Abnormal resting‐state functional connectivity of the nucleus accumbens in multi‐year abstinent heroin addicts

Abstract

Functional neuroimaging studies suggest that abnormal brain functional connectivity may be the neural underpinning of addiction to illicit drugs and of relapse after successful cessation therapy. Aberrant brain networks have been demonstrated in addicted patients and in newly abstinent addicts. However, it is not known whether abnormal brain connectivity patterns persist after prolonged abstinence. In this cross-sectional study, whole-brain resting-state functional magnetic resonance images (8 min) were collected from 30 heroin-addicted individuals after a long period of abstinence (more than 3 years) and from 30 healthy controls. We first examined the group differences in the resting-state functional connectivity of the nucleus accumbens (NAc), a brain region implicated in relapse-related processes, including craving and reactivity to stress following acute and protracted withdrawal from heroin. We then examined the relation between the duration of abstinence and the altered NAc functional connectivity in the heroin group. We found that, compared with controls, heroin-dependent participants exhibited significantly greater functional connectivity between the right ventromedial prefrontal cortex and the NAc and weaker functional connectivity between the NAc and the left putamen, left precuneus, and supplementary motor area. However, with longer abstinence time, the strength of NAc functional connectivity with the left putamen increased. These results indicate that dysfunction of the NAc functional network is still present in long-term-abstinent heroin-dependent individuals.

Neurogenetics of acute and chronic opiate opioid abstinence treating symptoms and the cause

“…The authors correctly suggest that sustained neural effect of opioid dependence on methadone maintenance including hyperactivation in the memory circuit and impairment in the control circuit, support the role of the memory circuitry in relapse, and may help redefine targets for treatment. Interestingly, our findings with KB220Z showed an enhanced resting state in abstinent heroin addicts accompanied with an enhanced functionality in the control circuit (cingulate gyrus) as well as a reduced or balanced activity of the hippocampus putamen seems to help explain the delayed onset of relapse in poly-drug abusers obtained, in earlier work (84).…”

“…The following aspects of the addiction process should be considered as the focus of research. The protracted seeking responses, as observed in heroin addicts (83,84), these impulses are controlled by stimuli in the environment (possibly epigenetic) and eventually become compulsive. After prolonged exposure to the drug (certainly beyond early withdrawal symptoms) and especially in some vulnerable individuals, addiction may be a life-long issue, due to genetic polymorphisms of reward genes (85).…”

“…Along these lines, Zou et al (84) using functional Magnetic Resonance Imaging (fMRI), showed that 30 heroin-addicted subjects with three years of abstinence compared to healthy controls had weaker connections between reward processing parts of the brain and the areas associated with motor skills. Moreover, some of the subjects showed potential for healing thereby reducing the risk for relapse.…”

“…This work demonstrates that the brain might heal following heroin insult, and indicates that treatment should be continued for at least three years. However, Zou et al (84) did not test for genetic reward gene polymorphisms. Certainly formal genetic testing will help the clinician decide the length of potential treatments.…”

The Negative Affect of Protracted Opioid Abstinence: Progress and Perspectives From Rodent Models

“…Notably, the opioid-abstinent human brain (at 2 weeks to 7 months of abstinence) shows alterations of functional connectivity strength between brain networks responsible for cognitive control, reward, and stress (26)(27)(28)(29). Furthermore, former heroin-dependent individuals who abstained for more than 3 years showed reduced positive correlation within the default mode and visual networks (30) and altered nucleus accumbens (NAc) functional connectivity, depending on the duration of the abstinence period (31). The latter reports demonstrate that the disruption of general brain connectivity and alterations in a main reward center persist, even after multiple years of abstention.…”