Faculty Bibliography

To synthesize current knowledge of the impact of pediatric neuropsychological evaluations on child functioning, we conducted a systematic review of the literature on parents' overall satisfaction with their child's evaluation and perceptions of how helpful the evaluation was for understanding their child's abilities and how useful the evaluation was for providing actionable information to elicit change. Parent satisfaction is important in this context because studies on healthcare consumption indicate a substantial relationship between patient satisfaction with services and implementation of recommendations and follow-up care. We followed PRISMA guidelines to conduct a systematic review of the literature on parent perception of pediatric neuropsychological evaluations for children aged 3-21 years. Using a set of predefined search terms, we identified 1,163 abstracts across PubMed, PsycINFO, Cochrane Library, and Web of Science electronic databases and included 12 studies in our qualitative synthesis. In general, parents reported high levels of satisfaction with their child's evaluation. Feedback from the evaluation was helpful for understanding their child's pattern of strengths and weaknesses and included useful information for obtaining support. Although parents did report improvement in their child's functional participation in home, school, and community settings, they tended to rate the usefulness of the evaluation for eliciting change lower than their overall satisfaction with the evaluation or how helpful the evaluation was for understanding their child's abilities. Additional effort appears to be needed for pediatric neuropsychological evaluations recommendations to result in durable, meaningful change in child functioning.

OBJECTIVE: Suboptimal functioning of the basal ganglia is implicated in attention-deficit/hyperactivity disorder (ADHD). These structures are important to the acquisition of associative knowledge, leading some to theorize that associative learning deficits might be expected, despite the fact that most extant research in ADHD has focused on effortful control. We present 2 studies that examined the acquisition of explicit rule-based (RB) and associative information integration (II) category learning among school-age children with ADHD. METHOD AND RESULTS: In Study 1, we found deficits in both RB and II category learning tasks among children with ADHD (n = 81) versus controls (n = 42). Children with ADHD tended to sort by the more salient but irrelevant dimension (in the RB paradigm) and were unable to acquire a consistent sorting strategy (in the II paradigm). To disentangle whether the deficit was localized to II category learning versus a generalized inability to consider more than 1 stimulus dimension, in Study 2 children completed a conjunctive RB paradigm that required consideration of 2 stimulus dimensions. Children with ADHD (n = 50) continued to underperform controls (n = 33). CONCLUSIONS: Results provide partial support for neurocognitive developmental theories of ADHD that suggest that associative learning deficits should be found, and highlight the importance of using analytic approaches that go beyond asking whether an ADHD-related deficit exists to why such deficits exist.

We examined whether error monitoring, operationalized as the degree to which individuals slow down after committing an error (i.e., posterror slowing), is differentially important in the learning of rule-based versus information-integration category structures. Rule-based categories are most efficiently solved through the application of an explicit verbal strategy (e.g., "sort by color"). In contrast, information-integration categories are believed to be learned in a trial-by-trial, associative manner. Our results indicated that posterror slowing predicts enhanced rule-based but not information-integration category learning. Implications for multiple category-learning systems are discussed.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is frequently responsible for chronic hyponatremia in the elderly due to age-related disruption of the inhibitory component of brain osmoregulatory mechanisms. Recent research has indicated that chronic hyponatremia is associated with gait disturbances, increased falls, and bone fragility in humans, and we have found that chronic hyponatremia causes increased bone resorption and reduced bone mineral density in young rats. In this study, we used a model of SIADH to study multi-organ consequences of chronic hyponatremia in aged rats. Sustained hyponatremia for 18 weeks caused progressive reduction of bone mineral density by DXA and decreased bone ash calcium, phosphate and sodium contents at the tibia and lumbar vertebrae. Administration of 10-fold higher vitamin D during the last 8 weeks of the study compensated for the reduction in bone formation and halted bone loss. Hyponatremic rats developed hypogonadism, as indicated by slightly lower serum testosterone and higher serum FSH and LH concentrations, markedly decreased testicular weight, and abnormal testicular histology. Aged hyponatremic rats also manifested decreased body fat, skeletal muscle sarcopenia by densitometry, and cardiomyopathy manifested as increased heart weight and perivascular and interstitial fibrosis by histology. These findings are consistent with recent results in cultured osteoclastic cells, indicating that low extracellular sodium concentrations increased oxidative stress, thereby potentially exacerbating multiple manifestations of senescence. Future prospective studies in patients with SIADH may indicate whether these multi-organ age-related comorbidities may potentially contribute to the observed increased incidence of fractures and mortality in this population.

We meta-analytically review 47 between-groups studies of continuous performance test (CPT) performance in children with attention-deficit/hyperactivity disorder (ADHD). Using a random effects model and correcting for both sampling error and measurement unreliability, we found large effect sizes (delta) for overall performance, but only small to moderate delta for performance over time in the handful of studies that reported that data. Smaller deltas for performance over time are likely attributable, in part, to the extensive use of stimuli for which targets and distractors are quite easily differentiated. Artifacts accounted for a considerable proportion of variance among observed deltas. Effect sizes reported in previous reviews were significantly attenuated because of the presence of uncorrected artifacts and highlight the necessity of accounting for artifactual variance in future work to determine the amount of true neurocognitive heterogeneity within ADHD. Signal detection theory and diffusion modeling analyses indicated that the ADHD-related deficits were because of decreased perceptual sensitivity (d') and slower drift rates (v). Results are interpreted the context of several recent models of ADHD.

The renal vasopressin V(2) receptor (V(2)R) plays a critical role in physiological and pathophysiological processes associated with arginine vasopressin (AVP)-induced antidiuresis. Because clinical data suggests that females may be more prone to hyponatremia from AVP-mediated antidiuresis, we investigated whether there are sex differences in the expression and function of the renal V(2)R. In normal Sprague-Dawley rat kidneys, V(2)R mRNA and protein expression was 2.6- and 1.7-fold higher, respectively, in females compared with males. To investigate the potential physiological implications of this sex difference, we studied changes in urine osmolality induced by the AVP V(2)R agonist desmopressin. In response to different doses of desmopressin, there was a graded increase in urine osmolality and decrease in urine volume during a 24-h infusion. Females showed greater mean increases in urine osmolality and greater mean decreases in urine volume at 0.5 and 5.0 ng/h infusion rates. We also studied renal escape from antidiuresis produced by water loading in rats infused with desmopressin (5.0 ng/h). After 5 days of water loading, urine osmolality of both female and male rats escaped to the same degree physiologically, but V(2)R mRNA and protein in female kidneys was reduced to a greater degree (-63% and -73%, respectively) than in males (-32% and -48%, respectively). By the end of the 5-day escape period, renal V(2)R mRNA and protein expression were reduced to the same relative levels in males and females, thereby abolishing the sex differences in V(2)R expression seen in the basal state. Our results demonstrate that female rats express significantly more V(2)R mRNA and protein in kidneys than males, and that this results physiologically in a greater sensitivity to V(2)R agonist administration. The potential pathophysiological implications of these results are that females may be more susceptible to the development of dilutional hyponatremia because of a greater sensitivity to endogenously secreted AVP.

Sex steroids influence the development and function of the songbird brain. Developmentally, the neural circuitry underlying song undergoes masculine differentiation under the influence of estradiol. In adults, estradiol stimulates song behavior and the seasonal growth of song control circuits. There is good reason to believe that these neuroactive estrogens are synthesized in the brain. At all ages, estrogens could act at the lateral ventricle, during migration, or where song nuclei exist or will form. We investigated the activity of two critical steroidogenic enzymes, 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD) and aromatase, using a slice culture system. Sagittal brain slices were collected from juvenile (posthatch day 20) and adult zebra finches containing either the lateral ventricle, where neurons are born, or the telencephalic song nuclei HVC and RA. The slices were incubated with (3)H-dehydroepiandrosterone or (3)H-androstenedione. Activity was determined by isolating certain products of 3beta-HSD (5alpha-androstanedione, 5beta-androstanedione, estrone, and estradiol) and aromatase (estrone and estradiol). Activities of both 3beta-HSD and aromatase were detected in all slices and were confirmed using specific enzyme inhibitors. We found no significant difference in activity between adult males and females in either region for either enzyme. Juvenile female slices containing the lateral ventricle, however, showed greater levels of 3beta-HSD activity than did similar slices from age-matched males. Determination of the activity of these critical steroidogenic enzymes in slice culture has implications for the role of neurosteroids in brain development.