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1. Functional Brain Network Identification in Opioid Use Disorder Using Machine Learning Analysis of Resting-State fMRI BOLD Signals

Author

Temtam, Ahmed, Witherow, Megan A., Ma, Liangsuo, Sadique, M. Shibly, Moeller, F. Gerard, and Iftekharuddin, Khan M.

Subjects
Quantitative Biology - Neurons and Cognition, Computer Science - Machine Learning
Abstract

Understanding the neurobiology of opioid use disorder (OUD) using resting-state functional magnetic resonance imaging (rs-fMRI) may help inform treatment strategies to improve patient outcomes. Recent literature suggests temporal characteristics of rs-fMRI blood oxygenation level-dependent (BOLD) signals may offer complementary information to functional connectivity analysis. However, existing studies of OUD analyze BOLD signals using measures computed across all time points. This study, for the first time in the literature, employs data-driven machine learning (ML) modeling of rs-fMRI BOLD features representing multiple time points to identify region(s) of interest that differentiate OUD subjects from healthy controls (HC). Following the triple network model, we obtain rs-fMRI BOLD features from the default mode network (DMN), salience network (SN), and executive control network (ECN) for 31 OUD and 45 HC subjects. Then, we use the Boruta ML algorithm to identify statistically significant BOLD features that differentiate OUD from HC, identifying the DMN as the most salient functional network for OUD. Furthermore, we conduct brain activity mapping, showing heightened neural activity within the DMN for OUD. We perform 5-fold cross-validation classification (OUD vs. HC) experiments to study the discriminative power of functional network features with and without fusing demographic features. The DMN shows the most discriminative power, achieving mean AUC and F1 scores of 80.91% and 73.97%, respectively, when fusing BOLD and demographic features. Follow-up Boruta analysis using BOLD features extracted from the medial prefrontal cortex, posterior cingulate cortex, and left and right temporoparietal junctions reveals significant features for all four functional hubs within the DMN., Comment: 20 pages, 7 figures, 8 tables

Published
2024

6. Geostatistical Modeling of Positive Definite Matrices: An Application to Diffusion Tensor Imaging

Author

Lan, Zhou, Reich, Brian J., Guinness, Joseph, Bandyopadhyay, Dipankar, Ma, Liangsuo, and Moeller, F. Gerard

Subjects
Statistics - Methodology, Statistics - Applications
Abstract

Geostatistical modeling for continuous point-referenced data has been extensively applied to neuroimaging because it produces efficient and valid statistical inference. However, diffusion tensor imaging (DTI), a neuroimaging characterizing the brain structure produces a positive definite (p.d.) matrix for each voxel. Current geostatistical modeling has not been extended to p.d. matrices because introducing spatial dependence among positive definite matrices properly is challenging. In this paper, we use the spatial Wishart process, a spatial stochastic process (random field) where each p.d. matrix-variate marginally follows a Wishart distribution, and spatial dependence between random matrices is induced by latent Gaussian processes. This process is valid on an uncountable collection of spatial locations and is almost surely continuous, leading to a reasonable means of modeling spatial dependence. Motivated by a DTI dataset of cocaine users, we propose a spatial matrix-variate regression model based on the spatial Wishart process. A problematic issue is that the spatial Wishart process has no closed-form density function. Hence, we propose approximation methods to obtain a feasible working model. A local likelihood approximation method is also applied to achieve fast computation. The simulation studies and real data analysis demonstrate that the working model produces reliable inference and improved performance compared to other methods.

Published
2019
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7. Cingulo-hippocampal effective connectivity positively correlates with drug-cue attentional bias in opioid use disorder.

Author

Ma, Liangsuo, Steinberg, Joel L, Bjork, James M, Taylor, Brian A, Arias, Albert J, Terplan, Mishka, Anastasio, Noelle C, Zuniga, Edward A, Lennon, Michael, Cunningham, Kathryn A, and Moeller, F Gerard

Subjects
Brain, Gyrus Cinguli, Hippocampus, Temporal Lobe, Humans, Opioid-Related Disorders, Analgesics, Opioid, Magnetic Resonance Imaging, Brain Mapping, Cognition, Cues, Reaction Time, Female, Male, Stroop Test, Attentional Bias, Attentional bias, Cue reactivity, Dynamic causal modeling, Effective connectivity, Opioid use disorder, Neurosciences, Clinical Research, Brain Disorders, Behavioral and Social Science, Substance Misuse, Basic Behavioral and Social Science, Drug Abuse (NIDA only), Mental health, Clinical Sciences, Cognitive Sciences, Psychiatry
Abstract

Individuals with opioid use disorder (OUD) often relapse when exposed to opioid-related cues. Previous functional magnetic resonance imaging (fMRI) studies have identified neuronal corticolimbic changes related to drug cue reactivity in OUD. However, the corresponding manner in which brain regions interact is still unclear. Effective (directional) connectivity was analyzed using dynamic causal modeling of fMRI data acquired from 27 OUD participants (13 with OUD and 14 with OUD and cocaine use disorder [OUD+CUD]), while performing an opioid-word Stroop task. Participants were shown opioid and neutral words presented in different colors and were instructed to indicate word color but ignore word meaning. The effects of opioid words relative to neutral words on effective connectivity and on behavioral reaction time were defined as modulatory change and attentional bias, respectively. For all the 27 participants, left anterior cingulate cortex (ACC) to right hippocampus effective connectivity exhibited the largest modulatory change, which was positively correlated with attentional bias. The findings for the ACC to hippocampus EC were consistent across OUD and CUD found in a previous study.

Published
2019

16. Insomnia symptoms and neurofunctional correlates among adults receiving buprenorphine for opioid use disorder.

Author

White, Augustus M., Eglovitch, Michelle, Parlier-Ahmad, Anna Beth, Dzierzewski, Joseph M., James, Morgan, Bjork, James M., Moeller, F. Gerard, and Martin, Caitlin E.

Subjects
INTEROCEPTION, OPIOID abuse, INSOMNIA, SLEEP interruptions, BUPRENORPHINE, ADULTS, MORBID obesity
Abstract

Objectives: Insomnia symptoms are negatively related to opioid use disorder (OUD) treatment outcomes, possibly reflecting the influence of sleep on neurofunctional domains implicated in addiction. Moreover, the intersection between OUD recovery and sleep represents an area well-suited for the development of novel, personalized treatment strategies. This study assessed the prevalence of clinically significant insomnia symptoms and characterized its neurofunctional correlates among a clinical sample of adults with OUD receiving buprenorphine. Methods: Adults (N = 129) receiving buprenorphine for OUD from an outpatient clinic participated in a cross-sectional survey. Participants completed an abbreviated version of NIDA's Phenotyping Assessment Battery, which assessed 6 neurofunctional domains: sleep, negative emotionality, metacognition, interoception, cognition, and reward. Bivariate descriptive statistics compared those with evidence of clinically significant insomnia symptoms (Insomnia Severity Index [ISI] score of ≥11) to those with minimal evidence of clinically significant insomnia symptoms (ISI score of ≤10) across each of the neurofunctional domains. Results: Roughly 60% of participants reported clinically significant insomnia symptoms (ISI score of ≥11). Experiencing clinically significant insomnia symptoms was associated with reporting greater levels of depression, anxiety, post-traumatic stress, stress intolerance, unhelpful metacognition, and interoceptive awareness (ps<0.05). Participants with evidence of clinically significant insomnia were more likely to report that poor sleep was interfering with their OUD treatment and that improved sleep would assist with their treatment (ps<0.05). Conclusions: Insomnia was prevalent among adults receiving buprenorphine for OUD. Insomnia was associated with neurofunctional performance, which may impact OUD treatment trajectories. Our findings indicate potential targets in the development of personalized treatment plans for patients with co-morbid insomnia and OUD. To inform the development of novel treatment strategies, more research is needed to understand the potential mechanistic links between sleep disturbances and substance use. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Measures of outcome for stimulant trials: ACTTION recommendations and research agenda

Author

Kiluk, Brian D, Carroll, Kathleen M, Duhig, Amy, Falk, Daniel E, Kampman, Kyle, Lai, Shengan, Litten, Raye Z, McCann, David J, Montoya, Ivan D, Preston, Kenzie L, Skolnick, Phil, Weisner, Constance, Woody, George, Chandler, Redonna, Detke, Michael J, Dunn, Kelly, Dworkin, Robert H, Fertig, Joanne, Gewandter, Jennifer, Moeller, F Gerard, Ramey, Tatiana, Ryan, Megan, Silverman, Kenneth, and Strain, Eric C

Subjects
Drug Abuse (NIDA only), Neurosciences, Prevention, Clinical Trials and Supportive Activities, Clinical Research, Brain Disorders, Substance Misuse, Alcoholism, Alcohol Use and Health, Good Health and Well Being, Amphetamine-Related Disorders, Central Nervous System Stimulants, Clinical Trials as Topic, Congresses as Topic, Humans, Practice Guidelines as Topic, Substance-Related Disorders, Treatment Outcome, Stimulant use disorders, Outcome measures, Clinical trials, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse
Abstract

BackgroundThe development and approval of an efficacious pharmacotherapy for stimulant use disorders has been limited by the lack of a meaningful indicator of treatment success, other than sustained abstinence.MethodsIn March, 2015, a meeting sponsored by Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) was convened to discuss the current state of the evidence regarding meaningful outcome measures in clinical trials for stimulant use disorders. Attendees included members of academia, funding and regulatory agencies, pharmaceutical companies, and healthcare organizations. The goal was to establish a research agenda for the development of a meaningful outcome measure that may be used as an endpoint in clinical trials for stimulant use disorders.Results and conclusionsBased on guidelines for the selection of clinical trial endpoints, the lessons learned from prior addiction clinical trials, and the process that led to identification of a meaningful indicator of treatment success for alcohol use disorders, several recommendations for future research were generated. These include a focus on the validation of patient reported outcome measures of functioning, the exploration of patterns of stimulant abstinence that may be associated with physical and/or psychosocial benefits, the role of urine testing for validating self-reported measures of stimulant abstinence, and the operational definitions for reduction-based measures in terms of frequency rather than quantity of stimulant use. These recommendations may be useful for secondary analyses of clinical trial data, and in the design of future clinical trials that may help establish a meaningful indicator of treatment success.

Published
2016

25. Turn the Next Page

Author

Cunningham, Kathryn A., primary, Price, Amanda E., additional, Gerard Moeller, F., additional, and Anastasio, Noelle C., additional

Published
2020
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36. Construction of accurate Kohn-Sham potentials for the lowest states of the helium atom: Accurate test of the ionization-potential theorem

Author

Lindgren, I., Salomonson, S., and Möller, F.

Subjects
Physics - Atomic Physics
Abstract

Accurate local Kohn-Sham potentials have been constructed for the ground $1s^2 ^1S$ state and, in particular, for the lowest triplet $1s2s ^{3}S$ state of the helium atom, using electron densities from many-body calculations and the procedure of van Leeuwen and Baerends (Phys. Rev. A{\bf49}, 2138 (1994)). The resulting Kohn-Sham orbitals reproduce the many-body densities very accurately, and furthermore we have demonstrated that the negative of the energy eigenvalue of the outermost electron orbital agrees with the corresponding ionization energy with extreme accuracy. The procedure is also applied to the Hartree-Fock density of the $1s2s ^{3}S$ state, and the Kohn-Sham eigenvalue of the $2s$ orbital is found to agree very well with the corresponding Hartree-Fock eigenvalue, which is the negative of the ionization energy in this model due to Koopmans' theorem. The results for the $1s2s ^{3}S$ state clearly demonstrate that there is no conflict between the locality of the Kohn-Sham potential and the exclusion principle, as claimed by Nesbet (Phys. Rev. A{\bf58}, R12 (1998))., Comment: 10 pages, 7 figures and 2 tables

Published
2004
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38. Epileptogenic Tubers Are Associated with Increased Kurtosis of Susceptibility Values: A Combined Quantitative Susceptibility Mapping and Stereoelectroencephalography Pilot Study

Author

Chari, A., primary, Sedlacik, J., additional, Seunarine, K., additional, Piper, R.J., additional, Hales, P., additional, Shmueli, K., additional, Mankad, K., additional, Löbel, U., additional, Eltze, C., additional, Moeller, F., additional, Scott, R.C., additional, Tisdall, M.M., additional, Cross, J.H., additional, and Carmichael, D.W., additional

Published
2023
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45. Rising Racial Disparities in Opioid Mortality and Undertreatment of Opioid Use Disorder and Mental Health Comorbidities in Virginia

Author

BritzMSPH, Jacqueline B., primary, O'Loughlin, Kristen M., additional, Henry, Tracey L., additional, Richards, Alicia, additional, Sabo, Roy T., additional, Saunders, Heather G., additional, Tong, Sebastian T., additional, Brooks, E. Marshall, additional, Lowe, Jason, additional, Harrell, Ashley, additional, Bethune, Christine, additional, Moeller, F. Gerard, additional, and Krist, Alex H., additional

Published
2023
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50. Measures of outcome for stimulant trials: ACTTION recommendations and research agenda

Author

Kiluk, Brian D., Carroll, Kathleen M., Duhig, Amy, Falk, Daniel E., Kampman, Kyle, Lai, Shengan, Litten, Raye Z., McCann, David J., Montoya, Ivan D., Preston, Kenzie L., Skolnick, Phil, Weisner, Constance, Woody, George, Chandler, Redonna, Detke, Michael J., Dunn, Kelly, Dworkin, Robert H., Fertig, Joanne, Gewandter, Jennifer, Moeller, F. Gerard, Ramey, Tatiana, Ryan, Megan, Silverman, Kenneth, and Strain, Eric C.

Published
2016
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