From learned value to sustained bias: how reward conditioning changes attentional priority.

Introduction: Attentional bias to reward-associated stimuli can occur even when it interferes with goal-driven behavior. One theory posits that dopaminergic signaling in the striatum during reward conditioning leads to changes in visual cortical and parietal representations of the stimulus used, and this, in turn, sustains attentional bias even when reward is discontinued. However, only a few studies have examined neural activity during both rewarded and unrewarded task phases. Methods: In the current study, participants first completed a reward-conditioning phase, during which responses to certain stimuli were associated with monetary reward. These stimuli were then included as non-predictive cues in a spatial cueing task. Participants underwent functional brain imaging during both task phases. Results: The results show that striatal activity during the learning phase predicted increased visual cortical and parietal activity and decreased ventro-medial prefrontal cortex activity in response to conditioned stimuli during the test. Striatal activity was also associated with anterior cingulate cortex activation when the reward-conditioned stimulus directed attention away from the target. Discussion: Our findings suggest that striatal activity during reward conditioning predicts the degree to which reward history biases attention through learning-induced changes in visual and parietal activities.

Brain network connectivity during peer evaluation in adolescent females: Associations with age, pubertal hormones, timing, and status.

Despite copious data linking brain function with changes to social behavior and mental health, little is known about how puberty relates to brain functioning. We investigated the specificity of brain network connectivity associations with pubertal indices and age to inform neurodevelopmental models of adolescence. We examined how brain network connectivity during a peer evaluation fMRI task related to pubertal hormones (dehydroepiandrosterone and testosterone), pubertal timing and status, and age. Participants were 99 adolescents assigned female at birth aged 9-15 (M = 12.38, SD = 1.81) enriched for the presence of internalizing symptoms. Multivariate analysis revealed that within Salience, between Frontoparietal - Reward and Cinguloopercular - Reward network connectivity were associated with all measures of pubertal development and age. Specifically, Salience connectivity linked with age, pubertal hormones, and status, but not timing. In contrast, Frontoparietal - Reward connectivity was only associated with hormones. Finally, Cinguloopercular - Reward connectivity related to age and pubertal status, but not hormones or timing. These results provide evidence that the salience processing underlying peer evaluation is jointly influenced by various indices of puberty and age, while coordination between cognitive control and reward circuitry is related to pubertal hormones, pubertal status, and age in unique ways.

Cognitive stimulation as a mechanism linking socioeconomic status and neural function supporting working memory: a longitudinal fMRI study.

Childhood experiences of low socioeconomic status are associated with alterations in neural function in the frontoparietal network and ventral visual stream, which may drive differences in working memory. However, the specific features of low socioeconomic status environments that contribute to these disparities remain poorly understood. Here, we examined experiences of cognitive deprivation (i.e. decreased variety and complexity of experience), as opposed to experiences of threat (i.e. violence exposure), as a potential mechanism through which family income contributes to alterations in neural activation during working memory. As part of a longitudinal study, 148 youth between aged 10 and 13 years completed a visuospatial working memory fMRI task. Early childhood low income, chronicity of low income in early childhood, and current income-to-needs were associated with task-related activation in the ventral visual stream and frontoparietal network. The association of family income with decreased activation in the lateral occipital cortex and intraparietal sulcus during working memory was mediated by experiences of cognitive deprivation. Surprisingly, however, family income and deprivation were not significantly related to working memory performance, and only deprivation was associated with academic achievement in this sample. Taken together, these findings suggest that early life low income and associated cognitive deprivation are important factors in neural function supporting working memory.

Does early nutrition predict cognitive skills during later childhood? Evidence from two developing countries.

The existing evidence linking early undernutrition to educational outcomes in developing countries is largely focused on assessing its impacts on grade attainment and achievement test scores, with limited evidence on the foundational cognitive skills required to perform well at school. We use unique data collected in Ethiopia and Peru as part of the Young Lives Study to investigate the relationship between early undernutrition and four foundational cognitive skills measured later in childhood, the first two of which measure executive functioning: working memory, inhibitory control, long-term memory, and implicit learning. We exploit the rich longitudinal data available to control for potential confounders at the household and individual level and for time-invariant community characteristics. We also take advantage of the availability of data for paired-siblings to obtain household fixed-effects estimates. In the latter specification, we find robust evidence that stunting at ~ age 5 is negatively related with executive functions measured years later, predicting reductions in working memory and inhibitory control by 12.6% and 5.8% of a standard deviation. Although the main cohort of Young Lives was around 12 years old when executive functions were measured, complementary results and analysis of the data available for the younger siblings suggest that the impact of stunting on executive functions-specifically, on working memory-starts at an earlier age. Our results shed light on the mechanisms that explain the relationship between early nutrition and school achievement tests suggesting that good nutrition is an important determinant of children's learning capacities.

Neural Correlates of the p Factor in Adolescence: Cognitive Control With and Without Enhanced Positive Affective Demands.

BACKGROUND: Recent research has aimed to characterize processes underlying general liability toward psychopathology, termed the p factor. Given previous research linking the p factor with difficulties in both executive functioning and affective regulation, the present study investigated nonaffective and positive affective inhibition in the context of a sustained attention/inhibition paradigm in adolescents exhibiting mild to severe psychopathology. METHODS: Functional magnetic resonance imaging data were collected during an integrated reward conditioning and go/no-go task in 138 adolescents assigned female at birth. We modeled the p factor using hierarchical confirmatory factor analysis. Positive affective inhibition was measured by examining responses to no-go stimuli with a history of reward conditioning. We examined associations between p factor scores and neural function and behavioral performance. RESULTS: Consistent with nonaffective executive function as a primary risk factor, p factor scores were associated with worse behavioral performance and hypoactivation in the left superior frontal gyrus and middle frontal gyrus during response initiation (go trials). The p factor scores were additionally associated with increased error-related signaling in the temporal cortex during incorrect no-go trials. CONCLUSIONS: During adolescence, a period characterized by heightened risk for emergent psychopathology, we observed unique associations between p factor scores and neural and behavioral indices of response initiation, which relies primarily on sustained attention. These findings suggest that shared variation in mental disorder categories is characterized in part by sustained attention deficits. While we did not find evidence that the p factor was associated with inhibition in this study, this observation is consistent with our hypothesis that the p factor would be related to nonaffective control processes.

From Maltreatment to Psychiatric Disorders in Childhood and Adolescence: The Relevance of Emotional Maltreatment.

Different forms of maltreatment are thought to incur a cumulative and non-specific toll on mental health. However, few large-scale studies draw on psychiatric diagnoses manifesting in early childhood and adolescence to identify sequelae of differential maltreatment exposures, and emotional maltreatment, in particular. Fine-grained multi-source dimensional maltreatment assessments and validated age-appropriate clinical interviews were conducted in a sample of N = 778 3 to 16-year-olds. We aimed to (a) substantiate known patterns of clinical outcomes following maltreatment and (b) analyse relative effects of emotional maltreatment, abuse (physical and sexual), and neglect (physical, supervisory, and moral-legal/educational) using structural equation modeling. Besides confirming known relationships between maltreatment exposures and psychiatric disorders, emotional maltreatment exerted particularly strong effects on internalizing disorders in older youth and externalizing disorders in younger children, accounting for variance over and above abuse and neglect exposures. Our data highlight the toxicity of pathogenic relational experiences from early childhood onwards, urging researchers and practitioners alike to prioritize future work on emotional maltreatment.

Threat exposure moderates associations between neural and physiological indices of emotion reactivity in adolescent females.

Early life adversity (ELA) characterized by threat (e.g., abuse, witnessing violence) impacts neural and physiologic systems involved in emotion reactivity; however, research on how threat exposure impacts the interplay between these systems is limited. This study investigates ELA characterized by threat as a potential moderator of the association between (a) neural activity during a negative image processing fMRI task and (b) cortisol production following a modified Trier Social Stress Test (TSST). The sample is comprised of 117 young adolescent females (Mage = 11.90 years, SD = 1.69) at elevated risk for internalizing problems. Whole-brain analyses revealed a positive association between cortisol production and increased right lateral orbitofrontal cortex activity during the emotion reactivity task. In moderation models, threat exposure interacted with bilateral amygdala activation (b = -3.34, p = 0.021) and bilateral hippocampal activation (b = -4.14, p = 0.047) to predict cortisol response to the TSST. Specifically, participants with low, but not high, levels of threat exposure demonstrated a positive association between cortisol production and neural activity in these regions, while no significant association emerged for participants with high threat exposure. Findings contribute to the growing field of research connecting physiological and neural emotion processing and response systems, suggesting that dimensions of ELA may uniquely disrupt associations between neural activation and cortisol production.

Conversation disruptions in early childhood predict executive functioning development: A longitudinal study.

Conversational turn-taking is a complex communicative skill that requires both linguistic and executive functioning (EF) skills, including processing input while simultaneously forming and inhibiting responses until one's turn. Adult-child turn-taking predicts children's linguistic, cognitive, and socioemotional development. However, little is understood about how disruptions to temporal contingency in turn-taking, such as interruptions and overlapping speech, relate to cognitive outcomes, and how these relationships may vary across developmental contexts. In a longitudinal sample of 275 socioeconomically diverse mother-child dyads (children 50% male, 65% White), we conducted pre-registered examinations of whether the frequency of dyads' conversational disruption during free play when children were 3 years old related to children's executive functioning (EF; 9 months later), self-regulation skills (18 months later), and externalizing psychopathology in early adolescence (age 10-12 years). Contrary to hypotheses, more conversational disruptions significantly predicted higher inhibition skills, controlling for sex, age, income-to-needs (ITN), and language ability. Results were driven by maternal disruptions of the child's speech, and could not be explained by measures of overall talkativeness or interactiveness. Exploratory analyses revealed that ITN moderated these relationships, such that the positive effect of disruptions on inhibition was strongest for children from lower ITN backgrounds. We discuss how adult-driven "cooperative overlap" may serve as a form of engaged participation that supports cognition and behavior in certain cultural contexts.

Neural Markers of Emotion Reactivity and Regulation Before and After a Targeted Social Rejection: Differences Among Girls With and Without Suicidal Ideation and Behavior Histories.

BACKGROUND: Suicidal thoughts and behaviors (STBs) are common among adolescent girls and increase risk for suicide death. Emotion regulation difficulties are linked with STBs, particularly in response to targeted social rejection. However, neural correlates of this link have not been investigated and may identify novel targets for interventions. Here, we examined neural correlates of emotion regulation before and after an experimentally delivered targeted social rejection in adolescent girls with STBs and girls without STBs (i.e., control participants). METHODS: Girls (N = 138; age range, 9-15 years; mean [SD] age = 11.6 [1.79] years) completed a functional neuroimaging emotion regulation task. In the middle of the task, participants were socially rejected by an unfamiliar confederate whom the participants had elected to meet. Participants also completed a multimethod STB assessment. RESULTS: Before rejection, girls with a history of STBs, compared with control participants, showed greater activation in the right superior frontal gyrus when passively viewing negative stimuli, and girls with suicidal behavior (SB) versus those without SB showed less activation in the right frontal pole during emotion regulation attempts. Following the rejection, girls with STBs, compared with control participants, showed greater activation in the right inferior frontal gyrus during emotion regulation. CONCLUSIONS: Before social rejection, girls with SB versus without SB may not activate brain regions implicated in emotion regulation, suggesting a vulnerability to poor regulation at their baseline emotional state. After social rejection, girls with any history of STBs showed altered activation in a brain region strongly associated with inhibition and emotion regulation success, possibly reflecting increased effort at inhibiting emotional responses during regulation following stress exposure.

Does alleviating poverty increase cognitive performance? Short- and long-term evidence from a randomized controlled trial.

In this Registered Report, we investigated the impact of a cash transfer based poverty alleviation program on cognitive performance. We analyzed data from a randomized controlled trial conducted on low-income, high-risk individuals in Liberia where a random half of the participants (n = 251) received a $200 lump-sum unconditional cash transfer - equivalent approximately to 300% of their monthly income - while the other half (n = 222) did not. We tested both the short-term (2-5 weeks) and the long-term (12-13 months) impact of the treatment via several executive function measures. The observed effect sizes of cash transfers on cognitive performance (b = .13 for the short- and b = .08 for the long-term) were roughly three and four times smaller than suggested by prior non-randomized research. Bayesian analyses revealed that the overall evidence supporting the existence of these effects is inconclusive. A multiverse analysis showed that neither alternative analytical specifications nor alternative processing of the dataset changed the results consistently. However cognitive performance varied between the executive function measures, suggesting that cash transfers may affect the subcomponents of executive function differently.

Early life adversity and psychopathology in preschoolers: mechanisms and moderators.

Developmental theories suggest that exposure to early life adversity (ELA) alters developing emotional response systems, predicting risk for psychopathology across the life span. The present study examines whether negative emotionality (NE), a trait-like measure of emotionality that develops during early childhood, mediates the association between ELA and psychopathology in a representative sample of 917 preschoolers (Mage = 3.84). Additionally, we explored whether cognitive control, which supports attentional focusing and inhibition and has been identified as a transdiagnostic protective factor, moderates the impact of heightened emotionality following adversity on psychopathology risk. We utilized parent report of adversity, psychopathology, and NE and parent report and task-based measures of cognitive control. Structural equation modeling of cross-sectional data revealed that NE partially mediated the link between ELA and psychopathology symptoms. Moreover, parent-reported cognitive control buffered this link such that the effect of ELA on psychopathology through NE was stronger in children with low versus high cognitive control. These results identify elevated NE as one mechanism linking ELA and psychopathology, specifically among children with poorer top-down control, informing our understanding of key risk and protective factors among adversity-exposed children.

The impact of national holidays on postoperative radiotherapy of squamous cell carcinoma of the head and neck.

Background: Delays in starting postoperative radiotherapy (PORT) have been established as negative predictors for clinical outcomes in head and neck squamous cell carcinomas (HNSCC). Our study aimed to examine the effect of delays during PORT, and the impact of national holidays in Canada, a publicly funded system, on oncologic outcomes such as Overall Survival (OS) and Local Recurrence (LR). Methods: The provincial cancer registry was queried to obtain demographic, pathologic, and outcomes data from cancer patients treated for all squamous cell carcinomas of the head and neck region treated between January 1, 2007 and November 30, 2019. All extracted information was cross-referenced and supplemented by chart review of patient electronic medical records. Extracted data were analyzed for OS and LR, in the context of Canadian national holidays causing delays during PORT. Results: 1433 patients treated for HNSCCs were identified, of whom 338 were treated curatively with surgery followed by PORT. 68.6% of patients experienced at least one day of interruption during treatments due to holidays. LR was 15.4% and OS was 59.6% at 5 years. Treatment interruptions by holidays were predictive of local recurrence (HR, 2.38; 95% CI 1.17-4.83; p = 0.017). Patients that developed early recurrence prior to PORT had very poor oncologic outcomes. Conclusion: Our findings were consistent with previously published studies in limiting the interval between surgery and PORT. We identified the novel finding of paired holidays as a significant predictor in determining LR, suggesting the importance of modifying RT delivery schedules and timing.

Building an ecological momentary assessment smartphone app for 4- to 10-year-old children: A pilot study.

OBJECTIVE: Ecological momentary assessment (EMA) minimizes recall burden and maximizes ecological validity and has emerged as a valuable tool to characterize individual differences, assess contextual associations, and document temporal associations. However, EMA has yet to be reliably utilized in young children, in part due to concerns about responder reliability and limited compliance. The present study addressed these concerns by building a developmentally appropriate EMA smartphone app and testing the app for feasibility and usability with young children ages 4-10 (N = 20; m age = 7.7, SD = 2.0). METHODS: To pilot test the app, children completed an 11-item survey about their mood and behavior twice a day for 14 days. Parents also completed brief surveys twice a day to allow for parent-child comparisons of responses. Finally, at the end of the two weeks, parents provided user feedback on the smartphone app. RESULTS: Results indicated a high response rate (nearly 90%) across child surveys and high agreement between parents and children ranging from 0.89-0.97. CONCLUSIONS: Overall, findings suggest that this developmentally appropriate EMA smartphone app is a reliable and valid tool for collecting in-the-moment data from young children outside of a laboratory setting.

The neural, stress hormone and inflammatory correlates of childhood deprivation and threat in psychosis: A systematic review.

Childhood adversity increases the risk of developing psychosis, but the biological mechanisms involved are unknown. Disaggregating early adverse experiences into core dimensions of deprivation and threat may help to elucidate these mechanisms. We therefore systematically searched the literature investigating associations between deprivation and threat, and neural, immune and stress hormone systems in individuals on the psychosis spectrum. Our search yielded 74 articles, from which we extracted and synthesized relevant findings. While study designs were heterogeneous and findings inconsistent, some trends emerged. In psychosis, deprivation tended to correlate with lower global cortical volume, and some evidence supported threat-related variation in prefrontal cortex morphology. Greater threat exposure was also associated with higher C-reactive protein, and higher and lower cortisol measures. When examined, associations in controls were less evident. Overall, findings indicate that deprivation and threat may associate with partially distinct biological mechanisms in the psychosis spectrum, and that associations may be stronger than in controls. Dimensional approaches may help disentangle the biological correlates of childhood adversity in psychosis, but more studies are needed.

Does reward processing moderate or mediate the link between childhood adversity and psychopathology: A longitudinal study.

Childhood adversity is common and associated with elevated risk for transdiagnostic psychopathology. Reward processing has been implicated in the link between adversity and psychopathology, but whether it serves as a mediator or moderator is unclear. This study examined whether alterations in behavioral and neural reward processing function as a mechanism or moderator of psychopathology outcomes following adversity experiences, including threat (i.e., trauma) and deprivation. A longitudinal community sample of 10-15-year-old youths was assessed across two waves (Wave 1: n = 228; Wave 2: n = 206). Wave 1 assessed adverse experiences, psychopathology symptoms, reward processing on a monetary incentive delay task, and resting-state fMRI. At Wave 2, psychopathology symptoms were reassessed. Greater threat experiences were associated with blunted behavioral reward sensitivity, which, in turn, predicted increases in depression symptoms over time and mediated the prospective association between threat and depression symptoms. In contrast, reward sensitivity moderated the association between deprivation experiences and prospective externalizing symptoms such that the positive association of deprivation with increasing externalizing symptoms was absent for children with high levels of reward sensitivity.

Childhood socioeconomic status and the pace of structural neurodevelopment: accelerated, delayed, or simply different?

Socioeconomic status (SES) is associated with children's brain and behavioral development. Several theories propose that early experiences of adversity or low SES can alter the pace of neurodevelopment during childhood and adolescence. These theories make contrasting predictions about whether adverse experiences and low SES are associated with accelerated or delayed neurodevelopment. We contextualize these predictions within the context of normative development of cortical and subcortical structure and review existing evidence on SES and structural brain development to adjudicate between competing hypotheses. Although none of these theories are fully consistent with observed SES-related differences in brain development, existing evidence suggests that low SES is associated with brain structure trajectories more consistent with a delayed or simply different developmental pattern than an acceleration in neurodevelopment.

Impact of the COVID-19 Pandemic on Medical Oncology Workload: A Provincial Review.

(1) Background: Cancer is the leading cause of death in Canada, with significant resource limitation impacting the delivery of cancer care nationwide. The onset of the COVID-19 pandemic forced additional resource restriction and diversion, further impacting care delivery. Our intention is to analyze the impact COVID-19 on a provincial medical oncology workload and bring attention to the limitations of the current workload metric for oncologists. (2) Methods: All medical oncology patient encounters were extracted and compared, collected by year and encounter type, from April 2014 through March 2022. (3) Results: There was an increase in all patient encounters by an average of 9.5% per year, including during the strictest COVID-19 restrictions. There was an increase in virtual care encounters from 37.9% to 52.1%. (4) Conclusions: Medical Oncology workloads have increased over time and estimates suggest growing demand. Little data exist to inform workforce requirements and actual workload is not captured by the current metric. Though volume of new consults continues to increase, COVID-19 has highlighted additional changes in the delivery of care, likely with lasting impact, little of which are included in the current workload metric.

Distinct Associations of Deprivation and Threat With Alterations in Brain Structure in Early Childhood.

OBJECTIVE: The dimensional model of adversity and psychopathology hypothesizes deprivation and threat impact distinct neurobiological pathways, such as brain structure. This hypothesis has not been examined longitudinally or in young children. This study tested longitudinal associations between threat and deprivation measured in preschool and brain structure in childhood. It was hypothesized that threat would be associated with amygdala and hippocampal subcortical volume and deprivation would be associated with cortical thickness in association cortex. METHOD: The study included T1-weighted scans from 72 children (5-10 years old, 54.2% female participants). Threat was measured by the presence of domestic violence, sexual abuse, physical abuse, or neighborhood violence. Deprivation was measured by the presence of neglect. Associations of deprivation or threat with brain structure were examined controlling for other dimension (deprivation or threat) and nuisance covariates using whole-brain vertex-wise analyses. Subcortical volume was extracted, and the same associations were examined using multiple regression. RESULTS: Threat was associated with widespread decreases in cortical surface area across the prefrontal cortex and other regions. Threat was not associated with amygdala or hippocampal volume. Deprivation was associated with increased thickness in occipital cortex, insula, and cingulate. CONCLUSION: Results suggest distinct associations of deprivation and threat on brain structure in early childhood. Threat is associated with widespread differences in surface area, and deprivation is associated with differences in cortical thickness. These observations are consistent with work in adolescence and adulthood and reflect how dimensions of adversity differentially impact neural structure.

Childhood trauma, earlier pubertal timing, and psychopathology in adolescence: The role of corticolimbic development.

Earlier pubertal development appears to be one pathway through which childhood trauma contributes to psychopathology in adolescence. Puberty-related changes in neural networks involved in emotion processing, namely the amygdala-medial prefrontal (mPFC) circuit, may be a potential mechanism linking trauma and adolescent psychopathology. Our participants were 227 youth between 10 and 13 years of age who completed assessments of threat and deprivation-related experiences of adversity, pubertal stage, and internalizing and externalizing symptoms. A subset (n = 149) also underwent a functional MRI scan while passively viewing fearful and calm faces. Potential mechanisms linking childhood trauma with psychopathology, encompassing earlier pubertal timing and neural response to aversive stimuli were explored. Earlier pubertal development was associated with childhood trauma as well as increased externalizing symptoms in boys only. Earlier pubertal timing in males and females was negatively associated with activation in bilateral amygdala, hippocampal, and fusiform regions when comparing fearful and calm faces. However, amygdala-mPFC connectivity showed no association with pubertal timing or psychopathology symptoms. These findings do not support accelerated amygdala-mPFC development as a mechanism linking childhood trauma and psychopathology, but instead provide support for the role of pubertal development in normative decreases in limbic activation across development.