Old Brains Prefer Young Blood

A paper published today in Nature finds that when younger mice are exposed to the blood of older mice, their brain cells behave more like those found in aging brains, and vice versa. The researchers who carried out the work also uncovered chemical signals in aged blood that can dampen the growth of new brain cells, suggesting that the decline in brain function with age could be caused in part by blood-borne factors rather than an intrinsic failure of brain cells. _TechnologyReview

It has been previously found that young blood can reverse certain signs of aging in the circulatory systems of old mice. Now there is evidence that young blood can help rejuvenate old brains.

To arrive at the discovery, the researchers studied pairs of old and young mice that were literally joined at the hip. They used a technique called parabiosis, in which two mice are surgically joined together along the flank, which causes them to develop a shared circulatory system. The technique has been used to study the development of the blood system, and more recently has been used to investigate the effects of age by joining old and young mice.

Lead author Tony Wyss-Coray, a neuroscientist at Stanford University, says that five weeks after creating these May-December pairings, "we found striking effects both on the young and old brains." The young mice had a reduction in the production of new neurons (neurogenesis), an increase in brain inflammation, and less activity in synapses connecting neurons.

The older mice, in contrast, had an increase in new neurons, less inflammation, and greater activity at synapses. "You could almost call this a rejuvenation effect," Wyss-Coray says.

...To see whether the effect could influence behavior, they injected, in separate experiments, young mice with plasma from older mice and vice versa, and found that old plasma impaired the younger animals' ability to perform learning and memory tasks, whereas young plasma improved the abilities of older mice.

Blood cells from one mouse cannot travel into the brain of the other because of the blood-brain barrier, so the team concluded that free-floating molecules in the blood, capable of passing through, must be responsible for the effects. By comparing more than 60 chemokines—chemical messengers secreted by cells that circulate in the blood—the researchers identified several associated with the detrimental effect of old blood. Administering one of these chemicals, called CCL11, to young mice dampened neurogenesis and impaired learning and memory. CCL11 has been studied for its role in allergies and asthma, but it's not clear how it influences neurons. _TechnologyReview

Does this mean that those of us who wish to stay young will have to prey on our young like vampires, sucking their life's blood for our own sustenance? No. For we are learning how to take our old cells and make them young again, in vitro -- in the test tube. The goal is to do the same thing, only better, and in vivo.

Such cellular rejuvenation treatments are likely to prove excellent stopgap methods of anti-aging, with significant -- but limited -- effects. The lifespans we live will be lived as younger, more vital monkey-men. And that is worth a very great deal.

But if we wish to live significantly longer lives, at significantly higher levels of awareness, intellect, and invention, we will need to go deeper than cellular replacement and humoral replacement therapies of this type.

Taken from an article published at Al Fin Longevity

Smarter Near the Poles, and Nearing Clockwork Orange?

WiredHumans apparently evolved larger eyes and brains as they migrated closer to the poles. The larger eyes would allow for better adaptation to lower light levels in the wintertime. The larger brains would allow for better adaptation to the greater challenges of radically changing seasons.

Anthropologists at Oxford University collected 55 skulls, dating from the 1800s, that represented 12 different populations from around the globe. The researchers measured the eye socket and brain volumes and plotted them against the latitude of each individual’s country of origin.

The team, lead by the Institute of Cognitive and Evolutionary Anthropology’s Eiluned Pearce, found a significant positive correlation between the size of brain and the latitude of the country. People from the northern-European countries of Scandinavia had the biggest brains, while Micronesians, from just north of the equator, had the smallest. _Wired

While political correctness forces the authors to deny that the larger brains have anything to do with the demonstrated higher intelligences of peoples who migrated farther from the equator, such higher intelligence has been shown to correlate with higher latitude as well as brain size, time after time. HBD (human biodiversity) deniers argue this point out of ignorance, but with the coming of advanced brain imaging techniques which can determine the comparative sizes of some of the very smallest brain nuclei, such denial is becoming infantile at best.

Meanwhile, Cal Tech researchers are homing in on a part of the brain which controls human aggression and violence. We may well be approaching a "Clockwork Orange" scenario, where violence-prone people will be conditioned or modified to remove their violent tendencies.

Our story starts in the hypothalamus, an ancient region of the brain, conserved throughout mammalian evolution. In humans, it is about the size of an almond, housing a motley collection of neurons. These cells regulate distinct bodily functions such as temperature, circadian rhythms, sleep, hunger, thirst, sex, anger, aggression and response to stress. Earlier work showed that electrical stimulation of some of these sites provokes cats and rats to sudden bouts of rage and that the ventromedial hypothalamus (VMH) has some involvement in sexual behaviors. Yet the precise location of attack-promoting neurons, their mode of action, and the interplay between aggression and mating—normally two opposing forms of social interactions—had remained deeply mysterious.

Enter a team from the California Institute of Technology, under the leadership of neurobiologist David J. Anderson. In four steps, the seven scientists, spearheaded by postdoctoral fellow Dayu Lin (now at New York University), nailed down the critical role of aggression neurons in the VMH. The setting was the home cage of an individually housed, sexually experienced male mouse. When another mouse, either a male or a sexually receptive female, entered the cage, the resident male mouse usually attacked the former but mated with the latter. The scientists video recorded the behavior so that the detailed time course of interaction of every pair of animals—the cautious sniffing and retreating, the pushing, shoving and biting, the mounting and consummatory activities—in hundreds of encounters could be statistically analyzed and time-aligned using software developed by machine vision engineers Piotr Dollar and Pietro Perona.

...Stimulating the VMHvl [Editor: The VMHvl is the ventrolateral portion of the ventromedial hypothalamus] when the mouse was by itself did not do anything. Yet in the presence of another animal, the mouse initiated a concerted attack, often by biting the back of the intruder. Unusually for this species, the illuminated male indiscriminately attacked female, castrated male or anesthetized mice—and sometimes even a blown-up latex glove. Aggression ceased once the light stopped. The infection and light delivery had to be targeted to the VMHvl nucleus; stimulating nearby regions did not produce such an effect. It is a striking and immediate demonstration of the link between neurons and behavior. Exciting VMHvl neurons causes aggression.

Finally, Anderson and his team turned to the question of whether the VMHvl cells are necessary for aggression to occur. Using a different technique, they genetically “silenced” VMHvl cells, turning them effectively off for days at a time. This silencing significantly reduced the chances of an aggressive encounter and lengthened the time it took to initiate an attack. _SciAm

The researchers were able to temporarily "dim down" the tendency for the mouse to resort to violence. The techniques for achieving this level of control over the mouse VMHvl nucleus are quite tedious. Eventually the same level of control will be achieved with a nasal spray containing nano-scale capsules of precisely targeted gene modifiers.

Violence is endemic to large parts of Asia, South America, and Africa. And even within the troubled multicultural urban areas of Europe, Oceania, and North America, deadly violence can be a daily phenomenon. Will human authorities utilise the coming tools of behaviour modification, even if they interfere with "free will?" Or is it better to pack prisoners in cages like mammalian sardines, and allow them to do with each other as they wish? The intersection of sophisticated brain and genetic research with widespread sociopathology is likely to prove interesting.

Brain from the Bottom Up: Spontaneous Birth of Synchrony in Small Neuronal Networks

More 13 July 2011: Brian Wang looks at the same research, with an emphasis on the hardware (electronic) aspect. It is fitting to look at both the neurons and the electronics, since the coming cybernetic biosingularity will be dependent upon both.

Human intelligence and consciousness are poorly understood, even by cognitive scientists, neuroscientists, and consciousness specialists. No one understands how to build a human intelligence from scratch, much less how to build a non-human intelligence capable of interacting with humans and the outside world on its own terms. But researchers at Tel Aviv University from the departments of Electrical Engineering and Physics, have taken a fascinating approach to building the basic components of brains: networks of biological neurons. Something wonderful happened when enough cultured neurons linked together in network: They spontaneously "synched up."

Background


Information processing in neuronal networks relies on the network's ability to generate temporal patterns of action potentials. Although the nature of neuronal network activity has been intensively investigated in the past several decades at the individual neuron level, the underlying principles of the collective network activity, such as the synchronization and coordination between neurons, are largely unknown. Here we focus on isolated neuronal clusters in culture and address the following simple, yet fundamental questions: What is the minimal number of cells needed to exhibit collective dynamics? What are the internal temporal characteristics of such dynamics and how do the temporal features of network activity alternate upon crossover from minimal networks to large networks?


Methodology/Principal Findings


We used network engineering techniques to induce self-organization of cultured networks into neuronal clusters of different sizes. We found that small clusters made of as few as 40 cells already exhibit spontaneous collective events characterized by innate synchronous network oscillations in the range of 25 to 100 Hz. The oscillation frequency of each network appeared to be independent of cluster size. The duration and rate of the network events scale with cluster size but converge to that of large uniform networks. Finally, the investigation of two coupled clusters revealed clear activity propagation with master/slave asymmetry.

Conclusions/Significance


The nature of the activity patterns observed in small networks, namely the consistent emergence of similar activity across networks of different size and morphology, suggests that neuronal clusters self-regulate their activity to sustain network bursts with internal oscillatory features. We therefore suggest that clusters of as few as tens of cells can serve as a minimal but sufficient functional network, capable of sustaining oscillatory activity. Interestingly, the frequencies of these oscillations are similar those observed in vivo. _PLoS

More papers by Mark Shein Idelson

Brain synchrony is an important topic of study, linked to consciousness, memory, learning, and normal function of general human brain activity. But synchronous oscillations are also programmed into the neurons themselves, at the smallest level of neuronal organisation. The challenge now, is to build "networks of networks", to discover the communications strategies which interconnected networks will evolve.

Contrast such a biological, bottom up approach with complex machine models of brain function such as the SpiNNaker project out of the University of Manchester, or the Human Brain Project (HBP) led by Henry Markram at Ecole Polytechnique de Lausanne.

Both of the above brain modeling approaches using computers, are based upon bottom-up theories of how brains work. The Lausanne project (HBP) is far more detailed -- going down to the ion channel level of neurons. The Manchester approach is impressive in its parallel computing ambitions, but it begins at the individual "neuronal spiking" level. SpiNNaker is more of a hybrid CompSci:Neurosci approach, than an actual model of the brain like the HBP.

Conventional artificial intelligence approaches do not mimic brain function closely, and are generally more "top-down" approaches, utilising conventional algorithmic concepts of mainstream computer science. Such approaches are doomed to failure before they even begin, as the last 70 years of conventional AI attempts continue to demonstrate.

In reality, brains must be grown. And new types of brains have to be evolved. Not necessarily from biological materials, but up until now the only working brains we know are biological. The first successful autonomous brains are likely to be evolved either from biological materials, or using ingenious abstractions of processes which emerge from biological mechanisms.

Al Fin cognitive scientists suggest that both the Lausanne approach and the Manchester approach are abstracted at the wrong level, to provide rapid paths to evolved intelligences. Creative human beings will have to discover the appropriate balance, but they will certainly be aided by computing systems in doing so. This is not gobbledygook nor is it AI-psychobabble. It is the genuine crux and pivot point of the problem.

What are the implications for the singularity? There will be no "uploading of consciousness" for the foreseeable future. The cyborg biosingularity is still on schedule for the decade between 2020 and 2030, if humans can avoid an extended Obama Dark Ages. The main question is how many of the cyborg components will be biological in origin, and how many will be non-biological (probably utilising nanotechnology).

Multi-Voxel Pattern Analysis of fMRI Reveals Brain Behind the Scenes

The research measured activity in a brain area known as the object-selective cortex (OSC) while participants were preparing to find a wide range of representational images of cars or people within briefly-displayed (100 ms) naturalistic scenes which they had not previously viewed. The subjects were first given visual cues that specified the category of objects (i.e., cars or people) to be located within the scenes. The key finding was that the cue alone – that is, even when no scene was subsequently shown – generated OSC responses determined through multivoxel pattern analysis (MVPA) that were strikingly similar to those that occurred when looking at actual examples of the cued category. Moreover, when looking at scenes, this neural activity pattern reliably predicted the subjects’ performance in detecting the cued visual target. (Unlike fMRI analysis, which focuses on individual brain voxels (volumetric pixels), MVPA enhances fMRI interpretation by identifying the information in broader patterns of brain activity.) _medXpress

medxpress
New tools of brain imaging are opening new windows into the brain's basic works. The study (PNAS, doi:10.1073/pnas.1101042108) described at the link breaks new ground in understanding "top-down" mechanisms used by the brain to identify objects -- when the brain has been pre-cued as to the nature of the sought object. This type of research builds general knowledge of brain function. As the tools are refined, it will become possible to better distinguish between brain responses of different individuals. The tools will then move into a clinical setting for diagnostic and screening (learning disorders, dementia, etc.) purposes.

While the technology used was already established, and so did not present significant challenges, Peelen notes that it takes six seconds to measure a neural signature – so it was needed to overcome the way neural measurements had previously been confounded with visual activity. “We came up with a clever design in which we showed the visual cue without subsequently displaying a scene,” he adds. “Since we primary gathered data using this technique, the measured signal reflected brain activity in the absence of visual input.”

Given the brain’s ability to perceive the world using various senses, and the fact that the research relied on symbolic (rather than visually-specific) cues invoked OSC activity, Peelen says that he expects that his results would be similar with different types of symbolic cues, whether these are spoken or textual. “Indeed, if we search for something in our daily life environment, the trigger to search can come from multiple sources – that is, a thought, but also an external demand – and it is unlikely that the brain has developed different mechanisms for each of these different cues. A very interesting question is how the brain transforms a symbolic cue, such as a word, a thought, or spoken text, to a visual ‘search template’ that effectively guides visual search. Very little is known about this transformation process.” _MedXpress

Different brains are wired differently. Early brain research finds ways in which brains work alike. More refined research discovers and delineates differences. As brain imaging tools grow ever more sophisticated, the powerful drive to learn more about the human brain will run head-on into the obstinate and entrenched forces of political correctness.

Which do you think will win, ultimately?

Human Brain Networks Can be Tattle Tales

Thanks to advanced brain imaging tools, scientists are getting better at judging general tasks the brain is doing at any given time. Stanford researchers Michael Greicius and colleagues used fMRI to detect particular brain networks being used by subjects performing one of four different tasks: silent singing, recalling the days events, counting backward by threes, or simple relaxation.

Greicius and his colleagues have previously shown that the brain operates, at least to some extent, as a composite of separate networks composed a number of distinct but simultaneously active brain regions. They have identified approximately 15 such networks. Different networks are associated with vision, hearing, language, memory, decision-making, emotion and so forth. _PO

_

The findings suggest that patterns for thousands of mental states might serve as a reference bank against which people's thoughts could be compared, potentially revealing what someone is thinking or how they are feeling. "In some dystopian future, you might imagine reference patterns for 10,000 mental states, but that would be a woeful application of this technology," says Greicius.

..."The most important potential for this is in the clinic where classifying and diagnosing and treating psychiatric disease could be really important," says Brodersen. "At the moment, psychiatry is often just trial and error." _NewScientist

Greicius has been studying brain networks for many years. He began looking at the brain's default mode network. Then he looked at dissociable intrinsic connectivity networks for salience processing and executive control. Now the team has progressed to the point where roughly 15 distinct networks have been identified, including some involving the cerebellum.

Government snoops, interrogators, marketing agencies, and other inquiring minds would like to be able to read your thoughts, of course. But it will be a while yet before brain scanners can read a brain from a distance. Since every brain is different, interpretation of scans will depend upon the ability to calibrate equipment for each brain without influencing the scan.

Remember that the ability to read a brain's network activity is just a step away from the ability to influence that brain's activity. After a certain point, wearing a tinfoil hat may begin to make sense. ;-)

Understanding the Brain: Videos via Simoleon Sense

via SimoleonSense
Simoleon Sense has been a particularly seminal website for the dissemination of ideas which underlie the economic behaviours of humans. Miguel links to a wide array of viewpoints, many of which contradict each other. That is the best -- perhaps the only -- approach to take in order to most closely approach a global maximum of "truth."

The videos for the day are meant to help understand how the human brain -- your brain -- works. Here is a list of links to scholarly videos from the Society for Social Neuroscience.

Larry Young: Effects of Oxytocin on social behaviour
Bruce McEwen: The brain as an organ of stress
David Amodio: Control of thinking processes

Unfortunately, modern educational systems are not helping students to make the best use of their amazing, complex brains (NYT via SimoleonSense)

Each human brain is a dynamic data point within the vast matrix of global human society. Understanding mass behaviour of societies is a challenging task, given that humans do not yet have a decent inkling of how individual brains work.

No matter how futile the task, however, chipping away at the challenge does occupy the time and can occasionally lead to profitable discoveries.

More: Peter Thiel pays 24 winners of the Thiel Fellowship $100,000 NOT TO ATTEND COLLEGE! The fellowship promotes entrepreneurship and the building of new businesses as a better way of learning about life. Face it: Being indoctrinated into dysfunctional groupthink -- whether at Harvard or at Podunk U. -- is worse than a waste of your brain's potential. Today's college indoctrination and academic lobotomisation is actually the destruction of yours and your children's potential, besides being a rapid route to debilitating debt.

Human Brain Project Moves Toward Human Cortex Model

Spiegel
Henry Markram's Human Brain Project in Lausanne, is competing for funding from the FET Flagship Initiative, to the tune of 1 billion Euros, disbursed over a ten year period. Markram's goals are extremely ambitious, and unprecedented. He aims to model the human cerebral cortex to an exquisite degree of precision. Markram expects that his model of the human brain will be so exact, that he will be able to study inaccessible brain diseases and devise impossible brain cures by using his model. He may be right. But in only ten years?

Scientists are paying particular attention to the cerebral cortex. This layer on the outside of brain, only a few millimeters thick, is the most important condition of it evolution. It is the starting point for efforts to understand what makes us tick -- and for endeavors to find solutions when things go wrong. Our brain builds its version of the universe in the cerebral cortex. The vast majority of what we see doesn't enter the brain through the eye. It is instead is based on the impressions, experiences and decisions in our brain.

Markham already completed important preparatory work for the computer modeling of the brain with his Blue Brain Project, an attempt to understand and model the molecular makeup of the mammalian brain. He modeled a tiny part of a rat brain, a so-called neocortical column, at the cell level. To understand what one of these columns does, it's helpful to imagine the cerebral cortex as a giant piano. There are millions of neocortical columns on the surface, and each of them produces a tone, in a manner of speaking. When they are simulated, the columns produce a symphony together. Understanding the design of these neocortical columns is a holy grail of sorts for neuroscientists.

It is important to understand the rules of communication among the nerve cells. The individual cells do not communicate at random, but instead seek specifically targeted communication partners. The axes of nerve cells intersect at millions of different points, where they can form a synapse. This makes communication between individual neurons possible. In a recent article in the journal Proceedings of the National Academy of Sciences, Markram writes that such connections are also developed entirely without external influence. This could indicate a sort of innate knowledge that all people have in common. Markram refers to it as the "Lego blocks" of the brain, noting that each person assembles his own world on the basis of this innate knowledge. _Spiegel

The object of study for the Human Brain Project may be the most complex dynamic system in the universe. The attempt would be impossible without the most sophisticated computing hardware and software available. And one must have more than a mere fistful of Euros to acquire such advanced goodies.

Modeling all of this in a computer is extremely complex. Markram's current model encompasses tens of thousands of neurons. But this isn't nearly enough to come within striking range of the secret of our brain. To do that, scientists will have to assemble countless other partial models, which are to be combined to create a functioning total simulation by 2023.

The supercomputers at the Jülich Research Center near Cologne are expected to play an important role in this process. The brain simulation will require an enormous volume of data, or what scientist Markram calls a "tsunami of data." One of the challenges for scientists working under Thomas Lippert, head of the Jülich Supercomputing Centre, is to figure out how to make the computer process only a certain part of the data at a given time, but without completely losing sight of the rest. They also have to develop an imaging method, such as large, three-dimensional holograms, to depict the massive amounts of data.

All it takes is a look at the work of Jülich neuroscientist Katrin Amunts to understand the sheer volume of information at hand. The team she heads is compiling a detailed atlas of the human brain. To do so, they cut a brain into 8,000 slices and digitized them with a high-performance scanner. The brain model generated in this way consists of cuboids, each measuring 10 by 10 by 20 micrometers, and the size of the data set is three terabytes. Brain atlases with higher resolutions, says Amunts, would probably consist of more than 700 terabytes _Spiegel

The answer to the question posed above is: No, this goal cannot be met within a time frame of ten years. Because the challenge is not merely quantitative -- a matter of compiling the precise assembly of terabytes to create a brain atlas. The goal is to create a dynamic, interactive model of incredible plasticity -- a model which changes itself moment to moment. The "700 terabyte" requirement mentioned above is just the starting point -- the bare beginning -- in the assembly of such a dynamic and ever-changing model.

But the problem is even harder -- much, much harder. The quantitative complexity -- even in dynamic flow -- is nothing when compared to the qualitative complexity, which is nowhere near to being solved by Markram's team.

The project as described in brief above is an excellent starting point. Much can be learned from such an approach. But starting points do not necessarily point directly toward the end that one seeks. Rather, they point somewhere "out there." It is for the questers to continuously adjust their headings -- and often they are forced to adjust their goals.

Good luck to Henry and his team -- with the funding and with the ongoing project. It is an ambitious goal worthy of any scientist.

Hippocampal Neurogenesis in Mice Key to New Brain Research

Scientists have found that antidepressants (sertraline and tofranil) can boost the growth of new neurons in the hippocampus of mice. This finding is important for treatment of depression, dementia, and brain trauma.

one of the ways that antidepressants work is by boosting neurogenesis in the hippocampus. Christoph Anacker and his colleagues at King's College London have now worked out how they do so.

Previous research has shown a link between some antidepressants and stress hormones called glucocorticoids. So Anacker's team decided to test whether the antidepressant sertraline acts on the glucocorticoid receptors of brain cells. They grew human hippocampal progenitor cells in a dish and added sertraline. Ten days later, the cultures showed a 25 per cent greater than expected increase in the number of new neurons.

When the researchers added a drug to block the glucocorticoid receptors before adding the antidepressant, the number of new neurons produced after 10 days was similar to that expected from natural growth. This suggests that the antidepressant does indeed exert its effect through this receptor (Molecular Psychiatry, DOI: 10.1038/mp.2011.26). _NewScientist

US researchers suspect that this neurogenic effect of antidepressants may prove useful in the treatment of brain injury.

Jason Huang, M.D., and colleagues undertook the study after noticing that patients with brain injuries who had been prescribed anti-depressants were doing better in unexpected ways than their counterparts who were not taking such medications. Not only did their depression ease; their memory also seemed improved compared to patients not on the medication.

"We saw these patients improving in multiple ways – their depression was improved, but so were their memory and cognitive functioning. We wanted to look at the issue more, so we went back to the laboratory to investigate it further," said Huang, associate professor of Neurosurgery and chief of Neurosurgery at Highland Hospital, an affiliate of the University of Rochester Medical Center.

The team's findings were published online recently in the Journal of Neurotrauma.

Huang said many patients who have a traumatic brain injury also experience depression – by some estimates, half of such patients are depressed. Doctors aren't sure whether the depression is a byproduct of the sudden, unfortunate change in circumstances that patients find themselves in, or whether the depression is a direct consequence of brain damage.

Previous research by other groups indicated that anti-depressants help generate new brain cells and keep them healthy in healthy animals. That, together with the experience of his patients, led Huang to study the effects of the anti-depressant imipramine (also known as Tofranil) on mice that had injuries to their brains.

Scientists found that imipramine boosted the number of neurons in the hippocampus, the part of the brain primarily responsible for memory. By one measure, mice treated with imipramine had approximately 70 percent more neurons after four weeks than mice that did not receive the medication.

That change was borne out on behavioral tests as well. The team tested mice by using what scientists call a novel object recognition test. Like human infants, mice tend to spend more time sizing up objects that they haven't encountered before – or don't remember encountering – than they do objects that they've seen before. This gives scientists a way to measure a mouse's memory.

The team found that mice that had been treated with imipramine had a better memory. They were more likely to remember objects they had seen previously and so spent more time exploring truly novel objects, compared to mice that did not receive the compound. _PO

Improvement of memory in mice follows naturally from the boost in neurogenesis within the hippocampus -- a part of the brain which is key to laying down new memories, among other things.

The fact that brain damaged humans also show cognitive improvement after treatment with antidepressants, points the way to new research to augment neurogenesis after brain trauma, stroke, tumour, and other forms of brain damage.

It is interesting that both tofranil -- one of the oldest antidepressants -- and sertraline, a newer antidepressant, were found to be effective in growing new hippocampal neurons. This approach may be used as a screening tool for antidepressant research, as well as a means to rank to likely effectiveness of antidepressants already on the market.

More: This PDF research article from research teams in France and the US, describes a new approach to antidepressant and anti-anxiety treatment which may take a paradoxical approach to nerve growth when compared to the antidepressants described in the above studies. Anyone who is significantly interested in understanding possible deep brain mechanisms for effective antidepressant therapy should take a look. Keep in mind that it is a research article, using mice as subjects.

Clear Genetic Links to Poor Impulse Control, Drug Dependency

University of Michigan medical researchers have identified genetic links to aberrant brain function leading to alcohol and drug dependencies.

The results, published online April 12 in Molecular Psychiatry, suggest that variations in the GABRA2 gene contribute to the risk of alcoholism by influencing impulsive behaviors, at least in part through a portion of the cerebral cortex known as the insula, says study senior author Margit Burmeister, Ph.D., research professor at U-M's Molecular and Behavioral Neuroscience Institute.

...Individuals under distress who also have the risky genetic variant tend to act impulsively, a behavior that may lead to the development of alcohol problems, says lead author Sandra Villafuerte, Ph.D., a research investigator at U-M's Molecular and Behavioral Neuroscience Institute and Department of Psychiatry.

"Developing deeper understandings of the various genetic and environmental factors involved in risky behaviors may guide prevention and treatment efforts in the future," Villafuerte says.

The study included 449 people, who came from 173 families – 129 of whom had at least one member diagnosed with alcohol dependence or abuse. Those with certain variations in the GABRA2 gene were more likely to have alcohol dependence symptoms and higher measures of impulsiveness in response to distress, the study found. Stronger associations were found in women than in men.

...Researchers also used functional magnetic resonance imaging (fMRI) to observe changes of blood flow in the brains of 44 young adults from these families as they performed a task in which they anticipated winning or losing money.

"The neuroimaging allowed us to see for the first time how these genetic variants create differences in how the brain responds in certain situations," says Mary M. Heitzeg, Ph.D., a research assistant professor in U-M's Department of Psychiatry and U-M's Addiction Research Center.

They found that individuals with one form of the GABRA2 gene associated with alcoholism showed significantly higher activation in the insula when anticipating rewards and losses than those with other combinations. This higher activation was also related to a greater level of impulsiveness in response to distress.

..."We believe these results suggest GABRA2 exerts an influence on an underlying neural system that impacts early risk factors and, later, alcohol dependency," says Burmeister, also a professor of psychiatry and human genetics at the U-M Medical School. "In the future, we hope to further examine the effects of family environment and other behavioral and environmental factors." _PO

Genetic influences on behaviours are too numerous to count, yet are extremely difficult to pin down with specificity. That is because multiple causes at several different levels are influencing the events which we observe. It will take many years to sort the many levels of causation -- many of them circular (incorporating feedbacks) in nature.

Persons who are indoctrinated into the religion of political correctness tend to eschew all discussion of genetic influences on behaviour. Funding for research can be difficult to obtain if highly indoctrinated "ethicists" feel that the valid findings of the research may be misconstrued in a way as to contradict politically correct dogma.

But such a PC approach only dooms persons who suffer from genetic disadvantages of behaviour to lifetimes of suffering. Much better to learn everything we can about these phenomena, so as to be able to compensate for these genetically based behavioural and cognitive disadvantages on as many levels as possible.

One approach to compensating for genetic defects in brain functioning is to run a low level dc current through the skull into the brain.

Getting to the Bottom of IQ Differences

The old IQ comparison studies that looked merely at skull size or head circumference as proxies for brain size, have been superceded by more advanced brain imaging capable of precise measurements of whole brain, total grey matter, total white matter, specific brain centers, and specific brain pathways and networks. These volumes are, to a large extent, under genetic control. A new era in comparing group IQs is dawning, thanks to advanced brain imaging and matching analysis of brain genetics. And a new era in improving gene expression relating to cognition is near to dawning -- as long as the key research is carried out and not obstructed out of a misguided sense of "political correctness."

Brain size as measured by MRI correlates highly with IQ. Specific brain networks and brain centers are even more highly correlated to IQ than gross brain size. In fact, a particular type of MRI analysis -- diffusion tensor imaging -- may supersede traditional IQ tests as the most objective means of testing IQ.

Anyone who truly wants to get to the bottom of the question of IQ differences between population groupings, will want to see the best designed, executed, and analysed research possible done on the subject. Anyone who is afraid of having such research done, does not truly want the question answered, and is lying to himself and everyone else when he claims that "there are no IQ differences, and even if there were it wouldn't matter!" Such persons' voices should be ignored as mere noise by all of those committed to finding the best answers to important questions.

A recent UK study at UCL Institute of Child Health, finds that teens who were delivered premature at birth have significantly lower brain white matter and IQ. (Abstract Annals of Neurology) For this study, it would be helpful to match by ethnicity, sex, and SES.

Between species, a longer gestation and breast feeding, correlate with larger brains, higher cognition, and longer lifespan.

And on and on. As brain genetic expression is correlated with advanced brain imaging with greater precision, and further correlated with IQ (and executive function), the larger global picture of human brain development should become clearer. At that point it will be impossible to deny the glaringly obvious group differences in brain function, and how these differences manifest themselves on a societal and economic level.

Being an HBD denier is growing more untenable every day.

A Race Against the Idiocracy

“I think we’re getting closer to harnessing neurogenesis to improve cognition and mood in humans. This research may also help explain a bit of a mystery in the field, which we still don’t understand, regarding how the hippocampus can be involved with both cognition – which is its classic function – and in mood and anxiety-related functions. Perhaps the fact that pattern separation affects both the cognitive and mood domains is the beginning of an answer to that paradox,” said Dr. Hen. _StemCells

René Hen, PhD, professor of Neuroscience and Pharmacology, in the Departments of Neuroscience and Psychiatry at Columbia University and the New York State Psychiatric Institute, has discovered a possible escape hatch by which some members of society might escape the Idiocracy. It involves the use of chemicals called "BAX inhibitors." Particular members of that class of drugs have the potential to preserve newborn stem cells in the brain's hippocampus. And doing that could make all the difference in the course of a person's life success and happiness.

After boosting the number of neurons in the hippocampus, an area of the brain involved in memory and mood, the researchers tested the mice in both learning and mood-related tasks and looked for changes in behavior. The researchers found specific effects on learning tasks that involve a process called pattern separation, which is the ability to distinguish between similar places, events and experiences.

“This process is crucial for learning because it enables us to know whether something is familiar or novel,” said Dr. Hen. “If it is familiar, you move on to the next bit of information; if it’s novel, you want to be able to recognize that it’s new and give it meaning. These mice, with just more adult-born neurons, and no other changes in the brain, basically learn better in tasks where they have to discriminate between similar contexts.”

Earlier strategies for manipulating neurogenesis, according to the investigators, were broader and less specific. “In addition to stimulating neurogenesis, these earlier methods exerted many other effects on the brain. As a result, you never knew with these older manipulations what’s due to neurogenesis, or what’s due to the other effects that these manipulations cause, and, indeed, what we find is that when you stimulate just adult neurogenesis, you actually get a subtle effect. Unlike broader manipulations, it does not affect all forms of learning, it’s very specific to tasks that require pattern separation,” said Dr. Hen.

Pattern separation is not only important for learning; it may also be important for anxiety disorders, including post traumatic stress disorder (PTSD) and panic disorder. People with PTSD, say the researchers, have a more generalized fear response, so that when they are placed in a situation that reminds them of even one aspect of their trauma, they frequently have a full fear response.

...The researchers say that the genetic strategy used to stimulate neurogenesis in their experiments can be mimicked pharmacologically, potentially leading to the development of new drugs to reverse pattern separation deficits. One such class of drugs the investigators are currently testing – BAX inhibitors – works by blocking cell death.

“These drugs are basically doing the same thing that we did with our genetic manipulation-namely, increasing the survival of the young neurons which normally undergo a process of cell death that eliminates at least half of these neurons. Now instead of dying, the neurons will go on to survive,” said Dr. Sahay.

Some BAX inhibitors have been developed for stroke research, where the goal has also been to prevent neurons from dying. The Columbia researchers plan to begin testing the BAX inhibitors in mice shortly. And if they produce cognitive benefits, the testing will be extended to clinical trials to determine if there’s also a beneficial effect in humans. _StemCells

This is all related to the length of time required before antidepressants are able to bring about a full "antidepressive response." The full effect of modern antidepressants requires new stem cell production in the hippocampus -- but that takes time to achieve. Drugs capable of rapid and prolonged increases of hippocampal stem cells could conceivably keep anxiety and depression at bay, while improving a person's cognitive capacity.

No, this is not NZT. As mentioned here previously, a drug that could achieve the effect of the fictional NZT would have to stimulate changes in gene expression on multiple levels, and across a wide range of brain centers.

Smart drugs alone will not achieve the goal of smarter, better-rounded, and happier humans. Educational and environmental interventions would also be necessary, to blunt the Idiocratic brainwashing effect of modern media, modern academia, and modern popular culture, while allowing the brain to develop newer, more functional pathways.

Realistically, it will take 15 years at the earliest to see the early promise of this type of medication come to fulfillment. But a single ray of hope in the distance is worth a lot to a person immersed in the modern rush to Idiocracy.

More 5April2001: An example of rapid brain plasticity in human adults
The PNAS Abstract from the actual study

Enlightening Video on Nerves into Brains

Starting with how neuroscientists mapped the brains of roundworms, the video moves ahead to the 3D mapping of a mouse retina and visual cortex. Finishing with the human brain connectome project, the video presents a useful introduction to how nerves fit together to make brains, for the curious.

Having a detailed 3D image of the static brain is just the beginning, of course. What you need is a dynamic 3D image of brain structure at all scales, superimposed by dynamic electromagnetic and blood flow data. In addition one would need dynamic detail at the molecular level for arterial, venous, lymphatic, CSF, intracellular and extracellular fluids and structures of the brain. Finally, one would need to know what was happening to the individual in real time -- both inside the body and outside the body.

At that point, one might begin to understand what was happening in the brain -- and perhaps take educated guesses about the mind. First person reports from the subject herself could refine one's approach.

From that preliminary position, you just take it from there, like in a jazz improvisation.

Video H/T neuropsychological.blogspot.com

Shining a Light On A Truly Brave, New World

There is a tide in the affairs of men
Which, taken at the flood, leads on to fortune;
Omitted, all the voyage of their life
Is bound in shallows and in miseries.
On such a full sea are we now afloat,
And we must take the current when it serves,
Or lose our ventures. _JuliusCaesar (IV.ii.269–276)

Sometimes the difference between success and disaster hinges upon a small decision. But making hard decisions requires courage -- or does it? Perhaps the requirement for making tough decisions is the ability to overcome the anxiety and fear that decision-making often entails? And the key to overcoming anxiety and fear may be as close as the nearest light source.

"I've never seen anything like it," says Kay Tye, a postdoctoral researcher in Deisseroth's lab and lead author on the study. Mice are naturally fearful of exploring open areas, she explains. Under normal circumstances, the animal "will poke its nose out and then scurry into a corner," says Tye. "But when you turn on the light, the animal begins exploring the platform with no visible signs of anxiety. Then you turn the light off, and it scurries back in to the corner."

...The researchers engineered mice to express light-sensitive proteins in specific cells in the amygdala that send out neural wires, known as axons, to different substructures. Using a specially designed fiber-optic cable implanted in the animal's brain, researchers found that aiming the light to activate one specific circuit had an immediate and potent effect on the animal's behavior.

..."Our understanding of the more precise circuitry within the amygdala is just now beginning to take off," says Kerry Ressler, a neuroscientist at Emory University who was not involved in the study. "Optogenetics, where scientist can activate specific cell populations and even parts of cells, is a powerful approach to dissect how the amygdala modulates fear and anxiety."

Ki Ann Goosens, a neuroscientist at MIT who was not involved in the study, says the research could help explain individual variation in baseline anxiety levels. "The findings tell us that this circuit contributes to an individual set point for anxiety," she says. _TechnologyReview

Tiny brain circuits can make all the difference in a person's life. A society comprising fearful, anxious, security - fixated persons, will have a far different destiny than a society made up of of imaginative, thoughtful, and courageous persons.

Perhaps it is no accident that most western societies find themselves clinging to present security at the expense of their own futures. That is the way of a cringing and shrinking death at one's own cowardly hands.

Besides a mastery of fear and anxiety, persons will also require wisdom and logical thinking skills, if they wish to catch the tide at its flood, sailing on to fortune. Logic must have both courage and wisdom, or it will be left either paralysed, or will find itself a force of wasted -- or even destructive -- effort.

Research can only reveal tiny, disconnected pieces of the current conundrum. But an integrated solution requires a wider-ranging mind than one finds in most lab rats, dependent on government funding and constraints of all kinds. Rather than huddling together in institutions and special-interest lobbies and unions, people of the next level will require courage, wisdom, logic -- and competence.

One must not only know what needs to be done when, and have the courage to do it, but also know how to do it properly and effectively.

A Bright Clear Knowledge Threatens the Established Order

No one comprehends the world in which he is immersed. Consider it a given starting point. There are ways to bring up a child capable of a far better understanding of his surroundings, but the established order has a vested interest in keeping things the way they are.

In Australia, scientists are working on a "thinking cap" which boosts creativity. They are at a very primitive stage, as of yet. But Allan Snyder, director of the University of Sydney's Centre for the Mind, thinks he is making progress.

Another interesting Australian innovation which may lead to improved thinking and brain development, is "Mathletics." Mathletics gives learning power to families and students themselves, leaving massive and extortionate educational systems with fewer justifications for their existence.

Scientists are learning more about how the brain is connected in networks. We are learning how young brains develop and prune themselves to become more efficient over time.

We are also becoming more interventionist when things go wrong. Brain implants are becoming smaller, more sophisticated, and more biocompatible. We are seeing a cyborg future, for many.

As we learn to grow more powerful, more imaginative, and clearer thinking brains, the massive infrastructure of inter-locking institutions grows at risk. Justification for the ruinously expensive system of institutions underlying modern societies is already vanishingly weak. As humans grow smarter and less tolerant of institutional bullshit from the power structure, a revolution will be brewing.

Diffusion Tensor Imaging Becoming Super Brain Assessment Tool

“While particular brain regions are important for specific functions, the capacity of information flow within and between regions is also crucial,” said study leader Scientia Professor Perminder Sachdev from UNSW’s School of Psychiatry.

“We all know what happens when road or phone networks get clogged or interrupted. It’s much the same in the brain.

“With age, the brain network deteriorates and this leads to slowing of the speed of information processing, which has the potential to impact on other cognitive functions.” _Science Alert

University of New South Wales researchers have utilised advanced diffusion tensor imaging (PDF research article) along with powerful computational tools to assess the efficiency of the total brain network of white matter, and watched overall brain processing speeds as they slow due to ageing.

The research team, led by Scientia Professor Perminder Sachdev from the UNSW School of Psychiatry, has mapped the network of fibres or ‘white matter’ for the first time, allowing them to examine the strength of connections between different cortical regions, or ‘grey matter’, which are responsible for specific functions. In the past, most research has focused on the more complicated grey matter without looking at how information flows between separate regions.

A new type of magnetic resonance imaging (MRI) called diffusion tensor imaging (DTI) combined with powerful computers allowed the team to create the map and see the whole network in great detail.

“Using a mathematical theory you can see how strongly the different regions are connected to each other,” Professor Sachdev said. “You can basically look at the efficiency of the network and with ageing, we can see a reduction in the efficiency of these networks.”

“What we wanted to see is how this relates to cognitive function, and we found that the best relationship was with processing speed, which makes sense because we’re talking about strength of information connections.”

Other areas strongly affected by the efficiency of neural networks were executive functions that manage other brain processes and the ability to navigate in space, known as visuospatial function.

Sachdev said the findings could help to some extent with dementia research, by offering another way of looking at the condition, but had already helped explain what happens in the brain when physical reaction time slows down in older people.

“It’s not that they can’t do the task, it just takes longer, and we have shown that this is related to structural changes in the brain, in terms of its neural networks.”

“The next step is looking at what determines the efficiency of these networks. We want to see if they are flexible or plastic, and whether maybe we can intervene.”

...The results of the study, which was based on a sample of 342 healthy people aged between 72 and 92, have been published in the January edition of the Journal of Neuroscience. _AustralianAgeingAgenda

Here is more from science alert Australia:

In the study, the researchers performed magnetic resonance imaging (MRI) scans on 342 healthy individuals aged 72 to 92, using a new imaging technique called diffusion tensor imaging (DTI).

Using a mathematical technique called graph theory, they plotted and measured the properties of the neural connectivity they observed.

“We found that the efficiency of the whole brain network of cortical fibre connections had an influence on processing speed, visuospatial function – the ability to navigate in space – and executive function,” said study first author Dr Wei Wen.

“In particular greater processing speed was significantly correlated with better connectivity of nearly all the cortical regions of the brain.”

Professor Sachdev said the findings help explain how cognitive functions are organised in the brain, and the more highly distributed nature of some functions over others. _Science Alert

It is important to stress the difference between speed of nerve transmission and speed of information processing for the brain. The two are related, and both are measurable (or calculable) using the DTI computational techniques, but information processing is a much higher order process than mere nerve conduction velocities. Knowing processing speeds -- particularly being able to compare whole brain processing and subsystem processing speeds and efficiencies -- provides more information.

Diffusion Tensor Imaging (DTI) can be used to assess several aspects of brain functioning, including general intelligence and executive function. It can also be used to assess multiple types of brain pathology, including schizophrenia.

Better brain imaging techniques provide clinicians and researchers with better information with which to form theories and plan therapies. As brain ageing comes to be seen more as a reversible pathology, more advanced diagnostic tools and therapeutic methods will be made available more widely.

Cross-posted from an earlier Al Fin Longevity posting

Beware the Spying Optical Needle: It Can See Your Thoughts

Dubbed the optical needle, it is 500 to 1,000 microns in diameter at its tip—about half the width of a grain of rice. While the device resembles a scaled-down version of the endoscopes now commonly used for surgery, the tiny lens is slightly different. The small size of the device means that a curved lens, typical in most microscopes, is impractical. Instead, its lens is made from a material that has internal variations in its refractive profile to guide rays of light.

...In the new study, published online this month in Nature Medicine, researchers demonstrate that they can use the micro-endoscope to observe the same spot in the brain over time. _TechnologyReview

Brain_Probe
Brain probes are becoming smaller and more clever. The "optical needle" is a micro-endoscopic probe from Stanford, which is capable of long-term direct observation of local brain circuits, deep inside the brain.

A new type of micro-endoscope lets scientists watch nerve cells and blood vessels deep inside the brain of a living animal over days, weeks, or even months. A team led by Mark Schnitzer, associate professor of biology and applied physics at Stanford University, developed the endoscope—an optical instrument used to peer into the body—along with a system to insert it into the same spot time after time. This feature allowed scientists to track changes in minute features, such as the connections between cells in the brain.

"I think it will be a potent tool for tracking properties of cells over long periods of time in response to changes in the environment, over the course of learning, during aging or the progression of disease," says Schnitzer. Some developmental and neurodegenerative diseases, for example, damage connections between neurons deep in the brain.

Of particular interest to neuroscientists is the hippocampus, an area deep in the brain that is crucial to memory. Previously, scientists had been able to look at regions such as this one in detail only with highly invasive methods and at a single point in time. "But a lot of brain disorders occur slowly," says Schnitzer. "We don't just want a snapshot, we want a time-lapse [movie] on a time scale that is relevant to the progression of the disease." _TechnologyReview

The researchers first insert a tiny indwelling guide tube, then pass the optical needle through the tube for optical micro-imaging. Since the tube remains in the same location, the researchers can come back time and again to image the same location -- providing an ongoing time-lapse record of changes in cellular structure at that spot. The tool should provide many opportunities for study, and eventual clinical application.

By placing guide tubes in strategic locations around a brain tumour, for example, clinicians might be able to monitor the effects of experimental treatments.

But what about seeing your thoughts? Be patient, grasshoppers. Current optical needle technology can observe changes in the micro-structure of local brain circuits. As the technology improves, distributed observers will be able to watch a brain learning with experience. Combined with sophisticated deep brain stimulation and advanced neurofeedback, a sufficiently motivated mad scientist could learn to play any human brain like a piccolo.

How Do Your Sparks Spray? How Do Your Dominos Fall?

PO

A human brain works very much like a chain of small explosions -- tiny sprays of spark strung together in chains of rising and falling energy potentials. Like falling dominos, the chain reactions trace tracks that were pre-determined years ago by unique combinations of novel experience working within a novel genetic substrate.

...the "synfire chain" model, in which neurons fire in a chain reaction -- each one triggering the next in the sequence, like a cascade of falling dominos.

In a new study, which appears in the October 24 online issue of Nature, Fee and colleagues have now tested this idea using intracellular recordings, an approach that can record tiny voltage fluctuations in individual HVC neurons. In a technical tour-de-force, they developed a method in which these recordings could be made while the bird was freely moving around his cage and engage in natural behaviors such as singing.

Their results support the chain of dominoes model. When individual HVC neurons fire, they do so suddenly, as if hit by the preceding domino. There was no prior build-up of activity; instead, each neuron remained silent until its turn came to fire, at which point it showed a sudden burst of activity, presumably caused by excitatory input from the previous neuron in the chain. In further experiments, the authors showed that this burst of activity is triggered suddenly by an all-or-none influx of calcium through specialized membrane channels that open in response to this excitatory input. _SD (MIT study)

But those chains of dominos had to be set up "just so." How were these patterns of chain-reaction set up to begin with?

When rats and human beings create a new memory, they are effectively forming a representation, or “mapping” that location or moment and encoding it in their brains. Using advanced monitoring technologies, Markus has been able to actually “hear” place cells in a rat’s mind firing as the animal creates a memory and encodes its route through a maze. The burst of place cell activity the rat experiences when it searches for a food source is conveyed as a staccato series of “pops,” like tiny firecrackers, when picked up by the high-tech monitors in the lab. _PO (U. of Connecticut)

The intermediate details of cascading memory formation depend upon the particular type of memory that is being laid down -- sensorial, spatial, experiential, conceptual etc. -- but the underlying neuronal process is the same, and intriguingly complex.

A human's brain becomes very much like a dynamic sculpture over time, revealing intricate sprays of light and dark, as circumstances inevitably vary in its environment. Circumstances change, but they often vary in cycles. As the cycles of circumstance repeat, so do the dynamic chain reactions of spraying sparks and falling dominos. For example: How do we know what someone close to us is going to say before they say it? How do we often anticipate the exact words an author will use to describe a character or a scene?

We are attracted to other brains both for their ability to surprise us, and for their ability to create a comforting stability around us. In that sense we are really not that different from children.

The differences in our genes place each of us in a different starting point on the path to a well-sculpted brain. Our brain dominos will fall differently -- and will form different chains of falling -- depending upon how our genes (and epigenetics) are laid out in the beginning. Take one simple example: sleep.

Simple gene variations determine how well a person can function on limited sleep. This difference in function can easily determine the fate of an individual in a highly competitive society.

...The people with the DQB1*0602 gene variant were sleepier and more fatigued while both fully rested and sleep deprived. Their sleep was more fragmented. For example, those with the gene variant woke up on average almost four times during the fifth night of sleep deprivation, compared to those without the gene variant, who woke up on average twice. Those with the gene variant also had a lower sleep drive, or desire to sleep, during the fully rested nights....“This gene may be a biomarker for predicting how people will respond to sleep deprivation, which has significant health consequences and affects millions of people around the world. It may be particularly important to those who work on the night shift, travel frequently across multiple time zones, or just lose sleep due to their multiple work and family obligations. However, more research and replication of our findings are needed,” said lead study author Namni Goel, PhD, of the University of Pennsylvania School of Medicine in Philadelphia. _AAN (U.Penn, NIH)

Sleep is a complex phenomenon which determines much of a person's trajectory through life. There are certain moments in time where an alert mind makes the difference between life and death, success and failure. One tick of the clock and that moment has passed. If sleep -- and the ability to function optimally on limited sleep -- is genetically determined, then how many other determinants of a person's quality and quantity of life are hidden in the molecules?
We are learning more about how the human brain is re-charged and re-built during sleep. A person's memories -- the "lay of the land" in a person's brain -- is re-built and re-furbished on a regular basis, with slight modifications over time. Sleep is a critical part of that ongoing program of maintenance.

And so we humans, we slightly advanced apes, blunder into the future riding a cresting trajectory of saccadic memories. It is a bit like riding a surfboard, except that we are the surf, the board, and the rider. The environment is the storm hundreds of miles offshore, and our genes are the shallowing seabottom and the reefs and kelp. Always a balancing act, never exactly the same wave twice. Learning to let go is the hardest part.

New Hope for Restoring Lost Memory

Researchers estimate that roughly 20 to 30 percent of people age 75 and older have elevated glucocorticoid levels (more precise figures aren't available). Most affected is so-called declarative memory, the ability to learn new facts and remember, for example, lists. People who suffer age-related memory loss are at higher risk for developing Alzheimer's and other forms of dementia, though the condition is not itself considered a form of dementia. _TechnologyReview

A research team at the University of Edinburgh have developed a new compound that appears to prevent and reverse age-related memory decline in mice. Their approach utilises a "gene knockout" approach against an amplifier of glucocorticoid effect present in brain cells.

"What's most surprising is that even short-term inhibition was able to reverse memory loss in old mice," says Jonathan Seckl, a professor of molecular medicine who was involved in the research. "I don't think people had realized this was so reversible. It takes [the animals] back to being relatively young."

The researchers hope to develop equivalent human therapies and are now more extensively studying the safety of a closely related compound in animals. They aim to begin human testing within a year.

Scientists have long known that glucocorticoids--a class of steroid hormones that mediate our response to stressful situations--play a role in age-related memory decline. Although short-term exposure to glucocorticoids enhances the formation of memories during stressful situations, chronically high levels of the hormones are linked to greater memory loss with age, both in humans and animals. The exact mechanism underlying this link is unclear, but researchers theorize that excess exposure to the hormones makes parts of the brain more vulnerable to damage.

Seckl and his collaborators focused on an enzyme called 11β-hydroxysteroid dehydrogenase type 1 (11 β-HSD1). This enzyme generates an active version of the key glucocorticoid hormone within brain cells and some other tissues, providing a target for fine-tuning the system without blocking the overall stress response. Tinkering with the enzyme seems to have little effect on blood levels of glucocorticoids, which are produced in the adrenal glands. Instead, "this enzyme acts as an intracellular amplifier of glucocorticoids," says Seckl. "If you take out the amplifier, you still have stress hormones, but they shout less loudly and cause less wear and tear."

The Edinburgh team showed that knocking out either one or both copies of the gene for this enzyme in mice preserved the animals' memory into old age. To determine whether blocking the enzyme could improve memory in already aged animals, researchers then developed a compound designed to cross into the brain and inhibit the enzyme. Just 10 days of treatment in two-year-old mice--the maximum lifespan for a typical lab mouse--was enough to improve the animals' performance on a test of spatial memory. The treatment "returned mice to the equivalent of when they were young and fully functioning," says Brian Walker, another researcher involved in the study. "It's important to emphasize that we are trying to target the pathology--the role that glucocorticoids play in age-related memory decline--not just globally improving memory." The research was published last week in the Journal of Neuroscience. _TechnologyReview

Brian Wang looks at another approach to augmenting human brainpower

The Brain: Wired and Introspective

ImageSource

The brain contains tens of billions of neurons, and trillions of synaptic connections (plus unknown numbers of other types of connections). Scientists from several universities are collaborating in an attempt to improve our understanding of the brain's "wiring diagram." At its best, it will still be crude compared to the real thing, but it's a start.

Working with $30 million and just half a decade, the Human Connectome Project aims to create a first-of-its-kind map of the brain’s complex circuitry, detailing every connection linking thousands of different regions of the brain.

The team consists of 33 researchers at nine different institutions, including Washington University School of Medicine in St. Louis and the University of Minnesota, the lead universities in the effort and the sites where much of the brain-scanning will take place. Their success will depend in part on another HCP grant to another research consortium headed up by Massachusetts General Hospital and UCLA that will develop advanced, custom brain scanners with higher spatial resolution and increased sensitivity. The funds themselves come from various bodies within the National Institutes of Health.

How big is the project? It’s at least 90 billion neurons big, but that doesn’t even convey the enormity and complexity of the human brain. There are something like 150 trillion synapses – the connections between neurons across which signals pass – that electrical signals must negotiate. These neurons and the connections between them make up the circuitry of the brain, and the HCP aims to create a better picture of that circuitry than we’ve ever had before. _PS

ImageSource

But brain researchers cannot sit around on their hands until others provide them with a more detailed map of the brain. They must continue to muddle through with what they've got, in trying to understand how the brain creates the world. One interesting aspect of brain function is the variation in accuracy between different persons' judgement of the accuracy of their own educated guesses. Scientists at University College London looked at this question of introspective accuracy recently.

A specific region of the brain appears to be larger in individuals who are good at turning their thoughts inward and reflecting upon their decisions, according to new research published in the journal Science. This act of introspection -- or "thinking about your thinking" -- is a key aspect of human consciousness, though scientists have noted plenty of variation in peoples' abilities to introspect...

...To begin, Fleming and Weil recruited 32 healthy human participants and showed them two screens, each containing six patterned patches. One of the screens, however, contained a single patch that was brighter than all the rest. The researchers asked the participants to identify which screen contained the brighter patch, and then to rate how confident they felt about their final answer. After the experiment, participants' brains were scanned using magnetic resonance imaging, or MRI.

Fleming and the researchers designed the task to be difficult, so that participants were never completely sure if their answer was correct. They reasoned that participants who are good at introspection would be confident after making correct decisions about the patch, and less confident when they were incorrect about the patch. By adjusting the task, the researchers ensured all of the participants' decision-making abilities were on par with each others'—only the participants' knowledge of their own decision-making abilities differed.

"It's like that show, 'Who Wants to Be a Millionaire?'" said Weil. "An introspective contestant will go with his or her final answer when they are quite sure of it, and perhaps phone a friend when they are unsure. But, a contestant who is less introspective would not be as effective at judging how likely their answer is to be correct."

So, although each participant performed equally well at the task, their introspective abilities did vary considerably, the researchers confirmed. By comparing the MRI scans of each participant's brain, they could then identify a correlation between introspective ability and the structure of a small area of the prefrontal cortex. An individual's meta-cognitive, or "higher-thinking," abilities were significantly correlated with the amount of gray matter in the right anterior prefrontal cortex and the structure of neighboring white matter, Rees and his team found.

...The new study will be published in the 17 September issue of the journal Science. Science is published by AAAS, the nonprofit science society. _PO

This variation of introspective accuracy and depth is likely to play a crucial role in the development of cultures and civilisations. There should be little question that both environment and genetics play a role in the ultimate complexity of the pre-frontal cortex and other cortical and sub-cortical centers which are involved. Testing the participants additionally for both IQ and executive functions (EF) would almost certainly reveal strong correlations between the three concepts.

Thinkers who develop complex cognitive structures must be able to "hold" multiple thoughts in their heads simultaneously, while weighing the "fitness" of slight variations in the cognitive models. These models must often be of a dynamic nature -- particularly for engineers and scientists of several types.

Popular culture tends to downplay the importance of the mental skills of top-level theorists and explorers of knowledge fields, but these are the people who determine the ongoing prosperity and security of a civilisation over time.

Western civilisation is going through a period of time when generations worth of capital is being skimmed and scavenged by a de facto ruling class, which values political correctness over real world validity -- as a matter of ruling class survival. That is too, too bad for the rest of us, who very much need for our institutions to be under the discipline of real world checks and balances....


Given how badly the ruling class is fucking up, I am mulling over a series of posts on the topic of "peaceful insurrection." You may want to consider what that term might mean. Hint: I am referring to something a bit more determined and forceful than the "Tea Party" type of anti-big-government political movement. Yet still peaceful. How can that be? More later.

Being Dustin Hoffman, as Rain Man

Update 14Aug10: Brian Wang discusses other modalities of brain stimulation which have analogous effects on various brain functions as TMS. For now, we are limited to such crude tools as described, but we are actually not that far away from genuine targeted brain augmentation. Needless to say, we are also not far from targeted brain disruption.

DailyMail
According to scientist Alan Snyder, autistic savant skills are latent inside everyone's brain. But the way to bring out these skills is by suppressing -- or damping down -- normal activity in certain parts of the brain, using magnetic pulses.

... the extraordinary skills of savants are latent in us all and that they can be induced artificially owing to the inhibiting influence of low-frequency rTMS, that is, by turning off part of the brain, not by exciting it. _RoyalSociety

DailyMail
In a recent publication in Royal Society Transactions, Biological Sciences, Snyder elaborated on techniques of artificial production of savant skills using transcranial magnetic stimulation.

Low-frequency rTMS temporarily inhibits neural activity in a localized area of the cerebral cortex, thereby creating ‘virtual lesions’ (Hilgetag et al. 1999; Walsh & Cowey 2000; Hoffman & Cavus 2002; Steven & Pascual-Leone 2006). As discussed below in §4, the LATL is implicated in the savant syndrome for both autistic savants as well as savants who emerge late in life as a result of frontotemporal lobe dementia (Miller et al. 1998, 2000; Hou et al. 2000). _RoyalSociety

Snyder was able to use localised low frequency TMS to induce a number of savant skills, including induced drawing skills, induced proofreading skills, induced numerosity (see graph below), and reduced false memories.

Snyder_RoyalSociety
TMS is applied from outside the brain, unlike deep brain stimulation (DBS). The effect of TMS on the brain depends upon several factors, including the frequency and amplitude of the pulses, and the proximity to particular parts of the brain. High frequency TMS over the frontal lobes, for example, has been beneficial in improving the language memories of Alzheimer's patients. So you see that TMS can be used to temporarily block neural activity, or to temporarily augment neural activity -- in chosen locations of the brain.

There are many approaches to using electromagnetic stimulation for brain research and therapy, which are quite promising "top-down" research approaches. Combined with the many "bottom-up" (example) approaches to the study of brain development and function, the future of brain research is very bright.

Infographic by Smarter.org
You may someday be wearing an electromagnetic cap which can be switched to different settings, depending upon the task you want to accomplish. Such brain augmentation devices will have the ability to simultaneously dampen some parts of the brain while boosting the activity of other parts -- depending upon which mental skills, attitudes, or emotions you wish to emphasise or minimise at the moment. But whatever you do, do not allow anyone else access to the remote control!

H/T Singularity Hub via Impact Lab