Inhibition explains the relationship between the efficiency of brain networks and adaptive outcomes in pediatric brain tumor survivors.

OBJECTIVE: Research has found altered brain network connectivity in pediatric brain tumor survivors. Efficient brain networks are critical for performing complex behaviors involved in adaptive functioning (AF). The present study explored relationships between structural brain network characteristics and AF in survivors. We examined whether this relationship is mediated by inhibition and cognitive flexibility, important cognitive abilities for AF. METHOD: Thirty-seven young adult survivors and 37 matched healthy controls (HC; overall Mage = 23.1, SD = 4.9) underwent neuropsychological assessment. Informants completed the Scales of Independent Behavior-Revised (SIB-R) interview. Color-Word Interference Inhibition and Inhibition-Switching from the Delis-Kaplan Executive Functioning System measured inhibition and cognitive flexibility performance. Deterministic tractography was performed on diffusion-weighted imaging, the Automated Anatomical Labeling (AAL) atlas defined nodes, and edges were the average fractional anisotropy between nodes. Global efficiency (GE), average clustering coefficient (CC), and density were computed. Partial correlations and analysis of indirect effects were conducted. RESULTS: There were significant relationships between GE and all SIB-R scales, but findings with CC were limited to two subscales. Inhibition was moderately related to GE, but this was no longer significant after Holm's correction. Cognitive flexibility was not found to be related to graph metrics. Finally, significant indirect effects were found such that inhibition explained the relationship between GE and SIB-R Motor and Social/Communication. CONCLUSIONS: Based on these findings, higher levels of brain network integration, as measured by GE, is related to inhibition in survivors, which facilitates proficient adaptive motor and social/communication skills. Future work should investigate tumor location and treatment factors as potential moderators of the relationships found in this study to better understand specific risk factors in this group. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Neuropsychological and Emotional Functioning in Patients with Cushing's Syndrome.

Patients with Cushing's syndrome (CS) frequently report impairments in cognitive and emotional functioning. Given neuroimaging research that implicates alterations in structure and function in the brain in this population, goals of this study were to investigate neuropsychological and emotional functioning, with particular emphasis on complex attention and memory. In a clinical sample of 18 adults with CS referred for neuropsychological evaluation (age 41.6 ± 10.6, 72% Caucasian), patients' most common subjective complaints were in attention and increased irritability. On objective testing, patients exhibited significant declines in the consistency of their sustained attention and visual-spatial functioning compared to normative peers. Patients exhibited on average significantly reduced initial learning following first exposure to visual and verbal stimuli but intact retention of information learned. Patients with CS endorsed highly elevated levels of somatization, depression, and anxiety, and 59% of them scored in the clinically elevated range for somatization and depressive symptomatology. Exploratory analyses suggested that the 11 patients with active Cushing's exhibited lower processing speed, poorer sustained attention, naming, and cognitive flexibility compared to the 7 patients who achieved biochemical remission. Patients with active Cushing's also reported higher levels of somatization and anxiety compared to patients in biochemical remission. Overall, this study provides new insights into complex attention and memory deficits in patients with CS and concern regarding cognitive and emotional issues despite resolution of hypercortisolism. Our study opens several avenues for further exploration.

Distinct neural networks for detecting violations of adjacent versus nonadjacent sequential dependencies: An fMRI study.

The ability to learn and process sequential dependencies is essential for language acquisition and other cognitive domains. Recent studies suggest that the learning of adjacent (e.g., "A-B") versus nonadjacent (e.g., "A-X-B") dependencies have different cognitive demands, but the neural correlates accompanying such processing are currently underspecified. We developed a sequential learning task in which sequences of printed nonsense syllables containing both adjacent and nonadjacent dependencies were presented. After incidentally learning these grammatical sequences, twenty-one healthy adults (age M = 22.1, 12 females) made familiarity judgments about novel grammatical sequences and ungrammatical sequences containing violations of the adjacent or nonadjacent structure while in a 3T MRI scanner. Violations of adjacent dependencies were associated with increased BOLD activation in both posterior (lateral occipital and angular gyrus) as well as frontal regions (e.g., medial frontal gyrus, inferior frontal gyrus). Initial results indicated no regions showing significant BOLD activations for the violations of nonadjacent dependencies. However, when using a less stringent cluster threshold, exploratory analyses revealed that violations of nonadjacent dependencies were associated with increased activation in subcallosal cortex, paracingulate cortex, and anterior cingulate cortex (ACC). Finally, when directly comparing the adjacent condition to the nonadjacent condition, we found significantly greater levels of activation for the right superior lateral occipital cortex (BA 19) for the adjacent relative to nonadjacent condition. In sum, the detection of violations of adjacent and nonadjacent dependencies appear to involve distinct neural networks, with perceptual brain regions mediating the processing of adjacent but not nonadjacent dependencies. These results are consistent with recent proposals that statistical-sequential learning is not a unified construct but depends on the interaction of multiple neurocognitive mechanisms acting together.

Caregiver- and Clinician-Reported Adaptive Functioning in Rett Syndrome: a Systematic Review and Evaluation of Measurement Strategies.

Rett syndrome is the second most common cause of intellectual disability in females worldwide. The severity of many individuals' impairment limits the effectiveness of traditional assessment. However, clinician and parent reports of adaptive functioning may provide insight into these patients' abilities. This review aims to synthesize the current literature assessing adaptive functioning in Rett syndrome and evaluate existing measurement tools in this population. A search was conducted on PubMed using the search term "Rett syndrome." Studies that quantitatively assessed adaptive functioning outcomes in Rett syndrome with published and normed questionnaire measures were included. Twenty-three studies met inclusion criteria. Overall results indicate that the population of people with Rett syndrome is highly impaired, both in overall adaptive functioning as well as in specific subdomains (e.g., mobility, activities of daily living). Atypical Rett syndrome groups performed better on measures of adaptive functioning relative to patients with classic Rett syndrome. Our findings identified measurement weaknesses, as many of the studies found floor effects and therefore were unable to capture meaningful variability in outcomes. Individuals with Rett syndrome are highly reliant on caregivers due to disrupted adaptive functioning abilities. Optimizing measurement of adaptive skills in Rett syndrome will facilitate the quantification of meaningful change in skills and the identification of efficacious interventions aimed at improving outcomes and quality of life.

Neurological predictor scale is associated with academic achievement outcomes in long-term survivors of childhood brain tumors.

INTRODUCTION: Survivors of childhood brain tumors exhibit impairments in academic performance and have lower rates of educational attainment compared to healthy same-aged peers. Prior research has demonstrated the concurrent validity of the Neurological Predictor Scale (NPS), a measure that incorporates tumor-related treatments and complications into one cumulative score, in predicting IQ, adaptive functioning, and core neurocognitive skills. The purpose of this study is to determine whether the NPS predicts academic achievement outcomes over and above the effects of individual treatment factors alone. METHODS: Sixty-two adult survivors completed four untimed measures of academic achievement from the Woodcock-Johnson III. RESULTS: NPS scores significantly predicted performance on all four academic measures: Letter Word ID (R2 = - 0.454, p < .01), Calculation (R2 = - 0.494, p < .01), Spelling (R2 = - 0.428, p < .01) and Passage Comprehension (R2 = - 0.447, p < .01). 16% of survivors were impaired on the Letter Word ID, 23% on Calculation, 19% on Spelling, and 11% on Passage Comprehension subtests with impairment defined as z ≤ - 1.5. The NPS predicted academic outcomes over and above chemotherapy, surgery, seizure medication, endocrine dysfunction, hydrocephalus, and radiation on all measures. CONCLUSION: This study extends prior research by demonstrating that the NPS is significantly associated with academic achievement in survivors on average 15.9 years after diagnosis. The NPS may be especially helpful in clinical research when studies lack the statistical power to investigate how treatments and neurological conditions individually contribute to outcomes.

Performance discrepancies on the Boston Naming Test in African-American and non-Hispanic White American young adults.

The Boston Naming Test (BNT) is one of the most commonly used naming measures in neuropsychology. Although research in the older adult population has shown that African-American (AA) adults perform more poorly on the BNT than non-Hispanic White American (WA) adults, these findings have yet to be replicated in younger adults. The BNT and measures of word reading (WJ-Letter Word ID) and vocabulary (Wechsler Abbreviated Scale of Intelligence Vocabulary) were administered to 50 WA and 33 AA young adults. Performance was age-normed based on published norms and transformed into z-scores. Despite being matched on age, gender, SES, and level of education, the AA group performed more poorly on the BNT (z = - 1.01(1.09)) than the WA group (z = - .28(.92)), t(104) = 3.44, p < .01, d = 0.73. AAs (18%) were more likely to perform in the impaired range than WAs (4%) when impairment cutoff was z-score≤ - 2. Healthy AA young adults are more likely to perform poorly on the BNT despite vocabulary and word reading being well within normal limits. Average BNT performance in both groups were at least one z-score lower than average vocabulary z-scores. Clinicians should interpret poor scores on the BNT with caution, and within the context of individual vocabulary or word reading performance.

White matter network topology relates to cognitive flexibility and cumulative neurological risk in adult survivors of pediatric brain tumors.

Adult survivors of pediatric brain tumors exhibit deficits in executive functioning. Given that brain tumors and medical treatments for brain tumors result in disruptions to white matter, a network analysis was used to explore the topological properties of white matter networks. This study used diffusion tensor imaging and deterministic tractography in 38 adult survivors of pediatric brain tumors (mean age in years = 23.11 (SD = 4.96), 54% female, mean years post diagnosis = 14.09 (SD = 6.19)) and 38 healthy peers matched by age, gender, handedness, and socioeconomic status. Nodes were defined using the Automated Anatomical Labeling (AAL) parcellation scheme, and edges were defined as the mean fractional anisotropy of streamlines that connected each node pair. Global efficiency and average clustering coefficient were reduced in survivors compared to healthy peers with preferential impact to hub regions. Global efficiency mediated differences in cognitive flexibility between survivors and healthy peers, as well as the relationship between cumulative neurological risk and cognitive flexibility. These results suggest that adult survivors of pediatric brain tumors, on average one and a half decades post brain tumor diagnosis and treatment, exhibit altered white matter topology in the form of suboptimal integration and segregation of large scale networks, and that disrupted topology may underlie executive functioning impairments. Network based studies provided important topographic insights on network organization in long-term survivors of pediatric brain tumor.

The Neurological Predictor Scale: A predictive tool for long-term core cognitive outcomes in survivors of childhood brain tumors.

OBJECTIVE: Prior research has demonstrated the reliability and validity of the Neurological Predictor Scale (NPS) in relation to intelligence and adaptive functioning in survivors of pediatric brain tumors. To extend these findings, this study examined the relationship between the NPS and core neurocognitive skills hypothesized to underlie broad outcome measures of IQ and adaptive functioning. METHOD: Sixty-one adulthood survivors of childhood brain cancers (Mage = 24 years, SD = 6) on average 16 years after diagnosis completed neuropsychological assessments examining attention (Wechsler Memory Scale Digit Span Forward), processing speed (Symbol Digit Modalities Test), and working memory (Auditory Consonant Trigrams). The medical information necessary to compute the NPS was extracted from a thorough medical record review. RESULTS: The NPS score significantly predicted processing speed (R2 = 0.28, P < 0.05) and working memory (R2 = 0.15, P < .05) outcomes over and above each individual risk factor. NPS was significantly associated with attention outcomes after covarying for age (R2 = 0.13, P < 0.05) over and above each risk factor except presence of hormone deficiency, hydrocephalus, and chemotherapy. These three variables were not significantly associated with attention outcomes in this sample. CONCLUSIONS: Our findings suggest that survivors with more treatments and neurological sequelae experience greater deficits in working memory, processing speed, and attention. Further, the NPS affords the ability to predict how cumulative neurological factors impact core cognitive outcomes many years after initial diagnosis.

Wechsler Intelligence Scale for Children-V: Test Review.

Changes from the fourth edition of the Wechsler Intelligence Scale for Children (WISC) to the fifth edition are discussed, with particular emphasis on how the electronic administration facilitated assessment. The hierarchical organization and conceptualization of primary indices have been adjusted, based on recent theory and research on the construct of intelligence. Changes also include updates to psychometric properties and consideration of cultural bias. The scoring program allows intelligence scores to be linked statistically to achievement measures to aid in diagnoses of learning disabilities. Electronic assessment was clunky at times but overall delivered on its promise of quicker and more accurate administration and scoring.

[Formula: see text]Cumulative neurological factors associated with long-term outcomes in adult survivors of childhood brain tumors.

Prior research has demonstrated the reliability and validity of the Neurological Predictor Scale (NPS) in relation to childhood brain tumor survivor outcomes; however, its use has not been examined in adult long-term survivors. The current study examines the concurrent validity of the NPS with long-term intellectual and adaptive outcomes in adult survivors of childhood brain tumors relative to individual variables alone. A total of 68 adult survivors of childhood brain tumors (M = 24 years old, SD = 4) almost 16 years post diagnosis (SD = 6) completed intellectual evaluations using the Wechsler Abbreviated Scale of Intelligence (WASI). Survivors' adaptive functioning skills were assessed via informant structured clinical interviews (SIB-R). NPS scores were computed from data acquired from medical records. The NPS was significantly associated with intellectual (R(2) = 0.208, p < .05) and adaptive outcomes (R(2) = 0.30, p < .05) over and above individual risk factors. Approximately 18% of long-term survivors were identified as impaired in intellectual outcomes, and 29% were identified as impaired in adaptive functioning in everyday life skills. The NPS quantifies the cumulative effects of treatment and neurological sequelae experienced by both short- and long-term survivors of childhood brain tumors. It is a useful and easy measure to employ in clinical research that focuses on quantifying the neurological risk factors associated with long-term intellectual and adaptive functioning outcomes in adult survivors of childhood brain tumors.

Neural Underpinnings of Working Memory in Adult Survivors of Childhood Brain Tumors.

Adult survivors of childhood brain tumors are at risk for cognitive performance deficits that require the core cognitive skill of working memory. Our goal was to examine the neural mechanisms underlying working memory performance in survivors. We studied the working memory of adult survivors of pediatric posterior fossa brain tumors using a letter n-back paradigm with varying cognitive workload (0-, 1-, 2-, and 3-back) and functional magnetic resonance imaging as well as neuropsychological measures. Survivors of childhood brain tumors evidenced lower working memory performance than demographically matched healthy controls. Whole-brain analyses revealed significantly greater blood-oxygen level dependent (BOLD) activation in the left superior / middle frontal gyri and left parietal lobe during working memory (2-back versus 0-back contrast) in survivors. Left frontal BOLD response negatively correlated with 2- and 3-back working memory performance, Auditory Consonant Trigrams (ACT), and Digit Span Backwards. In contrast, parietal lobe BOLD response negatively correlated with 0-back (vigilance task) and ACT. The results revealed that adult survivors of childhood posterior fossa brain tumors recruited additional cognitive control resources in the prefrontal lobe during increased working memory demands. This increased prefrontal activation is associated with lower working memory performance and is consistent with the allocation of latent resources theory.

Hippocampal volume and auditory attention on a verbal memory task with adult survivors of pediatric brain tumor.

OBJECTIVE: We examined the nature of verbal memory deficits and the possible hippocampal underpinnings in long-term adult survivors of childhood brain tumor. METHOD: 35 survivors (M = 24.10 ± 4.93 years at testing; 54% female), on average 15 years post-diagnosis, and 59 typically developing adults (M = 22.40 ± 4.35 years, 54% female) participated. Automated FMRIB Software Library (FSL) tools were used to measure hippocampal, putamen, and whole brain volumes. The California Verbal Learning Test-Second Edition (CVLT-II) was used to assess verbal memory. RESULTS: Hippocampal, F(1, 91) = 4.06, ηp² = .04; putamen, F(1, 91) = 11.18, ηp² = .11; and whole brain, F(1, 92) = 18.51, ηp² = .17, volumes were significantly lower for survivors than controls (p < .05). Hippocampus and putamen volumes were significantly correlated (r = .62, p < .001) with each other, but not with total brain volume (r = .09; r = .08), for survivors and controls. Verbal memory indices of auditory attention list span (Trial 1: F(1, 92) = 12.70, η² = .12) and final list learning (Trial 5: F(1, 92) = 6.01, η² = .06) were significantly lower for survivors (p < .05). Total hippocampal volume in survivors was significantly correlated (r = .43, p = .01) with auditory attention, but none of the other CVLT-II indices. Secondary analyses for the effect of treatment factors are presented. CONCLUSION: Volumetric differences between survivors and controls exist for the whole brain and for subcortical structures on average 15 years post-diagnosis. Treatment factors seem to have a unique effect on subcortical structures. Memory differences between survivors and controls are largely contingent upon auditory attention list span. Only hippocampal volume is associated with the auditory attention list span component of verbal memory. These findings are particularly robust for survivors treated with radiation.