Abstract
Cognitive and functional neural correlates of human immunodeficiency virus (HIV) are only partially understood at present. Variability in neural response, which has been noted in the literature, may relate to clinical factors associated with HIV, including time since HIV diagnosis, CD4 count and nadir, HIV viral load, and comorbid infectious processes, especially hepatitis C. The present investigation evaluated working memory-related functional neural activation in 26 HIV+ participants, 28 demographically matched HIV-seronegative individuals, and 8 HIV+ individuals with hepatitis C coinfection. Analyses examined impact of HIV infection duration, CD4 count and nadir, HIV viral load, and hepatitis C serostatus. Results showed that HIV-seronegative participants had fastest reaction times, and during the working memory task, HIV+ participants with hepatitis C coinfection showed strongest bias toward commission errors; however, signal detection (i.e., overall task performance) was equivalent across groups. Functional magnetic resonance imaging (fMRI) results showed HIV-related greater activation to an easier vigilance task and HIV-related lower activation to a more difficult working memory task, consistent with reduced cognitive reserve. Hepatitis C coinfection related to diffuse neural dysregulation. Correlational analyses suggested relationships of increasingly severe disease with poorer functioning in brain regions linked to error monitoring and attention regulation.
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Notes
Participants who met substance dependence criteria at later time points (i.e., 12 or 24-month visits) were not excluded from participation. For time points most proximal to participant MRI scan, 44 % of individuals qualified for lifetime diagnosis of alcohol dependence (3 % proximal to MRI; no significant differences between clinical groups). Lifetime cocaine dependence was met in 42 % of participants (5 % proximal to MRI). Kruskall-Wallis tests showed significant group differences for endorsement of lifetime (χ 2 = 10.143, p = 0.006) and MRI proximal cocaine dependence (χ 2 = 8.345; p = 0.015; highest rates in HIV/HCV coinfected participants). Lifetime narcotic dependence was met in 15 % of participants (2 % proximal to MRI), with significant differences among clinical groups for lifetime (χ 2 = 22.463, p < 0.001; highest rates in HIV/HCV coinfected participants) but not MRI proximal dependence.
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Acknowledgments
Support for this project came from NIH R01MH074368, 403 P01AA019072, K99AA020235, and P30AI042853 (Lifespan/Tufts/404 Brown Center for AIDS Research). Many thanks to the current and past students, fellows, and staff of the Cohen and Tashima laboratories, especially Kate Devlin, Skye Ross, Matthew Pinna, and Anna Folkers.
Conflict of interest
The following authors declare that they have no conflict of interest: Jessica Caldwell, Assawin Gongvatana, Bradford Navia, Lawrence Sweet, Karen Tashima, Mingzhou Ding, and Ronald Cohen.
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Caldwell, J.Z.K., Gongvatana, A., Navia, B.A. et al. Neural dysregulation during a working memory task in human immunodeficiency virus-seropositive and hepatitis C coinfected individuals. J. Neurovirol. 20, 398–411 (2014). https://doi.org/10.1007/s13365-014-0257-3
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DOI: https://doi.org/10.1007/s13365-014-0257-3