Category Archives: biology

On sticking out your tongue.

Muscles can only pull, not push, so how is it that you can stick out your tongue? In other words, since we have no muscle outside our mouths to pull our tongues out, the fact that muscles are incapable of pushing seems to imply that there is some sort of mechanism at work in producing this movement which doesn’t fit in with our general conception of all other movements (arms, legs, eyes, peristalsis, breathing, et cetera).

i am currently (4/29/08) attending the 18th Annual Neural Control of Movement (NCM) meeting in Naples, Florida, and this tongue question was brought up as a way to remind the attendants that we should be careful not to let dogma affect our thinking too much as such adherence to well-established ideas can prevent us from reaching new ways of understanding and new modes of analysis.


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The simple answer is that the tongue has constant volume, so if you sufficiently contract the muscles in your tongue laterally (from molar to molar), the tongue must increase its volume longitudinally (from throat to lips). Notice also that to really stick your tongue out, you must protrude your mandible significantly.

In any case, it was a perhaps frivolous but highly stimulating and poignant aside in a meeting otherwise devoted to the serious analysis of experimental data, thus kicking things off in a congenial tone.

On Bodies and Brains

Being a dyed in the wool materialist, I believe that the cellular material hidden in our skulls creates our conscious experience. I was reminded this week, however, of just how irrevocably the body is involved in the generative process as well.

I read a piece of work which appears in the journal Cell, about a newly identified form of stimulated muscle contraction. Apparently, in the nematode Caenorhabditis Elegans, the muscles involved in expunging digested foosdtuffs from the body can be stimulated to do so directly by the intestinal tract1. Asim A. Beg et al, working in the lab of Erik M. Jorgensen, demonstrates that these muscles can be signaled that it’s time to go to work by a high proton concentration, i.e. an acid. Thus, as the gut works, and the space between the intestine and the muscles becomes acidified, the muscles contract.

Normally, muscles are only commanded to produce a force by the release of neurotransmitter from neurons that specifically innervate these tissues. In other words, the nervous system must tell muscles when it’s time to act. Of course the heart represents a notable counter-example, but there one finds specialized muscle cells that endogenously signal the heart to beat at regular intervals; native activity, not native stimulus response. The worm-gut case is unique because it is an example of the body bypassing the need for neural intervention.

I was further disabused of my cephalocentric ideology by listening to an old episode of RadioLab titled “Where am I?” That program contained several magnificent examples of the theme I’m expounding on, and one in particular that caught my attention.

The hosts of this not to be ignored radiological phenomenon had as a guest the science writer and scientist Robert M. Sapolsky (amongst others). He commented on a theory concerning brain-body interactions first attributed to William James. It goes like this: not only do the bodily physiological manifestations of emotional states precede conscious awareness of the source-stimulus, but those responses can themselves cause emotional experiences. I found this fascinating, and being a student of the brain, I wanted a little bit more information than the show had to offer, so I got in touch with Professor Sapolsky (at Stanford), and he gave me the following distillation (of the first part):

“The basic story is that sensory information (with the exception of olfaction) gets to the amygdala by way of the usual projections to the cortex, where there is classical sensory cortical processing, and with information eventually passed on to the amygdala. But there is an alternative pathway going straight from the thalamus to the amgdala, bypassing Cortex, so that information gets there sooner. So there’s the potential for amygdaloid activation in response to stimuli before there is conscious (i.e., cortical) awareness of the stimuli. So very fast, but because the cortex really does do all the important transformations of sensory information, this fast short-cut can be quite inaccurate.”

This explains how — by activating the amygdala — emotions and concomitant corporal responses can occur before conscious awareness of their origins, but the bit about the body informing the emotional state goes further. The idea there is that even if you’ve decided on some rational level that there’s nothing to be upset about, the body’s state can convince the brain that there is.

I am not sure of the mechanism that the brain employs to read off the emotional state of the body, but this interplay between mental and body implies a couple of things. First, our body has the ability to inform our brains how we’re feeling, which is especially remarkable in light of the example of the body working independently of the brain, and second that how we’re feeling comes before what we think.

I suppose my dream of some day existing as a brain floating in a tank of reddish liquid is going to turn out far duller than I had imagined.

References

1. Beg AA, Ernstrom GG, Nix P, Davis MW, Jorgensen EM. (2008) Protons Act as a Transmitter for Muscle Contraction in C. elegans. Cell, 11;132(1):149-60.

Towards What Are We Evolving?

A group of researchers has found that our choice of diet has had an effect on our genomes. Specifically, they’ve found that individuals from groups with traditionally high-starch diets have more copies of the gene for Salivary Amylase, the enzyme which breaks down starches in our mouths and stomachs, as compared to those with low-starch diets. This is fascinating news because it is the beginning of an answer to the question: towards what are we evolving? What are the selective pressures acting on our genes to produce further iterations of our species’ existence? In general, this is an extremely difficult question to answer, if not impossible.

There are some examples of human intervention into evolution; our efforts at breeding plants and animals have yielded several well known successes (including the development of a transparent frog, see below) and we also use evolution to design molecules with specific properties (ref. 1). These, however, are examples where many generations can be generated rapidly and only those individuals with desired traits are allowed produce offspring.


Transparent Frog (HO / REUTERS)

Fitness is the term that is generally used to quantify how likely an individual is to be reproductively successful, and is thus a most relevant concept in determining the direction in which evolution is nudging us. When the environmental variables and set of possbile behaviors are simple, it is possible to make predictions concerning fitness. For instance, a salt marsh is an environment in which organisms are subject to varying levels of salinity. It is a fair bet that after continued but not overwhelming exposure to increased levels of salt, an initially non-salt-tolerant plant will become salt tolerant. This is the case because the individuals with some salt tolerance are presumably more fit than others, and their offspring will retain that advantage.

When one tries to analyze what makes a human being fit, however, there are several obstacles. First, the set of circumstances we’re adapting to are quite complex, meaking it no minor task to pick out which elements might be most important. Second, we define what constitutes fitness through our influence on social structure. Third, even if we’re somehow genetically most-fit, we can choose to thwart evolution by not having any children. One might think that the rich constitute a good candidate for the title of most-fit, but they certainly do not reproduce the most. If anything, the group with the highest reproductive success is the poor.

Even if we believe that Darwinian evolution is the dominant force in defining how we will change over the coming epochs, we must admit that it plays some roll. In attempting to understand the future of our species, and how to act in our own best interests, we must acknowledge the forces at work in shaping our selves. Darwinism is clearly important for analyzing broad trends, such as in the research presented above. However, the fast-and-faster acting influence of cultural evolution which currently influences every aspect of our lives, will undoubtedly be of paramount importance to understanding humanity as well. Our challenge is now to understand how the effects of cultural evolution will play out, feeding back on our biology.

References

1. Farinas ET, Bulter T, Arnold FH. (2001) Directed enzyme evolution. Curr Opin Biotechnol. 12(6):545-51
2. Perry GH, Dominy NJ, Claw KG, Lee AS, Fiegler H, Redon R, Werner J, Villanea FA, Mountain JL, Misra R, Carter NP, Lee C, Stone AC. (2007) Diet and the evolution of human amylase gene copy number variation. Nat Genet. 39(10):1256-60.

On Bacteria & Wiring

All known living things harvest high-energy electrons from hydrocarbons for power. Those creatures which reside in oxygen rich environments pass these waste electrons to oxygen while those that live near geothermal vents use sulfur as their dustbin.

(Shewanella oneidensis from ref. 1)

The bacteria pictured above, however, have access to neither. They live in minimal-sulfur soil at a depth where oxygen is unavailable. Instead, they pass their low-energy electrons to metals, readily available conductors in the earth. The idea that a metallic element may be substituted for something as “fundamental” to life as oxygen is food for the imagination. Beyond this, however, is an even more contentious concept. As you can see from the image, these bacteria produce nanoscale structures resembling wires. Furthermore, it has been demonstrated that these filaments conduct electricity (ref. 1). The researchers who demonstrated this fact believe that the bacteria are using their nano-wires to transport their electrons over long distances to the surface oxygen, creating a current source in the dirt.

This claim is by no means proven, but it is intriguing that the suggestion hasn’t even been considered until now. Also, the implications of an electrically connected community of bacteria are significant. Microorganisms have presented many examples of behaviors normally thought to be reserved to higher animals, and if the authors responsible for this work turns out to be true, studying the dynamic interactions of these communities has the potential to teach us about systems of electrically coupled cells like our brains. Taking speculation to the extreme, one might ask whether these creatures could constitute a biological-battery, yielding electricity for our own use.

References

1. Y. A. Gorby et al. (2006) Electrically conductive bacterial nanowires produced by Shewanella oneidensis strain MR-1 and other microorganisms Proc. Natl Acad. Sci. USA Vol. 103, pp. 11358–11363

2. Jestin JL, Kaminski PA. (2004) Directed enzyme evolution and selections for catalysis based on product formation. J Biotechnol. 113(1-3):85-103

On Corn & Carbon

In the fascinating, free 1st chapter of Michael Pollan’s new book The Omnivore’s Dilemma, he makes the point that American industrial agriculture is largely based on corn. Most of our livestock species are fed on corn, and a laundry list of comestibles contain additives derived from it. He goes on to explain that it is possible to quantify how much corn one consumes directly or indirectly due to the type of photosynthesis that corn engages in.

All forms of photosynthesis involve the fixation (harvesting) of carbon which is made into simple sugars subsequently consumed for energy. Photosynthetic types can be categorized, according to the specifics of the carbon fixation process, as C3, C4, or CAM. Corn is a C4 grass. This means that it has developed an adaptation to deal with dry, arrid climes. Specifically, the fixation of carbon is achieved first by PEP carboxylase, which basically buffers it. Plants absorb carbon in the form of CO2 through holes on their leaves called stomata. However, water can also be lost through these pores, so they must be closed to prevent dehyrdation. During these periods, the lack of available CO2 can become a problem because the costly reverse reaction of photosynthesis: photorespiration, occurs. Not so for corn and it’s C4 cronies; their buffer of carbon prevents wasteful photorespiring. In addition to this benefit, it turns out that there is another significant consequence of such a strategy: indiscriminate absoprtion of carbon isotopes.

Most (98.9%)of carbon is C-12, it has 6 protons and 6 neutrons. Almost the entirety of the remaining 1.1% is C-13, 6 protons and 7 neutrons, a mass difference of 1.6749 × 10^−27 kg. Most plants preferentially absorb C-12, but not C4 plants. Given such a minute difference between these atoms, it is quite amazing that plants have any ability to discriminate between them. It turns out that differences in the rate of (1) diffusion into the stomata, (2) absorption of C02 by water in the plant, and (3) diffusion of carbon out of the plant is what makes the difference1. Beyond these passive properties, PEP carboxylase has somehow managed to develop a bias in which type of CO2 (preferring C-13) it fixes. It is damned astounding that an enzyme can have such specificity, discriminating such a small mass difference (there is no charge & so probably not much of an electron-shell-structure difference). The end result of all this is that the ratio between the two isotopes in, for example, your flesh is informative about what type of plant supplies most of your carbon.

It is unclear if monitoring this value will ever be relevant to the individual. The potentially deleterious effects of eating large amounts of corn on health and well being are up for debate. It is immediately interesting, however, from a socio-cultural standpoint. Mr. Pollan makes this point quite well in an article he wrote for The New York Times2. He points out that the consequences of industrial monoculture farming are probably not sustainable in the long term. I firmly believe that questioning the long term feasibility of our life styles is important for continued human survival and happiness. The ability to measure corn consumption on a large scale will allow us to monitor and understand this potential problem in a very direct way.

References

1. Farquhar, G.D., Ehleringer, J.R., & Hubick, K.T. (1989) Carbon Isotope Discrimination and Photosynthesis, Annual Revews of Plant Physiology and Plant Molecular Biology, Vol. 40 pp. 503-537
2. Pollan, M. (2007) Unhappy Meals, The New York Times (http://www.nytimes.com/2007/01/28/magazine/28nutritionism.t.html)

On the Difficulty of Understanding Evolved Objects, Namely Biology

(a map of yeast protein interactions1

Imagine a machine designed to slice bread which, through some pathological design concept, posessed the trait that its blade was also somehow its power source. Removing the blade/power supply would clearly render the device inoperable, but understanding how this action had achieved its effect would be quite difficult. This is the essence one of the main problems which confronts anyone interested in teasing apart the complex web of interactions that is molecular biology.

For whatever reason, whether it be a basic feature of human intelligence or simply a sort of paradigmatic immaturity as a species, we tend not to design things in the same way the evolution does. By that I mean employing multi-purpose parts in the way the fictional device mentioned above does. One human-designed object posessing that property is the bicycle. There, it so happens, that the rotation of the wheels actually tends to keep the bike up-right. The wheels are like gyroscopes: their rotational intertia tends to keep them in their plane of rotation in the same way that the linear inertia of an object moving in a straight line tends to keep it on that trajectory. In the sense that the idea of the bicycle has retained this accidental advantage, it resembles an evolution-designed object. However, examples of human engineering that fit this category are few.

In biology, it appears, this type of overlapping, redundant functionality is the norm. For example, insulin is a molecule which is well known to many layman as being involved in the metabolism of glucose: the regulation of blood sugar. However, if one simply consults the wikipedia article on insulin, it immediately becomes clear that this is far to simple a tale. The functions of insulin listed there are:

1. Increased glycogen synthesis – insulin forces storage of glucose in liver (and muscle) cells in the form of glycogen; lowered levels of insulin cause liver cells to convert glycogen to glucose and excrete it into the blood. This is the clinical action of insulin which is directly useful in reducing high blood glucose levels as in diabetes.
2. Increased fatty acid synthesis – insulin forces fat cells to take in blood lipids which are converted to triglycerides; lack of insulin causes the reverse.
3. Increased esterification of fatty acids – forces adipose tissue to make fats (i.e., triglycerides) from fatty acid esters; lack of insulin causes the reverse.
4. Decreased proteinolysis – forces reduction of protein degradation; lack of insulin increases protein degradation.
5. Decreased lipolysis – forces reduction in conversion of fat cell lipid stores into blood fatty acids; lack of insulin causes the reverse.
6. Decreased gluconeogenesis – decreases production of glucose from non-sugar substrates, primarily in the liver (remember, the vast majority of endogenous insulin arriving at the liver never leaves the liver) ; lack of insulin causes glucose production from assorted substrates in the liver and elsewhere.
7. Increased amino acid uptake – forces cells to absorb circulating amino acids; lack of insulin inhibits absorption.
8. Increased potassium uptake – forces cells to absorb serum potassium; lack of insulin inhibits absorption.
9. Arterial muscle tone – forces arterial wall muscle to relax, increasing blood flow, especially in micro arteries; lack of insulin reduces flow by allowing these muscles to contract.

Even as I’m writing this, I have come across an article in Nature about a previously unknown action of insulin in a biochemical pathway involving a protein called TORC22.

Some would say that I am pointing to an inherent flaw in reductionist thinking. That our tendency to search for the smallest parts in order to build up a description of everything from the universe itself to the many varied forms of matter we find within it, cannot hope to penetrate these massively interconnected systems. It seems true that our current notions of what the smallest parts are will lead us to descriptions which are simply too large scale to be intuitively understood. However, this doesn’t necessarily point to a flaw in reductionism, especially since the alternative approach of holism doesn’t seem to offer any ways forward which circumnavigate such a problem. Rather, I would suggest that we need to fundamentally shift the way we think about evolved things in order to make significant progress towards understanding that which falls under the blanket term of “complex systems.”

Early in the last century, physics was spurred on by a shift in thinking: quantum theory, often thought of as one of the canonical scientific revolutions. I am hopeful that this century, or some time in mankind’s future, will do the same for biology, and complexity in general.

References

1. Durrett, Rick. Random Graph Dynamics New York: Cambridge University Press, 2006.
2. Dentin, R. Liu, Y., Koo, S.H., Hendrick, S., Vargas, T., Heredia, J., Yates, J. III, Montiminy, M. (2007) Insulin Modulated gluconeogenesis by inhibition of the coactivator TORC2 Nature 449: 366-369

Trees Can Talk to Each Other

How do plants converse with each other? As human beings, we posses probably the most sophisticated communication abilities of any species on the planet. This makes it very easy for us to forget that every form of life has some ability to transmit information between individuals. This is true even at a microscopic level where bacterial cell-to-cell signaling is a popular research topic (ref 1).

Having been around for a very long time and being unable to move much, it is no surprise that plants have developed many sophisticated adaptations for the purpose of communication. Plants can communcate in a host of ways, see (ref. 2) for a brief overview. One of the most fascinating of these is the use of “smoke signals.”

Ten years ago, researchers interested in plant biology and forest fires discovered that exposing seeds to smoke or certain nitrogenous compounds in smoke will induce germination (ref. 3). The evolutionary advantage of this behavior is presumed to be that forest fires leave an area rife for new growth.

The greater significance of this ability is our ongoing opportunity to learn from biological organisms. Although we use our intelligence to guide us in solving problems, we still use trial and error extensively. The greatest expert on trial and error is evolution. The process of evolving progressively more sophisticated life forms has relied on the use of trial and error for the last 3.7 billion years, and we would do well to realize that when it comes to the challenges of existing on earth, we’ve got a teacher who’s got a valuable store of experience.

References

1. Melissa B. Miller & ­ Bonnie L. Bassler Quorum Sensing in Bacteria Annual Review of Microbiology 55: 165-199 [doi:10.1146/annurev.micro.55.1.165]

2. Ragan M. Callaway & Bruce E. Mahall Plant ecology: Family roots Nature 448, 145-147 [DOI: 10.1038/448145a]

3. Jon E. Keeley & C. J. Fotheringham Trace Gas Emissions and Smoke-Induced Seed Germination Science 276: 1248-1250 [DOI: 10.1126/science.276.5316.1248]

Life Span

It is somewhat paradoxical that we cannot perform experiments on the animal we are most interested in studing, ourselves. It is difficult enough to deal with the moral implications of experimenting on non-humans. I frequently remind myself that the study of other creatures mitigates the suffering of my own species and this sometimes seems a paltry justification. Humans are investiaged non-invasively, or further when such intrusion is neccessary for medical purposes, but we are still limited in our understanding by such restrictions, the following science included.

It will come as no suprise that there is quite a bit of research into the possibility of extending the length of time that a living thing spends alive. To date, the only effective means of doing so have been based in some way on the concept of Calorie Restriction(CR), see ref. 1 for a review. This simply means that an animal takes in fewer calories than normal while maintaining adequate levels of nutrients. The results are reasonably unequivocal, from nematoads to mammals, lifespan is increased by this method. As one can see from the graph above, increased caloric restriction is effective up to around 65% fewer calories being taken in, at which point it plateaus.

Some recent research, however, (ref. 2) has found a seemingly non-CR-intertwined mechanism that also has an effect on mammalian lifespan. The authors of this study bred mice which lack the gene which codes for adenylyl cyclase 5 (AC5). ACs in general play a key role in beta-adrenergic receptor (β-AR) signaling. In the interest of brevity, I will not delve into the molecular biology of cell-to-cell communications, howiver it is important to know that the blockade of this particular signalling pathway has recently been demonstrated to sucessfully treat mild-to-moderate chronic heart failure (ref. 3). The research into mice which lack the AC5 gene shows that their lifespan is ~30% longer, “are protected from reduced bone density and susceptibility to fractures of aging. Old AC5 KO mice are also protected from aging-induced cardiomyopathy, e.g., hypertrophy, apoptosis, fibrosis, and reduced cardiac function.” (ref. 1)

With both of these examples of extended lifespan, however, a question arises. What quality of life do these animals have? This is perhaps more relevant for the research on calorie restriction, but the animals studied can never report to us how they are feeling though the scientist involved always take pains to minimize any outward signs of discomfort. Until such techniques have been tried in human beings the complete effects of these therapies remains a bit of a quesion mark in my mind. That is not to say that I’m not amazed and optimistic about this direction of progress, I simply find it incredible that such simple things as eating less or disrupting a single gene could have universally positive effects.

References

  1. D.A. Sinclair (2005) Toward a unified theory of caloric restriction and longevity regulation, Mech. Ageing Dev. 126, 987–1002.
  2. Lin Yan, Dorothy E. Vatner, J. Patrick O’Connor, Andreas Ivessa, Hui Ge, Wei Chen, Shinichi Hirotani, Yoshihiro Ishikawa, Junichi Sadoshima, and Stephen F. Vatner (2007) Type 5 Adenylyl Cyclase Disruption Increases Longevity and Protects Against Stress, Cell 130, 247-258
  3. M.R. Bristow (2000) beta-adrenergic receptor blockade in chronic heart failure, Circulation 101, 558–569.

Mirror Neurons & Autism

The Mirror Neuron system (MNS) is thought to underlie imitation in primates, and has been implicated in Autism Spectrum disorder in humans(1, 2). First observed in Macaques, mirror neurons are classified as units that selectively increase their firing rate both during the execution of a motor action by an individual and while that individual observes the same action performed by another . The interest in the MNS in relation to autism was sparked by the fact that two of its major symptoms are generalized social interaction & communication deficits which would seem to rely on something like the MNS. In order to explore how MNS properties might differ in normal vs. autistic patients, Hugo Théoret has been performing experiments in human subjects. His results suggest that a general deficit of something akin to the mirror neuron system is present in autistic individuals.

(EMG stuff)

Dr. Théoret uses two techniques in his research on the mirror neuron system. These are electromyography (EMG) and transcranial magnetic stimulation (TCMS or TMS). EMG measures the voltage difference between ground and the skin nearby a muscle group. Muscle contraction is accompanied by currents which cause a change in voltage or potential. The is sensitive enough to detect voltage changes when an individual even considers a movement involving the measured muscle group. TMS is a coarse method of selectively activating cortical regions(3). The combined use of these tools has allowed Dr. Théoret to use simple experiments to draw interesting conclusions about individuals with Autism.

(TMS-er)

Dr. Théoret’s main finding can be summarized by describing two experimental outcomes. First, in normal (non-autistic) individuals, there is a reliable deflection of the electromyogram produced by having the subjects watch a video of an action being performed which involves the measured muscle. For instance, if the right bicep is being measured, there will be an observable deflection of the potential in that muscle when the subject watches a video of an arm lifting an apple. There is also a measurable potential-deflection in that muscle when the proper area of motor cortex is stimulated via TMS. Beyond these individual effects, there is a summation effect such that the deflection is even larger when the subject both observes the video and receives the TMS.

Second, in autistic subjects, there is no deflection of the electromyogram upon a subject’s observation of the above described video. There is in these subjects a potential produced by TMS of the appropriate area, implying that there is no defect in the circuitry to produce such sub-threshold muscle activation. Needless to say there is no summation effect in these subjects.

Dr. Théoret feels that this work implies that understanding of others’ actions is achieved by an individual mapping actions onto their own motor cortex(4). This is an intriguing hypothesis, but there are really two possibilities which both fit with the data. One is as suggested by Dr. Théoret, the other would be that the mirror neuron system alone interprets the intention of the action, and (when possible) maps the action onto the motor cortex. The former possibility would require, for instance, that anybody receiving sufficiently strong TMS would necessarily experience the feeling that they were either observing somebody perform an action or that they were performing the action themselves. This is in keeping with the theory will laid out by Daniel M. Wegner in his book The Illusion of Conscious Will. Without getting too far afield, Dr. Wegner believes that we have a general ability to ascribe agency to observed acts, attributing them to either to ourselves or to others.


The implications of this work are that a defect in the mirror neuron system is responsible for social-interaction pathology in patients with autism. In fact, some researchers believe that defects in the mirror neuron system could lead to all the deficits associated with autism(5). Of course, others feel that such dysfunction cannot be responsible for all the symptoms of autism(6). It remains to be seen whether any definitive explanation of the role of the mirror neuron system in autism will arise, but it is clear that it plays some role in the interpretation of actions.

References

1. Rizzolatti, G., & Craighero, L., (2004) The Mirror Neuron System, Annu. Rev. Neurosci. 27, 169-192.
2. Oberman, L.M., & Ramachandran, V.S., (2007) The simulating social mind: the role of the mirror neuron system and simulation in the social and communicative deficits of autism spectrum disorders. Psychol. Bull., 133, 310-327.
3. Fitzgerald, P.B., Fountain, S. & Daskalakis, Z.J. (2006). A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition. Clinical Neurophysiology 117, 2584-2596
4. Théoret, H., Halligan, E., Kobayashi, M., Fregni, F., Tager-Flusberg, H. & Pascual-Leone, A. (2005) Impaired motor facilitation during action observation in individuals with autism spectrum disorder. Curr Biol. 2005 15, R84-R85.
5. Iacoboni, M., Dapretto, M. (2006) The mirror neuron system and the consequences of its dysfunction. Nat Rev Neurosci. 7, 942-951.
6. Hadjikhani, N., Joseph, R.M., Snyder, J. & Tager-Flusberg, H. (2006) Anatomical differences in the mirror neuron system and social cognition network in autism. Cereb. Cortex. 16, 1276-1282.