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!
Diagnoses: When Are Several Opinions Better Than One?
19.07.2016 | Max-Planck-Institut für Bildungsforschung
High in calories and low in nutrients when adolescents share pictures of food online
07.04.2016 | University of Gothenburg
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences