Category: Neuroscience

With the discovery that the unconscious mind plays a key role in the placebo effect, researchers have identified a novel mechanism that helps explain the power of placebos and nocebos.

Described in the Sept. 10 on-line issue of the Proceedings of the National Academy of Sciences (PNAS), the new findings demonstrate that the placebo effect can be activated outside of conscious awareness, and provide an explanation for how patients can show clinical improvement even when they receive treatments devoid of active ingredients or of known therapeutic efficacy.

"In this study, we used a novel experimental design and found that placebo and nocebo [negative placebo] effects rely on brain mechanisms that are not dependent on cognitive awareness," explains first author Karin Jensen, PhD, of the Department of Psychiatry and the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH) and the Program in Placebo Studies (PiPS) at Beth Israel Deaconess Medical Center/Harvard Medical School. "A person can have a placebo or nocebo response even if he or she is unaware of any suggestion of improvement or anticipation of getting worse."

It has long been believed that placebo responses are related to conscious beliefs or thoughts and that when given an inert pill or therapy, patients get better because they have the expectation that they will get better, or in the case of nocebos, get worse because they anticipate that they will get worse.

However, more recently, scientists have recognized that humans learn to expect either reward or threat quickly and automatically without needing to consciously register the idea in their brains. As the authors write, neuroimaging studies of the human brain have suggested that certain structures, such as the striatum and the amygdala, can process incoming stimuli before they reach conscious awareness, and, as a result, may mediate non-conscious effects on human cognition and behavior.

The scientists set out to determine whether placebo and nocebo responses might be activated outside of a person's conscious awareness, even if he or she has no expectation of either improving or declining.

Jensen, together with the study's senior author Jian Kong, MD, also of MGH and the PiPS, studied 40 healthy volunteers (24 female; 16 male, median age 23). Two experiments were conducted: In the first, researchers administered heat stimulation to participants' arms while simultaneously showing them images of male human faces on a computer screen. The first face was associated with low pain stimulations and the second image with high pain. Patients were then asked to rate their experience of pain on a scale of 0 to 100, 0 being no pain and 100 being the worst imaginable pain, but without the patient's knowledge that all heat stimulations would have the same moderate heat intensity. As predicted, the pain ratings correlated with the previously learned associations, with a pain rating of 19 when the subjects saw the low pain face while the high pain face resulted in subjects' mean reports of 53 on the pain scale (nocebo effect).

Then, in the second experiment, the participants were administered the same levels of thermal heat stimulation. Once again, the facial images were projected on the computer screen — but this time, they flashed by so quickly that subjects could not consciously recognize them. The participants once again rated their pain, and despite a lack of consciously recognizable cues, the participants reported a mean pain rating of 25 in response to the low pain face (placebo effect) and a mean pain rating of 44 in response to the high pain face (nocebo response) even though they did not consciously recognize the faces on the screen.

"Such a mechanism would generally be expected to be more automatic and fundamental to our behavior compared to deliberate judgments and expectations," explains Kong. "Most important, this study provides a unique model that allows us to further investigate placebo and nocebo mechanisms by using tools such as neuroimaging."

As PiPS Director and study coauthor Ted Kaptchuk notes, "It's not what patients think will happen [that influences outcomes] it's what the nonconscious mind anticipates despite any conscious thoughts. This mechanism is automatic, fast and powerful, and does not depend on deliberation and judgment. These findings open an entirely new door towards understanding placebos and the ritual of medicine."

In addition to Jensen, Kong and Kaptchuk, study coauthors include Jacqueline Raicek, Chantal Berna and Randy Gollub of MGH and the PiPS; Irving Kirsch of the PiPS and Plymouth (UK) University; and Kara M. Lindstrom and Martin Ingvar of the Karolinska Institute, Stockholm, Sweden.

This study was supported, in part, by grants from the Swedish Society for Medical Research and the Swedish Council for Working Life and Social Research and Grants R21AT004497 (National Center for Complementary and Alternative Medicine, NCCAM), R03AT218317 (National Institute on Drug Abuse), and R01AT006364 (NCCAM); K24AT004095 (NCCAM); and R01AT005280 (NCCAM).

Journal Reference:

1. Karin B. Jensen, Ted J. Kaptchuk, Irving Kirsch, Jacqueline Raicek, Kara M. Lindstrom, Chantal Berna, Randy L. Gollub, Martin Ingvar, and Jian Kong. Nonconscious activation of placebo and nocebo pain responses. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1202056109

The speed and apparent ease with which young infants learn the basics of a language regularly astound parents and scientists alike. Of course, adults are usually assumed to have the edge in sophisticated language learning. However, scientists Jutta Mueller, Angela D. Friederici and Claudia Maennel have now found that when it comes to extracting complex rules from spoken language, a three-month-old outperforms adult learners.

For 20 minutes, the scientists played a stream of syllables to babies while measuring their brain responses using electroencephalography (EEG). Pairs of syllables appeared together, but were separated by a third syllable. Jutta Mueller, first author of the study, stresses that “such dependencies between non-neighbouring elements are typical for natural languages and can be found in many grammatical constructions.” For instance, in the sentence “The boy always smiles,” the third-person-suffix “s” of the verb is dependent on the noun “boy.” In the study, this was reflected in the use of combinations like “le” and “bu” in sequences like “le-wi-bu.”

From time to time, however, combinations like “le-wi-to” would appear, in which one of the syllables was out of place. “EEG measurements showed us that the babies recognized this rule violation,” Mueller explains. Additionally, the scientists would occasionally change the tone of one syllable to a higher pitch — with an interesting outcome: Only those infants whose brains reacted to pitch changes in a more mature way could detect the syllable dependencies.

When facing the same task as the babies, adults only showed a reaction to the rule violations when asked to explicitly look for dependencies between the syllables. Mueller and her colleagues conclude that, evidently, the automatic recognition ability is lost later on. “What we found particularly interesting is that the small group of adults who did show evidence of rule learning also showed a stronger brain response to the pitch changes.”

These findings not only help understand how children manage to learn language so quickly during early development, but also point to a strong link between very basic auditory skills and sophisticated rule learning abilities. In a follow-up study, the scientists are now investigating whether differences the babies showed in response to pitch changes and in rule learning ability have any long-term effects on language development.

Story Source:

The above story is reprinted from materials provided by Max-Planck-Gesellschaft.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

1. Jutta L. Mueller, Angela D. Friederici, and Claudia Männel. Auditory perception at the root of language learning. PNAS, September 10, 2012 DOI: 10.1073/pnas.1204319109

 Cross a crow and it'll remember you for years.

Crows and humans share the ability to recognize faces and associate them with negative, as well as positive, feelings. The way the brain activates during that process is something the two species also appear to share, according to new research being published this week.

"The regions of the crow brain that work together are not unlike those that work together in mammals, including humans," said John Marzluff, University of Washington professor of environmental and forest sciences. "These regions were suspected to work in birds but not documented until now.

"For example it appears that birds have a region of their brain that is analogous to the amygdala of mammals," he said. "The amygdala is the region of the vertebrate brain where negative associations are stored as memories. Previous work primarily concerned its function in mammals while our work shows that a similar system is at work in birds. Our approach could be used in other animals — such as lizards and frogs — to see if the process is similar in those vertebrates as well."

Marzluff is the lead author of a paper being published the week of Sept. 10 in the online edition of the Proceedings of the National Academy of Sciences.

Previous research on the neural circuitry of animal behavior has been conducted using well-studied, often domesticated, species like rats, chickens, zebra finches, pigeons and rhesus macaques — and not wild animals like the 12 adult male crows in this study.

The crows were captured by investigators all wearing masks that the researchers referred to as the threatening face. The crows were never treated in a threatening way, but the fact they'd been captured created a negative association with the mask they saw. Then for the four weeks they were in captivity, they were fed by people wearing a mask different from the first, this one called the caring face. The masks were based on actual people's faces and both bore neutral expressions so the associations made by the crows was based on their treatment.

In most previous neurological studies of animals, the work usually starts by sedating the animals, Marzluff said. Instead the approach developed by the UW involved injecting a glucose fluid commonly used in brain imaging into the bodies of fully alert crows that then went back to moving freely about their cages. The fluid flooded to the parts of the crow brains that were most active as they were exposed for about 15 minutes to someone wearing either the threatening or caring mask.

Then the birds were sedated and scans made of their brains. All the birds were returned to the wild once all the work was completed.

"Our approach has wide applicability and potential to improve our understanding of the neural basis for animal behavior," wrote Marzluff and co-authors Donna Cross, Robert Miyaoka and Satoshi Minoshima, all faculty members with the UW's radiology department. The department funded the preliminary work while the main project was conducted using money from theUW's Royalty Research Fund.

Most neurological studies to date in birds have concerned their songs — how their brain registers what they hear, how they learn and come up with songs of their own. This new approach enables researchers to study the visual system of birds and how the brain integrates visual sensation into behavioral action, Marzluff said.

Among other things the findings have implications for lowering the stress of captive animals, he said.

"By feeding and caring for birds in captivity their brain activity suggests that the birds view their keepers as valued social partners, rather than animals that must be feared. So, to keep captive animals happy we need to treat them well and do so consistently," he said.

Intriguingly, Marzluff said the findings might also offer a way to reduce conflict between birds and endangered species on which they might be feeding. In the Mojave Desert, for instance, ravens prey on endangered desert tortoises. And on the West and East coasts, crows and ravens prey on threatened snowy plovers.

"Our studies suggest that we can train these birds to do the right thing," Marzluff said. "By paring a negative experience with eating a tortoise or a plover, the brain of the birds quickly learns the association. To reduce predation in a specific area we could train birds to avoid that area or that particular prey by catching them as they attempt to prey on the rare species."

The partnering of neuroscientists with ecologists could be used to better understand the neural basis of cognition in widely diverse animals, said co-author Cross. For example, her suggestion to use the glucose technique prior to brain scans, so the crows could be fully awake, could be used for other animals.

"This was a true collaboration that would never be possible without the people that were involved with very different areas of expertise," she said.

Journal Reference:

1. J. M. Marzluff, R. Miyaoka, S. Minoshima, D. J. Cross. Brain imaging reveals neuronal circuitry underlying the crow's perception of human faces. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1206109109

 A new study from USC researchers is the first to show that controlled fasting improves the effectiveness of radiation therapy in cancer treatments, extending life expectancy in mice with aggressive brain tumors.

Prior work by USC professor of gerontology and biological sciences Valter Longo, corresponding author on the study and director of the Longevity Institute at the USC Davis School of Gerontology, has shown that short-term fasting protects healthy cells while leaving cancer cells vulnerable to the toxic effects of chemotherapy.

The latest study, which appears in the online journal PLoS ONE, is the first to show that periods of fasting appear to have the same augmenting effect on radiation therapy in treating gliomas, the most commonly diagnosed brain tumor. Gliomas have a median survival of less than two years.

"With our initial research on chemotherapy, we looked at how to protect patients against toxicity. With this research on radiation, we're asking, what are the conditions that make cancer most susceptible to treatment? How can we replicate the conditions that are least hospitable to cancer?" Longo said.

Longo and his co-investigators, including Thomas Chen, co-director of the USC Norris neuro-oncology program, studied the combination of fasting with radiation therapy and with the chemotherapy drug Temozolomide, currently the standard treatment for the treatment of brain tumors in adults after an attempt at surgical removal.

The researchers found that controlled short-term fasting in mice, no more than 48 hours each cycle, improved the effectiveness of radiation and chemotherapy in treating gliomas. Despite the extremely aggressive growth of the type of brain tumor studied, more than twice as many mice that fasted and received radiation therapy survived to the end of the trial period than survived with radiation alone or fasting alone.

"The results demonstrate the beneficial role of fasting in gliomas and their treatment with standard chemotherapy and radiotherapy," the researchers wrote. They said the results indicated the benefits of short-term, controlled fasting for humans receiving treatment for brain tumors.

Longo cautioned that patients should consult with their oncologist before undertaking any fasting: "You want to balance the risks. You have to do it right. But if the conditions are such that you've run out of options, short-term fasting may represent an important possibility for patients."

USC Norris Cancer Center, Mayo Clinic and Leiden University Hospital are all conducting clinical trials on fasting and chemotherapy. A clinical trial on glioma, fasting and radiotherapy is being considered at USC.

Fernando Safdie of the USC Andrus Gerontology Center and Sebastian Brandhorst of Centre for Medical Biotechnology, Germany, were co-lead authors of the study. Min Wei, Changhan Lee and Saewon Hwang of the USC Andrus Gerontology Center; Weijun Wang and Chen of the USC Norris neuro-oncology program at the Keck School of Medicine of USC; and Peter Conti of the Molecular Imaging Center at the Keck School were co-authors of the study.

The research was funded by the National Institutes of Aging in the National Institute of Health (grants numbers: AG20642 and AG025135), the Bakewell Foundation, the V Foundation for Cancer Research and a USC Norris Cancer Center pilot grant.

Journal Reference:

1. Fernando Safdie, Sebastian Brandhorst, Min Wei, Weijun Wang, Changhan Lee, Saewon Hwang, Peter S. Conti, Thomas C. Chen, Valter D. Longo. Fasting Enhances the Response of Glioma to Chemo- and Radiotherapy. PLoS ONE, 2012; 7 (9): e44603 DOI: 10.1371/journal.pone.0044603

— It is commonly assumed that you can "work up an appetite" with a vigorous workout. Turns out that theory may not be completely accurate — at least immediately following exercise.

New research out of BYU shows that 45 minutes of moderate-to-vigorous exercise in the morning actually reduces a person's motivation for food.

Professors James LeCheminant and Michael Larson measured the neural activity of 35 women while they viewed food images, both following a morning of exercise and a morning without exercise. They found their attentional response to the food pictures decreased after the brisk workout.

"This study provides evidence that exercise not only affects energy output, but it also may affect how people respond to food cues," LeCheminant said.

The study, published online, ahead of print in the October issue of Medicine & Science in Sports & Exercise, measured the food motivation of 18 normal-weight women and 17 clinically obese women over two separate days.

On the first day, each woman briskly walked on a treadmill for 45 minutes and then, within the hour, had their brain waves measured. Electrodes were attached to each participant's scalp and an EEG machine then measured their neural activity while they looked at 240 images — 120 of plated food meals and 120 of flowers. (Flowers served as a control.)

The same experiment was conducted one week later on the same day of the week and at the same time of the morning, but omitted the exercise. Individuals also recorded their food consumption and physical activity on the experiment days.

The 45-minute exercise bout not only produced lower brain responses to the food images, but also resulted in an increase in total physical activity that day, regardless of body mass index.

"We wanted to see if obesity influenced food motivation, but it didn't," LeCheminant said. "However, it was clear that the exercise bout was playing a role in their neural responses to the pictures of food."

Interestingly, the women in the experiment did not eat more food on the exercise day to "make up" for the extra calories they burned in exercise. In fact, they ate approximately the same amount of food on the non-exercise day.

Larson said this is one of the first studies to look specifically at neurologically-determined food motivation in response to exercise and that researchers still need to determine how long the diminished food motivation lasts after exercise and to what extent it persists with consistent, long-term exercise.

"The subject of food motivation and weight loss is so complex," Larson said. "There are many things that influence eating and exercise is just one element."

Bliss Hanlon, a former graduate student at BYU, was the lead author on the study and Bruce Bailey, an associate professor of exercise science, was a co-author on the study.

By studying how birds master songs used in courtship, scientists at Duke University have found that regions of the brain involved in planning and controlling complex vocal sequences may also be necessary for memorizing sounds that serve as models for vocal imitation.

In a paper appearing in the September 2012 issue of the journal Nature Neuroscience, researchers at Duke and Harvard universities observed the imitative vocal learning habits of male zebra finches to pinpoint which circuits in the birds' brains are necessary for learning their songs.

Knowing which brain circuits are involved in learning by imitation could have broader implications for diagnosing and treating human developmental disorders, the researchers said. The finding shows that the same circuitry used for vocal control also participates in auditory learning, raising the possibility that vocal circuits in our own brain also help encode auditory experience important to speech and language learning.

"Birds learn their songs early in life by listening to and memorizing the song of their parent or other adult bird tutor, in a process similar to how humans learn to speak," said Todd Roberts, Ph.D., the study's first author and postdoctoral associate in neurobiology at Duke University. "They shape their vocalizations to match or copy the tutor's song."

A young male zebra finch, Roberts said, learns his song in two phases — memorization and practice. He said the pupil can rapidly memorize the song of an adult tutor, but may need to practice singing as many as 100,000 times in a 45-day period in order to accurately imitate the tutor's song.

During the study, voice recognition software was paired with optogenetics, a technology that combines genetics and optics to control the electrical activity of nerve cells, or neurons. Using these tools, the researchers were able to scramble brain signals coordinating small sets of neurons in the young bird's brain for a few hundred milliseconds while he was listening to his teacher, enabling them to test which brain regions were important during the learning process.

The study's results show that a song pre-motor region in the pupil's brain plays two different roles. Not only does it control the execution of learned vocal sequences, it also helps encode information when the pupil is listening to his tutor, Roberts said.

"We learn some of our most interesting behaviors, including language, speech and music, by listening to an appropriate model and then emulating this model through intensive practice," said senior author Richard Mooney, Ph.D., professor of neurobiology and member of the Duke Institute for Brain Sciences. "A traditional view is that this two-step sequence — listening followed by motor rehearsal — first involves activation by the model of brain regions important to auditory processing. This is followed days, weeks or even months later by activation of brain regions important to motor control."

"Here we found that a brain region that is essential to the motor control of song also has an essential role in helping in auditory learning of the tutor song," Mooney said. "This finding raises the possibility that the premotor circuits important to planning and controlling speech in our own brains also play an important role in auditory learning of speech sounds during early infancy." This brain region, known as Broca's area, is located in the frontal lobe of the left hemisphere.

The research has implications for the role of premotor circuits in the brain and suggests that these areas are important targets to consider when assessing developmental disorders that affect speech, language and other imitative behaviors in humans, Roberts said.

In addition to Roberts and Mooney, study authors include Sharon M. H. Gobes of Harvard University and Wellesley College; Malavika Murugan of Duke; and Bence P. Ölveczky of Harvard.

The research was supported by grants from the National Science Foundation and the National Institutes of Health (R01 DC02524) to Richard Mooney; and grants from NIH (R01 NS066408) and the Klingenstein, Sloan and McKnight Foundations to Bence P. Ölveczky; and a Rubicon fellowship from the Netherlands Organization for Scientific Research to Sharon M.H. Gobes.

Journal Reference:

1. Todd F Roberts, Sharon M H Gobes, Malavika Murugan, Bence P Ölveczky, Richard Mooney. Motor circuits are required to encode a sensory model for imitative learning. Nature Neuroscience, 2012; DOI: 10.1038/nn.3206

NewsPsychology (Sep. 18, 2012) — Misfolded proteins can cause various neurodegenerative diseases such as spinocerebellar ataxias (SCAs) or Huntington’s disease, which are characterized by a progressive loss of neurons in the brain. Researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, together with their colleagues of the Université Paris Diderot, Paris, France, have now identified 21 proteins that specifically bind to a protein called ataxin-1. Twelve of these proteins enhance the misfolding of ataxin-1 and thus promote the formation of harmful protein aggregate structures, whereas nine of them prevent the misfolding.

Proteins only function properly when the chains of amino acids, from which they are built, fold correctly. Misfolded proteins can be toxic for the cells and assemble into insoluble aggregates together with other proteins. Ataxin-1, the protein that the researchers have now investigated, is very prone to misfolding due to inherited gene defects that cause neurodegenerative diseases. The reason for this is that the amino acid glutamine is repeated in the amino acid chain of ataxin-1 very often — the more glutamine, the more toxic the protein. Approximately 40 repeats of glutamine are considered to be toxic for the cells.

Now, Dr. Spyros Petrakis, Dr. Miguel Andrade, Professor Erich Wanker and colleagues have identified 21 proteins that mainly interact with ataxin-1 and influence its folding or misfolding. Twelve of these proteins enhance the toxicity of ataxin-1 for the nerve cells, whereas nine of the identified proteins reduce its toxicity.

Furthermore, the researchers detected a common feature in the structure of those proteins that enhances toxicity and aggregation. It is a special structure scientists call “coiled-coil-domain” because it resembles a double twisted spiral or helix. Apparently this structure promotes aggregation, because proteins that interact with ataxin-1 and have this domain enhance the toxic effect of mutated ataxin-1. As the researchers said, this structure could be a potential target for therapy: “A careful analysis of the molecular details could help to discover drugs that suppress toxic processes.”

Story Source:

The above story is reprinted from materials provided by Helmholtz Association of German Research Centres.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

NewsPsychology (Sep. 19, 2012) — Kangaroo Mother Care — a technique in which a breastfed premature infant remains in skin-to-skin contact with the parent’s chest rather than being placed in an incubator — has lasting positive impact on brain development, revealed Université Laval researchers in the October issue of Acta Paediatrica. Very premature infants who benefited from this technique had better brain functioning in adolescence — comparable to that of adolescents born at term — than did premature infants placed in incubators.

Earlier research showed that infants born prior to the 33rd week of pregnancy experienced more cognitive and behavioral problems during childhood and adolescence. Université Laval researchers Cyril Schneider and Réjean Tessier, of the Department of Rehabilitation in the Faculty of Medicine and of the School of Psychology, respectively, and their Colombian colleagues Nathalie Charpak (Kangaroo Foundation) and Juan Ruiz-Peláez (Universidad Javeriana) wanted to determine if Kangaroo Mother Care could prevent these problems. To that end they compared, at age 15, 18 premature infants kept in incubators, 21 premature infants held in Kangaroo contact for an average of 29 days, and 9 term infants.

To assess participants’ brain functions, the researchers used transcranial magnetic stimulation. With this non-invasive and painless technique they could activate brain cells in targeted areas, namely the primary motor cortex that controls muscles. By measuring muscle responses to the stimulation, they were able to assess brain functions such as the level of brain excitability and inhibition, cell synchronization, neural conduction speed, and coordination between the two cerebral hemispheres.

The data collected by the researchers indicate that all brain functions of the adolescent Kangaroo group were comparable to those of the term infant group. On the other hand, premature infants placed in incubators significantly deviated from the other two groups 15 years after their birth.

“Thanks to Kangaroo Mother Care, infants benefited from nervous system stimulation — the sound of the parent’s heart and the warmth of their body — during a critical period for the development of neural connections between the cerebral hemispheres. This promoted immediate and future brain development,” suggests neurophysiologist Cyril Schneider.

Psychology researcher Réjean Tessier notes that “infants in incubators also receive a lot of stimulation, but often the stimulation is too intense and stressful for the brain capacity of the very premature. The Kangaroo Mother Care reproduces the natural conditions of the intrauterine environment in which the infants would have developed had they not been born premature. These beneficial effects on the brain are in evidence at least until adolescence and perhaps beyond.”

The two researchers, who are also associated with the Centre de recherche du CHU de Québec, will have the opportunity to shed more light on this subject. The Government of Canada, through its Grand Challenges Canada program, Saving Brains, just awarded their research team a $1 million grant to measure the neurological, cognitive, and psychosocial benefits of Kangaroo Mother Care in a group of 400 young adults, aged 18 to 20, who were born premature.

Story Source:

The above story is reprinted from materials provided by Université Laval, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

The results of this study are based on extensive analysis of the Allen Human Brain Atlas, specifically the detailed all-genes, all-structures survey of genes at work throughout the human brain. This dataset profiles 400 to 500 distinct brain areas per hemisphere using microarray technology and comprises more than 100 million gene expression measurements covering three individual human brains to date. Among other findings, these data show that 84% of all genes are expressed somewhere in the human brain and in patterns that are substantially similar from one brain to the next.

"This study demonstrates the value of a global analysis of gene expression throughout the entire brain and has implications for understanding brain function, development, evolution and disease," said Ed Lein, Ph.D., Associate Investigator at the Allen Institute for Brain Science and co-lead author on the paper. "These results only scratch the surface of what can be learned from this immense data set. We look forward to seeing what others will discover."

Key Findings

The results of this study show that, despite the myriad personalities and cognitive talents seen across the human population, our brains are more similar to one another than different. Individual human brains share the same basic molecular blueprint, and deeper analysis of this shared architecture reveals several further findings:

• Neighboring regions of the brain's cortex — the wrinkly outer rind — are more biochemically similar to one another than to more distant brain regions, which has implications for understanding the development of the human brain, both during the lifespan and throughout evolution.
• The right and left hemispheres show no significant differences in molecular architecture. This suggests that functions such as language, which are generally handled by one side of the brain, likely result from more subtle differences between hemispheres or structural variation in size or circuitry, but not from a deeper molecular basis.
• Despite controlling a diversity of functions, ranging from visual perception to planning and problem-solving, the cortex is highly homogeneous relative to other brain regions. This suggests that the same basic functional elements are used throughout the cortex and that understanding how one area works in detail will uncover fundamentals that apply to the other areas, as well.

In addition to such global findings, the study provides new insights into the detailed inner workings of the brain at the molecular level — the level at which diseases unfold and therapeutic drugs take action.

• 84% of all genes are expressed, or turned on, somewhere in the human brain.
• Many previously uncharacterized genes are turned on in specific brain regions and localize with known functional groups of genes, suggesting they play roles in particular brain functions.
• Synapse-associated genes — those related to cell-to-cell communication machinery in the brain — are deployed in complex combinations throughout the brain, revealing a great diversity of synapse types and remarkable regional variation that likely underlies functional distinctions between brain regions.

"The tremendous variety of synapses we see in the human brain is quite striking," said Seth Grant, FRSE, Professor of Molecular Neuroscience at the University of Edinburgh and collaborating author on the study. "Mutations in synaptic genes are associated with numerous brain-related disorders, and thus understanding synapse diversity and organization in the brain is a key step toward understanding these diseases and developing specific and effective therapeutics to treat them."

Journal Reference:

1. Michael J. Hawrylycz, Ed S. Lein, Angela L. Guillozet-Bongaarts, Elaine H. Shen, Lydia Ng, Jeremy A. Miller, Louie N. van de Lagemaat, Kimberly A. Smith, Amanda Ebbert, Zackery L. Riley, Chris Abajian, Christian F. Beckmann, Amy Bernard, Darren Bertagnolli, Andrew F. Boe, Preston M. Cartagena, M. Mallar Chakravarty, Mike Chapin, Jimmy Chong, Rachel A. Dalley, Barry David Daly, Chinh Dang, Suvro Datta, Nick Dee, Tim A. Dolbeare, Vance Faber, David Feng, David R. Fowler, Jeff Goldy, Benjamin W. Gregor, Zeb Haradon, David R. Haynor, John G. Hohmann, Steve Horvath, Robert E. Howard, Andreas Jeromin, Jayson M. Jochim, Marty Kinnunen, Christopher Lau, Evan T. Lazarz, Changkyu Lee, Tracy A. Lemon, Ling Li, Yang Li, John A. Morris, Caroline C. Overly, Patrick D. Parker, Sheana E. Parry, Melissa Reding, Joshua J. Royall, Jay Schulkin, Pedro Adolfo Sequeira, Clifford R. Slaughterbeck, Simon C. Smith, Andy J. Sodt, Susan M. Sunkin, Beryl E. Swanson, Marquis P. Vawter, Derric Williams, Paul Wohnoutka, H. Ronald Zielke, Daniel H. Geschwind, Patrick R. Hof, Stephen M. Smith, Christof Koch, Seth G. N. Grant, Allan R. Jones. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature, 2012; 489 (7416): 391 DOI: 10.1038/nature11405

When it comes to intelligence, what factors distinguish the brains of exceptionally smart humans from those of average humans?