Neurodevelopmental consequences of pediatric cancer and its treatment: applying an early adversity framework to understanding cognitive,behavioral, and emotional outcomes

Today, children are surviving pediatric cancer at unprecedented rates, making it one of modern medicine’s true success stories. However, we are increasingly becoming aware of several deleterious effects of cancer and the subsequent “cure” that extend beyond physical sequelae. Indeed, survivors of childhood cancer commonly report cognitive, emotional, and psychological difficulties, including attentional difficulties, anxiety, and posttraumatic stress symptoms (PTSS). Cognitive late- and long-term effects have been largely attributed to neurotoxic effects of cancer treatments (e.g., chemotherapy, cranial irradiation, surgery) on brain development. The role of childhood adversity in pediatric cancer – namely, the presence of a life-threatening disease and endurance of invasive medical procedures – has been largely ignored in the existing neuroscientific literature, despite compelling research by our group and others showing that exposure to more commonly studied adverse childhood experiences (i.e., domestic and community violence, physical, sexual, and emotional abuse) strongly imprints on neural development. While these adverse childhood experiences are different in many ways from the experience of childhood cancer (e.g., context, nature, source), they do share a common element of exposure to threat (i.e., threat to life or physical integrity). Therefore, we argue that the double hit of early threat and cancer treatments likely alters neural development, and ultimately, cognitive, behavioral, and emotional outcomes. In this paper, we (1) review the existing neuroimaging research on child, adolescent, and adult survivors of childhood cancer, (2) summarize gaps in our current understanding, (3) propose a novel neurobiological framework that characterizes childhood cancer as a type of childhood adversity, particularly a form of early threat, focusing on development of the hippocampus and the salience and emotion network (SEN), and (4) outline future directions for research.     

The construction of large number representations in adults

What is the nature of our mental representation of quantity? We find that human adults show no performance cost of comparing numerosities across vs. within visual and auditory stimulus sets, or across vs. within simultaneous and sequential sets. In addition, reaction time and performance in such tasks are determined by the ratio of the numerosities to be compared; absolute set size has no effect. These findings suggest that modality-specific stimulus properties undergo a non-iterative transformation into representations of quantity that are independent of the modality or format of the stimulus.     

A conservative inverse normal test procedure for combining p-values in integrative research

The use ofp-values in combining the results of independent studies often involves studies that are potentially aberrant either in quality or in actual values. A robust data analysis suggests the use of a statistic that takes these aberrations into account by trimming some of the largest and smallestp-values. We present a trimmed statistic based on an inverse cumulative normal transformation of the orderedp-values, together with a simple and convenient method for approximating the distribution and first two moments of this statistic.The author thanks Ingram Olkin, David Rogosa, Jim Hodges and two anonymous reviewers for providing many useful comments and suggestions.     

Long-term memory and retrieval at ages 2, 3, 4

Two experiments are reported examining the contents and accessibility of a subset of the knowledge represented in long-term memory by very young children. In Experiment 1, children aged 2 to 4 were asked in a production task to name items commonly found in particular rooms in a house, and then to verify the appropriate locations of a set of miniature replicas of household items in a dollhouse. In Experiment 2, object context was manipulated to observe if further external context improves or changes production. Children 3 and 4 years old were asked to produce appropriate room items under one of three conditons: either presented no room objects as in the first experiment, or given room objects highly- or less-frequently associated in the first study.Very young children revealed considerable knowledge in this domain, and even at the youngest ages, core defining information was retrieved. It was equally clear, however, that young children know much more than they can produce, that there is noticeable improvement in ability to retrieve information over this age range, and that additional external object context does not necessarily facilitate retrieval from long-term memory.     

Masking disrupts recovery of location information

In two experiments, we tested subjects’ ability to localize a letter in a character string with identification controlled by varying the delay of a mask, dimming the display, or deleting some of the dots used to define the letters on the cathode-ray screen. The first experiment involved two tasks. In the first task, subjects indicated whether or not a letter named verbally had been present in an eight-letter target string. In the second task, they localized a letter named verbally in the target string; the target string was presented by using display parameters shown in the first task to hold character identification between 70% and 75% correct. In the second experiment, we tallied errors in a partial-report bar-probe study after equating performance across the manipulations of display quality. Masking disrupted subjects’ ability to recover location information more than either a manipulation of stimulus luminance or a manipulation of its visual form.     

Harnessing the Power of a Novel Program for Dynamic Balance Perturbation with Supported Body Weight

Abstract

Self-initiated postural adjustments commonly occur in daily life. To accessibly measure this type of dynamic balance, we developed a simple computer program to induce virtual perturbations and combined it with a commercially available balance board and portable EMG system to measure resulting self-initiated postural adjustments. When performing perturbed balance tests, safety harness with body weight support (BWS) is often used. However, influences of these harnesses on postural reactions are not well known. This study investigated the sensitivity of our assessment tool under different BWS conditions and muscle responses during postural adjustments following perturbation at different directions. Fifteen neurologically intact participants performed self-initiated postural adjustments under conditions with: (1) no harness; (2) harness with no BWS; and (3) harness with 10% BWS. Postural adjustment time and muscle activities of the lower leg were measured. We observed significant increases in postural adjustment time in the harness with no BWS condition and differneces in lower leg muscles response to virtual perturbation. Our findings suggest that the combination of our customized program with EMG is a sensitive and convenient tool to measure postural adjustments that approximate real-world scenarios. This method can be used with light body weight support to ensure safety without influencing muscle synergies.