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. 2008 Jun;3(2):95-104.
doi: 10.1007/s11481-007-9092-0. Epub 2007 Oct 13.

Antiretroviral treatment is associated with increased attentional load-dependent brain activation in HIV patients

L Chang  1 , R Yakupov, H Nakama, B Stokes, T Ernst
Affiliations

Antiretroviral treatment is associated with increased attentional load-dependent brain activation in HIV patients

L Chang et al. J Neuroimmune Pharmacol. 2008 Jun.

Abstract

Objective: The purpose of this paper was to determine whether antiretroviral medications, especially the nucleoside analogue reverse transcriptase inhibitors, lead to altered brain activation due to their potential neurotoxic effects in patients with human immunodeficiency virus (HIV) infection.

Methods: Forty-two right-handed men were enrolled in three groups: seronegative controls (SN, n = 18), HIV subjects treated with antiretroviral medications (HIV+ARV, n = 12), or not treated with antiretroviral medications (HIV+NARV, n = 12). Each subject performed a set of visual attention tasks with increasing difficulty or load (tracking two, three or four balls) during functional magnetic resonance imaging.

Results: HIV subjects, both groups combined, showed greater load-dependent increases in brain activation in the right frontal regions compared to SN (p-corrected = 0.006). HIV+ARV additionally showed greater load-dependent increases in activation compared to SN in bilateral superior frontal regions (p-corrected = 0.032) and a lower percent accuracy on the performance of the most difficult task (tracking four balls). Region of interest analyses further demonstrated that SN showed load-dependent decreases (with repeated trials despite increasing difficulty), while HIV subjects showed load-dependent increases in activation with the more difficult tasks, especially those on ARVs.

Interpretation: These findings suggest that chronic ARV treatments may lead to greater requirement of the attentional network reserve and hence less efficient usage of the network and less practice effects in these HIV patients. As the brain has a limited reserve capacity, exhausting the reserve capacity in HIV+ARV would lead to declined performance with more difficult tasks that require more attention.

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Figures

Fig. 1
Fig. 1
Left panels: Parametric maps showing the significance of the attention effect across all three tasks, independent of load, in the two HIV groups and SN controls (cluster size> 100 voxels or 2.7 ml; voxel t threshold>5 or p<0.00001). Right panels: Parametric maps showing brain regions that show load-dependent increase in activation (attentional load effect), independent of mean activation, in each subject group (cluster size> 100 voxels 2.7 ml; voxel t threshold> 2.38 or p<0.05). See also Table 2 for the corresponding cluster volumes and significance of these brain regions that show load effects. SPL Superior parietal lobe; IPL inferior parietal lobule; SFG superior frontal gyrus; MFG middle frontal gyrus. R right; L left
Fig. 2
Fig. 2
Top row: Region of interest (ROI) analyses from local maxima of significant clusters (see red circles below) showing interaction effects between attentional load and subject groups. Load-dependent increases in BOLD signals were observed in the HIV+ subjects (orange dots) while BOLD signals decreased with greater attentional load (repeated trials) in the SN subjects (green triangles). Bottom row: Parametric maps showing brain regions with significantly greater attentional load effect in HIV+ subjects than SN subjects (cluster size> 100 voxels; t scores >2.38). The local maxima where the ROIs are extracted are indicated with red circles. See also Table 2
Fig. 3
Fig. 3
Top row: Region of interest (ROI) analyses from local maxima of significant clusters (see red circles below) showing interaction effects between attentional load and subject groups. Load-dependent increase in BOLD signals were observed in the HIV+ARV subjects (blue squares), while BOLD signals decreased with increased attentional load in the SN subjects (green triangles), and the BOLD signals for HIV+NARV subjects decreased from tracking two balls to three but increased only with tracking four balls (red dots). Bottom row: Parametric maps showing brain regions with significantly greater attentional load effect in HIV+ARV subjects than SN subjects (cluster size>100 voxels; t scores >2.38). The location of each of the ROIs at local cluster maxima are indicated with red circles. See also Table 2
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References

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