Steps to Better Human Brains

The main obstacle to a more abundant human future is the relatively poor quality of the average human brain. If only we could grow better human brains, and somehow make existing brains work better. Scripps Institute researchers may have discovered one piece of the puzzle, in the longer quest to the development of better human brains.

In mammals, the cortex is made up of six distinct anatomic layers holding different types of excitatory neurons. They are not the uniform layers of a cake, but rather, they are more like the layers wrapped around an onion. The smaller lower layers, on the inside, host neurons that connect to the brain stem and spinal cord to help regulate essential functions such as breathing and movement. The larger upper layers, closer to the outer surface of the brain, contain neurons that integrate information coming in from the senses and connect across the two halves of the brain.

The upper layers are a "relatively young invention," evolutionarily speaking, having been greatly expanded during primate evolution, said Mueller. They give humans in particular the unique abilities to think abstractly, plan for the future and problem-solve.

Previously, it was thought that all cortical neurons -- those making up both the lower and upper layers -- came from the same type of stem cell, called a radial glial cell, or RGC. A neuron's fate was thought to be determined by the timing of its birth date. The Scripps Research team, however, showed that there is a distinct stem cell progenitor that gives rise to upper layer neurons, regardless of birth date or place.

...Published in the August 10, 2012 issue of the journal Science, the new research reveals how neurons in the uppermost layers of the cerebral cortex form during embryonic brain development. _SD

They are saying that they think they have discovered a type of stem cell which gives birth to upper layer neurons, which seem to constitute one important difference between higher mammalian brains in primates, and lower mammalian brains, in neuroarchitecture.

More intriguing, they think the stem cell will migrate into the upper cortical layers regardless of when it is introduced. Would you like more upper layer neurons?

Cerebral Cortical Layering

Another fascinating bit of brain research comes from MIT, recently published in Nature:

There are hundreds of different types of neuron in the brain; most are excitatory, while a smaller fraction are inhibitory. All sensory processing and cognitive function arises from the delicate balance between these two influences. Imbalances in excitation and inhibition have been associated with schizophrenia and autism.

"There is growing evidence that alterations in excitation and inhibition are at the core of many subsets of neuropsychiatric disorders," says Sur, who is also the director of the Simons Center for the Social Brain at MIT. "It makes sense, because these are not disorders in the fundamental way in which the brain is built. They're subtle disorders in brain circuitry and they affect very specific brain systems, such as the social brain."

In the new Nature study, the researchers investigated the two major classes of inhibitory neurons. One, known as parvalbumin-expressing (PV) interneurons, targets neurons' cell bodies. The other, known as somatostatin-expressing (SOM) interneurons, targets dendrites -- small, branching projections of other neurons. Both PV and SOM cells inhibit a type of neuron known as pyramidal cells.

To study how these neurons exert their influence, the researchers had to develop a way to specifically activate PV or SOM neurons, then observe the reactions of the target pyramidal cells, all in the living brain.

First, the researchers genetically programmed either PV or SOM cells in mice to produce a light-sensitive protein called channelrhodopsin. When embedded in neurons' cell membranes, channelrhodopsin controls the flow of ions in and out of the neurons, altering their electrical activity. This allows the researchers to stimulate the neurons by shining light on them.

The team combined this with calcium imaging inside the target pyramidal cells. Calcium levels reflect a cell's electrical activity, allowing the researchers to determine how much activity was repressed by the inhibitory cells.

"Up until maybe three years ago, you could only just blindly record from whatever cell you ran into in the brain, but now we can actually target our recording and our manipulation to well-defined cell classes," Runyan says.

...The MIT team found that these inhibitory signals have two distinct effects: Inhibition by SOM neurons subtracts from the total amount of activity in the target cells, while inhibition by PV neurons divides the total amount of activity in the target cells.

"Now that we finally have the technology to take the circuit apart, we can see what each of the components do, and we found that there may be a profound logic to how these networks are naturally designed," Wilson says.

..."Conceptually, inhibition by subtraction and division is a very nice distinction," says Tony Zador, a professor of neuroscience at Cold Spring Harbor Laboratory who was not involved in the research. "It's a joy when something as theoretically appealing as division and subtraction actually maps onto the physiological substrate in such a fundamental way."

Increased inhibition by PV neurons also changes a trait known as the response gain -- a measurement of how much cells respond to changes in contrast. Inhibition by SOM neurons does not alter the response gain.

The researchers believe this type of circuit is likely repeated throughout the brain and is involved in other types of sensory perception, as well as higher cognitive functions. _SD

The Scripps paper in Science and the MIT paper in Nature are looking at different levels of brain architecture and activity, with some overlap.

To understand the brain we will have to piece together brain activity at multiple levels, from the molecular and genetic, up to electro-neurologic activity associated with specific behaviours. The two studies above fall somewhere in the middle of the range.

The challenge is to define how different levels of brain activity overlap and interlock, affecting each other from the bottom up and from the top down.

At that point, we may be in a position to modify particular cortical circuits, and alter the activity of particular areas of the brain.

Putting ourselves in a position to safely add stem cells to specific layers of cortex, or to modify the patterns of cortical inhibition in specific areas of the brain, might yield surprising dividends. Once we can do those things safely and well, we may be in a position to attempt much grander achievements.

We are already at the point where we can grow spontaneously oscillating 3D neuronal networks in the lab. As we better understand how the distinct architecture of different networks in various parts of the brain, and how they function within the whole, we will be in a better position to grow custom cortical columns and centres in the lab, to match different parts of the cortex -- sensory, motor, and associative.

In the meantime, expect a great deal of advancement in brain-machine interfacing, as we move into a parallel, cyborg future.

Al Fin cognitivists would prefer to replace damaged or malfunctioning white and gray matter with living replacement tissue -- wetware. But while we are learning how to do that, a wide array of hardware replacements, augments, interfaces, and workarounds are likely to find use in brain trauma rehab, routine neurology and neurosurgery, and in routine mental health therapies.

Brain-Building Through Early Childhood Music

Lately, parents have taken to playing Mozart to their infant children, in hopes that the music will provide an advantage in brain development for the child. Music and math, at least, are related. Many mathematicians are also skilled musicians. The long relationship between music and mathematics apparently runs deep in the structure of the human brain. But to provide a true advantage to the young, growing brain, may require more active participation than merely listening to the music.

Schlaug, now at Harvard Medical School in Boston, and colleagues including Marie Forgeard and Ellen Winner at Boston College, studied 31 children. The researchers collected detailed magnetic resonance images of the children's brains at age 6 and again at 9. Of the original group, six children faithfully practiced at least 2.5 hours a week in the time between the scans. In these budding musicians, a region of the corpus callosum that connects movement-planning regions on the two sides of the brain grew about 25% relative to the overall size of the brain. Children who averaged only an hour or two of weekly practice and those who dropped their instruments entirely showed no such growth. All of the children practiced instruments, such as a piano or a violin, that required two hands.

In every subject, the researchers found that the size of increase in the corpus callosum predicted the improvement on a nonmusical test that required the children to tap out sequences on a computer keyboard. Schlaug says the findings should settle the earlier debate by showing that musical training can enhance neural connections related to planning and coordinating movements between the two hands. His team is now following up with the same children to investigate whether their training had other benefits, such as improved memory or reasoning skills. __Science

Schlaug's findings appear quite significant, and you would expect that 25% growth in the corpus callosum, which connects the two cerebral hemispheres, would contribute to significant differences in other brain functions, and probably behaviours, besides musical performance. It is important to note that both instruments practised by the children required the use of both hands. Other instruments that require complex planning and coordination between the two hands would likely produce similar neuro-structural changes.

Music possesses an inner, mathematical structure. As young brains struggle to reproduce the inner structure of music through practise, is there any doubt but that their brains are changing--modifying themselves--to be better able to instantiate the musical structure through the musical instrument of choice?

The neuroanatomical changes only occurred in children who began regular musical practise before the age of 7, which suggests that an early start on musical training is important for those who eventually are to become virtuosos--for these particular instruments anyway.

The young brain develops along a sequential pathway. Critical periods or windows for different brain functions occur at different points in time. The window for vision is from two months to eight months. The social development and emotional control window is particularly open from ten to eighteen months. The window for math and logical skills is widely open between one and four years, and the window for musical development is between three and ten years--although perhaps one should not wait much beyond the sixth year to start. Source Other sources suggest waiting until five years before intense fingering training on musical instruments begins. Each child's developmental windows will be unique, although they should roughly follow the sequence suggested.

If children are to learn to speak a second language like a native, they should be introduced to the language by age ten. Source for more windows of development According to this source, social developmental windows remain open until ten years, particularly for empathy and envy.

The brain's neural axons myelinate in a roughly back-of-the-brain to front-of-the-brain direction, over the years. Trying to jump-start a particular brain function before the particular nerve pathways are myelinated, may produce less than satisfactory results. The windows of development for thought/emotional/motor skills follow the myelination sequence of the brain.

The pre-frontal lobes are the last parts of the brain to myelinate and mature--finally completing anywhere between the early twenties to the late twenties. Adolescents lack perspective and judgment at least partially due to the delayed maturity of the prefrontal lobes. Other neural functions can be mature, and the adolescent capable of phenomenal performance in many areas--and still lack basic adult-level maturity. This is common knowledge to any observer of adolescents and young adults.

We are all unique. We begin as unique individuals genetically, and grow more unique with every passing and diverging experience. Even identical twins display uniqueness in both genetics (copy number variants [CNV] and environmentally triggered epigenetic controls) and environment (intra- and extra-uterine).

The more we know about the unfolding of a child's being with time, the better able we will be to provide a more optimal environment for child development, and the acquisition of real world talents and competence.

But as the imaging technologies have become more sophisticated, the scientists have found many other neuroanatomical effects of the practice of music. Musicians have enlarged Broca's areas--the famous language area named after the 19th century psychiatrist.
Music practice correlates with an enlarged left planum temporale which is in Wernicke's area and lights up during both speech and music processing. What's going on with these language centers? One very clever study revealed the "bottomline". The scientists hooked up some musicians to the fMRI machines and had them listen to and follow the score of a Bach chorale. Unbeknownst to the musicians the investigators introduced an error into both teh performance and the score, to see what what would happen with this kind of 'exception processing' What happened was that the unexpected event lit up half a dozen areas of the brain which had prior thereto been considered part of the language-specific cortical circuitry.

So that's the bottom line of a decade of PET, MRI, fMRI and other imaging studies on the effect of the practice of music on the brain. The practice of music develops the language circuitry of the brain.
Source

Brain Rejuvenation Using Intravenous Cord Blood

Image Source

Researchers in Florida have managed to rejuvenate the brains of aging mice with a single injection of human cord blood cells in a peripheral vein. The single cord blood cell injection resulted in new progenitor stem cells in the mouse hippocampus, and new nerve cell formation.

Neurogenesis continues to occur throughout life but dramatically decreases with increasing age. This decrease is mostly related to a decline in proliferative activity as a result of an impoverishment of the microenvironment of the aged brain, including a reduction in trophic factors and increased inflammation.

We determined that human umbilical cord blood mononuclear cells (UCBMC) given peripherally, by an intravenous injection, could rejuvenate the proliferative activity of the aged neural stem/progenitor cells. This increase in proliferation lasted for at least 15 days after the delivery of the UCBMC. Along with the increase in proliferation following UCBMC treatment, an increase in neurogenesis was also found in the aged animals. The increase in neurogenesis as a result of UCBMC treatment seemed to be due to a decrease in inflammation, as a decrease in the number of activated microglia was found and this decrease correlated with the increase in neurogenesis.

The results demonstrate that a single intravenous injection of UCBMC in aged rats can significantly improve the microenvironment of the aged hippocampus and rejuvenate the aged neural stem/progenitor cells. Our results raise the possibility of a peripherally administered cell therapy as an effective approach to improve the microenvironment of the aged brain.

...Not only do the results of this study provide novel insight into the state of the aged stem cell niche, the ability of the UCBMC to exert their effects while being administered minimally invasively may make translation to the clinical setting more likely. For this reason it will be important in future studies to determine the most efficacious dose and dosing regimen. Nevertheless, this is the first time that a systemic injection of hematopoietic cells has been shown to restore the regenerative potential of the aged brain, providing a novel insight into how the regenerative potential of the aged stem cell niches could be restored.

...The effects of UCBMC have been attributed to changes in the microenvironment of the brain, through the release of trophic factors or by reducing inflammation, and not by a direct replacement of cells [21-23]. UCBMC contains a number of cell types including B-Cells and T-Cells, as well as, mesenchymal and endothelial progenitor cells. UCBMC is also a rich source of CD34⁺ hematopoietic stem cells [24-26]. It was recently demonstrated that a systemic injection of UCBMC cells could suppress inflammation in the brain following stroke. Moreover, the effects of UCBMC cells seemed to shift the cytokine expression from a Th1 response to a Th2 response [20,23,27]. In addition to the immune modulatory effects, UCBMC cells also produce a number of trophic factors including, but not limited to, VEGF, nerve growth factor, and cytokine colony stimulating factor-1, thrombopoietin, and IL11 [20,28,29]. ___BiomedCentral__via_madscience__via__TechnutNews

It is important to understand that the cells that were injected into the peripheral veins of mice were human umbilical cord blood mononuclear cells (HUCBMCs). The results are somewhat startling, given that the injected cells were not neural stem cells, the cells were not injected directly into the brain, and the cells were given in a single dose only. It will be important for the researchers to tease out the important cellular and trophic factors present in the UCBMC's that may have led to the rejuvenatory effects.

This is a line of research that I am interested in following further.

Case Study in Adult Neuroplasticity: Charles Darwin

Thanks to Alvaro at SharpBrains for this fascinating peek into how Charles Darwin's thinking changed over his adult life.

I have said that in one respect my mind has changed during the last twenty or thirty years. Up to the age of thirty, or beyond it, poetry of many kinds, such as the works of Milton, Gray, Byron, Wordsworth, Coleridge, and Shelley, gave me great pleasure, and even as a schoolboy I took intense delight in Shakespeare, especially in the historical plays. I have also said that formerly pictures gave me considerable, and music very great delight. But now for many years I cannot endure to read a line of poetry: I have tried lately to read Shakespeare, and found it so intolerably dull that it nauseated me. I have also almost lost my taste for pictures or music. Music generally sets me thinking too energetically on what I have been at work on, instead of giving me pleasure. I retain some taste for fine scenery, but it does not cause me the exquisite delight which it formerly did. On the other hand, novels which are works of the imagination, though not of a very high order, have been for years a wonderful relief and pleasure to me, and I often bless all novelists.

Darwin's Autobiography

Darwin's own writing style apparently changed over the years--to his own satisfaction.

Formerly I used to think about my sentences before writing them down; but for several years I have found that it saves time to scribble in a vile hand whole pages as quickly as I possibly can, contracting half the words; and then correct deliberately. Sentences thus scribbled down are often better ones than I could
have written deliberately.

ibid

That is a technique that I have found useful as well, even in short comments. The first sentence I write is often useful as a summary, after I work through the ideas a little better. It helps to put the ideas out in the open first for modification and reconstruction.

Darwin's brain experienced neuroplasticity and modification from the "overuse" of some faculties at the expense of other faculties--such as appreciation of poetry and music. His observations of the natural and human worlds may have gained a certain rigour and precision in this process of "selective cultivation" of cortical real estate.

If Darwin had been given the opportunity to relive his life, and thus was able to carry out his plan-in-hindsight of listening to music and reading poetry at least once a week--would his scientific writings have been as clean and precise? An interesting question.

While the neuroplasticity of both motor and sensory cortex following strokes, other denervation, and amputation, are well documented, the neuroplasticity of the associative cortex--prefrontal lobes etc--still requires study to delimit the possibilities. The old saying "you are what you think" is likely to be proven truer than many people would like.

You can find Darwin's works free online here or here.

Plastic Brains--Shaping Your Future Self

The human brain retains some capacity to learn and change throughout its life. Cortical neurons can not only change their wiring based upon inputs, but new neurons can be grown to reinforce (and replace?) existing networks. Neuroscientists are hot on the trail of brain plasticity, and the story is far from being told entire.

Focal hand dystonia (FHD) is a fascinating disorder of brain plasticity that particularly affects musicians. FHD involves plastic changes in the somatosensory cortex that receives inputs from the involved hand. The brain actually loses its ability to distinguish sensory input from the different fingers, leading to the inability of the musician to synchronize and sequence the intricate fingerings of difficult pieces for piano, violin, and other instruments. The reason for this brain confusion is that long practise sessions playing rapid, difficult pieces confuse the brain into thinking that input from different fingers is actually coming from the same finger. Input from one finger grows into the somatosensory map of a different finger as the brain adapts to this new input, until the brain can no longer distinguish one finger from another when attempting to play music. Here is more on focal dystonia.

We have only so much cortex to work with. The intricate folding of the neocortex provides us with more gray matter than we would have with smooth-surfaced brains, but there is a limit. If we lose an eye or a limb, the cortex serving that part of the body is freed up for other uses. Inputs from other sensory organs or other units of the same sense will typically grow into the unused area of cortex in those cases. Thus someone who goes blind may develop keener hearing and much better discrimination with his Braille reading hand.

Similar plastic remapping of motor cortex can occur, for example after a stroke (CVA). You should not be surprised that many scientists and mental health professionals believe that the associative cortex is capable of similar plastic remapping. In other words, it appears that you truly are shaped by the things you most commonly think about. Your brain accomodates your choices of thought and action by changing as you think, act, cogitate, and daydream.

Jeffrey Schwartz has gone beyond thinking about brain plasticity, to incorporating it into a therapy for his Obsessive Compulsive Disorder (OCD) patients. His results are promising.

While most educated persons may consider themselves too modern to fall for the admonitions of religious teachers and self-help gurus, who constantly drone that "you are what you think," perhaps it is time to go back to the underlying idea--without all the religious and other extraneous matter.

Humans are at a major turning point. They can either choose the path of accelerating change, or the path of stagnation--with its inherent vulnerability to more primitive, more vital ways of thinking and living. Al Fin frequently points out the stagnant and self-defeating ways of education and child-raising in the modern west. Here at Al Fin, the best alternative put forward to mainstream stagnation, is the next level. But the next level will require smarter humans--humans who can direct their own evolution.

The curve of forward development and accelerating change will not be a smooth, continuously upward curve. It will develop in fits and starts, with occasional relapses and reversals. We are missing much of the data we will need for many of our forward leaps, but more than that, we are missing the conceptual power we will need. If we--through our commitment to stagnant ideologies and customs--neglect basic advances we could be making, we will pay for our lapses dearly, in time.

Adult brains are not nearly as plastic as childhood and teenage brains. The one advantage that adult brains possess, is their life experience and possibly their fuller use of the prefrontal pathways of the brain. These advantages may be used exclusively for one's own benefit, or in addition, used to assist younger generations.

We will eventually utilise gene therapy to bring about higher intelligence in humans. This will be done first in neurodegenerative conditions of old age and childhood. As the methods improve, the benefits of better intelligence-conferring genes (and other augments) will be made available to everyone who can pay--even if the person must travel to Brasil or India to obtain the treatments. But I suspect that we are capable of significant improvement in our ability to learn and conceptualize simply by using the natural plasticity of our own brains. Certainly methods for teaching our children can result in much more capable and confident children if they work with the natural plasticity and the natural hunger for competence of the young brain.

The positive lessons of brain plasticity in Schwartz's treatments for OCD and the negative lessons of brain plasticity in FHD, should give a thoughtful person much to think about.

Previous posts at Al Fin discussed the importance of "purpose" in providing motivation for development and positive change. Learning the lessons of neuroplasticity provides a deeper rationale for discovering purpose in life, and using that purpose to motivate, and to set personal goals.

Religious and ideological zealots and terrorists have no lack of purpose or motivation. They simply want to destroy all competing ideologies and religions. Those of us with more constructive goals may need to focus a bit more.