Location of the Mind Remains a Mystery

Where does the mind reside? It’s a question that has occupied the best brains for thousands of years, including the Buddha’s.

Recent advances in functional magnetic resonance neuroimaging, a technique that measures brain activity in the hope of finding correlations between mental functions and specific regions of the brain, have led to a wealth of studies that map particular functions onto regions. Self-awareness is defined as being aware of oneself, including one’s traits, feelings, and behaviors. Previous neuroimaging studies had suggested that self-awareness (SA), which is central to human consciousness, depends critically on specific brain regions, namely the insular cortex, the anterior cingulate cortex (ACC), and the medial prefrontal cortex (mPFC). This proposal predicts that damage to these regions should disrupt or even abolish SA — an afflicted individual should be like a zombie, according to David Rudrauf, a neurologist at the University of Iowa in Iowa City.

University of Iowa researchers studied the brain of a patient with damage to three regions long considered integral to self-awareness — left to right, the insular cortex, anterior cingulate cortex, and medial prefrontal cortex. Image credit: UI Department of Neurology.

So when Rudrauf and his team heard about patient R, they immediately thought he could help set the record straight. Patient R is a 57-year-old man whose brain was damaged in 1980 following a severe episode of herpes simplex encephalitis. His brain damage is bilateral, more extensive on the right, and encompasses the target regions mentioned above: the insular cortex, the ACC, and the mPFC. Rudrauf et al reasoned that if any of the structures that are damaged in this patient are indeed critical for the different aspects of SA implicated by the hypothesis described above — i.e., insula, ACC, mPFC — the patient should show clear disruptions of the corresponding functions. Conversely, if these structures are not critical, R should show largely preserved SA.

In fact, R displays a strong concept of selfhood. Rudrauf’s team confirmed this by checking whether he could recognize himself in photographs and by performing the tickle test — based on the observation that you can’t tickle yourself. They concluded that many aspects of R‘s self-awareness remained unaffected. “Having interacted with him it was clear from the get go that there was no way that [the theories based on neuroimaging] could be true,” says Rudrauf. R also has an IQ within the normal range, although he does have severe amnesia, which prevents him from learning new information, and he struggles with social interaction.

The UI researchers estimate that R has ten percent of tissue remaining in his insula and one percent of tissue remaining in his anterior cingulate cortex. Some had seized upon the presence of tissue to question whether those regions were in fact being used for self-awareness. But neuroimaging results presented in the current study reveal that R’s remaining tissue is highly abnormal and largely disconnected from the rest of the brain.

The authors of the report conclude that:

R is a conscious, self-aware, and sentient human being despite the widespread destruction of cortical regions purported to play a critical role in SA, namely the insula, anterior cingulate cortex, and medial prefrontal cortex.

“Self-awareness corresponds to a brain process that cannot be localized to a single region of the brain,” says Rudrauf. “In all likelihood, self-awareness emerges from much more distributed interactions among networks of brain regions.”

Patient R demonstrates that the mind remains as elusive as ever.

References:

• Philippi CL, Feinstein JS, Khalsa SS, Damasio A, Tranel D, & et al. (2012). Preserved Self-Awareness following Extensive Bilateral Brain Damage to the Insula, Anterior Cingulate, and Medial Prefrontal Cortices Plos ONE, 7 (8) DOI: 10.1371/journal.pone.0038413

May 6, 1966 (a Friday)

On this date, American paleobotanist Elso S. Barghoorn of Harvard reported the discovery of Precambian spherical one-celled alga-like microfossils (named Eobacterium isolatum, which means “solitary dawn bacteria”) 3.4 billion years old, Earth’s earliest life forms. Barghoorn, with J. William Schopf, studied the 3.2 billion year old chert (a flintlike or quartz-like rock) of the Fig Tree formation in Transvaal, South Africa. Rubidium and strontium ratios in the chert suggested an age of over 3 billion years. The fossils are examples of prokaryotes, unicellular organisms that lack a nucleus and have a distinctive cell wall containing organic chemicals.

References:

• Barghoorn, E.S., Schopf, J.W. (1966). Microorganisms three billion years old from the Precambrian of South Africa. Science, 152(3723), 758-763. DOI: 10.1126/science.152.3723.758

April 6, 2006 (a Thursday)

*Tiktaalik roseae* fills in the evolutionary gap between fish and land animals.

On this date, two articles were published in the science journal Nature reporting the discovery of a fossil that might in time become as much of an evolutionary icon as the proto-bird Archaeopteryx. Several specimens of this transitional form, named Tiktaalik roseae, were found in late Devonian river sediments on Ellesmere Island in Nunavut, Arctic Canada.

References:

• Ahlberg, P.E., Clack, J.A. (2006). Palaeontology: A firm step from water to land. Nature, 440(7085), 747-749. DOI: 10.1038/440747a
• Daeschler, E.B., Shubin, N.H., Jenkins, F.A. (2006). A Devonian tetrapod-like fish and the evolution of the tetrapod body plan. Nature, 440(7085), 757-763. DOI: 10.1038/nature04639
• Shubin, N.H., Daeschler, E.B., Jenkins, F.A. (2006). The pectoral fin of Tiktaalik roseae and the origin of the tetrapod limb. Nature, 440(7085), 764-771. DOI: 10.1038/nature04637
• “What has the head of a crocodile and the gills of a fish?“, the Understanding Evolution website, the University of California Museum of Paleontology and the National Center for Science Education. Last updated June 2010, accessed on 26 April 2011. http://evolution.berkeley.edu/evolibrary/news/060501_tiktaalik

Lead, Violence, and Society

Big Business conducted a Big Experiment with America’s youth you never knew about.

When Rudy Giuliani ran for mayor of New York City in 1993, he campaigned on a platform of bringing down crime and making the city safe again. It was a comfortable position for a former federal prosecutor with a tough-guy image, but it was more than mere posturing. Since 1960, rape rates had nearly quadrupled, murder had quintupled, and robbery had grown fourteenfold. New Yorkers felt like they lived in a city under siege.

Giuliani won the election and selected Boston police chief Bill Bratton as the NYPD’s new commissioner. Bratton aggressively cracked down on small crimes, believing bigger crimes would drop as well. And they did.

But in fact, violent crime had actually peaked in New York City in 1990, four years before the Giuliani-Bratton era. By the time they took office, it had already dropped 12 percent. And it continued to drop. And drop. And drop. By 2010, violent crime rates in New York City had plunged 75 percent from their peak in the early ’90s.

It’s not just New York that saw a big drop in crime. In city after city, violent crime peaked in the early ’90s and then began a steady and spectacular decline. Washington, DC, didn’t have either Giuliani or Bratton, but its violent crime rate dropped 58 percent since its peak. Dallas’ fell 70 percent. Newark: 74 percent. Los Angeles: 78 percent.

The disappearance of lead from gas and paint is one of the most compelling hypotheses to explain the decline of violent crime in America, especially in cities — big cities, with their density and traffic, were particularly vulnerable to airborne lead.

It’s the only hypothesis that persuasively explains both the rise of crime in the ’60s and ’70s and its fall beginning in the ’90s. Two other hypotheses — the baby boom demographic bulge and the drug explosion of the ’60s — at least have the potential to explain both, but neither one fully fits the known data. Only gasoline lead, with its dramatic rise and fall following World War II, can explain the equally dramatic rise and fall in violent crime. In fact, gasoline lead may explain as much as 90 percent of the rise and fall of violent crime over the past half century.

Having said that, it’s important to note that the evidence so far is not conclusive in favor of any of the hypotheses.

References:

• Howard W. Mielke, Sammy Zahran. The urban rise and fall of air lead (Pb) and the latent surge and retreat of societal violence. Environment International, 2012; 43: 48 DOI: 10.1016/j.envint.2012.03.005
• Rick Nevin. How Lead Exposure Relates to Temporal Changes in IQ, Violent Crime, and Unwed Pregnancy. Environmental Research, May 2000; 83 (1): 1-22

March 7, 1930 (a Friday)

On this date, the American chemist and biologist Stanley Lloyd Miller was born. In 1953, he (under his University of Chicago mentor, Nobelist Harold C. Urey) performed a famous experiment (the so-called Miller-Urey experiment) to determine the possible origin of life from inorganic chemicals on the primeval, just-formed Earth. They passed electrical discharges (simulating thunderstorms) through mixtures of reducing gases, such as hydrogen, ammonia, methane and water, believed to have formed the earliest atmosphere. Analysis days later showed the resulting chemicals included five amino acids: aspartic acid, glycine, alpha-amino-butyric acid, and two versions of alanine. Aspartic acid, glycine, and alanine are common building blocks of natural proteins. Other compounds included urea, aldehydes, and carboxylic acids. This experiment showed that the basic molecules of life could be synthesized from simple molecules, suggesting that Darwin’s “warm little pond” was a feasible scenario.

The apparatus used for Miller's original experiment. Boiled water (1) creates airflow, driving steam and gases through a spark (2). A cooling condenser (3) turns some steam back into liquid water, which drips down into the trap (4), where chemical products also settle.

Interestingly, the 1953 Miller-Urey experiment had two sibling studies, neither of which was published. Vials containing the products from those experiments were recently recovered and reanalyzed using modern technology. The results were reported in the 17 October 2008 issue of the journal Science.

Miller relied on a blotting technique to identify the organic molecules he had created — primitive laboratory conditions by today’s standards. He would not have been able to identify anything present at very low levels.

Indiana University Biochemistry Program doctoral student Adam Johnson, Scripps Institution of Oceanography marine chemist Jeffrey Bada (the present Science paper’s principal investigator), National Autonomous University of Mexico biologist Antonio Lazcano, Carnegie Institution of Washington chemist James Cleaves, and NASA Goddard Space Flight Center astrobiologists Jason Dworkin and Daniel Glavin examined vials left over from Miller’s experiments of the early 1950s. Vials associated with the original, published experiment contained far more organic molecules than Stanley Miller realized — 14 amino acids and five amines.

The apparatus used for Miller's "second," initially unpublished experiment. Boiled water (1) creates airflow, driving steam and gases through a spark (2). A tapering of the glass apparatus (inlay) creates a spigot effect, increasing air flow. A cooling condenser (3) turns some steam back into liquid water, which drips down into the trap (4), where chemical products also settle.

However, “The apparatus Stanley Miller paid the least attention to gave the most exciting results,” said Johnson, lead author of the Science report. The difference between the published and two unpublished experiments is small — the unpublished experiments used a tapering glass “aspirator” that simply increased air flow through a hollow, air-tight glass device. Increased air flow created a more dynamic reaction vessel, or “vapor-rich volcanic” conditions, according to the present report’s authors. The 11 vials scientists recovered from Miller’s “second,” initially unpublished experiment produced 22 amino acids and the same five amines at yields comparable to the original experiment.

“We believed there was more to be learned from Miller’s original experiment,” Bada said. “We found that in comparison to his design everyone is familiar with from textbooks, the volcanic apparatus produces a wider variety of compounds.” Johnson added, “Many of these other amino acids have hydroxyl groups attached to them, meaning they’d be more reactive and more likely to create totally new molecules, given enough time.” The report’s authors bring up-to-date what is a plausible scenario for the origin of the earliest biochemical molecules on Earth:

Geoscientists today doubt that the primitive atmosphere had the highly reducing composition Miller used. However, the volcanic apparatus experiment suggests that, even if the overall atmosphere was not reducing, localized prebiotic synthesis could have been effective. Reduced gases and lightning associated with volcanic eruptions in hot spots or island arc–type systems could have been prevalent on the early Earth before extensive continents formed. In these volcanic plumes, HCN, aldehydes, and ketones may have been produced, which, after washing out of the atmosphere, could have become involved in the synthesis of organic molecules. Amino acids formed in volcanic island systems could have accumulated in tidal areas, where they could be polymerized by carbonyl sulfide, a simple volcanic gas that has been shown to form peptides under mild conditions.

Stanley Lloyd Miller

Miller’s third, also unpublished, experiment used an apparatus that had an aspirator but used a “silent” discharge. This third device appears to have produced a lower diversity of organic molecules.

“This research is both a link to the experimental foundations of astrobiology as well as an exciting result leading toward greater understanding of how life might have arisen on Earth,” said Carl Pilcher, director of the NASA Astrobiology Institute, headquartered at NASA Ames Research Center in Mountain View, Calif.

Suggested Reading:

• Johnson, A., Cleaves, H., Dworkin, J., Glavin, D., Lazcano, A., & Bada, J. (2008). The Miller Volcanic Spark Discharge Experiment Science, 322 (5900), 404-404 DOI: 10.1126/science.1161527
• Stanley L. Miller, “A production of amino acids under possible primitive Earth conditions, ” Science 117: 528 (15 May 1953) [DOI:10.1126/science.117.3046.528].

WARNING: The creationist Jonathan Wells of the Discovery Institute has made false and misleading claims about the Miller-Urey experiment and other abiogenesis research in his book Icons of Evolution: Science or Myth? Why Much of What We Teach About Evolution Is Wrong.

December 2, 2010 (a Thursday)

The backbone of standard DNA (the blue spiral ribbon-like structure in this drawing) contains an alternating chain of linked phosphate and sugar molecules. Strong evidence indicates that in GFAJ-1 the phosphate is replaced by arsenate.

Today, NASA scientists reported the discovery of a bacterium that can grow by using arsenic instead of phosphorus, most notably for making nucleic acids, in an article in the journal Science (Science DOI: 10.1126/ science.1197258).

The organism in question is a bacterium, GFAJ-1, cultured by Wolfe-Simon from sediments she and her colleagues collected along the shore of Mono Lake, California. Mono Lake is hypersaline and highly alkaline. It also has one of the highest natural concentrations of arsenic in the world.

Image of GFAJ-1 grown on arsenic. Image Credit: Jodi Switzer Blum

GFAJ-1 is apparently most closely related to the salt-loving bacteria in the genus Halomonas. Many of these bacteria are known to be able to tolerate high levels of arsenic. But unlike its relatives, when starved of phosphorus, GFAJ-1 can instead incorporate arsenic into its DNA and continue growing as though nothing remarkable had happened.

Image of GFAJ-1 grown on phosphorus. Image Credit: Jodi Switzer Blum

Paul Davies, the director of BEYOND: Center for Fundamental Concepts in Science at Arizona State University in Tempe, Arizona, said:

It is the first time in the history of biology that there’s been anything found that can use one of the different elements in the basic structure. . . . [Wolfe-Simon’s finding] can only reinforce people’s belief that life can exist under a much wider range of environments than hitherto believed. . . . [The discovery of GFAF-1 is] the beginning of what promises to be a whole new field of microbiology.

A Tale of Two Hypotheses

The cause of the rapid evolutionary growth in hominid brain size remains a mystery and a major point of contention among anthropologists. (Hominids are humans and human-like primates). Our brains weigh roughly twice as much as those of our similarly-sized earliest human relative, Homo habilis, which lived two million years ago. Also, humans have extraordinarily large and complex brains compared with non-human modern primates. The human brain is several times larger than that of the macaque monkey – even after correcting for body size – and it is far more complicated in terms of structure. Although humans weigh about 20 percent more than chimpanzees, our closest living relative, the human brain weighs 250 percent more. And keep in mind that a huge brain is a serious investment – neural tissue guzzles a lot of energy.

Two main hypotheses have been proposed to explain why humans have evolved larger brains than their primate relatives:

• The general intelligence hypothesis suggests that bigger brains make humans better and faster at all kinds of cognitive skills, such as memorizing, learning, and planning ahead. In other words, humans differ from apes uniformly across physical and social cognitive tasks because they have greater general intelligence. Physical skills involve understanding concepts of space, quantities, and causality. Social skills involve understanding nonverbal communications, imitating another’s solution to a problem, and understanding that other individuals have their own beliefs and intentions. For example, biting and trying to break a plastic tube to retrieve the food inside demonstrates a physical skill, while following another’s example to pop open the tube to retrieve the food demonstrates a social skill.
• The cultural (or social) intelligence hypothesis says that bigger brains have enabled humans to develop, in particular, more complex social cognitive skills to interact in cultural groups.

One way to distinguish between these two hypotheses is to compare the cognitive abilities and skills of humans with other non-human primates. If the general intelligence hypothesis is true, then we expect to see a difference between humans and apes in both physical and social skills. If the cultural intelligence hypothesis is true, then we expect to see a difference primarily in social skills.

This experiment is exactly what was performed by Esther Herrmann and her colleagues of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and recently reported in the September 7 issue of the journal Science. They put 105 young German children (Homo sapiens), 106 chimpanzees (Pan troglodytes), and 32 of the more evolutionarily distant orangutans (Pongo pygmaeus) through a series of complex tests. The children were all about 2.5 years old, an age when they have about the same physical skill level of chimpanzees, and had been speaking for at least a year. The apes ranged in age from 3 to 21 and had all been made accustomed to humans. The researchers designed 16 different puzzles to tease out the differences in ability between humans and apes. The tests took between three and five hours and were spread between five and eight days over two weeks. The apes were tested in the sanctuaries where they live in Africa and Indonesia.

The results found that chimpanzees, human children, and orangutans were all equally successful in the physical skills tests. But the human children were significantly better at the social skills tests – scoring around 74 percent correct on the tests compared to scores of 33 percent from both groups of apes.

The findings support the cultural intelligence hypothesis but contradict the general intelligence hypothesis. Joan Silk, an anthropologist at the University of California, Los Angeles, who was not involved in the study, observed that “compared [with] baboons we waste an awful lot of time gossiping about one another.” Aside from gossiping, these increased social skills appear to carry strong evolutionary advantages, enabling humans to sustain relationships with others and help each other out in times of need. A growing body of evidence suggests that the quality of social relationships has measurable fitness consequences for individuals. However, this may have come with some hidden costs. Silk commented that “the human brain is a really complicated machine that goes wrong with some frequency. Mental illness may be the evolutionary cost of this complexity.”

References:

• Herrmann, E., Call, J., Hernandez-Lloreda, M.V., Hare, B., Tomasello, M. (2007). Humans Have Evolved Specialized Skills of Social Cognition: The Cultural Intelligence Hypothesis. Science, 317(5843), 1360-1366. DOI: 10.1126/science.1146282
• Silk, J.B. (2007). Social Components of Fitness in Primate Groups. Science, 317(5843), 1347-1351. DOI: 10.1126/science.1140734

What’s a cell-adhesion protein like you doing in a unicellular organism like me?

The principle of common descent in evolutionary theory means that all living organisms are related to each other in a genealogical sense. In other words, many of the similarities between different organisms exist because they were inherited from a common ancestor with those features. Since inherited traits are encoded in the DNA of the organisms, comparisons of their genes is a way to infer descent from a common ancestor.

One of the similarities among all metazoans is their multicellularity, which requires proteins that enable cells to adhere and communicate. A number of cell adhesion and cell-cell signaling proteins do this in multicellular organisms, but only such proteins that exist in all (or nearly all) modern metazoans, but not in any other multicellular organisms such as fungi and plants, should have been present in the last common ancestor (LCA) of metazoans. The cadherin family of proteins apparently meets this criteria.

.Monosiga brevicollis

Cadherins have also been found in the choanoflagellates, which are unicellular and sometimes colony-forming organisms. Each cell has a single flagellum surrounded by a collar (choano comes from the Greek word for collar) of microvilli that it uses to swim and capture bacterial prey. As the flagellum beats, it draws water through the collar’s microvilli, which filter out bacteria and other tiny food particles. Choanoflagellates are nearly indistinguishable, in terms of shape and function, from the “collar cells” (choanocytes) of sponges, the simplest metazoans. The beating flagella of choanocytes generate a current that draws water and food particles through the body of the sponge, and their microvilli filter out food particles. Henry James-Clark first recognized this remarkable similarity over 130 years ago, which eventually led to the hypothesis that sponges, and, by implication, other animals, evolved from choanoflagellate-like ancestors.

To investigate this possibility, Abedin and King first examined the published genomes of a choanoflagellate, Monosiga brevicollis, and four diverse animals to identify cadherin genes in each. Surprisingly, despite the lack of obvious cell adhesion in M. brevicollis, its number of putative cadherin genes (23) is greater than the number of recognized cadherin genes in the fruitfly Drosophila melanogaster (17). Of the other animals they looked at, the mouse Mus musculus has the most cadherin genes (127), followed by the sea anemone Nematostella vectensis (46), and the sea squirt Ciona intestinalis (32). When compared as a percentage of the total number of genes in each genome, cadherins are more common in M. brevicollis than in any of the four metazoans except M. musculus.

Cadherin.

The cadherin repeat is a repeating domain (functional subunit of a protein) found in all cadherin proteins, which enables them to adhere to each other and which depends on calcium ions (Ca⁺²) to function (cadherins are named after it). A cadherin protein typically consists of an extracellular region, a single membrane-spanning region, and a cytoplasmic region. The cadherin repeat is found in the extracellular region; surprisingly, in comparing the five organisms, Abedin and King discovered that the average number of extracellular cadherin repeats (ECs) in M. brevicollis is highest (14.7), while the average in M. musculus is lowest (5.2).

In the extracellular and cytoplasmic regions of different cadherin proteins, other distinctive domains can be found. The extracellular domains EGF and LamG are shared by M. Brevicollis, N. vectensis, and M. musculus, while the extracellular domains N-hh and IG and the cytoplasmic domain SH2 are shared by M. brevicollis and N. vectensis. This suggests that these domains were present in the LCA of choanoflagellates and metazoans. A cytoplasmic domain called the classic cytoplasmic domain (CCD) is responsible for the ability of classic cadherin proteins (defined as those involved in cell-cell adherens junctions) to anchor, with the help of catenins, to the actin cytoskeleton. As a result, the actin cytoskeleton of one cell can be linked to the cadherins in the plasma membrane, which in turn attach through their extracellular regions to the cadherins in the neighboring cell membranes. However, since CCDs are found in N. vectensis and M. musculus but not in M. brevicollis, the CCD-containing cadherins probably evolved after the origin of the metazoans.

Given that Monosiga brevicollis leads a unicellular lifestyle and is not known to form cell-cell contacts, what are its putative cadherins doing? In an effort to answer this question, Abedin and King determined the locations in choanoflagellate cells of two nearly identical cadherin proteins, MBCDH1 and MBCDH2. Both of them resemble the inferred ancestral cadherin in having SH2 domains but not CCDs. The locations of polymerized actin in the cells were also determined. The experiments showed that actin, MBCDH1, and MBCDH2 proteins were localized together around the base of the choanoflagellate cell, where the choanoflagellate attaches to surfaces, and especially around the microvilli of the collar, where bacteria are captured and ingested. This implies that the associations between cadherins and actin filaments was present in the LCA of choanoflagellates and metazoans. But why?

The localization of these ancient cadherin proteins suggests that perhaps the choanoflagellate/metazoan LCA used them to bind and eat bacteria, while the multicellular metazoans adopted these proteins for gluing their cells together. Abedin and King support this hypothesis by pointing out that some pathogenic bacteria today bind to the extracellular region of metazoan cadherins, taking advantage of them to help invade the host cell. “Indeed, the transition to multicellularity likely rested on the co-option of diverse transmembrane and secreted proteins to new functions in intercellular signaling and adhesion,” they conclude in their report.

References:

• Abedin, M., King, N. (2008). The Premetazoan Ancestry of Cadherins. Science, 319(5865), 946-948. DOI: 10.1126/science.1151084
• King, N. (2004). The Unicellular Ancestry of Animal Development. Developmental Cell, 7(3), 313-325. DOI: 10.1016/j.devcel.2004.08.010
• Snell, E. (2001). Hsp70 sequences indicate that choanoflagellates are closely related to animals. Current Biology, 11(12), 967-970. DOI: 10.1016/S0960-9822(01)00275-5
• University of California – Berkeley. “Genome Of Marine Organism Tells Of Humans’ Unicellular Ancestors.” ScienceDaily 20 February 2008. 31 March 2008 .