Reward-related Brain Regions Research Articles

Abnormalities in deep-brain morphology and orbitofrontal cortical thinning relate to reward processing and body mass in adolescent girls.

Research examining the neural correlates of obesity has recently expanded. However, limited attention has focused on identifying unique brain signatures associated with obesity, particularly in adolescents. The aim of this study was to use surface-based approaches to examine the integrity of brain structures involved in processing the pleasurable effects of food with body mass and food reward sensitivity in adolescent girls. Structural morphology of the nucleus accumbens, amygdala, pallidum, and orbitofrontal cortex was examined in 89 adolescent girls with body mass ranging from normal to obese. High-resolution T1-weighted MPRAGE images were used to characterize deep-brain nuclei with high-dimensional diffeomorphic mapping procedures, while cortical thickness was derived from the FreeSurfer toolkit. Results revealed that zBMI was significantly associated with the shape of the left amygdala (β = -1.1, p < 0.021, 95% CI = -2.02, -0.16), volume of the right and left pallidum (β = 49.66, p < 0.010, 95% CI = 11.74, 87.58; β = 47.87, p < 0.017, 95% CI = 8.48, 87.25), and cortical thickness of the lateral and right medial orbitofrontal cortex (β = -0.06, p < 0.001, 95% CI = -0.09, -0.04; β = -0.05, p = 0.004, 95% CI = -0.08, -0.02). Sensitivity to food reward significantly predicted volume of the right nucleus accumbens (β = 0.66, p = 0.047, 95% CI = 0.01, 1). Contrast mapping for surface shape of the amygdala revealed significant outward deformation of the posterior lateral left amygdala and an inward deformation of the basolateral left amygdala in the group with overweight/obesity. Integrity of the left amygdala and orbitofrontal cortex varies as a function of body mass, with greater localized amygdalar volume loss, pallidum volume, and increased cortical thinning of the orbitofrontal cortex occurring as weight increases. Thus, overweight/obesity may be associated with surface-based abnormalities in brain structures associated with processing of reward value related to food. Overall, findings highlight the importance of understanding changes in reward-related brain regions and how they pertain to variability in body mass in adolescent girls.

More complex than you might think: Neural representations of food reward value in obesity

Obesity reached pandemic proportions and weight-loss treatments are mostly ineffective.The level of brain activity in the reward circuitry is proposed to be proportionate to the reward value of food stimuli, and stronger in people with obesity. However, empirical evidence is inconsistent. This may be due to the double-sided nature of high caloric palatable foods: at once highly palatable and high in calories (unhealthy).This study hypothesizes that, viewing high caloric palatable foods, a hedonic attentional focus compared to a health and a neutral attentional focus elicits more activity in reward-related brain regions, mostly in people with obesity. Moreover, caloric content and food palatability can be decoded from multivoxel patterns of activity most accurately in people with obesity and in the corresponding attentional focus.During one fMRI-session, attentional focus (hedonic, health, neutral) was manipulated using a one-back task with individually tailored food stimuli in 32 healthy-weight people and 29 people with obesity. Univariate analyses (p < 0.05, FWE-corrected) showed that brain activity was not different for palatable vs. unpalatable foods, nor for high vs. low caloric foods. Instead, this was higher in the hedonic compared to the health and neutral attentional focus. Multivariate analyses (MVPA) (p < 0.05, FDR-corrected) showed that palatability and caloric content could be decoded above chance level, independently of either BMI or attentional focus.Thus, brain activity to visual food stimuli is neither proportionate to the reward value (palatability and/or caloric content), nor significantly moderated by BMI. Instead, it depends on people's attentional focus, and may reflect motivational salience. Furthermore, food palatability and caloric content are represented as patterns of brain activity, independently of BMI and attentional focus. So, food reward value is reflected in patterns, not levels, of brain activity.

Electrocortical measures of win and loss processing are associated with mesocorticolimbic functional connectivity: A combined ERP and rs-fMRI study.

The reward positivity (RewP) event-related potential is a well-validated measure of reward processing implicated in internalizing psychopathologies. The RewP is thought to reflect reward reactivity in the mesocorticolimbic system; however, it is not clear how the RewP is related to the functional connectivity of reward-related brain regions. The current study examined associations between the RewP (Win and Loss residuals) and resting-state fMRI (rs-fMRI), among adults with internalizing psychopathology (IP) and healthy controls (HC). All participants (N=102) completed a validated monetary reward task during electroencephalogram and rs-fMRI. Regression analyses were conducted with (1) RewP-Win residual amplitude and striatal seeds (caudate, putamen, nucleus accumbens) and (2) RewP-Loss residual amplitude and anterior cingulate cortex (ACC) seeds. Overall, individuals with greater RewP-Win residual amplitude demonstrated increased rs-fMRI connectivity between striatal regions and the medial prefrontal cortex, as well as the parahippocampal gyrus, but decreased connectivity between striatal regions and regions involved in cognitive control and sensorimotor processing. Greater RewP-Loss residual was related to greater connectivity between the ACC and regions involved in reward/loss processing and motor control, but decreased connectivity between the ACC and regions involved in cognitive control. Relationships between the RewP and rs-fMRI were generally consistent across IP and HC. However, a few patterns were unique to IP. Results indicate the RewP is associated with resting-state functional connectivity of reward- and loss-related brain regions, suggesting connectivity of the mesocorticolimbic system may be an important individual difference factor in dimensions of attainment of reward and loss.

A novel HDAC1/2 inhibitor alleviates physical and emotional symptoms associated with spontaneous oxycodone withdrawal in neuropathic pain mice

The development of physical dependence and addiction disorders due to misuse of opioid analgesics is a major concern with pain therapeutics. In this study, we developed a mouse model of oxycodone misuse in order to gain insight into genes and molecular pathways in reward‐related brain regions that are affected by prolonged exposure to oxycodone and subsequent withdrawal in the presence or absence of chronic neuropathic pain. RNA‐sequencing (RNA‐seq) and bioinformatic analyses revealed that oxycodone withdrawal alone triggers robust gene expression adaptations in the nucleus accumbens (NAc), medial prefrontal cortex (mPFC), and ventral tegmental area (VTA), with numerous genes and pathways selectively affected by oxycodone withdrawal under peripheral nerve injury states. Our pathway analysis predicted that histone deacetylase 1 (HDAC1), an epigenetic modifier with a prominent role in striatal plasticity, is a top upstream regulator in opioid withdrawal in both the NAc and mPFC. Indeed, treatment with the novel HDAC1/2 inhibitor RCY1305 attenuated behavioral manifestations of oxycodone withdrawal, with the drug being more efficacious under states of neuropathic pain. Our studies also suggest that RCY1305 treated mice did not develop conditional place preference. Since RCY1305 displays antiallodynic actions with no rewarding effects in models of neuropathic pain, inhibition of HDAC1/2 may provide an avenue for chronic pain patients dependent on opioids to transition to non‐opioid analgesics. Overall, our study highlights transcriptomic events in components of the reward circuitry associated with oxycodone withdrawal under pain‐naïve and prolonged neuropathic pain states, thereby providing information on possible new targets for the treatment of physical dependence to opioids and transitioning individuals to non‐opioid medications for chronic pain management.

Fat Intake and Obesity-related Parameters Predict Striatal BDNF Gene Expression and Dopamine Metabolite Levels in Cafeteria Diet-fed Rats

Modern westernized diet is a major risk factor associated with the current obesity epidemic. To study the effects of dietary choices of Western societies, the cafeteria diet has been validated as a preclinical model of obesity. We aimed to investigate the behavioral and metabolic alterations induced by a cafeteria diet on gene expression and neurotransmitter contents involved in neural plasticity and reward processing. Male Wistar rats were exposed to either standard or cafeteria diet for 9 weeks. Food intake and body weight were scored daily. Behavioral effects were assessed in the elevated plus-maze (EPM) and open field (OFT) tests. Serum biochemical parameters, brain monoamines, and BDNF, TrkB, CRF, CREB, and Dnmt3A mRNA levels were analyzed in reward-related brain regions. We found that cafeteria-diet rats consumed more energy and food than the control group, leading to increased body weight gain and adiposity. The cafeteria-diet rats showed an anxiolytic-like effect in the OFT, but not in the EPM. The cafeteria diet increased BDNF expression in the dorsal striatum (DS), and norepinephrine, 5-HT, TrkB, CREB, and Dnmt3A levels in the hippocampus. Additionally, multiple regression analysis showed that accumbal DOPAC and BDNF mRNA levels were robustly predicted by hyperphagia, fat mass accumulation, and body weight gain only in the cafeteria group. Overall, cafeteria diet-induced hyperphagia could lead to alterations in hedonic and motivational control of food intake through changes in dopamine metabolism and BDNF signaling in the nucleus accumbens and the DS.

Pramipexole treatment attenuates mechanical hypersensitivity in male rats experiencing chronic inflammatory pain

Opioids are commonly prescribed for pain despite growing evidence of their low efficacy in the treatment of chronic inflammatory pain and the high potential for misuse. There is a clear need to investigate non-opioid alternatives for the treatment of pain. In the present study, we tested the hypothesis that acute and repeated dopamine agonist treatment would attenuate mechanical hypersensitivity in male Long-Evans rats experiencing chronic inflammatory pain. We used two clinically available therapeutics, l-DOPA (precursor of dopamine biosynthesis) and pramipexole (dopamine D2/3 receptor agonist), to examine the functional role of dopamine signaling on mechanical hypersensitivity using an animal model of chronic inflammatory pain (complete Freund's adjuvant, CFA). We found that both acute and repeated pramipexole treatment attenuated hyperalgesia-like behavior in CFA-treated animals but exhibited no analgesic effects in control animals. In contrast, there was no effect of acute or repeated l-DOPA treatment on mechanical hypersensitivity in either CFA- or saline-treated animals. Notably, we discovered some extended effects of l-DOPA and pramipexole on decreasing pain-like behavior at three days and one week post-drug treatment. We also examined the effects of pramipexole treatment on glutamatergic and presynaptic signaling in pain- and reward-related brain regions including the nucleus accumbens (NAc), dorsal striatum (DS), ventral tegmental area (VTA), cingulate cortex (CC), central amygdala (CeA), and periaqueductal gray (PAG). We found that pramipexole treatment decreased AMPA receptor phosphorylation (pGluR1845) in the NAc and DS but increased pGluR1845 in the CC and CeA. A marker of presynaptic vesicle release, pSynapsin, was also increased in the DS, VTA, CC, CeA, and PAG following pramipexole treatment. Interestingly, pramipexole increased pSynapsin in the NAc of saline-treated animals, but not CFA-treated animals, suggesting blunted presynaptic vesicle release in the NAc of CFA-treated animals following pramipexole treatment. To examine the functional implications of impaired presynaptic signaling in the NAc of CFA animals, we used ex vivo electrophysiology to examine the effects of pramipexole treatment on the intrinsic excitability of NAc neurons in CFA- and saline-treated animals. We found that pramipexole treatment reduced NAc intrinsic excitability in saline-treated animals but produced no change in NAc intrinsic excitability in CFA-treated animals. These findings indicate alterations in dopamine D2/3 receptor signaling in the NAc of animals with a history of chronic pain in association with the anti-hyperalgesic effects of pramipexole treatment.

Hippocampal Cannabinoid 1 Receptors Are Modulated Following Cocaine Self-administration in Male Rats.

Cocaine addiction is a complex pathology inducing long-term neuroplastic changes that, in turn, contribute to maladaptive behaviors. This behavioral dysregulation is associated with transcriptional reprogramming in brain reward circuitry, although the mechanisms underlying this modulation remain poorly understood. The endogenous cannabinoid system may play a role in this process in that cannabinoid mechanisms modulate drug reward and contribute to cocaine-induced neural adaptations. In this study, we investigated whether cocaine self-administration induces long-term adaptations, including transcriptional modifications and associated epigenetic processes. We first examined endocannabinoid gene expression in reward-related brain regions of the rat following self-administered (0.33mg/kg intravenous, FR1, 10days) cocaine injections. Interestingly, we found increased Cnr1 expression in several structures, including prefrontal cortex, nucleus accumbens, dorsal striatum, hippocampus, habenula, amygdala, lateral hypothalamus, ventral tegmental area, and rostromedial tegmental nucleus, with most pronounced effects in the hippocampus. Endocannabinoid levels, measured by mass spectrometry, were also altered in this structure. Chromatin immunoprecipitation followed by qPCR in the hippocampus revealed that two activating histone marks, H3K4Me3 and H3K27Ac, were enriched at specific endocannabinoid genes following cocaine intake. Targeting CB1 receptors using chromosome conformation capture, we highlighted spatial chromatin re-organization in the hippocampus, as well as in the nucleus accumbens, suggesting that destabilization of the chromatin may contribute to neuronal responses to cocaine. Overall, our results highlight a key role for the hippocampus in cocaine-induced plasticity and broaden the understanding of neuronal alterations associated with endocannabinoid signaling. The latter suggests that epigenetic modifications contribute to maladaptive behaviors associated with chronic drug use.

White matter microstructure associated with anhedonia among individuals with bipolar disorders and high-risk for bipolar disorders

BackgroundAnhedonia - a key symptom of depression - is highly associated with poorer outcomes and suicidal behavior. Alterations in the circuitry of reward-related brain regions have been robustly associated with anhedonia in unipolar depression, but not bipolar disorder (BD). We investigated white matter microstructures associated with anhedonia in participants with BD types I and II and first-degree relatives of patients with BD (BD-siblings). MethodsEighty participants (BD types I and II: 56 [70%], and BD-siblings: 24 [30%]) underwent diffusion tensor imaging (DTI); Fractional anisotropy (FA) of different tracts were computed. Anhedonia was assessed using item 8, (“inability to feel'') of the MADRS scale. General linear models were used to compare the FA of different tracts in participants with and without anhedonia controlling for several clinical and demographic variables. ResultsThe mean age of the sample was 37 (± 11) years old, and 68.8% were female. Participants with anhedonia (32.5%) presented lower mean FA in the left uncinate fasciculus (UF) (p = 0.005), right temporal endings of the superior longitudinal fasciculus (SLFT) (p = 0.04), and in the left and right parietal endings of the superior longitudinal fasciculus (SLFP) (p = 0.003, and p = 0.04, respectively). Similar comparisons between participants with or without current depressive episodes and between participants with or without inner tension according to the MADRS did not show significant differences, specificity of the findings for anhedonia. ConclusionsLower FA in the left UF and SLF are potential neuroimaging markers of anhedonia in individuals with BD and high-risk for BD.

Pilot study of food-specific go/no-go training for overweight individuals: brain imaging data suggest inhibition shapes food evaluation.

Food-specific go/no-go training might reduce overeating and facilitate weight loss. In this pilot study, we examined whether a food-specific go/no-go training over five weeks, as compared to a non-food-specific training, could produce changes in behavioral and neural responses to food images and body weight. Here, we used a sample of 51 overweight participants divided into training and control groups whose brain activity and food evaluation were measured before and after the training. Compared with the control group, in the training group we found significant reductions in high-calorie food evaluation. We also found lower activations in inhibitory control- and reward-related brain regions in response to high-calorie food images. Further, activation change of the mid-insula in response to the high-calorie food images was positively associated with change in the evaluation of those images. However, we found no evidence for a significant effect of food-specific go/no-go training on body weight change. Our findings highlight that food-specific go/no-go training in overweight individuals can reduce high-calorie food evaluation, but also neural activations in inhibitory control- and reward- related brain regions.

Effects of OPRM1 and DRD2 on brain structure in drug-naïve adolescents: Genetic and neural vulnerabilities to substance use.

Genetic variants in the opioid receptor mu 1 (OPRM1) and dopamine receptor d2 (DRD2) genes are implicated in behavioral phenotypes related to substance use disorders (SUD). Despite associations among OPRM1 (rs179971) and DRD2 (rs6277) genes and structural alterations in neural reward pathways implicated in SUDs, little is known about the contribution of risk-related gene variants to structural neurodevelopment. In a 3-year longitudinal study of initially SU-naïve adolescents (N = 129; 70 females; 11-14years old), participants underwent an MRI structural scan at baseline and provided genetic assays for OPRM1 and DRD2 with SU behavior assessed during follow-up visits. Baseline differences in key reward-related brain regions (i.e., bilateral caudate and cingulate cortex) were detected in those with genetic liability for SU in OPRM1 who went onto engage in SU at subsequent waves of data collection. In addition, main effects of OPRM1, DRD2, and SU were related to variability in structure of the putamen, anterior cingulate, and nucleus accumbens, respectively. These data provide preliminary evidence that genetic risk factors interact with future SU to confer structural variability prior to SU in regions commonly implicated in risk for SU and the development of SUDs.

Mitochondria-Related Nuclear Gene Expression in the Nucleus Accumbens and Blood Mitochondrial Copy Number After Developmental Fentanyl Exposure in Adolescent Male and Female C57BL/6 Mice.

The potency of the synthetic opioid fentanyl and its increased clinical availability has led to the rapid escalation of use in the general population, increased recreational exposure, and subsequently opioid-related overdoses. The wide-spread use of fentanyl has, consequently, increased the incidence of in utero exposure to the drug, but the long-term effects of this type of developmental exposure are not yet understood. Opioid use has also been linked to reduced mitochondrial copy number in blood in clinical populations, but the link between this peripheral biomarker and genetic or functional changes in reward-related brain circuitry is still unclear. Additionally, mitochondrial-related gene expression in reward-related brain regions has not been examined in the context of fentanyl exposure, despite the growing literature demonstrating drugs of abuse impact mitochondrial function, which subsequently impacts neuronal signaling. The current study uses exposure to fentanyl via dam access to fentanyl drinking water during gestation and lactation as a model for developmental drug exposure. This perinatal drug-exposure is sufficient to impact mitochondrial copy number in circulating blood leukocytes, as well as mitochondrial-related gene expression in the nucleus accumbens (NAc), a reward-related brain structure, in a sex-dependent manner in adolescent offspring. Specific NAc gene expression is correlated with both blood mitochondrial copy number and with anxiety related behaviors dependent on developmental exposure to fentanyl and sex. These data indicate that developmental fentanyl exposure impacts mitochondrial function in both the brain and body in ways that can impact neuronal signaling and may prime the brain for altered reward-related behavior in adolescence and later into adulthood.

Exploration of alcohol use disorder-associated brain miRNA\u2013mRNA regulatory networks

Transcriptomic changes in specific brain regions can influence the risk of alcohol use disorder (AUD), but the underlying mechanism is not fully understood. We investigated AUD-associated miRNA–mRNA regulatory networks in multiple brain regions by analyzing transcriptomic changes in two sets of postmortem brain tissue samples and ethanol-exposed human embryonic stem cell (hESC)-derived cortical interneurons. miRNA and mRNA transcriptomes were profiled in 192 tissue samples (Set 1) from eight brain regions (amygdala, caudate nucleus, cerebellum, hippocampus, nucleus accumbens, prefrontal cortex, putamen, and ventral tegmental area) of 12 AUD and 12 control European Australians. Nineteen differentially expressed miRNAs (fold-change>2.0 & P < 0.05) and 97 differentially expressed mRNAs (fold-change>2.0 & P < 0.001) were identified in one or multiple brain regions of AUD subjects. AUD-associated miRNA–mRNA regulatory networks in each brain region were constructed using differentially expressed and negatively correlated miRNA–mRNA pairs. AUD-relevant pathways (including CREB Signaling, IL-8 Signaling, and Axonal Guidance Signaling) were potentially regulated by AUD-associated brain miRNA–mRNA pairs. Moreover, miRNA and mRNA transcriptomes were mapped in additional 96 tissue samples (Set 2) from six of the above eight brain regions of eight AUD and eight control European Australians. Some of the AUD-associated miRNA–mRNA regulatory networks were confirmed. In addition, miRNA and mRNA transcriptomes were analyzed in hESC-derived cortical interneurons with or without ethanol exposure, and ethanol-influenced miRNA–mRNA regulatory networks were constructed. This study provided evidence that alcohol could induce concerted miRNA and mRNA expression changes in reward-related or alcohol-responsive brain regions. We concluded that altered brain miRNA–mRNA regulatory networks might contribute to AUD development.

Mental fatigue correlates with depression of task-related network and augmented DMN activity but spares the reward circuit

Long-lasting and demanding cognitive activity typically leads to mental fatigue (MF). Indirect evidence suggests that MF may be caused by altered motivational processes. Here, we hypothesized that if MF consists in an alteration of motivational states, brain functional changes induced by MF could specifically affect the brain motivation circuit. In order to test this hypothesis, we devised a functional neuroimaging protocol to detect altered brain activity in reward-related brain regions in relation to cognitively induced mental fatigue.Twenty-five healthy participants underwent a FATIGUE and a CONTROL session on different days. In the FATIGUE session, MF was induced by performing a demanding cognitive task (adapted Stroop task) during 90 min, whereas in the CONTROL session, participants were asked to read magazines for the same period of time. We measured the neural consequences of the MF induction during a working memory task (Missing Number task) while modulating extrinsic motivation with block-wise variations in monetary reward. We also tracked participants’ momentary fatigue, anxiety state and intrinsic motivation prior to and following the MF inducement and measurement.Accuracy on the Missing Number Task was lower in the FATIGUE than in the CONTROL condition. Furthermore, subjective MF, but not its behavioral manifestations, was associated with hypoactivity of the task-evoked neural responses. Importantly, activity in regions modulated by reward showed no differences between FATIGUE and CONTROL sessions. In parallel, subjective MF correlated with increased on-task activity and resting-state functional connectivity in the default mode network.These results indicate that subjective mental fatigue is not associated with altered activity in the brain motivation circuit but rather with hypoactivity in task-specific brain regions as well as relative increases of activity and connectivity in the default mode network during and after the task.

Test-retest reliability of functional MRI food receipt, anticipated receipt, and picture tasks

Functional MRI (fMRI) tasks are increasingly being used to advance knowledge of the etiology and maintenance of obesity and eating disorders. Thus, understanding the test-retest reliability of BOLD signal contrasts from these tasks is important. To evaluate test-retest reliability of responses in reward-related brain regions to food receipt paradigms (palatable tastes, anticipated palatable tastes), food picture paradigms (high-calorie food pictures), a monetary reward paradigm (winning money and anticipating winning money), and a thin female model picture paradigm (thin female model pictures). We conducted secondary univariate contrast-based analyses in data drawn from 4 repeated-measures fMRI studies. Participants (Study 1: N=60, mean [M] age=15.2±1.1 y; Study 2: N=109, M age=15.1±0.9 y; Study 3: N=39, M age=21.2±3.7 y; Study 4: N=62, M age=29.7±6.2 y) completed the same tasks over 3-wk to 3-y test-retest intervals. Studies 3 and 4 included participants with eating disorders and obesity, respectively. Test-retest reliability of the food receipt and food picture paradigms was poor, with average ICC values ranging from 0.07 to 0.20. The monetary reward paradigm and the thin female model picture paradigm also showed poor test-retest reliability: average ICC values 0.21 and 0.12, respectively. Although several regions demonstrated moderate to good test-retest reliability, these results did not replicate across studies using similar paradigms. In Studies 3 and 4, but not Study 1, test-retest reliability in visual processing regions was moderate to good when contrasting single conditions with a low-level baseline. Results underscore the importance of examining the temporal reliability of fMRI tasks and call for the development and use of well-validated standardized fMRI tasks in eating- and obesity-related studies that can provide more reliable measures of neural activation. The trials were registered at clinicaltrials.gov as NCT02084836, NCT01949636, NCT03261050, and NCT03375853.

Single Exposure to the Cathinones MDPV and α-PVP Alters Molecular Markers of Neuroplasticity in the Adult Mouse Brain.

Synthetic cathinones have gained popularity among young drug users and are widely used in the clandestine market. While the cathinone-induced behavioral profile has been extensively investigated, information on their neuroplastic effects is still rather fragmentary. Accordingly, we have exposed male mice to a single injection of MDPV and α-PVP and sacrificed the animals at different time points (i.e., 30 min, 2 h, and 24 h) to have a rapid readout of the effect of these psychostimulants on neuroplasticity in the frontal lobe and hippocampus, two reward-related brain regions. We found that a single, low dose of MDPV or α-PVP is sufficient to alter the expression of neuroplastic markers in the adult mouse brain. In particular, we found increased expression of the transcription factor Npas4, increased ratio between the vesicular GABA transporter and the vesicular glutamate transporter together with changes in the expression of the neurotrophin Bdnf, confirming the widespread impact of these cathinones on brain plasticity. To sum up, exposure to low dose of cathinones can impair cortical and hippocampal homeostasis, suggesting that abuse of these cathinones at much higher doses, as it occurs in humans, could have an even more profound impact on neuroplasticity.

Functional connectivity between the caudate and medial prefrontal cortex reflects individual honesty variations in adults and children

Deception emerges in early childhood and prevails in adults. Activation patterns in previous adults’ task-state functional magnetic resonance imaging (fMRI), though sensitive to state honesty on a specific decision, are less reliable reflecting trait honesty. Besides of state honesty, most previous neuroimaging studies about dishonesty suffer the generalization problem due to the major focus on adults with children unexplored. To investigate honesty associated functional brain networks variations, 98 healthy adults (Age: 18–28 y.o.; 49 males and 49 females) were invited to participate in a resting-state functional magnetic resonance imaging (rfMRI) study (Study 1). We investigated how functional connections between the caudate and the medial prefrontal cortex (mPFC) change among adults who differ in self-reported trait honesty. Results showed that adults with higher trait honesty have increased functional connectivity from the caudate to the mPFC, which is identified as an honesty-related hub region in global brain connectivity analysis and connects more tightly to a wide range of brain regions including the amygdala. Study 2 compared functional connectivity between children with high vs. low lying frequencies (Age: 6–16 y.o.; 61 males and 39 females) based on a publicly accessible database of rfMRI. Consistent with findings in adults, increased functional connectivity from the caudate to the mPFC was found in less frequently lying children. Despite different honesty indicators of self-reported honesty trait in adults and parent-reported lying patterns in children, consistent findings have been noted in the two samples with regards to functional connectivity variations between reward-related and self-related brain regions. These findings suggest functional connectivity alterations between the caudate and the mPFC contribute to honesty variations in both adults and children.

Increased Consumption of Sugar in Beverages Is Associated With Blunted Dopaminergic Brain Response to High Sugar Taste

ObjectivesThe 2020 dietary guidelines specifically recommended a decrease in sugar intake. Reward-related, brain-based models of overeating and obesity suggest that increased intake of highly palatable foods is linked to decreased dopaminergic (striatal and prefrontal) brain functioning. This reduction acts to increase consumption of food to achieve pleasure. Here, we examined whether increased dietary intake of sugar and fat would be associated with increased activation in reward-related brain regions during anticipation of a sugar sweetened beverage (SSB), but decreased activation during SSB receipt. MethodsYoung adults (n = 100, age = 21.8 ± 2.4 y, BMI = 23.3 ± 3.5, 70% female) underwent an fMRI scan examining brain responses to receipt of a SSB, a tasteless rinse, and response cue-induced anticipation of these tastes. The Block Food Frequency Questionnaire (FFQ) was used to assess average dietary intake, % daily caloric intake from SSBs, sugar, sugar from SSBs and fat. These were correlated with whole-brain BOLD responses to SSB anticipation and receipt contrasts (e.g., SSB > rinse). Significance was corrected for multiple comparisons; pFWE < .05. ResultsIncreased consumption of sugar calories from SSBs was correlated with decreased activity in regions associated with dopamine (posterior midbrain, dorsolateral/orbitofrontal cortices) and taste processing regions (postcentral gyrus) during receipt of SSB (> rinse). ConclusionsThese results directly support previous research (Burger & Stice 2012; AJCN) demonstrating that increased consumption of highly palatable foods is associated with reduced dopaminergic brain response during consumption specifically of those foods. Critically, we demonstrate these effects with SSBs which are far more widely consumed. Our results were specific to increased intake of sugar calories from SSBs and not total calories from SSBs or total sugar calories, suggesting that added sugars in these beverages have the potential to lead to altered frontostriatal brain responses. Funding SourcesNIDDK R01DK112317.

The social network: Neural control of sex differences in reproductive behaviors, motivation, and response to social isolation.

Social animal species present a vast repertoire of social interactions when encountering conspecifics. Reproduction-related behaviors, such as mating, parental care, and aggression, are some of the most rewarding types of social interactions and are also the most sexually dimorphic ones. This review focuses on rodent species and summarizes recent advances in neuroscience research that link sexually dimorphic reproductive behaviors to sexual dimorphism in their underlying neuronal circuits. Specifically, we present a few possible mechanisms governing sexually-dimorphic behaviors, by hypothalamic and reward-related brain regions. Sex differences in the neural response to social isolation in adulthood are also discussed, as well as future directions for comparative studies with naturally solitary species.

Hippocampal mu opioid receptors are modulated following cocaine self-administration in rat.

Cocaine addiction is a complex pathology induced by long-term brain changes. Understanding the neurochemical changes underlying the reinforcing effects of this drug of abuse is critical for reducing the societal burden of drug addiction. The mu opioid receptor plays a major role in drug reward. This receptor is modulated by chronic cocaine treatment in specific brain structures, but few studies investigated neurochemical adaptations induced by voluntary cocaine intake. In this study, we investigated whether intravenous cocaine-self administration (0.33mg/kg/injection, fixed-ratio 1 [FR1], 10days) in rats induces transcriptional and functional changes of the mu opioid receptor in reward-related brain regions. Epigenetic processes with histone modifications were examined for two activating marks, H3K4Me3, and H3K27Ac. We found an increase of mu opioid receptor gene expression along with a potentiation of its functionality in hippocampus of cocaine self-administering animals compared to saline controls. Chromatin immunoprecipitation followed by qPCR revealed no modifications of the histone mark H3K4Me3 and H3K27Ac levels at mu opioid receptor promoter. Our study highlights the hippocampus as an important target to further investigate neuroadaptive processes leading to cocaine addiction.

Reduced neural differentiation of rewards and punishment during passive avoidance learning in adolescents with generalized anxiety disorder.

It has been proposed that individuals with generalized anxiety disorder (GAD) show dysfunctional computations related to approach-avoidance decision-making. However, few studies have examined the neural basis of this impairment, particularly in adolescents with GAD. The goal of the current study was to address this gap in the literature. The study involved 51 adolescents with GAD and 51 typically developing (TD) comparison individuals matched on age (16.10 and 15.75 respective means), gender (30 F/21 M and 24 F/27 M), and IQ (103.20 and 103.18 respective means). Participants underwent functionalmagnetic resonance imaging during a passive avoidance task. We found a significant Group-by-Reinforcement interaction within reward-related brain regions including the caudate, putamen, mid cingulate/paracentral lobule, and superior and middle frontal gyrus. TD adolescents showed a greater differential response to reward versus punishment feedback within these regions relative to adolescents with GAD. In particular, this reflected reduced responses to rewards in the adolescents with GAD. There were no group differences in neural responses when making approach/avoidance responses. The results of this study suggest reduced differential responsiveness to reinforcement as a component of the pathophysiology seen in adolescents with GAD. This dysfunction likely underpins decision-making impairments that may exacerbate the participants' worry.