Researchers have found subtle damage in the brains of HIV-positive patients whose viral load is effectively suppressed by anti-retroviral therapy. In one of the first studies of its kind, researchers from the San Francisco Veterans Affairs Medical Center (SFVAMC) used a combination of MRI brain imaging, recording of electrical brain activity, and behavioral tests to compare the size and function of brains of HIV-positive patients on antiretroviral therapy with those of healthy subjects.
Although it is not known whether any or all of the damage occurred before patients started drug therapy, even minor damage that is present now should serve as a warning, says Linda Chao, PhD, the study’s lead author and an assistant adjunct professor with the Magnetic Resonance Unit of the SFVAMC and the Departments of Psychiatry and Radiology at University of California, San Francisco (UCSF). "People are starting to get lax about AIDS now," Chao says. "You see people on antiretroviral medications and they seem fine. But the take-home message of our study is that antiviral medications might not be stopping brain damage. When we put patients’ brains under closer scrutiny, we saw that they were affected."
"The results of our study raise the concern of brain injury in HIV subjects who are on treatment, even among those who are virally suppressed," says the study’s senior investigator, Michael Weiner, MD, of the Magnetic Resonance Unit, SFVAMC, and the Departments of Radiology, Psychiatry, Medicine and Neurology at UCSF. "What we don’t know is whether or not these changes occurred some time ago, prior to effective treatment, or whether these changes represent ongoing injury."
The biggest difference in test results between groups came from the contingent negative variation brainwave recordings. When Chao charted the magnitude of brainwaves during the computer task performance test, she found that while CNV activity among HIV-negative participants surged shortly after appearance of the first image, it remained nearly flat among both the viremic and virally suppressed HIV-positive participants. Lack of CNV response is generally an indication of damage or destruction to brain cells in the basal ganglia, a part of the brain that coordinates motor behavior and one of two brain structures where HIV tends to concentrate.
Chao also found that among control subjects, the stronger their CNV activity, the faster their response time. But there was no correlation between CNV activity and response time among HIV-positive participants. Nevertheless, HIV-positive participants had just as good response times as control subjects. There is a possible explanation, says Chao: the flat CNVs recorded among the HIV-positive participants are possibly an indication that HIV has damaged the normal neurological linkage between a stimulus (for example, a hand touching a hot pan) and a reaction (pulling the hand away). But the fact that response times were equal could mean that alternate neurological pathways that compensate for the disruption have developed in the brains of the HIV-positive subjects.
To assess where HIV-triggered damage might be occurring in the brain, Chao examined the relationship between the strength of CNV activity during the reaction-time test, with MRIs of study subjects’ caudate nuclei, a substructure of the basal ganglia. She found that the weaker the CNV among HIV-positive participants the more reduced the caudate volume. "The basal ganglia is a part of the brain known to carry one of the highest viral burdens," she says. Because there is also evidence that the CNV partially originates in this part of the brain, finding this correlation [between weak CNVs and reduced caudate volume] is a nice tie-in that gives us more confidence in our conclusions about where and how damage is occurring."
MRI measurements also revealed that the volume of the brain structure known as the thalamus was smaller both in viremic and in virally suppressed participants than in controls, an indication of damage in this region. The thalamus serves as a relay station for sensory information.
Results of the behavioral tests were mixed. On several tests, there were no differences between the three groups. And on all tests virally suppressed patients scored as well as the control group. But on three tests, scores of viremic participants were significantly lower than those of virally suppressed participants and the controls. "People with lower scores like these might not be able to do such things as type as fast as before, and they might not have as good attention or mental flexibility as the people who scored higher," Chao says. "But unless they were challenged daily, this is something they probably wouldn’t notice, because these are the kinds of things that are more easily compensated for."
Previous studies have already shown that when viral load is reduced by antiretroviral therapy, behavioral performance improves. But in running several kinds of tests and comparing their results, the research team was able to scrutinize their findings in a new light. To determine whether injury is ongoing, Weiner says, follow-up studies that assess HIV-positive patients over a longer time period are needed.
Additional study authors are Valerie A. Cardenas, PhD, assistant adjunct professor and Dieter J. Meyerhoff, PhD, associate professor, both of the Magnetic Resonance Unit, SFVAMC and Department of Radiology, UCSF; Johannes C. Rothlind, PhD, assistant adjunct professor, Department of Psychiatry, UCSF; and Derek L. Flenniken. B.S., and Joselyn A. Lindgren, M.S., staff research associate, both of the Magnetic Resonance Unit, SFVAMC.
The study was funded by a grant from the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health.
ADDITIONAL INFORMATION ON TESTS ADMINISTERED TO STUDY SUBJECTS:
* Recording of brainwaves during task performance. Study participants viewing a computer were shown two successive images. The first image, an X, served as an alert that the second image, a plus sign (+), would appear within two to 20 seconds. Immediately upon appearance of the second image, participants were to press a button with the index finger of their dominant hand. During the test, researchers recorded a type of brainwave called the contingent negative potential or CNV, which is considered to be a measure of the subjects’ anticipation and preparation potential as well as their ability to initiate physical action. The basal ganglia is one of the brain structures thought to contribute to the CNV. It coordinates motor behavior and is also one of two brain structures where HIV tends to concentrate.
* Neuropsychological testing. A battery of tests that assess mental agility were administered to participants. Among others, these included a test that requires connecting dots in sequence between letters and numbers, one that requires slipping different sizes of pegs into holes on a board, a memory test that entails recalling a list of 16 words immediately after hearing them read aloud and then again half an hour later, and a test that requires participants to quickly process information about the names of colors displayed either in the same color as the name (for example, "red" written in red) or in a different color ("red" written in blue.)
Liese Greensfelder | EurekAlert!
Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology
Pan-European study on “Smart Engineering”
30.03.2017 | IPH - Institut für Integrierte Produktion Hannover gGmbH
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Health and Medicine
30.03.2017 | Health and Medicine
30.03.2017 | Medical Engineering