Characterization of basal ganglia volume changes in the context of HIV and polysubstance use

Abstract

HIV and psychoactive substances can impact the integrity of the basal ganglia (BG), a neural substrate of cognition, motor control, and reward-seeking behaviors. This study assessed BG gray matter (GM) volume as a function of polysubstance (stimulant and opioid) use and HIV status. We hypothesized that comorbid polysubstance use and HIV seropositivity would alter BG GM volume differently than would polysubstance use or HIV status alone. We collected structural MRI scans, substance use history, and HIV diagnoses. Participants who had HIV (HIV +), a history of polysubstance dependence (POLY +), both, or neither completed assessments for cognition, motor function, and risk-taking behaviors (N = 93). All three clinical groups showed a left-lateralized pattern of GM reduction in the BG relative to controls. However, in the HIV + /POLY + group, stimulant use was associated with increased GM volume within the globus pallidus and putamen. This surpassed the effects from opioid use, as indicated by decreased GM volume throughout the BG in the HIV-/POLY + group. Motor learning was impaired in all three clinical groups, and in the HIV + /POLY + group, motor learning was associated with increased caudate and putamen GM volume. We also observed associations between BG GM volume and risk-taking behaviors in the HIV + /POLY- and HIV-/POLY + groups. The effects of substance use on the BG differed as a function of substance type used, HIV seropositivity, and BG subregion. Although BG volume decreased in association with HIV and opioid use, stimulants can, inversely, lead to BG volume increases within the context of HIV.

Cannabinoids modulate the microbiota–gut–brain axis in HIV/SIV infection by reducing neuroinflammation and dysbiosis while concurrently elevating endocannabinoid and indole-3-propionate levels

“…To determine the effect of THC on the brain during chronic SIV infection, we undertook a systems biology approach by profiling genome wide changes in transcriptome and microRNA expression in whole BG of chronically SIV-infected RMs. We selected the basal ganglia because this brain region controls motor activity [111] and is severely impacted by HIV/SIV due to its susceptibility to high levels of viral replication [112][113][114]. In line with the host response to active viral replication, a gene expression signature dominated by chemokines (CCL2, CXCL10), neuroimmune activation (NLRC5), NFκB activation (RNF31), and more importantly, type-I IFN response (ISG15, ISG20, HERC5, IFIT1, IRF1, IRF7), and type I IFN stimulated antiviral signaling (ZC3HAV1, TMRM173, DDX58, MX1, BST2, IFITM3, IFITM1), was significantly upregulated in BG of VEH/SIV RMs.…”

An fMRI analysis of verbal and non-verbal working memory in people with a past history of opioid dependence

“…The drug screen (Aim Screen Multidrug 9 by Germaine Laboratories) tested for the presence of the following substances in the urine: cocaine, amphetamine, methamphetamine, marijuana, methadone, opiates, phencyclidine, barbiturates, and benzodiazepines. A detailed history of lifetime drug and alcohol exposure was obtained in both groups using a modified version of the Lifetime Drug Use Questionnaire ( Czermak et al, 2005 ; Marvel et al, 2012 ; Anderson et al, 2013 , 2016 ; Monick et al, 2022 ). These measures can be seen in Table 2 , including age of first substance use, duration of use (time between the first and last substance use), abstinence duration since last substance use, and for some substances, the calculated average frequency of use during periods of use, as modeled after the calculation in Monick et al (2022) .…”

“…A detailed history of lifetime drug and alcohol exposure was obtained in both groups using a modified version of the Lifetime Drug Use Questionnaire ( Czermak et al, 2005 ; Marvel et al, 2012 ; Anderson et al, 2013 , 2016 ; Monick et al, 2022 ). These measures can be seen in Table 2 , including age of first substance use, duration of use (time between the first and last substance use), abstinence duration since last substance use, and for some substances, the calculated average frequency of use during periods of use, as modeled after the calculation in Monick et al (2022) . This measure for frequency of use further characterized the cocaine and opioid use in participants, providing a measure that took into consideration the changing frequencies with which participants used substances throughout their total duration of use.…”

“…Relatedly, neuroimaging studies have also revealed structural brain abnormalities in people with opioid dependence. For instance, reductions in gray matter volume have been reported in the right prefrontal cortex, left SMA, bilateral cingulate cortices (CC), basal ganglia, and insula for opioid-dependent subjects ( Liu et al, 2009 ; Tolomeo et al, 2016 , 2018 ; Bach et al, 2021 ; Monick et al, 2022 ). Reductions in gray matter have been reported in the prefrontal and temporal cortices of methadone maintenance patients ( Lyoo et al, 2006 ).…”

“…Reductions in gray matter have been reported in the prefrontal and temporal cortices of methadone maintenance patients ( Lyoo et al, 2006 ). Furthermore, the magnitudes of overall gray matter density reduction and resting-state functional connectivity between the prefrontal cortex, insula, basal ganglia, and cerebellum in opioid-dependent individuals have been reported as negatively correlated with duration of opioid use ( Upadhyay et al, 2010 ; Yuan et al, 2010a , b ; Monick et al, 2022 ).…”