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Abnormal salience attribution is implicated in heroin addiction. Previously, combining functional magnetic resonance imaging ( fMRI) and a drug cue-reactivity task, we demonstrated abnormal patterns of subjective response and brain reactivity in heroin-dependent individuals. However, whether the changes in cue-induced brain response were related to relapse was unknown. In a prospective study, we recruited 49 heroin-dependent patients under methadone maintenance treatment, a gold standard treatment (average daily dose 41.8 ± 16.0 mg), and 20 healthy subjects to perform the heroin cue-reactivity task during fMRI. The patients' subjective craving was evaluated. They participated in a follow-up assessment for 3 months, during which heroin use was assessed and relapse was confirmed by self-reported relapse or urine toxicology. Differences between relapsers and non-relapsers were analyzed with respect to the results from heroin-cue responses. Compared with healthy subjects, relapsers and non-relapsers commonly demonstrated significantly increased brain responses during the processing of heroin cues in the mesolimbic system, prefrontal regions and visuospatial-attention regions. However, compared with non-relapsers, relapsers demonstrated significantly greater cue-induced craving and the brain response mainly in the bilateral nucleus accumbens/subcallosal cortex and cerebellum. Although the cue-induced heroin craving was low in absolute measures, the change in craving positively correlated with the activation of the nucleus accumbens/subcallosal cortex among the patients. These findings suggest that in treatment-seeking heroin-dependent individuals, greater cue-induced craving and greater specific regional activations might be related to reward/craving and memory retrieval processes. These responses may predict relapse and represent important targets for the development of new treatment for heroin addiction. [ABSTRACT FROM AUTHOR]

The brain activity induced by heroin-related cues may play a role in the maintenance of heroin dependence. Whether the reinforcement or processing biases construct an everlasting feature of heroin addiction remains to be resolved. We used an event-related fMRI paradigm to measure brain activation in response to heroin cue-related pictures versus neutral pictures as the control condition in heroin-dependent patients undergoing short-term and long-term abstinence. The self-reported craving scores were significantly increased after cue exposure in the short-term abstinent patients (t = 3.000, P = 0.008), but no increase was found in the long-term abstinent patients (t = 1.510, P = 0.149). However, no significant differences in cue-induced craving changes were found between the two groups (t = 1.193, P = 0.850). Comparing between the long-term abstinence and short-term abstinence groups, significant decreases in brain activation were detected in the bilateral anterior cingulated cortex, left medial prefrontal cortex, caudate, middle occipital gyrus, inferior parietal lobule and right precuneus. Among all of the heroin dependent patients, the abstinence duration was negatively correlated with brain activation in the left medial prefrontal cortex and left inferior parietal lobule. These findings suggest that long-term abstinence may be useful for heroin-dependent patients to diminish their saliency value of heroin-related cues and possibly lower the relapse vulnerability to some extent. [ABSTRACT FROM AUTHOR]

Background: The formation of compulsive pattern of drug use is related to abnormal regional neural activity and functional reorganization in the heroin addicts’ brain, but the relationship between heroin-use-induced disrupted local neural activity and its functional organization pattern in resting-state is unknown. Methodology/Principal Findings: With fMRI data acquired during resting state from 17 male heroin dependent individuals (HD) and 15 matched normal controls (NC), we analyzed the changes of amplitude of low frequency fluctuation (ALFF) in brain areas, and its relationship with history of heroin use. Then we investigated the addiction related alteration in functional connectivity of the brain regions with changed ALFF using seed-based correlation analysis. Compared with NC, the ALFF of HD was obviously decreased in the right caudate, right dorsal anterior cingulate cortex (dACC), right superior medial frontal cortex and increased in the bilateral cerebellum, left superior temporal gyrus and left superior occipital gyrus. Of the six regions, only the ALFF value of right caudate had a negative correlation with heroin use. Setting the six regions as “seeds”, we found the functional connectivity between the right caudate and dorsolateral prefrontal cortex (dlPFC) was reduced but that between the right caudate and cerebellum was enhanced. Besides, an abnormal lateral PFC-dACC connection was also observed in HD. Conclusions: The observations of dysfunction of fronto-striatal and fronto-cerebellar circuit in HD implicate an altered balance between local neuronal assemblies activity and their integrated network organization pattern which may be involved in the process from voluntary to habitual and compulsive drug use. [ABSTRACT FROM AUTHOR]

Abstract: Craving is an important factor in relapse to drug abuse, and cue-induced craving is an especially powerful form of this construct. Neuroimaging methods have been utilized to study drug cue-induced craving and neural correlates in the human brain. However, very few studies have focused on characterizing craving and the neural responses to heroin-related cues in short-term abstinent heroin-dependent patients. Twenty-four heroin-dependent subjects and 20 demographically matched drug-naïve subjects participated in this study. An event-related cue-reactivity paradigm was employed, while changes in blood oxygen level-dependent (BOLD) signals were acquired by functional magnetic resonance imaging (fMRI). The heroin-dependent group reported significantly increased craving following exposure to heroin-related cues. Direct comparison between the two groups showed that brain activation to heroin-related minus neutral cues was significantly greater for the heroin-dependent group in the bilateral nucleus accumbens (NAc), caudate, putamen, amygdala, hippocampus/parahippocampus, midcingulate cortex, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), medial frontal gyrus (MeFG), midbrain, thalamus, left anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and subcallosal gyrus. Changes in craving in the heroin-dependent group correlated positively with brain activation in the bilateral NAc, caudate, right putamen, and left ACC. The abstinence duration correlated positively with brain activation in the left caudate and right parahippocampal gyrus. In conclusion, the cue-reactivity paradigm significantly activated neural responses in the mesolimbic dopamine (DA) system and prefrontal cortex (PFC) and induced increased craving in short-term abstinent heroin-dependent patients. We suggest that these response patterns characterize the high vulnerability of relapse in short-term abstinent heroin-dependent subjects. [Copyright &y& Elsevier]

Abstract: Methadone maintenance treatment (MMT) might cause the impairments of neuropsychological and neurotransmitter function in opioid addicts. Whether long-term MMT could lead to the impairment of white matter (WM) in heroin addiction brain is unclear. This study compared the WM integrity in the bilateral frontal lobe, temporal lobe, splenium and genu of corpus collasum (CC) between MMT patients (n =13), former heroin addicts (n =11) in prolonged abstinence (PA), and healthy control subjects (n =15) using diffusion tensor imaging (DTI). Fractional anisotropy (FA), apparent diffusion coefficient (ADC) and eigenvalues (λ ⊥, λ ||) were measured. The correlation between DTI measures and accumulated former heroin dose, total methadone consumption, and PA duration were determined. Although the PA subjects showed no difference in DTI measures relative to the controls, the extensive correlations between the former heroin consumption and the DTI measures were noted. The MMT subjects showed a decreased FA values in the left genu, as well as the increased ADC and λ ⊥ values in the left splenium of CC in comparison to the controls. Compared with the PA, the MMT subjects had a significantly increased ADC value in the bilateral splenium of CC. Importantly, the methadone dosage used in the MMT group was correlated with the FA value in the left splenium of CC and in the right frontal lobe. Our preliminary results suggest that methadone plays a role in the impairment of WM integrity in heroin users on long-term MMT and the normalization of WM injury may occur during abstinence. [Copyright &y& Elsevier]

Objective: To investigate the subjective craving and brain response to heroin-related cues in former heroin addicts on long-term methadone maintenance treatment. Methods: Fourteen participants completed an event-related functional magnetic resonance imaging task including heroin-related and nonheroin-related (neutral) cues. Craving self-reports were collected before and after the task. Results: Although no significant craving changes were associated with the task, blood oxygen-level dependence intensity was significantly greater during exposure to heroin-related cues, compared to neutral cues in brain areas studied. Conclusions and Scientific Significance: The results indicate that the learned brain response of former heroin addicts to drug-related stimuli may persist despite long-term methadone maintenance treatment. [ABSTRACT FROM AUTHOR]

Introduction: Methamphetamine has surpassed heroin as the most popular abused drug in China. Although the use of both heroin and methamphetamine leads to use disorders through dysfunction of the dopamine pathway, the incidence of psychiatric disorder caused by methamphetamine abuse is higher than the incidence of psychiatric disorder caused by heroin abuse. The difference in resting‐state function between heroin use disorder (HUD) and methamphetamine use disorder (MAUD) and the relationship between resting‐state function and psychiatric disorder related to MAUD are unknown. Methods: In the present study, 21 male individuals with MAUD, 21 demographically matched individuals with HUD, and 21 normal controls (NC) were recruited. The amplitude of low‐frequency fluctuation (ALFF) during resting‐state brain function was measured by magnetic resonance imaging. Psychiatric status was evaluated by the Symptom Checklist‐90 (SCL90). Results: Individuals with MAUD had increased SCL90 scores compared to those of the NC for anxiety, paranoia, and additional items, and the hostility score was significantly increased compared to that of individuals with HUD. There is no significant difference between HUD and NC individuals. Individuals with MAUD had increased ALFF compared to those of the NC for thalamus, right postcentral, and right inferior temporal gyri, but a decreased ALFF in the cerebellum. Individuals with HUD had significantly increased ALFF compared to those of the NC for left middle frontal gyrus but a decreased ALFF in the left postcentral gyrus. Individuals with MAUD had significantly increased ALFF compared to those of the HUD for thalamus, the right inferior temporal, and bilateral postcentral gyri, and the ALFF of cerebellum and left middle frontal was significantly increased. Conclusions: Methamphetamine can induce more serious psychiatric disorders than heroin. The resting‐state function involved in mood adjustment, the auditory, and memory‐related brain regions may affect psychotic symptoms related to MAUD. [ABSTRACT FROM AUTHOR]

Abstract: Exposure to addictive drugs has been associated with disrupted brain white matter integrity. A few studies have examined the white matter deficits in heroin users; however, the results were influenced by the use of substitution drugs such as methadone and buprenorphine. The present study assessed the alteration in white matter integrity and heroin-related neuropathology in heroin dependents who had not received any replacement therapy using quantitative diffusion tensor imaging (DTI). The study comprised 17 heroin-dependent (HD) subjects and 15 matched healthy controls (HC). Fractional anisotropy (FA) and eigenvalues (λ ┴, λ ||) of white matter in the whole brain were measured and compared using a voxel-based analysis. The correlation between DTI measurements in identified regions and history of heroin exposure was tested by partial correlation analysis. Compared with HCs, HD subjects displayed decreased FA in the bilateral frontal lobe sub-gyrus, cingulate gyrus, medial frontal gyrus, extra-nuclear, left temporal lobe sub-gyrus and right superior frontal gyrus. Among these regions, the HD group had significantly increased λ ┴ in the bilateral frontal lobe sub-gyrus, cingulate gyrus and extra-nuclear relative to the HC group. There were no group differences in λ ||. In addition, there were no significant correlations between duration of heroin use or accumulated dosage and FA or λ ┴ values. In conclusion, chronic heroin-dependent subjects had widespread disruption of white matter structural connectivity located mainly in anterior and superior regions of the brain. Damage to myelin other than axons was the primary pathological feature in the brain of the heroin user. [Copyright &y& Elsevier]

Abstract: Previous neuroimaging studies have demonstrated both structural and functional damages in heroin-dependent individuals. However, few studies investigated gray matter deficits and abnormal resting-state networks together in heroin-dependent individuals. In the present study, voxel-based morphometry (VBM) was used to identify brain regions with gray matter density reduction. Resting-state fMRI connectivity analysis was employed to assess potential functional abnormalities during resting-state. All clinical significances were investigated by examining their association with duration of heroin use. Compared with healthy subjects, heroin-dependent individuals showed significant reduction in gray matter density in the right dorsolateral prefrontal cortex (DLPFC) and a decrease in resting-state functional connectivity between the right DLPFC and left inferior parietal lobe (IPL). The gray matter density of the right DLPFC and its resting-state functional connectivity with the left IPL both showed significantly negative correlation with duration of heroin use, which were likely to be related to the functional impairments in decision-making and cognitive control exhibited by heroin-dependent individuals. Our findings demonstrated that long heroin dependence impairs the right DLPFC in heroin-dependent individuals, including structural deficits and resting-state functional impairments. [ABSTRACT FROM AUTHOR]

Abstract: Majority of previous heroin fMRI studies focused on abnormal brain function in heroin-dependent individuals. However, few fMRI studies focused on the resting-state abnormalities in heroin-dependent individuals and assessed the relationship between the resting-state functional connectivity changes and duration of heroin use. In the present study, discrete cosine transform (DCT) was employed to explore spatial distribution of low frequency BOLD oscillations in heroin-dependent individuals and healthy subjects during resting-state; meanwhile resting-state functional connectivity analysis was used to investigate the temporal signatures of overlapping brain regions obtained in DCT analysis among these two groups. Main finding of the present study is that the default mode network (DMN) and rostral anterior cingulate cortex (rACC) network of heroin-dependent individuals were changed compared with healthy subjects. More importantly, these changes negatively correlated with duration of heroin use. These resting-state functional abnormalites in heroin-dependent individuals provided evidence for abnormal functional organization in heroin-dependent individuals, such as functional impairments in decision-making and inhibitory control. [Copyright &y& Elsevier]

Abstract: Recent functional neuroimaging studies have examined cognitive inhibitory control, decision-making and stress regulation in heroin addiction using a cue-reactivity paradigm. Few studies have considered impairments in heroin users from an integrated perspective for evaluation of their brain functions. We hypothesized that the brain regions that are dysregulated in the chronic heroin users during cue-reactivity studies may also show dysfunctional connectivity in memory, inhibition and motivation-related dysfunctions during a resting state free of cues. The present study used resting functional magnetic resonance imaging (fMRI) to compare the interaction of brain regions between 12 chronic heroin users and 12 controls by employing a novel graph theory analysis (GTA) method. As a data-driven approach, GTA has the advantage of evaluating the strength as well as the temporal and spatial patterns of interactions among the brain regions. Abnormal topological properties were explored in the brain of chronic heroin users, such as the dysfunctional connectivity in the prefrontal cortex, ACC, SMA, ventral striatum, insula, amygdala and hippocampus. Our results suggest that GTA is a useful tool in defining dysregulated neural networks even during rest. This dysfunctional brain connectivity may contribute to decrease self-control, impaired inhibitory function as well deficits in stress regulation in chronic heroin users. [Copyright &y& Elsevier]