Monica Luciana

The functional emergence of prefrontally-guided working memory systems in four- to eight-year-old children

The neural processes that underlie the functional emergence of human cognitive functions, particularly those associated with the prefrontal cortex (PFC), are of growing interest to developmental psychologists and neuroscientists. Specifically, working memory functions have been correlated with PFC activity in nonhuman primates and adult humans but have not been extensively studied in children. We examined the developmental emergence of functions involved in working memory through the use of the Cambridge Neuropsychological Test Automated Battery (CANTAB), a computerized battery of nonverbal visually-presented neuropsychological tests designed to dissociate frontal from temporal lobe behavioral functions. Participants were normal children, aged 4-8 (n = 181) and a small group of young adults (n = 24) who completed measures of Spatial Memory Span, Spatial Working Memory, the Tower of London planning task, Visual Pattern and Spatial Recognition tasks, and a Set-Shifting task. Findings indicate a general age-related progression in ability levels on frontal lobe tasks, with 4-year-olds performing worse than 5- to 7-year-olds on all measures. Eight-year-olds are superior to younger children in their ability to solve complex problems but have not yet reached adult levels of performance on the most difficult items of the Tower of London and Spatial Working Memory tasks. We conclude that the development of working memory functions proceeds dimensionally, starting with refinement of basic perceptual and sensorimotor functions and culminating with the physiological maturation of widespread neural networks that integrate complex processing demands inherent to working memory tasks.

Adolescents' Performance on the Iowa Gambling Task: Implications for the Development of Decision Making and Ventromedial Prefrontal Cortex.

Healthy adolescents (79 girls, 66 boys), ages 9-17, completed the Iowa Gambling Task (IGT; A. Bechara, A. R. Damasio, H. Damasio, & S. W. Anderson, 1994) as well as working memory (digit span) and behavioral inhibition (go/no-go) tasks. Cross-sectional age-related changes were seen on all 3 tasks. Gender differences were seen in IGT deck preference and attentional variables (i.e., go/no-go hit rate and forward digit span). After age, gender, and general intellectual abilities were controlled for, IGT performance was not predicted by working memory or behavioral inhibition scores. Findings suggest that the ventromedial prefrontal cortex or its connections are functionally maturing during adolescence in a manner that can be distinguished from maturation of other prefrontal regions. Development of these functions may continue into young adulthood.

Assessment of neuropsychological function through use of the Cambridge Neuropsychological Testing Automated Battery: performance in 4- to 12-year-old children.

In this article, childrens performance on subtasks from the Cambridge Neuropsychological Testing Automated Battery (CANTAB) is described. Two samples were recruited, one of which included children who spoke English as a second language. Children in this group also completed subtests from the Wechsler Intelligence Scale for Children-Third Revision (WISC-III). Despite the fact that ESL children scored over 1 SD below the norm on the WISC-III Vocabulary subtest, there were no CANTAB performance distinctions between primary versus secondary English-language speakers. In addition, several aspects of CANTAB performance were significantly correlated with verbal and nonverbal IQ. When developmental trends were examined, findings indicated that several aspects of frontal lobe function (memory span, working memory, and planning skills) are not functionally mature by the age of 12 years. Implications for use of the CANTAB in clinical studies are discussed.

Facilitation of working memory in humans by a d2 dopamine receptor agonist

Recent studies on the neurobiology of cognition have focused on the ability of the prefrontal cortex (PFC) to support processes of working memory, i.e, mnemonic processes by which information relevant for a correct response is temporarily maintained to be reevaluated or updated on a trial-by-trial basis. Of most recent interest is the role played by dopamine (DA) in spatial working memory processes of the principal sulcal region of the PFC. Although D1 DA receptors appear to modulate these mnemonic processes in monkeys, several lines of research suggest that D2 DA receptors could also be relevant to cognitive functions. Therefore, we assessed the effects of a specific D2 receptor agonist (bromocriptine) and placebo on visuospatial delayed response performance in human subjects. During delay periods of 0 or 8 sec, subjects were required to remember the spatial location of rapidly presented visual cues displayed in peripheral vision within a 360 circumference. The extent to which D2 receptor activation by bromocriptine facilitated working memory in the 8sec delay condition relative to placebo performance was assessed. As a means of providing validation of bromocriptines D2 receptor effect, maximum inhibition of prolactin (PRL) secretion, which is inhibited specifically by activation of D2 receptor sites, was determined. Additionally, tasks having no working memory component were administered to rule out nonspecific effects of bromocriptine on sensory, arousal, attentional, and motor factors. Results demonstrated a significant facilitatory effect of bromocriptine on spatial delayed response performance (i.e., 8sec delay performance). Results could not be explained by nonspecific effects of bromocriptine. Thus, findings of this study suggest that spatial working memory is facilitated by D2 receptor activation. The role that DA may play in human cognitive processes is discussed within the larger theoretical framework of DAs general role in the facilitation of goal-directed behavior. In the case of cognition, DA may facilitate processes that serve to guide motivated behavior through complex environments.

Perinatal iron deficiency decreases cytochrome c oxidase (CytOx) activity in selected regions of neonatal rat brain.

Intrauterine growth retardation and diabetes mellitus during human gestation result in significant losses of fetal and neonatal brain iron. Brain iron deficiency is associated with impaired cognitive processes including memory and attention. The regional distribution of iron staining and cytochrome c oxidase (CytOx) activity have not been mapped in the iron-sufficient or -deficient neonatal rat. CytOx is the iron-containing terminal enzyme in oxidative phosphorylation; its activity reflects neuronal metabolism. We hypothesized that neonatal brain iron deficiency differentially decreases iron and CytOx activity in brain regions, with more pronounced losses in structures involved in recognition memory. Pregnant Sprague Dawley rats were fed either an iron-deficient or -fortified diet from gestational d 1 until postnatal d 10. Iron staining and CytOx activity of 20 brain structures were mapped histochemically in 25 rats from each group. Brain iron staining was reduced from 75% to 100% and CytOx staining was decreased from 0% to 42% in the iron-deficient group (p < 0.001). Areas with significantly reduced CytOx activity (p < 0.001) included all measured subareas of the hippocampus (CA1: 42%, CA3ab: 34%, CA3c: 33%, and dentate gyrus: 32%), the piriform cortex (17%), the medial dorsal thalamic nucleus (28%), and the cingulate cortex (41%). In contrast, the anterior thalamic nucleus, the lateral amygdaloid nucleus, and the medial habenula, areas not involved in higher cognitive functions, did not have significantly reduced CytOx activity (0%, 10%, and 16%, respectively). We conclude that perinatal iron deficiency differentially reduces neuronal metabolic activity, specifically targeting areas of the brain involved in memory processing.

Dopamine and the structure of personality: Relation of agonist-induced dopamine activity to positive emotionality.

Modern trait theories of personality include a dimension reflecting positive emotionality (PE) based on sensitivity to signals of incentive-reward. In animals, responsivity within an emotional system analog of PE is dependent on brain dopamine (DA) activity. To determine whether human PE trait levels are also associated with central DA, effects of a specific DA D2 receptor agonist were assessed in Ss who were widely distributed along the trait dimension of PE. The degree of agonist-induced reactivity in two distinct central DA indices was strongly and specifically associated with trait levels of PE, but not with other personality traits. The results suggest that the trait structure of personality may be related to individual differences in brain DA functioning.

Working Memory Performance in Typically Developing Children and Adolescents: Behavioral Evidence of Protracted Frontal Lobe Development

Post-mortem histological and in vivo neuroimaging findings both reveal frontal lobe development that extends beyond the adolescent years. Few studies have examined whether this protracted neurodevelopment coincides with improvements in adolescent performance on putative frontal lobe tasks. An instrumental function supported by the frontal lobes is working memory, the ability to maintain and manipulate information “online.” This study investigated the performance of typically developing children and adolescents on a battery of working memory tasks. Findings revealed an improvement in performance on most working memory tasks across the adolescent years. In contrast, no improvement was observed on tasks largely supported by more posterior neural substrates. Current findings indicate a similar unfolding of the executive aspects of verbal working memory as previously demonstrated with spatial working memory. Factor analysis revealed a grouping of working memory tasks based largely on task demands, irrespective of working memory domain, adding support for process-specific models of prefrontal organization. Important implications for typical and atypical frontal lobe development are discussed.

Practitioner review: computerized assessment of neuropsychological function in children: clinical and research applications of the Cambridge Neuropsychological Testing Automated Battery (CANTAB).

BACKGROUND Computers have been used for a number of years in neuropsychological assessment to facilitate the scoring, interpretation, and administration of a variety of commonly used tests. There has been recent interest in applying computerized technology to pediatric neuropsychological assessment, which poses unique demands based on the need to interpret performance relative to the childs developmental level. FINDINGS However, pediatric neuropsychologists have tended to implement computers in the scoring, but not administration, of tests. This trend is changing based on the work of experimental neuropsychologists who frequently combine data obtained from test batteries with lesion or neuroimaging data allowing descriptions of brain-behavior relations to be made with increasing confidence. One such battery is the Cambridge Neuropsychological Testing Automated Battery (CANTAB), and current studies in which the CANTAB has been used to measure executive functions in children are reviewed. CONCLUSIONS Computerized batteries of this type can record aspects of performance that are difficult for psychometrists to achieve, and these may reflect activity in developing neural networks with more sensitivity than can be achieved with traditional tests. However, before computerized test administration becomes a routine part of pediatric neuropsychological assessment, several obstacles must be overcome. Despite these limitations, it is concluded that computerized assessment can improve the field by facilitating the collection of normative and clinical data.

Neurobehavioral evidence for working-memory deficits in school-aged children with histories of prematurity.

Cognitive performance in 7‐ to 9‐year‐old preterm neonatal intensive‐care survivors was compared with that in age‐matched control children. Non‐verbal memory span, spatial working‐memory abilities, planning, set‐shifting, and recognition memory for both spatial and patterned stimuli were assessed using the Cambridge Neuropsychological Testing Automated Battery. Relative to children in the control group, neonatal intensive‐care unit (NICU) survivors demonstrated 25% more memory errors on the spatial working‐memory task. Their use of strategy on this task was similar to a control group of 5‐year‐olds. Planning times on‘Tower of London’problems were long relative to those of term controls. NICU survivors demonstrated poorer pattern recognition as well as a shorter spatial memory span. The groups did not differ in visual‐discrimination learning or in spatial‐recognition memory. No specific neonatal risk factor accounted for the observed differences, although scores on the Neurobiological Risk Score (NBRS), a composite measure of neonatal risk, did predict several aspects of later task performance. Whether these data reflect a developmental delay in brain maturation in NICU survivors or the presence of a permanent information‐processing deficit due to adverse neonatal events must be assessed through continued follow‐up.

Developmental changes in dopamine neurotransmission in adolescence: behavioral implications and issues in assessment.

Adolescence is characterized by increased risk-taking, novelty-seeking, and locomotor activity, all of which suggest a heightened appetitive drive. The neurotransmitter dopamine is typically associated with behavioral activation and heightened forms of appetitive behavior in mammalian species, and this pattern of activation has been described in terms of a neurobehavioral system that underlies incentive-motivated behavior. Adolescence may be a time of elevated activity within this system. This review provides a summary of changes within cortical and subcortical dopaminergic systems that may account for changes in cognition and affect that characterize adolescent behavior. Because there is a dearth of information regarding neurochemical changes in human adolescents, models for assessing links between neurochemical activity and behavior in human adolescents will be described using molecular genetic techniques. Furthermore, we will suggest how these techniques can be combined with other methods such as pharmacology to measure the impact of dopamine activity on behavior and how this relation changes through the lifespan.