Reduced Error-Related Default Mode Network Deactivations Linked with HIV and Medication Management

Poster No:

1682 

Submission Type:

Abstract Submission 

Authors:

Jessica Flannery1, Michael Riedel1, Taylor Salo1, Ranjita Poudel1, Angela Laird1, Raul Gonzalez1, Matthew Sutherland1

Institutions:

1Florida International University, Miami, FL

First Author:

Jessica Flannery, M.S.  
Florida International University
Miami, FL

Co-Author(s):

Michael Riedel, PhD  
Florida International University
Miami, FL
Taylor Salo  
Florida International University
Miami, FL
Ranjita Poudel  
Florida International University
Miami, FL
Angela Laird  
Florida International University
Miami, FL
Raul Gonzalez, Ph.D  
Florida International University
Miami, FL
Matthew Sutherland, Ph.D  
Florida International University
Miami, FL

Introduction:

Brain function supporting error-monitoring has rarely been examined among persons living with HIV (PLWH) despite its importance for recognizing and preventing maladaptive behavior (e.g., medication non-adherence) that could lead to worsened health outcomes among this vulnerable population. As medicinal and recreational cannabis use is prevalent among PLWH [1], we aimed to assess interactive impacts of HIV infection and chronic cannabis (CB) use on error-processing brain activity and investigate implications for clinically relevant disease management behaviors.

Methods:

Our sample of 103 participants (68.0% male, mean age=35.6 years) was stratified into four groups based on HIV serostatus and CB use history (HIV+/CB+, n=30; HIV+/CB-, n=25; HIV-/CB+, n=26; HIV-/CB-, n=22). To probe error-processing mechanisms, participants underwent fMRI scanning while completing a Go/NoGo, motor inhibition paradigm called the Error Awareness Task (EAT). Participants also completed a battery of well-validated instruments including the Revised Medication Management Test (MMT-R), an objective behavioral measure of medication management abilities [2], and self-reports of cannabis use history. Following preprocessing (FMRIPREP v1.1.1 [3]), six EAT runs were entered into a subject-level general linear model (GLM) including nuisance regressors and three task-related regressors. To characterize brain activity linked with cognitive control/failures, NoGo-correct minus NoGo-error [C-E] contrast values were assessed with a whole-brain, one-sample t-test (3dTtest++: two-tailed, pvoxel-wise=1.0e-10, cluster extent: 20 voxels). To assess HIV and CB main and interaction effects on these [C-E] contrast values, a whole-brain, 2(HIV) x 2(CB) ANOVA (3dMVM), including sex, age, and IQ as covariates, was performed. To assess brain-behavior relationships, we conducted Pearson's correlations between averaged error-related β coefficients, extracted from identified clusters/regions of interest (ROIs), and error frequency in the EAT (ERROR COUNT). To probe clinically-relevant implications of HIV-associated alterations, we examined relationships between error-related brain activity and behavioral performance on the MMT-R (MMT SCORE) by conducting HIV-status x MMT SCORE ANCOVAs. Additionally, we tested a meditation model in which error-related brain activity (M) mediated the effect of HIV-status (X) on MMT SCORE (Y) [4, 5]. Finally, to evaluate the impact of lifetime cannabis use amount (AMOUNT), we assessed HIV-status x AMOUNT interactions on error-related brain activity and MMT SCORE among cannabis using participants (n=55).

Results:

We observed error-related brain activity in the anterior insula that was associated with better EAT performance across the full sample. Regarding group effects, PLWH displayed a lack of error-related deactivation in two default mode network (DMN) hub regions (the posterior cingulate cortex [PCC] and medial prefrontal cortex [mPFC]) that was contrarily observed among HIV- controls (Fig.1A). Additionally, degree of PCC suppression was associated with improved EAT performance among HIV- controls but not among PLWH (Fig.1B). CB main and interaction effects were not detected. Across all groups, reduced error-related PCC deactivation was associated with poorer medication management performance (Fig.2A) and mediated the effect of HIV-status on medication management abilities (Fig.2B). Finally, amount of CB used over the lifetime was associated with reduced mPFC deactivation to errors among CB using, HIV- controls, and poorer medication management abilities across all CB users.
Supporting Image: Figure_1.jpg
Supporting Image: Figure_2.jpg
 

Conclusions:

Our results demonstrate diminished error-related DMN suppression among PLWH linked to poor medication management. Identifying this HIV-associated, neurobiological alteration, which may contribute to high rates of medication non-adherence among this population [6, 7], could inform treatment planning and tailor self-care education.

Disorders of the Nervous System:

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1

Modeling and Analysis Methods:

Activation (eg. BOLD task-fMRI) 2

Keywords:

Other - HIV; Cannabis; Error Processing; Medication Management; Medication Adherence; Default Mode Network; Posterior Cingulate Cortex; Medial Prefrontal Cortex; Insula

1|2Indicates the priority used for review

My abstract is being submitted as a Software Demonstration.

No

Please indicate below if your study was a "resting state" or "task-activation” study.

Task-activation

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Patients

Are you Internal Review Board (IRB) certified? Please note: Failure to have IRB, if applicable will lead to automatic rejection of abstract.

Yes

Was any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

Yes

Was any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Not applicable

Please indicate which methods were used in your research:

Functional MRI
Structural MRI
Behavior
Neuropsychological testing

For human MRI, what field strength scanner do you use?

3.0T

Which processing packages did you use for your study?

AFNI
Other, Please list  -   FMRIPREP v1.1.1 and other BIDs apps

Provide references using author date format

1. Pacek LR, Towe SL, Hobkirk AL, Nash D, Goodwin RD. Frequency of cannabis use and medical cannabis use among persons living with HIV in the United States: findings from a nationally representative sample. AIDS Educ Prev. 2018;30(2):169-81. doi:https://doi.org/10.1521/aeap.2018.30.2.169

2. Albert SM, Flater SR, Clouse R, Todak G, Stern Y, Marder K. Medication management skill in HIV: I. Evidence for adaptation of medication management strategies in people with cognitive impairment. II. Evidence for a pervasive lay model of medication efficacy. AIDS Behav. 2003;7(3):329-38. doi:https://doi.org/10.1023/A:1025404105378

3. Esteban O, Markiewicz CJ, Blair RW, Moodie CA, Isik AI, Erramuzpe A, Kent JD, Goncalves M, DuPre E, Snyder M, Oya H. fMRIPrep: a robust preprocessing pipeline for functional MRI. Nat Methods. 2019;16(1):111-6. doi:https://doi.org/10.1038/s41592-018-0235-4

4. Shrout PE. Commentary: Mediation analysis, causal process, and cross-sectional data. Multivariate Behav Res. 2011;46(5):852-60. doi:https://doi.org/10.1080/00273171.2011.606718

5. Hayes AF, Little TD. Introduction to mediation, moderation, and conditional process analysis: A regression-based approach. New York: The Guilford Press; 2018.

6. Gauchet A, Tarquinio C, Fischer G. Psychosocial predictors of medication adherence among persons living with HIV. Int J. Behav. Med. 2007;14(3):141-50. doi:http://doi.org/10.1007/BF03000185

7. Gao X, Nau DP. Congruence of three self-report measures of medication adherence among HIV patients. Ann Pharmacother. 2000;34(10):1117-22. doi:https://doi.org/10.1345/aph.19339