Providing medication for opioid use disorder and HIV pre-exposure prophylaxis at syringe services programs via telemedicine: a pilot study.

BACKGROUND: People who inject drugs (PWID) are at high risk for opioid overdose and infectious diseases including HIV. We piloted PARTNER UP, a telemedicine-based program to provide PWID with medication for opioid use disorder (MOUD) with buprenorphine/naloxone (bup/nx) and oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine through two syringe services programs (SSP) in North Carolina. We present overall results from this project, including participant retention rates and self-reported medication adherence. METHODS: Study participants met with a provider for an initial in-person visit at the SSP, followed by weekly telemedicine visits in month 1 and then monthly until program end at month 6. Participants were asked to start both MOUD and PrEP at initiation but could choose to discontinue either at any point during the study. Demographics and health history including substance use, sexual behaviors, and prior use of MOUD/PrEP were collected at baseline. Follow-up surveys were conducted at 3- and 6-months to assess attitudes towards MOUD and PrEP, change in opioid use and sexual behaviors, and for self-reported medication adherence. Participant retention was measured by completion of visits; provider notes were used to assess whether the participant reported continuation of medication. RESULTS: Overall, 17 persons were enrolled and started on both bup/nx and PrEP; the majority self-identified as white and male. At 3 months, 13 (76%) remained on study; 10 (77%) reported continuing with both MOUD and PrEP, 2 (15%) with bup/nx only, and 1 (8%) with PrEP only. At 6 months, 12 (71%) remained on study; 8 (67%) reported taking both bup/nx and PrEP, and 4 (33%) bup/nx only. Among survey participants, opioid use and HIV risk behaviors decreased. Nearly all reported taking bup/nx daily; however, self-reported daily adherence to PrEP was lower and declined over time. The most common reason for not continuing PrEP was feeling not at risk for acquiring HIV. CONCLUSIONS: Our study results show that MOUD and PrEP can be successfully administered via telemedicine in SSPs. PrEP appears to be a lower priority for participants with decreased continuation and adherence. Low perception of HIV risk was a reason for not continuing PrEP, possibly mitigated by MOUD use. Future studies including helping identify PWID at highest need for PrEP are needed. TRIAL REGISTRATION: Providing Suboxone and PrEP Using Telemedicine, NCT04521920. Registered 18 August 2020. https://clinicaltrials.gov/study/NCT04521920?term=mehri%20mckellar&rank=2 .

Cocaine Use Prediction With Tensor-Based Machine Learning on Multimodal MRI Connectome Data.

This letter considers the use of machine learning algorithms for predicting cocaine use based on magnetic resonance imaging (MRI) connectomic data. The study used functional MRI (fMRI) and diffusion MRI (dMRI) data collected from 275 individuals, which was then parcellated into 246 regions of interest (ROIs) using the Brainnetome atlas. After data preprocessing, the data sets were transformed into tensor form. We developed a tensor-based unsupervised machine learning algorithm to reduce the size of the data tensor from 275 (individuals) × 2 (fMRI and dMRI) × 246 (ROIs) × 246 (ROIs) to 275 (individuals) × 2 (fMRI and dMRI) × 6 (clusters) × 6 (clusters). This was achieved by applying the high-order Lloyd algorithm to group the ROI data into six clusters. Features were extracted from the reduced tensor and combined with demographic features (age, gender, race, and HIV status). The resulting data set was used to train a Catboost model using subsampling and nested cross-validation techniques, which achieved a prediction accuracy of 0.857 for identifying cocaine users. The model was also compared with other models, and the feature importance of the model was presented. Overall, this study highlights the potential for using tensor-based machine learning algorithms to predict cocaine use based on MRI connectomic data and presents a promising approach for identifying individuals at risk of substance abuse.

Longitudinal changes in neurocognitive performance related to drug use intensity in a sample of persons with and without HIV who use illicit stimulants.

BACKGROUND: Illicit stimulant use remains a public health concern that has been associated with multiple adverse outcomes, including cognitive deficits. The effects of stimulant use on cognition may be particularly deleterious in persons with HIV. Stimulant use intensity may be an important factor in the magnitude of observed deficits over time. METHODS: We completed neurocognitive testing in a sample of people who use stimulants with (n = 84) and without HIV (n = 123) at baseline and up to 4 follow-up time points over approximately 1 year. Participants reported on substance use at each visit, including frequency of use and stimulant dependence. Mixed effects models examined the relationship between stimulant-related factors and neurocognitive function over time. RESULTS: Participants were mostly male (57%), African American (86%), and 47.41 years old on average. All participants actively used stimulants at enrollment and use remained prevalent throughout the follow-up period, with an average of ≥24 days of use in the past 90 days at all time points. Retention was excellent, with 86% completing all 4 follow-up assessments. Mixed effects models showed that stimulant dependence was associated with lower neurocognitive performance independent of HIV status (p = 0.002), whereas frequency of use had a greater negative impact on performance in participants with HIV compared to those without HIV (p = 0.045). CONCLUSIONS: Our key finding is that stimulant-related factors are associated with neurocognitive performance over time, but in complex ways. These findings have important implications for harm reduction approaches, particularly those that target cognitive function.

Cocaine use is associated with cerebral white matter hyperintensities in HIV disease.

BACKGROUND: White matter hyperintensities (WMH), a marker of cerebral small vessel disease and predictor of cognitive decline, are observed at higher rates in persons with HIV (PWH). The use of cocaine, a potent central nervous system stimulant, is disproportionately common in PWH and may contribute to WMH. METHODS: The sample included of 110 PWH on antiretroviral therapy. Fluid-attenuated inversion recovery (FLAIR) and T1-weighted anatomical MRI scans were collected, along with neuropsychological testing. FLAIR images were processed using the Lesion Segmentation Toolbox. A hierarchical regression model was run to investigate predictors of WMH burden [block 1: demographics; block 2: cerebrovascular disease (CVD) risk; block 3: lesion burden]. RESULTS: The sample was 20% female and 79% African American with a mean age of 45.37. All participants had persistent HIV viral suppression, and the median CD4+ T-cell count was 750. Nearly a third (29%) currently used cocaine regularly, with an average of 23.75 (SD = 20.95) days in the past 90. In the hierarchical linear regression model, cocaine use was a significant predictor of WMH burden (ß = .28). WMH burden was significantly correlated with poorer cognitive function (r = -0.27). Finally, higher WMH burden was significantly associated with increased serum concentrations of interferon-γ-inducible protein 10 (IP-10) but lower concentrations of myeloperoxidase (MPO); however, these markers did not differ by COC status. CONCLUSIONS: WMH burden is associated with poorer cognitive performance in PWH. Cocaine use and CVD risk independently contribute to WMH, and addressing these conditions as part of HIV care may mitigate brain injury underlying neurocognitive impairment.

The Individualized Prediction of Neurocognitive Function in People Living with HIV Based on Clinical and Multimodal Connectome Data.

Neurocognitive impairment continues to be common comorbidity for people living with HIV (PLWH). Given the chronic nature of HIV disease, identifying reliable biomarkers of these impairments is essential to advance our understanding of the underlying neural foundation and facilitate screening and diagnosis in clinical care. While neuroimaging provides immense potential for such biomarkers, to date, investigations in PLWH have been mostly limited to either univariate mass techniques or a single neuroimaging modality. In the present study, connectome-based predictive modeling (CPM) was proposed to predict individual differences of cognitive functioning in PLWH, using resting-state functional connectivity (FC), white matter structural connectivity (SC), and clinical relevant measures. We also adopted an efficient feature selection approach to identify the most predictive features, which achieved an optimal prediction accuracy of r = 0.61 in the discovery dataset (n = 102) and r = 0.45 in an independent validation HIV cohort (n = 88). Two brain templates and nine distinct prediction models were also tested for better modeling generalizability. Results show that combining multimodal FC and SC features enabled higher prediction accuracy of cognitive scores in PLWH, while adding clinical and demographic metrics may further improve the prediction by introducing complementary information, which may help better evaluate the individual-level cognitive performance in PLWH.

HIV viremia contributes to neurocognitive impairments in persons who use cocaine.

Persons with HIV (PWH) who use illicit drugs are at elevated risk for neurocognitive impairment (NCI). This study investigated the effects of HIV disease and HIV viremia on NCI among adults who use cocaine. PWH who were not virologically suppressed showed greater global deficits compared to participants with HIV viral suppression and HIV-negative participants, but no differences emerged between the latter two groups. These findings highlight the adverse effects of poorly controlled HIV disease on NCI, beyond the independent effects of cocaine on cognition, and underscore the importance of strengthening the HIV care continuum for persons who use cocaine.

Imaging of Brain Structural and Functional Effects in People With Human Immunodeficiency Virus.

Before the introduction of antiretroviral therapy, human immunodeficiency virus (HIV) infection was often accompanied by central nervous system (CNS) opportunistic infections and HIV encephalopathy marked by profound structural and functional alterations detectable with neuroimaging. Treatment with antiretroviral therapy nearly eliminated CNS opportunistic infections, while neuropsychiatric impairment and peripheral nerve and organ damage have persisted among virally suppressed people with HIV (PWH), suggesting ongoing brain injury. Neuroimaging research must use methods sensitive for detecting subtle HIV-associated brain structural and functional abnormalities, while allowing for adjustments for potential confounders, such as age, sex, substance use, hepatitis C coinfection, cardiovascular risk, and others. Here, we review existing and emerging neuroimaging tools that demonstrated promise in detecting markers of HIV-associated brain pathology and explore strategies to study the impact of potential confounding factors on these brain measures. We emphasize neuroimaging approaches that may be used in parallel to gather complementary information, allowing efficient detection and interpretation of altered brain structure and function associated with suboptimal clinical outcomes among virally suppressed PWH. We examine the advantages of each imaging modality and systematic approaches in study design and analysis. We also consider advantages of combining experimental and statistical control techniques to improve sensitivity and specificity of biotype identification and explore the costs and benefits of aggregating data from multiple studies to achieve larger sample sizes, enabling use of emerging methods for combining and analyzing large, multifaceted data sets. Many of the topics addressed in this article were discussed at the National Institute of Mental Health meeting "Biotypes of CNS Complications in People Living with HIV," held in October 2021, and are part of ongoing research initiatives to define the role of neuroimaging in emerging alternative approaches to identifying biotypes of CNS complications in PWH. An outcome of these considerations may be the development of a common neuroimaging protocol available for researchers to use in future studies examining neurological changes in the brains of PWH.

Cortico-striatal networking deficits associated with advanced HIV disease and cocaine use.

Cocaine use is disproportionately prevalent in people with HIV (PWH) and is known to potentiate HIV neuropathogenesis. As both HIV and cocaine have well-documented cortico-striatal effects, PWH who use cocaine and have a history of immunosuppression may exhibit greater FC deficits compared to PWH without these conditions. However, research investigating the legacy effects of HIV immunosuppression (i.e., a history of AIDS) on cortico-striatal functional connectivity (FC) in adults with and without cocaine use is sparse. Resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessment data from 273 adults were analyzed to examine FC in relation to HIV disease: HIV-negative (n = 104), HIV-positive with nadir CD4 ≥ 200 (n = 96), HIV-positive with nadir CD4 < 200 (AIDS; n = 73), and cocaine use (83 COC and 190 NON). Using independent component analysis/dual regression, FC was assessed between the basal ganglia network (BGN) and five cortical networks: dorsal attention network (DAN), default mode network, left executive network, right executive network, and salience network. There were significant interaction effects such that AIDS-related BGN-DAN FC deficits emerged in COC but not in NON participants. Independent of HIV, cocaine effects emerged in FC between the BGN and executive networks. Disruption of BGN-DAN FC in AIDS/COC participants is consistent with cocaine potentiation of neuro-inflammation and may be indicative of legacy HIV immunosuppressive effects. The current study bolsters previous findings linking HIV and cocaine use with cortico-striatal networking deficits. Future research should consider the effects of the duration of HIV immunosuppression and early treatment initiation.

Additive cortical gray matter deficits in people living with HIV who use cocaine.

Cocaine use, which is disproportionately common in people living with HIV (PWH), is known to have neurotoxic effects that may exacerbate HIV neuropathogenesis. While both cocaine use and HIV disease are independently associated with deficits in gray matter (GM) volume, the additive effect of cocaine use to HIV disease on GM volume has not been explored. Here, we investigated subcortical and cortical brain volume differences between four groups of individuals with and without HIV disease and/or cocaine use. Participants also completed a comprehensive neuropsychological testing battery, and HIV disease characteristics were recorded. Within subcortical regions, cocaine use was independently associated with higher volume in the dorsal striatum and pallidum, while HIV disease was associated with lower volume in the nucleus accumbens and thalamus. For cortical regions, there was an additive effect of cocaine use on HIV disease in parietal and occipital lobe volume with PWH who used cocaine displaying the lowest GM volume. Within regions that differed between groups, higher neurocognitive function was positively associated with thalamic, nucleus accumbens, dorsal striatum, and occipital lobe volume. For regions that showed a significant main effect of HIV disease, lower nadir CD4 + T cell count was associated with lower nucleus accumbens and occipital lobe volume. Lower current CD4 + T cell count was associated with lower occipital lobe volume. These results suggest that PWH who use cocaine are at greater risk for cortical atrophy than cocaine use or HIV disease alone.

Neuroimaging and immunological features of neurocognitive function related to substance use in people with HIV.

This study sought to identify neuroimaging and immunological factors associated with substance use and that contribute to neurocognitive impairment (NCI) in people with HIV (PWH). We performed cross-sectional immunological phenotyping, neuroimaging, and neurocognitive testing on virally suppressed PWH in four substance groups: cocaine only users (COC), marijuana only users (MJ), dual users (Dual), and Non-users. Participants completed substance use assessments, multimodal MRI brain scan, neuropsychological testing, and blood and CSF sampling. We employed a two-stage analysis of 305 possible biomarkers of cognitive function associated with substance use. Feature reduction (Kruskal Wallis p-value < 0.05) identified 53 biomarkers associated with substance use (22 MRI and 31 immunological) for model inclusion along with clinical and demographic variables. We employed eXtreme Gradient Boosting (XGBoost) with these markers to predict cognitive function (global T-score). SHapley Additive exPlanations (SHAP) values were calculated to rank features for impact on model output and NCI. Participants were 110 PWH with sustained HIV viral suppression (33 MJ, 12 COC, 22 Dual, and 43 Non-users). The ten highest ranking biomarkers for predicting global T-score were 4 neuroimaging biomarkers including functional connectivity, gray matter volume, and white matter integrity; 5 soluble biomarkers (plasma glycine, alanine, lyso-phosphatidylcholine (lysoPC) aC17.0, hydroxy-sphingomyelin (SM.OH) C14.1, and phosphatidylcholinediacyl (PC aa) C28.1); and 1 clinical variable (nadir CD4 count). The results of our machine learning model suggest that substance use may indirectly contribute to NCI in PWH through both metabolomic and neuropathological mechanisms.

Participant perceptions on the acceptability and feasibility of a telemedicine-based HIV PrEP and buprenorphine/naloxone program embedded within syringe services programs: a qualitative descriptive evaluation.

BACKGROUND: People who inject drugs (PWID) are at risk for HIV and opioid overdose. We piloted PARTNER UP, a telemedicine-based program to provide PWID with access to both oral pre-exposure prophylaxis (PrEP) for HIV prevention and medication for opioid use disorder (MOUD) through two syringe services programs (SSPs) in North Carolina. We conducted a qualitative evaluation to assess the acceptability and feasibility of PARTNER UP from the participant perspective. METHODS: PARTNER UP participants met with a provider for an initial in-person visit at the SSP, followed by weekly telemedicine visits in month 1 and then monthly telemedicine visits until program end at month 6. Using a qualitative descriptive study design, we conducted in-depth interviews with a subsample of PARTNER UP participants at 1 month and 4 months. Informed by the technology acceptance model, we assessed participant perceptions of the usefulness and ease of use of PARTNER UP, as well as their intent to continue to use the program's components. We audio-recorded all interviews with participants' permission and used applied thematic analysis to analyze the verbatim transcripts. RESULTS: We interviewed 11 of 17 people who participated in PARTNER UP-10 in the month 1 interview and 8 in the month 4 interview. Nearly all participants were motivated to join for consistent and easy access to buprenorphine/naloxone (i.e., MOUD); only a few joined to access PrEP. Most were comfortable accessing healthcare at the SSP because of their relationship with and trust toward SSP staff, and accessing services at the SSP was preferred compared with other healthcare centers. Some participants described that telemedicine allowed them to be honest and share more information because the visits were not in-person and they chose the location, although the initial in-person meeting was helpful to build provider trust and rapport. Most participants found the visit schedule to be feasible, although half described needing to reschedule at least once. Nearly all participants who were interviewed intended to continue with MOUD after the program ended, whereas none were interested in continuing with PrEP. CONCLUSIONS: Participant narratives suggest that the PARTNER UP telemedicine program was acceptable and feasible. Future studies should continue to explore the benefits of embedding both PrEP and MOUD into SSPs with larger numbers of participants. Trial registration Clinicaltrials.gov Identifier: NCT04521920.

Strengthened and posterior-shifted structural rich-club organization in people who use cocaine.

BACKGROUND: People with cocaine use disorder (CUD) often have abnormal cognitive function and brain structure. Cognition is supported by brain networks that typically have characteristics like rich-club organization, which is a group of regions that are highly connected across the brain and to each other, and small worldness, which is a balance between local and long-distance connections. However, it is unknown whether there are abnormalities in structural brain network connectivity of CUD. METHODS: Using diffusion-weighted imaging, we measured structural connectivity in 37 people with CUD and 38 age-matched controls. We identified differences in rich-club organization and whether such differences related to small worldness and behavior. We also tested whether rich-club reorganization was associated with caudate and putamen structural connectivity due to the relevance of the dopamine system to cocaine use. RESULTS: People with CUD had a higher normalized rich-club coefficient than controls, more edges connecting rich-club nodes to each other and to non-rich-club nodes, and fewer edges connecting non-rich-club nodes. Rich-club nodes were shifted posterior and lateral. Rich-club reorganization was related to lower clustered connectivity around individual nodes found in CUD, to increased impulsivity, and to a decrease in caudate connectivity. CONCLUSIONS: These findings are consistent with previous work showing increased rich-club connectivity in conditions associated with a hypofunctional dopamine system. The posterior shift in rich-club nodes in CUD suggests that the structural connectivity of posterior regions may be more impacted than previously recognized in models based on brain function and morphology.

Transmission Of Tuberculosis Among illicit drug use Linkages (TOTAL): A cross-sectional observational study protocol using respondent driven sampling.

People who use illicit drugs (PWUDs) have been identified as a key at-risk group for tuberculosis (TB). Examination of illicit drug use networks has potential to assess the risk of TB exposure and disease progression. Research also is needed to assess mechanisms for accelerated TB transmission in this population. This study aims to 1) assess the rate of TB exposure, risk of disease progression, and disease burden among PWUD; 2) estimate the proportion of active TB cases resulting from recent transmission within this network; and 3) evaluate whether PWUD with TB disease have physiologic characteristics associated with more efficient TB transmission. Our cross-sectional, observational study aims to assess TB transmission through illicit drug use networks, focusing on methamphetamine and Mandrax (methaqualone) use, in a high TB burden setting and identify mechanisms underlying accelerated transmission. We will recruit and enroll 750 PWUD (living with and without HIV) through respondent driven sampling in Worcester, South Africa. Drug use will be measured through self-report and biological measures, with sputum specimens collected to identify TB disease by Xpert Ultra (Cepheid) and mycobacterial culture. We will co-enroll those with microbiologic evidence of TB disease in Aim 2 for molecular and social network study. Whole genome sequencing of Mycobacteria tuberculosis (Mtb) specimens and social contact surveys will be done for those diagnosed with TB. For Aim 3, aerosolized Mtb will be compared in individuals with newly diagnosed TB who do and do not smoke illicit drug. Knowledge from this study will provide the basis for a strategy to interrupt TB transmission in PWUD and provide insight into how this fuels overall community transmission. Results have potential for informing interventions to reduce TB spread applicable to high TB and HIV burden settings. Trial registration: Clinicaltrials.gov Registration Number: NCT041515602. Date of Registration: 5 November 2019.

Principal component analysis denoising improves sensitivity of MR diffusion to detect white matter injury in neuroHIV.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging is able to capture important information about cerebral white matter (WM) structure. However, diffusion data can suffer from MRI and biological noise that degrades the quality of the images and makes finding important features difficult. We investigated how effectively local and nonlocal denoising increased the sensitivity to detect differences in cerebral WM in neuroHIV. METHODS: We utilized principal component analysis (PCA) denoising to detect WM differences using fractional anisotropy. Local and nonlocal PCA denoising paradigms were implemented that varied in search area and number of components. We examined different-sized WM tracts that consistently show differences between people living with Human Immunodeficiency Virus (HIV) (PWH) and HIV-negative individuals (corpus callosum, forceps minor, and right uncinate fasciculus), and size-matched tracts not typically associated with HIV-related differences (spinothalamic, right medial lemniscus, and left occipitopontine). We first conducted a full sample comparison of WM differences between groups, and then randomly reduced the sample to the point where we still found differences in WM. RESULTS: Nonlocal PCA denoising allowed us to detect differences after a sample reduction of 35% in the forceps minor, 17% in the right uncinate fasciculus, and 6% in the corpus callosum. CONCLUSIONS: PCA denoising had a beneficial effect on detecting significant differences in PWH after sample size reduction. The smaller forceps minor tract and right uncinate fasciculus showed greater sensitivity to PCA denoising than the larger corpus callosum. These results show the importance of identifying the most effective PCA denoising strategy when investigating WM in PWH.

HIV, psychological resilience, and substance misuse during the COVID-19 pandemic: A multi-cohort study.

OBJECTIVE: The COVID-19 pandemic has dramatically impacted mental health, increasing rates of substance misuse. Resilience is a positive adaptation to stress that may act as a buffer against adverse mental health outcomes. Based on prior knowledge, we hypothesized that PLWH would display higher resilience than HIV-uninfected peers, and that high resilience would be associated with lower risk of substance misuse. METHODS: This analysis of the Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO) included data from six USA cohorts that administered a COVID-19-related survey with a 3-month follow-up during May 2020 and March 2021. All data was self-reported. The Brief Resilience Scale and General Anxiety Disorder-7 were utilized. Primary analyses consisted of multivariate generalized linear mixed models with random intercepts using binary logistic regression. RESULTS: A total of 1430 participants completed both surveys, of whom 670 (46.9%) were PLWH. PLWH had lower odds of anxiety (OR=0.67, 95% CI: 0.51-0.89) and higher odds of high resilience (OR=1.21, 95% CI: 1.02-1.44) than HIV-uninfected participants, adjusted for covariates. The presence of anxiety was associated with higher risk of misuse of all substances. High resilience was associated with lower risk of anxiety and misuse of substances, adjusted for covariates. CONCLUSIONS: Psychological resilience was associated with lower risk of anxiety and substance misuse, potentially serving as a buffer against poor mental and behavioral health during the COVID-19 pandemic. Further research is needed to identify pathways of resilience in the context of substance misuse and comprehensive resilience-focused interventions.

Effects of substance use on monetary delay discounting among people who use stimulants with and without HIV: An ecological momentary assessment study.

Exploration of the real-time relationship between substance use and delay discounting may reveal potential mechanisms driving high-risk behaviors. We conducted an ecological momentary assessment (EMA) study to investigate the effects of substance use on delay discounting in a sample of people who use stimulants (HIV+: 30; HIV-: 34). Participants completed multiple EMAs throughout the day for 28 days. The EMAs collected data on delay discounting and substance use (time since last substance use and level of intoxication). Delay discounting was assessed using a brief Monetary Choice Questionnaire (MCQ). Analyses were conducted using linear mixed effects modeling. Most participants (99.1%) used cocaine as their primary stimulant. Among participants without HIV, MCQ score remained relatively stable during the first 2 hr after stimulant use, followed by an increase during 2-6 hr (p < .05), before decreasing again. For alcohol and marijuana, the MCQ score was stable during the first 4 hr after use, with a sharp increase at 4-6 hr (p < .05), before decreasing again. Among participants with HIV, there were no changes in MCQ score as a function of time since recent substance use. These findings provide evidence of a plausible connection between delay discounting and acute withdrawal that may have relevance for risky behaviors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Brain multimodal co-alterations related to delay discounting: a multimodal MRI fusion analysis in persons with and without cocaine use disorder.

BACKGROUND: Delay discounting has been proposed as a behavioral marker of substance use disorders. Innovative analytic approaches that integrate information from multiple neuroimaging modalities can provide new insights into the complex effects of drug use on the brain. This study implemented a supervised multimodal fusion approach to reveal neural networks associated with delay discounting that distinguish persons with and without cocaine use disorder (CUD). METHODS: Adults with (n = 35) and without (n = 37) CUD completed a magnetic resonance imaging (MRI) scan to acquire high-resolution anatomical, resting-state functional, and diffusion-weighted images. Pre-computed features from each data modality included whole-brain voxel-wise maps for gray matter volume, fractional anisotropy, and regional homogeneity, respectively. With delay discounting as the reference, multimodal canonical component analysis plus joint independent component analysis was used to identify co-alterations in brain structure and function. RESULTS: The sample was 58% male and 78% African-American. As expected, participants with CUD had higher delay discounting compared to those without CUD. One joint component was identified that correlated with delay discounting across all modalities, involving regions in the thalamus, dorsal striatum, frontopolar cortex, occipital lobe, and corpus callosum. The components were negatively correlated with delay discounting, such that weaker loadings were associated with higher discounting. The component loadings were lower in persons with CUD, meaning the component was expressed less strongly. CONCLUSIONS: Our findings reveal structural and functional co-alterations linked to delay discounting, particularly in brain regions involved in reward salience, executive control, and visual attention and connecting white matter tracts. Importantly, these multimodal networks were weaker in persons with CUD, indicating less cognitive control that may contribute to impulsive behaviors.

Human immunodeficiency virus-related decreases in corpus callosal integrity and corresponding increases in functional connectivity.

People living with human immunodeficiency virus (PLWH) often have neurocognitive impairment. However, findings on HIV-related differences in brain network function underlying these impairments are inconsistent. One principle frequently absent from these reports is that brain function is largely emergent from brain structure. PLWH commonly have degraded white matter; we hypothesized that functional communities connected by degraded white matter tracts would show abnormal functional connectivity. We measured white matter integrity in 69 PLWH and 67 controls using fractional anisotropy (FA) in 24 intracerebral white matter tracts. Then, among tracts with degraded FA, we identified gray matter regions connected to these tracts and measured their functional connectivity during rest. Finally, we identified cognitive impairment related to these structural and functional connectivity systems. We found HIV-related decreased FA in the corpus callosum body (CCb), which coordinates activity between the left and right hemispheres, and corresponding increases in functional connectivity. Finally, we found that individuals with impaired cognitive functioning have lower CCb FA and higher CCb functional connectivity. This result clarifies the functional relevance of the corpus callosum in HIV and provides a framework in which abnormal brain function can be understood in the context of abnormal brain structure, which may both contribute to cognitive impairment.

On the down-sampling of diffusion MRI data along the angular dimension.

BACKGROUND: It has been established that the diffusion gradient directions in diffusion MRI should be uniformly distributed in 3D spherical space, so that orientation-dependent diffusion properties (e.g., fractional anisotropy or FA) can be properly quantified. Sometimes the acquired data need to be down-sampled along the angular dimension before computing diffusion properties (e.g., to exclude data points corrupted by motion artifact; to harmonize data obtained with different protocols). It is important to quantitatively assess the impact of data down-sampling on measurement of diffusion properties. MATERIALS AND METHODS: Here we report 1) a numerical procedure for down-sampling diffusion MRI (e.g., for data harmonization), and 2) a spatial uniformity index of diffusion directions, aiming to predict the quality of the chosen down-sampling schemes (e.g., from data harmonization; or rejection of motion corrupted data points). We quantitatively evaluated human diffusion MRI data, which were down-sampled from 64 or 60 diffusion gradient directions to 30 directions, in terms of their 1) FA value accuracy (using fully-sampled data as the ground truth), 2) FA fitting residuals, and 3) spatial uniformity indices. RESULTS: Our experimental data show that the proposed spatial uniformity index is correlated with errors in FA obtained from down-sampled diffusion MRI data. The FA fitting residuals that are typically used to assess diffusion MRI quality are not correlated with either FA errors or spatial uniformity index. CONCLUSIONS: These results suggest that the spatial uniformity index could be more valuable in assessing quality of down-sampled diffusion MRI data, as compared with FA fitting residual measures. We expect that our implemented software procedure should prove valuable for 1) guiding data harmonization for multi-site diffusion MRI studies, and 2) assessing the impact of rejecting motion corrupted data points on the accuracy of diffusion measures.

Using mobile health technologies to test the association of cocaine use with sexual desire and risky sexual behaviors among people with and without HIV who use illicit stimulants.

BACKGROUND: Cocaine use is broadly associated with risky sexual behavior potentially through elevated sexual desire. Understanding the within-person effects of cocaine on sexual desire and risky sexual behavior and the modification of HIV infection may inform primary and secondary HIV interventions. METHODS: We conducted a mobile health (mHealth) study in a community sample of males and females with (n = 28) and without (n = 32) HIV who use illicit stimulant drugs. Participants completed ecological momentary assessments (EMAs) and daily diaries over 28 days. Mixed effects models were employed to examine the within-person association of cocaine use with sexual desire and risky sexual behavior. RESULTS: Participants completed 3505 EMA responses, with 36 % involving recent cocaine use, including powder and/or crack cocaine. They completed 1427 daily diary responses, with cocaine use reported on 49 % of these days and sexual behavior on 21 % of these days. Sexual desire was highest in the first hour since cocaine use and gradually decreased with time. Sexual desire was lowest when participants had not used any cocaine in the past 6 h, and it correlated positively with the amount of use. Participants were more likely to have risky sexual behavior on days they used cocaine. These associations were similar for participants with and without HIV. CONCLUSION: This study demonstrates the dynamic and proximal effects of cocaine use on sexual desire and risky sexual behavior. Our findings support the development of HIV prevention interventions that utilize mHealth technology to reduce sexual risk behavior among persons who use stimulant drugs.