Mirror Neural Activity Evoked By Cue-related Cues In Heroin Abstainers

Finding effective treatments for drug dependency is one of the most challenging issues of modern times and psychological dependence is the key there-into. The cue-induced craving is one of the most main reasons for psychological dependence. The current study targeted the cue-induced craving and use the functional magnetic resonance imaging techniques (fMRI) method to study the activation of different areas in the drug dependent individual's brain when they were shown the related cues. The mirror neuron system(MNS) will be emphasized in order to illustrate the role and function of MNS during the process of craving elicitation and the possible relationship between the activation of mirror neuron system and craving elecited by drug related cues. Furthermore, we will analysis how the cue elicits the mirror neuron system and reward brain area and how they influence each other. We try to clarify the potential rules of psychological craving after the drug dependence individual has been in withdrawl and hope our research will provide a new thread and direction for the treatment of drug dependence and prevention.13abstinent heroin dependent individuals (AHD) and12no-drug use health participants (NDP) involved in the experiment. We conducted2(groups:abstinent drug dependent group, no-drug use group)×2(related condition:related cue, unrelated cue)×3(cue types:static object, tool and action) experiment design. The two within-subject variances constitute six kinds of specific stimulus, including addiction drug and "C-drug"(drug counterpart cue stimuli), tool (paraphernalia) and "C-tool"(paraphernalia counterpart cue stimuli), action (smoking and injection heroin) and "C-action"(action counterpart cue stimuli).We explored and analysis the neuro activation of cue-induced reactivity and differences between and within groups.All imaging data were acquired on a3.0T MRI scanner (Siemens Magneto TrioTime syngo). Anatomical sequence was run first, following the T1scans,36axial slices covering the whole brain were acquired with a gradient echo-planar imaging sequence. Image processing was carried out using SPM8, implemented in Matlab 2010a.Using standard SPM procedures, images were realigned and normalized to the Montreal Neurological Institute (MNI) standard brain. The normalized images of2×2×2mm were smoothed by a full-width half maximum8×8×8Gaussian kernel. This smoothing is necessary to fulfill the statistical assumptions of the random-effect analysis.Preprocessed data were analyzed subject-by-subject using the pre-procession batch, and then conducted group analysis using flexible factorial. Three t-contrast maps were calculated:drug versus "C-drug", tool versus "C-tool" and action versus "C-action" to study neural activity which was evoked by the drug-related cues and difference between the groups. Action versus drug and C-action versus C-drug were also calculated to explore the activities elicited by drug related cues and counterpart stimulus.Behavioral experimental data indicated that there was no significant difference in reaction time of cue-induced reactivity between AHD and the NDP for total trails, but both group showed significant difference when they were shown the different type of cues. The reaction time when participants shown the drug or C-drug cues were significant longer than they shown the tool or C-tool one. The interaction of cue relativity and cue type were significant, the ANOVA analysis indicated that the reaction time when they shown the action cues was longer than when they shown C-action cues.Multiple t-contrasts between related-cues and unrelated-cues were conducted to find out the cue neuroal reactivity which was accompanied with craving. The result showed that drug-related cues activated more brain regions than the corresponding cues which include the occipital-temporal cortex, superior parietal lobule and inferir parietal lobule, orbito-frontal cortex, anterior cingulate cortex and posterior cingulate, hippocampus, thalamus and midbrain. The comparison between activated brain area under drug and "C-drug" cues showed more activation in right hippocampus and the posterior cingulate activation for abstinent group, great signal change was elected in anterior cingulate gyrus and posterior cingulate when abstinent participants were observing the drug use action pictures as compared with counterpart action stimulus. The hemodynamic response in temporal and parietal lobe correlated was consistent when we performed t-contrasts between "C-action" and "C-drug" condition for both of the two group subjects. Abstinent subjects evoked the bilateral middle temporal gyrus, bilateral inferior parietal lobule, the left superior parietal lobule and the right inferior frontal gyrus when they watched drug taking pictures as compared to usual manual motion. The conjunction analysis showed that conjoined action versus drug and "C-action" versus "C-drug" contrast was executed; hippocampus and midbrain were detected for abstinent group. The health control group only evoked occipital-temporal cortex when compared between under "C-action" and "C-drug" cues. In particular, neither hippocampus nor midbrain had an evident response after the same analysis at the health counterpart group.The analysis of ROI on the activated area under the related cues of abstinent group showed that activation level of bilateral middle temporal gyrus, right inferior frontal gyrus, left superior parietal lobule/post-central gyrus, and bilateral inferior parietal lobule have significant difference during the observation of different type drug related cues. The activation level of these areas is consonance with the degree of craving which induced by the related cues.The result of the study indicated that abstinent drug dependent individuals still have craving for the drugs after a period of abstinent symptoms disappearing. The craving would be induced by the related cues which accompany with the activation of mediumtemporal gyrus, inferior parietal lobule, and inferior frontal gyrus and so on, which belong to mirror neuro system. The area was susceptible to different drug related cues and they might involved in the mental simulation of drug use activation which participates in quick automation processing to drug related cues. Anterior cingulate cortex, posterior cingulated cortex, hypothalamus, hypothalamus,mesocerebrumalong with the limbic system play the important role in the cue-induced craving. So, our conclusion for the study is that the cue-induced craving related to the activation of hypothalamus, cingulate cortex, prefrontal cortex, parietal lobe which correlated to psychological function, e.g. decision making, memory, stressresponse and inhibition control and so on. These areas might work with mirror neuro system under the related cues and constitute of the neuro basis of cue-induced craving.