"Search me" takes on new meanings.<br><br><div class="gmail_quote">---------- Forwarded message ----------<br>From: <b class="gmail_sendername">L. Stephen Coles, M.D., Ph.D.</b> <span dir="ltr"><<a href="mailto:scoles@grg.org">scoles@grg.org</a>></span><br>
Date: Wed, Dec 23, 2009 at 11:26 PM<br>Subject: [GRG] Building a Search Engine of HM's Brain, Slice by Slice<br>To: Gerontology Research Group <<a href="mailto:grg@lists.ucla.edu">grg@lists.ucla.edu</a>><br>Cc: "Harry Vinters, M.D." <<a href="mailto:HVinters@mednet.ucla.edu">HVinters@mednet.ucla.edu</a>><br>
<br><br>
<div>
<h1><font size="3">To Members and Friends of the Los Angeles Gerontology
Research Group: <br><br>
The brain
of an anterograde amnesia patient, </font></h1><font size="3">Henry
Molaison (HM), has opened the door to a much more<br>
ambitious brain project</font><h1> at UCSD... -- Steve
Coles</h1>______________<br>
<blockquote type="cite"><h1><font size="6" color="#0000ff">
<b>"Building a Search Engine of the Brain, Slice by
Slice"</b></font></h1><font size="2"><b>by</b></font><font size="3"><br>
Benedict Carey</font><br>
<img src="" alt="[]" height="330" width="600">
<font size="3"> <br>
Diego Mariscal/The Brain Observatory, University of California, San
Diego<br><br>
<b>DISSECTION:</b> A project with Henry Molaison's brain, shown in a mold
of gelatin, aims to create the first entirely reconstructed, whole-brain
atlas available to anyone. <br><br>
December 21, 2009; San Diego, CA (<i>The New York Times</i>, pp. D1, 6)
-- On a gray Wednesday afternoon here in early December, scientists
huddled around what appeared to be a two-gallon carton of frozen yogurt,
its exposed top swirling with dry-ice fumes.<br><br>
<img src="" alt="[]" height="128" width="190">
<br>
Diego Mariscal/The Brain Observatory, University of California, San
Diego<br><br>
<b>LAYERS:</b> “I feel like the world is watching over my shoulder,” said
Jacopo Annese, who dissected the brain of <b>Henry Molaison</b>, known as
<b>HM</b>. As the square container, fixed to a moving
platform, inched toward a steel blade mounted level with its surface, the
group held its collective breath. The blade peeled off the top layer,
rolling it up in slow motion like a slice of pale prosciutto.
“Almost there,” someone said. <br><br>
Off came
another layer, another, and another. And then there it was: a pink spot
at first, now a smudge, now growing with every slice like spilled rosé on
a cream carpet a human brain. Not just any brain, either, but the one
that had belonged to Henry Molaison, known worldwide as H. M., an amnesic
who collaborated on hundreds of studies of memory and died last year at
age 82. (Mr. Molaison agreed to donate his brain years ago, in
consultation with a relative.)<br><br>
“You can
see why everyone’s so nervous,” said Jacopo Annese, an Assistant
Professor of Radiology at the
<a href="http://topics.nytimes.com/topics/reference/timestopics/organizations/u/university_of_california/index.html?inline=nyt-org" target="_blank">
University of California, San Diego</a>, as he delicately removed a slice
with an artist’s paintbrush and placed it in a labeled tray of saline
solution. “I feel like the world is watching over my shoulder.” <br><br>
And so it
was: thousands logged on to view the procedure via live Webcast. The
dissection marked a culmination, for one thing, of H. M.’s remarkable
life, which was documented by Suzanne Corkin, a memory researcher at MIT
who had worked with Mr. Molaison for the last five decades of his life.
<br><br>
But it was
also a beginning of something much larger, Dr. Annese and many other
scientists hope. “The advent of brain imaging opened up so much,” said
Sandra Witelson, a neuroscientist with the Michael G. DeGroote School of
Medicine at McMaster University in Canada, who manages a bank of 125
brains, including
<a href="http://topics.nytimes.com/top/reference/timestopics/people/e/albert_einstein/index.html?inline=nyt-per" target="_blank">
Albert Einstein</a>’s. “But I think in all the excitement people have
forgotten how important the anatomical study of brain tissue still is,
and this is the sort of project that could really restart interest in
this area.”<br><br>
<a href="http://thebrainobservatory.ucsd.edu/" target="_blank">The Brain Observatory at
U.C. San Diego</a>, set up to accept many donated brains, is an effort to
bridge past and future. Brain dissection is a craft that goes back
centuries and has helped scientists to understand where functions like
language processing and vision are clustered, to compare gray and white
matter and cell concentrations across different populations and to
understand the damage done in ailments like
<a href="http://www.nytimes.com/info/alzheimers-disease/?inline=nyt-classifier" target="_blank">
Alzheimer’s disease</a> and stroke. <br><br>
Yet there
is no single standard for cutting up a brain. Some researchers slice from
the crown of the head down, parallel to the plane that runs through the
nose and ears; others cut the organ into several chunks, and proceed to
section areas of interest. No method is perfect, and any cutting can make
it difficult, if not impossible, to reconstruct circuits that connect
cells in disparate areas of the brain and somehow create a thinking,
feeling mind.<br>
<br>
To create
as complete a picture as possible, Dr. Annese cuts very thin slices
<i>70 microns each</i>, paper-thin from the whole brain, roughly
parallel with the plane of the forehead, moving from front to back.
Perhaps the best-known pioneer of such whole-brain sectioning is Dr. Paul
Ivan Yakovlev, who built a collection of slices from hundreds of brains
now kept at a facility in Washington.<br><br>
But Dr.
Annese has something Dr. Yakovlev did not: advanced computer technology
that tracks and digitally reproduces each slice. An entire brain produces
some 2,500 slices, and the amount of information in each one, once
microscopic detail is added, will fill about a<b> terabyte of computer
storage</b>. Computers at UCSD are now fitting all those pieces together
for Mr. Molaison’s brain, to create what Dr. Annese calls a “<i>Google-
Earthlike search engine</i>,” the first entirely reconstructed,
whole-brain atlas available to anyone who wants to log on. <br><br>
“We’re
going to get the kind of resolution, all the way down to the level of
single cells, that we have not had widely available before,” said Donna
Simmons, a Visiting Scholar at the Brain Architecture Center at the
<a href="http://topics.nytimes.com/top/reference/timestopics/organizations/u/university_of_southern_california/index.html?inline=nyt-org" target="_blank">
University of Southern California</a>. The thin whole-brain slicing “will
allow much better opportunities to study the connection between cells,
the circuits themselves, which we have so much more to learn
about.”<br><br>
Experts
estimate that there are about 50 brain banks in the world, many with
organs from medical patients with neurological or psychiatric problems,
and some with a stock donated by people without disorders. “Ideally,
anyone with the technology could do the same with their own specimens,”
Dr. Corkin said. <br><br>
The
technical challenges, however, are not trivial. To prepare a brain for
dissection, Dr. Annese first freezes it in a formaldehyde and sucrose
solution, to about -40 degrees Celsius. The freezing in the case of HM
was <b>done over four hours, a few degrees at a time:</b> the brain, like
most things, becomes more brittle when frozen. It can crack. <br>
<br>
<b>Mr.
Molaison lost his ability to form new memories after an operation that
removed a slug-size chunk of tissue from deep in each hemisphere of his
brain,</b> making it more delicate than most. <br><br>
“A crack
would have been a disaster,” Dr. Annese said. It did not happen.
<br><br>
With the
help of David Malmberg, a mechanical engineer at UCSD who had designed
equipment for use in the Antarctic, the laboratory fashioned a metal
collar to keep the suspended brain at just the right temperature. A few
degrees too cold and the blade would chatter instead of cutting cleanly;
too warm, and the blade wants to dip into the tissue. Mr. Malmberg held
the temperature steady by pumping ethanol through the collars
continually, at minus 40 degrees. He suspended the hoses using surfboard
leashes picked up days before the dissection.<br><br>
After the
slicing and storing, a process that took some<b> 53 hours</b>, Dr.
Annese’s laboratory will soon begin the equally painstaking process of
mounting each slice in a glass slide. The lab will stain slides at
regular intervals, to illustrate the features of the reconstructed organ.
And it plans to provide slides for study. Outside researchers can request
samples and use their own methods to stain and analyze the composition of
specific high-interest areas. <br><br>
“For the
work I do, looking at which genes are preferentially expressed in
different areas of the brain, this will be an enormous resource,” Dr.
Simmons said. <br><br>
If all
goes as planned, and the Brain Observatory catalogs a diverse collection
of normal and abnormal brains and if, crucially, other laboratories
apply similar techniques to their own collections brain scientists will
have data that will keep them busy for generations. In her own work, Dr.
Witelson has found interesting anatomical differences between male and
female brains; and, in Einstein’s brain, <b>a parietal lobe, where
spatial perception is centered, that was 15 percent larger than
average.<br>
</b><br>
“With more
of this kind of data,” Dr. Witelson said, “we'll be able to look at all
sorts of comparisons, for example, comparing the brain of people who are
superb at math with those who are not so good.” <br><br>
“You could
take someone like
<a href="http://topics.nytimes.com/top/reference/timestopics/people/g/wayne_gretzky/index.html?inline=nyt-per" target="_blank">
Wayne Gretzky</a>, for example,” she added, “who could know not only
where the puck was but where it was going to be who was apparently
seeing a fourth dimension, time and see whether he had any special
anatomical features.” (For the time being, Mr. Gretzky is still using his
brain.)<br>
<br>
So it is
that Mr. Molaison, who kicked off the modern study of memory by
cooperating in studies in the middle of the 20th century, may help
inaugurate a new era in the 21st century. That is, as soon as Dr. Annese
and his lab team finish sorting the slices they have collected. <br><br>
“It’s very
exciting work to talk about,” Dr. Annese said. “But to see it being done,
it’s like watching the grass grow.”<br>
</font><font size="6"><b>__________________________________</b></font><br>
<h1><font size="6" color="#0000ff"><b>"Dissection Begins on Famous
Brain"</b></font></h1><font size="2"><b>by </b></font><font size="3"><br>
Benedict Carey<br>
<br>
December 2, 2009; San Diego, CA (<i>NY Times</i>) -- The man who could
not remember has left scientists a gift that will provide insights for
generations to come: his brain, now being dissected and digitally mapped
in exquisite detail. <br><br>
The man,
Henry Molaison known during his lifetime only as H.M., to protect his
privacy lost the ability to form new memories after a brain operation
in 1953, and over the next half century he became the most studied
patient in brain science. <br><br>
He
consented years ago to donate his brain for study, and last February Dr.
Jacopo Annese, an assistant professor of radiology at the
<a href="http://topics.nytimes.com/topics/reference/timestopics/organizations/u/university_of_california/index.html?inline=nyt-org" target="_blank">
University of California, San Diego</a>, traveled across the country and
flew back with the brain seated next to him on Jet Blue. <br><br>
Just after
noon on Wednesday, on the first anniversary of Mr. Molaison’s death at 82
from pulmonary complications, Dr. Annese and fellow neuroscientists began
painstakingly slicing their field’s most famous organ. The two-day
process will produce about 2,500 tissue samples for analysis. <br><br>
A computer
recording each sample will produce a searchable Google Earth-like map of
the brain with which scientists expect to clarify the mystery of how and
where memories are created and how they are retrieved. <br><br>
“Ah ha
ha!” Dr. Annese said, as he watched a computer-guided blade scrape the
first shaving of gray matter from Mr. Molaison’s frozen brain. “One down,
2,499 more to go.”<br><br>
Dr. Annese
carefully dropped the shaving into fluid. The procedure is being shown
live on-line:
<a href="http://thebrainobservatory.ucsd.edu/hm_live.php" target="_blank">
thebrainobservatory.ucsd.edu/hm_live.php</a>.<br><br>
“It’s just
amazing that this one patient this one person would contribute so
much historically to the early study of
<a href="http://health.nytimes.com/health/guides/test/mental-status-tests/overview.html?inline=nyt-classifier" target="_blank">
memory</a>,” said Dr. Susumu Tonegawa, a Professor of Neuroscience at the
Picower Institute for Learning and Memory at
<a href="http://topics.nytimes.com/top/reference/timestopics/organizations/m/massachusetts_institute_of_technology/index.html?inline=nyt-org" target="_blank">
M.I.T.</a> “And now his brain will be available” for future
study.<br><br>
Good
fortune and very bad luck conspired to make Mr. Molaison one of science’s
most valuable resources and most productive collaborators. Growing up in
and around Hartford, he began to suffer
<a href="http://health.nytimes.com/health/guides/symptoms/seizures/overview.html?inline=nyt-classifier" target="_blank">
seizures</a> as a boy. The seizures grew worse after he was knocked to
the ground by a bicycle rider, and by the time he was 26 they were so
severe he consented to an experimental brain operation to relieve them.
<br><br>
His
doctor, the prominent brain surgeon William Beecher Scoville, suctioned
out two slug-sized slivers of tissue, one from each side of the brain.
The operation controlled the seizures, but it soon became clear that the
patient could not form new memories. <br><br>
“He loved
to converse, for example, but within 15 minutes he would tell you the
same story three times, with same words and intonation, without
remembering that he'd just told it,” said Suzanne Corkin, a
neuroscientist at the Massachusetts Institute of Technology who studied
and followed Mr. Molaison in the last five decades of his life.<br>
<br>
Each time he met a new acquaintance, each time he visited the corner
store, each time he strolled around the block, it was as if for the first
time. <br><br>
Before
H.M., scientists thought that memory was widely distributed throughout
the brain, not dependent on any one area. But by testing Mr. Molaison,
researchers in Montreal and Hartford soon established that the areas that
were removed in the medial temporal lobe, about an inch deep in the
brain level with the ear are critical to forming new memories. One
organ, the<i> hippocampus</i>, is especially crucial and is now the
object of intense study. <br><br>
In a
series of studies, Mr. Molaison soon altered forever the understanding of
learning by demonstrating that a part of his memory was fully intact. A
1962 paper by Dr. Brenda Milner of the Montreal Neurological Institute
described a landmark study in which she had Mr. Molaison try to trace a
line between two five-point stars, one inside the other. <br><br>
Each time
he tried the experiment, it seemed to him an entirely new experience. Yet
he gradually became more proficient showing that there are at least two
systems in the brain for memory, one for events and facts and another for
implicit or motor learning, for things like playing a guitar or riding a
bicycle. <br><br>
In the new
brain-mapping project here, set to catalog many donated brains,
scientists will have the ability to study areas of Mr. Molaison’s brain
at a level of detail that imaging cannot reveal, to solve lingering
mysteries about the man and the brain. <br><br>
Mr.
Molaison stunned researchers several times, for instance, by
demonstrating that he could hold onto some new memories. He could
reproduce exactly the floor map of his house on Crescent Drive in East
Hartford, where he lived for years after his operation with his parents.
<br>
<br>
These and
other scattered surprises suggest that Mr. Molaison’s brain, deprived of
its central memory hub, recruited other nearby areas to try to
compensate, scientists say. Now researchers can begin to study these
poorly understood areas more closely. One region, called the
parahippocampal cortex, appears to support “familiarity” memory, the
sensation that we have seen or heard something before, though we cannot
place it. <br><br>
“We've
learned a lot about memory, we’re getting close to the fire, and H.M.’s
brain will really help us clarify the division of labor in this area for
making memories,” said Dr. Lila Davachi, a neuroscientist at
<a href="http://topics.nytimes.com/top/reference/timestopics/organizations/n/new_york_university/index.html?inline=nyt-org" target="_blank">
New York University</a>. <br><br>
The
dissection, a novel whole-brain technique, is part of a project known as
the Brain Observatory and the culmination of a year of frantic
preparation. Dr. Corkin arranged for Mr. Molaison’s brain to be preserved
and imaged; up until Sunday the laboratory was tweaking its equipment,
buying surfboard leashes at the last minute to support some of its
freezing hoses.<br><br>
“We hope
that this project as it grows will catalyze cooperation across many
disciplines” to study disorders like
<a href="http://health.nytimes.com/health/guides/symptoms/memory-loss/overview.html?inline=nyt-classifier" target="_blank">
amnesia</a>, tremors, and dementias, Dr. Annese said. “But we wanted to
kick it off with the most famous brain of them
all.”</font></blockquote>_____________________________<br>
At 06:22 PM 12/22/2009, you wrote:<br>
<blockquote type="cite">Dr. George Martin,<br>
<br>
Thanks for this article. Note that the
preservation was with formaldehyde ("To prepare a brain for
dissection, Dr. Annese first freezes it in a formaldehyde and sucrose
solution, to about -40 degrees Celsius.") which would make a problem
for analyzing gene expression. Maybe, if we would combine freezing
with vitrification and then slicing like they did in the study of Henry
Molaison's brain, we could do even better. That would be the Rolls
Royce version!<br>
<br>
-- Stan<br><br>
<b>From:</b>
<a href="mailto:gmmartin@u.washington.edu" target="_blank">gmmartin@u.washington.edu</a>
<br>
<b>Sent:</b> Tuesday, December 22, 2009 8:32 PM<br>
<b>To:</b>
<a href="mailto:Stanley_Primmer@hotmail.com" target="_blank">
Stanley_Primmer@hotmail.com</a> <br>
<b>Subject:</b> NYTimes.com: Building a Search Engine of the Brain, Slice
by Slice<br><br>
Message from sender:<br><br>
Would they
try this out for three or four of our Supercentarians (two males &
two females)? Costs? -- George Martin</blockquote>
<p>
L. Stephen Coles, M.D., Ph.D., Co-Founder<font color="#888888"><br>
Los Angeles Gerontology Research Group<br>
<b>URL:</b>
<a href="http://www.grg.org/" target="_blank">
<font size="3" color="#0000ff">http://www.grg.org<br>
</font></a><font size="3"><b>E-mail:</b>
</font><font size="3" color="#0000ff"><u><a href="mailto:scoles@grg.org" target="_blank">scoles@grg.org</a><br>
</u></font><font size="3"><b>E-mail:
</b></font><font size="3" color="#0000ff"><u><a href="mailto:scoles@ucla.edu" target="_blank">scoles@ucla.edu</a></u></font>
<font size="3"> </font></font></p></div>
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<br></div><br><br clear="all"><br>-- <br>- Bryan<br><a href="http://heybryan.org/">http://heybryan.org/</a><br>1 512 203 0507<br>