Ageing and selective inhibition of irrelevant information in an attention-demanding rapid serial visual presentation task.

Attention involves both an ability to selectively focus on relevant information and simultaneously ignore irrelevant information (i.e. inhibitory control). Many factors impact inhibitory control such as individual differences, relative timing of stimuli presentation, distractor characteristics, and participant age. Previous research with young adults responding to an attention-demanding rapid serial visual presentations of pictures superimposed with task-irrelevant words evaluated the extent to which unattended information may be subject to inhibitory control. Surprise recognition tests following the rapid serial visual presentation task showed that recognition for unattended words presented with non-targets (i.e. non-aligned or 'NA' words) during the rapid serial visual presentation task were recognised at chance levels. However, when the unattended words were infrequently paired with the attended picture targets (i.e. target-aligned or 'TA' words), recognition rates were significantly below chance and significantly lower compared to NA words, suggesting selective inhibitory control for the previously unattended TA words. The current study adapted this paradigm to compare healthy younger and older adults' ability to engage in inhibitory control. In line with previous research, younger adults demonstrated selective inhibition with recognition rates for TA words significantly lower than NA words and chance, while NA words were recognised at chance levels. However, older adults showed no difference in recognition rates between word types (TA versus NA). Rather all items were recognised at rates significantly below chance suggesting inhibited recognition for all unattended words, regardless of when they were presented during the primary task. Finally, older adults recognised significantly fewer NA words compared to young adults. These findings suggest that older adults may experience a decline in their ability to selectively inhibit the processing of irrelevant information, while maintaining the capacity to exercise global inhibition over unattended lexical information.

Systemic Mitochondrial Oxidative Phosphorylation Protein Levels Correlate with Neuroimaging Measures in Chronically HIV-Infected Individuals.

Few studies have examined systemic mitochondrial function in conjunction with brain imaging in human immunodeficiency virus (HIV) disease. Oxidative phosphorylation enzyme protein levels of peripheral blood mononuclear cells were measured in association with neuroimaging indices in 28 HIV+ individuals. T1-weighted magnetic resonance imaging yielded volumes of seven brain regions of interest; diffusion tensor imaging determined fractional anisotropy (FA) and mean diffusivity (MD) in the corpus callosum (CC). Higher nicotinamide adenine dinucleotide dehydrogenase levels correlated with lower volumes of thalamus (p = .005) and cerebral white matter (p = .049) and, in the CC, with lower FA (p = .011, body; p = .005, genu; p = .009, total CC) and higher MD (p = .023, body; p = .035, genu; p = .019, splenium; p = .014, total CC). Greater cytochrome c oxidase levels correlated with lower thalamic (p = .034) and cerebellar gray matter (p = .021) volumes. The results indicate that systemic mitochondrial cellular bioenergetics are associated with brain health in HIV.

Sleep and neuropsychological performance in HIV+ subjects on efavirenz-based therapy and response to switch in therapy.

The antiretroviral drug efavirenz (EFV) has been linked to disordered sleep and cognitive abnormalities. We examined sleep and cognitive function and subsequent changes following switch to an alternative integrase inhibitor-based regimen. Thirty-two HIV-infected individuals on EFV, emtricitabine, and tenofovir (EFV/FTC/TDF) without traditional risk factors for obstructive sleep apnea (OSA) were randomized 2:1 to switch to elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/COBI/FTC/TDF) or to continue EFV/FTC/TDF therapy for 12 weeks. Overnight polysomnography and standardized sleep and neuropsychological assessments were performed at baseline and at 12 weeks. No significant differences in change over 12 weeks were noted between the two arms in any sleep or neuropsychological test parameter. At entry, however, the rate of sleep disordered breathing (SDB) was substantially higher in study subjects compared to published age-matched norms and resulted in a high assessed OSA rate of 59.4%. Respiratory Disturbance Index (RDI), a measure of SDB, correlated with age- and education-adjusted global neuropsychological Z-score (NPZ) (r = -0.35, p = 0.05). Sleep Maintenance Efficiency, Wake after Sleep Onset, REM Sleep and RDI correlated with domain-specific NPZ for learning and memory (all p-values ≤ 0.05). Among HIV-infected individuals on EFV-based therapy and without traditional risk factors for OSA, sleep and neuropsychological abnormalities do not readily reverse after discontinuation of EFV. High baseline rates of SDB and abnormalities in sleep architecture exist in this population correlating with neuropsychological impairment. The role of HIV immuno-virologic or lifestyle factors as contributing etiologies should be explored. OSA may be an under-recognized etiology for cognitive dysfunction during chronic HIV.

Resting-state connectivity and spontaneous activity of ventromedial prefrontal cortex predict depressive symptomology and peripheral inflammation in HIV.

Depression and chronic inflammation are common in persons infected with the human immunodeficiency virus (HIV+). Although depression and response to inflammatory challenge are shown to reflect activity in common neural networks, little is known regarding sub-clinical presentation in persons chronically infected with HIV. The relationship of resting-state functional connectivity (rsFC) between the subgenual anterior cingulate cortex (sgACC) and bilateral amygdala to Beck Depression Inventory-1 (BDI) scores were compared within a group of 23 HIV+ and 23 HIV-negative comparison adults. An interaction was found wherein lower rsFC between the sgACC and both right and left amygdala was associated with higher BDI scores in HIV+ individuals. Total BDI scores and plasma levels of IL-6, IL-8, TNF-α, and IL-10 made available from 10 of the HIV+ patients were regressed upon an index of spontaneous whole-brain activity at rest; i.e., the amplitude of low-frequency fluctuations (ALFFs). Elevated levels of depression and IL-6 were associated with increased ALFF in a cluster of voxels on the medial portion of the ventral surface of the frontal lobe (Brodmann Area 11). Within this sample of HIV+ individuals lower rsFC of the sgACC with subcortical limbic regions predicts greater burden of depressive symptomology whereas elevated activity in the adjacent BA 11 may reflect sickness, indexed by elevated IL-6, and associated depressive behaviors.

Improved Cognitive Performance and Reduced Monocyte Activation in Virally Suppressed Chronic HIV After Dual CCR2 and CCR5 Antagonism.

OBJECTIVE: To evaluate changes in neuropsychological (NP) performance and in plasma and cell surface markers of peripheral monocyte activation/migration after treatment with cenicriviroc (CVC), a dual C-C chemokine receptor type 2 (CCR2) and type 5 (CCR5) antagonist, in treatment-experienced, HIV-infected individuals. SETTING: Single-arm, 24-week, open-label clinical trial. METHODS: HIV-infected individuals on antiretroviral therapy ≥1 year with plasma HIV RNA ≤50 copies per milliliter and below-normal cognitive performance [defined as age-, sex-, and education-adjusted NP performance (NPZ) <-0.5 in a single cognitive domain or in global performance] were enrolled. Changes over 24 weeks were assessed for global and domain-specific NPZ scores, plasma markers of monocyte/macrophage activation [neopterin, soluble (s)CD14, and sCD163] quantified by ELISA, and CCR2 and CCR5 expression on monocytes, and T cells measured by flow cytometry. RESULTS: Seventeen of 20 enrolled participants completed the study. Improvements over 24 weeks were observed in global NPZ [median change (Δ) = 0.24; P = 0.008], and in cognitive domains of attention (Δ0.23; P = 0.011) and working memory (Δ0.44; P = 0.017). Plasma levels of sCD163, sCD14 and neopterin decreased significantly (P's < 0.01). CCR2 and CCR5 monocyte expression remained unchanged; however, CCR5 levels on CD4 and CD8 T cells and CCR2 expression on CD4 T cells increased (P's < 0.01). CONCLUSIONS: CVC given over 24 weeks was associated with improved NP test performance and decreased plasma markers of monocyte immune activation in virally suppressed, HIV-infected participants. These data potentially link changes in monocyte activation to cognitive performance. Further study of CVC for HIV cognitive impairment in a randomized controlled study is warranted.

Differential Processing for Actively Ignored Pictures and Words.

Previous work suggests that, when attended, pictures may be processed more readily than words. The current study extends this research to assess potential differences in processing between these stimulus types when they are actively ignored. In a dual-task paradigm, facilitated recognition for previously ignored words was found provided that they appeared frequently with an attended target. When adapting the same paradigm here, previously unattended pictures were recognized at high rates regardless of how they were paired with items during the primary task, whereas unattended words were later recognized at higher rates only if they had previously been aligned with primary task targets. Implicit learning effects obtained by aligning unattended items with attended task-targets may apply only to conceptually abstract stimulus types, such as words. Pictures, on the other hand, may maintain direct access to semantic information, and are therefore processed more readily than words, even when being actively ignored.