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Changes in the brain hinder addiction recovery in people who are HIV-positive

Monday, December 20, 2021

Researchers with the Del Monte Institute for Neuroscience at the University of Rochester are studying how the brain puts the 'brakes' on behavior. That may be different in individuals recovering from cocaine addiction and who are also HIV-positive.

“Scientists have long known that drug abuse can cause damage to the brain. We also know HIV infection can cause brain changes,” said John Foxe, Ph.D., director of the Del Monte Institute for Neurosciences and senior author of the study published in Neuropharmacology. “Since drug use is common in individuals with HIV, an important question is how brain deficits associated with both conditions might add up.”

Researchers used functional magnetic resonance imaging (fMRI) to measure the brain responses of cocaine addicts and patients with HIV while participants played a game that involved purposefully withholding responses to target stimuli. “The challenging thing about the game we asked participants to play isn’t exactly playing it, per se,” said Kathryn Mary Wakim, Ph.D., a recent graduate from the Neuroscience Graduate Program at the University of Rochester and the first author of the study. “What’s really hard is not playing the game. What we wanted to measure was how the brain holds back a response under certain task conditions.”

Difficulty withholding inappropriate responses are thought to be a central issue in addiction. Researchers found that participants diagnosed with both HIV and cocaine dependence had a difficult time holding back behavioral responses while playing the game, changes which were also reflected in brain activity. A companion study also published in Neuropharmacology found similar results while brain activity was measured using electroencephalography (EEG). Brain activity during response withholding in HIV+ participants in recovery from cocaine dependence was different than brain activity in HIV- participants in recovery.

“Currently, when someone who is HIV positive enters a recovery program they are treated in much the same fashion as any other person with an addiction issue,” said Foxe. “But our findings show that they, very likely, need to be treated differently or more intensively. HIV and drug addiction should be a dual diagnosis when it comes to recovery, and we will need to design specific targeted intervention approaches for this population, given their unique vulnerability.”

“When people with HIV relapse, it's a big deal. The majority of participants in our study contracted HIV – not by injecting cocaine – but by having unprotected sex,” Wakim said. “Relapse is an outcome that should be minimized in this population because cocaine use is strongly associated with risky sexual behavior, which makes the spread of HIV more likely when a relapse occurs.”

Additional co-authors are Edward Freedman, Ciara Molloy, Madalina Tivarus, Nicole Vieyto, and Zhewei Cao with the University of Rochester, and Armin Heinecke at Maastricht University in the Netherlands. The research was supported with funding from Eunice Kennedy Shriver National Institute of Child Health and Human Development and by the University of Rochester Center for AIDS Research, which is funded through the National Institute of Allergy and Infectious Diseases.

Kathryn-Mary Wakim's Thesis Paper Accepted in Neuropharmacology

Tuesday, June 1, 2021

When you see her, congratulate Kamy on her first authorship of "Assessing combinatorial effects of HIV infection and former cocaine dependence on cognitive control processes: A high-density electrical mapping study of response inhibition" which was accepted to the journal Neuropharmacology.

Stimulant drug use in HIV+ patients is associated with poor personal and public health outcomes, including high-risk sexual behavior and faster progression from HIV to AIDS. Inhibitory control--the ability to withhold a thought, feeling, or action--is a central construct involved in the minimization of risk-taking behaviors. Recent neuroimaging and behavioral evidence indicate normalization of inhibitory control processes in former cocaine users as a function of the duration of drug abstinence, but it is unknown whether this recovery trajectory persists in former users with comorbid HIV. Here, we investigate the neural correlates of inhibitory control in 103 human subjects using highdensity EEG recording as participants performed a Go/NoGo response inhibition task. Four groups of participants were recruited, varying on HIV and cocaine-dependence status. Electrophysiological responses to successful inhibitions and behavioral task performance were compared among groups. Results indicate persistent behavioral and neurophysiological impairment in HIV+ patients' response inhibition despite current abstinence from cocaine. Analysis of task performance showed that HIV+ abstinent cocaine-dependent participants demonstrate the lowest performance of all groups across all metrics of task accuracy. Planned comparisons of electrophysiological components revealed a main effect of scalp site and an interaction between HIV-status and scalp site on N2 amplitudes during successful inhibitions. Analysis of the P3 time region showed a main effect of scalp site and an interaction between HIV-status and cocaine dependence. These results suggest synergistic alterations in the neurophysiology of response inhibition and indicate that abstinence-related recovery of inhibitory control may be attenuated in patients with HIV.

Researchers find breastfeeding linked to higher neurocognitive testing scores

Monday, April 26, 2021

New research finds that children who were breastfed scored higher on neurocognitive tests. Researchers in the Del Monte Institute for Neuroscience at the University of Rochester Medical Center (URMC) analyzed thousands of cognitive tests taken by nine and ten-year-olds whose mothers reported they were breastfed, and compared those results to scores of children who were not.

"Our findings suggest that any amount of breastfeeding has a positive cognitive impact, even after just a few months." Daniel Adan Lopez, Ph.D. candidate in the Epidemiology program who is first author on the study recently published in the journal Frontiers in Public Health. "That's what's exciting about these results. Hopefully from a policy standpoint, this can help improve the motivation to breastfeed."

Hayley Martin, Ph.D., a fourth year medical student in the Medical Scientist Training Program and co-author of the study, focuses her research on breastfeeding. "There's already established research showing the numerous benefits breastfeeding has for both mother and child. This study's findings are important for families particularly before and soon after birth when breastfeeding decisions are made. It may encourage breastfeeding goals of one year or more. It also highlights the critical importance of continued work to provide equity focused access to breastfeeding support, prenatal education, and practices to eliminate structural barriers to breastfeeding."

Researchers reviewed the test results of more than 9,000 nine and ten-year-old participants in the Adolescent Brain Cognitive Development (ABCD) study. Variations were found in the cumulative cognitive test scores of breastfed and non-breastfed children. There was also evidence that the longer a child was breastfed, the higher they scored.

"The strongest association was in children who were breastfed more than 12 months," said Lopez. "The scores of children breastfed until they were seven to 12 months were slightly less, and then the one to six month-old scores dips a little more. But all scores were higher when compared to children who didn't breastfeed at all." Previous studies found breastfeeding does not impact executive function or memory, findings in this study made similar findings.

"This supports the foundation of work already being done around lactation and breastfeeding and its impact on a child's health," said Ed Freedman, Ph.D., the principal investigator of the ABCD study in Rochester and lead author of the study. "These are findings that would have not been possible without the ABCD Study and the expansive data set it provides."

MRIs from Study by John Foxe & Ed Freedman Reveal More Incidental Findings in Children

Wednesday, March 24, 2021

Photo of Ed Freedman Photo of John Foxe Published in JAMA Neurology, scan results from the Adolescent Brain Cognitive Development (ABCD) Study revealed one in 25 children needed further medical evaluation. The findings by the Del Monte faculty members and their colleagues could change our understanding of the prevalence of neurological problems in children and how neuroimaging is used to screen for these problems.

Brain changed by caffeine in utero, study finds

Thursday, February 4, 2021

New research finds caffeine consumed during pregnancy can change important brain pathways in baby.

New research finds caffeine consumed during pregnancy can change important brain pathways that could lead to behavioral problems later in life. Researchers in the Del Monte Institute for Neuroscience at the University of Rochester Medical Center (URMC) analyzed thousands of brain scans of nine and ten-year-olds, and revealed changes in the brain structure in children who were exposed to caffeine in utero.

"These are sort of small effects and it's not causing horrendous psychiatric conditions, but it is causing minimal but noticeable behavioral issues that should make us consider long term effects of caffeine intake during pregnancy," said John Foxe, Ph.D., director of the Del Monte Institute for Neuroscience, and principal investigator of the Adolescent Brain Cognitive Development or ABCD Study at the University of Rochester. "I suppose the outcome of this study will be a recommendation that any caffeine during pregnancy is probably not such a good idea."

Elevated behavioral issues, attention difficulties, and hyperactivity are all symptoms that researchers observed in these children. "What makes this unique is that we have a biological pathway that looks different when you consume caffeine through pregnancy," said Zachary Christensen, a M.D/Ph.D. candidate in the Medical Science Training Program and first author on the paper published in the journal Neuropharmacology. "Previous studies have shown that children perform differently on IQ tests, or they have different psychopathology, but that could also be related to demographics, so it's hard to parse that out until you have something like a biomarker. This gives us a place to start future research to try to learn exactly when the change is occurring in the brain."

Investigators analyzed brain scans of more than 9,000 nine and ten-year-old participants in the ABCD study. They found clear changes in how the white matter tracks -- which form connections between brain regions -- were organized in children whose mothers reported they consumed caffeine during pregnancy.

Pregnant woman standing at window holding mug.

Researchers analyzed the brain scans of more then 9,000 nine and ten-year-olds and found a change in important brain pathways in those whose mothers retrospectively reported consuming caffeine while pregnant.

URMC is one of 21-sites across the country collecting data for the ABCD study, the largest long-term study of brain development and child health. The study is funded by the National Institutes of Health. Ed Freedman, Ph.D., is the principal investigator of the ABCD study in Rochester and a co-author of the study.

"It is important to point out this is a retrospective study," said Foxe. "We are relying on mothers to remember how much caffeine they took in while they were pregnant."

Previous studies have found caffeine can have a negative effect on pregnancy. It is also known that a fetus does not have the enzyme necessary to breakdown caffeine when it crosses the placenta. This new study reveals that caffeine could also leave a lasting impact on neurodevelopment.

The researchers point out that it is unclear if the impact of the caffeine on the fetal brain varies from one trimester to the next, or when during gestation these structural changes occur.

"Current clinical guidelines already suggest limiting caffeine intake during pregnancy -- no more than two normal cups of coffee a day," Christensen said. "In the long term, we hope to develop better guidance for mothers, but in the meantime, they should ask their doctor as concerns arise."