GUEST AUTHOR ARCHIVES
June 29, 2004
Eyetech Pharmaceuticals and Pfizer recently applied with U.S. regulators to market their experimental drug for age-related macular degeneration (AMD), the leading cause of blindness in older people.
Eyetech is one of a growing group of sensoceutical companies developing therapeutics to stem sensory decline associated with aging. Today, over 15 million people in the United States suffer from some form of AMD. This number is expected to increase significantly in the coming years as life expectancy continues to climb. In addition to sight, other sensoceutical companies are currently working on treatments for other sensory system disorders, such as: hearing loss, taste disorders, and chronic pain.
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June 25, 2004
This week's Science also has an interesting proteomics tid-bit, titled, "Written in the Blood." The piece confirms the diagnostic potential of blood. "Blood teems with telltale proteins that can reveal incipient prostate cancer, for example, and help show whether a patient is cruising for a heart attack. Researchers hoping to discover more of these bio-markers might start with this new collection from the National Cancer Institute in Frederick, Maryland. The database catalogs more than 1400 blood proteins isolated during a recent exhaustive analysis, the largest haul yet." This just goes to show that we still don't know all the proteins that exist in our blood, or for that matter in our brains, and that we are still in need of effective high-throughput methods of detecting and identifying them. Where is that protein chip anyway?
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June 24, 2004
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"Psychologists and economists have long appreciated the contribution of reward history and expectation to decision-making," begins a brilliant research article in this week's Science. In "matching behavior and the representation of value in the parietal cortex," Stanford University researchers used neuroimaging, neurophysiology and neural computation to understand how "specific histories of choice and reward lead to an internal representation of the 'value' of possible actions."
To understand the ways that sensory input, choice, and decision-making occur in the brain, the researchers placed monkeys in a dynamic foraging environment in which they had to track the changing values of alternative choices through time. They found that a simple model based on reward history (that computationally is close to near-optimal behavior) can duplicate this behavior and that neurons in the parietal cortex represent the relative value of competing action predicted by this model.
As I wrote in "economics from the neurons up," neuroeconomics has a very bright and interesting future. Understanding the neurobiology of decision-making will surely impact our legal system in the years to come, as our understanding of choice, dependency and free will are called into question. This has been a major area of focus of Paul Zak's work on the neurobiology of trust which has been supported by the Gruter Institute over the years.
This line of research has broad societal implications, especially for those who believe we can significantly enhance human performance via neurotechnology. Note the fact that natural monkey behavior correlated well with near-optimal computational models. If it becomes possible to not just enable individuals to achieve a more balanced set of cognitive, emotional and sensory acuities that match the high end of natural performance, but to actually go beyond these bio-evolutionarily defined limits, then we will surely be heading towards a neurosociety where we will be faced with a new driver of social complexity that I call the "perception shift dilemma."
NOTE to email readers: Over the past two months, over 200 of you have joined Brain Waves distribution list. All of the pieces I write on Brain Waves contain a link at the beginning of the email that will take you to a website that not only contains the text of the article but usually five to ten well researched links to supporting information or my previous articles on a subject. For example, click on the above link to get to Brain Waves where there are links to other neuroeconomics articles, background on brain imaging technologies, and pieces I've written on perception shift. Thank you for your continued interest.
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June 23, 2004
In April of 2002, President Bush established the New Freedom Commission on Mental Health to conduct a "comprehensive study of the United States mental health service delivery system." In July of 2003, this commission issued its recommendations. This July, Bush will announce a massive plan to screen the entire U.S. population for mental illness and will direct more than 25 federal agencies to implement the committee's recommendations. At the core of the proposal are six goals:
1) Americans Understand that Mental Health Is Essential to Overall Health
2) Mental Health Care Is Consumer and Family Driven
3) Disparities in Mental Health Services Are Eliminated
4) Early Mental Health Screening, Assessment, and Referral to Services Are Common Practice
5) Excellent Mental Health Care Is Delivered and Research Is Accelerated
6) Technology Is Used to Access Mental Health Care and Information
So how does the government intend to implement such an ambitious program? A recent BMJ article written by Jeanne Lenzer suggests that the most likely avenue is through our schools. "Schools", wrote the commission, are in a "key position" to screen the 52 million students and 6 million adults who work at the schools.
While many view this plan as a step in the right direction, others are concerned that the initiative will "promote the use of expensive antidepressants and antipsychotic drugs favored by supporters of the administration." Indeed, Lenzer writes that the sweeping mental health initiative will use the Texas Medication Algorithm Project as a model, a model that has been criticized for promoting more recently approved drugs over older ones.
More on this story as it unfolds.
Update 7/7: Problems arise with Texas Mental health roll out
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June 18, 2004
Neuroelectronics device manufacturer Cyberonics received preliminary approval for a surgical implant to treat severe depression. It is the first time an implanted device has been recommended for the treatment of a psychiatric disorder.
Using a technique known as vagus nerve stimulation, the implanted device uses electrodes implanted in the neck to activate brain regions that are believed to regulate mood. The involves connecting a wire to the left vagus nerve in the side of the neck; a battery is implanted high in the left chest or under the armpit, and the amount of current can be regulated externally. Typically, the implant sends a 30-second pulse of current followed by a five-minute pause, 24 hours a day.
The Neurological Devices Panel of FDAs Medical Devices Advisory Committee voted 5 to 2 to recommend approval with conditions of Cyberonics VNS Therapy System as an adjunctive long-term treatment of chronic or recurrent depression for patients over the age of 18 who are experiencing a major depressive episode that has not had an adequate response to four or more adequate antidepressant treatments. The stock, CYBX, surged 70% on the news.
While it is clear from the committee's recommendation that several emoticeuticals to treat depression must first be tried, the recommendation highlights an important trend in the emerging neurotechnology industry: neuroceutical makers and neuroelectronics manufacturers will increasingly compete for market share as they strive towards developing for better tools to treat mental illnesses. Indeed, Cyberonics already has pilot studies underway to evaluate VNS Therapy as a potential treatment for anxiety disorders, Alzheimers disease and chronic headache/migraine.
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June 15, 2004
In a recent Fortune article, The End of Aging, Aubrey de Grey boldly predicts that life spans will increase dramatically in the coming years. Needless to say, his thoughts have created quite a bit of conversation (see the 100 comments logged on Randall Parker's de Grey post).
So what if Aubrey is right?
As people live physically longer and healthier lives, mental health will become the preeminent social and political issue of our time. Living longer physically does not mean living in better mental health. Mental health is the springboard of thinking, communication skills, learning, emotional growth, resilience, and self-esteem.
With longer life spans, the potential for mental illness follows. For example, dementia, the loss of function in multiple cognitive domains, increases with age. The largest number of persons with dementia occurs in people in their early eighties. As the number of people living over 80 years explodes to over 20% of the US population by 2040, dementia will take over as the leading cause of disability. That is, if appropriate tools for stemming cognitive decline, cogniceuticals, don't materialize.
Today, five of the ten leading causes of disability worldwide (major depression, schizophrenia, bipolar disorders, alcohol use and obsessive compulsive disorders) are mental illnesses. A recent report titled, Prevalence, Severity, and Unmet Need for Treatment of Mental Disorders in the World Health Organization World Mental Health Surveys shows that they are relevant in poor countries as they are in rich ones, and all predictions point to a dramatic increase in mental illness.
Neurotechnology will play the leading role in defining, diagnosing and treating mental health problems in the coming years as concerns about life expectancy turn towards the issues related to mental health expectancy.
Update: A nice fact I learned from Bobbi Low at Gruter: life spans of different organisms across the planet range from 5 minutes to 300 years.
Update 8/16/04: "Earth's oldest living thing is a bristlecone pine in California that's been around for an estimated 4,7000 years" (Deborah Gangloff, Executive Director of the American Forests journal). Thanks Brandon.
+ TrackBacks (0) | Category: NeuroWave 2050
June 14, 2004
Saegis Pharmaceuticals is a bright star among the dozens of private cogniceutical companies. Last week I had a chance to sit down with CEO Rodney Pearlman to discuss their unique approach to developing "medicines that protect and enhance the function of the human mind."
Saegis is a cogniceutical pioneer focused on age-related cognitive impairment disorders like Alzheimer's Disease, Mild Cognitive Impairment, as well as, psychiatric and trauma related cognitive impairment induced by schizophrenia and coronary artery bypass surgery. Cogniceuticals are neuropharmaceuticals that target the mental processes responsible for perception, attention, learning, memory, thought, and communication (see NIMH definition of cognition).
Unlike many neuroceutical companies whose research emphasizes specific neurochemical pathways that have been correlated to memory impairment, Saegis uses a high-throughput behaviorial model called Parallax to identify and validate preclinical compounds that improve memory. Instead of trying to discover molecules that can influence a specific molecular pathway which has shown some correlation to cognition, but may also impact emotional and sensory systems, the Saegis "phenotypic" approach looks for novel compounds that result in improved cognitive abilities as measured by overall behavioral improvement in memory related tasks after taking different cogniceuticals.
This pure focus on cognition should allow Saegis to compete effectively in almost every segment of the cogniceutical market. Saegis is nearing Phase II clinical trials this year in the two fastest growing neuroceutical markets, Alzheimer's Disease and Schizophrenia, but will likely attack other markets like OCD in the coming years as complex mental disorders are differentiated further. For example, "While currently marketed drugs are effective in treating the psychotic aspects of schizophrenia, Cognitive Impairment Associated with Schizophrenia (CIAS) is rapidly becoming recognized as an untreated area for these patients."
By differentiating the cognitive, emotion and sensory modalities associated with complex mental disorders, Saegis is recognizing cutting edge research that is emphasizing "the need to rethink how we categorize psychiatric disorders." As Dr. Sanjaya Saxena, who has led several recent brain imaging studies on OCD, "Diagnosis and treatment should be driven by biology rather than symptoms."
For this reason we should see an increasing trend towards the research and development of cogniceuticals, emoticeuticals and sensoceuticals that will be used in combination to treat complex mental disorders in the coming years.
While there is great hope for emerging cogniceutical treatments, the ever "sagacious" Rodney Pearlman reminds us that "the real proof is in the pudding." Fortunately for Saegis, he seems to have the right mix.
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June 10, 2004
Several months ago Dr. Rajaram contacted me from India about an idea he had to utilize neurotechnology to improve software engineering productivity. The following is a paper he has written about the project. He is currently looking for sponsors and will be visiting the U.S. in mid-June (in New York On June 11 and in SF on the 21st).
Written by L.N.Rajaram, PhD
The average experienced programmers inject as many as 10 defects in 100 lines of code, spending more than 40% of their development time finding and fixing defects.
There are many reasons for writing software in such an inefficient manner including inexperience, incompetence, and the intrinsic complexity of the problem to be solved. The most common reason is an inexplicable tendency to discard proven prescribed practices of systematic effort and indulge in practices that Watts Humphrey calls as those of 'American Cowboy Programmers'. This style is popular with even some experienced programmers and is characterized by a sporadic mixture of 'code-a-bit, test-a-bit' (called CABTAB) set of unplanned activities.
Many attempts have been made to stop such practices by introducing several organizational models, standards and certifications. The most effective of these have been the Personal Software Process and the Team Software Process of the Software Engineering Institute, as these address issues at the level of individuals and teams that develop software. The emphasis is on individuals planning their activities and working according to their plans. Such disciplined way of working has shown astounding results and those who for some reason have undergone such training and have seen their individual performance improve remain converted to that style of programming.
However, the crunch is in getting people to realize that there is a need to improve, to get them to undergo this training and to inculcate a discipline of self restraint against tempting short cuts that are actually counter productive.
There is a persistent delusion that software complexity can be overcome with some heroic intellectual effort. A kind of folklore romanticism exists amongst the software community that they are the intellectual cream of the society and can overcome all challenges by the sheer power of their brains. However, the evolutionary origins of the human brain suggest that it is not designed to tackle the challenges faced in software development. The mind is involved in sporadic switching between the real world problem and its symbolic representation, between high level conceptual abstraction and low level procedural detail, between the ambiguity and hence flexibility in user requirements and the rigidity of a dumb machine. The mind is ill equipped to handle this complexity and requires help. The evolutionary psychologist Leda Cosmides sums it up very succinctly in Our modern skulls house a stone age mind.
The 'triune brain' proposed by Paul Mclean is fascinating. The model talks of evolutionary layers of brain. The brain stem is a reptilian relic and forms the lowest layer and is primarily responsible for controlling body's basic metabolic functions, like heart rate and breathing. On top of that is the second layer known as paleo-mammalian brain, also known as the limbic system. This is the seat of emotion and memory, comprising the amygdala, the hyppocampus and the hypothalmus. "Our primary emotions, love and fear, sadness and joy-emerge from this region, coloring incoming stimuli with emotional valences we have associated with past events stored in the hyppocampus or the amygdala." The top most layer is the neo-cortex. This is the most distinctly human and evolutionarily youngest component of the brain's architecture. Only primates have something similar. The cortex is the seat of abstract thought, long term thinking and complex communications.
It is obvious that the cortex has a very big role to play in an objective and rational intellectual process required for software development. Within the cortex there are different centers that process sensory information, do mathematical abstraction, language and symbolic abstraction and construction, fill-in missing information by sub-consciously extrapolating known facts, implied contexts and so on. Different circuits come into play during different levels and types of abstractions undertaken while formulating software requirements, design specifications, detailed level logic and algorithms and while implementing the code. Disciplined methods of software programming help in the predominant functioning of one or the other part of the brain and the 'cow-boy style programming' encourages the unstructured chattering of different parts of the brain bidding quick-fix solutions.
But we have a more serious problem than the incoherent functioning of the different parts of the rational brain. Software work like all other work does carry the attendant emotional baggage. There is fear of failure, need for peer recognition, expectation of reward, competitive pressure. Thus the limbic system also climbs on to the center-stage of the orchestra in the mind involved in software development. The Stroop Interference Test enables us to appreciate how difficult it is concentrate on any one aspect and to stop one's brain from thinking different things. It is indeed a wonder that the human brain has had so many intellectual achievements to its credit, in spite of its 'primitive' design.
Until the maturing of the software industry in the last couple of decades, a very insignificant fraction of the society has been involved in intellectual pursuits. For the first time in the history of mankind millions of people are involved in the type of intellectual activity characterized by the knowledge economy. Hence it has become very critical to find ways of routinely enhancing the intellectual productivity of large representative sections of society not specially endowed with extraordinary abilities. These neuro-feedback techniques have to augment the ongoing efforts of evangelizing disciplined software methods.
The application of neurotechnology could provide us with a 'head cap' that provides us with a feedback to help us monitor our brain activity. With the help of this feedback, individuals can be trained to willfully chose and restrict activity to the most effective part in the brain to deal with the specific aspect of the software problem at hand. The feedback can be used to prevent the cacophony of all the parts of the brain to drown us in an overkill of rationality and emotions. Several experiments in different contexts have been reported to localize and even measure the electrical activity in different parts of the brain of a subject to see its correlation with what the subject was thinking at that time. Steven Johnson has reported in his book 'Mind Wide Open' as to how he could calm his mind to 'pay attention to one specific aspect and shutting out other activity by the observing the feedback obtained by measuring his 'Theta waves'. Many sports persons have benefited by this technique and great ones like Tiger Woods seem to have a natural ability to shut out all unrequired rational thought while performing.
I propose that several areas of research be undertaken to ultimately understand how software productivity can be enhanced with a better understanding and monitoring of brain activity. To start with I propose that several subject programmers be asked to volunteer to study the activity pattern in their brains under controlled conditions. The conditions could be varied systematically by first having volunteers who practice disciplined software methods and have a proven track record of very good results. Secondly, the volunteers could be drawn at random without any previous coaching in disciplined methods. They could then be subject to other conditions such as stress of schedule, reward, ridicule, etc. A correlation between the use of best practices, the spatial and temporal distribution of brain activity and the quality of software and individual productivity could be established.
This study could then lead to applying the results to train intellectual workers to enhance their concentration on one aspect of the problem and thus improve their productivity. By observing the impact of stress and other emotional aspects, the work environment including the corporate set-up can be reengineered to suit this kind of work.
If we could get an insight into how to help individuals write defect free software to a far greater degree than the prevailing state of art we would have unlocked a major productive force that could make this world a far better place to live in. If you are interested in learning more about this project please contact me directly at (rajaram-at-webcalltech-dot-com)