The Alteration Of Functional Connectivity In Heroin Dependent Individuals-A Resting State FMRI Study

ObjectiveIt is widely accepted that abnormal brain function of neural circuits involved in reward, cognitive control, memory and motivation/drive is the main reason for drug addiction. Dysfunction in the addicted brain makes the addicts in uncontrollable, compulsive drug seeking and use, and that persists even in spite of negative healthy and social consequences. Up to now, majority of fMRI studies explored addicted brain function by some special tasks. However, few fMRI studies focus on the alteration of brain function when addicts is not performing a explicit task (in resting state). Resting–state fMRI is a newly powerful tool to describing the spatial patterns of regional interaction in brain resting state and has been extensively applied in many mental disorders. To investigate the characteristic of correlation of regional functional connectivity in addicted brain, we assessed the alteration of the functional connectivity in heroin dependent people using resting-state fMRI based on brain seed-region analysis approach, in which the brain regions involved in addiction documented extensively in literature. Prefrontal cortex (PFC) and caudate were selected as the region of interest (ROI), which are implicated in inhibitory control, reward and habit learning.MethodsIn the functional connectivity analysis with the bilateral PFC as ROI (study one), twelve male chronic heroin users (mean age, 32.2±4.8 years; mean duration of education, 10.1±2.5 years; mean scores of Fagerstrom Test for Nicotine Dependence (FTND), 7.17±1.2) and 12 age-, gender- and nicotine dependence-matched healthy subjects(mean age, 33.3±7.8 years; mean duration of education, 11.6±2.3 years; mean scores of FTND, 7.0±1.2) participated in the study one. In the functional connectivity analysis with the caudate as ROI (study two), fifteen male chronic heroin users (mean age, 32.4±5.7 years; mean duration of education, 10.2±2.7 years; mean cigarettes per day, 19.0±5.7) and 15 age-, gender- and nicotine dependence- matched healthy subjects (mean age, 33.3±7.5 years; mean duration of education, 11.0±2.1 years; mean cigarettes per day, 17.7±5.3) participated in the study two. All the participants undertook a resting-state fMRI scan using General Electric 3.0 Tesla scanner with an 8-channels head coil. Functional connectivity was analyzed based on resting-state fMRI data in order to determine the temporal correlation between PFC as well as caudate and the other regions on the whole brain scale by Statistical Parametric Mapping (SPM). Finally, one-sample t-test and two-sample t-test were applied to determine the alterations of functional connectivity pattern of PFC and caudate in chronic heroin addicted brain. ResultsThere were no significant differences in the age (t = 0.8, P > 0.05),the level of education (t =1.5, P > 0.05), FTND scores (t =0.3, P > 0.05), between the heroin group and healthy controls by two-sample t-test in PFC- analysis. Similarly, no statistically significant differences in the age (t=0.4, P>0.05),the level of education (t=0.9, P>0.05), cigarettes per day (t =0.6, P>0.05), between the heroin group and healthy controls in caudate- analysis were found. The heroin group showed higher strength of functional connectivity between PFC and orbitofrontal cortex (OFC), lentiform nucleus, but lower between PFC and anterior cingutate cortex (ACC) than that in healthy subjects (t=3.5, P<0.001). In the caudate-seed region analysis, the heroin group showed higher strength of functional connectivity between caudate and lentiform nucleus, amygdala, hippocampus, but lower between caudate and dorsal ACC (t=2.8, P<0.005).ConclusionWe found the increased functional connectivity between ROIs and OFC, lentiform nucleus, amygdala and hippocampus, the decreased between ROIs and ACC. The brain regions of which the strength of functional connectivity significantly increased with ROIs were involved in reward, memory and motivation/drive, but the decreased were involved in cognitive control. These abnormal interaction between the neural circuits suggests that enhanced salience value of drug but weakened ability of cognitive control constitutes the main mechanisms of heroin addiction.