Effective Connectivity within the Mesocorticolimbic System during Resting-State in Cocaine Users

Abstract

Objective: Although effective connectivity between brain regions has been examined in cocaine users during tasks, no effective connectivity study has been conducted on cocaine users during resting-state. In the present functional magnetic resonance imaging study, we examined effective connectivity in resting-brain, between the brain regions within the mesocorticolimbic dopamine system, implicated in reward and motivated behavior, while the chronic cocaine users and controls took part in a resting-state scan by using a spectral Dynamic causal modeling (spDCM) approach.Method: As part of a study testing cocaine cue reactivity in cocaine users (Ray et al., 2015b), 20 non-treatment seeking cocaine-smoking (abstinent for at least 3 days) and 17 control participants completed a resting state scan and an anatomical scan. A mean voxel-based time series data extracted from four key brain areas (ventral tegmental area, VTA; nucleus accumbens, NAc; hippocampus, medial frontal cortex) within the mesocorticolimbic dopamine system during resting-state from the cocaine and control participants were used as input to the spDCM program to generate spDCM analysis outputs.Results: Compared to the control group, the cocaine group had higher effective connectivity from the VTA to NAc, hippocampus and medial frontal cortex. In contrast, the control group showed a higher effective connectivity from the medial frontal cortex to VTA, from the NAc to medial frontal cortex, and on the hippocampus self-loop.Conclusions: The present study is the first to show that during resting-state in abstaining cocaine users compared to controls, the VTA initiates an enhanced effective connectivity to NAc, hippocampus and medial frontal cortex areas within the mesocorticolimbic dopamine system, the brain’s reward system. Future studies of effective connectivity analysis during resting-state may eventually be used to monitor treatment outcome.

Parallel cortical-brainstem pathways to attentional analgesia

“…We employed stochastic DCM, which allows for modelling of random neuronal noise in 559 the system, to improve network resolution in brainstem areas significantly affected by physiological 560 noise (Brooks et al, 2013). This routine was shown to improve the characterization of network 561 structure and parameter inference over deterministic DCM (Daunizeau et al, 2012;Osório et al, 562 2015) and has been widely used in resting state and task-based fMRI studies since its release (Kahan 563 et al, 2014;Ma et al, 2015Ma et al, , 2014Ray et al, 2016;Zhang et al, 2015). Bayesian Model selection 564 validated the results of the gPPI by excluding, for lack of evidence, a model where no connection was 565 modulated by task.…”

The Mesolimbic Dopamine System in Chronic Pain and Associated Affective Comorbidities

“…The contribution of reduced VTA activity to mesolimbic affective disorders is supported by the finding that deep brain stimulation (DBS) of the VTA or the associated medial forebrain bundle is effective in treating chronic refractory cluster headaches and treatment-resistant depression (36,37). Alterations in VTA-NAc connectivity have also been observed in individuals with substance abuse disorders during active use as well as during abstinence phases; such changes may further affect executive or affective pain-processing centers (25,38,39). Specifically, changes in VTA-NAc connectivity in individuals with substance abuse disorders occur in an opposite direction to those observed in individuals with depression, with 3-day abstinent cocaine users showing increased effective connectivity from the VTA to the NAc and medial PFC (mPFC) (38).…”

“…Alterations in VTA-NAc connectivity have also been observed in individuals with substance abuse disorders during active use as well as during abstinence phases; such changes may further affect executive or affective pain-processing centers (25,38,39). Specifically, changes in VTA-NAc connectivity in individuals with substance abuse disorders occur in an opposite direction to those observed in individuals with depression, with 3-day abstinent cocaine users showing increased effective connectivity from the VTA to the NAc and medial PFC (mPFC) (38). However, another study found decreased functional connectivity between the VTA and NAc of active cocaine users (39).…”

Modeling Causal Relationships among Brain Areas in the Mesocorticolimbic System during Resting-State in Cocaine Users Utilizing a Graph Theoretic Approach

“…The purpose of the present research was to investigate EC among all the MCLS brain areas [ 2 ] in cocaine smokers at resting-state using fMRI. This research is an extension of Gu et al [ 9 ] and Ray et al [ 8 ], and provides the first comprehensive examination of EC within cocaine users’ MCLS, utilizing baseline BOLD signal. The spatial patterns of resting-state correlation data are stable, in that they are similar across multiple resting-states (such as eyes-open and fixation) and across individuals and sessions.…”

“…Using functional magnetic resonance imaging (fMRI) technique, resting-state functional connectivity (RSFC; how individual brain regions are integrated during resting-state) has been examined on MCLS in cocaine users [ 8 ]. Also, a few effective connectivity (EC; the causal influence that one brain region exerts over another) studies have been conducted on cocaine users during resting-state scans and experimental tasks (working memory, response inhibition) [ 8 ]. The purpose of the present research was to investigate EC among all the MCLS brain areas [ 2 ] in cocaine smokers at resting-state using fMRI.…”