Declined neural efficiency in cognitively stable human immunodeficiency virus patients

Abstract

Objective-To determine whether brain activation changes in clinically and neurocognitively normal human immunodeficiency virus (HIV)-infected and in HIV-seronegative control (SN) participants over a 1-year period.Methods-Functional magnetic resonance imaging (fMRI) was performed in 32 SN and 31 HIV patients (all with stable combination antiretroviral treatment) at baseline and after 1 year. Each participant performed a set of visual attention tasks with increasing attentional load (from tracking two, three, or four balls). All HIV and SN participants had normal neuropsychological function at both examinations.Results-Over 1 year, HIV patients showed no change in their neurocognitive status or in task performance during fMRI. However, HIV patients showed significant 1-year increases in fMRI signals in the prefrontal and posterior parietal cortices for the more difficult tasks, whereas SN control participants showed only decreases in brain activation in these regions. This resulted in significant interactions between HIV status and time of study in left insula, left parietal, left temporal, and several frontal regions (left and right middle frontal gyrus, and anterior cingulate). Interpretation-Because fMRI task performance remained unchanged in both groups, the HIV patients appeared to maintain performance by increasing usage of the attention network, whereas the control participants reduced usage of the attention network after 1 year. These findings suggest improved efficiency or a practice effect in the SN participants but declined efficiency of the neural substrate in HIV patients, possibly because of ongoing brain injury associated with the HIV infection, despite their apparent stable clinical course.Human immunodeficiency virus (HIV) can invade the brain and cause encephalitis, leukoencephalopathy, axonal damage, and variable neuronal loss.1 These neuropathological processes are accompanied by microglial and glial activation,1 which, in turn, may lead to the release of neurotoxic substances that may further contribute to neuronal apoptosis or neuronal dysfunction. These neuropathological alterations may ultimately lead to the clinical This study extends prior work by evaluating whether performance and brain activation change after 1 year during a set of visual attention tasks. Based on prior cross-sectional results, and our expectation that ongoing neuroinflammation and infection with HIV would lead to chronic and progressive brain injury, we hypothesized that neuroasymptomatic, cognitively stable HIV patients would show load-dependent increases in BOLD signals after 1 year to compensate for decreased neural efficiency while maintaining task performance. In contrast, HIV-seronegative (SN) participants with relatively unchanged neural substrate would show no significant signal changes in fMRI signals and task performances, or possibly signal decreases caused by increased efficiency from practice effects. Patients and Methods Research ParticipantsSixty-three individuals (30 male and 1 female HIV-infect...

Adaptive working memory training improved brain function in human immunodeficiency virus–seropositive patients

“…At baseline, HIV participants showed a reorganized neural network compared to SN participants even on the relatively simple 1‐back task, with greater activation in the medial and lateral frontal regions, but lesser activation in brainstem and bilateral cingulate gyri, which are consistent with previous studies of WM and sustained attention tasks in HIV participants 20, 22, 23, 41. Similarly, on the 2‐back task, the greater activation in bilateral medial frontal regions and the right precentral gyrus is also consistent with greater usage of the reserve attention network, or increased attentional modulation for this more‐difficult task in HIV patients 21, 24…”

“…However, in that follow‐up study, HIV neuroasymptomatic participants showed increased, rather than decreased, BOLD signals, suggesting declined efficiency with no practice effects 23. Future fMRI studies to evaluate brain activation after nonadaptive WMT is needed to delineate WMT from practice effects.…”

“…First, although improvements on nontrained WM tests were observed only in the adaptive WMT groups, the accompanied decreased BOLD signals may be partly attributed to practice effects, as shown in repeated task‐activated fMRI scans49 and in a 1‐year follow‐up fMRI study of SN controls without training 23. However, in that follow‐up study, HIV neuroasymptomatic participants showed increased, rather than decreased, BOLD signals, suggesting declined efficiency with no practice effects 23.…”

“…fMRI time series were analyzed with SPM8 software (Wellcome Department of Cognitive Neurology, London, UK). Preprocessing steps involved realignment, spatial normalization to MNI152 atlas, smoothing with an 8‐mm full width at half maximum isotropic kernel, segmentation, and coregistration as reported previously 23, 24. In a first‐level analysis, statistical maps reflecting the difference in activation between time points (eg, 1 month–baseline, 6 months–baseline) were calculated for each participant and task using a fixed‐effects model.…”

“…(2) To assess the neural correlates of adaptive WMT, we performed blood‐oxygenated‐level–dependent (BOLD) functional magnetic resonance (MR) imaging (MRI) (fMRI) to evaluate changes in the neural network at 1 and 6 months after the training. Based on previous work, we expect HIV patients to show a baseline reorganized or adapted WM network, with lesser activation within the normal WM network, but greater activation in the reserve networks, compared to controls 20, 21, 22, 23, 24. After the adaptive WMT, improved efficiency in the neural networks would lead to decreased activation in the extent and magnitude of the BOLD signal in both groups.…”