Background. Human immunodeficiency virus (HIV)–associated neurocognitive impairment remains a prevalent comorbidity
that impacts daily functioning and increases morbidity. While HIV infection is known to cause widespread disruptions in the brain,
different magnetic resonance imaging (MRI) modalities have not been effectively integrated. In this study, we applied 3-way supervised
fusion to investigate how structural and functional coalterations affect cognitive function.
Methods. Participants (59 people living with HIV and 58 without HIV) completed comprehensive neuropsychological testing
and multimodal MRI scanning to acquire high-resolution anatomical, diffusion-weighted, and resting-state functional images.
Preprocessed data were reduced using voxel-based morphometry, probabilistic tractography, and regional homogeneity, respectively.
We applied multimodal canonical correlation analysis with reference plus joint independent component analysis using global
cognitive functioning as the reference.
Results. Compared with controls, participants living with HIV had lower global cognitive functioning. One joint component was
both group discriminating and correlated with cognitive function. This component included the following covarying regions: fractional
anisotropy in the corpus callosum, short and long association fiber tracts, and corticopontine fibers; gray matter volume in the
thalamus, prefrontal cortex, precuneus, posterior parietal regions, and occipital lobe; and functional connectivity in frontoparietal
and visual processing regions. Component loadings for fractional anisotropy also correlated with immunosuppression.
Conclusions. These results suggest that coalterations in brain structure and function can distinguish people with and without
HIV and may drive cognitive impairment. As MRI becomes more commonplace in HIV care, multimodal fusion may provide neural
biomarkers to support diagnosis and treatment of cognitive impairment.