Uraina S. Clark

Effects of nadir CD4 count and duration of human immunodeficiency virus infection on brain volumes in the highly active antiretroviral therapy era

Cerebral atrophy is a well-described, but poorly understood complication of human immunodeficiency virus (HIV) infection. Despite reduced prevalence of HIV-associated dementia in the highly active antiretroviral therapy (HAART) era, HIV continues to affect the brains of patients with chronic infection. In this study we examine patterns of brain volume loss in HIV-infected patients on HAART, and demographic and clinical factors contributing to brain volume loss. We hypothesized that nadir CD4+ lymphocyte count, duration of HIV infection, and age would be associated with reduced cortical volumes. Volumes of cortical and subcortical regions in 69 HIV-infected neuroasymptomatic (NA) individuals and 13 with at least mild acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) were measured using voxel-based morphometry. Demographic and clinical factors (age, plasma HIV RNA level, current and nadir CD4 counts, duration of infection, central nervous system [CNS] penetration of antiretroviral regimen) along with their interactions were entered into a regression model selection algorithm to determine the final models that best described regional brain volumes. Relative to NA, individuals with ADC exhibited decreased total gray matter and parietal cortex volumes and increased total ventricular volumes. Final regression models showed overall cerebral volume, including gray and white matter volume and volumes of the parietal, temporal, and frontal lobes and the hippocampus, were most strongly associated with disease history factors (nadir CD4 and duration of infection). In contrast, basal ganglia volumes were related most strongly to current disease factors, most notably plasma HIV RNA. These findings indicate that individuals with a history of chronic HIV infection with previous episodes of severely impaired immune function, as reflected by reduced nadir CD4+ lymphocyte count, may be at greatest risk for cerebral atrophy. The pattern of HIV-associated brain loss may be changing from a subcortical to a cortical disease among patients who are largely asymptomatic on HAART.

Specific impairments in the recognition of emotional facial expressions in Parkinson's disease.

Studies investigating the ability to recognize emotional facial expressions in non-demented individuals with Parkinsons disease (PD) have yielded equivocal findings. A possible reason for this variability may lie in the confounding of emotion recognition with cognitive task requirements, a confound arising from the lack of a control condition using non-emotional stimuli. The present study examined emotional facial expression recognition abilities in 20 non-demented patients with PD and 23 control participants relative to their performance on a non-emotional landscape categorization test with comparable task requirements. We found that PD participants were normal on the control task but exhibited selective impairments in the recognition of facial emotion, specifically for anger (driven by those with right hemisphere pathology) and surprise (driven by those with left hemisphere pathology), even when controlling for depression level. Male but not female PD participants further displayed specific deficits in the recognition of fearful expressions. We suggest that the neural substrates that may subserve these impairments include the ventral striatum, amygdala, and prefrontal cortices. Finally, we observed that in PD participants, deficiencies in facial emotion recognition correlated with higher levels of interpersonal distress, which calls attention to the significant psychosocial impact that facial emotion recognition impairments may have on individuals with PD.

Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes.

Cerebral metabolite disturbances occur among human immunodeficiency virus (HIV)-infected people, and are thought to reflect neuropathology, including proinflammatory processes, and neuronal loss. HIV-associated cortical atrophy continues to occur, though its basis is not well understood, and the relationship of cerebral metabolic disturbance to structural brain abnormalities in HIV has not been well delineated. We hypothesized that metabolite disturbances would be associated with reduced cortical and subcortical volumes. Cerebral volumes were measured in 67 HIV-infected people, including 10 people with mild dementia (acquired immunodeficiency syndrome [AIDS] dimentia complex [ADC] stage >1) via automated magnetic resonance imaging (MRI) segmentation. Magnetic resonance spectroscopy (MRS) was used to measure levels of cerebral metabolites N-acetylaspartate (NAA), myo-inositol (MI), choline-containing compounds (Cho), glutamate/glutamine (Glx), and creatine (Cr) from three brain regions (frontal gray matter, frontal white matter, basal ganglia). Analyses were conducted to examine the associations between MRS and cerebral volumetric measures using both absolute and relative metabolite concentrations. NAA in the mid-frontal gray matter was most consistently associated with cortical (global, frontal, and parietal), ventricular, and caudate volumes based on analysis of absolute metabolite levels, whereas temporal lobe volume was associated with basal ganglia NAA and Glx, and Cho concentrations in the frontal cortex and basal ganglia. Hippocampal volume was associated with frontal white matter NAA, whereas thalamic volume was associated with both frontal white matter NAA and basal ganglia Glx. Analyses of relative metabolite concentrations (referenced to Cr) yielded weaker effects, although more metabolites were retained as significant predictors in the models than the analysis of absolute concentrations. These findings demonstrate that reduced cortical and subcortical volumes, which have been previously found to be linked to HIV status and history, are also strongly associated with the degree of cerebral metabolite disturbance observed via MRS. Reduced cortical and hippocampal volumes were most strongly associated with decreased NAA, though reduced Glx also tended to be associated with reduced cortical and subcortical volumes (caudate and thalamus) as well, suggesting both neuronal and glial disturbances. Interestingly, metabolite-volumetric relationships were not limited to the cortical region from which MRS was measured, possibly reflecting shared pathophysiological processes. The relationships between Cho and volumetric measures suggest a complicated relationship possibly related to the effects of inflammatory processes on brain volume. The findings demonstrate the relationship between MRI-derived measures of cerebral metabolite disturbances and structural brain integrity, which has implication in understanding HIV-associated neuropathological mechanisms.

Alcoholism and Judgments of Affective Stimuli

This study sought to differentiate alcoholism-related changes in judgments of emotional stimuli from those of other populations in which such changes have been documented. Two sets of visual stimuli, one containing words and the other containing drawings of faces (representing a range of emotional content), were presented to abstinent alcoholic adults with and without Korsakoffs syndrome, as well as to a healthy control group and four groups of patients with other neurobehavioral disorders: Parkinsons disease, schizophrenia, depression, and posttraumatic stress disorder. Participants rated the stimuli according to emotional valence and intensity of emotion. Results implicated bi-hemispheric frontal and subcortical involvement in the abnormalities of emotion identification associated with alcoholism, and they also support the notion of age-related vulnerabilities in conjunction with alcoholism.

Visual scanning patterns and executive function in relation to facial emotion recognition in aging

ABSTRACT Objective: The ability to perceive facial emotion varies with age. Relative to younger adults (YA), older adults (OA) are less accurate at identifying fear, anger, and sadness, and more accurate at identifying disgust. Because different emotions are conveyed by different parts of the face, changes in visual scanning patterns may account for age-related variability. We investigated the relation between scanning patterns and recognition of facial emotions. Additionally, as frontal-lobe changes with age may affect scanning patterns and emotion recognition, we examined correlations between scanning parameters and performance on executive function tests. Methods: We recorded eye movements from 16 OA (mean age 68.9) and 16 YA (mean age 19.2) while they categorized facial expressions and non-face control images (landscapes), and administered standard tests of executive function. Results: OA were less accurate than YA at identifying fear (p < .05, r = .44) and more accurate at identifying disgust (p < .05, r = .39). OA fixated less than YA on the top half of the face for disgust, fearful, happy, neutral, and sad faces (p values < .05, r values ≥ .38), whereas there was no group difference for landscapes. For OA, executive function was correlated with recognition of sad expressions and with scanning patterns for fearful, sad, and surprised expressions. Conclusion: We report significant age-related differences in visual scanning that are specific to faces. The observed relation between scanning patterns and executive function supports the hypothesis that frontal-lobe changes with age may underlie some changes in emotion recognition.

The adverse effects of reduced cerebral perfusion on cognition and brain structure in older adults with cardiovascular disease

It is well established that aging and vascular processes interact to disrupt cerebral hemodynamics in older adults. However, the independent effects of cerebral perfusion on neurocognitive function among older adults remain poorly understood. We examined the associations among cerebral perfusion, cognitive function, and brain structure in older adults with varying degrees of vascular disease using perfusion magnetic resonance imaging (MRI) arterial spin labeling (ASL).

The impact of hypertension on cerebral perfusion and cortical thickness in older adults.

Hypertension may increase risk for dementia possibly because of its association with decreased cortical thickness. Disturbed cerebral autoregulation is one plausible mechanism by which hypertension impacts the cerebral structure, but the associations among hypertension, brain perfusion, and cortical thickness are poorly understood. The current sample consisted of 58 older adults with varying levels of vascular disease. Diagnostic history of hypertension and antihypertensive medication status was ascertained through self-report, and when available, confirmed by medical record review. All participants underwent arterial spin labeling and T1-weighted magnetic resonance imaging to quantify total and regional cortical perfusion and thickness. Analysis of covariance adjusting for medical variables showed that participants with hypertension exhibited reduced temporal and occipital brain perfusion and total and regional cortical thickness relative to those without hypertension. The effects of hypertension on total brain perfusion remained unchanged even after adjustment for age, although no such pattern emerged for cortical thickness. Decreased total brain perfusion predicted reduced thickness of the total brain and of the frontal, temporal, and parietal lobe cortices. Antihypertensive treatment was not associated with total cerebral perfusion or cortical thickness. This study provides initial evidence for the adverse effects of a diagnostic history of hypertension on brain hypoperfusion and reduced cortical thickness. Longitudinal studies are needed to investigate the role of hypertension and its interaction with other contributing factors (e.g., age) in the manifestation of cerebral hypoperfusion and reduced cortical thickness.

Early life stress is associated with greater default network deactivation during working memory in healthy controls: a preliminary report

Early life stress (ELS) is a common risk factor for psychopathology, but there are few functional neuroimaging studies investigating its effects. In this preliminary study, we investigated the correlates of ELS exposure on the default network (DN) through measurements of task-associated DN deactivation. Data were analyzed from 19 subjects without psychiatric illness (10 with ELS). Subjects performed the working memory (WM) N-back task (including a 2-back WM and 0-back control condition) while undergoing functional MRI. We compared brain responses in the two groups across 5 bilateral DN regions using an a priori region of interest (ROI) analysis. The ELS group demonstrated significantly greater DN deactivation, observed in the right posterior cingulate cortex PCC, bilateral medial prefrontal cortex, left middle/superior frontal gyrus and right middle temporal region. These preliminary results indicate subjects with ELS demonstrate greater DN deactivations to WM challenges compared to non-ELS controls, potentially reflecting a biomarker of long-term effects of ELS exposure.

Effects of HIV and early life stress on amygdala morphometry and neurocognitive function.

Both HIV infection and high levels of early life stress (ELS) have been related to abnormalities in frontal-subcortical structures, yet the combined effects of HIV and ELS on brain structure and function have not been previously investigated. In this study we assessed 49 non-demented HIV-seropositive (HIV+) and 47 age-matched HIV-seronegative healthy control (HC) adults. Levels of ELS exposure were quantified and used to define four HIV-ELS groups: HC Low-ELS (N = 20); HC High-ELS (N = 27); HIV+ Low-ELS (N = 24); HIV+ High-ELS (N = 25). An automated segmentation tool measured volumes of brain structures known to show HIV-related or ELS-related effects; a brief neurocognitive battery was administered. A significant HIV-ELS interaction was observed for amygdala volumes, which was driven by enlargements in HIV+ High-ELS participants. The HIV+ High-ELS group also demonstrated significant reductions in psychomotor/processing speed compared with HC Low-ELS. Regression analyses in the HIV+ group revealed that amygdala enlargements were associated with higher ELS, lower nadir CD4 counts, and reduced psychomotor/processing speed. Our results suggest that HIV infection and high ELS interact to increase amygdala volume, which is associated with neurocognitive dysfunction in HIV+ patients. These findings highlight the lasting neuropathological influence of ELS and suggest that high ELS may be a significant risk factor for neurocognitive impairment in HIV-infected individuals.

Facial emotion recognition impairments in individuals with HIV.

Characterized by frontostriatal dysfunction, human immunodeficiency virus (HIV) is associated with cognitive and psychiatric abnormalities. Several studies have noted impaired facial emotion recognition abilities in patient populations that demonstrate frontostriatal dysfunction; however, facial emotion recognition abilities have not been systematically examined in HIV patients. The current study investigated facial emotion recognition in 50 nondemented HIV-seropositive adults and 50 control participants relative to their performance on a nonemotional landscape categorization control task. We examined the relation of HIV-disease factors (nadir and current CD4 levels) to emotion recognition abilities and assessed the psychosocial impact of emotion recognition abnormalities. Compared to control participants, HIV patients performed normally on the control task but demonstrated significant impairments in facial emotion recognition, specifically for fear. HIV patients reported greater psychosocial impairments, which correlated with increased emotion recognition difficulties. Lower current CD4 counts were associated with poorer anger recognition. In summary, our results indicate that chronic HIV infection may contribute to emotion processing problems among HIV patients. We suggest that disruptions of frontostriatal structures and their connections with cortico-limbic networks may contribute to emotion recognition abnormalities in HIV. Our findings also highlight the significant psychosocial impact that emotion recognition abnormalities have on individuals with HIV.