Multimodal neuroimaging evidence of alterations in cortical structure and function in HIV‐infected older adults

Abstract

Combination antiretroviral therapy transformed 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 fronto-parietal 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 was examined using advanced beamforming methods, and sMRI data was 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.

Effects of HIV and combination antiretroviral therapy on cortico-striatal functional connectivity

“…Our current rs-fc results are in agreement with previous studies by our group that did not observe cortical functional connectivity changes in the SMN due to HIV [16,61]. Of note, recent magnetoencephalography (MEG) studies have showed both structural and functional connectivity loss in the SMN [62,63]. Additional studies are necessary to investigate these discrepancies amongst various imaging modalities.…”

“…With these guidelines in place, it is important to determine the effects of cART on brain functional connectivity. In general, most research groups have found cART to have beneficial effects on cognitive status and neurobiology [28,63–66]. While cART may have detrimental effects [65], these do not outweigh the tremendous benefit in restoring overall health and lifestyle [66].…”

Neuroimaging with magnetoencephalography: A dynamic view of brain pathophysiology

“…Of particular clinical interest, we computed sensitivity and specificity indices for HAND using the peak amplitude values of the two main MEG findings (i.e., left postcental gyrus and prefrontal cortices) in conjunction, and found that the sensitivity and specificity for HAND were over 85%. 86 These findings strongly suggest that MEG metrics may serve as powerful classifiers in the context of HAND and HIV-associated brain dysfunction. Furthermore, another recent MEG study reported excellent test-retest reliability after ∼24 weeks in both HIV-infected and uninfected participants, 87 which of course is a critical property for any biomarker of disease.…”

“…We found reduced neural responses in the left postcentral gyrus (contralateral to stimulation) shortly after onset of the tactile stimulus in HIV-infected patients, along with increased alpha activity in the prefrontal cortices. 86 HIV-infected patients also had reduced gray matter in parahippocampal, lingual, and other areas, as well as a region of the left postcentral gyrus that spatially coincided with the abnormal MEG response (see Figure 6). 86 This latter finding suggests that some of the functional MEG aberrations observed in HIV disease may reflect alterations in the underlying neural structure, whereas others are more purely functional in nature (e.g., prefrontal cortices).…”

“…86 HIV-infected patients also had reduced gray matter in parahippocampal, lingual, and other areas, as well as a region of the left postcentral gyrus that spatially coincided with the abnormal MEG response (see Figure 6). 86 This latter finding suggests that some of the functional MEG aberrations observed in HIV disease may reflect alterations in the underlying neural structure, whereas others are more purely functional in nature (e.g., prefrontal cortices). Of particular clinical interest, we computed sensitivity and specificity indices for HAND using the peak amplitude values of the two main MEG findings (i.e., left postcental gyrus and prefrontal cortices) in conjunction, and found that the sensitivity and specificity for HAND were over 85%.…”