Chronic and repeated overstimulation of the endocannabinoid system by regularly smoking marijuana can dampen the brain’s natural response to the essential neurotransmitter and cannabinoid receptor activator, dopamine. When abstaining, lower stimulation of cannabinoid receptors can result in the need, be it deemed psychological or physical, to continue use or ride out the negative consequences, i.e. adverse withdrawal symptoms.

Marijuana Withdrawal Syndrome: The Symptoms

So, what will someone addicted to marijuana expect to experience during withdrawal?

We found no research on gradual cannabis abstinence in the literature. However, as the gradual reduction of an agonist substance of dependence is typically associated with less severe and clinically significant withdrawal, The National Cannabis Prevention and Information Centre, NCPIC, surmize that:

“The relatively long plasma half-life of various active cannabis metabolites (typically cited as 1-4 days), suggests that a gradual reduction in cannabis use would be an effective strategy for people with cannabis dependence, where individuals are able to exert some control over their use or where access to their cannabis is regulated by a third party… Advice on gradual cannabis reduction may include smoking smaller bongs or joints, smoking fewer bongs or joints, commencing use later in the day and having goals to cut down by a certain amount by the next review.”

This is an area of research worthy of looking into, although not as profitable or evidently as popular as the many studies already published on a monthly basis investigating the use of pharmaceuticals to aid cannabis cessation.

On the flipside, for those going cold-turkey, 50% of dependent users experience mild to no symptoms, while the other 50% experience DSM-V worthy symptoms of cannabis withdrawal syndrome:

  • Within the first week, insomnia, loss of appetite or increase in appetite (considered equally as common), physical symptoms (stomach pain, shakiness/tremors, sweating, fever, chills or headache) and restlessness tend to approach a peak in their severity. Physical symptoms are generally reported as lower rates than other symptoms.
  • In the later phase of withdrawal,  irritability/anger and vivid, unpleasant dreams, tend to be at their worst more than a week after cessation. There are less reports of depressed moods in comparison with irritability and nervousness (see next point).
  • The symptom of nervousness has shown differing time-courses between studies. One study observed nervousness immediately after cessation, for another, nervousness was at its worst after 9 days.
  • Generally, cannabis withdrawal has been reported to follow a clear time-course with a peak in overall severity of symptoms at ~10 days after last use, followed by a gradual decline over the next 20 days.

That sounds much like the personal reports of marijuana withdrawal symptoms in BrainBlogger’s first ever post on Marijuana Withdrawal Syndrome. For example:

“After using heavily for the past 7 years, and basically all day every day for the last 6 months my side effects are major. i still cant sleep properly although at least now im getting 6 hours which isnt too bad. nausea every day. i have a bad stomach to begin with but i usually dont get sick every day. hot and cold sweats. im freezing right now but about half an hour ago i was boiling. i havent eaten properly since i stopped. the thing i dont like is that i feel spaced out constantly. i feel like im bent even when im not. and not bent in a calm relaxing way either.”

Spice Addiction and Withdrawal

Although deserving of a dedicated article it is important we mention the marijuana-based drug you may never have heard about, spice. Spice is actually a series of synthetic cannabinoids originally developed by pharmaceutical companies that fully activate cannabinoid receptors in the brain, whereas the main active substance in marijuana, THC, is merely a partial agonist in comparison.

While governments around the world are debating the legalization of marijuana, these largely legal synthetic drugs, that compared with marijuana next to nothing is known about, are beginning to ring serious alarm bells.

With natural cannabis, although many of the active chemicals have not been fully investigated, some, like CBD are known to have antipsychotic, anticonvulsive, anti-anxiety and neuroprotective properties that are considered to offset the potential negative side-effects from the main active ingredient THC. With spice products on the otherhand, they don’t contain these protective chemicals and instead only a super-potent version of THC.

Not only is the high itself is totally different and can be highly hallucinogenic and disorientating, it can even cause seizures, overdose and death, with seizures also known to be a symptom of withdrawal. There are a lot of potentially dangerous unknowns with spice. Just because its a legal pharmaceutical doesn’t mean its safe or effective.

Marijuana Withdrawal Syndrome: A Step Too Far?

Have you heard of nicotine withdrawal syndrome? Nope. Why? Because it has never been defined as such in any newspaper I could find online. Even drugs with the worst reputation when it comes to withdrawal symptoms, like heroin, crack and cocaine, have NEVER been defined as a “syndrome” by the mainstream media, although they are referred to as such in science journals. In fact, did you know that caffeine withdrawal has also been given the syndrome title?

Although syndrome simply means a group of signs and symptoms that occur together and characterize a particular abnormality or condition, it seems that journalists have unrightfully ganged up on ganja, portraying it as the only drug deserved of being associated with the more serious sounding term, syndrome.

With promise in being equal to or more effective than some pharmaceutical drugs in treating a number of illnesses (the list is eye-bogglingly phenomenal), shouldn’t we drop the “syndrome” fear mongering in the mainstream media?

It’s simple. It’s not widely addictive. The overwhelming majority of adults can enjoy its effects and not become addicted, and only half of those that become dependent will feel severe withdrawal symptoms. Indeed measures should be taken to understand and protect those at greatest risk from harm, yet we should not blow this out of proportion to prevent hindering the effective and beneficial uses of the cannabis plant.

Let’s not create smoke where there is no fire. Unless we equally apply the term, withdrawal syndrome, to other drugs, let’s drop the currently damaging term, syndrome, from popular media and stick with the bold, the descriptive, the representative, the simple: marijuana withdrawal.


Allsop DJ, Norberg MM, Copeland J, Fu S, & Budney AJ (2011). The Cannabis Withdrawal Scale development: patterns and predictors of cannabis withdrawal and distress. Drug and alcohol dependence, 119 (1-2), 123-9 PMID: 21724338

Budney AJ, & Hughes JR (2006). The cannabis withdrawal syndrome. Current opinion in psychiatry, 19 (3), 233-8 PMID: 16612207

Gorelick DA, Levin KH, Copersino ML, Heishman SJ, Liu F, Boggs DL, & Kelly DL (2012). Diagnostic criteria for cannabis withdrawal syndrome. Drug and alcohol dependence, 123 (1-3), 141-7 PMID: 22153944

Hesse M, & Thylstrup B (2013). Time-course of the DSM-5 cannabis withdrawal symptoms in poly-substance abusers. BMC psychiatry, 13 PMID: 24118963

Lopez-Quintero C, Pérez de los Cobos J, Hasin DS, Okuda M, Wang S, Grant BF, & Blanco C (2011). Probability and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine: results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Drug and alcohol dependence, 115 (1-2), 120-30 PMID: 21145178

Nutt DJ, King LA, Phillips LD, & Independent Scientific Committee on Drugs (2010). Drug harms in the UK: a multicriteria decision analysis. Lancet, 376 (9752), 1558-65 PMID: 21036393

Sampson CS, Bedy SM, & Carlisle T (2015). Withdrawal Seizures Seen In the Setting of Synthetic Cannabinoid Abuse. The American journal of emergency medicine PMID: 25825034

Image via Yarygin / Shutterstock.

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Best and Worst of Neuroscience and Neurology – April 2015 Sat, 09 May 2015 12:00:33 +0000 In this article, I will present a selection of research articles published in April. As usual, many new interesting findings were made public this month, and the selection presented in this article reflects mostly my personal opinion of their importance.

27 April was the birthday of Edward Moser, director of the Kavli Institute for Systems Neuroscience and Centre for Neural Computation in Trondheim, Norway, and the receiver of the last year’s Nobel Prize in Physiology and Medicine. Prof. Mozer is heralded for discovering the brain’s positioning system, which helps us navigate in space and works, in a way, similar to GPS.

This month, a number of interesting articles shedding light on how our brain works and how the memories are formed were published.


Being slightly overweight helps the aging brain

People who are slightly overweight tend to have fewer health problems in the older age. In the midst of the current obesity crisis, this fact is rarely mentioned by the popular media.

It turns out that metabolic processes behind this phenomenon are directly linked with the brain. The process involves an enzyme called NAMPT, which is involved in the generation of energy and is produced mostly in the adipose tissue. NAMPT is released from the fat cells and is used elsewhere in the body, including the brain. Low amounts of fat result in low levels of NAMPT and, as a consequence, an insufficient energy supply to the brain. Hypothalamus is particularly affected by the low level of NAMPT. This is important, since the hypothalamus is a key regulator of many physiological functions such as body temperature, blood pressure, sleep cycle and others.

Same metabolic regulator is involved in physical and mental activities

Both physical activities such as running, and mental activities such as memorizing require lots of energy. It turned out that this is not the only similarity between the two. The energy flow in both cases is controlled by the same key metabolic regulator.

Researchers found that the protein ERR-gamma that activates various metabolic pathways turns on fat-burning in muscles and sugar-burning in brain. It is known that activation of ERR-gamma energizes muscles. Mice with missing ERR? were shown to be a very poor learners. Researchers hypothesize that increasing the levels of ERR-gamma may help to enhance learning skills and pave the way to improve the treatment of learning disorders.

Molecular mechanisms behind memory formation further deciphered

Molecular mechanisms underlying the formation of memories remain poorly studied. New paper published this month by neuroscientists from Vanderbilt University makes an important contribution to our understanding of these processes.

Formation of memories involves the formation of dendritic spines, tiny filaments making electrochemical connections between neurons. Researchers have identified a key signalling protein, Asef2, involved in the process of adhering between dendrites and axons. In response to yet unidentified signals, Asef2 triggers the production of actin. Actin is a key component of cytoskeleton that makes possible cell movement and stabilizes the newly formed connections. Formation of dendritic spines is affected in many neurological conditions such as autism and Alzheimer’s disease. It is possible that this process can be restored by targeting the specific proteins involved.

Sleep as a management tool for Alzheimer’s?

Like most of other neurodegenerative conditions, Alzheimer’s disease currently has no effective treatments. But can a simple lifestyle modification, such as getting enough sleep, help in the management of this condition? At least, this appears to be true for the fruit flies with Alzheimer’s-like syndromes.

Scientists have shown that extra sleep helps to restore their ability to form new memories. It remains to be seen if such simple intervention can be helpful for human patients. It was recently shown that a short daytime nap can improve memory as much as 5-fold in healthy humans.

Complex nature of nicotine withdrawal symptoms

Quitting smoking is not an easy task. Nicotine appears to be a very addictive substance, and withdrawal symptoms such as anxiety contribute substantially to the failure of many smokers to get rid of the habit. In a new article published this month, researchers revealed specific neuronal circuits behind the withdrawal symptoms.

Researchers found that signals from two brain regions, the ventral tegmental area (part of the brain associated with pleasure and rewards) and the medial habenula, come together to the interpeduncular nucleus and trigger a number of processes, including the elevation of corticotropin releasing factors (CRF) level. The latter is known to be involved in response to the stress. This increased stimulation of interpeduncular nucleus triggers the feeling of anxiety. The good news is that the drugs blocking CRF receptors already exist, and it might be possible to use them to reduce the stimulation of interpeduncular nucleus and, thus, anxiety.


As usual, this month we have seen a number of publications that have changed our views on some important issues. We may consider them as negative developments, but gaining any knowledge is always a positive thing.

Alcohol consumption in early adulthood: unexpected impact on brain development

It is well known that excessive consumption of alcohol by teenagers affects their memory and learning ability. A new study by researchers at Duke University has now demonstrated that alcohol can also damage the brain of young adults.

The brain continues to mature until the mid-20s, and this is a period when many young people start to drink frequently. Researchers measured the long-term potentiation (LTP) in the hippocampus of rats exposed to the excess of alcohol at the age that corresponds to human early 20s. LTP is involved in the strengthening of synapses and thus the formation of memory, and it was clearly affected in the experimental animals. In addition, the dendritic spines in the hippocampus of rats appeared immature. Scientists think that excess alcohol in early adulthood disrupts the brain’s maturation process.

The impact of air pollution on brain health is seriously underestimated

Long-term exposure to air pollution is known to be damaging for health. Recent data indicate that brain health can also be affected by this environmental factor, as air pollution is statistically linked to increased risk of stroke, anxiety and suicide.

New findings published this month suggest that the damage may be more severe than previously thought. It was found that exposure to the fine particles found in the polluted air increases the risk of covert brain infarcts by as much as 46%. Covert brain infarct is a form of silent stroke which is associated with dementia and worsened cognitive functions.

Intense aggression: unexpected complexity

Extremely aggressive behavior in males is known to be linked to the elevated level of neurotransmitter serotonin. This is the same compound which is central for our feeling of happiness. The level of serotonin, however, is regulated by several other neurotransmitters.

A new study by Japanese researchers focused on the dorsal raphe nucleus – a major hub for serotonin in the brain – located in its most primitive part. Using a novel in vivo technique, researchers found that the intense aggression-linked surge in serotonin in this location is caused by the increased release of neurotransmitter glutamate in the dorsal raphe nucleus. The findings may help in identifying a suitable pharmaceutical target for developing drugs against psychopathy in humans. They also point to the importance of more probing investigations when we want to target specific conditions without affecting other important mechanisms in the brain.

Assumptions on gender-specific brain development proven wrong

The brains of males and females are rather different – certain parts are different in size and have different numbers of neurons, which are also differently connected. It was long assumed that the brain acquires its gender-specific characteristics during a short period of prenatal development, and once this period is over, the window for further changes is closed. But new findings published this month demonstrate that these assumptions are incorrect.

Researchers found that inhibiting of DNA methyltransferases, the enzymes involved in the repressing of genes, in preoptic area of the rats brain, may “un-silence” some genes and lead to masculinization of female brains. Female rats who received the injections of DNA methyltransferase inhibitors went on to develop more masculine brain feature. Moreover, these rats demonstrated typically male characteristics in their reproductive behavior. It would be interesting to investigate if some related processes in the human postnatal development may be linked to homosexuality.

Death of lactate shuttle theory?

The brain consumes one-fifth of all energy generated in the body. It was always believed that this extreme energy consumption is facilitated by the brain support cells, astrocytes, that produce energy from sugar and pass it to neurons. However, a new article published in Nature Communication this month is likely to prove that this lactate shuttle theory is wrong.

Using a new technique called 2-photon microscopy, the scientists observed the lactate consumption by different cells in the brain directly in real time. They found that neurons and not astrocytes take up glucose directly. Moreover, stimulation of cells led to the increased glucose consumption by neuron while no changes in the glucose consumption by astrocytes were observed. The findings are important – it appears that some chapters in the basic neuroscience textbooks will now need to be rewritten.


Dissel, S., Angadi, V., Kirszenblat, L., Suzuki, Y., Donlea, J., Klose, M., Koch, Z., English, D., Winsky-Sommerer, R., van Swinderen, B., & Shaw, P. (2015). Sleep Restores Behavioral Plasticity to Drosophila Mutants Current Biology DOI: 10.1016/j.cub.2015.03.027

Evans, J., Robinson, C., Shi, M., & Webb, D. (2015). The Guanine Nucleotide Exchange Factor (GEF) Asef2 Promotes Dendritic Spine Formation via Rac Activation and Spinophilin-dependent Targeting Journal of Biological Chemistry, 290 (16), 10295-10308 DOI: 10.1074/jbc.M114.605543

Lundgaard, I., Li, B., Xie, L., Kang, H., Sanggaard, S., Haswell, J., Sun, W., Goldman, S., Blekot, S., Nielsen, M., Takano, T., Deane, R., & Nedergaard, M. (2015). Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism Nature Communications, 6 DOI: 10.1038/ncomms7807

Nugent, B., Wright, C., Shetty, A., Hodes, G., Lenz, K., Mahurkar, A., Russo, S., Devine, S., & McCarthy, M. (2015). Brain feminization requires active repression of masculinization via DNA methylation Nature Neuroscience, 18 (5), 690-697 DOI: 10.1038/nn.3988

Pei, L., Mu, Y., Leblanc, M., Alaynick, W., Barish, G., Pankratz, M., Tseng, T., Kaufman, S., Liddle, C., Yu, R., Downes, M., Pfaff, S., Auwerx, J., Gage, F., & Evans, R. (2015). Dependence of Hippocampal Function on ERR?-Regulated Mitochondrial Metabolism Cell Metabolism, 21 (4), 628-636 DOI: 10.1016/j.cmet.2015.03.004

Risher, M., Fleming, R., Risher, W., Miller, K., Klein, R., Wills, T., Acheson, S., Moore, S., Wilson, W., Eroglu, C., & Swartzwelder, H. (2015). Adolescent Intermittent Alcohol Exposure: Persistence of Structural and Functional Hippocampal Abnormalities into Adulthood Alcoholism: Clinical and Experimental Research DOI: 10.1111/acer.12725

Takahashi, A., Lee, R., Iwasato, T., Itohara, S., Arima, H., Bettler, B., Miczek, K., & Koide, T. (2015). Glutamate Input in the Dorsal Raphe Nucleus As a Determinant of Escalated Aggression in Male Mice Journal of Neuroscience, 35 (16), 6452-6463 DOI: 10.1523/JNEUROSCI.2450-14.2015

Wilker, E., Preis, S., Beiser, A., Wolf, P., Au, R., Kloog, I., Li, W., Schwartz, J., Koutrakis, P., DeCarli, C., Seshadri, S., & Mittleman, M. (2015). Long-Term Exposure to Fine Particulate Matter, Residential Proximity to Major Roads and Measures of Brain Structure Stroke, 46 (5), 1161-1166 DOI: 10.1161/STROKEAHA.114.008348

Yoon, M., Yoshida, M., Johnson, S., Takikawa, A., Usui, I., Tobe, K., Nakagawa, T., Yoshino, J., & Imai, S. (2015). SIRT1-Mediated eNAMPT Secretion from Adipose Tissue Regulates Hypothalamic NAD+ and Function in Mice Cell Metabolism, 21 (5), 706-717 DOI: 10.1016/j.cmet.2015.04.002

Zhao-Shea, R., DeGroot, S., Liu, L., Vallaster, M., Pang, X., Su, Q., Gao, G., Rando, O., Martin, G., George, O., Gardner, P., & Tapper, A. (2015). Increased CRF signalling in a ventral tegmental area-interpeduncular nucleus-medial habenula circuit induces anxiety during nicotine withdrawal Nature Communications, 6 DOI: 10.1038/ncomms7770

Image via bikeriderlondon / Shutterstock.

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Preventing Alzheimer’s Disease – Interview with Dean Sherzai of Cedars-Sinai Wed, 06 May 2015 12:00:51 +0000 Numerous studies show promise in the prevention of Alzheimer’s disease in animal models, but invariably fail in humans. However, time after time, lifestyle changes have been shown to alter the course of illness in large population studies. My interview with Dean Sherzai, MD, PhD, director of the Alzheimer’s Disease Prevention Program at Cedars-Sinai, aims to shed light on preventing Alzheimer’s Disease with both therapeutics and lifestyle modifications.

Shaheen Lakhan: What does the Alzheimer’s Disease Prevention Program at Cedars-Sinai offer to patients, caregivers, and the biomedical community?

Dean Sherzai: The Alzheimer’s Disease Prevention Program offers a new approach to Alzheimer’s care, emphasizing prevention and focusing on the creation of an all-encompassing support network for patients and their families.

Prevention is a part of the Alzheimer’s spectrum that rarely has been talked about, due somewhat to the fact that we only recently have begun to identify many of the factors that influence risk. The insidious nature of the disease – with onset starting many years before its seemingly irreversible symptoms appear – has reinforced a sense that Alzheimer’s strikes at random, without warning and without recourse. Now, with the growing recognition that its course can be changed if the disease is diagnosed early enough, we are working to make innovative early detection screening technologies available.

Even in cases where disease exists and prevention no longer is possible, we look to slow disease progress and spare patients and families the heaviest burdens for as long as possible.

Caring for a person with Alzheimer’s hits families hard financially, through lost work and wages, and emotionally, with the grief that comes from gradually losing a loved one. The effects are physical, too. According to the Alzheimer’s Association, people caring for patients with Alzheimer’s and dementia had $9.3 billion in additional health care costs of their own in 2013. Too often, patients and families are left on their own after a diagnosis is made, and the tensions and financial burdens tear them apart.

Our center is designed to serve as a coordinating resource, working with other professionals and community agencies to provide education, counseling and support. If we can help families foresee and manage the inevitable challenges they will encounter, we can help them draw closer instead of being driven apart.

We are only at the beginning of our understanding of all the factors that come together to produce Alzheimer’s, and we have a lot to learn about stopping, reversing and curing the disease. But we have strong clues with basic and animal research pointing us in promising directions. Several studies are about to start at Cedars-Sinai, and as these and many other research projects are translated from pre-clinical to clinical trials, we will need patient volunteers.

A program like ours, based at a hospital with a strong research component, will provide doctors and researchers with a large number of well-documented cases, enabling them to provide the latest advances to patients while collecting immense amounts of data in the search for treatments and cures.

SL: Why do potential therapeutics for dementia work in animal models and not humans?

DS: About 50 drugs have worked in animal models, but not in humans. Part of the answer lies in the fact that even the best models do not perfectly represent disease in humans. But a much more significant factor, we believe, is that therapeutics that have worked in animals were initiated in humans too late in the disease process to be beneficial. We have learned that Alzheimer’s causes damage in the brain many years before symptoms appear, by which time more than half of brain cells are irreversibly injured.

It may be that some of the therapies do work – but only if they are initiated early enough. This is one reason our center aims to identify people at risk and provide early detection screening.

SL: What lifestyle changes can alter the development of neurodegenerative diseases? What is the evidence regarding nutrition and risk of dementia?

DS: Nutrition, exercise and certain kinds of mental activity can affect quality and quantity of life. Thirty minutes of moderate exercise most days, adopting a Mediterranean-style diet, and engaging in enjoyable activities that stimulate the brain appear to be helpful in delaying onset and influencing progression of Alzheimer’s. So far, no drug can do that.

The Alzheimer’s Association summarizes some of the nutrition guidelines coming from recent research. Many studies, such as those at the Fisher Center for Alzheimer’s Research Foundation, indicate that a diet that is good for the heart also is beneficial for brain health.

There is evidence that a vegetable-based diet has a positive effect on cognitive health and disease modification. There is also evidence that regular
not only has positive influence on disease progression, but may actually slow down brain atrophy. The data on cognitive exercises is still weak, but the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (the FINGER study) and others have shown that the positive effect one sees in relation to cognitive exercises is usually in the context of support and social activity.

SL: Where should we focus federal research funding for dementia?

DS: For the last few decades we have been focusing on this devastating disease at a later stage of the disease, which appears not to have responded to any therapies. Today we need to focus on early detection and intervention. This means that a significant amount of dollars must be directed to three major areas:

  • identification of early biomarkers of the disease,
  • larger screening programs that catch a greater proportion of the population at risk for the disease, and
  • intervention trials at these earlier stages when we believe there is greater hope for disease modification and abatement.

SL: What are the most promising technologies/therapeutics for dementia prevention, early detection and treatment?

DS: Many different avenues are being explored. Researchers at Cedars-Sinai will be investigating two drugs already on the market for other conditions, and we are studying ways to spur the immune system to help fend off Alzheimer’s.

In the area of early detection, several innovative approaches have been proposed. One noninvasive, relatively inexpensive technology, pioneered at Cedars-Sinai and now in clinical trials in the U.S. and Australia, is believed to detect Alzheimer’s-associated changes in the retina at the back of the eye even before they develop in the brain. If the device receives Food and Drug Administration approval, it could offer an easy, painless, widely available, early detection screening, which in turn could lead to early intervention with lifestyle modifications and eventually medications to stop or slow the disease.

SL: Any closing remarks for the readers of Brain Blogger?

DS: We as a society and as treatment professionals must do more for patients and caregivers affected by Alzheimer’s. A center like ours, with a network of community partners, can make a tremendous difference in the way the disease affects a family. Also, we must all work to move from a sense of helplessness to one of empowerment. Certainly, there is a genetic component of Alzheimer’s, but there are steps we can take to change the course of the disease and reduce its impact in individual lives and globally.

Image via Ocskay Bence / Shutterstock.

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How Does Meditation Make You Smarter? Sat, 02 May 2015 12:00:38 +0000 Unless you’ve been living under a rock, you don’t need to be told about the relaxing effects of meditation. The practitioners vouch for it; and those who don’t, do not dispute it either. Those in the Far East have known for centuries that meditating brings mental peace and spiritual bliss. Now scientists claim that meditation can even alter the brain’s chemistry and functionality.

Over the years, neuroscientists have carried out brain imaging tests on long-term practitioners of meditation, including several Tibetan monks. According to the results of these studies, not only sustained meditative practices but also short-term meditation can produce profound physical, biochemical, and functional changes in the brain.

The Dalai Lama, Meditation, and the Neuroplasticity of the Brain

The slew of research studies into the neural effects of meditation is believed to have been influenced by His Holiness the Dalai Lama. Buddhists have a long tradition of intensive meditation. The Dalai Lama sent some of his most accomplished meditation practitioners to the University of Wisconsin to have their meditating brains probed into by neuroscientist Richard Davidson. What followed was a revolutionary experiment that eventually proved the phenomenon of “neuroplasticity” – the ability of the human brain to continuously evolve structurally and functionally.

Davidson conducted his experiment on two groups of subjects. The Dalai Lama’s disciples had undergone extensive meditation training for 5,000-10,000 hours, spanning periods between 15 and 40 years. The other group consisted subjects who had no prior experience with meditation but were made to go through a week-long meditation training session before the experiment.

The brain scan and EEG results of these two groups showed that the monks had greater gamma wave activity in their brains than the non-meditating subjects. The non-meditating subjects, however, recorded a slight increase in gamma wave activity in their brains after undergoing the meditation training.

The Role of Gamma Waves

Electrical activity in the brain manifests as waves. These waves have different frequencies, and at greater than 40 Hertz, gamma waves have some of the highest frequencies of all brain waves. High-frequency gamma waves have frequencies greater than 80 Hertz. Gamma wave activity is associated with higher mental processes like thinking, cognition, and memory formation and recall.

Sustained meditative practices can result in improved brain functionality by increasing the gamma wave activity. Here’s how:

When nerve cells “fire” synchronously, there is improved communication between the different regions of the brain. This aids higher mental processes. High gamma wave activity in the brain indicates thousands of neural cells are firing in unison and sending out signals to different parts of the brain at great speeds. Synchronized neural activity not only improves cognitive functioning but also keeps the brain active and energized to prevent age-related neural degeneration.

According to one study published this year, the brains of long-term meditation practitioners can produce very high frequency gamma waves, ranging between 100 and 245 Hertz. In particular, the increased gamma wave activity is seen in areas of the brains involved in monitoring (dorso-lateral prefrontal cortex), focused attentiveness (superior frontal sulcus, intraparietal sulcus, and the supplementary motor region), and engaging attention (visual cortex). These areas of the brain are associated with awareness and attention that are crucial to perform higher mental tasks like learning new skills. The studies indicate that long-term meditation practice improves attention in the practitioners that translates into more efficient learning.

Another recent study has reported that long-term meditation practitioners are generally able to process information more efficiently than non-practitioners.

Researchers have found that the ability to attend to a task with full focus is also greater in long-term meditation practitioners than novices because the former show less activity in the amygdala region in response to distracting sounds. This finding suggests that advanced meditation practitioners have greater control over how they react to emotions rising within them. Emotionally reactive behavior hampers steady concentration.

The Long-Term Effects of Meditation

The above-mentioned experiments were conducted on subjects while they were meditating. But those who have just made the foray into meditation or are contemplating embarking on the journey would be pleased to know that the effects of meditation continue well after they get up from their mats and change out of their robes!

It was recently demonstrated that experienced meditation practitioners exhibit higher gamma wave activity in the parietal-occipital region of the brain even when they are asleep. This proves that long-term meditation alters the pattern of spontaneous activity in the brain and the effects are long-lasting. This is one of the seminal studies on the neuroplasticity of the brain.

Implications of the Meditation Studies

Neuroscientists have brought into the limelight the benefits of meditation that Eastern seers, mystics, and monks knew from time immemorial. But the discovery of the phenomenon of neuroplasticity of the brain has turned everything neuroscientists believed about the workings of the brain on its head (pun not intended). Earlier scientists believed the neural connections become fixed when an individual reaches adulthood and remain so throughout his life. The connections that get lost due to any trauma or a disease can never be replaced. Fortunately, they have been proved wrong.

The concept of neuroplasticity of the brain and the effects of meditation give hope to countless victims of traumatic brain injury or those suffering from potentially debilitating psychological conditions like ADHD. These people can now dream of restoring the connections in their brains, rediscovering memories, and re-learning the skills they had forgotten. Educationists, teachers, and parents can consider introducing children to meditative practices at a young age. In fact, child psychologists and school counselors can explore meditation as a way to help children with learning disabilities acquire new skills and apply these successfully.

Meditation is an ancient Eastern practice, and it seems that Tibetan monks living in secluded monasteries high up in the mountains had decoded the secrets of the human brain long before EEGs and MRIs came along.


Brefczynski-Lewis, J., Lutz, A., Schaefer, H., Levinson, D., & Davidson, R. (2007). Neural correlates of attentional expertise in long-term meditation practitioners Proceedings of the National Academy of Sciences, 104 (27), 11483-11488 DOI: 10.1073/pnas.0606552104

Davidson RJ, & Lutz A (2008). Buddha’s Brain: Neuroplasticity and Meditation. IEEE signal processing magazine, 25 (1), 176-174 PMID: 20871742

Ferrarelli, F., Smith, R., Dentico, D., Riedner, B., Zennig, C., Benca, R., Lutz, A., Davidson, R., & Tononi, G. (2013). Experienced Mindfulness Meditators Exhibit Higher Parietal-Occipital EEG Gamma Activity during NREM Sleep PLoS ONE, 8 (8) DOI: 10.1371/journal.pone.0073417

Hauswald, A., Übelacker, T., Leske, S., & Weisz, N. (2015). What it means to be Zen: Marked modulations of local and interareal synchronization during open monitoring meditation NeuroImage, 108, 265-273 DOI: 10.1016/j.neuroimage.2014.12.065

Kim, D., Rhee, J., & Kang, S. (2014). Reorganization of the brain and heart rhythm during autogenic meditation Frontiers in Integrative Neuroscience, 7 DOI: 10.3389/fnint.2013.00109

Moran, L., & Hong, L. (2011). High vs Low Frequency Neural Oscillations in Schizophrenia Schizophrenia Bulletin, 37 (4), 659-663 DOI: 10.1093/schbul/sbr056

Tang, Y., Ma, Y., Fan, Y., Feng, H., Wang, J., Feng, S., Lu, Q., Hu, B., Lin, Y., Li, J., Zhang, Y., Wang, Y., Zhou, L., & Fan, M. (2009). Central and autonomic nervous system interaction is altered by short-term meditation Proceedings of the National Academy of Sciences, 106 (22), 8865-8870 DOI: 10.1073/pnas.0904031106

Image via Ditty_about_summer / Shutterstock.

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How Does the Brain Respond to Gossip? Sat, 25 Apr 2015 16:31:17 +0000 Newspapers use up reams of paper to report it. The air around your office cubicle, or in the cafeteria, hangs heavy with it. When best friends meet, they discuss it in hushed whispers. Gossip is an integral part of our communication. And if evolutionary psychologist Robin Dunbar is to be believed, gossip makes up the lion’s share—a whopping two-thirds—of our conversations. We talk about other topics like music, sports, politics, and the weather in the remaining time. That is a lot of time we spend discussing other people’s affairs, some of which are not in good light.

So why do perfectly sensible, reasonably intelligent, and genuinely compassionate people engage in gossiping? What do they gain from it? Do only women do it? And do people who love gossiping get a malicious pleasure out of listening to stories of failed romances and scandals? Neuroscientists have probed into the brains of people when they gossip to unearth the science behind it.

How Does Gossip Affect Us?

Gossip affects us; it either tickles us or makes us shudder. But did you know that different kinds of gossip affect us in different ways?

According to a study published this year and carried out on a random sampling of men and women, the subjects were generally more pleased to hear positive gossip than negative news. However, they were more distressed by negative gossip about themselves than about other people like their friends, acquaintances, and celebrities. Not many surprises there.

These findings were arrived at after the subjects were made to fill out a questionnaire. The scientists also carried out fMRI scans of the subjects’ brains as they listened to positive and negative gossip about themselves, their best friends, and celebrities.

According to the findings from these scan reports, listening to gossip about themselves heightened activity in the superior medial prefrontal cortex of the subjects’ brains. This region also responded to negative gossip about others. The subjects recorded increased activity in the orbital prefrontal cortex region of their brains in response to positive gossip about themselves.

The prefrontal cortex is one of the brain regions involved in social cognition and executive control. Social cognition is the ability to regulate our thoughts, behavior, and actions based on the real, imaginary, or assumed presence of other people. In other words, social cognition is a trait that makes us want to conform to the accepted norms and rules of society. Executive control is the ability to channelize our thought patterns, behavior, and actions based on internal goals. The neurotransmitter dopamine regulates the functionality of this region and activates the reward system.

The activation of prefrontal cortex region of the brain in response to positive gossip about oneself indicates that most human beings want to be seen as conforming to social standards of morality and success. They see more rewards in being “seen” in a positive light by the world at large than staying true to their internal moral compass.

On the other hand, we think that we are repulsed by negative gossip about others. But the fMRI images obtained during the above study bust this myth. The activation of the superior medial prefrontal cortex region in response to negative gossip about others indicates that although we are not elated by the falling-from-grace stories of other people, we are amused. This finding would seem morally unacceptable to many. After all, we don’t like to think of ourselves as fiends who gloat at others’ miseries and misfortunes.

But don’t be so hard on yourself. Gossiping is good for you!

Is Gossip Good or Bad?

Although moral purists might frown upon the practice, scientists say that gossip serves self-preservation purposes. According to them, there are also definite social benefits of gossiping.

Social scientists believe that gossip is an integral tool for observational learning. We exchange information about others when we gossip. Negative gossip makes you realize how society perceives acts of moral transgression, and you indirectly learn a lesson on how to live within a community and adhere to its rules. In this instance, negative gossip serves as a tool for indirect learning; you learn how to act correctly without having to bear the costs and consequences of a negative action.

Gossip acts as a self-improvement tool in another way. Positive gossip about ourselves gives us the motivation to carry on with our good behavior or sustain positive habits. It also provides us with hints about acceptable behavioral traits within the context of a particular society.

Some scientists point out to the benefit of prosocial gossip. They say exchanging negative information about the reputation of another person puts vulnerable people on alert and protects them from future anti-social or exploitative acts of the person who is the subject of the gossip. According to scientists, prosocial gossip promotes cooperation and bonding amongst people and creates a safety net.

At another level, the sharing of negative reputational information also acts as a check on the anti-social behavioral traits of people. According to scientists, when negative reputational information is shared with many people, the group as a whole usually chooses to ostracize the wrongdoer. Ostracism compels the person excluded from his group to resort to better behavior to win approval. Ostracism may also act as a deterrent to anti-social behavior by others.

Researchers also claim that sharing negative gossip promotes social bonds. They say that indulging in negative gossiping with another person usually triggers conversations that involve downward social comparisons. These conversations are powerful ego-boosters. What is more, by sharing negative information about another person, we unknowingly create distinct social identities—the gossiper brings the person he is gossiping with into his ambit and creates an in-group while the person being gossiped about is made out to be an outsider (the creation of an out-group).

It seems that gossiping is not entirely a wasteful pursuit of time and energy. Our brains get a kick from exchanging juicy tidbits of information about someone we know intimatel (our best friends) or can only observe from a distance (celebrities). Gossip about ourselves is like a mirror to our actions and behavior and lets us rectify ourselves, so we can become more responsible members of the society.


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Feinberg, M., Willer, R., Stellar, J., & Keltner, D. (2012). The virtues of gossip: Reputational information sharing as prosocial behavior. Journal of Personality and Social Psychology, 102 (5), 1015-1030 DOI: 10.1037/a0026650

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Image via g-stockstudio / Shutterstock.

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Correlates between the Science of Learning and the Practice of Teaching Thu, 23 Apr 2015 22:48:57 +0000 The phenomenon of human learning is not a unitary construct, rather it comprises a gamut of cognitive traits including memory, attention, decision making and social functioning. According to David Ausubel, an eminent educational psychologist: “The single most important factor influencing learning is what the learner already knows. Ascertain this and teach him accordingly”.

What we already know and can retrieve is underpinned by the neural system of memory, and the use of pre-existing neural networks can form the basis of further learning. Retrospective evaluations of events in the “long term” (in behavioural neuroscience, this refers to a period longer than a day) have found memory processing to be a high fidelity system. However, the transient storage of information, i.e., working memory, appears to be less resilient and prone to rapid deterioration.

“Consolidation” is the term attributed to the hypothetical transformation of a memory trace from an unstable, short-term form to a stable, long-term form. Recent research has focused on a rather enigmatic aspect of memory processing, dubbed “reconsolidation” – it is a special state brought about by the retrieval of items in the long-term memory, which makes them prone to alterations.

Learning is not simply based on enhanced neural activity, but also structural modifications that can be determined by changes in synaptic density (synaptogenesis). In a study involving rats, this question was explored by training a test group for a low-intensity but challenging motor skill, compared to the other groups that were exposed to high-intensity physical exercise but with relatively little learning involved. Notably, a higher density of blood vessels was found in the latter (angiogenesis, a compensatory response to increased/repetitive synaptic activity), but a significant increase in synaptic density was only found in the former, thereby demonstrating that learning is underpinned by neuro-structural changes in the brain.

The cortical-hippocampal system – comprising complex, bi-directional flow of information between the neocortex, the parahippocampal region and the hippocampus – underpins the neural coding mechanisms of conscious memory. The latter is particularly important in the organisation of memories in space and time.

Consistent with the recent advances in the neurobiology of learning, a list of potential correlates will be discussed from the literature that either inform the basis of accepted teaching practices or provide ideas for further exploration with the aim of improving the current design of learning environments. It must be acknowledged, however, that cognitive neuroscience has not advanced to a point yet where it could translate into guidelines for effective teaching practices (nor would such a circumscribed approach necessarily provide the desired outcomes), but drawing parallels between the two fields illustrate the neural underpinnings of the pedagogy of education, and highlight some of the pervasive ‘neuromyths’ that have taken root in the education sector and the society at large by courtesy of the so-called ‘brain-based learning’ industry.


It has been proposed that repetition of information can improve normal retention and retrieval processes. The neural execution of the reconsolidation phase is energy efficient (using pre-existing neural connections). Moreover, it provides an opportunity to modify the memory trace both in terms of content and structure.

Previous psychophysiological studies in humans have used a range of somatosensory stimuli or verbal suggestions (stressors) during the retrieval phase in order to improve memory performance; immersion of arm in ice-cold water and the use of negatively arousing pictures are amongst the different stressors used in experimental conditions. In the real world, students can exploit reconsolidation by practicing self-testing. This can produce a moderate level of stress – a mnemonic enhancer – by facilitating synaptic potentiation mediated by a moderate release of stress hormones, glucocorticoids. In contrast, high levels of stress/glucocorticoids can have the opposing effect on memory and learning processes. The seeming malleability of memory trace upon retrieval/reactivation has an important clinical implication in the context of consolidated fear memories which could then be blocked by amnesic agents.

Repeated testing has been shown to improve the retention of information, a phenomenon termed the “testing effect”, over and above any effect of repeated study. This effect is particularly robust when the tests require effortful recall, e.g. mechanistic questions rather than recognition tests such as multiple choice, and when testing is spaced out over time.

Spacing of learning

In addition to repeated retrieval, the value of spacing in learning is another interesting concept. However, further examination is warranted of the optimal intervals/spacing times for revisiting content for long-term consolidation. These observations support the concept of the spiral curriculum, which advocates revisiting topics in increasing levels of difficulty throughout the course. The latter point of the deepening of content upon successive encounters is equally important. It appears that our brains are better at retaining information when it is structured/mechanistic, context-based and goal-oriented. The use of similes, metaphors, analogies and other short mnemonics can also be helpful in memory retention.

Small learning groups

It could be argued that teaching in small groups is beneficial, not least because of the potential activation of stressor pathways triggered by the need to share the underlying reasoning processes. Breaking down a question into small parts could facilitate incremental/structured learning across the multiple levels of difficulty. Such an approach may also facilitate active engagement of students, including those who otherwise opt out from the learning process often with little engagement in the first place. With interactive, small-group teaching, as compared to the traditional, didactic forms of teaching to large groups of students, the students are more likely to embrace responsibility and ownership of the learning process, in part due to the engagement of the motivational and reward circuitry.


Reward is an important tenet of the learning process. It appears that our brains engage in “temporal discounting” to measure the relative value of a choice. For example, the seemingly short-term reward of having learnt a new skill as compared to the more long-term, greater reward of having a respected career, income, etc.

It is plausible that the reward system could be incorporated into the learning design by, for example, sharing with the students the scientific rationale underpinning the instructor’s choice for a particular learning model or teaching practice. It is tempting to suggest a more dynamic role of a tutor with the position being swapped with the students following an initial period of formalised tutorship. Indeed, it has been shown that social and cognitive concordance between the teacher and the learner can improve the latter’s perception of their learning experience.

While inclusion of a reward component in the learning design seems important, it may well be equally important to address the fear of failure associated with learning. Could it be a learnt effect? If so, could it be unlearnt then? In a sense, this is what the pain rehabilitation specialists do to reverse those avoidance/compensatory responses that contribute to the therapeutic intractability of chronic pain. Indeed, the phenomenon of fear is complicated, not least because of the myriad social and cultural connotations. However, it is plausible that individuals who find the learning process intrinsically rewarding are less likely to be overwhelmed by the fear of failure.

While emphasising the value of interactive, small-group teaching, it is important to acknowledge that learning preferences can vary greatly across individuals, and hence a combination of different teaching strategies should be adopted. Mental rehearsal of actions or thoughts, regardless of an external or an internal trigger, could facilitate the learning of an advanced skill, e.g. a complex surgical procedure. Likewise, it may help to overcome the fear of failure, for instance, in case of public speaking. The mirror neuron system is believed to subserve the inner imitation of an external event. Where feasible, visualisation technologies could be incorporated into the established learning paradigms. More generally, a multi-media approach of content delivery might also help to minimise cognitive distraction and improve attention, in addition to promoting memory retention by repetition of content.

Emotional state

Consistent with the findings in brain-damaged patients, our apparent rational thinking is in fact underpinned by hidden emotional processes. The role of emotions is vitally important as all the cognitive traits pertinent to education are inextricably linked to emotion. This poses a serious question in terms of the translation of knowledge from a structured educational setting to a real-world situation. According to Immordino-Yang and Damasio (2007):

“Knowledge and reasoning divorced from emotional implications and learning lack meaning and motivation and are of little use in the real world.”

Hence, it is important that a learning environment is not devoid of emotion, and that students are provided ample opportunities to engage in real-life problem solving as an integral part of the learning experience.


A greater integration between the science of learning and the practice of teaching is highly warranted, not least because of the “frequently exaggerated” and “at times misleading” claims of the brain-based learning industry about “improvements in the speed and efficiency of cognitive processing and dramatic gains in “intelligence”” by the use of “brain-training games”. These observations were shared in a consensus report by The Stanford Center on Longevity and the Berlin Max Planck Institute for Human Development.

While there is some evidence of short-term task-specific improvements in working memory, there is no clear evidence that these effects are transferrable to other untrained working memory tasks or broader everyday skills. Not to mention, financial, social and other opportunity costs associated with brain-training games warrant due consideration. Indeed, a range of other strategies are promoted to improve learning: for instance, choosing a learning design based on whether a student is “left-brained” or “right-brained” or the use of “brain buttons” (by applying pressure to an area between the first and second ribs under the collar bone) to reorganise/refocus the brain for reading and writing. Such learning strategies are often based on an exaggerated or flawed interpretation of scientific facts.

Scientific progression is underpinned by incremental and seemingly small discoveries; however, the claims of the brain-based learning industry are anything but that. Although an effort has been made by the scientific community in recent years to raise awareness about these issues, a lot more work needs to be done in particular to raise awareness amongst the educators as well as the broader community. The role of science communicators could be useful in bridging the current gap between the real neuroscience of learning and the pervasive propaganda of the commercial “brain-based” programs.


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