Decreased MEG beta oscillations in HIV-infected older adults during the resting state

Abstract

The introduction of combination antiretroviral therapy significantly reduced the prevalence of the most severe form of HIV-associated neurocognitive disorders (HAND). Despite this decline, 35-70 % of HIV-infected patients continue to develop mild motor and cognitive impairments. Although neuropsychological studies have shown that HAND affects a wide array of cognitive functions, a formal diagnosis is still based on the exclusion of opportunistic infections and other common ailments, as no specific tests or biomarkers are currently available. In this study, we used magnetoencephalography (MEG) to measure neural activity during the resting-state in 15 HIV-infected older patients and a demographically matched group of 15 uninfected controls. MEG is a noninvasive and direct measure of neural activity with excellent spatiotemporal resolution. All MEG data were coregistered to structural magnetic resonance images, corrected for head motion, fitted to a regional-level source model, and subjected to spectral analyses to quantify population-level neural oscillatory activity. We found that HIV-infected persons exhibited decreased beta oscillations in the supplementary motor area bilaterally, paracentral lobule, posterior cingulate, and bilateral regions of the superior parietal lobule relative to healthy controls. Beta oscillations in the posterior cingulate, a critical component of the default mode network, were also positively correlated with patient scores on the memory recall aspect of the Hopkins Verbal Learning Test-Revised. These results demonstrate that chronic HIV infection does not uniformly disturb cortical function, and that neuronal populations in dorsomedial motor and parietal cortices are especially affected. These findings also suggest that resting-state MEG recordings may hold significant promise as a functional biomarker for identifying HAND and monitoring disease progression.

Figure 1

Representative Example of the 29-node Regional Source Model. For each participant, a 29-node (grid-point) model with dual orthogonal orientations was fitted to the T1-weighted MRI following coregistrati on. This model was used to estimate regional neuronal activity during the resting-state MEG recording using inverse spatial filtering. In the figure above, the model can be seen overlaid on the MRI of a HIV-infected participant. The same 3D rendition is shown in both the left and right panels, although the orientation of the image differs between the two panels to facilitate visualization of the spatial location of each source. For example, using the left panel one can discern that the regional sources that appear to be in the orbits on the right panel are actually located in the ventral prefrontal cortices. Likewise, the nodes that appear to be located within the sinuses on the right panel can be discerned as medial frontal sources using the left panel. The different colors are only meant to aid in visually distinguishing the regional sources. Note that the regional sources are spaced equidistant apart and that each represents activity over an extended cortical area (i.e., > 1cm³). Thus, the time series of each node reflects the average neuronal activity over that brain region, and not the amount of activation at a precise neuroanatomical coordinate (e.g., a voxel in MNI space). Following spectral analyses, the current amplitude (in nAm) was summed across the dual orthogonal orientations to yield the total amplitude for the given brain region.

Figure 2

HIV-related Neuronal Activity Differences during the Resting-State. Neuronal activity in the beta-band (14–30 Hz) was significantly reduced in superior parietal areas, medial motor regions, and the posterior cingulate of HIV-infected patients (red) compared to uninfected controls (black) during the awake resting-state. Neuronal activity in the other frequency bins did not significantly differ between patients and controls. Error bars indicate one standard error of the mean. PCC: posterior cingulate; SMA: supplementary motor area; * = p < 0.05; † = p < 0.08