The Female Brain's Reaction to Stress

Rutgers
Psychology professor Tracey Shores of Rutgers has discovered some interesting gender differences between the brains of male and female rats in their ability to learn immediately after being stressed.

The research, published Dec. 1 in the Journal of Neuroscience, has implications for the way stress-related disorders are treated in men and women.

Shors and her co-authors, graduate student Lisa Maeng and post-doctoral scholar Jaylyn Waddell, examined two brain regions important in learning and stress, the amygdala and the prefrontal cortex. The amygdala, a small almond-shaped structure located deep within the brain, senses stressful situations. The prefrontal cortex, in the front of the brain, is necessary for higher cognitive functions.

“These two structures are intimately connected to one another,” Shors said. “Therefore, we examined whether they communicate with one another to influence learning after stress.”

The researchers exposed male and female rats to stress, and then presented them with an associative learning task. During training, the rats learned to associate one event with another that occurred later in time. They played a tone and later stimulated the rats’ eyelids to elicit a blink. After the stimulus was taken away, most of the male rats responded to the tone by blinking on their own. Most of the females, however, did not blink in response to the tone, indicating that they had failed to learn that association. But the research also contained a neurological surprise for Shors, Maeng and Waddell.

When Shors and her colleagues disrupted the connections between the prefrontal cortex and the amygdala in some of the females, those females were able to learn the association.

“This wasn’t true for males," Shors said. "So, males and females are using different brain structures to learn after stress. In other words, females can learn after stress if the prefrontal cortex can’t ‘talk’ to the amygdala. From this, we conclude that males and females can use different brain circuits to learn after stressful life events.” _Rutgers

This study's findings are somewhat consistent with studies in humans from both USC in Los Angeles and researchers in Polish labs. Human males are more likely to analyse the dynamics of a stressful situation with the aim of taking definitive action to resolve the stressful stimulus. This male reaction requires the brain to assess a situation as clearly as possible, which may involve adapting known strategies to the situation or adopting entirely new strategies -- which requires learning.

Human females in the face of stress, tend to look for assistance from sympathetic onlookers, bystanders, or companions. This response requires reading facial expressions of others in the vicinity, as well as their capacity to render assistance. Such abilities are rather instinctive in the female brain, and require minimal learning or creative adaptation.

As to the female rats inability to learn (basic stimulus response conditioning) immediately after stress, the extent of applicability of the finding to human females would require further study. All that can be said with respect to the USC and Polish studies, is that the stereotyped human female response to stress does not typically require new learning, not that she would be unable to learn if necessary (either stimulus-response conditioning or more conventional conscious learning).

No one is proposing cutting frontal cortex pathways in human females for such studies, but brain researchers may soon have tools to allow temporary, selective disruption of targeted pathways. At this time, transcranial magnetic stimulation can disrupt particular cortical areas -- since the cortex is closest to the skull, and easiest to reach with extra-cranial magnetic fields. As scientists find better ways to focus such pulsed fields deeper into the white matter of the brain, more selective targeting should be achievable.

fMRI Neurofeedback Opening Windows into the Brain

TechnologyReviewWhen most psychologists think of neurofeedback, they think of EEG feedback. Certainly EEG feedback has accomplished some amazing clinical and scientific results, and is even beginning to show up in mainstream gaming applications. But the state of the art in neurofeedback and brain-machine interfacing is shifting to fMRI, due to a superior spatial resolution over the entire brain. (the actual state of the art may be combined EEG plus fMRI, but let's just look at fMRI for now)

U Penn researchers recently used fMRI neurofeedback in an attempt to discover if they could teach cocaine addicts to control certain brain functions.

Childress asked 11 healthy controls and three cocaine addicts to watch a feedback screen while alternately envisioning two 30-second scenarios: Repeatedly swatting a tennis ball to someone, and navigating from room to room in a familiar place. By analyzing whole-brain activity, researchers found that a part of the brain called the supplementary motor area was most active during an imagined game of tennis. They then linked this pattern to an upward movement of a computer cursor. They did the same with the navigation task, linking it to downward movement of the cursor. After four cycles or fewer—less than five minutes of training—the subjects had learned to alternate between the two states of mind, as well as associate each one with its corresponding cursor position. From there onward, they could move the cursor up or down with their thoughts.

...The researchers found that both addicts and healthy people could control their state of mind equally well, something Childress says is encouraging for future studies. "The patients who have trouble controlling their craving could still demonstrate control over this sort of non-emotional test," she says. That confirms what earlier studies had suggested: Addicts' cognitive control issues are not linked to more general thinking, but instead limited to more emotionally charged thoughts, like cravings.

However, Childress's team will need to develop specialized tasks to figure out how to apply this to addiction and other disorders. For therapy, "You really need feedback from localized regions that have to do with their disease, and have people learn to control them," says Rainer Goebel, a professor of psychology at the University of Maastricht in the Netherlands who has done similar work with depression patients. _TechnologyReview

As mentioned parenthetically above, the combination of EEG plus fMRI neurofeedback offers a superior tool, in that both spatial and time resolutions are optimised. When using neurofeedback to facilitate a brain-machine interface, one wants to optimise time resolution. When using neurofeedback to train in controlling brain responses, one would want optimal spatial resolution. As training programs become more specialised, each small improvement in spatial and temporal resolution will be treasured by researchers.

Powerful EEG neurofeedback tools have been used for assisting in brain rehabilitation after brain trauma or infarct, in treating severe autism, for treating depression, and in other neuro-psychiatric conditions. Clinicians are typically more daring than researchers when using such relatively safe tools, given the difference between the clinical environment and the research culture. Researchers are quite cautious, and appear almost plodding in their careful step by step approach to scientific knowledge. Clinicians, on the other hand, are often desperate to help in cases which seem hopeless. They are willing to take intuitive leaps, and work with what they find.

The difference between attempting to build a structure of knowledge from the bottom up, brick by brick, vs. the sudden achievement of disconnected but profound findings when taking a leap of faith, contributes to the wall of incomprehension which often grows between the research and the applied branches of a given science.

As fMRI neurofeedback tools (and combined fMRI-EEG tools) eventually move from the hospital and lab into the outpatient clinical setting, the possibilities of sophisticated feedback tools combined with VR techniques in normal brains, should be astounding. Non-invasive, non-toxic tools such as neurofeedback, offer little risk in comparison with surgical, pharmaceutical, invasive electrical, and radiologic tools that might be used in a clinical setting. Clinicians typically feel free to try new and unconventional approaches when there is little to lose and much to gain.

Al Fin Futurists place the transformative potential of advanced neurofeedback technologies at the highest setting.

In the Brain, Inhibition Sets Us Free

Our brains would not be able to function without inhibitory inter-neurons. The best description that I have read describing how interneurons control brain activity comes from Gyorgy Buzsaki's excellent book, "Rhythms of the Brain."

Scholarpedia presents a nice, brief description of inhibitory interneurons:

The importance of inhibition in the brain is aptly illustrated by the fact that in addition to excitatory principal cells, the brain contains diverse classes of specialized inhibitory interneurons that selectively innervate specific parts of the somatodendritic surfaces of principal cells and other interneurons. In the cortex, axon terminals of interneurons release gamma amino butyric acid (GABA) onto their synaptic targets, where the inhibitory action can compete with the excitatory forces brought about by the principal cells. However, inhibitory interneurons do much more than just provide stop signals for excitation. Proper dynamics in neuronal networks can only be maintained if the excitatory forces are counteracted by effective inhibitory forces. With only excitatory cells, it would be difficult to create form or order or secure some autonomy for transiently active groups, the hypothetical "cell assemblies", because in interconnected networks, excitation begets more excitation. Interneurons, by way of their inhibitory actions, provide the necessary autonomy and independence to neighboring principal cells. The functional diversity of principal cells can also be enhanced by the membrane domain-specific actions of GABAergic interneurons. Additionally, the opposing actions of excitation and inhibition often give rise to membrane and network oscillations which, in turn, provide temporal coordination of the messages conveyed by principal cells. _Scholarpedia

The image above and to the right illustrates a simple 2 neuron oscillator composed of an excitatory neuron and an inhibitory (inter) neuron. Input from the outside is always excitatory, and it is the turning on and off of the inhibitory neuron which accounts for the assembly's oscillation. The image below illustrates a 3 neuron oscillator, with the assembly on the left oscillating at 40 Hz and the assembly on the right oscillating at 30 Hz. The input from the NMDA neuron at the upper left determines which of the two oscillators is operating.

Image SourceReal neuronal assemblies in the brain are far more complex than these simple oscillators. But it helps to picture something simple before thinking about more complex and realistic assemblies -- which have a lot more things that can go wrong. Researchers at Baylor University have recently discovered a genetic variation that leads to dysfunction of inhibitory interneurons in Rett Syndrome -- a devastating neurologic disease of early childhood leading to severe problems of intellectual and motor development.

Children, mostly girls, born with Rett syndrome, appear normal at first, but stop or slow intellectual and motor development between three months and three years of age, losing speech, developing learning and gait problems. Some of their symptoms resemble those of autism.

These inhibitory (gamma-amino-butyric-acid [GABA]-ergic) neurons make up only 15 to 20 percent of the total number of neurons in the brain. Loss of MeCP2 causes a 30 to 40 percent reduction in the amount of GABA, the specific signaling chemical made by these neurons. This loss impairs how these neurons communicate with other neurons in the brain. These inhibitory neurons keep the brakes on the communication system, enabling proper transfer of information.

"In effect, the lack of MeCP2 impairs the GABAergic neurons that are key regulators governing the transfer of information in the brain," said Dr. Hsiao-Tuan Chao, an M.D./Ph.D student in Zoghbi's laboratory and first author of the report.

..."This study taught us that an alteration in the signal from GABAergic neurons is sufficient to produce features of autism and other neuropsychiatric disorders," said Zoghbi, a Howard Hughes Medical Institute investigator and director of the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital. _SD

It does not require much interference in the normal operation of the molecular biology of the brain to cause severe dysfunction. The pathway of the dysfunction -- from molecule to synapse to cell assembly to developmental and behavioural dysfunction -- is intriguingly complex on many levels.

My main interest in this regard, is the transient long distance synchrony of cell assembly oscillatory activity in different parts of the brain. It would take several lifetimes to understand such phenomena in all their variation, origination, and modification. The implications of such understanding to human learning, creativity, health and disease, personality, and so on, are profound.


Inhibitory Interneurons and Network Oscillations

Some background reading on the phase-locking of neural populations via inhibitory interneurons PDF [Notice: Opening PDF documents can tie up a browser for several moments. If you think you want to download a PDF document, you may want to right click and select "save linked content as" option.]

Human Oscillatory Brain Activity near 40 Hz Correlates with Cognitive Temporal Binding PDF

What Are You Afraid Of, Senorita Amygdala?

Scientists are beginning to learn how the brain learns to be afraid, and how learned fears are activated at the level of individual nuclei and cells in the amygdala.

In this week's issue of the journal Nature, a research team led by scientists at the California Institute of Technology (Caltech) has taken an important step toward understanding just how this kickoff occurs by beginning to dissect the neural circuitry of fear. In their paper, these scientists—led by David J. Anderson, the Benzer Professor of Biology at Caltech and a Howard Hughes Medical Institute investigator—describe a microcircuit in the amygdala that controls, or "gates," the outflow of fear from that region of the brain.

The microcircuit in question, Anderson explains, contains two subtypes of neurons that are antagonistic—have opposing functions—and that control the level of fear output from the amygdala by acting like a seesaw. _Eurekalert

Antagonistic neuronal types allow for finer control of output -- which allows us to preserve some of our dignity when surprised, at least.

Brain-Mind
A team of European scientists has looked at different parts of the central nucleus of the amygdala, and have discovered that the lateral subdivision of the central nucleus is involved in learning a fear response. The medial subdivision of the central nucleus is involved in the behavioural manifestation of a fear response.

Now, research involving several Swiss and German teams and a researcher from Inserm Unit 862, “Neurocentre Magendie”, in Bordeaux, has been able to identify, for the first time, distinct neuronal circuits within the central nucleus of the amygdala which are specifically involved in acquisition and control of behavioural fear responses. Details of these results are published in this week’s edition of the journal Nature.

...In that second step, real-time recording of the activity of the neurons in the lateral and medial subdivisions of the central amygdala, using unique electrophysiological techniques, made it possible for the researchers to identify the specific neurons, within the structures, which were involved in conditioning and behavioural manifestation of fear responses.

These neurons are inhibitor cells belonging to very organized and strongly interconnected neuronal circuits. Modification of the activity of these circuits enables the relevant behavioural fear response to be selected as a function of the environmental situation. _SB

Fear is at the center of primate learning, particularly the earlier stages. Much of the late early, middle, and latter parts of our lives involves the "papering over" of our raw learned fear responses, in order to avoid the unpleasantness of feeling afraid, and to allow us to act in groups without triggering contagious fear response chain reactions. Anxiety emerges when we are not sure what it is that we are afraid of at the moment.

There are good reasons why benzodiazepines, alcohol, and other anxiolytics account for so much economic activity.

Babies Born Ready for Introspection and Daydreaming?

Resting state networks are connected systems of neurons in the brain that are constantly active, even when a person is not focusing on a particular task, or during sleep. The researchers found that these networks were at an adult-equivalent level by the time the babies reached the normal time of birth.

One particular resting state network identified in the babies, called the default mode network, has been thought to be involved in introspection and daydreaming. MRI scans have shown that the default mode network is highly active if a person is not carrying out a defined task, but is much less active while consciously performing tasks. _SD

The resting state default mode network (DMN) appears as a particular mode of brain activity in the resting brain, primarily made in the posterior cingulate cortex (PCC) and the medial prefrontal cortex (MPFC), but also in the ventral anterior cingulate cortex (vACC), and lateral parietal cortex. The characteristic synchronised activity between these regions in the awake resting state, in light sleep, and even during anesthesia in monkeys. This network is supposed to represent mental activity in casual monitoring of the self and the environment and in daydreaming.

The discovery that such a network appears to be functional by the 40th week of gestation in newborns -- but not much before the 40th week -- suggests that the DMN may be important in the learning deluge which is triggered by the fact of the child's birth. Its development and activation appears to be timed to coincide with the normal time of delivery.

In other brain news:

EEG sleep spindles in stage II sleep may represent the transfer of memories from sub-cortical centers such as the hippocampus to cortical centers.

Transfer of motor skills to the frontal cortex from the basal ganglia appears to be crucial for these skills to become automatic

University of Utah researchers have made some important discoveries about how brain attentional networks are mapped in the intraparietal sulcus according to the specific type of stimulus being attended to.

University of the Netherlands researchers have discovered that besides being a great motivator, experiencing anger can bring pleasure.

Two studies looking at the brain's mitochondrial energy supply suggest that it is possible to determine a brain's metabolic age independent of chronological age, and to identify potential energy crises which may lead to Parkinson's Disease -- long before actual disease occurs, by understanding the brains energy and metabolic networks.

A thorough understanding of the brain requires intense study on many different levels, and via several different disciplines. Few individual researchers are capable of achieving such study at any significant depth or breadth. Fortunately we have computers to help us correlate findings across the wide array of the cognitive sciences, including neuroscience.

Brains of Children and Adolescents Inefficient, Details Emerge

More details are emerging from research at the Ecole Polytechnique Fédérale de Lausanne (EPFL) and the University of Lausanne (UNIL). Swiss scientists worked with researchers from Harvard and the Indiana University to map the brains of 30 children from age 2 to age 18.

A young child's brain is similar to the early Internet with isolated, poorly linked hubs and inefficient connections, say the researchers from EPFL and UNIL. An adult brain, on the other hand, is more like a modern day, fully integrated fiber optic network. The scientists hypothesized that while the brain does not undergo significant topographical changes in childhood, its white matter -- the bundles of nerve cells connecting different parts of the brain -- transitions from weak and inefficient connections to powerful neuronal highways. To test their idea, the team worked with colleagues at Harvard Medical School and Indiana University to map the brains of 30 children between the ages of two and 18.

With MRI, they tracked the diffusion of water in the brain and, in turn, the fibers that carry this water. Thiran and UNIL professor Patric Hagmann, in the Department of Radiology, then created a database of the various fiber cross-sections and graphed the results. In the end, they had a 3D model of each brain showing the thousands of strands that connect different regions.

These individual models provide insight not only into how a child's brain develops but also into the structural differences in the brain between left-handed and right-handed people, for example, or between a control and someone with schizophrenia or epilepsy. The models may also help inform brain surgeons of where, or where not, to cut to relieve epilepsy symptoms. _SD

We also know that the brain continues to mature into the middle and later 20s, with improved frontal lobe development and myelination. Some individuals may not achieve maximum maturation until they are nearly 30 years of age. (Psychological neotenates, of course, tend to never mature)

Unfortunately, the energy of youth begins to subside at almost the same time that the brain achieves its maximum power. The brain itself continues to change and develop throughout the rest of a person's life, but the absolute computing power of the brain -- for most persons -- begins to subside sometime in the 40s. This is most clearly seen in the careers of mathematicians and theoretical physicists, whose individual novel contributions generally drop off rapidly after they reach their 50s.

The experience and wisdom a person may accumulate in adulthood often helps to compensate for the loss of thinking speed and absolute cognitive power. As population demographics in the developed world continues to shift toward an older population, some of these issues will need to be confronted -- more money will need to be spent on research into reversing the mental and physical decline of aging.

Emory's Smart New Mice are Cognitive Knockouts

Image Source

The hippocampus plays a key role in our ability to remember what happens to us, and in navigating our way through the world around us. There is a great deal about the hippocampus which remains unknown. Consider the hippocampal area CA2, pictured above. Recent research from the medical school at Emory University has found that in mice, knocking out a gene (RGS14) radically changes the activity of hippocampal CA2 -- leading to mice with markedly enhanced spatial learning and object recognition abilities, when compared with their littermate controls.

Here is more:

Mice with a disabled RGS14 gene are able to remember objects they'd explored and learn to navigate mazes better than regular mice, suggesting that RGS14's presence limits some forms of learning and memory.
The results were published online in the Early Edition of the Proceedings of the National Academy of Sciences.
Since RGS14 appears to hold mice back mentally, John Hepler, PhD, professor of pharmacology at Emory University School of Medicine, says he and his colleagues have been jokingly calling it the "Homer Simpson gene."
RGS14 is primarily turned on in one particular part -- called CA2 -- of the hippocampus, a region of the brain known for decades to be involved in consolidating new learning and forming new memories. However, the CA2 region lies off the beaten path scientifically and it's not clear what its functions are, Hepler says.
RGS14, which is also found in humans, was identified more than a decade ago. Hepler and his colleagues have previously shown that the RGS14 protein can regulate several molecules involved in processing different types of signals in the brain that are known to be important for learning and memory. They believe RGS14 is a key control protein for these signals. _SD

Although the researchers have not identified any problems in the RGS14 knockout mice in terms of development or behaviour, it is too early to know whether such a simple gene knockout procedure in humans would be safe or effective -- for purposes of cognitive enhancement.

The finding is intriguing in the sense that the deletion of a single gene can have such a profound effect on the cognitive prospects of a mouse. A mutation in the right place could have the same result, in terms of improved learning. How many similar transformational surprises are waiting in the human genome?

We should not expect that any environmental intervention could come close to achieving a similar transformation of these specific cognitive skills as the genetic deletion achieved. Considering the somewhat conservative nature of evolution since the last great extinction event, it is unlikely that we have evolved in a way to take the greatest advantage of the potentials of our brains. In other words, our brains are likely to have many such genetic tweaks that are waiting to be discovered, to give us a leg up on our present and future challenges.

At this time it is still possible to envision a "next level" of human development. But such a hypothetical plane of development can only be reached by genetic means. How radical must such a transformation be? That depends upon where one starts. If humans continue on the present descent into Idiocracy, there will come a time when it will be too late to reverse the trend.

The easiest choice is to go back to sleep. Because, if you choose to be awake, the things you are forced to experience may be more than you can bear.

H/T Brian Wang

More on the "molecular conspiracy against plasticity" occurring in CA2

Oligodendroglial Progenitor Cells Suddenly Sprout Neurons!

The study identified the new pyramidal neurons in a part of the brain not typically associated with neurogenesis, the piriform cortex. The piriform cortex receives not only olfactory information, but also inputs from regions of the brain that are involved in emotion regulation and memory formation. Because of its privileged access to diverse brain regions, the piriform cortex is capable of tying odor representations to other types of information that are important for a wide range of behaviors. In animals and humans, activation in the piriform cortex is linked to odor memory and the emotional qualities of odors. In rodents, activity in this region is related to sexual behavior. _HND

Source

Scientists from UC Davis have discovered that neurons are being created from non-neuron progenitor cells in the brains of mice in early adulthood. These new neurons can apparently go on to play an important role in transmitting signals to "widespread" parts of the brain.

"We used to think that the sole destiny of oligodendroglial progenitor cells was to become myelin-forming oligodendroglia," Pleasure said. "Later it was shown that they also can generate other kinds of glial cells as well. We now have demonstrated that these oligodendroglial progenitor cells, which are widely distributed in the brain, and persist throughout life, also give rise to a group of large cerebral cortical neurons. Thus, oligodendroglial progenitor cells are truly multipotent."

The researchers found that precursors of glial cells, called proteolipid promoter-expressing NG2 progenitors (PPEPs, pronounced Pee-peps), give rise to glutamatergic pyramidal neurons, an important type of brain cell that sends long-range excitatory signals. PPEPs belong to a class of glial precursor cells called oligodendroglial progenitor cells (OPCs). These cells have been discovered only recently, and they hold tremendous promise for stem-cell regenerative medicine. They are the largest proliferating population of cells in the mammalian brain and spinal cord, and they could replace or repair injured cells.

“This study shows very definitively that PPEPs generate new neurons, that these new neurons have all the morphological and structural features which suggest that they are functionally integrated into the existing circuitry,” said Fuzheng Guo, the study’s lead author and a postdoctoral fellow in the Department of Neurology in the UC Davis School of Medicine.

...The current study follows findings published in 2009 that PPEPs in the immature mouse brain generate neurons in multiple regions, including the hippocampus and piriform cortex, and that these neurons survive into adulthood. They also found that PPEPs produced GABA-ergic interneurons in the immature brain. Prior to that study, scientists had assumed that the general class of glial precursor cells, called oligodendroglial progenitor cells (OPCs), could produce only glial cells, which create insulating sheets that wrap around neuronal projections and ensure speedy and reliable signal transmission. Instead, their results showed that these cells generate all three major cell types in the brain and spinal cord.

“Whether or not OPCs could form new neurons was not at all clear until our prior study,” Pleasure said.

The researchers focused on the piriform cortex in the current study because it was found to be a “hot spot” for PPEPs in the earlier study. The study was conducted using a genetic fate-mapping technique to track the lineage, or cell fates, of OPCs in the young adult brains of genetically-engineered mice. _HND

The study was in mice, but if similar mechanisms are at play in late adolescent and early adult humans, they might explain more of the differences between the adolescent and the adult brain.

We know that pathways of the brain develop over time, and that full maturation and myelinisation does not complete until the mid-twenties or slightly later. Late development of the pre-frontal cortex is probably part of the explanation for emotional and mental maturation in adulthood, but the development in early adulthood of new pathways involved in memory formation, emotional regulation, and sexual behaviours -- as described in the above study -- may provide deeper explanations into human emotional maturation.

Scientists will now have to look more carefully -- cast a wider net -- to try to understand the many nuances of brain development and the origination of new neurons and neuronal pathways. A few new answers, a lot of new questions.

20,000 Genes Under the Brain: Genes->Brain->Man

This image from a gene chip shows the activity of thousands of genes from tissue taken from a section of the hippocampus. Each spot denotes activity from a separate, single gene; the brighter the spot, the more active that gene is in the tissue sample tested.

_SciAm

An online interactive atlas of the human brain can show the activity of over 20,000 genes. Genes make the brain -- in conjunction with the environment. The brain makes the man. If we can observe the ongoing interplay of brain genes with environment, we will have a much clearer concept of why certain brains (men) behave the way they do.

Scientists can now determine where in the brain genes that encode specific proteins are active—including proteins that are affected by medications. Such information may help predict a drug’s benefits and side effects.

Using the atlas, researchers can zoom in on brain structures thought to be altered in mental disorders such as schizophrenia to find the molecular footprint of these diseases.
The atlas may provide molecular clues to memory, attention, motor coordination, hunger, and perhaps emotions such as happiness or anxiety.

Scientists have long sought to understand the biological basis of thought. In the second century A.D., physician and philosopher Claudius Galen held that the brain was a gland that secreted fluids to the body via the nerves—a view that went unchallenged for centuries. In the late 1800s clinical researchers tied specific brain areas to dedicated functions by correlating anatomical abnormalities in the brain after death with behavioral or cognitive impairments. French surgeon Pierre Paul Broca, for example, found that a region on the brain’s left side controls speech. In the first half of the 20th century, neurosurgeon Wilder Penfield mapped the brain’s functions by electrically stimulating different places in conscious patients during neurosurgery, triggering vivid memories, localized body sensations, or movement of an arm or toe.

In recent years new noninvasive ways of viewing the human brain in action have helped neuroscientists trace the anatomy of thought and behavior. Using functional magnetic resonance imaging, for instance, researchers can see which areas of the brain “light up” when people perform simple movements such as lifting a finger or more complex mental leaps such as recognizing someone or making a moral judgment. These images reveal not only how the brain is divided functionally but also how the different areas work together while people go about their daily activities. Some investigators are using the technology in an attempt to detect lies and even to predict what kinds of items people will buy; others are seeking to understand the brain alterations that occur in disorders such as depression, schizophrenia, autism and dementia. _SciAm

To assess gene expression in each small bit of tissue, researchers expose its RNA to a gene chip, or DNA microarray. These small devices are coated with clusters of identical DNA molecules, called probes, within separate areas. Each probe binds to the RNA of a specific gene—the one that contains a complementary set of chemical units, or bases. In a DNA molecule, the base adenine (A) sticks to thymine (T), and guanine (G) pairs with cytosine (C). Thus, the sequence that would bind to the strand illustrated above is (from top to bottom): T, C, C, T, G, C, A. In this way, a chip records which genes are active, and to what extent they are active, in the tissue sample

._SciAm

We will need to be able to detect brain-gene activity without chopping up the brain first, of course. Most people -- except perhaps for conscientious members of the Voluntary Human Extinction Movement, perhaps -- would balk at volunteering for a brain-gene map, if they knew their brains would have to be removed and sliced into sheets.

Peepholes Into a Coherent World: BrainWorks Series

NewScientist

To most of us, the brain is a "black box." It creates a seemingly coherent world with which we can interact, but we have only limited understanding how it does what it does. But when focal brain damage happens to persons, neurologists and neuroscientists can begin to see how the brain puts the pieces of the puzzle together to create the world.

It's here that people with visual agnosias come in handy. Behrmann had previously studied people with integrative agnosia, who have difficulty recognising and naming complex objects as a whole, and instead seem to pay unusual attention to their individual features. One person, for example, mistook a picture of a harmonica for a computer keyboard, presumably thinking the row of air-holes in the mouthpiece were computer keys (Journal of Experimental Psychology: Human Perception and Performance, vol 29, p 19). Others have mistaken a picture of an octopus for a spider, and a pretzel for a snake.

In 2006, Behrmann put one of her patients, known as SM, through a series of experiments alongside people with normal vision. All were shown a set of three-dimensional objects on a screen, each made from two simple geometric shapes. Afterwards, the volunteers were shown a stream of these images, with a few new objects thrown in. Their task was to report whether or not they had seen the objects before.

While those with normal vision performed with nearly 100 per cent accuracy, SM made some intriguing mistakes. He knew he hadn't seen an object before if it contained a new part, but those that had the same parts in a different configuration confused him. About half the time he mistook these for the familiar objects (Journal of Experimental Psychology: Human Perception and Performance, vol 32, p 1169).

To Behrmann, the results suggest that our brains normally construct objects from a series of smaller building blocks, which she calls our "visual vocabulary". To recall our concept of an object, she says, we form a mental map of the way these parts fit together. It was at this stage that SM failed. "He had a good representation of the parts, but understood little of how they were combined," Behrmann says. _NewScientist

NewScientist

Advanced brain imaging is helping neuroscientists to sort between the different the different varieties of visual agnosias. This helps us understand the different functional brain modules, and to learn where they are located.

Brain scans have revealed that people with visual form agnosia tend to have damage to the ventral (lower) part of the brain's visual area. People with optic ataxia, on the other hand, have damage to the dorsal (upper) part. This led to the idea that we have two streams of visual processing. The ventral pathway is necessary for perceiving or recognising an object, while the dorsal pathway deals with an object's physical location in our visual field and, if we need to perform an action on it, guides the movement of our bodies. For this reason, scientists often refer to the two processes as the perception-action, or the what-where, streams of visual processing.

...In fact, the closer neuroscientists look, the more modular our visual systems appear. MRI scans of people with and without agnosias have suggested that within the ventral stream, separate aspects of appearance are processed independently. This year, psychologist Cristiana Cavina-Pratesi at Durham University in the UK found that shape, texture and colour are all processed in individual regions (Cerebral Cortex, DOI: 10.1093/cercor/bhp298).

Yet our experience feels markedly different. When we consciously see something, all these disparate elements are stitched seamlessly together, so we know instantly that an apple is smooth, green and round. The question of how we accomplish this is central to the study of conscious perception.

...So important is the role vision plays in most people's everyday lives that most research has concentrated on visual agnosias. Now the hunt is on for similar disorders that affect the other senses. Recently, for example, neurologists found a person who could understand speech but not other sounds. Coslett, meanwhile, is investigating whether simultanagnosics also have trouble binding other sensory sensations together, such as sights and sounds.

Now you see it...

There are many visual disorders, typically caused by damage to specific parts of the brain.

• Simultanagnosia - Seeing only one object at a time, even when viewing a scene comprising many items
  
• Integrative agnosia - Inability to recognise whole objects, tending to focus instead on individual features of an object
  
• Visual form agnosia - Inability to describe the shape, size or orientation of objects, yet exhibiting no problem in manipulating them
  
• Optic ataxia - Ability to report the shape and size of an object, though attempts to manipulate it are clumsy
  
• Prosopagnosia - Failure to recognise the faces of familiar people
  
• Pure alexia (aka agnosia for words) - Inability to identify individual characters or read text, even though subjects are sometimes able to write
  
• Agnosia for scenes - Inability to recognise known landmarks or scenes
  
• Colour agnosia - Ability to perceive colours without being able to identify, name or group them according to similarity

_NewScientist

We have discussed the binding problem before, but it is important to begin to zero in on the parts of the brain which are involved in binding different aspects of reality together into a "coherent whole."

It is also important to begin to learn the actual dynamic mechanisms which are responsible for creating the actual "sensation of consciousness." Or, "The Feeling of What Happens," as Antonio Damasio expresses it.

It is only by delving deeply into these processes that we will be able to conceptualise ways in which we may profitably reverse-engineer a human brain. But that will mean letting go of the "algorithmic theory of conscious intelligence" which has waylaid so many well-meaning artificial intelligence researchers in the past.

Scientific American has a short piece on a parallel topic

Telling On the Brain...

OTBThe human brain is at an awkward stage in its evolution. Our brains have traveled part of the path away from ape consciousness. But only a small part.

Our brains are limited in many ways. Speed, for example. Our brains are able to detect and react to stimuli far more slowly than the brains of some insects. That is simply a result of how our brains are made and wired -- and is a good thing in many ways. But who wouldn't want to have quicker detection and reaction times, at least in sports such as basketball or boxing? Achieving such an advance would require a lot more overhaul of the human body and brain than most people realise.

Human brains tend to subconsciously ignore the unexpected. This is particularly true when our expectations are focused on something in particular. Admittedly, our brains are lazy. We tend to look for confirmation of believed hypotheses.

Overcoming the natural laziness of the brain is a never-ending chore. But we need to be clever about it. When practising a new skill, for example, we should vary our practise to prevent our brains from falling into too-well-practised ruts. This is as true for learning mental concepts and skills as it is for learning physical skills.

Our brains develop along fairly predictable paths to maturity. And then our brains begin to degenerate. We have very few "peak years" before this degeneration of matured brains begins to occur. We are developing some intriguing methods for treating this degeneration. Which is very fortunate, since we are also developing some early warning diagnostic tools for detecting particular sorts of degenerative changes. It would do little good to specifically identify the problem if we could not treat it.

Our brains will continue to evolve. Biological organisms cannot help evolving, just as the climate cannot help changing. It is the nature of complex, adaptive, quasi-chaotic systems to change. It is the nature of this brain evolution that is in question.

Now that we better understand which parts of the brain give humans cognitive advantages over their primate cousins, and now that we better understand how to promote the growth, survival, and differentiation of neural stem cells, it falls within the power of humans to influence their own brains' evolution.

Bolt on a few co-processor chips, advanced interfaces, and deep brain electrodes, and humans of the future are likely to resemble humans of today as much as modern humans resemble apes.

A Distributed and Most Plastic Brain

TED Talk by Michael Merzenich
The brain is more plastic than most of us believe.  We need to believe in the brain's plasticity, because there are many ways in which we could help our brains to better help us -- by taking the effort to strengthen weak brain functions which may be holding us back.

Our brains help determine who we are, but your brain is not just inside your skull.  It is also below your belt. We are led by our guts more than we know.  Whenever we let our brains fall back into its "default state", when we are not thinking about anything in particular, we are led down many a subconscious path whose origin and destination may lie well outside our skulls.  This is why many approaches to the rehabilitation of malfunctioning brains also involve the rest of the body.

The reason why it is important to consider ways in which we may help our brains help us, is that it is likely that all of us have run into particular obstacles and blockages -- over and over again.  Like "strange attractors", our own particular weaknesses tend to pull us toward them repeatedly.  But what if we could learn to change our default brain circuits so that such weaknesses no longer held us back?

In fact, particular parts of our default brains inform us as to "who we are" and "what we can do."  That is fine when our brain is telling us accurately that we can indeed do what we need and want to do.  But when our default brain states are telling us that we are helpless to achieve our needs and valid wants, we have a problem.

Although many of the parameters of our default brain states are largely determined by genetic factors, that is not to say that we are helpless to alter these states.  Persons who are depressed may find changing dysfunctional defaults to be particularly difficult.   But the brain can change for the better, and along with it the person.  But not without work.

That is where it is particularly important to understand that the rest of the body contains a significant proportion of the human nervous system.  Your digestive system may be especially important, but also the musculoskeletal system, the endocrine system, and the cardiorespiratoryvascular system.  Or maybe it is better to just think of it as the body-brain, working alongside the head-brain.

We need to be better than the zombies, led their entire lives by forces outside of themselves.  In a world that has devolved to suit zombies rather than free individuals, it is hugely important that we make the most of who we are.   First we have to understand what is possible.

A Burst of Consciousness: Out of Chaos

The line between mental chaos and a clear awareness is measured in milliseconds. If the brain can be distracted at just the right time, it will not be able to see what is in front of its nose. Researchers at the Weizman Institute of Science studied patients with implanted brain electrodes (in preparation for surgery). They were able to observe the sudden burst of brain activity in the higher visual brain centers signifying comprehension of an image.

The subjects looked at a computer screen, which briefly presented a 'target' image -- a face, house, or man-made object.

This image was followed by a 'mask' -- a meaningless picture for distraction -- at different time intervals after the target image had been presented. This allowed the experimenter to control the visibility of the images -- the patients sometimes recognized the targets and sometimes failed to do so. By comparing the electrode recordings to the patients' reports of whether they had correctly recognized the image or not, the scientists were able to pinpoint when, where and what was happening in the brain as transitions in perceptual awareness took place.

Malach: 'We found that there was a rapid burst of neural activity occurring in the high-order visual centers of the brain -- centers that are sensitive to entire images of objects, such as faces -- whenever patients had correctly recognized the target image.' The scientists also found that the transition from not seeing to seeing happens abruptly. Fisch: 'When the mask was presented too soon after the target image, it 'killed' the visual input signals, resulting in the patients being unable to recognize the object. The patients suddenly became consciously aware of the target image at a clear threshold, suggesting that the brain needs a specific amount of time to process the input signals in order for conscious perceptual awareness to be 'ignited.'' _SD

Consciousness is a time-critical process. The time constraints of conscious awareness depend upon electro-physiological activity across the cortical and sub-cortical brain. These electro-physiological activities are in turn dependent upon lower level physiological and biochemical activities in cerebral neurons, glia, and vasculature. But there is a great deal of subtle detail hidden out of sight, for now. It will require our brightest scientists to tease out the complexity from the chaos.

Earlier research by same researchers using fMRI to identify neuronal correlates of conscious activity

Global Neuronal Workspace Theory of Consciousness

PDF Look at how prefrontal activity can be temporarily "shut down" by perceptual processes PDF

PDF A glimpse at active unconscious assistance processes in conscious reading of handwritten materials PDF

300 milliseconds to conscious awareness