Researchers at Georgetown University's Department of Physiology
and Biophysics use negative-stiffness vibration isolators
to help measure micron-level patterns of neuronal activity
in the mammalian neocortex. The research is shedding new
light into brain sensory and motor processing functions
relating to cardiac fibrillation and epilepsy.
Isolating a laboratory's sensitive microscopy equipment
against low-frequency vibration has become increasingly
more vital to maintaining imaging quality and data integrity
for neurobiology researches. Ever more frequently, laboratory
researchers are discovering that conventional air tables
and the more recent active (electronic) vibration isolation
systems are not able to adequately cancel out the lower
frequency perturbations derived from air conditioning systems,
outside vehicular movements and ambulatory personnel. Such
was the case with the Department of Physiology and Biophysics
at Georgetown University Medical Center, where Professor
Jian-Young Wu, Ph.D. has been conducting research on waves
of neuronal activity in the neocortex of the brain
.
Propagating Waves in Neocortical Slices
Wu and his colleagues visualize wave-like patterns in the
brain cortex using a new method called voltage-sensitive
dye imaging. They use a special dye that binds to the membrane
of neurons and changes color when electrical potential changes
on the membrane of active neurons. The neuronal sample is
derived from slices of rat neocortex.
The neocortex is the outer layer of the cerebral hemispheres
in the brain of mammals. Made up of six layers, it is involved
in higher functions such as sensory perception, generation
of motor commands and, in humans, language.
The neurons of the neocortex are arranged in vertical structures
called neocortical columns. These are patches of the neocortex
with a diameter of about 0.5 mm and a depth of 2 mm. Each
column typically responds to a sensory stimulus representing
a certain body part, or region of sound or vision. In the
human neocortex, it is postulated that there are about a
half-million of these columns, each of which contains approximately
60,000 neurons.
The neocortex can be viewed as a huge web, consisting of
billions to trillions of neurons and hundred of trillions
of interconnections. While individual neurons are too simple
to have intelligence, the collective behavior of the billions
of interneuronal interactions occurring each second can
be highly intelligent.
Traditionally, scientists have studied brain activity by
placing a few electrodes in the brain and measuring the
electrical signals of the neurons close to the electrodes.
This method is workable for understanding the function of
the cortex and interactions between individual neurons,
but it is not suitable for studying the emerging properties
of the nervous system.
"It is like viewing a few pixels on a television screen
and trying to figure out the story," explains Dr. Jian-Young
Wu. "Now, with optical methods and voltage-sensitive
dyes, we can visualize the activation in a large area of
the neocortex when the brain is processing sensory information,
similar to watching the whole television screen."
"Voltage-sensitive dye is a compound that stains neuronal
membrane and changes its color when the neuron is excited,"
continues Dr. Wu. "This allows us to visualize population
neuronal activity dynamically in the cortex. We study how
individual neurons in the neocortex interact to generate
population neuronal activities that underlie sensory and
motor processing functions. Population activities are composed
of the coordinated activity of up to billions of neurons.
Currently, we study how oscillations and propagating waves
can be generated by small ensembles of neocortical neurons."
Viewing the spatiotemporal patterns of neuronal population
in the cortex is markedly different from recording individual
neurons. Here the cortical activity is viewed as "population
activity", that can be more complex than the linear
addition of an individual neuron's activity. Voltage-sensitive
dye and optical recording techniques give the neuroscientist
a new tool for figuring out how brain cortex works.
Spiraling Waves in the Brain Shed Light on Cardiac Fibrillation
and Epilepsy
Wu's imaging team has uncovered spiraling wave patterns
resembling little hurricanes in the brain. He believes that
this hurricane-like spiral pattern is an emergent behavior
of the network. "A metrological hurricane is an emergent
behavior of a large volume of air molecules," says
Dr. Wu. "If you were to dissect a hurricane into individual
air molecules you would not find any special process that
generates a hurricane. Similarly, in the nervous system,
spiral waves are an emergent process of the neuronal population
and there might be no special cellular process attributed
to spirals". But like a hurricane, spiral waves can
be a powerful force for organizing the activity of a neuronal
population. Spirals generated in a small area can send out
a powerful storm that invades large, normal brain areas
and starts a seizure attack. This hypothesis would mean
that epilepsy could be viewed not just as mis-wiring in
the brain, but as an abnormal wave pattern that invades
normal tissue.
Similarly, during cardiac fibrillation, spiral waves form
in the heart emitting rotating and scroll waves in two and
three dimensions. As a leading life-threatening situation,
these rotating waves can kill the patient instantly as the
pumping function of the heart is disrupted by the 5 to 10Hz
rotations which drives chaotic and abnormally rapid cardiac
contractions.
Wu believes that propagating waves are a basic pattern
of cortical neuronal activity, and that these wave patterns
may play an important role in initiating and organizing
brain activity involving millions to billions of neurons.
Studying the spatiotemporal patterns of neuronal population
activity may provide insight into normal brain functions
and pathological disorders. This research has the potential
to help scientists understand abnormal waves that are generated
in the brains of patients with epilepsy.
Vibration Isolation
Since voltage-sensitive dye signals are small, usually a
change of 0.1 to 1.0 percent of the illumination intensity,
Wu's team has used a high-dynamic-range camera, photodiode
array to detect the voltage-sensitive dye signals of the
cortical activity. The photodiode array can resolve extremely
small changes in light, usually one part of ten thousands.
(Human eyes and ordinary digital cameras register light
changes of one part to a hundred). Detecting such small
signals requires an extreme isolation of vibration. The
lab had to contend with low frequency vibrations from air
conditioning equipment, people walking and wind blowing
against the building. Vibrations as low as 1Hz were inhibiting
the integrity of the images and data.
"At first, we used high quality air tables, but they
were not adequate for isolating low frequency vibrations,"
Dr. Wu continues. "We tried putting a second air table
on top of the first one, but that still did not give us
the isolation we needed. Then we tried an active, electronic
system, but we were still spending much time fighting with
floor vibrations. We were dealing with an unresolved vibration
problem for many years."
The Georgetown lab eventually tested, and settled upon
negative-stiffness mechanism vibration isolation systems
from Minus K Technology, which enabled the lab to get vibration
isolation down to a level of 1Hz. This effectively cancelled
out any vibration noise difficulties that were inhibiting
image and data readings.
Negative-stiffness mechanism (NSM) isolators have the flexibility
of custom tailoring resonant frequencies vertically and
horizontally. They employ a completely mechanical concept
in low-frequency vibration isolation. Vertical-motion isolation
is provided by a stiff spring that supports a weight load,
combined with a NSM. The net vertical stiffness is made
very low without affecting the static load-supporting capability
of the spring.
Beam-columns connected in series with the vertical-motion
isolator provide horizontal-motion isolation. The horizontal
stiffness of the beam-columns is reduced by the "beam-column"
effect. A beam-column behaves as a spring combined with
a NSM. The result is a compact passive isolator capable
of very low vertical and horizontal natural frequencies
and very high internal structural frequencies.
Transmissibility with negative-stiffness is substantially
improved over air systems, which can make vibration isolation
problems worse since they have a resonant frequency that
can match that of floor vibrations. Transmissibility is
a measure of the vibrations that transmit through the isolator
relative to the input vibrations. The NSM isolators, when
adjusted to 0.5Hz, achieve 93 percent isolation efficiency
at 2Hz; 99 percent at 5Hz; and 99.7 percent at 10Hz.
NSM transmissibility is also improved over active systems.
Because they run on electricity, active systems can be negatively
influenced by problems of electronic dysfunction and power
modulations, which can interrupt scanning. They also have
a limited dynamic range - which is easy to exceed - causing
the isolator to go into positive feedback and generate noise
underneath the equipment. Although active isolation systems
have fundamentally no resonance, their transmissibility
does not roll off as fast as negative-stiffness isolators.
Continuing Research
Within the past ten years, Dr.Wu's team has documented a
variety of waveforms (e.g., plane wave and spirals) in brain
slices during artificially induced oscillations. Using neocortical
slices and mathematic models they are studying the initiation
of the waves and the factors that control their propagating
direction and velocity.
The lab is also involved in the development of new optical
imaging techniques - relying on the negative-stiffness vibration
isolation systems - such as imaging propagating waves in
vivo, in intact brains. "This is technically difficult,"
says Dr. Wu. "Other imaging methods (MRI, PET or MEG)
provide inadequate spatiotemporal resolution. Large scale
neuronal activity is a hallmark of a living brain. We are
improving the optical imaging techniques with a hope to
visualize the waves in the cortex in vivo during sensory
processes and in awake animals while behavioral and cognitive
tasks are performed."
About Jian-Young Wu, Ph.D.
Jian-Young Wu, Ph.D. is Professor, Department of Physiology
and Biophysics, at Georgetown University Medical Center.
He holds a Ph.D. in Neurobiology, 1986, from Peking University,
China. Dr. Wu has co-authored a number of papers on the
subject of neuronal activity.
Dr. Wu can be reached at Georgetown University, Department
of Physiology and Biophysics; SE-106, Medical-Dental Building,
3900 Reservoir Road, NW, Washington DC, 20057; email wuj@georgetown.edu;
http://www.georgetown.edu/faculty/wuj/.
About Minus K Technology
Minus K® Technology, Inc. was founded in 1993 to develop,
manufacture and market state-of-the-art vibration isolation
products based on the company's patented negative-stiffness-mechanism
technology. Minus K products are used in a broad spectrum
of applications including nanotechnology, biological sciences,
semiconductors, materials research, zero-g simulation of
spacecraft, and high-end audio. The company is an OEM supplier
to leading manufactures of scanning probe microscopes, micro-hardness
testers and other vibration-sensitive instruments and equipment.
Minus K customers include private companies and more than
200 leading universities and government laboratories in
30 countries.
|
Dr. David L. Platus is the inventor of negative-stiffness
mechanism vibration isolation systems, and President and
Founder of Minus K Technology, Inc. (www.minusk.com). He
earned a B.S. and a Ph.D. in Engineering from UCLA, and
a diploma from the Oak Ridge School of (Nuclear) Reactor
Technology. Prior to founding Minus K Technology , he worked
in the nuclear, aerospace and defense industries conducting
and directing analysis and design projects in structural-mechanical
systems. He became an independent consultant in 1988. Dr.
Platus holds over 20 patents related to shock and vibration
isolation.
For more information on negative-stiffness vibration isolation
please contact Steve Varma, Minus K Technology, Inc.; 460
South Hindry Ave., Unit C, Inglewood, CA 90301; Phone: 310-348-9656;
Fax: 310-348-9638; email: sales@minusk.com; www.minusk.com.
