Impaired Functional Connectivity Within and Between Frontostriatal Circuits and Its Association With Compulsive Drug Use and Trait Impulsivity in Cocaine Addiction

Abstract

IMPORTANCE Converging evidence has long identified both impulsivity and compulsivity as key psychological constructs in drug addiction. Although dysregulated striatal-cortical network interactions have been identified in cocaine addiction, the association between these brain networks and addiction is poorly understood. OBJECTIVES To test the hypothesis that cocaine addiction is associated with disturbances in striatal-cortical communication as captured by resting-state functional connectivity (rsFC), measured from coherent spontaneous fluctuations in the blood oxygenation level-dependent functional magnetic resonance imaging signal, and to explore the relationships between striatal rsFC, trait impulsivity, and uncontrolled drug use in cocaine addiction. DESIGN, SETTING, AND PARTICIPANTS A case-control, cross-sectional study was conducted at the National Institute on Drug Abuse Intramural Research Program outpatient magnetic resonance imaging facility. Data used in the present study were collected between December 8, 2005, and September 30, 2011. Participants included 56 non-treatment-seeking cocaine users (CUs) (52 with cocaine dependence and 3 with cocaine abuse) and 56 healthy individuals serving as controls (HCs) matched on age, sex, years of education, race, estimated intelligence, and smoking status. MAIN OUTCOMES AND MEASURES Voxelwise statistical parametric analysis testing the rsFC strength differences between CUs and HCs in brain regions functionally connected to 6 striatal subregions defined a priori. RESULTS Increased rsFC strength was observed predominantly in striatal-frontal circuits; decreased rsFC was found between the striatum and cingulate, striatal, temporal, hippocampal/amygdalar, and insular regions in the CU group compared with the HCs. Increased striatal-dorsal lateral prefrontal cortex connectivity strength was positively correlated with the amount of recent cocaine use (uncorrected P < .046) and elevated trait impulsivity in the CUs (uncorrected P < .012), and an index reflecting the balance between striatal-dorsal anterior cingulate cortex and striatal-anterior prefrontal/orbitofrontal cortex circuits was significantly associated with loss of control over cocaine use (corrected P < .012). CONCLUSIONS AND RELEVANCE Cocaine addiction is associated with disturbed rsFC in several specific striatal-cortical circuits. Specifically, compulsive cocaine use, a defining characteristic of dependence, was associated with a balance of increased striatal-anterior prefrontal/orbitofrontal and decreased striatal-dorsal anterior cingulate connectivity; trait impulsivity, both a risk factor for and a consequence of cocaine use, was associated with increased dorsal striatal-dorsal lateral prefrontal cortex connectivity uniquely in CUs. These findings provide new insights toward the neurobiological mechanisms of addiction and suggest potential novel therapeutic targets for treatment.

Internet Game Overuse Is Associated With an Alteration of Fronto-Striatal Functional Connectivity During Reward Feedback Processing

“…This reduced functional coupling between the ventral striatum and dACC is consistent with previous findings. Intrinsic connectivity of the ventral striatum-dACC has been shown to be associated with greater severity of nicotine (59) and cocaine addiction (60). Also, Crane et al (61) have reported that the high-risk group in alcohol-use disorder (i.e., binge drinkers) have difficulty engaging this network during reward processing.…”

Mobilization of Medial and Lateral Frontal-Striatal Circuits in Cocaine Users and Controls: An Interleaved TMS/BOLD Functional Connectivity Study

“…While the functional connectivity of these circuits in cocainedependent individuals has been measured in a resting state Hu et al, 2015;Li et al, 2000;Tomasi et al, 2010), the goal of this study was to investigate the functional connectivity in these circuits when they were engaged by an external source. The primary results demonstrate that (1) ventral striatal areas responsible for limbic arousal are not as responsive to the same level of medial prefrontal stimulation in cocaine users as controls (consistent with opponent process theory), (2) dorsal striatal areas typically implicated in cognitive control and habit formation have similar response profiles in cocaine users and controls, and (3) the reciprocal relationship between DLPFC stimulation and Brodmann 10 (MPFC) attenuation observed in controls is disrupted in cocaine users.…”

“…This was motivated by the knowledge that cocaine users appear to have a very low neural response to natural rewards (Cheetham et al, 2010), which typically engage the limbic system (eg the ventral MPFC, ACC, and striatum) (Asensio et al, 2010a;Kelley and Berridge, 2002). In addition, several resting state functional MRI studies have demonstrated lower baseline resting state functional connectivity with the MPFC in cocaine users Gu et al, 2007;Tomasi et al, 2010), though other studies have demonstrated that cocaine users have higher connectivity in these circuits (Camchong et al, 2011;Hu et al, 2015). The present study demonstrated that left frontal pole stimulation in the controls led to an increase in BOLD signal in a network of limbic regions including the caudate, parahippocampal gyrus, and the amygdala.…”

“…While task-based neuroimaging studies that probe frontalstriatal circuitry involved in arousal to non-drug cues typically reveal 'hypofrontality' among cocaine users (Asensio et al, 2010a), recent resting state neuroimaging studies investigating these limbic circuits have revealed higher resting state functional connectivity in mesolimbic frontal-striatal circuits relative to controls (Camchong et al, 2011;Hu et al, 2015) (Note: lower connectivity between anterior cingulate-striatal circuit has also been observed (Hu et al, 2015)). There are several possible interpretations to the apparent gap in the results of task-based neuroimaging and resting state neuroimaging studies.…”

Disrupted Resting-State Brain Functional Architecture in Amphetamine-Type Stimulant Abusers

“…Rs-fMRI involves analysis of spontaneous brain function using blood oxygen level-dependent contrasts in the absence of a task, rendering it suitable for clinical applications [11]. Rs-fMRI has been successfully applied to the characterization of brain function disturbances in substance-dependent populations, including individuals addicted to heroin [12][13][14][15], nicotine [16][17][18][19], and cocaine [20,21]. These rs-fMRI findings provide evidence that regions related to reward, memory and learning, cognitive control, motivation, and salience evaluation are involved in addiction [22].…”