Combined impact of HIV and cannabis use on insular functional connectivity
Neurocognitive alterations have been independently documented among individuals with human immunodeficiency virus (HIV) and those who regularly use cannabis (CB), but the combined impact on functional connectivity (FC) has yet to be considered. Given the neurocognitive deficits caused by HIV (Heaton et al., 2011) and the suggested brain metabolic alterations in frontal white matter pathways from HIV and cannabis (Chang et al., 2006), we delineated alterations in FC of various insular (INS) regions presumably subserving cognitive functions among HIV and CB-using participants.73 individuals (21 HIV+/CB+; 19 HIV+/CB-; 21 HIV-CB+; 12 HIV-CB-) underwent resting-state fMRI. Resting-state FC analyses were performed using bilateral anterior (a), middle (m), and posterior (p) INS seeds. To investigate the independent and combined impact of HIV and CB, whole-brain connectivity maps were generated for each ROI and compared across groups (threshold: p-voxel<0.001; p-cluster: p<0.05).Among HIV+ participants (main effect) the left aINS demonstrated reduced FC with the anterior and posterior cingulate, the right aINS showed reduced FC with the bilateral dorsomedial prefrontal cortex and striatum, and the right mINS showed reduced FC with the left insula and striatum. The right pINS showed an HIV x CB interaction with the left inferior parietal lobule/supramarginal gyrus (IPL; Figure 1 inset). Specifically, among HIV- participants pINS-IPL FC was reduced in CB users, however, among HIV+ individuals such FC was increased among CB users (Figure 1).We identified alterations in INS FC associated with HIV in frontal, striatal, and cingulate regions. These outcomes are consistent with HIV-related fronto-striatal dysfunction and associated cognitive impairment (Plessis et al., 2014). Interestingly, CB use among HIV+ individuals appeared to normalize insula-parietal lobe FC. INS FC alterations may mediate some aspects of cognitive dysfunction associated with HIV infection and/or CB use.