Relationship between reward-related evoked potentials and real-world motivation in older people living with human immunodeficiency virus.

Apathy, a clinical disorder characterized by low motivation, is prevalent in people living with Human Immunodeficiency Virus (HIV). It affects mental and physical health-related quality-of-life, medication adherence, and is associated with cognitive decline. However, the causes of apathy and the underlying brain mechanisms in HIV are unknown. Brain responses to reward may be relevant to understanding apathy and might serve as biomarkers for diagnosis or treatment response. Electroencephalogram (EEG) responses to gain and loss feedback in simple guessing tasks have been related to apathy in neurodegenerative conditions and healthy individuals. The primary aim of this study is to contribute evidence regarding the relationship between two EEG correlates of reward processing, the Reward Positivity, and the Feedback-P300, and real-world motivated behavior indicated by self-reported hours engaged in goal-directed leisure activities per week, in older individuals with well-controlled HIV infection. High-density EEG was collected from 75 participants while they performed a guessing task with gain or loss feedback. We found that a later component of reward processing, the Feedback-P300, was related to real-world engagement, while the earlier Reward Positivity was not. The Feedback-P300 measured with EEG holds promise as a biomarker for motivated behavior in older people living with HIV. These findings lay the groundwork for a better understanding of the neurobiology of apathy in this condition.

Multimodal neuroimaging markers of variation in cognitive ability in older HIV+ men.

OBJECTIVE: This study used converging methods to examine the neural substrates of cognitive ability in middle-aged and older men with well-controlled HIV infection. METHODS: Seventy-six HIV+ men on antiretroviral treatment completed an auditory oddball task and an inhibitory control (Simon) task while time-locked high-density EEG was acquired; 66 had usable EEG data from one or both tasks; structural MRI was available for 43. We investigated relationships between task-evoked EEG responses, cognitive ability and immunocompromise. We also explored the structural correlates of these EEG markers in the sub-sample with complete EEG and MRI data (N = 27). RESULTS: EEG activity was associated with cognitive ability at later (P300) but not earlier stages of both tasks. Only the oddball task P300 was reliably associated with HIV severity (nadir CD4). Source localization confirmed that the tasks engaged partially distinct circuits. Thalamus volume correlated with oddball task P300 amplitude, while globus pallidus volume was related to the P300 in both tasks. INTERPRETATION: This is the first study to use task-evoked EEG to identify neural correlates of individual differences in cognition in men living with well-controlled HIV infection, and to explore the structural basis of the EEG markers. We found that EEG responses evoked by the oddball task are more reliably related to cognitive performance than those evoked by the Simon task. We also provide preliminary evidence for a subcortical contribution to the effects of HIV infection severity on P300 amplitudes. These results suggest brain mechanisms and candidate biomarkers for individual differences in cognition in HIV.

Does effort-cost decision-making relate to real-world motivation in people living with HIV?

INTRODUCTION: Low motivation is frequent in older people with HIV, yet poorly understood. Effort-cost decision-making (ECDM) tasks inspired by behavioral economics have shown promise as indicators of motivation or apathy. These tasks assess the willingness to exert effort to earn a monetary reward, providing an estimate of the subjective "cost" of effort for each participant. Here we sought evidence for a relationship between ECDM task performance and self-reported motivation in a cross-sectional study involving 80 middle-aged and older people with well-controlled HIV infection, a chronic health condition with a high burden of mental and cognitive health challenges. METHODS: Participants attending a regular follow-up visit for a Canadian longitudinal study of brain health in HIV completed a computerized ECDM task and a self-report measure of motivation. Other brain health measures were available, collected for the parent study (cognition, depression, anxiety, and vitality, as well as self-reported time spent on real-world leisure activities). RESULTS: Contrary to our hypothesis, we found no relationship between ECDM performance and self-reported motivation. However, those willing to accept higher effort in the ECDM task also reported more time engaged in real-world activities. This association had a small-to-moderate effect size. CONCLUSIONS: The behavioral economics construct of subjective cost of effort, measured with a laboratory ECDM task, does not relate to motivation in people living with chronic HIV. However, the task shows some relationship with real-world goal-directed behavior, suggesting this construct has potential clinical relevance. More work is needed to understand how the subjective cost of effort plays out in clinical symptoms and everyday activities.

The electrophysiology of neuroHIV: A systematic review of EEG and MEG studies in people with HIV infection since the advent of highly-active antiretroviral therapy.

OBJECTIVE: The Human Immunodeficiency Virus (HIV) has an impact on the brain, even when the infection is well-controlled with modern highly-active antiretroviral therapy (HAART). While dementia is rare in those on HAART, milder cognitive impairment is common. The causes, patterns, and evolution of brain dysfunction in people living with HIV remain uncertain. We evaluate whether electrophysiological methods provide informative measures of brain dysfunction in this population. METHODS: A systematic literature search identified studies that used EEG or MEG to evaluate persons living with HIV published between 1996 (when HAART became available) and 2016. RESULTS: Twenty-eight studies were identified. Most involved small samples, and all but four were cross-sectional. Reduced amplitude of Event Related Potentials and decreased power in the alpha band at rest were the most frequent differences between people with and without HIV infection. Of the 16 studies that also assessed cognitive ability, 13 found a significant relationship between cognition and electrophysiological changes in the HIV+ groups. Five of those studies also reported a significant relationship with current immunosuppression, suggesting a direct effect of HIV on the brain. There were few longitudinal studies; whether these electrophysiological changes progress over time, or respond to treatment, remains unclear. CONCLUSIONS: EEG and MEG can provide useful information about brain dysfunction in people with HIV infection, but more consistent assessments of both cognition and EEG patterns, as well as longitudinal studies with larger, better characterized samples are needed. SIGNIFICANCE: This is the first systematic review of electrophysiological findings in HIV since the availability of HAART. EEG and MEG measures are sensitive to brain dysfunction in this population, and could complement other approaches in improving the assessment, understanding and treatment of neurocognitive disorders in HIV.

Regionally Specific Brain Volumetric and Cortical Thickness Changes in HIV-Infected Patients in the HAART Era.

BACKGROUND: Cognitive impairment still occurs in a substantial subset of HIV-infected patients, despite effective viral suppression with highly active antiretroviral therapy (HAART). Structural brain changes may provide clues about the underlying pathophysiology. This study provides a detailed spatial characterization of the pattern and extent of brain volume changes associated with HIV and relates these brain measures to cognitive ability and clinical variables. METHODS: Multiple novel neuroimaging techniques (deformation-based morphometry, voxel-based morphometry, and cortical modeling) were used to assess regional brain volumes in 125 HIV-infected patients and 62 HIV-uninfected individuals. Ninety percent of the HIV-infected patients were on stable HAART with most of them (75%) having plasma viral suppression. Brain volumetrics and cortical thickness estimates were compared between the HIV-infected and uninfected groups, and the relationships between these measures of brain volume and indices of current and past infection severity, central nervous system penetration of HAART, and cognitive performance were assessed. RESULTS: Regionally specific patterns of reduced thalamic and brainstem volumes and reduced cortical thickness in the orbitofrontal cortex, cingulate gyrus, primary motor and sensory cortex, temporal, and frontal lobes were seen in HIV-infected patients compared to HIV-uninfected participants. Observed white matter loss and subcortical atrophy were associated with lower nadir CD4 cell counts, while reduction in cortical thickness was related to worse cognitive performance. CONCLUSIONS: Our findings suggest that distinct mechanisms may underlie cortical and subcortical injury in people with HIV and argues for the potential importance of early initiation of HAART to protect long-term brain health.