Genes and the Brain: Research reports

evolution

March 2007

Humans aren’t the only ones to think about what they know

As we get smarter about designing experiments and working out how to ask the right questions, the gap between human and non-human cognition keeps closing. Now a rat study has found evidence that rats can think about whether they know something or not. The study involved offering rats rewards for classifying a brief tone as either short or long. A right answer led to a large food reward; a wrong one, nothing. But on some tests runs, before starting, the rats were given a chance to back out of the test, in which case they got a small reward anyway. In some of the tests, the signal lengths were very different, making the discrimination very easy. But in others the difference was a lot harder to discern. In such a case, if the rats realized they couldn’t be sure of the answer, they would be better to forego the test and get the small, but guaranteed prize. Which was what was found.
The findings appeared online ahead of print on March 8 in Current Biology. Full reference
http://www.world-science.net/othernews/070308_rats.htm
http://www.eurekalert.org/pub_releases/2007-03/cp-mfw030607.htm

February 2007

Size of brain areas does matter -- but bigger isn't necessarily better

In a fascinating mouse study that overturns our simplistic notion that, when it comes to the brain, bigger is better, researchers have found that there is an optimal size for regions within the brain. The study found that if areas of the cortex involved in body sensations and motor control are either smaller or larger than normal, mice couldn’t run an obstacle course, keep from falling off a rotating rod, or perform other tactile and motor behaviors that require balance and coordination as well as mice with normal-sized areas could. It now seems that the best size in one that is best tuned to the context of the neural system within which that area functions — which is not really so surprising when you consider that every brain region acts as part of a network, in conjunction with other regions. This study builds upon a previous discovery by the same researchers, that a gene controls how the cortex in mice is divided during embryonic development into its functionally specialized areas. Different levels of the protein expressed by this gene changes the size of the sensorimotor areas of the cortex. It is known that significant variability in cortical area size exists in humans, and this may explain at least in part variability in human performance.
The findings appeared online before print February 27 in the Proceedings of the National Academy of Sciences. Full reference
Full text is available at http://tinyurl.com/2tpyhe
http://www.physorg.com/news92051236.html

Common gene version optimizes thinking but carries a risk

On the same subject, another study has found that the most common version of DARPP-32, a gene that shapes and controls a circuit between the striatum and prefrontal cortex, optimizes information filtering by the prefrontal cortex, thus improving working memory capacity and executive control (and thus, intelligence). However, the same version was also more prevalent among people who developed schizophrenia, suggesting that a beneficial gene variant may translate into a disadvantage if the prefrontal cortex is impaired. In other words, one of the things that make humans more intelligent as a species may also make us more vulnerable to schizophrenia.
The study was published online February 8, and in the March 1 issue of the Journal of Clinical Investigation. Full reference
http://www.sciencedaily.com/releases/2007/02/070208230059.htm
http://www.eurekalert.org/pub_releases/2007-02/niom-cgv020707.htm

December 2006

Neurons targeted by dementing illness may have evolved for complex social cognition

Special elongated nerve cells called spindle neurons, also known as Von Economo neurons (VENs), are found in two parts of the cerebral cortex known to be associated with social behavior, consciousness, and emotion (the anterior cingulate and fronto-insular cortex). They have only been found in humans and great apes, and, recently, whales. Because of this link with social behaviour, and because these brain regions are targeted by frontotemporal dementia, a recent study investigated whether VENs play a role in this type of dementia that causes people to lose inhibition in social situations. Autopsies revealed that among FTD sufferers, the anterior cingulate cortex had a dramatic reduction in the number of VENs compared to controls. In contrast, Alzheimer's patients had only a small and statistically insignificant reduction.
The finding is reported in the December 22 on-line issue of Annals of Neurology. Full reference
http://sciencenow.sciencemag.org/cgi/content/full/2006/1222/1?etoc
http://www.sciencedaily.com/releases/2006/12/061222090935.htm
http://www.eurekalert.org/pub_releases/2006-12/uoc--wih122106.htm

September 2006

A cognitive strategy shared by human infants and our great-ape kin

There are two basic strategies for remembering the location of something: either remembering the features of the item (it was a tree, a stone, etc.), or knowing the spatial placement (left, right, middle, etc.). All animal species tested so far seem to employ both strategies, but some species (e.g. fish, rats and dogs) have a preference for locational strategies, while others (e.g. toads, chickens and children) favor those which use distinctive features. A comparison of the cognitive strategies of humans, chimpanzees, bonobos, gorillas, and orangutans, has revealed that all non-human great apes and 1-year-old human infants prefer a locational strategy, even when an object strategy would be more efficient. This suggests that the common ancestor of all great apes enacted a similar strategy preference in employing spatial memory. However, 3-year-old human children in these circumstances chose the more efficient strategy.
The findings were reported in the September 5 issue of Current Biology. Full reference
http://www.eurekalert.org/pub_releases/2006-09/cp-acs083006.htm
http://www.eurekalert.org/pub_releases/2006-09/m-hdo090606.htm

August 2006

Genetic variations that may be key to the evolution of the human brain

It has been thought that most genetic variations between people and between species are due to small changes in the sequence of DNA lettering, but a new idea that’s becoming popular is that the number of copies of genes is an important source of variation that may be driving evolution. Comparison of the DNA sequences of humans, chimpanzees and monkeys, has now revealed that a gene that codes for a piece of protein called DUF1220 exists in 212 copies in humans, but only 37 in chimpanzees and 30 in monkeys. Mice and rats have only one. The protein is found in the heart, spleen, skeletal muscle, and small intestine, and particularly in brain regions associated with higher cognitive function.
The report appeared in the 1 September issue of Science. Full reference
http://www.nature.com/news/2006/060828/full/060828-5.html
http://sciencenow.sciencemag.org/cgi/content/full/2006/831/4?etoc

An exploration of those 49 areas of the genome that have changed most between human and chimpanzee has revealed one area that's changed dramatically in a relatively short period of time. The gene is found only in mammals and birds, and hasn’t changed much in other animals — between a chimp and a chicken, there are only two differences in the 118 letters of DNA code that make up HAR1 (human accelerated region 1). But there are 18 differences in that one gene between human and chimp. That is a lot of change to happen in five million years. HAR1 is part of two overlapping genes -- both the rare RNA genes, not genes that code for proteins -- one of which (HAR1F) is active in nerve cells that appear early in embryonic development and play a critical role in the formation of the layered structure of the human cerebral cortex. The other also appears to be involved in cortical development.
The study was published on August 16 as an advance online publication in Nature. Full reference
http://news.yahoo.com/s/ap/20060817/ap_on_sc/brain_evolution
http://www.newscientist.com/article/dn9767?DCMP=NLC-nletter&nsref=dn9767
http://www.sciencedaily.com/releases/2006/08/060817102730.htm

July 2006

Avoiding predators may be the reason for our large brains

A study of predators in Africa and South America suggests a new theory for why we evolved big brains. Apparently predators prefer prey with smaller brains, suggesting that more smarts help you outwit your enemies. A popular theory has been that the complexities of being social pushed the increase in brain size, and it does seem that this is also a factor, but predation is probably behind this as well — living in a group protects against predators, because group mates help keep an eye out for danger. However, the study found that while predators did prefer less sociable prey, the strongest pattern was for predators to prefer prey with relatively small brains. The researchers suggest that the need for a larger brain was strengthened when our primate ancestors came down out of the trees, and entered a much more dangerous environment.
The study was published online ahead of print in Biology Letters. Full reference
http://www.guardian.co.uk/science/story/0,,1835615,00.html

Bigger brains associated with domain-general intelligence

Analysis of hundreds of studies testing the cognitive abilities of non-human primates provides support for a general intelligence, and confirms that the great apes are more intelligent than monkeys and prosimians. Individual studies have always been criticized for not clearly ensuring that one species wasn’t out-performing another simply because the particular testing situation was more suited to them. However, by looking at so many varied tests, the researchers have overcome this criticism. Although there were a few cases where one species performed better than another one in one task and reversed places in a different task, overall, some species truly outperformed others. The smartest species were clearly the great apes — orangutans, chimpanzees, and gorillas. Moreover, there was no evidence that any species performed especially well within a particular paradigm, contradicting the theory that species differences in intelligence only exist for narrow, specialized skills. Instead, the results argue that some species possess a broad, domain-general type of intelligence that allows them to succeed in a variety of situations.
The study was published online August 1 in Evolutionary Psychology. Full reference
Full-text available at http://human-nature.com/ep/downloads/ep04149196.pdf
http://www.sciencedaily.com/releases/2006/08/060801231359.htm

June 2006

Asymmetrical brains let fish multitask

A fish study provides support for a theory that lateralized brains allow animals to better handle multiple activities, explaining why vertebrate brains evolved to function asymmetrically. The minnow study found that nonlateralized minnows were as good as those bred to be lateralized (enabling it to favor one or other eye) at catching shrimp. However, when the minnows also had to look out for a sunfish (a minnow predator), the nonlateralized minnows took nearly twice as long to catch 10 shrimp as the lateralized fish.
The research was reported online 19 June in Animal Behaviour. Full reference
http://sciencenow.sciencemag.org/cgi/content/full/2006/623/2?etoc

Primates take weather into account when searching for fruits

In recent times, a popular hypothesis for why primates, and especially humans, have more strongly developed cognitive skills than other mammals, is that they result from the need for complex social skills. There is quite a lot of support for this argument. But it is not the only possibility and a recent study has looked at an alternative: that it evolved to deal with ecological problems, such as foraging for food. Researchers followed a group of wild gray-cheeked mangabeys from dawn to dusk over 210 days in their natural rainforest habitat, obtaining an almost complete record of their foraging decisions in relation to their preferred food, figs. The findings are consistent with the idea that monkeys make foraging decisions on the basis of episodic ("event-based") memories of whether or not a tree previously carried fruit, combined with knowledge of recent and present weather conditions and a more generalized understanding of the relationship between temperature and solar radiation and the maturation rate of fruit and insect larvae.
The report appeared in the June 20th issue of Current Biology. Full reference
http://www.eurekalert.org/pub_releases/2006-06/cp-ptw061406.htm

November 2005

'Perception' gene tracked humanity's evolution

A gene thought to influence perception and susceptibility to drug dependence is expressed more readily in human beings than in other primates, and this difference coincides with the evolution of our species. The gene encodes prodynorphin, an opium-like protein implicated in the anticipation and experience of pain, social attachment and bonding, as well as learning and memory. Although the protein prodynorphin is identical in humans and chimps, in the gene's promoter sequence (that controls how much of the protein is expressed) some 10% is different (this compares to the overall 1 to 1.5% difference between human and chimpanzee genes). There is high genetic variation in the prodynorphin promoter among humans, but not among other primates. Variants have been tentatively linked to schizophrenia, cocaine addiction, and epilepsy. The report supports a growing consensus among evolutionary anthropologists that hominid divergence from the other great apes was fueled not by the origin of new genes, but by the quickening (or slowing) of the expression of existing genes.
The report was published online 15 November in Public Library of Science Biology. Full reference
Full text available at http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0030387
http://www.eurekalert.org/pub_releases/2005-11/iu-gt111405.htm

September 2005

Human brains still evolving

Two genes active in the brain — Microcephalin and ASPM — have now been sequenced. Both regulate brain size. The sequencing has revealed a distinctive mutation in both genes, both of which change the protein the gene codes for. For the Microcephalin gene, the mutation is now in the brains of about 70% of humans, and half of this group carry completely identical versions of the gene, suggesting the mutation arose recently (between 60,000 and 14,000 years ago) and spread quickly through the human species due to selection pressure, rather than accumulating random changes through neutral genetic drift. The new variant of ASPM appeared in humans even more recently — somewhere between 14,000 and 500 years ago — and is already present in about a quarter of people alive today.
The reports appeared in the September 9 issue of Science. Full reference 2
http://www.newscientist.com/article.ns?id=dn7974
http://www.sciencentral.com/articles/view.htm3?article_id=218392658

July 2005

Human cerebellum and cortex age in very different ways

Analysis of gene expression in five different regions of the brain's cortex has found that brain changes with aging were pronounced and consistent across the cortex, but changes in gene expression in the cerebellum were smaller and less coordinated. Researchers were surprised both by the homogeneity of aging within the cortex and by the dramatic differences between cortex and cerebellum. They also found that chimpanzees' brains age very differently from human brains; the findings cast doubt on the effectiveness of using rodents to model various types of neurodegenerative disease.
The study was reported in the open-access journal PLoS Biology. Full reference
http://www.eurekalert.org/pub_releases/2005-08/hu-hca072805.htm

June 2005

New light on speech evolution in humans

A new monkey study challenges thinking that speech developed as a result of new structures that evolved in the human brain. A distinct brain region that controls jaw movements in macaque monkeys has been found in the same area and with the same anatomical characteristics as Broca's area. The discovery suggests that this area of the brain evolved originally to perform high-order control over the mouth and the jaw, and that as humans evolved this area came to control the movements necessary for speech.
The study was published in the 30 June issue of Nature. Full reference
http://www.eurekalert.org/pub_releases/2005-06/mu-nrp062905.htm

March 2005

Primitive brain learns faster than the "thinking" part of our brain

A study of monkeys has revealed that a primitive region of the brain known as the basal ganglia learns rules first, then “trains” the prefrontal cortex, which learns more slowly. The findings turn our thinking about how rules are learned on its head — it has been assumed that the smarter areas of our brain work things out; instead it seems that primitive brain structures might be driving even our most high-level learning.
The report appeared in the Feb. 24 issue of Nature. Full reference
http://web.mit.edu/newsoffice/2005/basalganglia.html

September 2004

Another clue to the evolution of the human brain

A new study suggests that the birth of a gene that fueled neurotransmission may have been a key advance in the evolution of the hominoid brain. GLUD2, a gene gene involved in glutamate metabolism, is found in humans and apes, but not in Old World monkeys, indicating that the gene appeared after monkeys and hominoids went their separate ways (some 23 million years ago), but before the gibbon lineage split from humans and great apes around 18 million years ago. Over time, GLUD2 acquired two amino acid changes that increased glutamate flux, possibly enhancing cognitive function in the hominoid brain.
The study appeared in the October issue of Nature Genetics. Full reference
http://www.biomedcentral.com/news/20040920/02

June 2004

More support for social skill theory of brain evolution

Why do we have such large brains? Brains are very costly — they require a lot of energy. Gaining credence in recent years has been the idea that the advantage of our brain has been through the complex social skills it allows. Evidence supporting this has come from a study of records of primates deceiving each other for personal gain. The bigger the neocortex, it seems, the more likely a primate is to practice deception. The researchers gathered instances of deception across 18 species of primate and found no link with overall brain size, but a clear match between devious deeds and neocortex volume.
The study will be reported in the Proceedings of the Royal Society: Biological Sciences. Reference
http://www.guardian.co.uk/life/dispatch/story/0,12978,1250723,00.html
http://www.newscientist.com/news/news.jsp?id=ns99996090

February 2004

More complex brain may have pre-dated Homo genus

New research supports Raymond Dart’s suggestion (in 1925) that the human brain started evolving its unique characteristics much earlier than has previously been supposed. One of the differences between human and ape brains is the position of the primary visual striate cortex (PVC), an area of the brain devoted exclusively to vision. In the ape brain, this is situated further forward than it is in human brains, making the PVC larger. It has been claimed that the PVC only decreased in size once the brain had grown substantially in size – when big-brained Homo (the hominid group that includes humans) appeared around 2.4 million years ago. However, new examination of an endocast of the brain of an Australopithecus africanus (Australopithecines pre-dated Homo, and their brains were similar in size to those of chimpanzees) has found evidence of a decreased PVC. This suggests an increase in the region lying in front of the PVC - the posterior parietal cerebral cortex, which is associated in humans with a variety of complex behaviors such as the appreciation of objects and their qualities, facial recognition and social communication.
The findings were reported in the journal Comptes Rendus Palevol. Full reference
http://news.bbc.co.uk/1/hi/sci/tech/3496549.stm

January 2004

Gene may be key to evolution of larger human brain

Researchers have now identified a gene that appears to have played a significant role in the expansion of the human brain's cerebral cortex. The gene is called the Abnormal Spindle-Like Microcephaly Associated (ASPM) gene, and dysfunction in this gene is linked to human microcephaly — a severe reduction in the size of the cerebral cortex. Comparison of the gene sequence in humans with that of 6 other primates (progressively less related to humans) revealed that the ASPM gene showed clear evidence of changes accelerated by evolutionary pressure in the lineage leading to humans, and the acceleration was most prominent in recent human evolution after humans diverged from chimpanzees (our closest primate relative) some five million years ago. A massive population-wide genetic change in the gene seems to have occurred in the human lineage every 300,000 to 400,000 years since then, with the last such change occurring between 200,000 and 500,000 years ago. Such strong evidence of evolutionary change is most unusual. No such change was found when other (non-primate) mammals were investigated.
An advance access article was published on January 13, in Human Molecular Genetics. Full reference
http://www.eurekalert.org/pub_releases/2004-01/hhmi-gmb011204.htm

November 2003

Evolution of the mammalian brain

Two recent studies cast light on the evolution of the mammalian brain. A study of the brains of cetaceans, has found that that the cortex of a killer whale is dramatically more “folded” than that of an Amazon River dolphin (the deep and complex folding, or gyrification, of the cortex surface is what allows the human brain to have far more informational capacity than would be expected from its mass). The whales’s brain was particularly convoluted in the area of the corpus callosum, the main “bridge” between the hemispheres. In other comparative study of mammalian brains, it was found that the larger the brain, the larger the mean diameter of the axons. Axons were also less densely packed and more heavily myelinated. Across all species studied, fast cross-brain conduction times were maintained at 1-2 milliseconds.
http://gateways.bmn.com/news/story?day=031201&story=1(BioMedNet: free registration required)

February 2002

Human frontal cortex not proportionately larger compared to great apes

Humans are widely considered to have a disproportionately large frontal cortex compared to other animals, and the disparity in cognitive capabilities is partly attributed to this difference. However, a comparison of the relative size of the frontal cortex in humans versus other great apes reveals that human frontal cortices are not disproportionately large in comparison to those of the great apes. The authors suggest that the human advantage may be due to differences in individual cortical areas and to a richer interconnectivity, rather than an overall size difference.
The report was published in Nature Neuroscience. Full reference
http://www.nature.com/cgi-taf/DynaPage.taf?file=/neuro/journal/v5/n3/abs/nn814.html (registration required)

Living in large groups could give you a better memory

A study into the brains of songbirds found that birds living in large groups have more new neurons and probably a better memory than those living alone. Does this have relevance for humans? We don't know yet, but it has been observed that social animals such as elephants tend to have better memories than loners.
The study will be published in the journal Behavioural Brain Research. A report appeared in the February 23 issue of New Scientist. www.newscientist.com
http://www.eurekalert.org/pub_releases/2002-02/ns-lil022002.htm

September 2001

Manipulating a signaling protein in a developing mouse brain caused radical changes in the cortex and may provide a clue about how the cerebral cortex changes in evolution

Using a newly developed technique, University of Chicago researchers have manipulated one of the signaling proteins in the developing mouse brain and found such manipulations cause radical changes in the cortex. Fibroblast Growth Factor 8 (FGF8), a member of a family of signaling proteins involved in forming other structures in the embryo, is normally found near the front of the developing cortex. Using a new microsurgical technique, the researchers were able to manipulate the amount and position of this signaling protein in the embryo and look for changes in the cortical pattern much later. The researchers increased the amount of the signaling protein in its normal position, decreased it by inserting a gene for a receptor able to soak up the protein, or expressed it in a new position. Each manipulation profoundly affected cortical area pattern. "Most dramatic, when a new source of the signaling protein was generated close to the back of the embryonic cortex, the whole program changed." The generation of a new cortical area by a molecular manipulation has not been seen before and may provide a clue about how the cerebral cortex changes in evolution. One way that evolution seems to generate more functionally complex brains is by adding new areas to the cortex.
The paper appeared In the September 20, 2001 edition of Science Express. Full reference
http://www.eurekalert.org/pub_releases/2001-09/uocm-anm091801.htm

genes & proteins

February 2007

A gene that influences intelligence

A study involving more than 2000 people from 200 families has found a link between the gene CHRM2, that activates multiple signaling pathways in the brain involved in learning, memory and other higher brain functions, and performance IQ. Researchers found that several variations within the CHRM2 gene (which is on chromosome 7) could be correlated with slight differences in performance IQ scores, which measure a person's visual-motor coordination, logical and sequential reasoning, spatial perception and abstract problem solving skills, and when people had more than one positive variation in the gene, the improvements in performance IQ were cumulative. Intelligence is a complex attribute that results from a combination of many genetic and environmental factors, so don’t interpret this finding to mean we’ve found a gene for intelligence.
The study's findings were published online December 12, and in the March issue of Behavior Genetics. Full reference
http://www.eurekalert.org/pub_releases/2007-02/wuso-gag022607.htm

Common gene version optimizes thinking but carries a risk

On the same subject, another study has found that the most common version of DARPP-32, a gene that shapes and controls a circuit between the striatum and prefrontal cortex, optimizes information filtering by the prefrontal cortex, thus improving working memory capacity and executive control (and thus, intelligence). However, the same version was also more prevalent among people who developed schizophrenia, suggesting that a beneficial gene variant may translate into a disadvantage if the prefrontal cortex is impaired. In other words, one of the things that make humans more intelligent as a species may also make us more vulnerable to schizophrenia.
The study was published online February 8, and in the March 1 issue of the Journal of Clinical Investigation. Full reference
http://www.sciencedaily.com/releases/2007/02/070208230059.htm
http://www.eurekalert.org/pub_releases/2007-02/niom-cgv020707.htm

January 2007

Genetic cause for word-finding disease

Primary Progressive Aphasia is a little-known form of dementia in which people lose the ability to express themselves and understand speech. People can begin to show symptoms of PPA as early as in their 40's and 50's. A new study has found has discovered a gene mutation in two unrelated families in which nearly all the siblings suffered from PPA. The mutations were not observed in the healthy siblings or in more than 200 controls.
The study was published in the January issue of Archives of Neurology. Full reference
http://www.eurekalert.org/pub_releases/2007-01/nu-rdg011507.htm

December 2006

Longevity gene also helps retain cognitive function

The Longevity Genes Project has studied 158 people of Ashkenazi, or Eastern European Jewish, descent who were 95 years of age or older. Those who passed a common test of mental function were two to three times more likely to have a common variant of a gene associated with longevity (the CETP gene) than those who did not. When the researchers studied another 124 Ashkenazi Jews between 75 and 85 years of age, those subjects who passed the test of mental function were five times more likely to have this gene variant than their counterparts. The gene variant makes cholesterol particles in the blood larger than normal.
The findings were reported in the December 26 issue of Neurology. Full reference
http://tinyurl.com/yrf5s4
http://www.eurekalert.org/pub_releases/2006-12/aaon-lga121906.htm

October 2006

'Memory gene' identified

Analysis of the human genome has revealed a gene associated with memory performance. The gene is called Kibra, and is expressed in the hippocampus. According to brain scans, people with the version of the gene related to poorer memory potential had to tax their brains harder to remember the same amount of information.
The report appeared in the October 20 issue of Science. Full reference
http://www.eurekalert.org/pub_releases/2006-10/ttgr-rti101906.htm

August 2005

Protein found to inhibit conversion to long-term memory

In a study using genetically engineered mice, researchers have found that mice without a protein called GCN2 acquire new information that doesn’t fade as easily as it does in normal mice. After weak training on the Morris water maze, their spatial memory was enhanced, but it was impaired after more intense training. The researchers concluded that GCN2 may prevent new information from being stored in long-term memory, suggesting the conversion of new information into long-term memory requires both the activation of molecules that facilitate memory storage, and the silencing of proteins such as GCN2 that inhibit memory storage.
The study was published in the August 25 issue of Nature. Full reference
http://www.eurekalert.org/pub_releases/2005-08/uom-mrp082905.htm

July 2005

Closing in on the genes involved in human intelligence

A genetic study claims to have identified two regions of the human genome that appear to explain variation in IQ. Previous research has suggested that between 40% and 80% of variation in human intelligence (as measured by IQ tests) can be attributed to genetic factors, but research has so far failed to identify these genes. The new study has identified specific locations on Chromosomes 2 and 6 as being highly influential in determining IQ, using data from 634 sibling pairs. The region on Chromosome 2 that shows significant links to performance IQ overlaps a region associated with autism. The region on Chromosome 6 that showed strong links with both full-scale and verbal IQ marginally overlapped a region implicated in reading disability and dyslexia.
The study was published in the July issue of the American Journal of Human Genetics. Full reference
http://www.qimr.edu.au/news/index.html

February 2005

More light on a common developmental disorder

Chromosome 22q11.2 deletion syndrome is the most common genetic deletion syndrome, and causes symptoms such as heart defects, cleft palate, abnormal immune responses and cognitive impairments. Two related studies have recently cast more light on these cognitive impairments. Previously it was known that numerical abilities were impaired more than verbal skills. The new study found children with the chromosome deletion performed more poorly on experiments designed to test visual attention orienting, enumerating, and judging numerical magnitudes. All three tasks relate to how the children mentally represent objects and the spatial relationships among them, supporting previous arguments that such visual-spatial skills are a fundamental foundation to the later learning of counting and mathematics. The second study found that such children had changes in the shape, size and position of the corpus callosum, the main bridge between the two hemispheres.
The first study appeared in the April issue of Cortex. Full reference
The second study appeared in the March issue of NeuroImage. Full reference
http://www.eurekalert.org/pub_releases/2005-03/chop-lbt030205.htm

July 2004

Closing in on the genes involved in context learning

A study involving the worm C. elegans (whose genome has been completely sequenced) has demonstrated that even such simple animals demonstrate memory that is sensitive to context. In the study, the worms were trained in a salt medium to associate a particular smell with starvation. When placed in a different salt medium, the worms didn’t respond to the smell, but showed distaste when experiencing the smell in the context of the salt medium in which they were trained. More importantly, use of this animal has enabled the researchers to identify a genetic mutation that affects this type of memory. The next step will be to identify the specific gene involved in processing environmental cues.
The study was published in the July 27 issue of Current Biology. Full reference
http://www.eurekalert.org/pub_releases/2004-07/uot-eil072704.htm

June 2004

Some brains age more rapidly than others

Investigation of the patterns of gene expression in post-mortem brain tissue has revealed two groups of genes with significantly altered expression levels in the brains of older individuals. The most significantly affected were mostly those related to learning and memory. One of the most interesting, and potentially useful, findings, is that patterns of gene expression were quite similar in the brains of younger adults. Very old adults also showed similar patterns, although the similarity was less. But the greatest degree of individual variation occurred in those aged between 40 and 70. Some of these adults showed gene patterns that looked more like the young group, whereas others showed gene patterns that looked more like the old group. It appears that gene changes start around 40 in some people, but not in others. It also appears that those genes that are affected by age are unusually vulnerable to damage from agents such as free radicals and toxins in the environment, suggesting that lifestyle in young adults may play a part in deciding rate and degree of cognitive decline in later years.
The study appeared in the June 24 issue of Nature. Full reference
http://www.eurekalert.org/pub_releases/2004-06/chb-dgi060204.htm

February 2004

Could memory performance and spatial learning be genetically based?

A new rat study provides evidence that individual differences in some cognitive functions (specifically spatial navigation, in this experiment) may have a genetic basis.
The report appeared in the February issue of Physiological Genomics. Full reference
http://www.eurekalert.org/pub_releases/2004-02/aps-cmp020404.htm

January 2004

Gene may be key to evolution of larger human brain

Researchers have now identified a gene that appears to have played a significant role in the expansion of the human brain's cerebral cortex. The gene is called the Abnormal Spindle-Like Microcephaly Associated (ASPM) gene, and dysfunction in this gene is linked to human microcephaly — a severe reduction in the size of the cerebral cortex. Comparison of the gene sequence in humans with that of 6 other primates (progressively less related to humans) revealed that the ASPM gene showed clear evidence of changes accelerated by evolutionary pressure in the lineage leading to humans, and the acceleration was most prominent in recent human evolution after humans diverged from chimpanzees (our closest primate relative) some five million years ago. A massive population-wide genetic change in the gene seems to have occurred in the human lineage every 300,000 to 400,000 years since then, with the last such change occurring between 200,000 and 500,000 years ago. Such strong evidence of evolutionary change is most unusual. No such change was found when other (non-primate) mammals were investigated.
An advance access article was published on January 13, in Human Molecular Genetics. Full reference
http://www.eurekalert.org/pub_releases/2004-01/hhmi-gmb011204.htm

Gene essential for development of normal brain connections discovered

After birth, learning and experience change the architecture of the brain dramatically. The structure of individual neurons, or nerve cells, changes during learning to accommodate new connections between neurons. Neuroscientists believe these structural changes are initiated when neurons are activated, causing calcium ions to flow into cells and alter the activity of genes. Now the first gene, CREST, known to mediate these changes in the structure of neurons in response to calcium, has been discovered. In the study, it was found that mice lacking this gene didn’t develop normally in response to sensory experience, and their brains, while normal at birth, later showed far less interconnectivity between neurons. The gene produces a protein that, in adult humans, is produced in the hippocampus. It is therefore speculated that the protein may be necessary for learning and memory storage. The discovery of this gene may have implications for certain types of learning disorders in humans.
The paper featured on the cover of the January 9 issue of Science. Full reference
http://www.eurekalert.org/pub_releases/2004-01/uoc--gef010804.htm

Brain protein affecting learning and memory discovered

A significant new brain protein has been identified. Cypin is found throughout the body, but in the brain it now appears that it regulates neuron branching in the hippocampus. Such branching is thought to increase when learning occurs, and a reduction in branching is associated with certain neurological diseases. Discovery of this protein opens the possibility of new drug therapies for treating neurological disorders, and perhaps even memory-enhancing drugs.
The paper was published online 18 January, and appeared in the February issue of Nature Neuroscience. Full reference
http://www.eurekalert.org/pub_releases/2004-01/rtsu-rsd011204.htm
http://news.independent.co.uk/world/science_medical/story.jsp?story=482567

May 2003

Amphetamine helps or hinders cognitive function depending on your genes

Everyone inherits two copies of the catecho-O-methyltransferase (COMT) gene, that codes for the enzyme that metabolizes neurotransmitters like dopamine and norepinephrine. It comes in two common versions. One version, met, contains the amino acid methionine at a point in its chemical sequence where the other version, val, contains a valine. Depending on the mix of variants inherited, a person's COMT genes can be typed met/met, val/val, or val/met. People with the val/val variant appear to have reduced prefrontal dopamine activity and less efficient prefrontal information processing, along with slightly increased risk for schizophrenia. People with val/met have more efficient prefrontal function, and people with met/met the most efficient.
In a recent imaging study, 27 volunteers (10 val/val, 11 val/met, and 6 met/met) performed a variety of cognitive tasks that involved working memory and executive functioning, after taking either amphetamine or a placebo. Since amphetamine boosts dopamine activity in the prefrontal cortex, the researchers predicted that the drug would enable val/val types to boost their low level of dopamine and perform better on cognitive tasks that depend on the prefrontal cortex. On the other hand, those with met/met should be hindered by amphetamine. The study confirmed these predictions - val/val subjects on amphetamine performed comparably to met/met types in normal conditions, while met/met subjects on amphetamine performed worse than subjects with val/val types in normal conditions.
Amphetamines and other drugs that affect prefrontal dopamine systems are used to treat Attention Deficit Hyperactivity Disorder (ADHD), and other psychiatric illnesses, and some people respond better than others to these medications. About 15-20% of individuals in populations of European ancestry have the met/met COMT gene type.
The study was reported in the May 13 issue of Proceedings of the National Academy of Sciences. Full reference
http://www.eurekalert.org/pub_releases/2003-05/niom-gep050703.htm

January 2003

Gene linked to poor episodic memory

Brain derived neurotrophic factor (BDNF) plays a key role in neuron growth and survival and, it now appears, memory. We inherit two copies of the BDNF gene - one from each parent - in either of two versions. Slightly more than a third inherit at least one copy of a version nicknamed "met," which the researchers have now linked to poorer memory. Those who inherit the “met” gene appear significantly worse at remembering events that have happened to them, probably as a result of the gene’s effect on hippocampal function. Most notably, those who had two copies of the “met” gene scored only 40% on a test of episodic (event) memory, while those who had two copies of the other version scored 70%. Other types of memory did not appear to be affected. It is speculated that having the “met” gene might also increase the risk of disorders such as Alzheimer’s and Parkinsons.
The study was reported in the January 24 issue of Cell. Full reference
http://www.nih.gov/news/pr/jan2003/nimh-23.htm
http://www.eurekalert.org/pub_releases/2003-01/niom-hga012203.htm
http://news.bbc.co.uk/1/hi/health/2687267.stm