Multimodal imaging evidence for the brain basis of cognitive dysfunction in older HIV+ men

Abstract

ObjectiveThis study used converging methods to define the structural and functional characteristics of the neural substrates underlying variation in cognitive ability in older men with well-controlled HIV infection. MethodsSeventy-six HIV+ men treated with combination antiretrovirals completed attention and inhibitory control tasks tapping different cortico-subcortical circuits while time-locked high-density EEG was acquired. Fifty-four also underwent structural MRI. We investigated relationships between task-evoked EEG responses, cognitive ability and immunocompromise. MRI suggested a subcortical basis for the observed EEG effects. ResultsEEG activity was associated with cognitive ability at later (P300) but not earlier processing stages of both tasks. However, only the P300 evoked by the attention task was associated with past HIV infection severity. Source localization confirmed that the tasks engaged different brain circuits. Thalamus volumes correlated with P300 amplitudes evoked by the attention task, while globus pallidus volumes were related to the P300 in both tasks. InterpretationThis is the first study to combine structural and functional imaging in an overlapping sample to address the neural circuits related to cognitive dysfunction in HIV. Neural substrates of attention were more affected than those supporting inhibitory control. Preliminary evidence suggests these differences may relate to vulnerability of the thalamus to the effects of HIV. Our results suggest high-yield tasks and circuit targets for future work.