Addiction related alteration in resting-state brain connectivity
Introduction
Drug addiction is a major health problem in modern society. It is characterized by the failure to resist one's impulses to obtain and take certain types of addictive drugs despite serious negative consequences (Volkow and Li, 2004). Chronic addictive drug use is often related to abnormal functional organization in the brain, which leads to habitually hypersensitivity to the drug and drug-related cues and ensures their compulsive patterns of drug-seeking behavior (Kalivas and Volkow, 2005).
Resting-state functional connectivity is assessed by the correlation of spontaneous fluctuations of blood oxygen level-dependent (BOLD) signals in different regions of the “resting” brain and is thought to provide a measure of its functional organization (Fox and Raichle, 2007). Studies have outlined a number of resting-state networks corresponding to critical brain functional organizations including movement, vision, audition, language, episodic memory, executive function, and salience detection (Fox and Raichle, 2007). During the acquisition of resting-state functional magnetic resonance imaging (fMRI) data, participants are asked to rest quietly instead of performing tasks, making it potentially more readily applicable than functional activation MRI in clinical settings. A number of groups have begun to study the resting-state connectivity in a variety of neuropsychiatric disorders such as Alzheimer's disease, depression, and schizophrenia (Greicius, 2008, Liu et al., 2007, Wang et al., 2007, Zhou et al., 2008).
According to models of addiction, the main brain regions underlying addiction make up a network of, at a minimum, four interdependent and overlapping circuits (Baler and Volkow, 2006): (i) reward, involving the nucleus accumbens and ventral pallidum; (ii) memory and learning, including the amygdala and hippocampus; (iii) cognitive control, located in the prefrontal cortex and dorsal anterior cingulate cortex; and (iv) motivation and/or drive and salience evaluation, located in the orbital frontal cortex. In addition, amygdala and ventral/rostral anterior cingulate cortex (including subgenual area), regions that are associated with craving and emotional regulation, are also likely to affect the reactivity of the above circuits and parts of this network (Bechara, 2005, Bush et al., 2000, Volkow et al., 2005). These regions are modulated by dopamine and interconnected mostly through glutamatergic and GABA-ergic projections. The interactions between these regions are integrated to generate the behavioral output toward a reinforcing stimulus (O'Doherty, 2004), such that addictive drugs intensely activate the reward and motivation circuits, usurp systems underlying reward-related learning and memory, and hijack cognitive control resources (Baler and Volkow, 2006, Bechara, 2005, Everitt and Robbins, 2005, Garavan and Hester, 2007, Goldstein and Volkow, 2002). As a result, under addiction, the saliency value of a drug and its related cues are enhanced, while the inhibitory control is weakened, setting up the stage for an unrestrained cycle which leads to compulsive drug-seeking without regard to its negative consequences.
The neurobiological foundation of these models is mainly based on the results of functional activation studies in human addicts and the observation that exposure to addictive drugs produces persistent structural and functional changes on cells within this network (Garavan et al., 2000, Goldstein et al., 2007, Kalivas and O'Brien, 2008, Tomasi et al., 2007, Yang et al., 2009). To date, the resting-state functional connectivity within the key regions of drug addiction has not been extensively studied in human addicts. Therefore, in this study, we investigated whether there is any addiction related alteration in resting-state functional connectivity in this network with fMRI data acquired during resting state from chronic heroin users and non-addicted controls.
Section snippets
Participants
Twenty-seven right-handed male volunteers, including 14 chronic heroin users (HU, heroin using (from the time of their initial heroin use until the time of scanning) for 7.11 ± 2.82 years, range from 2 to 10 years) and 13 non-addicted controls (CN), participated in this study. All HU were recruited from Anhui Detoxification and Rehabilitation Center (Hefei, Anhui province, China), sought medical help on their own initiative and had a DSM-IV diagnosis of heroin dependence or abuse, and urine tests
Results
The results are shown in Table 2 and Fig. 2. Compared to controls, heroin users showed significantly (p < 0.05, corrected) stronger functional connectivity between NAc and ventral/rostral ACC, between NAc and medial OFC, between amygdala and lateral OFC, between lateral OFC and medial OFC, and within medial OFC. On the other hand, compared to controls, heroin users exhibited significantly weaker functional connectivity between lateral OFC and medial, dorsolateral PFC, within lateral OFC, between
Discussion
Addiction related alteration in functional connectivity within the key regions implicated in addiction is demonstrated with resting-state fMRI data acquired from chronic heroin users and non-addicted controls. Compared with controls, chronic heroin users showed increased functional connectivity between nucleus accumbens (NAc) and ventral/rostral anterior cingulate cortex (ACC), between NAc and orbital frontal cortex (OFC), and between amygdala and OFC; but reduced functional connectivity
Acknowledgments
We thank two anonymous reviewers and the editor of Neuroimage for their helpful comments and suggestions. This research is supported by the National Nature Science Foundation of China (30770713, 30870764, and 30670683), Ministry of Science and Technology of China (2006CB500705), Academic Exchange Fund of International Medical MR (N7014), and the US National Institutes of Health (RO1EB002009 and RO1DA17795). We thank Dr. De-Lin Sun, Xiao-Song He, and Zu-Ji Chen for their advice.
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Equally contributed to this work.