Taylor P. Kuhn

Combined effects of HIV and marijuana use on neurocognitive functioning and immune status

ABSTRACT The current study examined the independent and combined effects of HIV and marijuana (MJ) use (no use, light use, and moderate-to-heavy use) on neurocognitive functioning among a convenience sample of HIV-positive (HIV+) and HIV-negative (HIV–) individuals recruited from HIV community care clinics and advertisements in the Greater Los Angeles area. MJ users consisted of individuals who reported regular use of MJ for at least 12 months, with last reported use within the past month. Participants included 89 HIV+ (n = 55) and HIV– (n = 34) individuals who were grouped into non-users, light users, and moderate-to-heavy users based on self-reported MJ use. Participants were administered a brief cognitive test battery and underwent laboratory testing for CD4 count and viral load. HIV+ individuals demonstrated lower performance on neurocognitive testing than controls, and moderate-to-heavy MJ users performed more poorly on neurocognitive testing than light users or non-users. Moderate-to-heavy HIV+ users performed significantly lower on learning/memory than HIV– moderate-to-heavy users (MD = −8.34; 95% CI: −16.11 to −0.56) as well as all other comparison groups. In the domain of verbal fluency, HIV+ light users outperformed HIV– light users (MD = 7.28; 95% CI: 1.62–12.39), but no HIV group differences were observed at other MJ use levels. HIV+ MJ users demonstrated lower viral load (MD = −0.58; 95% CI: −1.30 to 0.14) and higher CD4 count than non-users (MD = 137.67; 95% CI: 9.48–265.85). The current study findings extend the literature by demonstrating the complex relationship between HIV status and MJ use on neurocognitive and clinical outcomes.

The effects of HIV and aging on subcortical shape alterations: A 3D morphometric study

Standard volumetric neuroimaging studies have demonstrated preferential atrophy of subcortical structures among individuals with HIV. However, to our knowledge, no study has investigated subcortical shape alterations secondary to HIV and whether advancing age impacts that relationship. This study employed 3D morphometry to examine the independent and interactive effects of HIV and age on shape differences in nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus in 81 participants ranging in age from 24 to 76 including 59 HIV+ individuals and 22 HIV‐seronegative controls. T1‐weighted MRI underwent a preprocessing pipeline followed by automated subcortical segmentation. Parametric statistical analyses were used to determine independent effects of HIV infection and age on volume and shape in each region of interest (ROI) and the interaction between age and HIV serostatus in predicting volume/shape in each ROI. Significant main effects for HIV were found in the shape of right caudate and nucleus accumbens, left pallidum, and hippocampus. Age was associated with differences in shape in left pallidum, right nucleus accumbens and putamen, and bilateral caudate, hippocampus, and thalamus. Of greatest interest, an age × HIV interaction effect was found in the shape of bilateral nucleus accumbens, amygdala, caudate, and thalamus as well as right pallidum and putamen such that increasing age in HIV participants was associated with greater shape alterations. Traditional volumemetric analyses revealed main effects for both HIV and age but no age × HIV interaction. These findings may suggest that age and HIV infection conferred additional deleterious effects on subcortical shape abnormalities beyond the independent effects of these factors. Hum Brain Mapp 38:1025–1037, 2017.

Marijuana effects on changes in brain structure and cognitive function among HIV+ and HIV- adults.

BACKGROUND The current study examined the independent and interactive effects of HIV and marijuana (MJ) use on brain structure and cognitive function among a sample of HIV-positive (HIV+) and HIV-negative (HIV-) individuals. METHODS Participants (HIV+, n=48; HIV-, n=29) individuals underwent cognitive testing, questionnaires about substance use, and brain MRI. The HIV+ group was clinically stable based upon current plasma CD4 count, 50% had undetectable viral load (i.e.,<20 copies/mL), and all were on a stable regimen of cART. RESULTS For HIV+ and HIV- participants, higher levels of MJ use were associated with smaller volumes in the entorhinal cortex and fusiform gyrus. HIV status (but not MJ use) was associated with cingulate thickness, such that HIV+ participants evidenced smaller thickness of the cingulate, as compared to HIV- controls. Regarding neurocognitive functioning, there was a HIV*MJ interactive effect on global cognition, such that when the amount of MJ use was less than 1.43g per week, the HIV- group displayed significantly better neurocognitive performance than the HIV+ group (t=3.14, p=0.002). However, when MJ use reached 1.43g per week, there were no significant HIV group differences in global cognitive performance (t=1.39, p=0.168). CONCLUSIONS Our results show independent and interactive effects of HIV and MJ on brain structure and cognition. However, our results do not support that HIV+ MJ users are at greater risk for adverse brain or cognitive outcomes compared to HIV- MJ users.

Mild Cognitive Impairment is Associated With White Matter Integrity Changes in Late-Myelinating Regions Within the Corpus Callosum

Degenerative brain changes in Alzheimer’s disease may occur in reverse order of normal brain development based on the retrogenesis model. This study tested whether evidence of reverse myelination was observed in mild cognitive impairment (MCI) using a data-driven analytic approach based on life span developmental data. Whole-brain high-resolution diffusion tensor imaging scans were obtained for 31 patients with MCI and 79 demographically matched healthy older adults. Comparisons across corpus callosum (CC) regions of interest (ROIs) showed decreased fractional anisotropy (FA) in the body but not in the genu or splenium; early-, middle-, and late-myelinating ROIs restricted to the CC revealed decreased FA in late- but not early- or middle-myelinating ROIs. Voxelwise group differences revealed areas of lower FA in MCI, but whole-brain differences were equally distributed across early-, middle-, and late-myelinating regions. Overall, results within the CC support the retrogenesis model, although caution is needed when generalizing these results beyond the CC.

Test-retest reliability of high angular resolution diffusion imaging acquisition within medial temporal lobe connections assessed via tract based spatial statistics, probabilistic tractography and a novel graph theory metric

This study examined the reliability of high angular resolution diffusion tensor imaging (HARDI) data collected on a single individual across several sessions using the same scanner. HARDI data was acquired for one healthy adult male at the same time of day on ten separate days across a one-month period. Environmental factors (e.g. temperature) were controlled across scanning sessions. Tract Based Spatial Statistics (TBSS) was used to assess session-to-session variability in measures of diffusion, fractional anisotropy (FA) and mean diffusivity (MD). To address reliability within specific structures of the medial temporal lobe (MTL; the focus of an ongoing investigation), probabilistic tractography segmented the Entorhinal cortex (ERc) based on connections with Hippocampus (HC), Perirhinal (PRc) and Parahippocampal (PHc) cortices. Streamline tractography generated edge weight (EW) metrics for the aforementioned ERc connections and, as comparison regions, connections between left and right rostral and caudal anterior cingulate cortex (ACC). Coefficients of variation (CoV) were derived for the surface area and volumes of these ERc connectivity-defined regions (CDR) and for EW across all ten scans, expecting that scan-to-scan reliability would yield low CoVs. TBSS revealed no significant variation in FA or MD across scanning sessions. Probabilistic tractography successfully reproduced histologically-verified adjacent medial temporal lobe circuits. Tractography-derived metrics displayed larger ranges of scanner-to-scanner variability. Connections involving HC displayed greater variability than metrics of connection between other investigated regions. By confirming the test retest reliability of HARDI data acquisition, support for the validity of significant results derived from diffusion data can be obtained.

Differential relationships between social adversity and depressive symptoms by HIV status and racial/ethnic identity.

Objective: Historically marginalized groups are likely to be exposed to social adversity, which predicts important mental health outcomes (e.g., depression). Despite the well-established relationship between adversity and poor health, few studies have examined how adversity differentially predicts mental health among people living with multiple, co-occurring marginalized identities or statuses. The current study fills this gap by examining whether relationships between social adversity and depressive symptoms differed between those living with or without a stigmatized disease (i.e., HIV) and/or marginalized racial/ethnic identity (i.e., African American). Method: A community sample of men and women (N = 149) completed questionnaires assessing demographics and depressive symptoms. Additionally, a composite index of social adversity was derived from measures of perceived discrimination, socioeconomic status, financial restriction to receiving medical care, and perceived neighborhood characteristics. Multiple regression was used to test whether relationships between adversity and depressive symptoms differed as a function of HIV status and racial/ethnic identity. Results: A significant 3-way interaction between social adversity, HIV status, and racial/ethnic identity indicated that there was a direct relationship between adversity and depressive symptoms for HIV-positive (HIV+) African Americans but not for HIV-negative (HIV–) African Americans, HIV+ Caucasians, or HIV– Caucasians. Further, HIV+ African Americans evidenced a significantly greater relationship between adversity and depressive symptoms compared with HIV– African Americans, but not compared with other groups. Conclusions: The findings suggest that HIV+ African Americans may be at risk for higher depressive symptoms amid adversity, highlighting the importance of evaluating intersectional identities/statuses in the context of mental health.

An augmented aging process in brain white matter in HIV

HIV infection and aging are both associated with neurodegeneration. However, whether the aging process alone or other factors associated with advanced age account for the progression of neurodegeneration in the aging HIV‐positive (HIV+) population remains unclear. Methods: HIV+ (n = 70) and HIV‐negative (HIV−, n = 34) participants underwent diffusion tensor imaging (DTI) and metrics of microstructural properties were extracted from regions of interest (ROIs). A support vector regression model was trained on two independent datasets of healthy adults across the adult life‐span (n = 765, Cam‐CAN = 588; UiO = 177) to predict participant age from DTI metrics, and applied to the HIV dataset. Predicted brain age gap (BAG) was computed as the difference between predicted age and chronological age, and statistically compared between HIV groups. Regressions assessed the relationship between BAG and HIV severity/medical comorbidities. Finally, correlation analyses tested for associations between BAG and cognitive performance. Results: BAG was significantly higher in the HIV+ group than the HIV− group F (1, 103) = 12.408, p = .001). HIV RNA viral load was significantly associated with BAG, particularly in older HIV+ individuals (R2 = 0.29, F(7, 70) = 2.66, p = .021). Further, BAG was negatively correlated with domain‐level cognitive function (learning: r = −0.26, p = .008; memory: r = −0.21, p = .034). Conclusions: HIV infection is associated with augmented white matter aging, and greater brain aging is associated with worse cognitive performance in multiple domains.

Longitudinal Intra-Individual Variability in Neuropsychological Performance Relates to White Matter Changes in HIV.

Objectives: Recent studies suggest that intraindividual variability (IIV) of neuropsychological performance may be sensitive to HIV-associated neurologic compromise. IIV may be particularly dependent upon the integrity of frontal-subcortical systems, and therefore may be a meaningful phenotype in HIV. We examined the relationship between change in IIV and white matter integrity among HIV seropositive (HIV+) and HIV seronegative (HIV−) individuals. Method: The sample consisted of 38 HIV+ participants and 26 HIV− control participants who underwent neuroimaging and a neuropsychological evaluation at baseline and at 2-year follow-up evaluation. Results: Among HIV+ participants, increases in IIV (greater dispersion) were related to lower fractional anisotropy (FA) values in the anterior thalamic radiations (ATR) and the superior longitudinal fasciculus (SLF). Changes in mean-level global cognitive functioning were not significantly related to white matter integrity. Additionally, there was a significant Group × IIV interaction effect in the SLF demonstrating that the relationship between IIV and white matter integrity was specific to HIV. Conclusions: Overall, findings suggest that IIV may be more sensitive, relative to mean-level global cognitive functioning, in the detection of neurologic compromise among HIV+ individuals.

Improving language mapping in clinical fMRI through assessment of grammar

Introduction Brain surgery in the language dominant hemisphere remains challenging due to unintended post-surgical language deficits, despite using pre-surgical functional magnetic resonance (fMRI) and intraoperative cortical stimulation. Moreover, patients are often recommended not to undergo surgery if the accompanying risk to language appears to be too high. While standard fMRI language mapping protocols may have relatively good predictive value at the group level, they remain sub-optimal on an individual level. The standard tests used typically assess lexico-semantic aspects of language, and they do not accurately reflect the complexity of language either in comprehension or production at the sentence level. Among patients who had left hemisphere language dominance we assessed which tests are best at activating language areas in the brain. Method We compared grammar tests (items testing word order in actives and passives, wh-subject and object questions, relativized subject and object clauses and past tense marking) with standard tests (object naming, auditory and visual responsive naming), using pre-operative fMRI. Twenty-five surgical candidates (13 females) participated in this study. Sixteen patients presented with a brain tumor, and nine with epilepsy. All participants underwent two pre-operative fMRI protocols: one including CYCLE-N grammar tests (items testing word order in actives and passives, wh-subject and object questions, relativized subject and object clauses and past tense marking); and a second one with standard fMRI tests (object naming, auditory and visual responsive naming). fMRI activations during performance in both protocols were compared at the group level, as well as in individual candidates. Results The grammar tests generated more volume of activation in the left hemisphere (left/right angular gyrus, right anterior/posterior superior temporal gyrus) and identified additional language regions not shown by the standard tests (e.g., left anterior/posterior supramarginal gyrus). The standard tests produced more activation in left BA 47. Ten participants had more robust activations in the left hemisphere in the grammar tests and two in the standard tests. The grammar tests also elicited substantial activations in the right hemisphere and thus turned out to be superior at identifying both right and left hemisphere contribution to language processing. Conclusion The grammar tests may be an important addition to the standard pre-operative fMRI testing.

Medication adherence in HIV-positive African Americans: The roles of age, health beliefs, and sensation seeking

Abstract We examined how two critical constructs, health beliefs and sensation seeking, influence combination antiretroviral therapy adherence in HIV + African Americans, and whether these factors mediate the association between age and adherence. Two hundred and eighty-six HIV + African Americans participated in this observational study. Path analyses revealed that higher levels of a specific health belief, perceived utility of treatment, and lower levels of a sensation seeking component, Thrill and Adventure Seeking, directly predicted optimal adherence. The influence of age on adherence was partially mediated by lower Thrill and Adventure Seeking levels. Depression predicted adherence via perceived utility of treatment and Thrill and Adventure Seeking, whereas current substance abuse and dependence did via Thrill and Adventure Seeking. Poorer neurocognitive function had a direct, adverse effect on adherence. Our findings suggest that supporting the development of more positive perceptions about HIV treatment utility may help increase medication adherence among African Americans. This may be particularly relevant for those with higher levels of depression symptoms, which were directly associated with negative perceptions about treatment. Additionally, clinicians can assess sensation seeking tendencies to help identify HIV + African Americans at risk for suboptimal adherence. Compensatory strategies for medication management may help improve adherence among HIV + individuals with poorer neurocognitive function.