Opioid antagonism modulates wanting-related frontostriatal connectivity
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ABSTRACT:
SUBMITTER: Soutschek A
PROVIDER: S-EPMC8598157 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Chronic opioid misuse is associated with reduced sensitivity to natural rewards and social motivation deficits that include impaired caregiving. The neurobiological mechanisms underlying these deficits and their response to treatment are not well understood. Baby schema (Kindchenschema) is a set of juvenile physical features, which is perceived as "cute" and triggers motivation for caregiving. Recent studies suggest that the "baby schema effect" is mediated by the brain "reward" network. We studied the impact of opioid antagonist treatment on the baby schema response in patients with opioid use disorder. METHODS:Forty-seven (24 F) recently detoxified patients with opioid use disorder underwent functional magnetic resonance imaging (fMRI) while viewing infant portraits that were parametrically manipulated for baby schema content and rating them for cuteness, at baseline and during treatment with the injectable extended release opioid antagonist naltrexone (XRNTX). The study was not placebo-controlled. RESULTS:The behavioral effect of baby schema, indexed by "cuteness" ratings, was present and unaffected by XRNTX. The brain response to baby schema was absent at baseline, but present in the bilateral ventral striatum after two weeks of XRNTX treatment. The decline in self-reported craving for opioids was positively correlated with the brain fMRI response to baby schema in the bilateral ventral striatum. CONCLUSIONS:Opioid antagonist treatment modulated the brain reward system response to a marker of caregiving motivation in patients with opioid use disorder. Neural response to baby schema may offer a novel probe of social motivation and affiliative behaviors in this population.
| S-EPMC6043353 | biostudies-literature
Project description:Preclinical studies have shown effects of chronic exposure to addictive drugs on glutamatergic-mediated neuroplasticity in frontostriatal circuitry. These initial findings have been paralleled by human functional magnetic resonance imaging (fMRI) research demonstrating weaker frontostriatal resting-state functional connectivity (rsFC) among individuals with psychostimulant use disorders. However, there is a dearth of human imaging literature describing associations between long-term prescription opioid use, frontostriatal rsFC, and brain morphology among chronic pain patients. We hypothesized that prescription opioid users with chronic pain, as compared with healthy control subjects, would evidence weaker frontostriatal rsFC coupled with less frontostriatal gray matter volume (GMV). Further, those opioid use-related deficits in frontostriatal circuitry would be associated with negative affect and drug misuse. Prescription opioid users with chronic pain (n = 31) and drug-free healthy controls (n = 30) underwent a high-resolution anatomical and an eyes-closed resting-state functional scan. The opioid group, relative to controls, exhibited weaker frontostriatal rsFC, and less frontostriatal GMV in both L.NAc and L.vmPFC. Frontostriatal rsFC partially mediated group differences in negative affect. Within opioid users, L.NAc GMV predicted opioid misuse severity. The current study revealed that prescription opioid use in the context of chronic pain is associated with functional and structural abnormalities in frontostriatal circuitry. These results suggest that opioid use-related abnormalities in frontostriatal circuitry may undergird disturbances in affect that may contribute to the ongoing maintenance of opioid use and misuse. These findings warrant further examination of interventions to treat opioid pathophysiology in frontostriatal circuitry over the course of treatment.
| S-EPMC6776713 | biostudies-literature
Project description:Adolescence is a developmental period associated with an increase in impulsivity. Impulsivity is a multidimensional construct, and in this study we focus on one of the underlying components: impatience. Impatience can result from (i) disregard of future outcomes and/or (ii) oversensitivity to immediate rewards, but it is not known which of these evaluative processes underlie developmental changes. To distinguish between these two causes, we investigated developmental changes in the structural and functional connectivity of different frontostriatal tracts. We report that adolescents were more impatient on an intertemporal choice task and reported less future orientation, but not more present hedonism, than young adults. Developmental increases in structural connectivity strength in the right dorsolateral prefrontal tract were related to increased negative functional coupling with the striatum and an age-related decrease in discount rates. Our results suggest that mainly increased control, and the integration of future-oriented thought, drives the reduction in impatience across adolescence.
| S-EPMC4517266 | biostudies-other
Project description:BackgroundAbnormalities of the striatum and frontal cortex have been reported consistently in studies of neural structure and function in major depressive disorder (MDD). Despite speculation that compromised connectivity between these regions may underlie symptoms of MDD, little work has investigated the integrity of frontostriatal circuits in this disorder.MethodsFunctional magnetic resonance images were acquired from 21 currently depressed and 19 never-disordered women during wakeful rest. Using four predefined striatal regions-of-interest, seed-to-whole brain correlations were computed and compared between groups.ResultsCompared to controls, depressed participants exhibited attenuated functional connectivity between the ventral striatum and both ventromedial prefrontal cortex and subgenual anterior cingulate cortex. Depressed participants also exhibited stronger connectivity between the dorsal caudate and dorsal prefrontal cortex, which was positively correlated with severity of the disorder.ConclusionsDepressed individuals are characterized by aberrant connectivity in frontostriatal circuits that are posited to support affective and cognitive processing. Further research is required to examine more explicitly the link between patterns of disrupted connectivity and specific symptoms of depression, and the extent to which these patterns precede the onset of depression and normalize with recovery from depressive illness.
| S-EPMC3384258 | biostudies-literature
Project description:It is estimated that nearly a third of people who abuse drugs started with prescription opioid medicines. Approximately, 11.5 million Americans used prescription drugs recreationally in 2016, and in 2018, 46,802 Americans died as the result of an opioid overdose, including prescription opioids, heroin, and illicitly manufactured fentanyl (National Institutes on Drug Abuse (2020) Opioid Overdose Crisis. https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis . Accessed 06 June 2020). Yet physicians will continue to prescribe oral opioids for moderate-to-severe pain in the absence of alternative therapeutics, underscoring the importance in understanding how drug choice can influence detrimental outcomes. One of the opioid prescription medications that led to this crisis is oxycodone, where misuse of this drug has been rampant. Being one of the most highly prescribed opioid medications for treating moderate-to-severe pain as reflected in the skyrocketed increase in retail sales of 866% between 1997 and 2007, oxycodone was initially suggested to be less addictive than morphine. The false-claimed non-addictive formulation of oxycodone, OxyContin, further contributed to the opioid crisis. Abuse was often carried out by crushing the pills for immediate burst release, typically by nasal insufflation, or by liquefying the pills for intravenous injection. Here, we review oxycodone pharmacology and abuse liability as well as present the hypothesis that oxycodone may exhibit a unique pharmacology that contributes to its high likability and abuse susceptibility. We will discuss various mechanisms that likely contribute to the high abuse rate of oxycodone including clinical drug likability, pharmacokinetics, pharmacodynamics, differences in its actions within mesolimbic reward circuity compared to other opioids, and the possibility of differential molecular and cellular receptor interactions that contribute to its selective effects. We will also discuss marketing strategies and drug difference that likely contributes to the oxycodone opioid use disorders and addiction.
| S-EPMC8155122 | biostudies-literature
Project description:Reward mediates the acquisition and long-term retention of procedural skills in humans. Yet, learning under rewarded conditions is highly variable across individuals and the mechanisms that determine interindividual variability in rewarded learning are not known. We postulated that baseline functional connectivity in a large-scale frontostriatal-limbic network could predict subsequent interindividual variability in rewarded learning. Resting-state functional MRI was acquired in two groups of subjects (n = 30) who then trained on a visuomotor procedural learning task with or without reward feedback. We then tested whether baseline functional connectivity within the frontostriatal-limbic network predicted memory strength measured immediately, 24 h and 1 month after training in both groups. We found that connectivity in the frontostriatal-limbic network predicted interindividual variability in the rewarded but not in the unrewarded learning group. Prediction was strongest for long-term memory. Similar links between connectivity and reward-based memory were absent in two control networks, a fronto-parieto-temporal language network and the dorsal attention network. The results indicate that baseline functional connectivity within the frontostriatal-limbic network successfully predicts long-term retention of rewarded learning.
| S-EPMC4883096 | biostudies-literature
Project description:A heightened sense of self-esteem is associated with a reduced risk for several types of affective and psychiatric disorders, including depression, anxiety and eating disorders. However, little is known about how brain systems integrate self-referential processing and positive evaluation to give rise to these feelings. To address this, we combined diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) to test how frontostriatal connectivity reflects long-term trait and short-term state aspects of self-esteem. Using DTI, we found individual variability in white matter structural integrity between the medial prefrontal cortex and the ventral striatum was related to trait measures of self-esteem, reflecting long-term stability of self-esteem maintenance. Using fMRI, we found that functional connectivity of these regions during positive self-evaluation was related to current feelings of self-esteem, reflecting short-term state self-esteem. These results provide convergent anatomical and functional evidence that self-esteem is related to the connectivity of frontostriatal circuits and suggest that feelings of self-worth may emerge from neural systems integrating information about the self with positive affect and reward. This information could potentially inform the etiology of diminished self-esteem underlying multiple psychiatric conditions and inform future studies of evaluative self-referential processing.
| S-EPMC4350482 | biostudies-literature
Project description:Alcohol use disorder (AUD) is associated with changes in frontostriatal connectivity, but functional magnetic resonance imaging (fMRI) functional connectivity (FC) approaches are usually not adapted to these circuits. We developed a circuit-specific fMRI analysis approach to detect dynamic changes in frontostriatal FC inspired by medial-ventral-rostral to lateral-dorsal-caudal frontostriatal gradients originally identified in nonhuman primate tract-tracing data. In our PeaCoG ("peak connectivity on a gradient") approach we use information about the location of strongest FC on empirical frontostriatal connectivity gradients. We have recently described a basic PeaCoG version with conventional FC, and now developed a dynamic PeaCoG approach with sliding-window FC. In resting state data of n = 66 AUD participants and n = 40 healthy controls we continue here the analyses that we began with the basic version. Our former result of an AUD-associated ventral shift in right orbitofrontal cortex PeaCoG is consistently detected in the dynamic approach. Temporospatial variability of dynamic PeaCoG in the left dorsolateral prefrontal cortex is reduced in AUD and associated with self-efficacy to abstain and days of abstinence. Our method has the potential to provide insight into the dynamics of frontostriatal circuits, which has so far been relatively unexplored, and into their role in mental disorders and normal cognition.
| S-EPMC7721230 | biostudies-literature
Project description:Despite the far-reaching evolutionary implications of sexual conflict, the effects of metapopulation structure, when populations are subdivided into several demes connected to some degree by migration, on sexual conflict dynamics are unknown. Here, we used experimental evolution in an insect model system, the seed beetle Callosobruchus maculatus, to assess the independent and interacting effects of selection histories associated with mating system (monogamy vs. polygamy) and population subdivision on sexual conflict evolution. We confirm traditional predictions from sexual conflict theory by revealing increased resistance to male harm in females from populations with a history of intense sexual selection (polygamous populations) compared to females from populations with a history of relaxed sexual selection (monogamous populations). However, selection arising from metapopulation structure reversed the classic pattern of sexually antagonistic coevolution and led to reduced resistance in females from polygamous populations. These results underscore that population spatial structure moderates sexual selection and sexual conflict, and more broadly, that the evolution of sexual conflict is contingent on ecological context. The findings also have implications for population dynamics, conservation biology, and biological control.
| S-EPMC8327942 | biostudies-literature
Project description:Connectivity of the prefrontal cortex (PFC) matures through adolescence, coinciding with emergence of adult executive function and top-down inhibitory control over behavior. Alcohol exposure during this critical period of brain maturation may affect development of PFC and frontolimbic connectivity. Adult rats exposed to adolescent intermittent ethanol (AIE; 5 g/kg ethanol, 25 percent v/v in water, intragastrically, 2-day-on, 2-day-off, postnatal day 25-54) or water control underwent resting-state functional MRI to test the hypothesis that AIE induces persistent changes in frontolimbic functional connectivity under baseline and acute alcohol conditions (2 g/kg ethanol or saline, intraperitoneally administered during scanning). Data were acquired on a Bruker 9.4-T MR scanner with rats under dexmedetomidine sedation in combination with isoflurane. Frontolimbic network regions-of-interest for data analysis included PFC [prelimbic (PrL), infralimbic (IL), and orbitofrontal cortex (OFC) portions], nucleus accumbens (NAc), caudate putamen (CPu), dorsal hippocampus, ventral tegmental area, amygdala, and somatosensory forelimb used as a control region. AIE decreased baseline resting-state connectivity between PFC subregions (PrL-IL and IL-OFC) and between PFC-striatal regions (PrL-NAc, IL-CPu, IL-NAc, OFC-CPu, and OFC-NAc). Acute ethanol induced negative blood-oxygen-level-dependent changes within all regions of interest examined, along with significant increases in functional connectivity in control, but not AIE animals. Together, these data support the hypothesis that binge-like adolescent alcohol exposure causes persistent decreases in baseline frontolimbic (particularly frontostriatal) connectivity and alters sensitivity to acute ethanol-induced increases in functional connectivity in adulthood.
| S-EPMC5760482 | biostudies-literature