HIV, hepatitis study

MARQUETTE – A neuropsychologist at Marquette General Hospital belongs to a team of neuroscientists at the forefront of research into how Hepatitis C and the human immunodeficiency virus affect brain function and performance.

Dr. Jessica Caldwell and her colleagues used functional magnetic resonance imaging to measure the brain functions of 26 participants with HIV, 28 demographically matched people who are HIV-negative as a control group and eight people positive for both HIV and Hepatitis C.

While in the fMRI machine, Caldwell said, the participants performed two tests. The first was a simple memory test, where they looked at a screen, which displayed a single letter at a time; participants had to press a button if the letter was the same as the one that preceded it. The second test, a ‘working memory’ test, was almost identical, but participants were told the press a button if the screen matched the letter displayed just before the previous letter.

“And then we just look at their brain activation while they’re doing that test,” Caldwell said.

What she and the other researchers found was that all three groups of participants performed the same on the test overall, but the brains of HIV-positive participants and the group with HIV and Hepatitis C worked much harder to do so.

“They were able to press the button just as well and just as accurately, but their brain activity looked different,” she said.

The eight subjects with both viruses also made more “commission errors,” Caldwell said – “so they tended to press the button when it wasn’t correct; they’re biased toward making an error rather than playing it safe.”

Caldwell and her colleagues aren’t sure yet what aspects of the viruses are causing the brains of afflicted people to have to work harder to achieve the same level of cognitive function.

“I think that’s something that’s under active investigation at this point,” Caldwell said. “One of the hypotheses is that HIV itself has an inflammatory effect on the brain, so the immune response that your body has to the infection causes some swelling within pathways in your brain. And the swelling actually leads to less efficient processing in basically the fiber pathways between regions of your brain that lead to efficient thinking. Some of the other things are, HIV infection and fighting that infection within the brain causes differences in neurochemicals within the brain. And something about the imbalance of the actual neurochemicals also can lead to inefficient communication between regions.”

The fMRI ‘working memory’ study was published in the medical Journal of NeuroVirology at the end of May, and Caldwell said she’s moved on to studying what effects HIV and Hepatitis C could have on those neurochemicals.

“Right now, the piece that I’m involved in is looking at the brain metabolites that I mentioned, so really looking within the areas of the brain where activity was different, looking at the neurochemistry,” she said. “So the frontal lobe of the brain, where part of attention is housed, and also a deeper structure called the basal ganglia, which is important for regulatory control, and trying to figure out whether we can see differences in the chemistry that might play a role in differences in those activations.”

Caldwell came into the “working memory” study as an expert on fMRI with more than a decade of experience with the imaging technology. She met the other researchers during her postdoctoral fellowship at Brown University.

“(Dr.) Ronald Cohen, who’s the final author on the paper, he’s the principal investigator who’s been investigating HIV for a long time, and I kind of came in as someone with a really strong background in functional MRI but not knowing HIV as well,” she said. “And so I was able to learn a lot about the chemical processes and HIV population and really come in and use my expertise in functional MRI to add to the lab.”

Caldwell said as medical treatments, drugs and technologies have allowed people with HIV to live full and even healthy lives, the focus has shifted to improving the quality of those lives.

“I think with HIV the research went through the phase where the biggest goal was really just to help people live longer and live healthier,” she said. “And now it’s really, OK, we’re doing that, but people are still struggling, and so what can we do to address some of the problems that people are having? And step one is really, why? Why are they still struggling with some of these things?”

In participating in the study, Caldwell said she was probably most surprised by how little is known about brain activity and functionality in people with HIV. The small sample sizes also make things difficult. In many ways, she and her colleagues are trailblazing into work that has never been done, where they hope to learn enough to begin to answer some of those questions.

But as with any pioneers, there are potential pitfalls.

“…(B)ecause you’re on the cutting edge, there’s chances that you could have it right and chances that someone could find that there’s more to the story than you’re finding,” Caldwell said.

Zach Jay can be reached at 906-486-4401.