Imbalanced functional link between valuation networks in abstinent heroin-dependent subjects.
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ABSTRACT:
SUBMITTER: Xie C
PROVIDER: S-EPMC4524350 | biostudies-literature | 2014 Jan
REPOSITORIES: biostudies-literature
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Project description:Advanced neuroimaging studies have identified brain correlates of pathological impulsivity in a variety of neuropsychiatric disorders. However, whether and how these spatially separate and functionally integrated neural correlates collectively contribute to aberrant impulsive behaviors remains unclear. Building on recent progress in neuroeconomics toward determining a biological account of human behaviors, we employed resting-state functional MRI to characterize the nature of the links between these neural correlates and to investigate their impact on impulsivity. We demonstrated that through functional connectivity with the ventral medial prefrontal cortex, the δ-network (regions of the executive control system, such as the dorsolateral prefrontal cortex) and the β-network (regions of the reward system involved in the mesocorticolimbic pathway), jointly influence impulsivity measured by the Barratt impulsiveness scale scores. In control nondrug-using subjects, the functional link between the β- and δ-networks is balanced, and the δ-network competitively controls impulsivity. However, in abstinent heroin-dependent subjects, the link is imbalanced, with stronger β-network connectivity and weaker δ-network connectivity. The imbalanced link is associated with impulsivity, indicating that the β- and δ-networks may mutually reinforce each other in abstinent heroin-dependent subjects. These findings of an aberrant link between the β- and δ-networks in abstinent heroin-dependent subjects may shed light on the mechanism of aberrant behaviors of drug addiction and may serve as an endophenotype to mark individual subjects' self-control capacity.
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Project description:Methamphetamine (MA) use disorders are pervasive global social problems that produce large medical and public health burdens. Abnormalities in pituitary hormonal regulation have been observed in preclinical models of substance abuse and in human substance abusers. They have, however, not been studied before in MA-dependent human subjects.To determine if MA-dependent research volunteers differ from healthy control subjects in plasma levels of adrenocorticotropic hormone (ACTH), cortisol, or prolactin, or in pituitary dopamine D(2) receptor availability during early abstinence from MA.MA-dependent subjects (N = 31), who were not seeking treatment, resided on an inpatient ward for up to 5 weeks. Abstinence was confirmed by daily urine drug screening. Venous blood was sampled for plasma hormone levels, and positron emission tomography with [(18)F]fallypride was performed to determine dopamine D(2) receptor availability during the first week of abstinence. Venous blood was sampled again for hormone levels during the fourth week of abstinence. Matched healthy volunteers (N = 23) participated as a comparison group.MA-dependent and healthy comparison subjects did not differ in plasma ACTH or cortisol levels, but had an elevated plasma prolactin at both the first week and fourth week of abstinence. There was no group difference in pituitary dopamine D(2) receptor availability.MA-dependent individuals have abnormalities in prolactin regulation, which is not likely due to alterations in pituitary dopamine D(2) receptor availability.MA dependence is associated with elevated prolactin levels, which may contribute to medical comorbidity in afflicted individuals.
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Project description: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.
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Project description:Abnormal decision making is a behavioral characteristic of drug addiction. Indeed, drug addicts prefer immediate rewards at the expense of future interests. Assessing the neurocognitive basis of decision-making related to drug dependence, combining event-related potential (ERP) analysis and source localization techniques, may provide new insights into understanding decision-making deficits in drug addicts and further guide withdrawal treatment. In this study, EEG was performed in 20 abstinent heroin addicts (AHAs) and 20 age-, education- and gender-matched healthy controls (HCs) while they participated in a simple two-choice gambling task (99 vs. 9). Our behavioral results showed that AHAs tend to select higher-risk choices compared with HCs (i.e., more "99" choices than "9"). ERP results showed that right hemisphere preponderance of stimulus-preceding negativity was disrupted in AHAs, but not in HCs. Feedback-related negativity of difference wave was higher in AHAs than HCs, with the P300 amplitude associated with risk magnitude and valence. Using source localization that allows identification of abnormal brain activity in consequential cognitive stages, including the reward expectation and outcome evaluation stages, we found abnormalities in both behavioral and neural responses on gambling in AHAs. Taken together, our findings suggest AHAs have risk-prone tendency and dysfunction in adaptive decision making, since they continue to choose risky options even after accruing considerable negative scores, and fail to shift to a safer strategy to avoid risk. Such abnormal decision-making bias to risk and immediate reward seeking may be accompanied by abnormal reward expectation and evaluation in AHAs, which explains their high risk-seeking and impulsivity.
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Project description:Neuroimaging studies have shown that heroin addiction is related to abnormalities in widespread local regions and in the functional connectivity of the brain. However, little is known about whether heroin addiction changes the topological organization of whole-brain functional networks. Seventeen heroin-dependent individuals (HDIs) and 15 age-, gender-matched normal controls (NCs) were enrolled, and the resting-state functional magnetic resonance images (RS-fMRI) were acquired from these subjects. We constructed the brain functional networks of HDIs and NCs, and compared the between-group differences in network topological properties using graph theory method. We found that the HDIs showed decreases in the normalized clustering coefficient and in small-worldness compared to the NCs. Furthermore, the HDIs exhibited significantly decreased nodal centralities primarily in regions of cognitive control network, including the bilateral middle cingulate gyrus, left middle frontal gyrus, and right precuneus, but significantly increased nodal centralities primarily in the left hippocampus. The between-group differences in nodal centralities were not corrected by multiple comparisons suggesting these should be considered as an exploratory analysis. Moreover, nodal centralities in the left hippocampus were positively correlated with the duration of heroin addiction. Overall, our results indicated that disruptions occur in the whole-brain functional networks of HDIs, findings which may be helpful in further understanding the mechanisms underlying heroin addiction.
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Project description:Literatures have shown that Internet gaming disorder (IGD) subjects show impaired executive control and enhanced reward sensitivities than healthy controls. However, how these two networks jointly affect the valuation process and drive IGD subjects' online-game-seeking behaviors remains unknown. Thirty-five IGD and 36 healthy controls underwent a resting-states scan in the MRI scanner. Functional connectivity (FC) was examined within control and reward network seeds regions, respectively. Nucleus accumbens (NAcc) was selected as the node to find the interactions between these two networks. IGD subjects show decreased FC in the executive control network and increased FC in the reward network when comparing with the healthy controls. When examining the correlations between the NAcc and the executive control/reward networks, the link between the NAcc - executive control network is negatively related with the link between NAcc - reward network. The changes (decrease/increase) in IGD subjects' brain synchrony in control/reward networks suggest the inefficient/overly processing within neural circuitry underlying these processes. The inverse proportion between control network and reward network in IGD suggest that impairments in executive control lead to inefficient inhibition of enhanced cravings to excessive online game playing. This might shed light on the mechanistic understanding of IGD.
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Project description:In this study, we generate genomic maps of Mediator, Rad2, Pol II, TBP and TFIIH, by ChIP coupled to next generation sequencing technology (ChIP-seq), in wild type strains from Saccharomyces cerevisiae. A related study involving ChIP-chip analysis of Rad2 occupany is also deposited at ArrayExpress under accession number E-MEXP-3875 ( http://www.ebi.ac.uk/arrayexpress/experiments/E-MEXP-3875 ).
2013-12-01 | E-MTAB-1595 | biostudies-arrayexpress
Project description:In this study, we generate genomic maps of Mediator, Pol II, TBP, TFIIH, TFIIA, TFIIB, TFIIE, TFIIF, by ChIP coupled to next generation sequencing technology (ChIP-seq), in wild type strains from Saccharomyces cerevisiae and in a mutant for the Mediator essential subunit Med10
2017-01-24 | E-MTAB-4607 | biostudies-arrayexpress
Project description:Background and purposeOpioids and cannabinoids interact in drug addiction and relapse. We investigated the effect of the opioid receptor antagonist naloxone and/or the cannabinoid CB(1) receptor antagonist rimonabant on cannabinoid-induced reinstatement of heroin seeking and on cannabinoid substitution in heroin-abstinent rats. EXPERIMENTAL APPROACH Rats were trained to self-administer heroin (30 µg·kg(-1) per infusion) under a fixed-ratio 1 reinforcement schedule. After extinction of self-administration (SA) behaviour, we confirmed the effect of naloxone (0.1-1 mg·kg(-1)) and rimonabant (0.3-3 mg·kg(-1)) on the reinstatement of heroin seeking induced by priming with the CB(1) receptor agonist WIN55,212-2 (WIN, 0.15-0.3 mg·kg(-1)). Then, in a parallel set of heroin-trained rats, we evaluated whether WIN (12.5 µg·kg(-1) per infusion) SA substituted for heroin SA after different periods of extinction. In groups of rats in which substitution occurred, we studied the effect of both antagonists on cannabinoid intake.Key resultsCannabinoid-induced reinstatement of heroin seeking was significantly attenuated by naloxone (1 mg·kg(-1)) and rimonabant (3 mg·kg(-1)) and fully blocked by co-administration of sub-threshold doses of the two antagonists. Moreover, contrary to immediate (1 day) or delayed (90 days) drug substitution, rats readily self-administered WIN when access was given after 7, 14 or 21 days of extinction from heroin, and showed a response rate that was positively correlated with the extinction period. In these animals, cannabinoid intake was increased by naloxone (1 mg·kg(-1)) and decreased by rimonabant (3 mg·kg(-1)).Conclusions and implicationsOur findings extend previous research on the crosstalk between cannabinoid and opioid receptors in relapse mechanisms, which suggests a differential role in heroin-seeking reinstatement and cannabinoid substitution in heroin-abstinent rats.
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Project description:ObjectiveThe objective of the study was to describe psychological features of abstinent heroin users undergoing rehabilitation in Saint Petersburg, Russia. Study subjects (n = 197) were recruited prospectively at the time of their admission to rehabilitation between March 2010 and May 2011 at 7 inpatient opiate addiction rehabilitation centers in Saint-Petersburg and neighboring regions, Russia. The centers provided varying rehabilitation programs; 6 of them were religious centers. Socio-demographic information and self-reported HIV status were collected. Personality profiles and severity of drug-associated problems were estimated before and after rehabilitation using the Minnesota Multiphasic Personality Inventory 2 (MMPI-2), and the Addiction Severity Index (ASI).ResultsThirty-three (17%) subjects dropped out before completing rehabilitation (non-completers). All subjects (completers and non-completers) had psychopathological personality profiles according to MMPI-2. These profiles were refractory to clinically significant improvement after rehabilitation, although some statistically significant changes toward improvement were observed. ASI scores showed statistically and clinically significant improvements after rehabilitation on all scales. Participants in longer-term versus shorter-term rehabilitation programs showed similar changes in their pre- and post-rehabilitation MMPI-2 and ASI scores. Our results suggest that unmet psychiatric needs should be addressed to potentially improve treatment completion in this population.
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