Saturday, June 30, 2012

Antonio Damsio Big Think Video Interviews

About Antonio Damasio

Dr. Antonio Damasio is a renowned neuroscientist who directs the USC Brain and Creativity Institute. Before that he was the Head of Neurology at the University of Iowa Hospitals and Clinics. His research focuses on the neurobiology of mind and behavior, with an emphasis on emotion, decision-making, memory, communication, and creativity. His research has helped describe the neurological origins of emotions and has shown how emotions affect cognition and decision-making.  He is the author of a number of books, including "Self Comes to Mind: Constructing the Conscious Brain," which will be published in November, 2010. Dr. Damasio is also the 2010 winner of the Honda Prize, one of the most important international awards for scientific achievement.

Dr. Damasio is a Big Think Delphi Fellow.!video_idea_id=23021

Friday, June 29, 2012

Death by Desperation

I think I mentioned how roughed-up I got by my untreated chronic insomnia in 2010. Ugh! During my relentless internet research (not always a good idea for someone with OCD tendencies, but whaddya gonna do to find relief, otherwise?) I would often come across the medical meme, "except for extremely rare cases of fatal familia insomnia, chronic insomnia is not life-threatening." Right, if you can stand it. Some people can, they manage to keep working and living, despite their lousy sleep. How they do this is beyond me.

Two infamous celebrity deaths have showcased how desperate the sleep-deprived can become. Take the tragic cases of actor Heath Ledger and pop star Michael Jackson.

Heath Ledger.

According to Wikipedia, "Heath Andrew Ledger (1979-2008) was an Australian television and film actor. After performing roles in Australian television and film during the 1990s, Ledger left his homeland for the United States in 1998 to develop his film career. His work comprised nineteen films, including 10 Things I Hate About You (1999), The Patriot (2000), A Knight's Tale (2001), Brokeback Mountain (2005), and The Dark Knight (2008). In addition to acting, he produced and directed music videos and aspired to be a film director.
In a New York Times interview, published on 4 November 2007, Ledger told reporter Sarah Lyall that his recently completed roles in I'm Not There (2007) and The Dark Knight (2008) had taken a toll on his ability to sleep: "Last week I probably slept an average of two hours a night. ... I couldn't stop thinking. My body was exhausted, and my mind was still going." At that time, he told Lyall that he had taken two Ambien pills, after taking just one had not sufficed, and those left him in "a stupor, only to wake up an hour later, his mind still racing."

Prior to his return to New York from his last film assignment, in London, in January 2008, while he was apparently suffering from some kind of respiratory illness, he reportedly complained to his co-star Christopher Plummer that he was continuing to have difficulty sleeping and taking pills to help with that problem: "Confirming earlier reports that Ledger hadn't been feeling well on set, Plummer says, 'we all caught colds because we were shooting outside on horrible, damp nights. But Heath's went on and I don't think he dealt with it immediately with the antibiotics.... I think what he did have was the walking pneumonia.' [...] On top of that, 'He was saying all the time, 'dammit, I can't sleep'... and he was taking all these pills to help him.' "

In talking with Interview magazine after his death Ledger's former fiancée Michelle Williams also confirmed reports the actor had experienced trouble sleeping. "For as long as I'd known him, he had bouts with insomnia. He had too much energy. His mind was turning, turning turning -- always turning."

At about 2:45 p.m., on 22 January 2008, Ledger was found unconscious in his bed by his housekeeper, Teresa Solomon, and his masseuse, Diana Wolozin, in his fourth-floor loft apartment at 421 Broome Street in the SoHo neighborhood of Manhattan.

After two weeks of intense media speculation about possible causes of Ledger's death, on 6 February 2008, the Office of the Chief Medical Examiner of New York released its conclusions, based on an initial autopsy of 23 January 2008, and a subsequent complete toxicological analysis. The report concludes, in part, "Mr. Heath Ledger died as the result of acute intoxication by the combined effects of oxycodone, hydrocodone, diazepam, temazepam, alprazolam and doxylamine." It states definitively: "We have concluded that the manner of death is accident, resulting from the abuse of prescription medications." The medications found in the toxicological analysis are commonly prescribed in the United States for insomnia, anxiety, depression, pain, or common cold symptoms, or any combination thereof.

Yow! It sounds as though Mr. Ledger had prescriptions for the antihistamine and benzodiazopine "sleep aids" of vallium, restoril, xanax, and unisom, as well as the infamous "controlled" pain medications, oxycodone and hydrocodone.

It seems plausible from these accounts that Mr. Ledger was so desperate for sleep, he chowed down one or more of everything he had previously tried, resulting in a fatal "drug cocktail."

The later photos of Michael Jackson are so disturbing, I decided to use this portrait for my post.

Even more notorious was the death of Michael Jackson (1958-2009). Linda Deutsch reported in her Associated Press article:

"Los Angeles -- Michael Jackson was physically exhausted from a day of grueling rehearsals for his marathon 50-night comeback tour. But his nightly battle with insomnia had just begun. After showering and getting into bed, he called for his "milk," a powerful drug he had been using to escape into unconsciousness.

Jackson saw the anesthetic known as propofol as his salvation. On June 25, 2009, it became the King of Pop's death potion.

How he overdosed in his mansion on a drug intended for hospital use is at the center of the manslaughter trial this week of the doctor he hired to be his highly paid personal physician for the "This is It" tour.

Testimony about the drug is expected to dominate the trial of Dr. Conrad Murray, a Houston cardiologist who has pleaded not guilty to a charge of involuntary manslaughter in Los Angeles Superior Court.

The prosecution claims Murray was grossly negligent in giving Jackson propofol at home without proper lifesaving equipment available and then left the room long enough to find his patient not breathing when he returned.

His defense team claims the singer, desperate for sleep, swallowed an additional dose of the drug when his doctor was out of the room.
Getting to the truth of it will come down to sometimes technical testimony from an array of medical experts, pathologists and even the police officers and paramedics who inspected Murray's equipment in the bedroom where Jackson went into cardiac arrest.

The defense theory, based on evidence that a trace amount of propofol -- .13 milligrams -- was found in Jackson's stomach, may be a hard sell.

The drug is administered intravenously, usually during surgery. Scientific witnesses may be asked to explain how it could have gotten into his stomach. Some doctors say ingesting it orally is almost unheard of.

"It's an odd, on-the-edge defense theory," said Dr. Gil Tepper, chief of staff at Miracle Mile Medical Center in Los Angeles. "It would not put you to sleep and it would move through the system very rapidly, causing awful diarrhea."

There are few authoritative studies and few statistics on deaths caused by the drug. It remains uncertain if the judge will allow a Chilean doctor's study of students who voluntarily drank the drug or a study of pigs who received it rectally.

The prosecution has a key expert witness, as well as forensic experts from the Los Angeles County coroner's office who are considered at the top of the field.

The defense boasts an advantage in one of its lawyers, J. Michael Flanagan, who says he is the only California attorney ever to try a propofol death case.

Flanagan represented one of a pair of nurses charged with killing a cancer patient who died after propofol was allegedly given without proper authorization by an anesthesiologist. Flanagan's client was acquitted and the other nurse pleaded no contest to a lesser charge.

Abuse of the drug is said to occur among medical professionals but rarely among patients.
In anesthesia, propofol is known as something of a wonder drug. Tepper said it's ideal for short term procedures such as colonoscopies or cataract surgery. Patients report feeling energized when they come out of it and there is no grogginess.

"But it's absolutely not recommended as a sleep aid," said Tepper. "You would never reach restful sleep and you would have to have constant monitoring."

In a hospital setting, Tepper said the doctor would have heart and blood oxygenation monitors as well as surgical equipment to do intubation if the patient stops breathing. Witnesses have said no such equipment was in Jackson's bedroom.

"It's a very dangerous drug," said Dr. Mark Schlesinger, head of anesthesiology at Hackensack University Medical Hospital in New Jersey, who said he has administered it thousands of times in his 25-year career. "The difference between unconsciousness and no longer breathing is a very slim margin of safety."

In the hands of a trained anesthesiologist, he added: "It's a wonderful drug and a very safe drug. It's not the drug that kills somebody. It's the way it is used."

Murray was not the first doctor to give Jackson the drug as a sleep aid, although others have not been publicly named.

Jackson's reliance on propofol was first disclosed to The Associated Press days after Jackson's death. Cherilyn Lee, a nurse nutritionist who treated Jackson with vitamins, said he pleaded unsuccessfully with her to get the drug he knew as Diprivan. He said his doctor told him it was safe and he described falling asleep as soon as the drug dripped from an IV into his vein.
"I said, `Michael, the only problem with you taking this medication,' and I had a chill in my body and tears in my eyes ... , "`You're going to take it and you're not going to wake up.'"

Lee, who said she treated him from January to April 2009, is on the trial witness list. She said she never saw Jackson use other drugs.

"He wasn't looking to get high or feel good and sedated from drugs," she said. "This was a person who was not on drugs. This was a person who was seeking help, desperately, to get some sleep, to get some rest."

Murray, who had been consulted by Jackson in his Las Vegas office, was promised $150,000 a month when he signed on as Jackson's personal physician six weeks before he died. He closed the doors of his offices there and in Houston to devote himself to the singer.

An autopsy report showed that Jackson was generally healthy, indicating his key problem was insomnia. Murray has told police he administered other drugs known as benzodiazepines, which are also used as sleep aids. But when they did not work, Jackson demanded propofol.
Murray told police he was trying to wean him from the drug and gave him a minimal dosage, then left the room for five minutes to use the bathroom. However, cell phone records suggest he was making phone calls for a longer time. His actions after he found Jackson not breathing are also central to the case.

In the two years since Jackson died, doctors have been known to refer to propofol as "The Michael Jackson drug." Some fear a backlash for its use.

Dr. Lawrence Koblinksy, head of forensic science at John Jay College in New York, said the situation of a famous man demanding propofol is an anomaly and should not cast doubt on its effectiveness in hospitals.

"If you have a drug that is wonderful, just because a celebrity dies doesn't mean you take it off the market," he said."

So in conclusion to this nightmarish post, while the insomnia itself may not be life-threatening, the deadly combination of severe desperation and too much readily-available prescription medicine lying about can prove fatal over time. Even having your own in-house personal physicians to monitor your situation cannot guarentee safety from this doubly-dangerous risk. Before I suffered my own insomnia, I didn't fully appreciate how desperate the chronically sleep-deprived can become. Thankfully, my own treatment, while also desperate at first, has brough me some much-needed rest. I hope that the awareness and treatment of chronic insomnia will soon improve. As things stand now, it is sorely lacking.

Leave it to Underground Comix legend Robert Crumb to capture the appropiate mood.

Stress and the hypothalamic-pituitary-adrenal axis

Here's an aha moment -- perhaps the HPA axis has a lot to do with my insomnia. Once more -- to the Wikipedia. This is a pretty dry, technical entry even by my standards. You might just want to skip it, unless you are stressed. I write some of these posts  just so I can nag Dr. R to "read my blog, dammit" and also maintain my amateur standing as a Proto-Aspie (formerly a Nerd, as in, "talk nerdy to me.")

The cortisol molecule. Don't you love these stick-and-ball molecular models? I do. I'd also like to see one for a McDonalds' Chicken McNugget.

The hypothalamic-pituitary-adrenal axis (HPA or HTPA axis), also known as the limbic-hypothalamic-pituitary-adrenal axis (LHPA axis) and, occasionally, as the hypothalamic-pituitary-adrenal-gonadotropic axis, is a complex set of direct influences and feedback interactions among the hypothalamus, the pituitary gland (a pea-shaped structure located below the hypothalamus), and the adrenal (also called "suprarenal") glands (small, conical organs on top of the kidneys).

The interactions among these organs constitute the HPA axis, a major part of the neuroendocrine system that controls reactions to stress and regulates many body processes, including digestion, the immune system, mood and emotions, sexuality, and energy storage and expenditure. It is the common mechanism for interactions among glands, hormones, and parts of the midbrain that mediate the general adaptation syndrome.

The key elements of the HPA axis are:

The paraventricular nucleus of the hypothalamus, which contains neuroendocrine neurons that synthesize and secrete vasopressin and corticotropin-releasing hormone (CRH). These two peptides regulate:
The anterior lobe of the pituitary gland. In particular, CRH and vasopressin stimulate the secretion of adrenocorticotropic hormone (ACTH), once known as corticotropin. ACTH in turn acts on:

The adrenal cortices, which produce glucocorticoid hormones (mainly cortisol) in response to stimulation by ACTH. Glucocorticoids in turn act back on the hypothalamus and pituitary (to suppress CRH and ACTH production) in a negative feedback cycle.

CRH and vasopressin are released from neurosecretory nerve terminals at the median eminence. CRH is transported to the anterior pituitary through the portal blood vessel system of the hypophyseal stalk and vasopressin is transported by axonal transport to the posterior pituitary.

There, CRH and vasopressin act synergistically to stimulate the secretion of stored ACTH from corticotrope cells. ACTH is transported by the blood to the adrenal cortex of the adrenal gland, where it rapidly stimulates biosynthesis of corticosteroids such as cortisol from cholesterol.

Cortisol is a major stress hormone and has effects on many tissues in the body, including on the brain. In the brain, cortisol acts at two types of receptor  -- mineralocorticoid receptors and glucocorticoid receptors, and these are expressed by many different types of neurons. One important target of glucocorticoids is the hypothalamus, which is a major controlling center of the HPA axis.

Vasopressin can be thought of as "water conservation hormone" and is also known as "antidiuretic hormone." It is released when the body is dehydrated and has potent water-conserving effects on the kidney. It is also a potent vasoconstrictor.

Book, books, and more books. I approve!

Important to the function of the HPA axis are some of the feedback loops:

Cortisol produced in the adrenal cortex will negatively feedback to inhibit both the hypothalamus and the pituitary gland. This reduces the secretion of CRH and vasopressin, and also directly reduces the cleavage of proopiomelanocortin (POMC) into ACTH and β-endorphins.
Epinephrine and norepinephrine are produced by the adrenal medulla through sympathetic stimulation and the local effects of cortisol (upregulation enzymes to make E/NE). E/NE will positively feedback to the pituitary and increase the breakdown of POMCs into ACTH and β-endorphins.

The major communication center for brain-body interaction, the hypothalamus works with the pituitary gland to regulate your body’s hormones. When you have a “stress response,” these two structures throw the adrenal glands into high gear for “fight or flight.” (Image credit: Kathryn Born)


Release of CRH from the hypothalamus is influenced by stress,physical activity, illness, by blood levels of cortisol and by the sleep/wake cycle (circadian rhythm). In healthy individuals, cortisol rises rapidly after wakening, reaching a peak within 30–45 minutes. It then gradually falls over the day, rising again in late afternoon. Cortisol levels then fall in late evening, reaching a trough during the middle of the night. An abnormally flattened circadian cortisol cycle has been linked with chronic fatigue syndrome, insomnia, and burnout.

Anatomical connections between brain areas such as the amygdala, hippocampus, and hypothalamus facilitate activation of the HPA axis. Sensory information arriving at the lateral aspect of the amygdala is processed and conveyed to the central nucleus, which projects to several parts of the brain involved in responses to fear. At the hypothalamus, fear-signaling impulses activate both the sympathetic nervous system and the modulating systems of the HPA axis.

Increased production of cortisol mediates alarm reactions to stress, facilitating an adaptive phase of a general adaptation syndrome in which alarm reactions including the immune response are suppressed, allowing the body to attempt countermeasures.

Glucocorticoids have many important functions, including modulation of stress reactions, but in excess they can be damaging. Atrophy of the hippocampus in humans and animals exposed to severe stress is believed to be caused by prolonged exposure to high concentrations of glucocorticoids. Deficiencies of the hippocampus may reduce the memory resources available to help a body formulate appropriate reactions to stress.
Stress and disease:

The HPA axis is involved in the neurobiology of mood disorders and functional illnesses, including anxiety disorder, bipolar disorder, insomnia, post-traumatic stress disorder, borderline personality disorder, ADHD, major depressive disorder, burnout, chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, and alcoholism.[

Antidepressants, which are routinely prescribed for many of these illnesses, serve to regulate HPA axis function.

Experimental studies have investigated many different types of stress, and their effects on the HPA axis in many different circumstances. Stressors can be of many different type -- in experimental studies in rats, a distinction is often made between "social stress" and "physical stress", but both types activate the HPA axis, though via different pathways. Several monoamine neurotransmitters are important in regulating the HPA axis, especially dopamine, serotonin and norepinephrine (noradrenaline). There is evidence that an increase in oxytocin, resulting for instance from positive social interactions, acts to suppress the HPA axis and thereby counteracts stress, promoting positive health effects such as wound healing.

The HPA axis is a feature of mammals as well as other vertebrates. For example, biologists studying stress in fish showed that social subordination leads to chronic stress, related to reduced aggressive interactions, to lack of control and to the constant threat imposed by dominant fish. Serotonin (5HT) appeared to be the active neurotransmitter involved in mediating stress responses, and increases in serotonin are related to increased plasma α-MSH levels, which causes skin darkening (a social signal in salmonoid fish), activation of the HPA axis, and inhibition of aggression. Inclusion of the amino acid L-tryptophan, a precursor of 5HT, in the feed of rainbow trout made the trout less aggressive and less responsive to stress.However, the study mentions that plasma cortisol was not affected by dietary L-tryptophan.

Studies on people show that the HPA axis is activated in different ways during chronic stress depending on the type of stressor, the person's response to the stressor and other factors. Stressors that threaten physical integrity, are uncontrollable or involve trauma tend to have a high, flat diurnal profile of cortisol release with lower than normal levels of cortisol in the morning and higher than normal levels in the evening, resulting in a high overall level of cortisol release during the day. Controllable stressors on the other hand tend to produce higher than normal morning cortisol. Stress hormone release tends to gradually reduce as time passes since the stress occurred. In post-traumatic stress disorder there appears to be lower than normal cortisol, and it is thought that a blunted hormonal response to stress may predispose a person to develop PTSD.

Here's the cortisol feedback loop at work. Cool, right? It seems many of the health concerns of today are made worse by modern stress, diet, and lifestyle on our still Flintstones-like bodies.

Cortisol, also known more formally as hydrocortisone (INN, USAN, BAN), is a steroid hormone, more specifically a glucocorticoid, produced by the zona fasciculata of the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat, protein and carbohydrate metabolism. It also decreases bone formation. Various synthetic forms of cortisol are used to treat a variety of diseases.

Thursday, June 28, 2012

Mangus Family Lore: Marvin D. Mangus 1924-2009

Bob Hallinen / Anchorage Daily News Archive 2004 Marvin D. Mangus was among the most highly regarded Alaska artists.
Marvin Mangus, artist and geologist, dies at 84.
Admired artist was also a geologist who helped find Prudhoe Bay oil
by Mike Dunham

February 24th, 2009

Marvin Dale Mangus, one of Alaska's leading artists for more than a half a century and a history-making geologist, died on Friday at Providence Alaska Medical Center. He was 84.
Mangus was widely considered in the front ranks of Alaska painters from the 1950s on. Art historian Kesler Woodward, in "Painting in the North," praised "his energy and openness to new ideas in his own work and that of others."

Artist and former art dealer Jean Shadrach compared him favorably with old Alaska masters like Ted Lambert and Fred Machetanz. "He's (Machetanz's) equal," she told the Daily News in 2004. "And he's never gotten the recognition."

Connoisseurs, however, recognized his talent. He won several local and national awards, was among the first artists to hold a solo show at the then-new Anchorage Museum in the 1960s and was the featured artist for the museum's annual fundraising gala five years ago.
Even Alaskans who care nothing for painting are in his debt for his work as a geologist. In 1947, fresh from earning his masters degree from Penn State University, he joined the U. S. Geological Survey's Navy Oil Unit searching for formations likely to hold oil on the North Slope of Alaska. In 1958 he joined Atlantic Refining Co., endured an unpleasant stint in Guatemala -- "It's hot and sweaty and full of prickly thorns and snakes. Bad snakes," he later recalled.

He returned to Alaska in 1962 as the senior surface geologist in charge of the Arctic Slope. He was part of the Atlantic-Richfield field team credited with finding oil at Prudhoe Bay.
"I took the big iron rod down there and put it in the tundra" making the spot to drill, he said in a 2004 interview, and he was there when the drill touched oil.

He continued to work as a geologist into the 1990s.
His years in the field informed his work on canvas. "When you make a living surveying land and doing things like looking at an outcrop in a river bend for 20 minutes, describing it in minute detail," he told the Daily News in 1990, "things like composition, texture and structure just become basic to you."

Geology paid the bills, but painting was not just a hobby. He took it seriously, studying out of state with several well-known teachers. He was keenly aware of contemporary art trends and employed expressionist and impressionist techniques with his colors and brushwork. His was a bold, even avant-garde style for the Alaska art scene in the decades before and after statehood.
His subjects, on the other hand, were classic Alaskana -- landscapes, cabins, stern-wheelers, pack horses, dog teams, fish camps, images of the vanishing last frontier he arrived just in time to see and record.
"I'm painting an Alaska that isn't here anymore," he told the Daily News in 2004.

By that time arthritis had slowed him down, but he continued to paint at his home in Rogers Park and his work remained in demand. His paintings have been displayed in public and private venues from the Anchorage Museum and Alaska State Museum to the Smithsonian Institution and Corcoran Gallery in Washington, D.C.

Mangus was born Sept. 13, 1924, in Altoona, Pennylvania.  He is survived by his wife of 58 years, Jane, and sons, Alfred and Donald. A memorial service will be at 6:30 p.m. Thursday at Anchor Park United Methodist Church.

Brain Networks

The human brain contains 100 billion (10^11) neurons, which combine to form almost 1 quadrillion (10^15) electro-chemical connections. Neurons are also affected by chemical signals that come via the blood, interstitial tissues, and glial cells. If we had to understand all the activity in the brain in order to understand the brain itself, we would be lost.

Fortunately, the brain organises itself in specific ways which simplify the task of discovering how the brain works.
2007 M. Raichle PNAS
The image above reveals particular nodes which participate in important brain networks. It is important that these nodes are able to communicate with other nodes participating in specific networks. Loss of nodes -- or the communication links between them -- can have devastating effects on normal brain function.

2011 van den Heuvel and Sporns Jnl Neurosci
The image above reveals the complexity of an average "connectome" which intervenes between the brain nodes participating in the 12 most important brain networks -- as measured by numbers of connections and activity levels. These networks begin to develop sometime between the 20th and 36th weeks of pregnancy.
Teasing out these connections, and following their activity in real time, is quite difficult work. But it is nothing when compared to the effort involved if one tried to follow the activity of 100 billion neurons simultaneously.

It is not only the ability of the brain nodes to function that counts, it is also vital that the nodes be able to communicate with each other. Depending upon which nodes or interconnections are disrupted, different types of alteration in normal brain function will take place.

Sporns' 'Networks of the Brain': a roadmap to new research in brain mapping, virtual models

Indiana Univeristy Newsroom, February 2011

Bloomington , Indiana  -- In the emerging discipline of network neuroscience, Indiana University neuroscientist Olaf Sporns is playing a diverse and important role. His book Networks of the Brain, recently published by MIT Press, aims to synthesize the current knowledge and theory pertaining to mapping the brain and presents a fundamental text on this complex subject.
Networks of the Brain
Networks of the Brain focuses on how different parts of the brain are connected to one another and how this network architecture relates to brain function and disease. His book further investigates the anatomy, development and evolution of complex brain networks and provides a roadmap for future research including two projects Sporns himself is currently involved with.

"There's a big movement all across the social and natural sciences to look at things in terms of networks," said Sporns, professor in the Department of Psychological and Brain Sciences in IU Bloomington's College of Arts and Sciences. "In the neurosciences, increasingly we aren't looking at only one part of the brain, but seeing how the interactions between different parts make them work together."

The human brain contains billions of cells that are connected through numerous pathways and networks that remain to be fully traced and charted. This task of mapping these connections can be likened to cartographers constructing maps of a vast and unknown continent. Identifying the large features like rivers or mountain ranges may not be so difficult, but being able to determine how all these features are geographically related in ever finer detail becomes increasingly more challenging. Investigating the web of connections between the countless areas of the brain would be like mapping the Everglades in the 1700s.

In addition to writing his book, Sporns devotes much of his time to two projects that are naturally linked to the research included in Networks. Both of these projects are collaborations with researchers from other universities. The first of these projects is to develop a "virtual brain," a powerful computational model that can simulate brain function; and the second is called the Human Connectome Project, established to map the human brain's major connections.

"Both of these projects are the first of their kind," said Sporns, a co-investigator in the Human Connectome and virtual brain research projects. "The connectome project is spearheading the mapping of human brain connectivity, and the virtual brain project is about building a computational model of the human brain that may become useful in a clinical setting."

The Virtual Brain project is being funded by the McDonnell Foundation and is led by the University of Toronto, with 11 other sites -- including University College London, Universitee Mediterannee Marseille, UPF Barcelona, University of California, Irvine, and the University of Wisconsin, Madison. Scientists are aiming to compile all of the information pertaining to brain function and connectivity so that they can design a model of the healthy brain. This would allow researchers to test the effects of neural stimulation or changes in neural connectivity in various neurological scenarios and see how they affect different parts of the brain in a way they never have been able to before.

The Human Connectome Project seeks to discover the neural pathways that underlie brain function. This massive undertaking is being funded by the National Institutes of Health with more than $30 million, and the main partners are Washington University, the University of Minnesota and the University of Oxford. This five-year study, which began last fall, is examining the brains of 1,200 healthy individuals using various types of neuro-imaging to understand the network architecture of connections in the brain. The Human Connectome Project will also look at behavioral and genomic data to determine how they relate to brain connectivity.

"There are many parallels between the Human Connectome and Human Genome projects in that both projects will give us a unique map," Sporns said. "The Connectome project isn't going to solve all of the problems we face in studying the brain but like the Genome project, it is going to provide us with a great new foundation for asking new research questions and for understanding the network basis of neuroscience."

Thus far, neuroscience research utilizing network approaches is producing very promising results. Scientists are acquiring a wealth of new and useful information that is getting them closer to understanding how the brain works, and how disruptions of networks can lead to brain disorders.

"In the next five to 10 years we are going to have a much better and much more refined understanding of brain structure and function," said a confident Sporns. "Network approaches will open up new horizons in neuroscience."

Olaf Sporns.

Olaf Sporns (b. Kiel, West Germany) is Professor and Associate Department Chair at Indiana University.
Dr. Sporns received his degree from Eberhard Karls University of Tübingen in Tübingen, West Germany before going to New York to study at the Rockefeller University under Gerald Edelman. After receiving his doctorate, he followed Edelman to the Neurosciences Institute in La Jolla, California.

His focus is in the area of computational cognitive neuroscience. His topics of study include functional integration and binding in the cerebral cortex; neural models of perception and action; network structure and dynamics; applications of information theory to the brain; and embodied cognitive science using robotics. He was awarded a Guggenheim Fellowship in 2011 in the Natural Sciences category.

Mangus Family Lore: Marvin Mangus in his Anchorage, Alaska home studio

Here's the magnificent Marv in his studio/showroom c. 1980s.

The Phantom by Paul Ryan

When I'm not busy studying neuroscience and finance, I still enjoy collecting comic book art. Some things never change. This Phantom cover was drawn for the Swedish market where the Phantom is known as Fantomen.

TED video Sebastian Seung: I am my connectome

Sebastian Seung is a Korean American multi-disciplinary expert whose research efforts have spanned the fields of neuroscience, physics and bioinformatics. He is a professor of Computational Neuroscience in the Department of Brain and Cognitive Sciences and a professor of Physics at the Massachusetts Institute of Technology. He also is an Investigator of the Howard Hughes Medical Institute. He is the son of the renowned philosopher, T. K. Seung.

Inside the Battle to Define Mental Illness

By Gary Greenberg, Wired January 2011

Photo: Garry Mcleod; origami: Robert Lang
Photo: Garry Mcleod; Origami: Robert Lang

Every so often Al Frances says something that seems to surprise even him. Just now, for instance, in the predawn darkness of his comfortable, rambling home in Carmel, California, he has broken off his exercise routine to declare that there is no definition of a mental disorder. It’s BS. I mean, you just can’t define it.” Then an odd, reflective look crosses his face, as if he’s taking in the strangeness of this scene: Allen Frances, lead editor of the fourth edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (universally known as the DSM-IV), the guy who wrote the book on mental illness, confessing that these concepts are virtually impossible to define precisely with bright lines at the boundaries.” For the first time in two days, the conversation comes to an awkward halt.
But he recovers quickly, and back in the living room he finishes explaining why he came out of a seemingly contented retirement to launch a bitter and protracted battle with the people, some of them friends, who are creating the next edition of the DSM. And to criticize them not just once, and not in professional mumbo jumbo that would keep the fight inside the professional family, but repeatedly and in plain English, in newspapers and magazines and blogs. And to accuse his colleagues not just of bad science but of bad faith, hubris, and blindness, of making diseases out of everyday suffering and, as a result, padding the bottom lines of drug companies. These aren’t new accusations to level at psychiatry, but Frances used to be their target, not their source. He’s hurling grenades into the bunker where he spent his entire career.

One influential advocate for diagnosing bipolar disorder in kids failed to disclose money he received from the makers of the bipolar drug Risperdal.

As a practicing psychotherapist myself, I can attest that this is a startling turn. But when Frances tries to explain it, he resists the kinds of reasons that mental health professionals usually give each other, the ones about character traits or personality quirks formed in childhood. He says he doesn’t want to give ammunition to his enemies, who have already shown their willingness to “shoot the messenger.” It’s not an unfounded concern. In its first official response to Frances, the APA diagnosed him with “pride of authorship” and pointed out that his royalty payments would end once the new edition was published -- a fact that “should be considered when evaluating his critique and its timing.”

Frances, who claims he doesn’t care about the royalties (which amount, he says, to just 10 grand a year), also claims not to mind if the APA cites his faults. He just wishes they’d go after the right ones—the serious errors in the DSM-IV.We made mistakes that had terrible consequences,” he says. Diagnoses of autism, attention-deficit hyperactivity disorder, and bipolar disorder skyrocketed, and Frances thinks his manual inadvertently facilitated these epidemics -- and, in the bargain, fostered an increasing tendency to chalk up life’s difficulties to mental illness and then treat them with psychiatric drugs.

The insurgency against the DSM-5 (the APA has decided to shed the Roman numerals) has now spread far beyond just Allen Frances. Psychiatrists at the top of their specialties, clinicians at prominent hospitals, and even some contributors to the new edition have expressed deep reservations about it. Dissidents complain that the revision process is in disarray and that the preliminary results, made public for the first time in February 2010, are filled with potential clinical and public relations nightmares. Although most of the dissenters are squeamish about making their concerns public m-- especially because of a surprisingly restrictive nondisclosure agreement that all insiders were required to sign -- they are becoming increasingly restive, and some are beginning to agree with Frances that public pressure may be the only way to derail a train that he fears will “take psychiatry off a cliff.”

At stake in the fight between Frances and the APA is more than professional turf, more than careers and reputations, more than the $6.5 million in sales that the DSM averages each year. The book is the basis of psychiatrists’ authority to pronounce upon our mental health, to command health care dollars from insurance companies for treatment and from government agencies for research. It is as important to psychiatrists as the Constitution is to the US government or the Bible is to Christians. Outside the profession, too, the DSM rules, serving as the authoritative text for psychologists, social workers, and other mental health workers; it is invoked by lawyers in arguing over the culpability of criminal defendants and by parents seeking school services for their children. If, as Frances warns, the new volume is an “absolute disaster,” it could cause a seismic shift in the way mental health care is practiced in this country. It could cause the APA to lose its franchise on our psychic suffering, the naming rights to our pain.

Photo: Garry Mcleod; Origami: Robert Lang
Allen Frances is worried that the DSM-5 will "take psychiatry off a cliff."
Photo: Susanna Howe; photographed at Café Sabarsky, Neue Galerie, NYC

This is hardly the first time that defining mental illness has led to rancor within the profession. It happened in 1993, when feminists denounced Frances for considering the inclusion of “late luteal phase dysphoric disorder” (formerly known as premenstrual syndrome) as a possible diagnosis for DSM-IV. It happened in 1980, when psychoanalysts objected to the removal of the word neurosis -- their bread and butter -- from the DSM-III. It happened in 1973, when gay psychiatrists, after years of loud protest, finally forced a reluctant APA to acknowledge that homosexuality was not and never had been an illness. Indeed, it’s been happening since at least 1922, when two prominent psychiatrists warned that a planned change to the nomenclature would be tantamount to declaring that “the whole world is, or has been, insane.”

Some of this disputatiousness is the hazard of any professional specialty. But when psychiatrists say, as they have during each of these fights, that the success or failure of their efforts could sink the whole profession, they aren’t just scoring rhetorical points. The authority of any doctor depends on their ability to name a patient’s suffering. For patients to accept a diagnosis, they must believe that doctors know -- in the same way that physicists know about gravity or biologists about mitosis -- that their disease exists and that they have it. But this kind of certainty has eluded psychiatry, and every fight over nomenclature threatens to undermine the legitimacy of the profession by revealing its dirty secret: that for all their confident pronouncements, psychiatrists can’t rigorously differentiate illness from everyday suffering. This is why, as one psychiatrist wrote after the APA voted homosexuality out of the DSM, there is a terrible sense of shame among psychiatrists, always wanting to show that our diagnoses are as good as the scientific ones used in real medicine.”
If bad tests are sanctioned in the DSM, insurance companies might use them to cut off coverage for patients deemed not sick enough. It could be a disaster.

Since 1980, when the DSM-III was published, psychiatrists have tried to solve this problem by using what is called descriptive diagnosis: a checklist approach, whereby illnesses are defined wholly by the symptoms patients present. The main virtue of descriptive psychiatry is that it doesn’t rely on unprovable notions about the nature and causes of mental illness, as the Freudian theories behind all those “neuroses” had done. Two doctors who observe a patient carefully and consult the DSM‘s criteria lists usually won’t disagree on the diagnosis -- something that was embarrassingly common before 1980. But descriptive psychiatry also has a major problem: Its diagnoses are nothing more than groupings of symptoms. If, during a two-week period, you have five of the nine symptoms of depression listed in the DSM, then you have “major depression,” no matter your circumstances or your own perception of your troubles. “No one should be proud that we have a descriptive system,” Frances tells me. “The fact that we do only reveals our limitations.” Instead of curing the profession’s own malady, descriptive psychiatry has just covered it up.

The DSM-5 battle comes at a time when psychiatry’s authority seems more tenuous than ever. In terms of both research dollars and public attention, molecular biology -- neuroscience and genetics -- has come to dominate inquiries into what makes us tick. And indeed, a few tantalizing results from these disciplines have cast serious doubt on long-held psychiatric ideas. Take schizophrenia and bipolar disorder: For more than a century, those two illnesses have occupied separate branches of the psychiatric taxonomy. But research suggests that the same genetic factors predispose people to both illnesses, a discovery that casts doubt on whether this fundamental division exists in nature or only in the minds of psychiatrists. Other results suggest new diagnostic criteria for diseases: Depressed patients, for example, tend to have cell loss in the hippocampal regions, areas normally rich in serotonin. Certain mental illnesses are alleviated by brain therapies, such as transcranial magnetic stimulation, even as the reasons why are not entirely understood.

Some mental health researchers are convinced that the DSM might soon be completely revolutionized or even rendered obsolete. In recent years, the National Institute of Mental Health has launched an effort to transform psychiatry into what its director, Thomas Insel, calls clinical neuroscience. This project will focus on observable ways that brain circuitry affects the functional aspects of mental illness -- symptoms, such as anger or anxiety or disordered thinking, that figure in our current diagnoses. The institute says it’s “agnostic” on the subject of whether, or how, this process would create new definitions of illnesses, but it seems poised to abandon the reigning DSM approach. “Our resources are more likely to be invested in a program to transform diagnosis by 2020,” Insel says, “rather than modifying the current paradigm.”

Although the APA doesn’t disagree that a revolution might be on the horizon, the organization doesn’t feel it can wait until 2020, or beyond, to revise the DSM-IV. Its categories line up poorly with the ways people actually suffer, leading to high rates of patients with multiple diagnoses. Neither does the manual help therapists draw on a body of knowledge, developed largely since DSM-IV, about how to match treatments to patients based on the specific features of their disorder. The profession cannot afford to wait for the science to catch up to its needs. Which means that the stakes are higher, the current crisis deeper, and the potential damage to psychiatry greater than ever before.

Allen Frances’ revolt against the DSM-5 was spurred by another unlikely revolutionary: Robert Spitzer, lead editor of the DSM-III and a man believed by many to have saved the profession by spearheading the shift to descriptive psychiatry. As the DSM-5 task force began its work, Spitzer was “dumbfounded” when Darrel Regier, the APA’s director of research and vice chair of the task force, refused his request to see the minutes of its meetings. Soon thereafter, he was appalled, he says, to discover that the APA had required psychiatrists involved with the revision to sign a paper promising they would never talk about what they were doing, except when necessary for their jobs. “The intent seemed to be not to let anyone know what the hell was going on,” Spitzer says.

In July 2008, Spitzer wrote a letter to Psychiatric News, an APA newsletter, complaining that the secrecy was at odds with scientific process, which “benefits from the very exchange of information that is prohibited by the confidentiality agreement.” He asked Frances to sign onto his letter, but Frances declined; a decade into his retirement from Duke University Medical School, he had mostly stayed on the sidelines since planning for the DSM-5 began in 1999, and he intended to keep it that way. “I told him I completely agreed that this was a disastrous way for DSM-5 to start, but I didn’t want to get involved at all. I wished him luck and went back to the beach.”

But that was before Frances found out about a new illness proposed for the DSM-5. In May 2009, during a party at the APA’s annual convention in San Francisco, he struck up a conversation with Will Carpenter, a psychiatrist at the University of Maryland. Carpenter is chair of the Psychotic Disorders work group, one of 13 DSM-5 panels that have been holding meetings since 2008 to consider revisions. These panels, each comprising 10 or so psychiatrists and other mental health professionals, report to the supervising task force, which consists of the work-group chairs and a dozen other experts. The task force will turn the work groups’ proposals into a rough draft to be field-tested, revised, and then ratified -- first by the APA’s trustees and then by its 39,000 members.

At the party, Frances and Carpenter began to talk about “psychosis risk syndrome,” a diagnosis that Carpenter’s group was considering for the new edition. It would apply mostly to adolescents who occasionally have jumbled thoughts, hear voices, or experience delusions. Since these kids never fully lose contact with reality, they don’t qualify for any of the existing psychotic disorders. But “throughout medicine, there’s a presumption that early identification and intervention is better than late,” Carpenter says, citing the monitoring of cholesterol as an example. If adolescents on the brink of psychosis can be treated before a full-blown psychosis develops, he adds, “it could make a huge difference in their life story.”

This new disease reminded Frances of one of his keenest regrets about the DSM-IV: its role, as he perceives it, in the epidemic of bipolar diagnoses in children over the past decade. Shortly after the book came out, doctors began to declare children bipolar even if they had never had a manic episode and were too young to have shown the pattern of mood change associated with the disease. Within a dozen years, bipolar diagnoses among children had increased 40-fold. Many of these kids were put on antipsychotic drugs, whose effects on the developing brain are poorly understood but which are known to cause obesity and diabetes. In 2007, a series of investigative reports revealed that an influential advocate for diagnosing bipolar disorder in kids, the Harvard psychiatrist Joseph Biederman, failed to disclose money he’d received from Johnson & Johnson, makers of the bipolar drug Risperdal or risperidone. (The New York Times reported that Biederman told the company his proposed trial of Risperdal in young children “will support the safety and effectiveness of risperidone in this age group.”) Frances believes this bipolar “fad” would not have occurred had the DSM-IV committee not rejected a move to limit the diagnosis to adults.

Frances found psychosis risk syndrome particularly troubling in light of research suggesting that only about a quarter of its sufferers would go on to develop full-blown psychoses. He worried that those numbers would not stop drug companies from seizing on the new diagnosis and sparking a new treatment fad -- a danger that Frances thought Carpenter was grievously underestimating. He already regretted having remained silent when, in the 1980s, he watched the pharmaceutical industry insinuate itself into the APA’s training programs. (Annual drug company contributions to those programs reached as much as $3 million before the organization decided, in 2008, to phase out industry-supported education.) Frances didn’t want to be “a crusader for the world,” he says. But the idea of more “kids getting unneeded antipsychotics that would make them gain 12 pounds in 12 weeks hit me in the gut. It was uniquely my job and my duty to protect them. If not me to correct it, who? I was stuck without an excuse to convince myself.”

At the party, he found Bob Spitzer’s wife and asked her to tell her husband (who had been prevented from traveling due to illness) that he was going to join him in protesting the DSM-5.
Throughout 2009, Spitzer and Frances carried out their assault. That June, Frances published a broadside on the website of Psychiatric Times, an independent industry newsletter. Among the numerous alarms the piece sounded, Frances warned that the new DSM, with its emphasis on early intervention, would cause a “wholesale imperial medicalization of normality” and “a bonanza for the pharmaceutical industry,” for which patients would pay the “high price [of] adverse effects, dollars, and stigma.” Two weeks later, the two men wrote a letter to the APA’s trustees, urging them to consider forming an oversight committee and postponing publication, in order to avoid an “embarrassing DSM-5.” Such a committee was convened, and it did recommend a delay, because—as its chair, a former APA president, later put it -- ”the revision process hadn’t begun to coalesce as much as it should have.” In December 2009, the APA announced a one-year postponement, pushing publication back to 2013. (The organization insists that Frances “did not have an impact” on the rescheduling of the revision.)

Illustration: Owen Gildersleeve
Illustration: Owen Gildersleeve

James Scully, medical director of the APA, fills the big leather chair in his office overlooking the Potomac River and the government buildings beyond. He’s a large, ruddy-faced man with a shock of white hair, and when he leans forward, his monogrammed cuffs perched on his knees, to deliver his assessment of Frances, even though it’s only two words -- ”he’s wrong” -- you can hear his rising gorge and the sense of betrayal that seems to be swelling behind it.

Of all the things that Frances is wrong about -- and there are many, Scully says, including his position on psychosis risk syndrome -- the confidentiality agreement seems to be the one that really galls. First of all, it’s simply an intellectual property agreementabout who owns the product.” Second, he insists, this is the most open and transparent DSM revision ever, certainly more open than the process that produced Spitzer’s and Frances’ manuals, which were written in the pre-Internet era, before it was possible to field, as the task force has, 8,000 online comments on the proposed changes.

The agreement may well be mere intellectual property boilerplate. But, as I explain to Scully and later to APA research chief Darrel Regier, that hasn’t reassured all the psychiatrists who’ve had to sign it. They fret privately that the DSM-5 will create “monumental screwups” that will turn the field into a “laughingstock.” They accuse the task force of “not knowing where they’re going” and of “not having managed this right from the very beginning.” They worry that the “slipshod nature of the whole process” will lead to a “crappy product” that alienates clinicians even as it makes psychiatry “look capricious and silly.” None of them, however, are willing to go on record, for fear—unfounded or not—of “retaliation” and “reprisal.”

Regier wants to know who said these things.

Not all the dissidents are insisting on anonymity. E. Jane Costello, codirector of the Center for Developmental Epidemiology at Duke Medical School, says she doesn’t mind going on record because she’s “too small a fish” for them to bother with. Costello was one of two psychiatrists who resigned from the Childhood Disorders work group in spring 2009. In her resignation letter, which she subsequently made public, Costello excoriated the DSM committee for refusing to wait for the results of longitudinal studies she was planning and for failing to underwrite adequate research of its own. The proposed revisions, she wrote, “seem to have little basis in new scientific findings or organized clinical or epidemiological studies.” (In a response, the APA cited “several billions of dollars” already spent over the past 40 years on research the revision is drawing upon.)

To critics, the greatest liability of the DSM-5 process is precisely this disconnect between its ambition on one hand and the current state of the science on the other. Of particular concern is a proposal to institute “dimensional assessment” as part of all diagnostic evaluations. In this approach, clinicians would use standardized, diagnostic-specific tests to assign a severity rating to each patient’s illness. Regier hopes that these ratings, tallied against data about the course and outcome of illnesses, will eventually lead to psychiatry’s holy grail: “statistically valid cutpoints between normal and pathological.” Able to reliably rate the clinical significance of a disorder, doctors would finally have a scientific way to separate the sick from the merely suffering.

No one, not even Frances, thinks it’s a bad idea to augment the current binary approach to diagnosis, in which you either have the requisite symptoms or you don’t, with a method for quantifying gradations in illness. Dimensional assessment could provide what Frances calls a “governor” on absurdly high rates of diagnosis -- by DSM criteria, epidemiologists have noted, a staggering 30 percent of Americans are mentally ill in any given year -- and thereby solve both a public health problem and a public relations problem.

But Michael First, a Columbia University psychiatrist who headed up the DSM-5′s Prelude Project to solicit feedback before the revision, believes that implementing dimensional assessment right now is a tremendous mistake. The tests, he says, are nowhere near ready for use; while some of them have a long track record, “it seems that many of them were made up by the work groups” without any real-world validation. Bad tests could be disastrous not just for the profession, which would erect its diagnostic regime on a shaky foundation, but also for patients: If the tests have been sanctioned in the DSM, insurance companies could use them to cut off coverage for patients deemed not sick enough. “If they really want to do dimensional assessment,” First says, “they should wait the five or 10 years it would take for the scales to be ready.

Regier won’t say how many of the tests are usable yet. “I don’t think it will be useful to get into this level of detail,” he emails. He acknowledges that dimensional assessment is still evolving, and he says the DSM-5 field trials—studies in which doctors will test the rough draft of the manual with patients—will help refine the tests. But the field trials, too, are bumping up against formidable deadlines. Although trials were scheduled to begin in May 2010, as of October only a pilot study was actually under way—and protocols for the rest of the trials couldn’t be finalized until that study was completed. Meanwhile, Regier has pegged May 2013 as a drop-dead date for publication of the new manual, which means that two sets of field trials and revisions must be completed by September 2012.

The time crunch only gives critics more fuel. Frances, on hearing of the trials’ delay, BlackBerried out a communiqué about the task force’s “Keystone Kops” missteps—the “Rube Goldberg design,” the “numerous measures signifying nothing,” the “criteria sets that are unusable because so poorly written.” All of which, he wrote, will lead to “a mad dash to dreck at the end.”

When the rough draft of the DSM-5 was released, in February 2010, the diagnosis that had galvanized Frances—psychosis risk syndrome—wasn’t included. But another new proposed illness had taken its place: “attenuated psychotic symptoms syndrome,” which has essentially the same symptoms but with a name that no longer implies the patient will eventually develop a psychosis. In principle, Carpenter says, that change “eliminates the false-positive problem.” This is not as cynical as it might sound: Carpenter points out that a kid having even occasional hallucinations, especially one distressed enough to land in a psychiatrist’s office, is probably not entirely well, even if he doesn’t end up psychotic. Currently, a doctor confronted with such a patient has to resort to a diagnosis that doesn’t quite fit, often an anxiety or mood disorder.
But attenuated psychotic symptoms syndrome still creates a mental illness where there previously was none, giving drugmakers a new target for their hard sell and doctors, most of whom see it as part of their job to write prescriptions, more reason to medicate. Even Carpenter worries about this. “I wouldn’t bet a lot of money that clinicians will hold off on antipsychotics until there’s evidence of more severe symptoms,” he says. Nonetheless, he adds, “a diagnostic manual shouldn’t be organized to try to adjust to society’s problems.”

His implication is that the rest of medicine, in all its scientific rigor, doesn’t work that way. But in fact, medicine makes adjustments all the time. As obesity has become more of a social problem, for instance, doctors have created a new disease called metabolic syndrome, and they’re still arguing over the checklist of its definition: the blood pressure required for diagnosis, for example, and whether waist circumference should be a criterion. As Darrel Regier points out, diabetes is defined by a blood-glucose threshold, one that has changed over time. Whether physical or mental, a disease is really a statistical construct, a group of symptoms that afflicts a group of people similarly. We may think our doctors are like Gregory House, relentlessly stalking the biochemical culprits of our suffering, but in real medicine they are more like Darrel Regier, trying to discern the patterns in our distress and quantify them.

The fact that diseases can be invented (or, as with homosexuality, uninvented) and their criteria tweaked in response to social conditions is exactly what worries critics like Frances about some of the disorders proposed for the DSM-5—not only attenuated psychotic symptoms syndrome but also binge eating disorder, temper dysregulation disorder, and other “sub-threshold” diagnoses. To harness the power of medicine in service of kids with hallucinations, or compulsive overeaters, or 8-year-olds who throw frequent tantrums, is to command attention and resources for suffering that is undeniable. But it is also to increase psychiatry’s intrusion into everyday life, even as it gives us tidy names for our eternally messy problems.

I recently asked a former president of the APA how he used the DSM in his daily work. He told me his secretary had just asked him for a diagnosis on a patient he’d been seeing for a couple of months so that she could bill the insurance company. “I hadn’t really formulated it,” he told me. He consulted the DSM-IV and concluded that the patient had obsessive-compulsive disorder.

Did it change the way you treated her?” I asked, noting that he’d worked with her for quite a while without naming what she had.


So what would you say was the value of the diagnosis?

I got paid.”

As scientific understanding of the brain advances, the APA has found itself caught between paradigms, forced to revise a manual that everyone agrees needs to be fixed but with no obvious way forward. Regier says he’s hopeful that “full understanding of the underlying pathophysiology of mental disorders” will someday establish an “absolute threshold between normality and psychopathology.” Realistically, though, a new manual based entirely on neurosciencewith biomarkers for every diagnosis, grave or mild—seems decades away, and perhaps impossible to achieve at all. To account for mental suffering entirely through neuroscience is probably tantamount to explaining the brain in toto, a task to which our scientific tools may never be matched. As Frances points out, a complete elucidation of the complexities of the brain has so far proven to be an “ever-receding target.”

What the battle over DSM-5 should make clear to all of us—professional and layman alike—is that psychiatric diagnosis will probably always be laden with uncertainty, that the labels doctors give us for our suffering will forever be at least as much the product of negotiations around a conference table as investigations at a lab bench. Regier and Scully are more than willing to acknowledge this. As Scully puts it, “The DSM will always be provisional; that’s the best we can do.” Regier, for his part, says, “The DSM is not biblical. It’s not on stone tablets.” The real problem is that insurers, juries, and (yes) patients aren’t ready to accept this fact. Nor are psychiatrists ready to lose the authority they derive from seeming to possess scientific certainty about the diseases they treat. After all, the DSM didn’t save the profession, and become a best seller in the bargain, by claiming to be only provisional.

It’s a problem that bothers Frances, and it even makes him wonder about the wisdom of his crusade against the DSM-5. Diagnosis, he says, is “part of the magic,” part of the power to heal patients -- and to convince them to endure the difficulties of treatment. The sun is up now, and Frances is working on his first Diet Coke of the day. “You know those medieval maps?” he says. “In the places where they didn’t know what was going on, they wrote ‘Dragons live here.’

He went on: “We have a dragon’s world here. But you wouldn’t want to be without that map.”

Gary Greenberg is the author of Manufacturing Depression: The Secret History of a Modern Disease

Wired April 2012

MIT’s Sebastian Seung Wants Computers to Map the Brain

By Matthew Hutson

Sebastian Seung wants to get computers to connect our thoughts.Photo: Rainer Hosch

As a first-year MIT professor, Sebastian Seung taught neuroscience—even though he had never taken a neuroscience class. He was trained as a theoretical physicist, but a random conversation with some brain scientists made him want to study the ultimate emergent physical phenomenon: human intelligence. “How do you take dumb neurons and put them together to make an intelligent mind?” he asks. Seung is now a professor of computational neuroscience in MIT’s Department of Brain and Cognitive Sciences His career-changing encounter proves once again that it’s not what you know, it’s who you know. And as we learn from his new book, Connectome, the same goes for neurons, whose roles are defined primarily by the neurons they communicate with. Seung’s work explores a growing field called connectomics, the mapping and study of neural networks. It’s usually done by examining the brain with an electron microscope and manually identifying cells and synapses. This is an incredibly slow process; it took scientists a dozen years to map the connections between the 300 neurons in a tiny worm. The human brain has 100 billion neurons. To speed things up, Seung has begun developing computer-vision algorithms that pinpoint the boundaries between individual neurons. It’s a nice payback for all of the brain power we’ve invested in AI research. “Ask not what the brain can do for the computer,” Seung says. “Ask what the computer can do for the brain.” His work could someday lead to a better understanding of memory, personality, and pathologies. For now, Seung is just following his curiosity—and one nagging question: Are we all simply the sum of our connectome?

Wednesday, June 27, 2012

3-D Jonny Quest

Check out the 3-D Jonny Quest vid below.

The Who: My Generation 1966

The Who.

Buddy Rich : A Typically Outrageous Drum Solo

The one and only Buddy Rich (1917-1987) often billed as "the World's Greatest Drummer."

Link Wray: Rumble 1998

Link Wray.

The Ultimate Brain Quest

Deciphering how human thought works is mind-bendingly difficult, but researchers now know where to start.


By Sebastian Seung
Houghton Mifflin Harcourt, 359 pages

[CONNECT1] Thomas Deerinck/NCMIR/Photo Researchers
Nerve cells in the brain. Neurons are supported and protected by smaller, and even more numerous, glial cells.

"Every day we recall the past, perceive the present and imagine the future. How do our brains accomplish these feats? It's safe to say that nobody really knows," Sebastian Seung writes early in Connectome, his exploration of how researchers have at least made a start toward understanding how those feats are accomplished. Mr. Seung, a professor of brain science at the Massachusetts Institute of Technology, is an amiable guide, witty and exceptionally clear in describing complex matters for the general reader.

He begins with the observation that each of us is unique, differing from one another in uncountable ways. These differences arise in part because we have different genes that influence brain development and, accordingly, behavior. Also important are gene-by-environment interactions and gene expression: You might have a genetic predisposition toward alcoholism, but without the right environmental triggers, that gene may never become active. The sequencing of the human genome has provided a map of our 20,000 genes, and we are gradually gaining insights into what these genes do, individually and in combination.

Neuroscientists posit that all of our hopes, desires, beliefs and experiences are encoded in the brain as patterns of neural firings. Just how this happens is not precisely understood, as the author attests, but we have made great strides in understanding how neurons communicate with one another. Progress has also been made in mapping which brain systems control which kinds of operations (my own field of research): One system is responsible for lifting your foot, another senses the pain when you stub your toe; one system helps you to solve arithmetic problems, another enjoys "La Bohème." A new approach to studying brains and individual differences involves making maps of how neurons connect to one another. Following the term genome, these are called connectomes.
"Why study connectomes if genomics is already so powerful?" Mr. Seung asks. "The answer is simple: Genes alone cannot explain how your brain got to be the way it is. As you lay nestled in your mother's womb, you already possessed your genome but not yet the memory of your first kiss."

The human brain contains 100 million neurons, and each neuron makes thousands of connections on average. If we assume that each distinct connection pattern gives rise to a distinct brain state—like the effervescent sensation after that first kiss—the number of brain states exceeds the number of known particles in the universe. Your experiences, memories, personality and thoughts are thus encoded in the ways your neurons connect to one another. The next big frontier is mapping those trillions of neural connection patterns to their brain states. By observing a particular network of neurons firing, researchers should know (in theory) whether you are thinking about love or money, beer or burgers.

The associational networks of your brain determine to a large degree how you understand the world and your place in it. When prompted with "red" you might respond "apple," while another person may respond "flame." Your fears and phobias, likes and attractions, were influenced by a lifetime of outcomes and associations. The information thus contained in your connectome is what sets you apart from everyone else, what describes your unique personality. "Information," according to Mr. Seung, "is the new soul."

But before readers can profitably learn about the connections, they need to understand something about neural physiology, neurotransmitters, synapses and neuroanatomy. Mr. Seung is equal to the task: Connectome offers the equivalent of a college course on neuroscience, covering such technical matters as spike trains, cortical layering, ion channels, and the function and structure of axons and dendrites. He also throws in a bit of neurochemistry, assuming no prior knowledge of biology, chemistry or psychology.

Except for the last two chapters, the book is not so much about connectomes as about how to use connectomes to frame neuroscience. We learn about the tools of the neuroscience trade—how they work and why they are important. From there we learn how patterns of neural connections give rise to our perceptions of the world, our reactions to perception and, ultimately, our uniqueness. Although obtaining connectomes for even the simpler brain of the mouse is beyond our technological abilities today, Mr. Seung lays out the technical hurdles and proposes some more attainable near-term goals. But he also makes a passionate case for a decade-long investment of time and energy, comparable to the Human Genome Project, to advance the cause.

Even in the current speculative realm, the connectome is a fascinating, occasionally frustrating, subject. One view is that each connectome or connectivity map will give rise to one and only one brain state and that different connectomes cannot give rise to the same state. Yet the widespread use of pharmaceutical agents such as Prozac and Ritalin suggests otherwise—that knowing the connectome is unlikely to tell us all we need to know about a person's thoughts, feelings, opinions and personality.

The levels of various chemicals in our brains can clearly be altered pharmaceutically. They are also influenced by diet, exercise, stress and normal biological cycles. Even if we know how the neurons are connected and the strength of their synapses, the amount of dopamine, for example, that is available in the brain at any given moment will influence firing patterns. This could cause the same neural network (a group of connected neurons) to give rise to different thoughts or different networks to give rise to similar thoughts.

Despite the fact that we have different brains and different neuronal configurations, when you and I smell a skunk it seems likely that we have equivalent mental states that lead to the same conclusions. Knowing the wiring is a crucial operation in understanding the nature of thought, but it seems not to be enough; we also need to know the precise chemical soup du jour in the brain. And one more additional, crucial step is understanding which types of experiences and environmental events can change the brain's wiring and in what ways.

The last two chapters of Connectome will be catnip for futurists, as Mr. Seung lays out two possible benefits of understanding connectomes: the repair of cryogenically frozen brains and subsequent restoration of consciousness and the uploading of consciousness into computer simulations. In the best (but unlikely) case, either could lead to cognitive immortality. Although the claims are far-fetched, they are beautifully explained and analyzed—as I might have expected from a writer who has produced the best lay book on brain science I've ever read.

Mr. Levitin is a professor of psychology and neuroscience at McGill University in Montreal. His books include This Is Your Brain on Music.