Modeling Causal Relationship Between Brain Regions Within the Drug-Cue Processing Network in Chronic Cocaine Smokers

Abstract

The cues associated with drugs of abuse have an essential role in perpetuating problematic use, yet effective connectivity or the causal interaction between brain regions mediating the processing of drug cues has not been defined. The aim of this fMRI study was to model the causal interaction between brain regions within the drug-cue processing network in chronic cocaine smokers and matched control participants during a cocaine-cue exposure task. Specifically, cocaine-smoking (15M; 5F) and healthy control (13M; 4F) participants viewed cocaine and neutral cues while in the scanner (a Siemens 3 T magnet). We examined whole brain activation, including activation related to drug-cue processing. Time series data extracted from ROIs determined through our General Linear Model (GLM) analysis and prior publications were used as input to IMaGES, a computationally powerful Bayesian search algorithm. During cocaine-cue exposure, cocaine users showed a particular feed-forward effective connectivity pattern between the ROIs of the drug-cue processing network (amygdala → hippocampus → dorsal striatum → insula → medial frontal cortex, dorsolateral prefrontal cortex, anterior cingulate cortex) that was not present when the controls viewed the cocaine cues. Cocaine craving ratings positively correlated with the strength of the causal influence of the insula on the dorsolateral prefrontal cortex in cocaine users. This study is the first demonstration of a causal interaction between ROIs within the drug-cue processing network in cocaine users. This study provides insight into the mechanism underlying continued substance use and has implications for monitoring treatment response.

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

“…Abstinence from alcohol was confirmed with a breathalyzer. At the end of the study, participants were compensated with a gift certificate worth $100 for their participation and were paid for their transportation expenses (Ray et al, 2015b). This research was approved by the Rutgers University Institutional Review Board.…”

“…To the best of our knowledge, only three functional magnetic resonance imaging (fMRI) effective connectivity studies have been done with cocaine users. As part of the study described here, we have reported effective connectivity among brain regions within the drug cue processing network using IMaGES (Ramsey et al, 2010), a Bayesian search algorithm, while chronic cocaine users viewed cocaine-related picture cues (Ray et al, 2015b). During cocaine cue exposure, cocaine users demonstrated a unique feed-forward effective connectivity pattern between the ROIs of the drug-cue processing network (amygdala→hippocampus→dorsal striatum→insula→medial frontal cortex, dorsolateral prefrontal cortex, anterior cingulate cortex) that was absent when the controls viewed the cocaine cues.…”

“…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.…”

“…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.…”

Brain Mapping of drug addiction in witdrawal condition based P300 Signals

“…The brain signal activity used in BCI can be measured using invasive or noninvasive techniques. The BCI based EEG equipment is one of the noninvasive techniques and it is not only used by patients but also by healthy users with various applications [1][2][3][4][5][6][7].Over the last few decades, EEG activities have been widely used to study the brain cognitive dysfunction and neurobiological alterations among drug addicts [8]. In addition to EEG spectral analysis to examine the effects of drug abuser on brain functionality (Davydov and Polunina, 2004;Franken et al, 2004;Polunina and Davydov, 2006;Fingelkurts et al, 2009) [9][10][11][12], brain event-related potential (ERP) components were evaluated as a reliable approach to study cognitive abilities related to information processing, selective attention, and memory updating of addicts [8].…”