Dopamine projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and from the substantia nigra (SN) to the dorsal striatum are involved in addiction. However, relatively ...little is known about the implication of these circuits in Internet gaming disorder (IGD). This study examined the alteration of resting-state functional connectivity (RSFC) and diffusion tensor imaging (DTI) -based structural connectivity of VTA/SN circuits in 61 young male participants (33 IGD and 28 healthy controls). Correlation analysis was carried out to investigate the relationship between the neuroimaging findings and the behavioral Internet Addiction Test (IAT). Both the NAc and medial orbitofrontal cortex (mOFC) showed lower RSFC with VTA in IGD subjects compared with controls. Moreover, the RSFC strength of VTA-right NAc and VTA-left mOFC correlated negatively with IAT in IGD subjects. The IGD subjects also showed lower structural connectivity in bilateral VTA-NAc tracts compared with controls, but the connectivity did not correlate with IAT in IGD. We provide evidence that functional and structural connectivity of the VTA-NAc pathway, and functional connectivity of the VTA-mOFC pathway are implicated in IGD. Since these pathways are important for dopamine reward signals and salience attribution, the findings suggest involvement of the brain DA reward system in the neurobiology of IGD. The association of functional but not structural connectivity of VTA circuits with IAT suggests that while lower structural connectivity might underlie vulnerability for IGD, lower functional connectivity may modulate severity. These results strengthen the evidence that IGD shares similar neuropathology with other addictions.
Objective
The goal of this study was to investigate laparoscopic sleeve gastrectomy (LSG)‐induced changes in choice impulsivity and the neural correlates in individuals with obesity (OB).
Methods
The ...study employed functional magnetic resonance imaging with a delay discounting task in 29 OB tested before and 1 month after LSG. Thirty participants with normal weight matched to OB with gender and age were recruited as the control group and underwent an identical functional magnetic resonance imaging scan. Alterations in activation and functional connectivity between pre‐ and post‐LSG were investigated and compared with participants with normal weight.
Results
OB exhibited significantly reduced discounting rate after LSG. During the delay discounting task, hyperactivation in dorsolateral prefrontal cortex, right caudate, and dorsomedial prefrontal cortex decreased in OB after LSG. LSG additionally engaged compensatory effects through increased activation in bilateral posterior insula and functional connectivity between caudate and dorsomedial prefrontal cortex. Those changes were associated with decreased discounting rate and BMI as well as improved eating behaviors.
Conclusions
These findings indicate that decreased choice impulsivity following LSG was associated with the changes in regions involved in executive control, reward evaluation, interoception, and prospection. This study may provide neurophysiological support for the development of nonoperative treatments such as brain stimulation for individuals with obesity and overweight.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Dopamine mediates the rewarding effects of food that can lead to overeating and obesity, which then trigger metabolic neuroadaptations that further perpetuate excessive food consumption. We tested ...the hypothesis that the dopamine response to calorie intake (independent of palatability) in striatal brain regions is attenuated with increases in weight.
We used positron emission tomography with 11Craclopride to measure dopamine changes triggered by calorie intake by contrasting the effects of an artificial sweetener (sucralose) devoid of calories to that of glucose to assess their association with body mass index (BMI) in nineteen healthy participants (BMI range 21-35).
Neither the measured blood glucose concentrations prior to the sucralose and the glucose challenge days, nor the glucose concentrations following the glucose challenge vary as a function of BMI. In contrast the dopamine changes in ventral striatum (assessed as changes in non-displaceable binding potential of 11Craclopride) triggered by calorie intake (contrast glucose - sucralose) were significantly correlated with BMI (r = 0.68) indicating opposite responses in lean than in obese individuals. Specifically whereas in normal weight individuals (BMI <25) consumption of calories was associated with increases in dopamine in the ventral striatum in obese individuals it was associated with decreases in dopamine.
These findings show reduced dopamine release in ventral striatum with calorie consumption in obese subjects, which might contribute to their excessive food intake to compensate for the deficit between the expected and the actual response to food consumption.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The use of Positron emission tomography (PET) to study the effects of acute and chronic alcohol on the human brain has enhanced our understanding of the mechanisms underlying alcohol's rewarding ...effects, the neuroadaptations from chronic exposure that contribute to tolerance and withdrawal, and the changes in fronto-striatal circuits that lead to loss of control and enhanced motivation to drink that characterize alcohol use disorders (AUD). These include studies showing that alcohol's reinforcing effects may result not only from its enhancement of dopaminergic, GABAergic and opioid signaling but also from its caloric properties. Studies in those suffering from an AUD have revealed significant alterations in dopamine (DA), GABA, cannabinoids, opioid and serotonin neurotransmission and in brain energy utilization (glucose and acetate metabolism) that are likely to contribute to compulsive alcohol taking, dysphoria/depression, and to alcohol-associated neurotoxicity. Studies have also evaluated the effects of abstinence on recovery of brain metabolism and neurotransmitter function and the potential value of some of these measures to predict clinical outcomes. Finally, PET studies have started to provide insights about the neuronal mechanisms by which certain genes contribute to the vulnerability to AUD. These findings have helped identify new strategies for prevention and treatment of AUD.
This article is part of the Special Issue entitled “Alcoholism”.
•Calories in alcohol might contribute to its rewarding effects.•Alcohol abuse increases reliance on acetate as an energy source in the brain.•Loss of control in AUD is associated with reduced striatal D2 receptor signaling.•Enhanced striatal D2 receptor signaling is protective to those vulnerable to AUD.•Chronic alcohol reduces μ opioid and CB1 receptors and GABAergic signaling in brain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, SAZU, SBCE, UL, UM, UPCLJ, UPUK, ZRSKP
Trauma in childhood and adolescence has long-term negative consequences in brain development and behavior and increases the risk for psychiatric disorders. Among them, post-traumatic stress disorder ...(PTSD) during adolescence illustrates the connection between trauma and substance misuse, as adolescents may utilize substances to cope with PTSD. Drug misuse may in turn lead to neuroadaptations in learning processes that facilitate the consolidation of traumatic memories that perpetuate PTSD. This reflects, apart from common genetic and epigenetic modifications, overlapping neurocircuitry engagement triggered by stress and drug misuse that includes structural and functional changes in limbic brain regions and the salience, default-mode, and frontoparietal networks. Effective strategies to prevent PTSD are needed to limit the negative consequences associated with the later development of a substance use disorder (SUD). In this review, we will examine the link between PTSD and SUDs, along with the resulting effects on memory, focusing on the connection between the development of an SUD in individuals who struggled with PTSD in adolescence. Neuroimaging has emerged as a powerful tool to provide insight into the brain mechanisms underlying the connection of PTSD in adolescence and the development of SUDs.
Sex differences in the prevalence of dopamine-related neuropsychiatric diseases and in the sensitivity to dopamine-boosting drugs such as stimulants is well recognized. Here we assessed whether there ...are sex differences in the brain dopamine system in humans that could contribute to these effects. We analyzed data from two independent
Craclopride PET brain imaging studies that measured methylphenidate-induced dopamine increases in the striatum using different routes of administration (Cohort A = oral 60 mg; Cohort B = intravenous 0.5 mg/kg; total n = 95; 65 male, 30 female), in blinded placebo-controlled designs. Females when compared to males reported stronger feeling of "drug effects" and showed significantly greater dopamine release in the ventral striatum (where nucleus accumbens is located) to both oral and intravenous methylphenidate. In contrast, there were no significant differences in methylphenidate-induced increases in dorsal striatum for either oral or intravenous administration nor were there differences in levels of methylphenidate in plasma. The greater dopamine increases with methylphenidate in ventral but not dorsal striatum in females compared to males suggests an enhanced sensitivity specific to the dopamine reward system that might underlie sex differences in the vulnerability to substance use disorders and to attention-deficit/hyperactivity disorder (ADHD).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The value of rewards (natural rewards and drugs) is associated with dopamine increases in the nucleus accumbens and varies as a function of context. The prefrontal cortex has been implicated in the ...context dependency of rewards and in the fixated high value that drugs have in addiction, although the mechanisms are not properly understood. Here we test the hypothesis that the prefrontal cortex regulates the value of rewards by modulating dopamine increases in nucleus accumbens and that this regulation is disrupted in addicted subjects. We used positron emission tomography to evaluate the activity of the prefrontal cortex (measuring brain glucose metabolism with 18Ffluorodeoxyglucose) and dopamine increases (measured with 11Craclopride, a D2/D3 receptor ligand with binding that is sensitive to endogenous dopamine) induced by the stimulant drug methylphenidate in 20 controls and 20 detoxified alcoholics, most of whom smoked. In all subjects, methylphenidate significantly increased dopamine in striatum. In ventral striatum (where the nucleus accumbens is located) and in putamen, dopamine increases were associated with the rewarding effects of methylphenidate (drug liking and high) and were profoundly attenuated in alcoholics (70 and 50% lower than controls, respectively). In controls, but not in alcoholics, metabolism in orbitofrontal cortex (region involved with salience attribution) was negatively associated with methylphenidate-induced dopamine increases in ventral striatum. These results are consistent with the hypothesis that the orbitofrontal cortex modulates the value of rewards by regulating the magnitude of dopamine increases in the ventral striatum and that disruption of this regulation may underlie the decreased sensitivity to rewards in addicted subjects.
Traditional functional magnetic resonance imaging (fMRI) studies exploit endogenous brain activity for mapping brain activation during "periodic" cognitive/emotional challenges or brain functional ...connectivity during the "resting state". Previous studies demonstrated that these approaches provide a limited view of brain function which can be complemented by each other. We hypothesized that graph theory functional connectivity density (FCD) mapping would demonstrate regional FCD decreases between resting-state scan and a continuous "task-state" scan. Forty-five healthy volunteers underwent functional connectivity MRI during resting-state as well as a continuous visual attention task, and standard fMRI with a blocked version of the visual attention task. High-resolution data-driven FCD mapping was used to measure task-related connectivity changes without a priori hypotheses. Results demonstrate that task performance was associated with FCD decreases in brain regions weakly activated/deactivated by the task. Furthermore, a pronounced negative correlation between blood oxygen level-dependent-fMRI activation and task-related FCD decreases emerged across brain regions that also suggest the disconnection of task-irrelevant networks during task performance. The correlation between improved accuracy and stronger FCD decreases further suggests the disconnection of task-irrelevant networks during task performance. Functional connectivity can potentiate traditional fMRI studies and offer a more complete picture of brain function.
Gastric distention during meal ingestion activates vagal afferents, which send signals from the stomach to the brain and result in the perception of fullness and satiety. Distention is one of the ...mechanisms that modulates food intake. We measured regional brain activation during dynamic gastric balloon distention in 18 health subjects using functional magnetic resonance imaging and the blood oxygenation level-dependent (BOLD) responses. The BOLD signal was significantly changed by both inflow and outflow changes in the balloon's volume. For lower balloon volumes, water inflow was associated with activation of sensorimotor cortices and right insula. The larger volume condition additionally activated left posterior amygdala, left posterior insula and the left precuneus. The response in the left amygdala and insula was negatively associated with changes in self-reports of fullness and positively with changes in plasma ghrelin concentration, whereas those in the right amygdala and insula were negatively associated with the subject's body mass index. The widespread activation induced by gastric distention corroborates the influence of vagal afferents on cortical and subcortical brain activity. These findings provide evidence that the left amygdala and insula process interoceptive signals of fullness produced by gastric distention involved in the controls of food intake.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The translocator protein (TSPO) transports cholesterol into mitochondria and is involved in steroidogenesis. The TSPO polymorphism rs6971 influences binding of cholesterol and other TSPO ligands ...including positron‐emission tomography (PET) imaging radiotracers. Although it is recognized that alcohol increases plasma high‐density lipoproteins (HDLs), its effects on total cholesterol and triglycerides along with its relationship to TSPO genotype have not been assessed. Here, we evaluated whether plasma cholesterol and triglycerides are disrupted in alcohol use disorder (AUD) and their association with rs6971 in 932 AUD participants (DSM IV or 5) and 546 controls. AUD participants compared with controls had significantly higher plasma levels of total cholesterol, HDL, and triglycerides, but not of low‐density lipoprotein (LDL). In the AUD group only, TSPO rs6971 had a significant effect on plasma levels of cholesterol, LDL, and triglycerides (AA (n = 62) > AG (n = 319) > GG (n = 551)), but not on HDL levels. Additionally, we showed a significant effect of TSPO rs6971 on withdrawal scores (Clinical Institute Withdrawal Assessment for Alcohol CIWA), with higher scores in AA (n = 50) compared with AG (n = 238) and GG (n = 428). CIWA scores in AUD participants correlated negatively with LDL and positively with HDL, but not with total cholesterol or triglycerides. These findings corroborate elevated plasma cholesterol and HDL levels in AUD and document significant increases in triglycerides. We also reveal for the first time an association in AUD participants between TSPO rs6971 genotype and plasma cholesterol, LDL, and triglyceride levels (not for HDL) and with withdrawal severity. Mediation analyses revealed that LDL (but not HDL) influenced the association between TSPO and alcohol withdrawal severity.
Here we reveal for the first time an association between TSPO rs6971 genotype and plasma cholesterol levels, LDL and triglycerides and with alcohol withdrawal severity in AUD. We also provide evidence for elevated plasma cholesterol levels (total and HDL)and triglycerides in AUD and document an opposite association between alcohol withdrawal severity with HDL (positive) to that with LDL (negative) levels.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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