Brain Connectivity Inhibited in HIV-Positive Youth

By impairing brain connectivity, an HIV infection may affect cognition in young patients, according to a recent imaging study.

“Collectively, the results support a model of diffuse network changes in young HIV positive individuals with limited or no treatment history and corresponding cognitive dysfunction,” the study’s senior author, Robert H. Paul PhD (pictured), director of the University of Missouri’s Institute of Mental Health, and his co-authors wrote.

The researchers used diffusion MRI-based tractography and graph-theoretic approaches to gain insights into communication between regions of the brain. The team discovered that changes in the organization of white matter in the young HIV positive patients was related to cognitive deficits detected by neuropsychological testing.

Weaker connectivity in the brains of the HIV positive test subjects correlated with significantly poorer learning/recall. Network global connection strength was measured at 385.99 standard deviations in the HIV positive group and 312.58 in the HIV negative sample. This difference had a P value of .006. There also were clinically significant differences in network global clustering co-efficient and global characteristic path length, which were other metrics for connectivity, according to the study. Psychomotor/processing speeds, executive functioning, fine motor skills and dexterity, and visuospatial skills did not appear to be affected.

These findings “were not significantly related to HIV clinical status (CD4 cell count and viral load,” the study added. “It is extremely rare to detect any changes in brain structure and function in a population of young adults unless there is a serious neurological disease or condition present,” Christopher Pawela PhD, the editor-in-chief of the journal, Brain Connectivity, said in a May 10 press release. “The fact that the authors were able to detect changes in such a resilient young population gives credence to the hypothesis that HIV infection is associated with brain alterations and corresponding abnormalities in cognitive abilities.”

The study explained that neuronal loss and injury in HIV are believed to be caused in part by inflammation, which occurs soon after the virus infects the central nervous system. The infection then triggers several inflammatory and neurotoxic processes.

“These injuries are distributed widely throughout the brain and correspond to white matter damage as well as cognitive impairment, the study added.

Other research has shown that the HIV virus crosses the blood-brain barrier about 8 days after seroconversion and before symptoms of immune dysfunction or cognitive dysfunction is apparent.

“Despite the efficacy of combination antiretroviral therapy (cART) in reducing viral load, current treatments do not appear to prevent or reverse existing brain damage.”

The test subjects were 29 HIV positive and 16 demographically matched HIV negative individuals. The mean age in the HIV positive group was of 25.9 and their ages ranged from 18 to 45. Men represented 17% of the HIV positive sample and 31% of the HIV negative sample.

The mean month of infection was 9.33, and 83% of these participants had not yet started treatment or had begun it within 3 months before joining the study. The HIV positive patients were selected from a group in pre-treatment counseling at HIV clinics in Cape Town, South Africa. Patients, whose cognition potentially could be affected by psychiatric and neurological conditions, head injuries, infections, and current substance abuse, were excluded from the sample.

A National Institutes of Health grant had finances the study. Co-authors came from the University of Missouri St. Louis, Washington University, the University of Southern California, Brown University, the University of Cape Town, and the Missouri Institute of Mental Health. “Topical Organization of Whole-Brain White Matter in HIV Infection” was published in the March 1 issue of Brain Connectivity.