Neural response to rewards moderates the within-person association between daily positive events and positive affect during a period of stress exposure.

Stress and neural responses to reward can interact to predict psychopathology, but the mechanisms of this interaction are unclear. One possibility is that the strength of neural responses to reward can affect the ability to maintain positive affect during stress. In this study, 105 participants completed a monetary reward task to elicit the reward positivity (RewP), an event-related potential sensitive to rewards. Subsequently, during a stressful period, participants reported on their affect nine times a day and on daily positive and negative events for 10 days. Even during heightened stress, experiencing more positive events was associated with increased positive affect. The RewP significantly moderated this association: Individuals with a larger RewP reported greater increases in positive affect when they experienced more positive events, relative to individuals with a smaller RewP. A blunted RewP might contribute to stress susceptibility by affecting how much individuals engage in positive emotion regulation during stress.

Chronic stress in peer relationships moderates the association between pubertal development and neural response to emotional faces in adolescence.

Adolescence is a period of heightened risk for multiple forms of psychopathology, partly due to greater exposure to interpersonal stress. One way that interpersonal stress may increase risk for psychopathology is by altering the normative development of neural systems that support socio-affective processing. The late positive potential (LPP) is an event-related potential component that reflects sustained attention to motivationally-salient information and is a promising marker of risk for stress-related psychopathology. However, it is not clear how the LPP to socio-affective information changes across adolescence, nor whether exposure to stress with peers interferes with normative developmental differences in the LPP to socio-affective content during this period. In 92 adolescent girls (10-19 years old), we assessed the LPP to task-irrelevant emotional and neutral faces, as well as behavioural measures of interference following the presentation of these faces. Adolescents at more advanced stages of puberty showed a smaller LPP to emotional faces, but adolescents exposed to greater peer stress exhibited a larger LPP to these stimuli. Additionally, for girls exposed to lower levels of peer stress, more advanced pubertal development was associated with a smaller LPP to emotional faces, whereas for girls exposed to higher levels of peer stress, the association between pubertal development and the LPP to emotional faces was not significant. Neither stress nor pubertal stage was significantly associated with behavioural measures. Combined, these data suggest that one pathway through which stress exposure increases risk for psychopathology during adolescence is by interfering with the normative development of socio-affective processing.

Effects of the COVID-19 Pandemic on Neural Responses to Reward: A Quasi-experiment.

BACKGROUND: The COVID-19 pandemic has been a prolonged period of stress due to social isolation, illness, death, and other major life disruptions. Neural reward sensitivity, essential for healthy functioning, may become reduced under major naturalistic stressors, though few studies have examined this. The present study sought to test whether neural responses to rewards were significantly blunted by the stress of the pandemic. METHODS: We compared 2 groups of young adult participants, who completed a monetary reward task while an electroencephalogram was recorded, at 2 time points, 1 to 3 years apart. Our measure of reward sensitivity was the reward positivity (RewP), a neural marker enhanced to gain relative to loss feedback. The magnitude of the RewP is sensitive to stress exposure and can prospectively predict depression. The pre-pandemic group (n = 41) completed both time points before the pandemic, while the pandemic group (n = 39) completed the baseline visit before the pandemic and the follow-up visit during its second year. RESULTS: The pandemic group reported having experienced significant stressors over the course of the pandemic. We did not observe a significant decrease in the RewP from baseline to follow-up in the pre-pandemic group. In contrast, in the pandemic group, the RewP was significantly blunted at the follow-up visit to the extent that it no longer distinguished gain from loss feedback. CONCLUSIONS: These results suggest that prolonged naturalistic stressors can result in adaptations in neural responses to rewards. Our findings also highlight a possible mechanism linking stress to the development of depression.

Family History of Depression and Neural Reward Sensitivity: Findings From the Adolescent Brain Cognitive Development Study.

BACKGROUND: Previous studies have found that offspring of depressed parents exhibit reduced striatal reward response to anticipating and receiving rewards, suggesting that this may constitute a neurobiological risk marker for depression. The present study aimed to assess whether maternal and paternal depression history have independent effects on offspring reward processing and whether greater family history density of depression is associated with increased blunting of striatal reward responses. METHODS: Data from the baseline visit of the ABCD (Adolescent Brain Cognitive Development) Study were used. After exclusion criteria, 7233 9- and 10-year-old children (49% female) were included in analyses. Neural responses to reward anticipation and receipt in the monetary incentive delay task were examined in 6 striatal regions of interest. Using mixed-effects models, we evaluated the effect of maternal or paternal depression history on striatal reward response. We also evaluated the effect of family history density on reward response. RESULTS: Across all 6 striatal regions of interest, neither maternal nor paternal depression significantly predicted blunted response to reward anticipation or feedback. Contrary to hypotheses, paternal depression history was associated with increased response in the left caudate during anticipation, and maternal depression history was associated with increased response in the left putamen during feedback. Family history density was not associated with striatal reward response. CONCLUSIONS: Our findings suggest that family history of depression is not strongly associated with blunted striatal reward response in 9- and 10-year-old children. Factors contributing to heterogeneity across studies need to be examined in future research to reconcile these results with past findings.

Risk factors for the intergenerational transmission of depression in women and girls: Understanding neural correlates of major depressive disorder and the role of early-onset maternal depression.

Deficits in neural reward processing have been implicated in the etiology of depression and have been observed in high-risk individuals. However, depression is a heterogeneous disorder, and not all depressed individuals exhibit blunted neural reward response, suggesting the need to examine more specific depression phenotypes. Early-onset depression, a well-defined phenotype, has been associated with greater intergenerational transmission of depression and appears more closely linked to neural reward processing deficits. The present study examined whether a maternal history of early-onset depression was associated with neural reward response among mothers and their daughters. Mothers with and without a history of depression, as well as their biological, adolescent daughters (N = 109 dyads), completed a monetary reward guessing task while electroencephalogram was collected. Analyses focused on the Reward Positivity (RewP), an event-related potential following reward receipt. Adjusting for current depressive symptoms, maternal early-onset depression was associated with a blunted RewP in the mothers and a numerically smaller RewP in their never-depressed, adolescent daughters. Maternal adult-onset depression was not statistically associated with a blunted RewP in mothers or daughters. Thus, a blunted RewP appears to be a trait-like vulnerability marker for depression that emerges before depression onset and relates to more specific depression phenotypes (e.g., early-onset depression). These findings have implications for early identification of individuals at risk of depression and for developing more targeted interventions.

Neural response to social but not monetary reward predicts increases in depressive symptoms during the COVID-19 pandemic.

The prevalence of depressive symptoms has increased during the COVID-19 pandemic, especially among those with greater pandemic-related stress exposure; however, not all individuals exposed to pandemic stress will develop depression. Determining which individuals are vulnerable to depressive symptoms as a result of this stress could lead to an improved understanding of the etiology of depression. This study sought to determine whether neural sensitivity to monetary and/or social reward prospectively predicts depressive symptoms during periods of high stress. 121 participants attended pre-pandemic laboratory visits where they completed monetary and social reward tasks while electroencephalogram was recorded. Subsequently, from March to August 2020, we sent eight questionnaires probing depressive symptoms and exposure to pandemic-related stressors. Using repeated-measures multilevel models, we evaluated whether neural response to social or monetary reward predicted increases in depressive symptoms across the early course of the pandemic. Furthermore, we examined whether neural response to social or monetary reward moderated the association between pandemic-related episodic stressors and depressive symptoms. Pandemic-related stress exposure was strongly associated with depressive symptoms. Additionally, we found that blunted neural response to social but not monetary reward predicted increased depressive symptoms during the pandemic. However, neither neural response to social nor monetary reward moderated the association between episodic stress exposure and depressive symptoms. Our findings indicate that neural response to social reward may be a useful predictor of depressive symptomatology under times of chronic stress, particularly stress with a social dimension.

Maternal symptoms of depression and anxiety during the postpartum period moderate infants' neural response to emotional faces of their mother and of female strangers.

Affective exchanges between mothers and infants are key to the intergenerational transmission of depression and anxiety, possibly via adaptations in neural systems that support infants' attention to facial affect. The current study examined associations between postnatal maternal symptoms of depression, panic and social anxiety, maternal parenting behaviours, and infants' neural responses to emotional facial expressions portrayed by their mother and by female strangers. The Negative Central (Nc), an event-related potential component that indexes attention to salient stimuli and is sensitive to emotional expression, was recorded from 30 infants. Maternal sensitivity, intrusiveness, and warmth, as well as infant's positive engagement with their mothers, were coded from unstructured interactions. Mothers reporting higher levels of postnatal depression symptoms were rated by coders as less sensitive and warm, and their infants exhibited decreased positive engagement with the mothers. In contrast, postnatal maternal symptoms of panic and social anxiety were not significantly associated with experimenter-rated parenting behaviours. Additionally, infants of mothers reporting greater postnatal depression symptoms showed a smaller Nc to their own mother's facial expressions, whereas infants of mothers endorsing greater postnatal symptoms of panic demonstrated a larger Nc to fearful facial expressions posed by both their mother and female strangers. Together, these results suggest that maternal symptoms of depression and anxiety during the postpartum period have distinct effects on infants' neural responses to parent and stranger displays of emotion.

Neural response to rewarding social feedback in never-depressed adolescent girls and their mothers with remitted depression: Associations with multiple risk indices.

Prevention of depression requires a clear understanding of etiology. Previous studies have identified reduced neural responses to monetary reward as a risk factor for depression, but social reward processing may be particularly relevant to depression. This study investigated associations between neural responses to social reward and three well-established risk factors for depression: personal history, family history, and interpersonal stress. We examined the reward positivity (RewP), an event-related potential sensitive to rewarding feedback, in a sample of 85 women with and without remitted depression and their never-depressed adolescent daughters. In never-depressed daughters, maternal history of depression predicted a blunted social RewP, but interpersonal stress did not. In the mothers, greater interpersonal stress predicted a blunted RewP, but personal depression history was not significant. Combined, these data suggest that personal history, family history, and interpersonal stress may converge on social reward sensitivity, which may advance future research to understand the development of depression. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Intergenerational transmission of depression risk: Mothers' neural response to reward and history of depression are associated with daughters' neural response to reward across adolescence.

Impaired reward responsiveness, a construct of the RDoC positive valence systems (PVS), prospectively predicts depression onset and may therefore represent an important marker of risk. Neural structures implicated in reward processing undergo substantial change during adolescence, a period of heightened risk for depression, particularly for those with a family history of the disorder. However, it is not clear whether familial transmission of PVS functioning also changes across adolescence, nor whether a family history of depression influences normative development of the PVS. To address these questions, mothers and their adolescent daughters each completed a monetary reward guessing task while an electroencephalogram was recorded (N = 109 dyads). Daughters' pubertal status significantly moderated the association between mothers' and daughters' reward processing in the delta frequency, such that there was a negative association for daughters in early puberty that shifted toward a positive association in later puberty. Furthermore, for never-depressed daughters without a maternal history of depression, more advanced pubertal development was associated with increased reward-related power in the delta frequency, whereas, for daughters with a maternal history of depression, more advanced pubertal development was associated with reduced power in the delta frequency. These data indicate that biomarkers of risk for psychopathology may differ as a function of both familial risk and developmental status. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Conscious and unconscious brain responses to food and cocaine cues.

Visual presentation of appetitive and negative cues triggers fast responses in the human brain. Here we assessed functional MRI (fMRI) responses to food, cocaine, and neutral cues presented at a subliminal ("unconscious", 33 ms) and supraliminal ("conscious", 750 and 3000 ms) level in healthy, cocaine naïve volunteers. Because there is evidence of circadian variability in reward sensitivity, our second aim was to assess diurnal variability in the brain's reactivity to cues. Sixteen participants completed two randomly ordered fMRI sessions (once 9-11 AM and another 5-7 PM). in which food, cocaine, and neutral cues were presented for 33, 750 and 3000 ms. Participants rated food cues as positive and "wanted" (more so in evenings than mornings), and cocaine cues as negative (no diurnal differences). fMRI showed occipital cortex activation for food>neutral, cocaine>neutral and cocaine>food; dorsolateral prefrontal cortex for cocaine>neutral and cocaine>food, and midbrain for cocaine>food (all pFWE < 0.05). When comparing unconscious (33 ms) > conscious (750 and 3000 ms) presentations, we observed significant differences for cocaine>neutral and cocaine>food in occipital cortex, for cocaine>neutral in the insula/temporal lobe, and for food>neutral in the middle temporal gyrus (pFWE < 0.05). No diurnal differences for brain activations were observed. We interpret these findings to suggest that negative items (e.g., cocaine) might be perceived at a faster speed than positive ones (e.g., food), although we cannot rule out that the higher saliency of cocaine cues, which would be novel to non-drug using individuals, contributed to the faster speed of detection.

Neural responses to social acceptance predict behavioral adjustments following peer feedback in the context of a real-time social interaction task.

Strong social connections are important predictors of both mental and physical health. The ability to effectively process social feedback from other people and adjust behavior accordingly is a critical part of skillfully navigating the social landscape. However, relatively few studies have considered neural systems driving these behavioral adjustments. In this study, 254 participants engaged in a peer interaction game while electroencephalogram (EEG) was recorded. In this game, participants repeatedly "interact" with a small set of virtual peers over a series of rounds, in which they provide feedback to their peers, and receive feedback from them in turn. A reward-sensitive event-related potential called the Reward Positivity (RewP) was extracted from the EEG following positive feedback from peers, and multilevel modeling was used to examine whether the RewP moderated associations between the feedback participants received during the task and their subsequent behavior. Participants were more likely to accept coplayers who had previously voted to accept them, and to like coplayers who had voted to accept them on the same round. A larger RewP was associated with a stronger tendency to modify behavior following feedback from peers, both in terms of voting behavior and expressions of liking. These data suggest that initial neural responsiveness to reward within 300 ms of positive social feedback may guide social behaviors. Thus, this line of research represents an important step toward a more complete understanding of the ways in which neural responses to feedback are involved in human social behaviors.

Neural response to rewards predicts risk-taking in late but not early adolescent females.

Risk-taking peaks in adolescence and reflects, in part, hyperactivity of the brain's reward system. However, it has not been established whether the association between reward-related brain activity and risk-taking varies across adolescence. The present study investigated how neural reward sensitivity is associated with laboratory risk-taking in a sample of female adolescents as a function of age. Sixty-three female adolescents ages 10-19 completed the Balloon Analogue Risk Task, a laboratory measure of risk-taking behavior, as well as a forced choice monetary gambling task while an electroencephalogram (EEG) was recorded. This gambling task elicits the reward positivity (RewP), a frontocentral event-related potential component that is sensitive to feedback signaling reward. We observed a negative quadratic association between age and risk-taking, such that those in early and late adolescence had lower relative risk-taking compared to mid-adolescence, with risk-taking peaking at around 15 years of age. In predicting risk-taking, we observed an interaction between age and RewP, such that reward-related brain activity was not associated with risk-taking in early adolescence but was associated with a greater propensity for risk in later adolescence. These findings suggest that for females, neural response to rewards is an important factor in predicting risk-taking only in later adolescence.

Association Between Reduced Brain Glucose Metabolism and Cortical Thickness in Alcoholics: Evidence of Neurotoxicity.

BACKGROUND: Excessive alcohol consumption is associated with reduced cortical thickness (CT) and lower cerebral metabolic rate of glucose (CMRGlu), but the correlation between these 2 measures has not been investigated. METHODS: We tested the association between CT and cerebral CMRGlu in 19 participants with alcohol use disorder (AUD) and 20 healthy controls. Participants underwent 2-Deoxy-2-[18F]fluoroglucose positron emission tomography to map CMRGlu and magnetic resonance imaging to assess CT. RESULTS: Although performance accuracy on a broad range of cognitive domains did not differ significantly between AUD and HC, AUD had widespread decreases in CT and CMRGlu. CMRGlu, normalized to cerebellum (rCMRGlu), showed significant correlation with CT across participants. Although there were large group differences in CMRGlu (>17%) and CT (>6%) in medial orbitofrontal and BA 47, the superior parietal cortex showed large reductions in CMRGlu (~17%) and minimal CT differences (~2.2%). Though total lifetime alcohol (TLA) was associated with CT and rCMRGlu, the causal mediation analysis revealed significant direct effects of TLA on rCMRGlu but not on CT, and there were no significant mediation effects of TLA, CT, and rCMRGlu. CONCLUSIONS: The significant correlation between decrements in CT and CMRGlu across AUD participants is suggestive of alcohol-induced neurotoxicity, whereas the findings that the most metabolically affected regions in AUD had minimal atrophy and vice versa indicates that changes in CT and CMRGlu reflect distinct responses to alcohol across brain regions.

Neural correlates of visual attention in alcohol use disorder.

Numerous studies have documented cognitive impairments in multiple domains in patients with an alcohol use disorder (AUD), including perceptuomotor, executive, and visuospatial functions. Although the neural underpinnings of cognitive deficits in AUD have been studied extensively, the neural basis of attention deficits in AUD remains relatively unexplored. Here, we investigated neural responses to a visual attention task (VAT) in 19 recently abstinent patients with AUD and 23 healthy control participants (HC) using functional MRI (fMRI). AUD had a mean number of 62 ± 34SD drinks per week and 29 ± 13 years' history of alcohol use. Results show that there were no behavioral differences (accuracy or reaction time) between groups during the VAT. For both groups, the VAT activated brain areas associated with visual attention load (i.e., parietal and prefrontal cortices) and visual processing (i.e., occipital cortex), which is in line with previous reports on the same task in healthy volunteers. Despite similar behavioral performances, AUD participants showed decreased VAT activation in regions of the dorsal and ventral attention networks, including parietal and prefrontal cortices, and in the insula as compared to controls. These findings corroborate differences in attention networks in AUD compared to HC that might underlie attention deficits in AUD, whereas impairments in the insula could reflect a disruption of interoception processing as found in other addictions.

Apparent diffusion coefficient changes in human brain during sleep - Does it inform on the existence of a glymphatic system?

The role of sleep in brain physiology is poorly understood. Recently rodent studies have shown that the glymphatic system clears waste products from brain more efficiently during sleep compared to wakefulness due to the expansion of the interstitial fluid space facilitating entry of cerebrospinal fluid (CSF) into the brain. Here, we studied water diffusivity in the brain during sleep and awake conditions, hypothesizing that an increase in water diffusivity during sleep would occur concomitantly with an expansion of CSF volume - an effect that we predicted based on preclinical findings would be most prominent in cerebellum. We used MRI to measure slow and fast components of the apparent diffusion coefficient (ADC) of water in the brain in 50 healthy participants, in 30 of whom we compared awake versus sleep conditions and in 20 of whom we compared rested-wakefulness versus wakefulness following one night of sleep-deprivation. Sleep compared to wakefulness was associated with increases in slow-ADC in cerebellum and left temporal pole and with decreases in fast-ADC in thalamus, insula, parahippocampus and striatal regions, and the density of sleep arousals was inversely associated with ADC changes. The CSF volume was also increased during sleep and was associated with sleep-induced changes in ADCs in cerebellum. There were no differences in ADCs with wakefulness following sleep deprivation compared to rested-wakefulness. Although we hypothesized increases in ADC with sleep, our findings uncovered both increases in slow ADC (mostly in cerebellum) as well as decreases in fast ADC, which could reflect the distinct biological significance of fast- and slow-ADC values in relation to sleep. While preliminary, our findings suggest a more complex sleep-related glymphatic function in the human brain compared to rodents. On the other hand, our findings of sleep-induced changes in CSF volume provide preliminary evidence that is consistent with a glymphatic transport process in the human brain.

Methylation of the dopamine transporter gene in blood is associated with striatal dopamine transporter availability in ADHD: A preliminary study.

Dopamine transporters (DAT) are implicated in the pathogenesis and treatment of attention-deficit hyperactivity disorder (ADHD) and are upregulated by chronic treatment with methylphenidate, commonly prescribed for ADHD. Methylation of the DAT1 gene in brain and blood has been associated with DAT expression in rodents' brains. Here we tested the association between methylation of the DAT1 promoter derived from blood and DAT availability in the striatum of unmedicated ADHD adult participants and in that of healthy age-matched controls (HC) using Positron Emission Tomography (PET) and [11 C]cocaine. Results showed no between-group differences in DAT1 promoter methylation or striatal DAT availability. However, the degree of methylation in the promoter region of DAT1 correlated negatively with DAT availability in caudate in ADHD participants only. DAT availability in VS correlated with inattention scores in ADHD participants. We verified in a postmortem cohort with ADHD diagnosis and without, that DAT1 promoter methylation in peripheral blood correlated positively with DAT1 promoter methylation extracted from substantia nigra (SN) in both groups. In the cohort without ADHD diagnosis, DAT1 gene expression in SN further correlated positively with DAT protein expression in caudate; however, the sample size of the cohort with ADHD was insufficient to investigate DAT1 and DAT expression levels. Overall, these findings suggest that peripheral DAT1 promoter methylation may be predictive of striatal DAT availability in adults with ADHD. Due to the small sample size, more work is needed to validate whether DAT1 methylation in blood predicts DAT1 methylation in SN in ADHD and controls.

Emotion Recognition Biases in Alcohol Use Disorder.

BACKGROUND: Alcohol use disorder (AUD) has been associated with impairments in cognitive and emotional function, including difficulty identifying emotional facial expressions. However, it is unclear whether these deficits are associated with alcohol consumption or related anxious and depressive symptoms. METHODS: We compared the recognition of emotional faces expressing happiness, surprise, sadness, fear, anger, and disgust in 19 AUD participants and 19 healthy volunteers using the Cambridge Neuropsychological Test Automated Battery Emotion Recognition Task. We analyzed group differences in response latency, accuracy, and misidentification patterns (as defined by the tendency to mislabel facial expressions as exhibiting specific emotions). To assess whether misidentification patterns were associated with drinking severity, we also examined associations with alcohol consumption over the past 90 days. RESULTS: There were no differences in response latency or accuracy between groups. However, there were group differences in misidentification patterns. While controls tended to misidentify emotional expressions as happy, those with AUD tended to misidentify expressions as angry or disgusted. In AUD participants, the degree to which individuals were biased toward anger or disgust was positively correlated with the number of drinks they consumed in the past 90 days but was not associated with depression or anxiety scores. CONCLUSIONS: Our findings suggest that individuals with AUD have a bias toward misidentifying emotional facial expressions as hostile, which is not mediated by associated mood changes. This provides further evidence of disrupted social cognition in AUD.

Impact of sugar on the body, brain, and behavior.

Sugar is highly palatable and rewarding, both in its taste and nutritive input. Excessive sugar consumption, however, may trigger neuroadaptations in the reward system that decouple eating behavior from caloric needs and leads to compulsive overeating. Excessive sugar intake is in turn associated with adverse health conditions, including obesity, metabolic syndrome, and inflammatory diseases. This review aims to use recent evidence to connect sugar's impact on the body, brain, and behavior to elucidate how and why sugar consumption has been implicated in addictive behaviors and poor health outcomes.

Influence of alcoholism and cholesterol on TSPO binding in brain: PET [11C]PBR28 studies in humans and rodents.

Neuroinflammation appears to contribute to neurotoxicity observed with heavy alcohol consumption. To assess whether chronic alcohol results in neuroinflammation we used PET and [11C]PBR28, a ligand that binds to the 18-kDa translocator protein (TSPO), to compare participants with an alcohol use disorder (AUD: n = 19) with healthy controls (HC: n = 17), and alcohol-dependent (n = 9) with -nondependent rats (n = 10). Because TSPO is implicated in cholesterol's transport for steroidogenesis, we investigated whether plasma cholesterol levels influenced [11C]PBR28 binding. [11C]PBR28 binding did not differ between AUD and HC. However, when separating by TSPO genotype rs6971, we showed that medium-affinity binders AUD participants showed lower [11C]PBR28 binding than HC in regions of interest (whole brain, gray and white matter, hippocampus, and thalamus), but no group differences were observed in high-affinity binders. Cholesterol levels inversely correlated with brain [11C]PBR28 binding in combined groups, due to a correlation in AUD participants. In rodents, we observed no differences in brain [11C]PBR28 uptake between alcohol-dependent and -nondependent rats. These findings, which are consistent with two previous [11C]PBR28 PET studies, may indicate lower activation of microglia in AUD, whereas failure to observe alcohol effects in the rodent model indicate that species differences do not explain the discrepancy with prior rodent autoradiographic studies reporting increases in TSPO binding with chronic alcohol. However, reduced binding in AUD participants could also reflect competition from endogenous TSPO ligands such as cholesterol; and since the rs6971 polymorphism affects the cholesterol-binding domain of TSPO this could explain why differences were observed only in medium-affinity binders.