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\u27 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 (R2 = 0.208, p \u3c .05) and adaptive outcomes (R2 = 0.30, p \u3c .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

Disruption of White Matter Integrity in Adult Survivors of Childhood Brain Tumors: Correlates with Long-Term Intellectual Outcomes

Background Although chemotherapy and radiation treatment have contributed to increased survivorship, treatment-induced brain injury has been a concern when examining long-term intellectual outcomes of survivors. Specifically, disruption of brain white matter integrity and its relationship to intellectual outcomes in adult survivors of childhood brain tumors needs to be better understood. Methods Fifty-four participants underwent diffusion tensor imaging in addition to structural MRI and an intelligence test (IQ). Voxel-wise group comparisons of fractional anisotropy calculated from DTI data were performed using Tract Based Spatial Statistics (TBSS) on 27 survivors (14 treated with radiation with and without chemotherapy and 13 treated without radiation treatment on average over 13 years since diagnosis) and 27 healthy comparison participants. Whole brain white matter fractional anisotropy (FA) differences were explored between each group. The relationships between IQ and FA in the regions where statistically lower FA values were found in survivors were examined, as well as the role of cumulative neurological factors. Results The group of survivors treated with radiation with and without chemotherapy had lower IQ relative to the group of survivors without radiation treatment and the healthy comparison group. TBSS identified white matter regions with significantly different mean fractional anisotropy between the three different groups. A lower level of white matter integrity was found in the radiation with or without chemotherapy treated group compared to the group without radiation treatment and also the healthy control group. The group without radiation treatment had a lower mean FA relative to healthy controls. The white matter disruption of the radiation with or without chemotherapy treated survivors was positively correlated with IQ and cumulative neurological factors. Conclusions Lower long-term intellectual outcomes of childhood brain tumor survivors are associated with lower white matter integrity. Radiation and adjunct chemotherapy treatment may play a role in greater white matter disruption. The relationships between white matter integrity and IQ, as well as cumulative neurological risk factors exist in young adult survivors of childhood brain tumors

Neural underpinnings of working memory in adult survivors of childhood brain tumors

Objective: 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. Method: 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. Results: 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. Conclusions: 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

Characteristics of Executive Functioning in a Small Sample of Children with Tourette Syndrome

Tourette Syndrome (TS) is a disorder that involves at least one vocal tic and two or more motor tics, however associated symptoms of Obsessive Compulsive Disorder (OCD) and Attention Deficit Disorder with or without hyperactivity (ADHD) are common. Many children with TS exhibit educational difficulties and one possible explanation may be deficits in executive functioning. The focus of this study was to look at the severity of symptoms often associated with TS (tics, OCS, and ADHD symptoms) and its potential relationship with the Behavior Rating Inventory of Executive Function (BRIEF) parent form in eleven children diagnosed with Tourette syndrome, ages 8-14. The BRIEF was completed by the parent of the child along with symptom measures evaluating tics, obsessive-compulsive behaviors and attention deficit symptoms. Despite relative low mean scores on the symptom measures and just a few children exhibiting clinically significant scores on the BRIEF indexes, at least half the children exhibited abnormal scores on the working memory, inhibit, and shift subscales on the BRIEF. Varying patterns of relationships were found on the BRIEF subscales for each symptom severity scales. Results suggest that the BRIEF may be useful in determining the specific areas of difficulty in a population with variable symptomatology

The mediating role of visuospatial planning skills on adaptive function among young adult survivors of childhood brain tumors

The Boston Qualitative Scoring System (BQSS) was used as a method to examine executive skills on the Rey-Osterrieth complex figure (ROCF). Young adult survivors of childhood brain tumor (N = 31) and a demographically-matched comparison group (N = 33) completed the ROCF copy version and Grooved Pegboard, and informants were administered the Scales of Independent Behavior-Revised (SIB-R) and Behavior Rating Inventory of Executive Function (BRIEF). Survivors had significantly lower BQSS planning and SIB-R community living skills and greater perseveration. Mediation analyses found that BQSS planning skills mediate the relationship between group and community living skills. Convergent findings of the BRIEF Planning, and discriminant findings with the BQSS Fragmentation, BRIEF Emotional Control, and Grooved Pegboard support the planning construct as the specific mediator in this model. Together, these findings highlight the role of planning skills in adaptive functions of young adult survivors of childhood brain tumor

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 (pr=.62, pr=.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 (pr=.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

Concurrent Learning of Adjacent and Nonadjacent Dependencies in Visuo-Spatial and Visuo-Verbal Sequences

Both adjacent and non-adjacent dependencies (AD and NAD) are present in natural language and other domains, yet the learning of non-adjacent sequential dependencies generally only occurs under favorable circumstances. It is currently unknown to what extent adults can learn AD and NAD, presented concurrently in spatial and verbal sequences during a single session, and whether a second session improves performance. In addition, the relationship between AD and NAD learning and other theoretically related cognitive and language processes has not yet been fully established. In this study, participants reproduced two types of sequences generated from an artificial grammar: visuo-spatial sequences with stimuli presented in four spatial locations, and visuo-verbal sequences with printed syllables. Participants were tested for incidental learning by reproducing novel sequences, half consistent with the grammar and half containing violations of either AD or NAD. The procedure was repeated on a second day. Results showed that both AD and NAD were learned in both visuo-spatial and visuo-verbal tasks, although AD learning was better than NAD and learning of NAD decreased over time. Furthermore, NAD learning for both spatial and verbal tasks was positively correlated with a language measure, whereas AD learning for both spatial and verbal tasks was negatively associated with working memory measures in the opposite domain. These results demonstrate that adults can learn both AD and NAD within a single session, but NAD learning is more easily disrupted than AD and both types of learning are sub-served by partially distinct cognitive processes. These findings increase our understanding of the processes governing the learning of AD and NAD in verbal and spatial domains

Reading Skill in Adult Survivors of Childhood Brain Tumor: A Theory-Based Neurocognitive Model

Objective: This study investigated the relationship between word reading and white matter (WM) integrity within a neuroanatomical-based reading system comparing adult survivors of childhood brain tumors and controls. It was predicted that the association between WM integrity and word reading would be mediated by processing speed, and this indirect effect would be moderated by group. Method: Thirty-seven adult survivors of childhood brain tumor and typically developing adults participated (age M=24.19±4.51 years, 62% female). DTI Tractography identified the WM tract for three of the reading system connections: inferior fronto-occipital fasciculus (IFOF), arcuate fasciculus (AF), and parietotemporal-occipitotemporal connection (PT-OT). Results:Fractional anisotropy values (FA) of the PT-OT tract were significantly correlated with word reading in survivors and controls (r=.45, .58, respectively; p Conclusion: Results suggest the tracts emerging from the occipitotemporal area are a critical component of the reading system in adults. The finding that processing speed was the mechanism by which WM was associated with reading in survivors is in alignment with the developmental cascade model. Current findings bolster the existing theory-based models of reading using innovative diffusion tensor imaging and moderated mediation statistical neurodevelopmental model, establishing the role of processing speed and specific WM pathway integrity in word reading skill

Short Report: The Role of Emotion Perception in Adaptive Functioning of People with Autism Spectrum Disorders

Cognitive functioning has historically been used to predict adaptive outcomes of people with autism spectrum disorders (ASDs); however, research shows that it is not a complete predictor. The current study explored whether emotion perception was a predictor of adaptive outcomes, and more specifically, hypothesized that emotion perception (DANVA-2 error scores) would mediate adaptive functioning of people with ASDs (Vineland-II). People with ASDs demonstrated significantly lower adaptive functioning and emotion perception skills compared to typically-developing individuals. Emotion perception acted as a significant mediator for socialization, but not communication or daily living skills, highlighting that in people with ASDs, lower socialization abilities is the result, in part, of emotion perception deficits. It was unexpected that emotion perception was not a mediator for communication skills. This may be related to sample restrictions, or the narrow focus on emotion perception. Future research should involve a larger, more inclusive ASD sample, broaden approaches to exploring relationships between social perception and adaptive outcomes, and relate findings to brain mechanisms underlying emotion perception