New HIV study finds clues, not in the immune system, but in the human brain

In addition to damaging the immune system, HIV may also damage brain circuitry. Fifty percent of HIV patients develop cognitive decline, which is associated with a poor prognosis and reduced survival time. Diagnosis of early HIV associated neurocognitive disorder (HAND) has been limited because brain damage may be occurring prior to changes in cognitive abilities. Early detection of changes in brain function is essential because the brain may be irreversibly damaged by the time cognitive decline occurs. Detection of these changes may require physiological measures, rather than symptom-based approaches. Resting state functional connectivity could provide information about early changes in brain function. Research in the lab of Ann Ragin shows that resting state functional connectivity in the lateral occipital cortex, which plays a role in visuo-motor coordination, is reduced in HIV patients within one year of diagnosis compared to controls. This study supports the use of functional connectivity studies as physiological measures of central nervous system damage early in HIV infection.

 

Despite known neurotoxic injury from the autopsies of AIDs patients, the effects of early infection on brain injury has been rarely explored. Initially, during infection, HIV virus particles rise quickly in the plasma and move throughout the body and brain. Although the immune system eventually reduces the number of viral particles, keeping them at a steady state for many years, the virus is not eradicated and is able to continue to replicate. In the brain, the blood brain barrier may keep out antibodies and antiviral therapies. This can result in continued replication of the infection in the brain. Understanding the effects of early infection on brain networks may help in determining vulnerability for cognitive decline.

 

Traditionally, imaging studies focused on the function of individual brain regions. Although these types of studies provide valuable information, brain regions are not islands and individual regions modulate each other within networks. Functional connectivity analyses provide insight into the interaction of brain regions in a network. “Functional connectivity” models neuronal interactions by the temporal correlation in activity patterns between regions. This means that functional connectivity only determines correlational activation between regions and cannot imply physical pathways or a causal effect. Despite this limitation, studies evaluating functional connectivity provide valuable insight into the effects of specific variables, such as a virus, genetic alteration, drug response, etc, on brain function.

 

Although the HIV virus targets the immune system, the prevalence of cognitive decline in HIV/AIDs patients suggests that the virus also damages neural circuitry. Symptom-based approaches to cognitive impairment may miss early alterations in brain function, which appear to occur prior to cognitive impairment. Detecting changes in brain function that occur early in the disorder is essential for understanding susceptibility to cognitive decline in HIV patients. Functional connectivity analyses may provide insight into these early changes.