X-Message-Number: 15750
From: "Mark Plus" <>

Subject: "New MRI Approach Can Identify Sources Of Memory Loss In Humans And 
Date: Mon, 26 Feb 2001 10:33:37 -0800



Source:   Columbia University College Of Physicians And Surgeons 

Date:   Posted 2/26/2001

New MRI Approach Can Identify Sources Of Memory Loss In Humans And Mice

Researchers have found a way to pinpoint changes in brain activity that may 
underlie memory impairment, even before structural damage occurs. Dr. Scott 
Small and colleagues report in the December issue of Neuron that with a new 
high-resolution MRI technique, alterations in resting activity in subregions 
of the hippocampus, a brain circuit important for learning and memory. By 
enabling researchers to detect activity changes in mice genetically altered 
to model age-related memory loss, the approach may further understanding of 
the mechanisms of the disease in humans.
As a potentially valuable tool for diagnosing memory disorders from specific 
causes, the use of MRI to precisely map blood oxygenation in the brain at 
rest could also lead to more effective treatment for memory loss in its 
early stages. "This is encouraging data. We may be able to use this 
technique as an early diagnostic for Alzheimer's disease," says Dr. Small, 
Irving assistant professor of Neurology at Columbia University College of 
Physicians & Surgeons and first author of the paper. Dr. Small collaborated 
with Dr. Ed X. Wu, Assistant Professor of Radiology; Dr. Dusan Bartsch; 
Gerard Perera; Clay Lacefield; Dr. Robert DeLaPaz, Professor of Radiology; 
Dr. Richard Mayeux, Sergievsky Professor of Psychiatry, Neurology and Public 
Health; Dr. Yaakov Stern, professor of clinical neurology and psychiatry; 
and Dr. Eric Kandel, University Professor of Physiology & Cell Biophysics, 
Psychiatry, and Biochemistry & Molecular Biophysics.

The new technique is a variant of functional MRI, an approach frequently 
used by cognitive scientists to show rapid changes in brain activity during 
certain tasks in perception or thinking. Usually, researchers investigating 
how the brain works look at rapid, dynamic changes in blood oxygenation that 
reveal sudden increases in activity during a particular mental task. 
Functional MRI gives good information about what general areas are involved 
during a precise stage of the task but has difficulty pinpointing precise 
activity to small regions of the brain-such as the hippocampal subregions. 
"To get fast temporal resolution, you sacrifice spatial resolution," says 
Dr. Small.

To precisely locate changes of resting activity over very small regions of 
the brain, however, Dr. Small and colleagues took a different approach to 
this trade-off. Stable, disease-related abnormalities in resting 
oxygenation, or ROXY, can be detected within tiny regions of the brain by 
analyzing similar MRI signals over longer periods. "In disease, you have 
static changes, so you can get better spatial resolution; you don't need 
temporal resolution," says Dr. Small. "We felt the technique had the 
resolution to narrow down damage to specific subregions."

ROXY also offers advantages to researchers studying memory disorders: using 
functional MRI to evaluate a patient or subject requires them to understand 
and follow directions, but resting activity can be measured even with 
patients in the advanced stages of memory loss or in genetic mouse models of 
disease. Says Dr. Small, "In memory deficient mice that show similar 
physiological changes in memory formation, R(AB) mice, Eric Kandel and his 
colleagues Ted Abel and Rusiko Bourtchouladze found changes in brains, and 
used histology to look for lesions-there were no structural defects," 
demonstrating that the high-resolution ROXY measurements with MRI reveal 
genetic alterations in activity even without visible tissue damage. Because 
the molecular workings of memory are well studied in mice, comparing 
physiological changes in human patients and mouse models might be able to 
suggest possible molecular mechanisms involved in human memory disorders. 
Likewise, ROXY imaging might be useful in evaluating other genetic mouse 
models for human brain disorders. Although human behavioral criteria may be 
hard to evaluate in mice, changes in physiology in particular brain regions 
might be easier to compare between patients and mouse models of a disease.

Although specific anatomical changes in the hippocampus are typically seen 
in the late stages of several forms of memory disorders, detectable 
structural changes are not prominent in early stages, when the impairment 
first presents itself. "When an elderly patient presents with mild 
forgetfulness, right now, we can't tell if it's normal or abnormal," says 
Dr. Small. "Is it early Alzheimer's disease, or is it something else? With 
this technique [using MRI to map resting activity], we may be able to detect 
Alzheimer's disease more accurately." Finding a way to determine exactly 
what part of the hippocampus isn't working normally might give early cues 
about the origin of the memory deficit and, therefore, how best to treat it.

Memory disorders may differ in their underlying causes, as well as 
appropriate treatments. "Some mechanisms can cause structural changes, but 
others can cause changes in function without noticeable structural damage," 
says Dr. Small. "The hippocampus is not a simple structure-it's actually a 
circuit. This means the best way to evaluate hippocampal function is to 
evaluate each node in the circuit," in other words, each subregion of the 
hippocampus. According to Dr. Small, different processes that accompany 
aging impair memory by targeting distinct regions of the hippocampal area, 
so the precise location of the problem spot may give clues about what caused 
the memory loss. "Vascular changes primarily target the CA1 region, and 
testosterone changes affect the dentate gyrus. If we can validate this 
technique, we'll be able to tell that, if the physiological defect is in 
entorhinal cortex, we can diagnose the patient with Alzheimer's disease. If, 
on the other hand, we find it in the dentate gyrus, we may suspect that 
hormonal changes are behind the deterioration. If the damage is principally 
in CA1, we might be inclined to do a cardiovascular workup."

"The technique we used to gather human data doesn't require new equipment. 
It has the potential for widespread use," says Dr. Small of their ROXY 
measurements with MRI. Although measuring rapid changes in blood oxygenation 
requires a set-up generally only available in an academic research facility, 
commonly available clinical MRI facilities could be used to measure ROXY. 
"This would require collection of data normally, it would just be processed 
in a new way." Potentially, data collected at conventional MRI centers 
without any retrofitting could then be processed at a central location to 
provide ROXY profiles for each patient, making it easier for patients 
virtually anywhere in the U.S. to gain access to the technique.

The work was supported by federal grants from the National Institutes of 
Aging and Mental Health, the Beeson Faculty Scholar Award from the American 
Federation of Aging, the Banbury Fund, the Taub Foundation, the G. Harold 
and Leila Y. Mathers Charitable Foundation, and the Howard Hughes Medical 


Note: This story has been adapted from a news release issued by Columbia 
University College Of Physicians And Surgeons for journalists and other 
members of the public. If you wish to quote from any part of this story, 
please credit Columbia University College Of Physicians And Surgeons as the 
original source. You may also wish to include the following link in any 


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