Increased corticolimbic connectivity in cocaine dependence versus pathological gambling is associated with drug severity and emotion-related impulsivity

Abstract

Neural biomarkers for the active detrimental effects of cocaine dependence (CD) are lacking. Direct comparisons of brain connectivity in cocaine-targeted networks between CD and behavioural addictions (i.e. pathological gambling, PG) may be informative. This study therefore contrasted the resting-state functional connectivity networks of 20 individuals with CD, 19 individuals with PG and 21 healthy individuals (controls). Study groups were assessed to rule out psychiatric co-morbidities (except alcohol abuse and nicotine dependence) and current substance use or gambling (except PG). We first examined global connectivity differences in the corticolimbic reward network and then utilized seed-based analyses to characterize the connectivity of regions displaying between-group differences. We examined the relationships between seed-based connectivity and trait impulsivity and cocaine severity. CD compared with PG displayed increased global functional connectivity in a large-scale ventral corticostriatal network involving the orbitofrontal cortex, caudate, thalamus and amygdala. Seed-based analyses showed that CD compared with PG exhibited enhanced connectivity between the orbitofrontal and subgenual cingulate cortices and between caudate and lateral prefrontal cortex, which are involved in representing the value of decision-making feedback. CD and PG compared with controls showed overlapping connectivity changes between the orbitofrontal and dorsomedial prefrontal cortices and between amygdala and insula, which are involved in stimulus-outcome learning. Orbitofrontal-subgenual cingulate cortical connectivity correlated with impulsivity and caudate/amygdala connectivity correlated with cocaine severity. We conclude that CD is linked to enhanced connectivity in a large-scale ventral corticostriatal-amygdala network that is relevant to decision making and likely to reflect an active cocaine detrimental effect.

Shared Microstructural Features of Behavioral and Substance Addictions Revealed in Areas of Crossing Fibers

“…FA within this region has been positively associated with reward-related nucleus accumbens activity in healthy adults (53). Thus, it is possible that reduced internal capsule anisotropy may be a neural structural mechanism for blunted ventral striatal activity previously reported in both GD and CUD populations(4, 59, 60), or for alterations in ventral striatal functional connectivity recently reported in both GD and CUD individuals (9). …”

“…To our knowledge, no prior studies have assessed the effects of acute cocaine on dMRI measures, and this will be an important area for further research. A further limitation of this study is the absence of a common measure of addiction severity which would have allowed us to explore relationships between neuroimaging measures and illness severity, as has been done in functional MRI studies; e.g., (9, 67). …”

“…Neuroimaging data suggest similarities between behavioral and substance addictions which may relate to disease etiology (1–9). However, direct comparisons between addiction subtypes are needed to confirm this hypothesis and to advance pathophysiological understanding of disorder subtypes via identification of unique versus shared neurobiological characteristics (10), as is consistent with ongoing transdiagnostic research efforts (11–13).…”

“…In addition, recent studies indicate neural functional similarities between CUD and gambling disorder GD (4, 9). However, the extent to which neural structural alterations are truly shared across addictive disorders has not been assessed previously.…”

Unseen scars: Cocaine patients with prior trauma evidence heightened resting state functional connectivity (RSFC) between the amygdala and limbic-striatal regions

“…Cocaine use disorder (CUD) patients also evidence “heightened coupling” of RSFC signatures, with the amygdala exhibiting stronger connectivity with nodes of the motivational circuitry including the caudate, putamen, nucleus accumbens, and insula (Contreras-Rodriguez et al, 2016; Gu et al, 2010; Konova et al, 2015). Though RSFC has promise for characterizing dysfunctional neural circuitry in addiction, the findings across CUD studies are not always consistent (Ma et al, 2015).…”