Friday, October 23, 2009

Free Will Exists: Morat Fribourg, 2009

This year's race from Morat to Fribourg, held Oct. 3 in its 76th edition (erratum: My count was one off, when I posted first), was won again by Helen Musyoka (1:01:29 h) and John Mwangangi (0:52:37 h), both from Kenya. Congratulations!

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Thursday, October 22, 2009

Absolutes, Relatives, Brain Imaging & Steroids

The functional brain imaging methods most commonly used in humans today are functional magnetic resonance imaging (fMRI) using blood oxygen-level dependent (BOLD) signals and the subtractive water method with positron emission tomography (PET). Both procedures record changes in local cerebral blood flow from a baseline. Local cerebral blood flow is associated with energy demands of activated nerve cells. The cells consume glucose sugar and oxygen to process information which cannot be stored in the brain and must be supplied on demand with the blood stream. Hence, blood flow increases with increased nerve cell activity. In the simplest conception of both procedures known as block design, measurements acquired over several minutes of mental activation are compared with measurements acquired during equivalent epochs of rest. The statistically significant difference is considered the result of cerebral activation.

In conventional fMRI, blood oxygen-level dependent signals are used to detected changes in blood flow (Ogawa and others, 1993). With the subtractive water method (Fox and others, 1984), water labeled with 15O, a radioactive positron-emitting isotope of oxygen, is used as tracer that freely diffuses into the brain tissue. The local concentration of the tracer is commensurate with local blood flow and can be imaged in a PET scanner. However, calibration for absolute blood flow is wrought with difficulty and has not found wide-spread application. Because the blood flow is not quantified, the differences between the compared mental states remain relative. That is, cerebral activation is usually expressed in percent difference from the state used as reference or in units of statistically significant difference (statistical parametric mapping).

By contrast, the cerebral glucose consumption is more directly related to nerve cell activity than cerebral blood flow. The deoxyglucose method of Sokoloff and others (1977) permits us to measure the local cerebral rate of glucose utilization. Deoxyglucose is an analogue to glucose that accumulates in the brain tissue commensurate with glucose consumption. Tagging deoxyglucose with 18F, a radioactive positron-emitting isotope of fluorine, the tracer's accumulation in the brain can be imaged with PET. The [18F]fluorodeoxyglucose method, therefore, provides a snapshot of the brain's energy consumption (Reivich and others, 1979). Although this snapshot needs 90 minutes to develop because of the tracer kinetics involved, the procedure constitutes an indispensable tool for the detection of long-term, pseudo-stationary changes in absolute cerebral metabolic activity as a consequence of disease or trauma. Below, I discuss one example.

After the collapse of the regime of Nicolae Ceauşescu at the end of 1989, U.S. parents began to adopt children from Romanian orphanages. The children had been kept in circumstances of great depravity, producing profound behavioral problems similar to autism (American RadioWorks report, 2006). Visiting scientists reported behavioral patterns resembling those the eminent American psychologist Harry Harlow had so aptly described in primates raised in isolation and with surrogates.

Although the adoptees were brought to the U.S. at very young age, some developed cognitive and behavioral differences, including impulsive reactions as well as attention and social deficits, in the years after their arrival.

Research at the orphanages provided evidence that the children had persistently augmented levels of cortisol n their blood stream as a result of the severe stress they endured (Carlson and Earls, 1997). Cortisol is a known steroid stress hormone produced in the adrenal glands and can fundamentally affect brain maturation. The hormone suppresses the activity of glia. A type of glia, astrocytes, helps regulate the extracellular glutamate concentration. Glutamate constitutes the most prevalent excitatory neurotransmitter in the brain, playing a major role in the stabilization of connections between nerve cells during brain maturation. Elevated concentrations of extracellular glutamate can trigger pre-programmed cell death known as apoptosis, otherwise occurring only during early stages of brain development. Presumably, the orphans' excessive stress-related exposure to cortisol led to modifications of nerve cell networks, underlying the children's behavioral differences. Imaging the brain's energy consumption provided a method to uncover whether and where nerve cell activity changed in cerebral cortex as a consequence of the children's stay in the orphanages. 

Using the fluorodeoxyglucose method, Chugani and others (2001) could show that the use of glucose was drastically reduced in the cerebral cortex of the orphans enrolled in the study, particularly in temporal and prefrontal cortical areas and in structures of the limbic system, notably the amygdala. The cortical regions are involved in executive functions and short-term memory crucial for social behavior and affect. The amygdala play an important role in fearful reactions. The observed reductions in energy consumption could not have been detected with the standard fMRI or PET procedures discussed above. The fluorodeoxyglucose method, hence, constitutes the procedure of choice when the fundamental metabolic state of the brain is in question.

  • Take some time and listen to this show on National Public Radio's This American Life with the title "Unconditional Love". The first half of the show is about an orphaned Romanian boy adopted by an American couple at the age of eight. It demonstrates in great clarity the at times overwhelming difficulties the family faced to remedy important steps of personality development that were missed early in the boy's life. Finally, the challenges were overcome with passion and a professional attitude. It is reassuring to find out that success is possible (10/23/10).


Monday, October 12, 2009

The Quest for the Infrasound Acoustic Fovea

In my post dated Sep. 30, 2009, I briefly discussed the discovery of echolocation as a means for bats to navigate their environment in total darkness and identify insects to feast on. I noted that in echolocating bats a large part of the auditory system is devoted to the processing of ultrasound, that is frequencies higher than the human audible (>20 kHz).  A disproportionate number of auditory nerve cells are tuned to analyze the frequencies of the echos of the echolocation calls bats emit. I worked on research with echolocating bats in Gerhard Neuweiler's laboratory at the Institute of Zoology of the Johann Wolfgang Goethe University, Frankfurt am Main. I helped show that exposing a bat to its echolocation frequency activated prominent regions in its auditory midbrain structure known as inferior colliculus (Melzer, 1985). The proclivity in the bat auditory system for a narrow band of ultrasound used for echolocation is known as high frequency filter or acoustic fovea (Neuweiler and others, 1980).

As informative contrast to the bats' fovea for extremely high pitch, a mammal was sought with a fovea for extremely low pitch. It was hoped that a similar association between behaviorally relevant sound and its representation in the brain might exist in species whose hearing is particularly sensitive to infrasound, that is at frequencies beneath the human audible (<20 Hz). Elephants (Herbst and others, 2012) and humpbacked whales are known to produce and hear infrasound, but were considered difficult to study.

By contrast, burrowing rodents were thought to constitute suitable candidates, because they spend much of the day underground and were observed to be able to use seismic vibrations to identify and locate conspecifics and predators. Particularly, gerbils were of interest. They are essentially crepuscular, that is most active above ground at dawn and dusk. They live in semi-arid deserts where compacted gravel and sand carry low frequency sound long distances. Gerbils use hind foot drumming as means of communication. The drumming exhibits species-specific differences and has been observed to alert companions to one's own presence in as much as to approaching predators (Randall, 1997). Differences in the signature of the sound may permit the animals to distinguish between various types of predator, e.g. snakes or birds. Moreover, the sounds may convey to predators that they have been discovered (Randall, 2001).

Christian Winter recruited Jürgen Möller as a junior faculty member to investigate whether gerbils may represent the small mammals with an acoustic fovea for infrasound. He had extensive experience in acoustics, micro-electrode recordings of electrical nerve cell discharges, and animal behavior.

courtesy J. Möller
In addition to the well-known Mongolian gerbil (Meriones unguiculatus), Jürgen succeeded in bringing a number of gerbil species from Israel to the laboratory, testing their hearing for low frequency sensitivity with audiograms. Field studies on the animals' behavior were conducted in Israel.

The photograph depicts a sand rat (Psammomys obesus) in the Negev desert at dusk. Sand rats were the largest gerbils in Jürgen's collection.  Power density spectra of their drumming's acoustic frequency components were recorded to examine whether the drumming produced infrasound. Broad spectrum audiograms were constructed from recordings of small voltage changes in the inner ear (cochlear microphonics) and from nerve cell activity in the auditory midbrain (inferior colliculus) to investigate whether the animals could hear infrasound.

The results were presented at a joint symposium of Hebrew University of Jerusalem, Université de Lyon, and Johann Wolfgang von Goethe University entitled "Neurobiology and Strategies of Adaptation". The symposium was convened in Frankfurt am Main in 1981. The two figures below show representative results of the frequencies of the sound produced by drumming (A) and of the sound processed by the auditory system (B). The green band covers the frequency range between 0.5 and 1.0 kHz in which the audiograms (B) show peculiar low frequency sensitivity.

(A) Power Density Spectrum
The frequency of the drumming's acoustic components [kHz] (y-axis) is plotted versus time [ms] (x-axis; courtesy J. Möller).

(B) Audiograms
The sound pressure level [dB SPL] of the most sensitive response (y-axis) is plotted versus sound frequency [kHz] (x-axis). Cochlear microphonics: CM; nerve cell responses in the inferior colliculus: IC (courtesy J. Möller).
Analysis of the power spectra revealed that the animals' drumming contained low frequencies of significant power, infrequently dipping into infrasound. Yet, the audiograms of the animals provided no evidence of an acoustic fovea for such low frequencies. Regardless, the findings clearly suggested that the drumming produced sound to which that the animals' hearing was sensitive.

My project's aim was to visualize pitch-related nerve cell activation in the brain with a functional imaging method (Melzer, 1984). M. Müller (now private docent at the J.W. Goethe University) helped me substantially in this endeavor. The project would not have been possible without the use of the whole-body cryotome in H.-M. Kellner's division at the Hoechst AG's Radiochemical Laboratory.

Animals were exposed to sound of low, medium and high pitch. Pitch is represented tonotopically on the transverse plane through the inferior colliculus. That is, nerve cells in the upward (dorsal) aspect of the structure are particularly sensitive to low frequency sound and become progressively more sensitive to higher frequencies with increasing depth. Functional imaging would reveal the isofrequency domains, permitting us to assess the prominence of low frequency processing in the auditory system.

The figure below shows frequency-related nerve cell activation in transverse slices through the inferior colliculus. Nerve cell activation is coded in pseudo colors (blue: low; red: high). The narrow blue/purple lines near the top are the animals' scalp, that is dorsal is up. The brainstem is at the bottom, that is ventral is down. The animals' left side is on the right.

Neurofunctional Images
The slices were obtained from sand rats exposed to tone pips of (clockwise from top, left) 0.8, 2.5 and 17.0 kHz, respectively. Stimulus-unrelated nerve cell activity was obtained from unexposed animals (bottom, left). The inferior colliculus is the distinctly sound-activated, double-lobed structure at the center of the images. Unexposed animals revealed slightly elevated nerve cell activity in the top aspect of the structure on both sides (bottom, left). Low frequency stimulation produced wide-spread activation, peaking in a band at the top of the structure (top, left). This activation partially overlapped with the observed stimulus-unrelated activity (bottom, left). By contrast, the middle frequency activated a narrow band at mid-depth of the structure on both sides (top, right), whereas activity at the top was almost completely suppressed. High frequency stimulation resulted in similarly narrow bands of activation on both sides. Only in this case, the bands were located at the bottom of the inferior colliculus (bottom, right). In addition, prominent activity was distinct at the top of the structure.

The progression of bands of elevated nerve cell activation from top to bottom with increasing frequency of stimulation is consistent with the notion of a tonotopic map where frequencies are represented in logarithmic progression. Intriguingly, the low part of the sound spectrum was slightly disproportionally represented. However, such disproportionality is not uncommon and has been observed in a number of species (N. Suga, personal communication).

The narrow bands of activation observed with the middle stimulus frequency conformed most distinctly with a representation of frequencies in discrete isofrequency layers. According to the cochlear microphonics, the animals' ear is most sensitive at this frequency. By contrast, the wide-spread activation at the low frequency and the additional foci at the top of the inferior colliculus at the low and the high frequency did not precisely adhere to the principle of discrete frequency representation. We did not know how to interpret these results.

In hindsight, we were perhaps too narrowly focused on auditory responses. Parts of the inferior colliculus are known to receive somatic sensory input. Sand rats have long mystacial whiskers that are in frequent contact with the soil. Cytoarchitectonic structures known as barrels represent the mystacial whiskers topographically in a large swath of the gerbil's cerebral somatic sensory cortex (Rice and others, 1985). Distinct septa separate the barrels. Nerve cells in the septa are known to be particularly attuned to the processing of stimulus frequency (Melzer and others, 2006). Recent observations show that whiskers may resonate (Moore, 2004) to low frequency vibrations, touch receptors in the whisker follicles transduce frequencies up to 1.0 kHz and possibly greater (Gottschaldt and Vahle-Hinz, 1981), and nerve cells in the somatic sensory pathway may process this information (Kleinfeld and others, 2006). Perhaps, gerbils do possess an infrasound fovea after all! Only the processing of this sound may not be strictly auditory.

  • Watching gerbils around the time of an earthquake may prove insightful. A tiny whiskered burrowing rodent, the Northern Pocket Gopher Thomomys talpoides, survived the catastrophic eruption of Mt. St. Helens in 1980 (11/06/09).
  • Caldwell and others (2010) produced an impressive demonstration of the importance of vibrations in vertebrate sensation and behavior. The research feature on National Public Radio's Talk of the Nation (Science Friday) yesterday with the title "Rumble in The Jungle" shows red-eyed treefrogs (Agalychnis callidryas) from the rain forests of central America communicating with vibrations mediated by the twig they sit on. Listen to the podcast of Ira Flatow's conversation with Flora Lichtman entitled "Red-Eyed Treefrogs Rumble in the Jungle". The authors of the study, affiliated with Boston University, contributed excellent footage of the frogs' interactions (05/22/10).
  • On Apr. 8, 2011, National Public Radio's Talk of the Nation/Science Friday broadcast an insightful segment with the title "Seeing The World Through Whiskers" on the research of Mitra Hartman and her colleagues (Towal and others, 2011) examining whisking in rats with high-speed video (04/11/2011):
  • The magnitude 5.8 earthquake on the East Coast on Aug. 23, 2011, centered near Mineral, Virginia, was felt roughly 120 miles away by animals of the National Zoo in Washington D.C., in some instances tens of minutes before humans did. Listen to Ira Flatow's interview with Brandie Smith, Senior Curator of the National Zoological Park, Smithsonian Institution, Washington D.C., entitled "Did you feel it?" on National Public Radio's Talk of the Nation/Science Friday broadcast today (08/26/2011).
  • Listen to Dr. Tecumseh Fitch explaining to Audie Cornish of National Public Radio's All Things Considered in his interview with the title "Study: Humans, Elephants User Similar Vocalizations" broadcast today how elephants produce and may use infrasound (08/09/2012).
  • The text of this post is available for download in pdf-format from the scribd store.
Related Posts
I attached this amateur video of a pet gerbil drumming in the cage. The clip provides an idea of drumming speed and periodicity. Keep in mind that a gerbil in a burrow will sound quite different.

Friday, October 9, 2009

Water & the Mind

“All day I've faced the barren waste
Without the taste of, water.
Ole Dan and I, with throats burned dry ,
and souls that cry
for, clear water.”
We need water to live. In the developed world, we take abundant water supply for granted. However, where I live the recent past demonstrated in all harshness that we are cradling ourselves in a false sense of security. Water is in fact in short supply. In contrast to the Southwestern states of the U.S., the Southeastern states look emerald green most of the year when you look down on the beautiful land of rolling mountains from an airplane. You would never believe that there is not enough water for this land!

However, severe drought struck this land two years ago. After several years of insufficient rainfall, hardly any came. The grass turned brown already in June, the hack berry trees dropped their leaves in August. Our willow dropped a ton of whip-like branches and is half dead today. Metropolitan Atlanta was much worse off. A major source of the city's potable water, Lake Lanier, reached historic low levels (Shaila Dewan and Brenda Goodman for The New York Times, Oct. 23, 2007, "New to Being Dry the South Struggles to Adapt"). Severe restrictions for the use of water were imposed.

Legal fights ensued between users in the region. The states of Florida, Alabama and Georgia, sharing the Chattahoochee River basin, began to quarrel about water rights with the U.S. Army Corps of Engineers (Shaila Dewan for The New York Times, Aug. 15, 2009, "River Basin Fight Pits Atlanta Against Neighbors"). The Corps administers the river's flow. Georgia became so desperate that lawmakers briefly resurrected a 19th century border dispute with its neighbor Tennessee in a vain attempt to gain access to the Tennessee River (Shaila Dewan and Brenda Goodman for The New York Times, Feb. 22, 2008, "Georgia Claims a Sliver of the Tennessee River").

The state of Tennessee was not much better off (Adam Nossiter for The New York Times, Jul. 4, 2007, "Drought Saps the Southeast, and its Farmers"). Water had to be trucked in with fire engines for a number of communities where the wells were running dry. Entire counties declared water emergencies. On top of this calamity, deep cracks were discovered in the bedrock under several large dams the Tennessee Valley Authority had built in the wake of the Great Depression, e.g. Wolf Creek Dam (Ian Urbina and Bob Dreihaus for The New York Times, Mar. 4, 2007, "Fears for a Dam's Safety Put Tourist Area on Edge"). Water had to be released, leaving the intake pipes of a number of lakeside communities on dry ground. Obviously, improved water management was direly needed.

This year, by contrast, we saw record rainfall down here. Georgia and Tennessee experienced catastrophic flash floods (Robbie Brown and Liz Robbins for The New York Times, Sep. 24, 2009, "Georgians Grappling With Flood Damage"). Our house is built on an unfinished basement. In normal years, the dirt is dry for nine months. This year it never dried. The grass in the yard never turned brown. The hackberry trees have only begun to shed their leaves this month.

Unfortunately, this year's abundance of water could not be stored. The water levels behind the damaged dams had to be kept below capacity because of the repair work underway. The repairs are substantial, will cost hundreds of millions of dollars and will take several years to complete. Meanwhile, millions of gallons of precious water are flushed down the spill ways. For the first time, I saw all spill ways wide open at Percy Priest Dam. A truly majestic sight!

Clearly, we cannot afford to waste our most vital resource without paying a price. Tonight at 20 hours EDT, Guy Laliberté, the founder of Cirque du Soleil, will host a multi-media show from the International Space Station. The show entitled "Moving Stars and Earth for Water" will raise awareness to this simple, but important fact.

You may wish to tune in online here tonight:

  • Guy is back!
  • On the weekend of May 2, 2010, a 500-year flood of the Cumberland River system in Tennessee overwhelmed the U.S. Army Corps of Engineers' ability of containing the rising waters below catastrophic levels. The Corps had to release water, flooding its own facilities downstream, to protect the integrity of its dams. Eleven lives were lost. More than 2000 families suffered flood damage to their homes. Nashville's downtown was underwater to an extent unseen in 80 years. One of the two water treatment plants that supply the city with drinking water was out of order for several weeks. The estimated economic losses in the metropolitan area top two billion dollars. The Tennessean devotes a continuously updated online report entitled "Nashville Flood" on the incident and its impact. The dam and levee system in the region is underfunded and has not seen large-scale upgrades since its inception. Obviously, improved water control is direly needed (08/05/10).
  • Southeastern cities manage their drinking water on shoe-string budgets. According to an Associated Press report with the title "New Orleans Issues Boil-Water Order" published online in The Wall Street Journal today, citizens of New Orleans are advised to boil their tap water before consumption this weekend, because mechanical failure forced a water treatment plant to shut down (11/20/10).