DRD2 TaqIA polymorphism-related functional connectivity between anterior insula and dorsolateral prefrontal cortex predicts the retention time in heroin-dependent individuals under methadone maintenance treatment.

BACKGROUND: Dopamine receptor D2 (DRD2) TaqIA polymorphism has an influence on addiction treatment response and prognosis by mediating brain dopaminergic system efficacy. Insula is crucial for conscious urges to take drugs and maintain drug use. However, it remains unclear about the contribution of DRD2 TaqIA polymorphism to the regulation of insular on addiction behavioral and its relation with the therapeutic effect of methadone maintenance treatment (MMT). METHODS: 57 male former heroin dependents receiving stable MMT and 49 matched male healthy controls (HC) were enrolled. Salivary genotyping for DRD2 TaqA1 and A2 alleles, brain resting-state functional MRI scan and a 24-month follow-up for collecting illegal-drug-use information was conducted and followed by clustering of functional connectivity (FC) patterns of HC insula, insula subregion parcellation of MMT patients, comparing the whole brain FC maps between the A1 carriers and non-carriers and analyzing the correlation between the genotype-related FC of insula sub-regions with the retention time in MMT patients by Cox regression. RESULTS: Two insula subregions were identified: the anterior insula (AI) and the posterior insula (PI) subregion. The A1 carriers had a reduced FC between the left AI and the right dorsolateral prefrontal cortex (dlPFC) relative to no carriers. And this reduced FC was a poor prognostic factor for the retention time in MMT patients. CONCLUSION: DRD2 TaqIA polymorphism affects the retention time in heroin-dependent individuals under MMT by mediating the functional connectivity strength between left AI and right dlPFC, and the two brain regions are promising therapeutic targets for individualized treatment.

Abnormal cerebral metabolism and metabolic connectivity in individuals with heroin dependence: an integrated resting-state PET/fMRI study in large-scale networks.

BACKGROUND: Increasing evidence suggests that heroin addiction may be related to the dysfunction among the triple brain network (default mode network [DMN], salience network [SN] and executive control network [ECN]). However, the characteristics of glucose metabolism and metabolic connectivity among core regions of the triple brain network remain unknown. Therefore, we hypothesized that individuals with heroin dependence would show abnormal glucose metabolism and accompanied abnormal metabolic connectivity within the triple brain network. METHODS: Individuals with heroin dependence and healthy controls matched for age and sex underwent integrated positron emission tomography/magnetic resonance imaging (PET/MRI). Differences in glucose metabolism and metabolic connectivity among the DMN, SN and ECN were analyzed based on 18F-fluorodeoxyglucose PET and resting-state fMRI data. RESULTS: We included 36 individuals with heroin dependence and 30 matched healthy controls in our study. The heroin dependence group showed a significant reduction of glucose metabolism in the bilateral anterior insula (AI) and inferior parietal lobule (IPL), and a significantly decreased metabolic connectivity between the right AI and the left dorsolateral prefrontal cortex (DLPFC). The daily dose of methadone was negatively correlated with glucose metabolism of the right AI and right IPL. LIMITATIONS: The results revealed the glucose metabolism alterations and metabolic connectivity only within the triple brain network in individuals with heroin dependence; additional brain networks should be investigated in future studies. Although methadone is an opioid with a similar neurophysiological mechanism as heroin, the specific chronic effects of methadone on cerebral metabolism and metabolic connectivity should also be investigated in future studies. CONCLUSION: Our findings suggest that long-term opioid use might, to some extent, be associated with reduced synergistic ability between the SN and ECN, which may be associated with the dysfunction of cognitive control. In particular, the right AI, which showed hypometabolism and related reduction in SN-ECN metabolic connectivity, should receive increasing attention in future studies.

Potential brain recovery of frontostriatal circuits in heroin users after prolonged abstinence: A preliminary study.

Neuroscientists have devoted efforts to explore potential brain recovery after prolonged abstinence in heroin users (HU). However, not much is known about whether frontostriatal circuits can recover after prolonged abstinence in HU. An eight-month longitudinal study was carried out for HU. Two MRI scans were obtained at baseline (HU1) and 8-month follow-up (HU2). The functional and structural connectivities of dorsal and ventral frontostriatal pathways were measured by resting-state functional connectivity (RSFC) and diffusion tensor imaging (DTI). Correlation analyses were employed to reveal the associations between neuroimaging and behavioral changes. Results suggested that relative to healthy controls (HCs), HU1 showed lower fractional anisotropy (FA) in the right dorsolateral prefrontal cortex (DLPFC)-to-caudate tracts and medial orbitofrontal cortex (mOFC)-to-nucleus accumbens (NAc) tracts as well as decreased RSFC in the left mOFC-NAc circuits. Longitudinal results revealed reduced craving and enhanced cognitive control in HU2 compared with HU1. After prolonged abstinence, HU2 showed increased FA values in the right DLPFC-caudate and mOFC-NAc tracts as well as increased RSFC strength in the bilateral mOFC-NAc circuits compared with HU1. In addition, changes in RSFC and FA values in the right mOFC-NAc circuit were negatively correlated with craving score changes. Similarly, negative correlations were also found between changes of RSFC in the bilateral DLPFC-caudate circuits and TMT-A scores. We provided scientific evidence for brain recovery of the dorsal and ventral frontostriatal circuits in HU after prolonged abstinence, and these circuits may be potential neuroimaging biomarkers for cognition and craving changes.

The effect of long-term methadone maintenance treatment on coupling among three large-scale brain networks in male heroin-dependent individuals: A resting-state fMRI study.

PURPOSE: Methadone maintenance treatment (MMT) is considered as an effective and mainstream therapy for heroin dependence. However, whether long-term MMT would improve the coupling among the three core large-scale brain networks (salience, default mode, and executive control) and its relationship with the craving for heroin is unknown. METHODS: Forty-four male heroin-dependent individuals during long-term MMT, 27 male heroin-dependent individuals after short-term detoxification/abstinence (SA), and 26 demographically matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging. We analyzed the difference in coupling among the salience, default mode, and executive control networks among the three groups and examined how the coupling among these large-scale networks was associated with craving before and after drug-cue exposure. RESULTS: Compared with the SA group, the MMT group showed lower craving before and after cue exposure and stronger connectivity between the dorsal anterior cingulate cortex (a key node of the salience network) and key regions of the bilateral executive control network, including the bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and dorsomedial prefrontal cortex. Among the heroin-dependent individuals, the functional connectivity was negatively correlated with the craving before and after heroin-cue exposure. CONCLUSION: Our findings suggest that long-term MMT could increase the coupling between the salience and bilateral executive control networks and decrease craving for heroin. These findings contribute to the understanding of the neural mechanism of MMT, from the perspective of large-scale brain networks.

Heroin Addiction Induces Axonal Transport Dysfunction in the Brain Detected by In Vivo MRI.

Heroin is a highly addictive drug that causes axonal damage. Here, manganese-enhanced magnetic resonance imaging (MEMRI) was used to dynamically monitor axonal transport at different stages of heroin addiction. Rat models of heroin addiction (HA) and prolonged heroin addiction (PHA) were established by injecting rats with heroin at different stages. Heroin-induced learning and memory deficits were evaluated in the Morris water maze (MWM), and MEMRI was used to dynamically evaluate axonal transport in the olfactory pathway. The expression of proteins related to axonal structure and function was also assessed by Western blotting. Transmission electron microscopy (TEM) was used to observe ultrastructural changes, and protein levels of neurofilament heavy chain (NF-H) were analyzed by immunofluorescence staining. HA rats, especially PHA rats, exhibited worse spatial learning and memory than control rats. Compared with HA rats and control rats, PHA rats exhibited significantly longer escape latencies, significantly fewer platform-location crossings, and significantly more time in the target quadrant during the MWM test. Mn2+ transport was accelerated in HA rats. PHA rats exhibited severely reduced Mn2+ transport, and the axonal transport rate (ATR) was significantly lower in these rats than in control rats (P < 0.001). The levels of cytoplasmic dynein and kinesin-1 were significantly decreased in the PHA group than in the control group (P < 0.001); additionally, the levels of energy-related proteins, including cytochrome c oxidase (COX) IV and ATP synthase subunit beta (ATPB), were lower in the PHA group (P < 0.001). The brains of heroin-exposed rats displayed an abnormal ultrastructure, with neuronal apoptosis and mitochondrial dysfunction. Heroin exposure decreased the expression of NF-H, as indicated by significantly reduced staining intensities in tissues from HA and PHA rats (P < 0.05). MEMRI detected axonal transport dysfunction caused by long-term repeated exposure to heroin. The main causes of axonal transport impairment may be decreases in the levels of motor proteins and mitochondrial dysfunction. This study shows that MEMRI is a potential tool for visualizing axonal transport in individuals with drug addictions, providing a new way to evaluate addictive encephalopathy.

Recovery of superior frontal gyrus cortical thickness and resting-state functional connectivity in abstinent heroin users after 8 months of follow-up.

Compared with healthy controls, heroin users (HUs) show evidence of structural and functional brain alterations. However, little is known about the possibility of brain recovery after protracted heroin abstinence. The purpose of this study was to investigate whether brain recovery is possible after protracted abstinence in HUs. A total of 108 subjects with heroin addiction completed structural and functional scans, and 61 of those subjects completed 8-month follow-up scans. Resting-state data and 3D-T1 MR images were collected for all participants, first at baseline and again after 8 months. Cognitive function and craving were measured by the Trail Making Test-A (TMT-A) and Visual Analog Scale for Craving, respectively. The cortical thickness and resting-state functional connectivity (RSFC) differences were then analyzed and compared between baseline and follow-up, and correlations were obtained between neuroimaging and behavioral changes. HUs demonstrated improved cognition (shorter TMT-A time) and reduced craving at the follow-up (HU2) relative to baseline (HU1), and the cortical thickness in the bilateral superior frontal gyrus (SFG) was significantly greater at HU2 than at HU1. Additionally, the RSFC of the left SFG with the inferior frontal gyrus (IFG), insula, and nucleus accumbens and that of the right SFG with the IFG, insula and orbitofrontal cortex (OFC) were increased at HU2. The changes in TMT-A time were negatively correlated with the RSFC changes between the left SFG and the bilateral IFG, the bilateral caudate, and the right insula. The changes in craving were negatively correlated with the RSFC changes between the left OFC and the bilateral SFG. Our results demonstrated that impaired frontal-limbic neurocircuitry can be partially restored, which might enable improved cognition as well as reduced craving in substance-abusing individuals. We provided novel scientific evidence for the partial recovery of brain circuits implicated in cognition and craving after protracted abstinence.

Difference in topological organization of white matter structural connectome between methamphetamine and heroin use disorder.

The psychological symptoms caused by heroin and methamphetamine are significantly different in people with substance use disorders. The topological organization of structural connections that may underlie these differences remains unknown. The study sample consisted of 23 males with methamphetamine use disorder (MAUD), 20 males with heroin use disorder (HUD), and 21 male healthy controls (HCs) who were demographically matched. Diffusion tensor imaging and probabilistic tractography were used for white matter network construction. Psychological symptoms were evaluated by the Symptom Checklist-90. Using graph theoretical analysis, we examined the difference in graph-level and nodal-level properties among the groups. The network Hubs distribution and the relationship between the network alterations and psychological symptoms were identified. The MAUD group demonstrated significantly higher scores on anxiety, hostility, and symptoms of schizophrenia than the HUD and HCs groups. The HUD group showed significantly higher global efficiency and network strength than the HCs group, and higher network strength than the MAUD group. Compared with the HUD group, the MAUD group showed significantly lower Nodal Strength and efficiency, distributed mainly in the temporal, parietal, and occipital regions. We also found the network Hubs were decreased in the MAUD group, but increased in the HUD group. The Nodal Strength in the right superior temporal gyrus was significantly correlated with psychological symptoms in the MAUD group. These findings reflect the significant differences in topological structural connection between HUD and MAUD. This evidence helps shed some light on the neurobiological mechanisms of the psychological differences between HUD and MAUD, and extend our understanding of the structural disruption underlying MAUD-related psychological symptoms.

Brain responses to drug cues predict craving changes in abstinent heroin users: A preliminary study.

BACKGROUND: Loss of control over drug intake occurring in drug addiction is believed to result from disruption of reward circuits, including reduced responsiveness to natural rewards (e.g., monetary, sex) and heightened responsiveness to drug reward. Yet few studies have assessed reward deficiency and related brain responses in abstinent heroin users with opioid use disorder, and less is known whether the brain responses can predict cue-induced craving changes following by prolonged abstinence. METHOD: 31 heroin users (age: 44.13±7.68 years, male: 18 (58%), duration of abstinence: 85.2 ± 52.5 days) were enrolled at a mandatory detoxification center. By employing a cue-reactivity paradigm including three types of cues (drug, sexual, neutral), brain regional activations and circuit-level functional coupling were extracted. Among the 31 heroin users, 15 were followed up longitudinally to assess cue induced craving changes in the ensuing 6 months. RESULTS: One way analysis of variance results showed that heroin users have differential brain activations to the three cues (neutral, drug and sexual) in the left dorsolateral prefrontal cortex (DLPFC), insula, orbiotofrontal cortex (OFC) and the bilateral thalamus. Drug cue induced greater activations in left DLPFC, insula and OFC compared to sexual cue. The psychophysiological interactions (PPI) analysis revealed negative couplings of the left DLPFC and the left OFC, bilateral thalamus, putamen in heroin users during drug cue exposure. In the 6-month follow-up study, both drug cue induced activation of the left DLPFC and the functional coupling of the left DLPFC-bilateral thalamus at baseline was correlated with craving reductions, which were not found for sexual cues. CONCLUSION: Our preliminary study provided novel evidence for the reward deficiency theory of opioid use disorder. Our findings also have clinical implications, as drug cue induced activation of the left DLPFC and functional coupling of left DLPFC-bilateral thalamus may be potential neuroimaging markers for craving changes during prolonged abstinence. Evidently, the findings in the current preliminary study should be confirmed by large sample size in the future.

Fronto-temporal cortical atrophy in 'nyaope' combination heroin and cannabis use disorder.

Sub-Saharan Africa is one of the top three regions with the highest rates of opioid-related premature mortality. Nyaope is the street name for what is believed to be a drug cocktail in South Africa although recent research suggests that it is predominantly heroin. Nyaope powder is most commonly smoked together with cannabis, a drug-use pattern unique to the region. Due to the increasing burden of this drug in low-income communities and the absence of human structural neuroimaging data of combination heroin and cannabis use disorder, we initiated an important cohort study in order to identify neuroanatomical sequelae. Twenty-eight male nyaope users and thirty healthy, matched controls were recruited from drug rehabilitation centers and the community, respectively. T1-weighted MRI images were obtained using a 3 T General Electric Discovery and cortical thickness was examined and compared. Nyaope users displayed extensive grey matter atrophy in the right hemispheric medial orbitofrontal, rostral middle frontal, superior temporal, superior frontal, and supramarginal gyri (two-sided t-test, p < 0.05, corrected for multiple comparisons). Our findings indicate cortical abnormality in nyaope users in regions involved in impulse control, decision making, social- and self-perception, and working memory. Importantly, affected brain regions show large overlap with the pattern of cortical abnormalities shown in heroin use disorder.

Reduced thalamic resting-state functional connectivity and impaired cognition in acute abstinent heroin users.

As a critical component of cortico-striato-thalamo-cortical loop in addiction, our understanding of the thalamus in impaired cognition of heroin users (HU) has been limited. Due to the complex thalamic connection with cortical and subcortical regions, thalamus was divided into prefrontal (PFC), occipital (OC), premotor, primary motor, sensory, temporal, and posterior parietal association subregions according to white matter tractography. We adopted seven subregions of bilateral thalamus as regions of interest to systematically study the implications of distinct thalamic nuclei in acute abstinent HU. The volume and resting-state functional connectivity (RSFC) differences of the thalamus were investigated between age-, gender-, and alcohol-matched 37 HU and 33 healthy controls (HCs). Trail making test-A (TMT-A) was adopted to assess cognitive function deficits, which were then correlated with neuroimaging findings. Although no significant different volumes were found, HU group showed decreased RSFC between left PFC_thalamus and middle temporal gyrus as well as between left OC_thalamus and inferior frontal gyrus and supplementary motor area relative to HCs. Meanwhile, the higher TMT-A scores in HU were negatively correlated with PFC_thalamic RSFC with inferior temporal gyrus, fusiform, and precuneus. Craving scores were negatively correlated with OC_thalamic RSFC with accumbens, hippocampus, and insula. Opiate Withdrawal Scale scores were negatively correlated with left PFC/OC_thalamic RSFC with orbitofrontal cortex and medial PFC. We indicated two thalamus subregions separately involvement in cognitive control and craving to reveal the implications of thalamic subnucleus in pathology of acute abstinent HU.

Assessing effect of long-term abstinence on coupling of three core brain networks in male heroin addicts: A resting-state functional magnetic resonance imaging study.

Abstinence is one of the important measures for heroin addiction. However, it is unknown whether long-term abstinence (LA) would improve the coupling among three core brain networks (salience, default mode, and executive control) and decrease craving in treated heroin addicts. Forty-three heroin addicts with LA, 27 heroin addicts with short-term abstinence (SA), and 46 demographically matched healthy controls (HC) participated in the resting-state functional magnetic resonance imaging study. The authors compared the functional connectivity among the three groups and examined how the coupling among salience, default mode, and executive control networks related to duration of abstinence and craving before and after drug cue exposure among heroin addicts. Compared with the SA group, with a tendency toward the HC group, the LA group showed lower drug cue-induced craving, stronger connectivity between the dorsal anterior cingulate cortex (a key node of salience network) and left dorsolateral prefrontal cortex and right posterior parietal cortex (key nodes of executive control network), and stronger connectivity between the right dorsolateral prefrontal cortex and precuneus (a key node of default mode network). Meanwhile, the right dorsolateral prefrontal cortex-precuneus connectivity positively correlated with duration of abstinence. The LA and SA groups demonstrated lower connectivity between the left anterior insula (a key node of salience network) and dorsolateral prefrontal cortex and lower connectivity within the left dorsolateral prefrontal cortex, compared with the HC group. Our findings revealed that LA is associated with lower drug cue induced craving and improve the coupling among the three core brain networks in heroin addicts.

Gray matter alteration in heroin-dependent men: An atlas-based magnetic resonance imaging study.

Previous imaging studies on heroin addiction have reported brain morphological alterations. However, the effects of heroin exposure on gray matter volume varied among different studies due to different factors such as substitution treatment or mandatory abstinence. Meanwhile, the relationship between gray matter and heroin use history remains unknown. Thirty-three male heroin-dependent (HD) individuals who are not under any substitution treatment or mandatory abstinence and 40 male healthy controls (HC) were included in this structural magnetic resonance imaging study. With an atlas-based approach, gray matter structures up to individual functional area were delineated, and the differences in their volumes between the HD and HC groups were analyzed. In addition, the relationship between gray matter volume and duration of heroin use was explored. The HD group demonstrated significantly lower cortical volume mainly in the prefrontal cortex and mesolimbic dopaminergic regions across different parcellation levels, whereas several visual and somatosensory cortical regions in the HD group had greater volume relative to the HC group at a more detailed parcellation level. The duration of heroin use was negatively correlated with the gray matter volume of prefrontal cortex. These findings suggest that heroin addiction be related to gray matter alteration and might be related to damage/maladaption of the inhibitory control, reward, visual, and somatosensory functions of the brain, although cognitive correlates are warranted in future study. In addition, the atlas-based morphology analysis is a potential tool to help researchers search biomarkers of heroin addiction.

Machine learning: assessing neurovascular signals in the prefrontal cortex with non-invasive bimodal electro-optical neuroimaging in opiate addiction.

Chronic and recurrent opiate use injuries brain tissue and cause serious pathophysiological changes in hemodynamic and subsequent inflammatory responses. Prefrontal cortex (PFC) has been implicated in drug addiction. However, the mechanism underlying systems-level neuroadaptations in PFC during abstinence has not been fully characterized. The objective of our study was to determine what neural oscillatory activity contributes to the chronic effect of opiate exposure and whether the activity could be coupled to neurovascular information in the PFC. We employed resting-state functional connectivity to explore alterations in 8 patients with heroin dependency who stayed abstinent (>3 months; HD) compared with 11 control subjects. A non-invasive neuroimaging strategy was applied to combine electrophysiological signals through electroencephalography (EEG) with hemodynamic signals through functional near-infrared spectroscopy (fNIRS). The electrophysiological signals indicate neural synchrony and the oscillatory activity, and the hemodynamic signals indicate blood oxygenation in small vessels in the PFC. A supervised machine learning method was used to obtain associations between EEG and fNIRS modalities to improve precision and localization. HD patients demonstrated desynchronized lower alpha rhythms and decreased connectivity in PFC networks. Asymmetric excitability and cerebrovascular injury were also observed. This pilot study suggests that cerebrovascular injury in PFC may result from chronic opiate intake.

Heroin addiction engages negative emotional learning brain circuits in rats.

Opioid use disorder (OUD) is associated with the emergence of persistent negative emotional states during drug abstinence that drive compulsive drug taking and seeking. Functional magnetic resonance imaging (fMRI) in rats identified neurocircuits that were activated by stimuli that were previously paired with heroin withdrawal. The activation of amygdala and hypothalamic circuits was related to the degree of heroin dependence, supporting the significance of conditioned negative affect in sustaining compulsive-like heroin seeking and taking and providing neurobiological insights into the drivers of the current opioid crisis.

Long-term results after deep brain stimulation of nucleus accumbens and the anterior limb of the internal capsule for preventing heroin relapse: An open-label pilot study.

BACKGROUND: Deep brain stimulation (DBS) is currently used to treat addiction, with the nucleus accumbens (NAc) as one promising target. The anterior limb of the internal capsule (ALIC) is also a potential target, as it carries fiber tracts connecting the mesocorticolimbic circuits that are crucially involved in several psychiatric disorders, including addiction. Stimulating the NAc and ALIC simultaneously may have a synergistic effect against addiction. METHODS: Eight patients with a long history of heroin use and multiple relapses, despite optimal conventional treatments, were enrolled. Customized electrodes were implanted through the ALIC into the NAc, and deep brain stimulation (DBS) treatment began two weeks after surgery. The patients were followed for at least 24 months. The duration of drug-free time, severity of drug cravings, psychometric evaluations, and PET studies of glucose metabolism before and after DBS were conducted. All adverse events were recorded. RESULTS: With DBS, five patients were abstinent for more than three years, two relapsed after abstaining for six months, and one was lost of follow-up at three months. The degree of cravings for drug use after DBS was reduced if the patients remained abstinent (p < 0.001). Simultaneous DBS of the NAc and ALIC also improved the quality of life, alleviated psychiatric symptoms, and increased glucose metabolism in addiction-related brain regions. Moreover, stimulation-related adverse events were few and reversible. CONCLUSIONS: Simultaneous DBS of the NAc and ALIC appears to be safe, with few side effects, and may prevent long-term heroin relapse after detoxification in certain patients. (This trial was registered at ClinicalTrials.gov, NCT01274988).

Altered gray matter volume and disrupted functional connectivity of dorsolateral prefrontal cortex in men with heroin dependence.

AIM: Chronic heroin use can cause various neuropathological characteristics that may compromise brain function. The present study evaluated the alteration of gray matter volume (GMV) and its resting-state functional connectivity (rsFC) over the dorsolateral prefrontal cortex (DLPFC) among male heroin users. METHODS: Thirty heroin-dependent men undergoing methadone maintenance therapy and 30 educational-level- and age-matched male controls were recruited for this study. To assess their GMV and rsFC, the participants were evaluated using spoiled gradient echo and gradient-recalled echo planar imaging sequences with a 3-Tesla General Electric MR scanner under resting state. RESULTS: The heroin-dependent men showed lower GMV over the right DLPFC in comparison with the controls. Further evaluation of the rsFC of the right DLPFC revealed a marked decrease in interhemispheric DLPFC connectivity among those with heroin dependence under control of head movement and GMV of the right DLPFC. CONCLUSION: Although the mechanism remains unclear, the present study shows that chronic heroin use is associated with alteration of morphology as well as rsFC over the right DLPFC. As the DLPFC plays an imperative role in various domains of cognitive function, service providers for heroin users should consider the impacts of possible DLPFC-related cognitive deficits on treatment effectiveness.

Acute progressive paraplegia in heroin-associated myelopathy.

As the opioid epidemic continues, understanding manifestations of abuse, including heroin-associated myelopathy remains essential. Here we describe a young man with a past medical history significant for polysubstance abuse who developed acute-onset, rapidly progressive myelopathy after resumption of intravenous heroin use. He had significant spinal cord involvement with findings suggestive of heroin-associated myelopathy. The salient features of this case include diffusion imaging of the spine and spinal angiography supporting a possible vasculopathy as the pathophysiologic mechanism underlying heroin-associated myelopathy. Additionally, CSF studies showed the transition from a neutrophilic pleocytosis to a lymphocytic pleocytosis suggesting an inflammatory component.

Resting-state Abnormalities in Heroin-dependent Individuals.

Drug addiction is a major health problem worldwide. Recent neuroimaging studies have shed light into the underlying mechanisms of drug addiction as well as its consequences to the human brain. The most vulnerable, to heroin addiction, brain regions have been reported to be specific prefrontal, parietal, occipital, and temporal regions, as well as, some subcortical regions. The brain regions involved are usually linked with reward, motivation/drive, memory/learning, inhibition as well as emotional control and seem to form circuits that interact with each other. So, along with neuroimaging studies, recent advances in resting-state dynamics might allow further assessments upon the multilayer complexity of addiction. In the current manuscript, we comprehensively review and discuss existing resting-state neuroimaging findings classified into three overlapping and interconnected groups: functional connectivity alterations, structural deficits and abnormal topological properties. Moreover, behavioral traits of heroin-addicted individuals as well as the limitations of the currently available studies are also reviewed. Finally, in need of a contemporary therapy a multimodal therapeutic approach is suggested using classical treatment practices along with current neurotechonologies, such as neurofeedback and goal-oriented video-games.

Nonlinear Dynamic Complexity and Sources of Resting-state EEG in Abstinent Heroin Addicts.

It has been reported that chronic heroin intake induces both structural and functional changes in human brain; however, few studies have investigated the carry-over adverse effects on brain after heroin withdrawal. In this paper, we examined the neurophysiological differences between the abstinent heroin addicts (AHAs) and healthy controls (HCs) using nonlinear dynamic analysis and source localization analysis in resting-state electroencephalogram (EEG) data; 5 min resting EEG data from 20 AHAs and twenty age-, education-, and gender-matched HCs were recorded using 64 electrodes. The results of nonlinear characteristics (e.g., the correlation dimension, Kolmogorov entropy, and Lempel-Ziv complexity) showed that the EEG signals in alpha band from AHAs were significantly more irregular. Moreover, the source localization results confirmed the neuronal activities in alpha band in AHAs were significantly weaker in parietal lobe (BA3 and BA7), frontal lobe (BA4 and BA6), and limbic lobe (BA24). Together, our analysis at both the sensor level and source level suggested the functional abnormalities in the brain during heroin abstinence, in particular for the neuronal oscillations in alpha band.

Availability of dopamine transporters in heroin-dependent subjects: A 18F-FECNT PET imaging study.

This study was to reconfirm the reduced dopamine transporter (DAT) availability in heroin-dependent subjects and validate the use of 2ß-carbomethoxy-3ß-(4-chlorophenyl)-8-(2-fluoroethyl)-nortropane (18F-FECNT) as a PET radiotracer to assess the changes of striatal DAT in drug addicted subjects. Herein, we assessed DAT standardized uptake values (SUV) of 18F-FECNT in the striatum and cerebellum of 20 heroin-dependent subjects and 10 healthy controls and analyzed the correlation between DAT availability and heroin withdrawal symptom scores and anxiety/depression rating scales in heroin-dependent subjects, as well as the relationship between the withdrawal symptoms scores and age. The striatal DAT availability in heroin-dependent subjects was significantly lower (by ~15.7-17.6%) than that in healthy controls. Age was positively related to heroin withdrawal symptom scores. The withdrawal symptom scores in older patients (Age: 49.5±2.5) were significantly higher (by ~20%) than those in younger patients (Age: 30.9±4.8). These results confirm that chronic heroin use induces striatal DAT reduction, suggesting that 18F-FECNT could be used as an alternative PET imaging radioligand for in vivo imaging of DAT in drug addicted subjects. Moreover, older patients might suffer more severe withdrawal symptoms than younger patients, suggesting that older patients with heroin withdrawal could be given more medication.