Adaptive functioning and academic achievement in pediatric survivors of acute lymphoblastic leukemia: Associations with executive functioning, socioeconomic status, and academic support.

OBJECTIVES: This study examines associations of functional outcomes (adaptive functioning and academic achievement) with executive functioning (EF), socioeconomic status (SES), and academic support in pediatric acute lymphoblastic leukemia (ALL) survivors. METHODS: Fifty survivors of B-lineage ALL treated with chemotherapy-only (42% female, 76% NHW, ages 6-19) were evaluated on performance-based EF and academic achievement, and parent-rated EF and adaptive functioning. Area deprivation and child opportunity (i.e., SES) were extracted using census blocks and tracts. Academic support data were extracted from chart review. RESULTS: Compared to population norms, pediatric ALL survivors demonstrated significantly lower overall adaptive skills and performance in word reading and math calculation (all p ≤ .011). Frequencies of impairment were significantly elevated on all adaptive scales and in math calculation compared to the population (all p ≤ .002). Parent-rated EF significantly predicted overall adaptive skills (p < .001), while performance-based EF significantly predicted word reading and math calculation (all p < .05). Adaptive functioning was not associated with neighborhood-specific variables or academic support. However, academic support predicted word reading (p < .001), while area deprivation and academic support predicted performance-based EF (all p ≤ .02). CONCLUSIONS: Screening of functional outcomes, targeted intervention, and neuropsychological monitoring are necessary to support pediatric ALL survivors' neurocognitive and psychosocial development.

Convergent Validity of In-Person Assessment of Inpatients With Traumatic Brain Injury Using the Brief Test of Adult Cognition by Telephone (BTACT).

OBJECTIVE: To examine convergent validity of the Brief Test of Adult Cognition by Telephone (BTACT) by determining correlation with established neuropsychological tests, administered an average of 4.4 days apart, in an inpatient traumatic brain injury (TBI) population. SETTING: Acute inpatient rehabilitation hospital. PARTICIPANTS: Fifty-five patients receiving inpatient rehabilitation for new-onset TBI (69.1% male; mean age = 37 years, SD = 14 years). DESIGN: Cross-sectional, secondary data analysis. MAIN MEASURES: BTACT; California Verbal Learning Test-second edition (CVLT-2); Wechsler Adult Intelligence Scale-IV (WAIS-IV) Digit Span; Trail Making Test; semantic fluency; phonemic fluency; Symbol Digit Modalities Test; Wisconsin Card Sorting Test. RESULTS: The BTACT was significantly associated with established neuropsychological tests across composite scores of overall cognition (r = 0.64, P < .001), episodic verbal memory (r = 0.66, P < .001), and executive function (r = 0.56, P < .001). For BTACT subtests, Word List Immediate Recall and Word List Delayed Recall were correlated with CVLT-2 learning trials total score (r = 0.57, P < .01) and long delay free recall (r = 0.60, P < .001), respectively. BTACT Digits Backward correlated with WAIS-IV Digit Span (r = 0.51, P < .01). BTACT Animal Fluency was associated with semantic fluency (r = 0.65, P < .01), phonemic fluency (r = 0.60, P < .01), and Trail Making Test Part B (r = 0.39, P < .01). CONCLUSION: BTACT composite scores of overall cognition, verbal memory, and executive function demonstrate initial convergent validity in a TBI inpatient population. Future research should examine validity in a larger sample of individuals with TBI.

Emotional and physiological desensitization to real-life and movie violence.

Youth are exposed to large amounts of violence in real life and media, which may lead to desensitization. Given evidence of curvilinear associations between exposure to violence and emotional distress, we examined linear and curvilinear associations of exposure to real-life and movie violence with PTSD symptoms, empathy, and physiological arousal, as well emotional and physiological reactivity to movie violence. College students (N = 209; mean age = 18.74) reported on their exposure to real-life and televised violence, PTSD symptoms, and empathy. Then, students were randomly assigned to view a series of violent or nonviolent high-action movie scenes, providing ratings of emotional distress after each clip. Blood pressure was measured at rest and during video viewing. Results showed that with increasing exposure to real-life violence, youth reported more PTSD symptoms and greater identification with fictional characters. Cognitive and emotional empathy increased from low to medium levels of exposure to violence, but declined at higher levels. For males, exposure to higher levels of real-life violence was associated with diminishing (vs. increasing) emotional distress when viewing violent videos. Exposure to televised violence was generally unrelated to emotional functioning. However, those with medium levels of exposure to TV/movie violence experienced lower elevations of blood pressure when viewing violent videos compared to those with low exposure, and those with higher levels of exposure evidenced rapid increase in blood pressure that quickly declined over time. The results point to diminished empathy and reduced emotional reactivity to violence as key aspects of desensitization to real-life violence, and more limited evidence of physiological desensitization to movie violence among those exposed to high levels of televised violence.

Effect of Sleep Restriction on Adolescent Cognition by Adiposity: A Randomized Crossover Trial.

Importance: Pediatric obesity is associated with impaired cognitive function; however, the mechanisms underlying this association demand assessment. Sleep may be a relevant moderator, as poor sleep predicts both increased adiposity and impaired cognitive function. Objective: To determine the effects of adiposity and sleep on adolescent cognitive function. Design, Setting, and Participants: This single-blind randomized crossover trial was conducted from September 2020 to October 2022. Parents or caregivers provided demographic information for adolescent participants. Body mass index percentile and bioelectrical impedance analysis assessed adiposity. Adolescents completed 2 actigraphy-confirmed sleep conditions, adequate and restricted, followed by in-person cognitive assessment. No additional follow-up was provided. Data collection for this population-based study took place in a behavioral medicine clinic in Birmingham, Alabama. A total of 323 participants were assessed for eligibility (ages 14-19 years and healthy). Of the 244 eligible adolescents, 157 declined participation. Eighty-seven were randomized and 26 dropped out postenrollment. The final sample included 61 adolescents, 31 with healthy weight and 30 with overweight or obesity. Data were analyzed from April to October 2023. Interventions: Following a 2-day washout period of adequate sleep, adolescents completed 2 sleep conditions: adequate (mean [SD] duration, 8 hours, 54 minutes [58.0 minutes]) and restricted (mean [SD] duration, 4 hours, 12 minutes [50.7 minutes]). Main Outcomes and Measures: The National Institutes of Health Cognitive Toolbox assessed global and fluid cognition, cognitive flexibility, working and episodic memory, attention, and processing speed. The Stroop Task assessed inhibition. Results: The final sample included 61 adolescents (mean [SD] age, 16.3 [1.6] years; 35 [57.4%] female). Restricted sleep predicted poorer global cognition scores (restricted mean [SD], 98.0 [2.8]; adequate mean [SD], 103.2 [2.9]), fluid cognition scores (restricted mean [SD], 94.5 [3.2]; adequate mean [SD], 102.0 [3.6]), and cognitive flexibility scores (restricted mean [SD], 84.8 [3.0]; adequate mean [SD], 92.8 [3.0]) for adolescents with overweight or obesity. No differences emerged for adolescents with healthy weight. Adolescents with overweight or obesity also had poorer attention scores (mean [SD], 80.0 [2.3]) compared to adolescents with healthy weight (mean [SD], 88.4 [SD, 2.3]) following restricted sleep. No differences emerged following adequate sleep. Findings were similar for total body fat percentage (TBF%); however, for adolescents with TBF% above 42, restricted sleep also predicted poorer processing speed, and the association between sleep and attention did not vary based on TBF%. Conclusions and Relevance: Adolescents with overweight or obesity may be more vulnerable to negative cognitive effects following sleep restriction. Improved sleep hygiene and duration in this group may positively impact their cognitive health. Trial Registration: ClinicalTrials.gov Identifier: NCT04346433.

fMRI reactivity to high-calorie food pictures predicts short- and long-term outcome in a weight-loss program.

Behavioral studies have suggested that food cues have stronger motivating effects in obese than in normal-weight individuals, which may be a risk factor underlying obesity. Previous cross-sectional neuroimaging studies have suggested that this difference is mediated by increased reactivity to food cues in parts of the reward system in obese individuals. To date, however, only a few prospective neuroimaging studies have been conducted to examine whether individual differences in brain activation elicited by food cues can predict differences in weight change. We used functional magnetic resonance imaging (fMRI) to investigate activation in reward-system as well as other brain regions in response to viewing high-calorie food vs. control pictures in 25 obese individuals before and after a 12-week psychosocial weight-loss treatment and at 9-mo follow-up. In those obese individuals who were least successful in losing weight during the treatment, we found greater pre-treatment activation to high-calorie food vs. control pictures in brain regions implicated in reward-system processes, such as the nucleus accumbens, anterior cingulate, and insula. We found similar correlations with weight loss in brain regions implicated by other studies in vision and attention, such as superior occipital cortex, inferior and superior parietal lobule, and prefrontal cortex. Furthermore, less successful weight maintenance at 9-mo follow-up was predicted by greater post-treatment activation in such brain regions as insula, ventral tegmental area, putamen, and fusiform gyrus. In summary, we found that greater activation in brain regions mediating motivational and attentional salience of food cues in obese individuals at the start of a weight-loss program was predictive of less success in the program and that such activation following the program predicted poorer weight control over a 9-mo follow-up period.

fMRI reactivity on a delay discounting task predicts weight gain in obese women.

Obesity can be accompanied by abnormalities in executive function and related neural circuitry. A useful task for studying executive function is delay discounting (DD), in which an individual chooses between sooner and delayed, but greater, amounts of money or other commodities. We previously found that obese compared to normal-weight women made more immediate choices on a monetary DD task, or had greater delay discounting. In the present study, we performed functional magnetic resonance imaging (fMRI) of obese women during performance of a DD of money task. Confirming the results of previous studies, we found that more difficult compared to easy DD trials resulted in activation in putative executive function areas of the brain, the middle and inferior frontal gyri, and medial prefrontal cortex. Most interestingly, we also found that less activation in executive function areas such as the inferior, middle, and superior frontal gyri on difficult vs. easy DD trials predicted a greater rate of weight gain over the subsequent 1.3-2.9 years. These results suggest that suboptimal functioning of executive function areas such as prefrontal cortex contributes to the progression of obesity.

A method for standardizing procedures in rehabilitation: use in the extremity constraint induced therapy evaluation multisite randomized controlled trial.

OBJECTIVE: An enduring problem in the field of rehabilitation has been the lack of standardization in the protocols of treatments and tests. To develop a process evaluation method to standardize the administration of rehabilitation procedures used in the Extremity Constraint Induced Therapy Evaluation (EXCITE) Trial, a randomized controlled trial of upper-extremity constraint-induced therapy implemented across 7 sites. DESIGN: Process evaluation. SETTING: Research laboratory. PARTICIPANTS: Convenience sample or research personnel. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Checklist scoring sheets were developed to rate videotapes using systematic application of prescribed steps for each of 5 procedures across 3 time periods. Time periods were immediately after training, and 1 and 2 years later. A performance score of at least 90% was required before individual research personnel were allowed to participate in the trial. RESULTS: Overall performance scores ranged from 85.8% to 95% of performance items correctly executed. There was a significant improvement in standard performance of procedures between the first time period (immediately after training) and each of the subsequent time periods for all but 1 procedure. The scoring of standardized performance when carried out with routine participant testing and training did not differ significantly from scoring from videotaped sessions submitted for standardization rating for 2 of the procedures, suggesting adequate validity of scoring from videotape. CONCLUSIONS: The present method was successful in assessing protocol fidelity for the EXCITE research personnel and represents 1 means of addressing the longstanding problem in rehabilitation of the lack of standardization in administering different treatments and tests.

Greater impulsivity is associated with decreased brain activation in obese women during a delay discounting task.

Impulsivity and poor inhibitory control are associated with higher rates of delay discounting (DD), or a greater preference for smaller, more immediate rewards at the expense of larger, but delayed rewards. Of the many functional magnetic resonance imaging (fMRI) studies of DD, few have investigated the correlation between individual differences in DD rate and brain activation related to DD trial difficulty, with difficult DD trials expected to activate putative executive function brain areas involved in impulse control. In the current study, we correlated patterns of brain activation as measured by fMRI during difficult vs. easy trials of a DD task with DD rate (k) in obese women. Difficulty was defined by how much a reward choice deviated from an individual's 'indifference point', or the point where the subjective preference for an immediate and a delayed reward was approximately equivalent. We found that greater delay discounting was correlated with less modulation of activation in putative executive function brain areas, such as the middle and superior frontal gyri and inferior parietal lobule, in response to difficult compared to easy DD trials. These results support the suggestion that increased impulsivity is associated with deficient functioning of executive function areas of the brain.

Effective connectivity of a reward network in obese women.

Exaggerated reactivity to food cues in obese women appears to be mediated in part by a hyperactive reward system that includes the nucleus accumbens, amygdala, and orbitofrontal cortex. The present study used functional magnetic resonance imaging (fMRI) to investigate whether differences between 12 obese and 12 normal-weight women in reward-related brain activation in response to food images can be explained by changes in the functional interactions between key reward network regions. A two-step path analysis/General Linear Model approach was used to test whether there were group differences in network connections between nucleus accumbens, amygdala, and orbitofrontal cortex in response to high- and low-calorie food images. There was abnormal connectivity in the obese group in response to both high- and low-calorie food cues compared to normal-weight controls. Compared to controls, the obese group had a relative deficiency in the amygdala's modulation of activation in both orbitofrontal cortex and nucleus accumbens, but excessive influence of orbitofrontal cortex's modulation of activation in nucleus accumbens. The deficient projections from the amygdala might relate to suboptimal modulation of the affective/emotional aspects of a food's reward value or an associated cue's motivational salience, whereas increased orbitofrontal cortex to nucleus accumbens connectivity might contribute to a heightened drive to eat in response to a food cue. Thus, it is possible that not only greater activation of the reward system, but also differences in the interaction of regions in this network may contribute to the relatively increased motivational value of foods in obese individuals.

Widespread reward-system activation in obese women in response to pictures of high-calorie foods.

Behavioral studies have suggested that exaggerated reactivity to food cues, especially those associated with high-calorie foods, may be a factor underlying obesity. This increased motivational potency of foods in obese individuals appears to be mediated in part by a hyperactive reward system. We used a Philips 3T magnet and fMRI to investigate activation of reward-system and associated brain structures in response to pictures of high-calorie and low-calorie foods in 12 obese compared to 12 normal-weight women. A regions of interest (ROI) analysis revealed that pictures of high-calorie foods produced significantly greater activation in the obese group compared to controls in medial and lateral orbitofrontal cortex, amygdala, nucleus accumbens/ventral striatum, medial prefrontal cortex, insula, anterior cingulate cortex, ventral pallidum, caudate, putamen, and hippocampus. For the contrast of high-calorie vs. low-calorie foods, the obese group also exhibited a larger difference than the controls did in all of the same regions of interest except for the putamen. Within-group contrasts revealed that pictures of high-calorie foods uniformly stimulated more activation than low-calorie foods did in the obese group. By contrast, in the control group, greater activation by high-calorie foods was seen only in dorsal caudate, whereas low-calorie foods were more effective than high-calorie foods in the lateral orbitofrontal cortex, medial prefrontal cortex, and anterior cingulate cortex. In summary, compared to normal-weight controls, obese women exhibited greater activation in response to pictures of high-calorie foods in a large number of regions hypothesized to mediate motivational effects of food cues.

Obese women show greater delay discounting than healthy-weight women.

Delay discounting (DD) is a measure of the degree to which an individual is driven by immediate gratification vs. the prospect of larger, but delayed, rewards. Because of hypothesized parallels between drug addiction and obesity, and reports of increased delay discounting in drug-dependent individuals, we hypothesized that obese individuals would show higher rates of discounting than controls. Obese and healthy-weight age-matched participants of both sexes completed two versions of a DD of money task, allowing us to calculate how subjective value of $1000 or $50,000 declined as delay until hypothetical delivery increased from 2 weeks to 10 years. On both tasks, obese women (N=29) showed greater delay discounting than control women did (N=26; P values <.02). Subsequent analyses showed that these differences were not related to differences in IQ or income. Obese (N=19) and healthy-weight (N=21) men did not differ significantly. Further research is needed to determine why greater delay discounting was not also observed in obese men.

Motivational state modulates the hedonic value of food images differently in men and women.

We investigated visual alimentary alliesthesia in non-fasted (N = 369) and fasted participants (N = 257) viewing photographs of food. Fasted participants were asked to not eat for 12 h before the session. Each participant was shown food and non-food images and rated each image on valence (i.e., pleasantness). The strongest evidence of alliesthesia was found in women. Fasting enhanced the pleasantness of food images for each of the food categories in women, although this alliesthesia effect was smaller in response to dessert foods compared to the less-pleasantly-rated food categories. In addition, non-fasting women exhibited significant positive correlations between hunger ratings and valence ratings of three of the five food categories. There was no significant difference in valence ratings of food between fasting vs. non-fasting men, but non-fasting men showed correlations between hunger and valence that were similar to those observed among the women. No evidence was found of hunger- or fasting-induced enhancement of hedonic ratings of non-foods in women or men, indicating the specificity of the alliesthesia effect for the food images only.