Gene by Disease Interaction on Orbitofrontal Gray Matter in Cocaine Addiction

Chronic cocaine use has been associated with structural deficits in brain regions having dopamine receptive neurons. However, the concomitant use of other drugs and common genetic variability in monoamine regulation present additional structural variability. We therefore examined variations in gray matter volume (GMV) as a function of lifetime drug use and the monoamine oxidase A (MAOA) genotype in cocaine use disorders (CUD) and healthy controls

Multimodal evidence of regional midcingulate gray matter volume underlying conflict monitoring

Functional neuroimaging studies have long implicated the mid-cingulate cortex (MCC) in conflict monitoring, but it is not clear whether its structural integrity (i.e., the gray matter volume) influences its conflict monitoring function. In this multimodal study, we used T1-weighted MRI scans as well as event-related potentials (ERPs) to test whether the MCC gray matter volume is associated with the electrocortical marker (i.e., No-go N200 ERP component) of conflict monitoring in healthy individuals. The specificity of such a relationship in health was determined in two ways: by (A) acquiring the same data from individuals with cocaine use disorder (CUD), known to have deficits in executive function including behavioral monitoring; and (B) acquiring the P300 ERP component that is linked with attention allocation and not specifically with conflict monitoring. Twenty-five (39.1 ± 8.4 years; 8 females) healthy individuals and 25 (42.7 ± 5.9 years; 6 females) individuals with CUD underwent a rewarded Go/No-go task during which the ERP data was collected, and they also underwent a structural MRI scan. The whole brain regression analysis showed a significant correlation between MCC structural integrity and the well-known ERP measure of conflict monitoring (N200, but not the P300) in healthy individuals, which was absent in CUD who were characterized by reduced MCC gray matter volume, N200 abnormalities as well as reduced task accuracy. In individuals with CUD instead, the N200 amplitude was associated with drug addiction symptomatology. These results show that the integrity of MCC volume is directly associated with the electrocortical correlates of conflict monitoring in healthy individuals, and such an association breaks down in psychopathologies that impact these brain processes. Taken together, this MCC–N200 association may serve as a biomarker of improved behavioral monitoring processes in diseased populations

Predictive sparse modeling of fMRI data for improved classification, regression, and visualization using the k-support norm

We explore various sparse regularization techniques for analyzing fMRI data, such as the ℓ1 norm (often called LASSO in the context of a squared loss function), elastic net, and the recently introduced k-support norm. Employing sparsity regularization allows us to handle the curse of dimensionality, a problem commonly found in fMRI analysis. In this work we consider sparse regularization in both the regression and classification settings. We perform experiments on fMRI scans from cocaine-addicted as well as healthy control subjects. We show that in many cases, use of the k-support norm leads to better predictive performance, solution stability, and interpretability as compared to other standard approaches. We additionally analyze the advantages of using the absolute loss function versus the standard squared loss which leads to significantly better predictive performance for the regularization methods tested in almost all cases. Our results support the use of the k-support norm for fMRI analysis and on the clinical side, the generalizability of the I-RISA model of cocaine addiction.publisher: Elsevier articletitle: Predictive sparse modeling of fMRI data for improved classification, regression, and visualization using the k-support norm journaltitle: Computerized Medical Imaging and Graphics articlelink: http://dx.doi.org/10.1016/j.compmedimag.2015.03.007 content_type: article copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.status: publishe

Low Striatal Dopamine D2-type Receptor Availability is Linked to Simulated Drug Choice in Methamphetamine Users.

Individuals with drug use disorders seek drugs over other rewarding activities, and exhibit neurochemical deficits related to dopamine, which is involved in value-based learning and decision-making. Thus, a dopaminergic disturbance may underpin drug-biased choice in addiction. Classical drug-choice assessments, which offer drug-consumption opportunities, are inappropriate for addicted individuals seeking treatment or abstaining. Fifteen recently abstinent methamphetamine users and 15 healthy controls completed two laboratory paradigms of 'simulated' drug choice (choice for drug-related vs affectively pleasant, unpleasant, and neutral images), and underwent positron emission tomography measurements of dopamine D2-type receptor availability, indicated by binding potential (BPND) for [18F]fallypride. Thirteen of the methamphetamine users and 10 controls also underwent [11C]NNC112 PET scans to measure dopamine D1-type receptor availability. Group analyses showed that, compared with controls, methamphetamine users chose to view more methamphetamine-related images on one task, with a similar trend on the second task. Regression analyses showed that, on both tasks, the more methamphetamine users chose to view methamphetamine images, specifically vs pleasant images (the most frequently chosen images across all participants), the lower was their D2-type BPND in the lateral orbitofrontal cortex, an important region in value-based choice. No associations were observed with D2-type BPND in striatal regions, or with D1-type BPND in any region. These results identify a neurochemical correlate for a laboratory drug-seeking paradigm that can be administered to treatment-seeking and abstaining drug-addicted individuals. More broadly, these results refine the central hypothesis that dopamine-system deficits contribute to drug-biased decision-making in addiction, here showing a role for the orbitofrontal cortex

Low Striatal Dopamine D2-type Receptor Availability is Linked to Simulated Drug Choice in Methamphetamine Users.

Individuals with drug use disorders seek drugs over other rewarding activities, and exhibit neurochemical deficits related to dopamine, which is involved in value-based learning and decision-making. Thus, a dopaminergic disturbance may underpin drug-biased choice in addiction. Classical drug-choice assessments, which offer drug-consumption opportunities, are inappropriate for addicted individuals seeking treatment or abstaining. Fifteen recently abstinent methamphetamine users and 15 healthy controls completed two laboratory paradigms of 'simulated' drug choice (choice for drug-related vs affectively pleasant, unpleasant, and neutral images), and underwent positron emission tomography measurements of dopamine D2-type receptor availability, indicated by binding potential (BPND) for [18F]fallypride. Thirteen of the methamphetamine users and 10 controls also underwent [11C]NNC112 PET scans to measure dopamine D1-type receptor availability. Group analyses showed that, compared with controls, methamphetamine users chose to view more methamphetamine-related images on one task, with a similar trend on the second task. Regression analyses showed that, on both tasks, the more methamphetamine users chose to view methamphetamine images, specifically vs pleasant images (the most frequently chosen images across all participants), the lower was their D2-type BPND in the lateral orbitofrontal cortex, an important region in value-based choice. No associations were observed with D2-type BPND in striatal regions, or with D1-type BPND in any region. These results identify a neurochemical correlate for a laboratory drug-seeking paradigm that can be administered to treatment-seeking and abstaining drug-addicted individuals. More broadly, these results refine the central hypothesis that dopamine-system deficits contribute to drug-biased decision-making in addiction, here showing a role for the orbitofrontal cortex

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Studium humanitní vzdělanosti - Společenskovědní modulLiberal Arts and Humanities - Social Sciences ModuleFaculty of HumanitiesFakulta humanitních studi