Multimodal neuroimaging evidence of alterations in cortical structure and function in HIV-infected older adults.
Combination antiretroviral therapy transformed human immunodeficiency virus (HIV)-infection from a terminal illness to a manageable condition, but these patients remain at a significantly elevated risk of developing cognitive impairments and the mechanisms are not understood. Some previous neuroimaging studies have found hyperactivation in frontoparietal networks of HIV-infected patients, whereas others reported aberrations restricted to sensory cortices. In this study, we utilize high-resolution structural and neurophysiological imaging to determine whether alterations in brain structure, function, or both contribute to HIV-related cognitive impairments. HIV-infected adults and individually matched controls completed 3-Tesla structural magnetic resonance imaging (sMRI) and a mechanoreception task during magnetoencephalography (MEG). MEG data were examined using advanced beamforming methods, and sMRI data were analyzed using the latest voxel-based morphometry methods with DARTEL. We found significantly reduced theta responses in the postcentral gyrus and increased alpha activity in the prefrontal cortices of HIV-infected patients compared with controls. Patients also had reduced gray matter volume in the postcentral gyrus, parahippocampal gyrus, and other regions. Importantly, reduced gray matter volume in the left postcentral gyrus was spatially coincident with abnormal MEG responses in HIV-infected patients. Finally, left prefrontal and postcentral gyrus activity was correlated with neuropsychological performance and, when used in conjunction, these two MEG findings had a sensitivity and specificity of over 87.5% for HIV-associated cognitive impairment. This study is the first to demonstrate abnormally increased activity in association cortices with simultaneously decreased activity in sensory areas. These MEG findings had excellent sensitivity and specificity for HIV-associated cognitive impairment, and may hold promise as a potential disease marker.
Department of Pharmacology and Experimental Neurosciences, University of Nebraska Medical Center (UNMC), Omaha, Nebraska; Department of Neurological Sciences, UNMC, Omaha, Nebraska; Center for Magnetoencephalography, UNMC, Omaha, Nebraska.
Tony W
TW
Wilson
Elizabeth
E
Heinrichs-Graham
Katherine M
KM
Becker
Joseph
J
Aloi
Kevin R
KR
Robertson
Uriel
U
Sandkovsky
Matthew L
ML
White
Jennifer
J
O'Neill
Nichole L
NL
Knott
Howard S
HS
Fox
Susan
S
Swindells
D015526:AIDS Dementia Complex / Q000473:pathology* / Q000503:physiopathology*; D000368:Aged; D058256:Brain Waves / Q000502:physiology*; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D015225:Magnetoencephalography; D008297:Male; D008875:Middle Aged; D020534:Parahippocampal Gyrus / Q000473:pathology / Q000503:physiopathology; D013003:Somatosensory Cortex / Q000473:pathology / Q000503:physiopathology
AIDS; HIV-associated neurocognitive disorder; biomarker; cognitive disorders; magnetoencephalography; oscillation