Saturday, January 31, 2009

Higher Education & Humanistic Decline

On Jan. 18, 2009, Stanley Fish published an opinion article in The New York Times entitled "The Last Professor", lamenting the decline of Liberal Arts and humanistic education in American colleges and universities. I seconded Professor Fish on his stance and re-post my comment (#449) with added links below:

This editorial informs us about the pedagogic difference between illumination, that is a traditional humanistic education, and academic training of professional skills. The latter has taken precedent during the last century and dominates American higher education today. The author cites Phoenix University as case in point.

In support of a higher education that is more oriented toward learning how to examine complex processes, less focused on the solution of a single issue, and less translational, we may consider fundamental scientific research. The eminent virologists, who shared last year’s Nobel Prize for their breakthrough discoveries in AIDS research, did not start out on their careers with AIDS on their mind. Actually, when they set out, AIDS was not known. They were interested in understanding a certain type of virus, retroviruses. The AIDS virus serendipitously happened to be a retrovirus. The prior knowledge about this type helped to unravel the virus’ secrets. Phoenix University is not going to educate such people.

Professor Fish probably meant University of Phoenix as an example of for-profit institutions of higher learning that offer courses mainly online. On Jan. 25, Colby Sledge of The Tennessean reported in an article entitled "Tennessee could discipline for-profit colleges" on the low in-state completion rates for the student body at private for-profit colleges and universities. The newspaper hosts an informative database on enrollments, completion and placements rates at such institutions in Tennessee. Most offer specialized professional training and report successful in-field placement for more than three quarters of their graduates. According to this database, University of Phoenix at Nashville reports 869 students enrolled. The completion rate is listed at 39.6% without placement. (Akademos, Inc.)

Friday, January 23, 2009

Imaging Discord in the Brain

The advent of functional brain imaging has revolutionized the fashion in which psychologists and psychiatrists look at the brain. The pictures of behavior-related cerebral activation provide unprecedented information leading to new hypotheses about the workings of our mind.

However, it is of utmost importance to keep in mind that non-invasive functional brain imaging methods do not allow us to record nerve cell activity directly. With positron emission tomography (PET), single photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI), the most-frequently used procedures detect changes in local cerebral blood flow while the participants are exposed to sensory stimulation or execute tasks. Brain cells need sugar and oxygen to fuel the chemical reactions necessary for information processing. Both resources cannot be stored in the brain and thus have to be delivered on demand. Hence, local blood flow increases when nerve cells are activated, resulting in a tight association between nerve cell activity and blood flow under normal physiological conditions.

The molecular mechanisms that couple blood flow to nerve cells activity are not yet fully understood. Glutamate constitutes the predominant excitatory neurotransmitter in the cerebral cortex. This neurotransmitter, its precursors and metabolites as well as its cellular receptors may play a crucial role in the coupling of the two events. However, molecules unrelated to glutamate may also be important. Nitric oxide (NO) and adenosine are known to influence the blood flow response.

In addition to our lack of knowledge on the coupling between the nervous and the vascular response, blood flow measurements inherently cover a volume of brain tissue and do not permit us to identify precisely which nerve cells drive the observed change in flow.

In this week's issue of the journal Nature, Kerri Smith informs us on new findings relevant to the interpretation of functional brain imaging. Yevgeniy Sirotin and Aniruddha Das demonstrate the consequences of the uncertainties discussed above in a letter to Nature entitled "Anticipatory haemodynamic signals in sensory cortex not predicted by local neuronal activity" (Nature 457:475-479). The authors used optical imaging for the fine-grain mapping of changes in blood flow in exposed primary visual cortex of monkeys. The animals were trained to react to a small visual cue. As anticipated, blood flow increased locally in visual cortex after stimulus onset, and the researchers could record concomitantly increased nerve cell activity with wire electrodes inserted into the brain tissue at this location.

Remarkably, blood flow also increased, when the monkeys expected the visual cue to appear, but it was not presented. The anticipation alone was sufficient to significantly increase the local blood flow. By contrast, Sirotin and Das were not able to detect any increase in nerve cell activity that could be related to the anticipatory increase in blood flow.

The apparently discordant findings may not be entirely surprising. The monkeys were accustomed to treats as reward for their participation. Their readiness for the task may have activated neuromodulatory inputs to visual cortex that remain sub-threshold under ordinary conditions and do not trigger nerve cell activity directly, but facilitate the nerve cell response to the imminent stimulus. How such sub-threshold nerve cell signals may increase local blood flow remains an open question.

The discrepancy between blood flow and nerve cell activity Sirotin and Das observed suggests that blood-flow based brain imaging data must be considered with utter prudence, when complex behaviors are examined that involve the subjects' active participation and anticipation. The findings should caution those who strive to correlate patterns of cerebral blood flow with socio-affective mental disorders and criminality in the hope of developing novel predictors for our actions.

Neurolaw is an attempt to associate patterns of brain activity with criminal behavior. Terry Gross interviewed the eminent American neuroscientist Michael Gazzaniga on this issue on National Public Radio's Fresh Air broadcast July 28, 2008. I once wrote down my thoughts on this idea in secret ink. If you wish to spare a few minutes, click on the video, let the magic unfold and enjoy!

Sunday, January 18, 2009

Parent Scientists, Children & Informed Consent

On Jan. 17, 2009, Pam Belluck published an article online in the The New York Times with the title "Test Subjects Who Call the Scientist Mom or Dad", in which she describes scientists using their own children in their research. The methods employed were observation of behavior and non-invasive diagnostic techniques, e.g. magnetic resonance imaging (MRI) of brain development and electroencephalography (EEG). In MRI, a scanner maps tiny realignments to high radio-frequency pulses in the spin axes of atomic nuclei inside the body that have been lined up in a strong magnetic field. The measurements are used to reconstruct our body's interior in image slices. With EEG, tiny electrical signals from the nerve cells in the brain are recorded with wire electrodes attached to the surface of the scalp. I conducted such studies as principal investigator. The research is summarized in a chapter of a book entitled "Blindness and Brain Plasticity in Navigation and Object Perception." Some essential findings are described in the posts dated Dec. 31, 2008, and Dec. 9, 2007, on this blog. Both techniques do not pose any known health risks to the participants. I submitted the following comment with the article (comment #9): 

Asking someone to participate in a scientific research study resembles in many ways ancient rites of hospitality. If we are invited to stay with friends, we take it for granted that they shall take good care of us and protect us from harm within their limits.

People who wish to participate in a research study that does not benefit them directly, but furthers scientific knowledge at large, expect to be well informed about the risks that the study may pose. They certainly will expect that the principal investigator is not going to put them knowingly in harms way and that, in case of an accident, everything possible will be done for them within reasonable limits.

Commonly, MRI studies do not pose any risk greater than everyday life for healthy people who do not wear magnetic parts or electronic devices in their bodies. However, the procedure may be quite intimidating, particularly when children are involved. Therefore, it certainly is reassuring for the participants to know that they and/or their children are asked to undergo a procedure that the principal investigator and her/his children have undergone before. Of course, the participants have the right to stop the procedure at any time without any negative consequences and, implicitly, this right extends to the children of principal investigators.

The same rationale applies to EEG and, in principle, to behavior studies. However, while the MRI scanner and the EEG recorder deliver objective results, it is questionable whether parents can be impartial observers of their children's behavior.

Important to all studies with very young children, the question remains to be answered whether the mind of a five-year old has developed sufficiently to understand risk and give informed consent.

Saturday, January 10, 2009

Fundamental Research: Progress & Renewal

About a century ago, a group of German academic luminaries led by the theologian Adolf von Harnack approached Kaiser Wilhelm II with a bold idea. In the preceding century, the era of the founders had brought unprecedented economic growth to the country through a seemingly never ending chain of technological innovations and breath-taking industrialization. Progress in biomedical research had resulted in improvements in public health that extended life expectancy by 20 years. The first laws instituting health care and pension plans for the public had been passed and German citizens had come to enjoy the benefits of a welfare state.

However, the learned gentlemen felt that despite this progress, there was no time for complacency. Germany was about to lose her competitive edge in fundamental research. The country would fall behind the other great European powers, if she could not maintain the creativity necessary to meet the challenges of the new century. The state-funded universities as the only sites for fundamental research were not equipped to support the ever-rising costs of ever-more complex scientific research. Germany desperately needed a new organization that had sufficient resources in order to plunge ahead successfully. Local governments would be able to provide some support for infrastructure, but the national government needed to finance the costs of research and salaries for the investigators. It was only natural that the scientists turned to the Emperor for help. He was the nation's greatest philanthropist with a penchant for science and technology.

Regardless of his love of innovation, the Prussian Wilhelm II ran an utmost exacting government. The scientists understood that they needed a solid proposal to put forth to his Majesty, if they wanted to be successful.  In order to develop a promising model for the venture, they sent a delegation to New York City to visit the newly founded Rockefeller Institute for Medical Research and learn how an organization purely dedicated to research was run. The Germans must have found good advice, because the Emperor was impressed with their proposal. In 1911, he enthusiastically agreed to found the Kaiser Wilhelm Society for the Advancement of Science. The Rockefeller Foundation contributed a part of the outside funding.

The former Institute for Biophysics, a hotel in 2012.
The Kaiser Wilhelm Institute that I learned to know as a student was the Institute for Biophysics in Frankfurt am Main. This institute was created in the 1930s from a predecessor founded in the early 1920s as the Institute for Physics in Medicine (free translation). Some research facilities, the obligatory bust of Max Planck greeting the visitor, a library, and a small auditorium were housed in a majestic villa with Romanesques arches near Johann Wolfgang Goethe University's medical school on the other side of the river (Kennedy Allee). A pictures of the building's interior is shown on page 4 of the 2003 Institute Guide.

Future Nobel Prize laureates would conduct their research in this building. I heard lectures on irreversible thermodynamics in the auditorium which inspired my post dated Dec. 16, 2007. The lectures were announced in a glass case hung next to the high entrance portal with dark-brown doors milled from solid oak. The case was adorned with a beautifully carved wooden frame still bearing the name "Kaiser Wilhelm Institute" between oak leaves on top.

After the second world war, the Kaiser Wilhelm Society was transformed into the Max Planck Society. In 2003, the laboratories of the Max Planck Institute for Biophysics strewn across several locations were consolidated in one new facility. Today, the Max Planck Society maintains 80 research institutes with a great variety of emphases ranging from history of arts to plasma physics. Still the Society is providing most funding for the research, including the salaries for principal investigators and staff, thus protecting its scientists to a large degree from the colossal strain and time investment involved in grant writing. The exclusive support may enable the scientists to pursue their research less impeded. However, it does not come without strings attached. Scientific councils rigorously review the research projects and institutes periodically to ensure the best quality of science and progress into important novel directions.

In the United States, the Rockefeller Institute has evolved into an eminent postgraduate private research university. However, federal agencies almost fully fund the research conducted there today. Principal investigators spend much of their time writing grant proposals with ever-diminishing chances for funding. I have explicitly written about the worsening funding situation in this country in my posts dated Oct. 30 , Oct. 23, and Oct. 1, 2008. The receding support for scientific research in the passed eight years is particularly astounding, since already 60 years ago the administration of Harry S. Truman fully recognized that maintaining an environment conducive to fundamental research was in the vital interest of the nation. President Truman's special adviser William T. Golden wrote a now historical expertise in favor of federal funding for fundamental research, influencing federal budgetary decisions for the second half of the last century.

However, the focus of federal funding in this country has shifted over the decades. Translational research from the bench to the bedside has become the overarching theme, obscuring the fact that translational research will not be possible without the understanding of fundamental mechanisms. Today, the private Howard Hughes Medical Institute (HHMI) is the only organization that supports fundamental research nationwide in the fashion of the Max Planck Society. But the HHMI's operations are much more limited in scope and support than the enterprises of the Max Planck Society. For example, there is only one HHMI research laboratory with own facilities.

Maintaining funding for cutting-edge research at private universities with extensive overhead may become less and less tenable as the current economic crisis unfolds with full force. Institutions that rely too heavily on rapidly eroding investment portfolios (see my post dated Dec. 9, 2008) may not be able to sustain the momentum and focus necessary for bold discovery in the future. Top research universities project a shrinkage in endowment of up to 30 percent in the current fiscal year. If the United States wishes to maintain worldwide leadership in research and innovation, drastic steps need to be taken immediately to counteract the imminent loss in research assets.

In ten days, this country will welcome a new leadership under President Obama with great challenges, great expectations, and unprecedented opportunities. Perhaps with the new president's inauguration the time has come at this historical moment of national refocus and renewal for another group of eminent scientists to step forward and approach the government with a well-studied proposal for the foundation of a new chain of research institutes dedicated to fundamental research. National preserves for bright ideas that can be pursued less burdened with indirect cost in the mold of the original Rockefeller Institute.

  • Today, I submitted this idea to the new government on the CITIZEN'S BRIEFING BOOK site. Follow this link, if you wish to read about Save Basic Science, or SBS for short (01/15/09).
  • On Jan. 26, Katie Zezima reports in The New York Times that, according to assessments by the Commonfund Institute and the National Association of College and University Business Officers, the endowments of private nonprofit colleges and universities lost on average 22% in value between July 1 and Nov. 30, 2008, and those of public institutions lost 25%; the steepest declines in more than 30 years (01/26/09).
  • This year, the Max-Planck Society has founded its first research institute in the United States. The Max-Planck Florida Institute in Jupiter, FL, will be dedicated to basic brain research in mice under the scientific guidance of the Nobel Prize-laureate Bert Sakmann (12/08/09).

Friday, January 2, 2009

The Versatile Mind: Seeing without Visual Cortex

On Dec. 22, 2008, Benedict Carey published an article online in The New York Times with the title "Blind, Yet Seeing: The Brain’s Subconscious Visual Sense" in which he describes a recent demonstration of blindsight. Researchers in Switzerland reported a remarkable performance of a patient who had recovered from a massive stroke that completely destroyed the visual areas of cerebral cortex on both hemispheres (de Gelder and others, 2008). Despite this impediment the patient successfully managed to negotiate an obstacle course set out for him in a hallway. Already 60 years ago, the eminent American neuroscientist Karl Lashley observed in a series of meticulous cortical ablation experiments that decerebrated rats were able to wend their way through their environment with surprising competence.

Nerve cells in a midbrain structure known as superior colliculus may play a crucial role in this process. When the cortical hemispheres of our brain are parted at the midline, the observer recognizes four small mounds rising from the surface of the underlying midbrain. To the early anatomists, the structures resembled little hills, called colliculi in Latin. One pair rises somewhat higher than the other, and thus was named the colliculi superior. The superior colliculi are composed of layers of nerve cells and nerve cell fibers. Three layers were shown to contain maps of our visual, acoustic and tactile space from the top to the bottom, respectively. The space maps normally overlap with great accuracy. As a consequence, the three senses permit us to localize an object in the same location with great precision. The congruence of spatial representation in three senses evolves during a critical period in brain development. Thirty years ago, Mazakasu Konishi and colleagues demonstrated a remarkable degree of plasticity in these maps in a series of elegant studies on barn owls in which the midbrain space representations realigned in compensation for manipulations of sensory input (Goldberg, 2008). Therefore, the recent observations in Switzerland do not come entirely as a surprise. A major focus of neurological research will remain on which additional functions are preserved after strokes that destroy visual cortex only partially.


  • You may wish to read my post dated Dec. 18, 2007, on recovery of function after stroke (02/25/2009).
  • In her report on Reuters today, Maggie Fox describes a research study that provides evidence for improved recovery through visual exercise, perhaps aided by blind sight (04/01/09).
  • If you are considering stem cell therapy, you may find the information on the International Society for Stem Cell Research site helpful (07/26/10).