Executive control network resting state fMRI functional and effective connectivity and delay discounting in cocaine dependent subjects compared to healthy controls.

Resting state functional magnetic resonance imaging (fMRI) has been used to study functional connectivity of brain networks in addictions. However, most studies to-date have focused on the default mode network (DMN) with fewer studies assessing the executive control network (ECN) and salience network (SN), despite well-documented cognitive executive behavioral deficits in addictions. The present study assessed the functional and effective connectivity of the ECN, DMN, and SN in cocaine dependent subjects (CD) (n = 22) compared to healthy control subjects (HC) (n = 22) matched on age and education. This study also investigated the relationship between impulsivity measured by delay discounting and functional and effective connectivity of the ECN, DMN, and SN. The Left ECN (LECN), Right ECN (RECN), DMN, and SN functional networks were identified using FSL MELODIC independent component analysis. Functional connectivity differences between CD and HC were assessed using FSL Dual Regression analysis and FSLNets. Effective connectivity differences between CD and HC were measured using the Parametric Empirical Bayes module of Dynamic Causal Modeling. The relationship between delay discounting and functional and effective connectivity were examined using regression analyses. Dynamic causal modeling (DCM) analysis showed strong evidence (posterior probability > 0.95) for CD to have greater effective connectivity than HC in the RECN to LECN pathway when tobacco use was included as a factor in the model. DCM analysis showed strong evidence for a positive association between delay discounting and effective connectivity for the RECN to LECN pathway and for the DMN to DMN self-connection. There was strong evidence for a negative association between delay discounting and effective connectivity for the DMN to RECN pathway and for the SN to DMN pathway. Results also showed strong evidence for a negative association between delay discounting and effective connectivity for the RECN to SN pathway in CD but a positive association in HC. These novel findings provide preliminary support that RECN effective connectivity may differ between CD and HC after controlling for tobacco use. RECN effective connectivity may also relate to tobacco use and impulsivity as measured by delay discounting.

Dynamic Causal Modeling Self-Connectivity Findings in the Functional Magnetic Resonance Imaging Neuropsychiatric Literature.

Dynamic causal modeling (DCM) is a method for analyzing functional magnetic resonance imaging (fMRI) and other functional neuroimaging data that provides information about directionality of connectivity between brain regions. A review of the neuropsychiatric fMRI DCM literature suggests that there may be a historical trend to under-report self-connectivity (within brain regions) compared to between brain region connectivity findings. These findings are an integral part of the neurologic model represented by DCM and serve an important neurobiological function in regulating excitatory and inhibitory activity between regions. We reviewed the literature on the topic as well as the past 13 years of available neuropsychiatric DCM literature to find an increasing (but still, perhaps, and inadequate) trend in reporting these results. The focus of this review is fMRI as the majority of published DCM studies utilized fMRI and the interpretation of the self-connectivity findings may vary across imaging methodologies. About 25% of articles published between 2007 and 2019 made any mention of self-connectivity findings. We recommend increased attention toward the inclusion and interpretation of self-connectivity findings in DCM analyses in the neuropsychiatric literature, particularly in forthcoming effective connectivity studies of substance use disorders.

Resting-State Directional Connectivity and Anxiety and Depression Symptoms in Adult Cannabis Users.

BACKGROUND: Anxiety and depression symptoms are common among cannabis users and could be a risk factor for cannabis use (CU) disorder. Thus, it is critical to understand the neuronal circuits underlying the associations between CU and these symptoms. Alterations in resting-state functional connectivity within and/or between the default mode network and salience network have been reported in CU, anxiety, and depressive disorders and thus could be a mechanism underlying the associations between CU disorder and anxiety/depression symptoms. METHODS: Using resting-state functional magnetic resonance imaging, effective connectivities (ECs) among 9 major nodes from the default mode network and salience network were measured using dynamic causal modeling in 2 datasets: the Human Connectome Project (28 CU participants and 28 matched non-drug-using control participants) and a local CU study (21 CU participants and 21 matched non-drug-using control participants) in separate and parallel analyses. RESULTS: Relative to the control participants, right amygdala to left amygdala, anterior cingulate cortex to left amygdala, and medial prefrontal cortex to right insula ECs were greater, and left insula to left amygdala EC was smaller in the CU group. Each of these ECs showed a reliable linear relationship with at least one of the anxiety/depression measures. Most findings on the right amygdala to left amygdala EC were common to both datasets. CONCLUSIONS: Right amygdala to left amygdala and anterior cingulate cortex to left amygdala ECs may be related to the close associations between CU and anxiety/depression symptoms. The findings on the medial prefrontal cortex to right insula and left insula to left amygdala ECs may reflect a compensatory mechanism.

Preliminary Findings of Weaker Executive Control Network Resting State fMRI Functional Connectivity in Opioid Use Disorder compared to Healthy Controls.

Objective: Resting state functional magnetic resonance imaging (fMRI) functional connectivity has been used as a tool to study brain mechanisms associated with addictions. Recent research in substance use disorders has focused on three brain networks termed the default mode network (DMN), salience network (SN), and executive control network (ECN). The purpose of this study was to examine the functional connectivity of those three networks in opioid use disorder (OUD) subjects compared to healthy control subjects (HC). Methods: The present study investigated functional connectivity differences between OUD subjects compared to HC using independent component analysis. This study also examined the relationship between functional connectivity and negative urgency scores, as well as compared the functional connectivity of severe OUD to mild or moderate OUD. Results: In OUD subjects (n=25) compared to HC (n=25), a cluster in the left dorsolateral prefrontal cortex within the left ECN had significantly weaker functional connectivity. No significant differences were found between groups for the functional connectivity of the DMN, SN, or right ECN. No significant associations were found between functional connectivity and negative urgency, and no differences were found between severe OUD and mild or moderate OUD. Conclusion: These novel preliminary results suggest that ECN functional connectivity may differ between OUD and HC. This finding is consistent with previous research showing altered executive function in OUD and supports further examination of ECN functional connectivity in association with treatment response in OUD. Given our relatively small sample size (50 subjects total; 25 subjects per group), our results should be treated as preliminary for hypothesis generation, and replication will be needed in future studies.