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Interactive Effects of HIV Infection and Cannabis Use on Insula Subregion Functional Connectivity

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Abstract

Chronic inflammation in the central nervous system is one mechanism through which human immunodeficiency virus (HIV) may lead to progressive cognitive decline. Given cannabis’s (CB’s) anti-inflammatory properties, use prevalence among people living with HIV (PLWH), and evidence implicating the insula in both, we examined independent and interactive effects of HIV and CB on insular circuitry, cognition, and immune function. We assessed resting-state functional connectivity (rsFC) of three insula subregions among 106 participants across four groups (co-occurring: HIV+/CB+; HIV–only: HIV+/CB−; CB–only: HIV−/CB+; controls: HIV−/CB−). Participants completed a neurocognitive battery assessing functioning across multiple domains and self-reported somatic complaints. Blood samples quantified immune function (T-cell counts) and inflammation (tumor necrosis factor alpha [TNF–α]). We observed interactive HIV × CB effects on rsFC strength between two anterior insula (aI) subregions and sensorimotor cortices such that, CB appeared to normalize altered rsFC among non-using PLWH. Specifically, compared to controls, HIV–only and CB–only groups displayed decreased dorsal anterior insula (DI) – postcentral gyrus rsFC and increased ventral anterior insula (VI) – supplementary motor area rsFC, whereas the co-occurring group displayed DI and VI rsFC more akin to that of controls. Altered DI – postcentral rsFC correlated with decreased processing speed and somatic complaints, but did not significantly correlate with inflammation (TNF–α). These outcomes implicate insula – sensorimotor neurocircuitries in HIV and CB and are consistent with prior work suggesting that CB use may normalize insula functioning among PLWH.

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Availability of Data and Material and Code

The authors have released all code associated with this manuscript. The code and tabular data are available on GitHub (https://github.com/Flanneryg3/HIVCB_ProjectCode), and unthresholded brain maps are available on NeuroVault (https://neurovault.org/collections/8659/).

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Acknowledgements

Primary support for this project was provided by the National Institutes of Health (NIH) [K01DA037819] (JSF, MTS), and [R01DA033156] (RG), and the Florida International University (FIU) Graduate School Dissertation Year Fellowship (JSF). Contributions from authors were also supported by NIH [U54MD012393] (JSF, MTS), [R01DA041353] (MTS, ARL, MCR, RP), and National Science Foundation (NSF) [1631325] (ARL, MCR, TS). We thank the FIU Instructional & Research Computing Center (IRCC, http://ircc.fiu.edu) for providing access to the HPC computing resources that contributed to the generation of the research results reported herein.

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  1. Department of Psychology, Florida International University, Miami, FL, USA

    Jessica S. Flannery, Taylor Salo, Lauren D. Hill-Bowen, Ranjita Poudel, Ashley R. Adams, Raul Gonzalez & Matthew T. Sutherland

  2. Department of Physics, Florida International University, Miami, FL, USA

    Michael C. Riedel & Angela R. Laird

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Flannery, J.S., Riedel, M.C., Salo, T. et al. Interactive Effects of HIV Infection and Cannabis Use on Insula Subregion Functional Connectivity. J Neuroimmune Pharmacol 17, 289–304 (2022). https://doi.org/10.1007/s11481-021-10005-8

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