Behavioral Effects of a Locomotor-Based Physical Activity Intervention in Preschoolers.

BACKGROUND: Poor adaptive learning behaviors (ie, distractibility, inattention, and disruption) are associated with behavior problems and underachievement in school, as well as indicating potential attention-deficit hyperactivity disorder. Strategies are needed to limit these behaviors. Physical activity (PA) has been suggested to improve behavior in school-aged children, but little is known about this relationship in preschoolers. This study examined the effects of a PA intervention on classroom behaviors in preschool-aged children. METHODS: Eight preschool classrooms (n = 71 children; age = 3.8 ± 0.7 y) with children from low socioeconomic environments were randomized to a locomotor-based PA (LB-PA) or unstructured free playtime (UF-PA) group. Both interventions were implemented by classroom teachers and delivered for 30 minutes per day, 5 days per week for 6 months. Classroom behavior was measured in both groups at 3 time points, whereas PA was assessed at 2 time points over a 6-month period and analyzed with hierarchical linear modeling. RESULTS: Linear growth models showed significant decreases in hyperactivity (LB-PA: -2.58 points, P = .001; UF-PA: 2.33 points, P = .03), aggression (LB-PA: -2.87 points, P = .01; UF-PA: 0.97 points, P = .38) and inattention (LB-PA: 1.59 points, P < .001; UF-PA: 3.91 points, P < .001). CONCLUSIONS: This research provides promising evidence for the efficacy of LB-PA as a strategy to improve classroom behavior in preschoolers.

Memory maintenance and inhibitory control differentiate from early childhood to adolescence.

Existing evidence suggests that the organization of cognitive functions may differentiate during development. We investigated two key components of executive functions, memory maintenance and inhibitory control, by applying latent factor models appropriate for examining developmental differences in functional associations among aspects of cognition. Two-hundred and sixty-three children (aged 4 to 14 years) were administered tasks that required maintaining rules in mind or inhibiting a prepotent tendency to respond on the same side as the stimulus. Memory maintenance and inhibitory control were not separable in children of 4-7 or 7-9.5 years, but were differentiated in an older group (9.5-14.5 years).

Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation.

Early adversity, for example poor caregiving, can have profound effects on emotional development. Orphanage rearing, even in the best circumstances, lies outside of the bounds of a species-typical caregiving environment. The long-term effects of this early adversity on the neurobiological development associated with socio-emotional behaviors are not well understood. Seventy-eight children, who include those who have experienced orphanage care and a comparison group, were assessed. Magnetic resonance imaging (MRI) was used to measure volumes of whole brain and limbic structures (e.g. amygdala, hippocampus). Emotion regulation was assessed with an emotional go-nogo paradigm, and anxiety and internalizing behaviors were assessed using the Screen for Child Anxiety Related Emotional Disorders, the Child Behavior Checklist, and a structured clinical interview. Late adoption was associated with larger corrected amygdala volumes, poorer emotion regulation, and increased anxiety. Although more than 50% of the children who experienced orphanage rearing met criteria for a psychiatric disorder, with a third having an anxiety disorder, the group differences observed in amygdala volume were not driven by the presence of an anxiety disorder. The findings are consistent with previous reports describing negative effects of prolonged orphanage care on emotional behavior and with animal models that show long-term changes in the amygdala and emotional behavior following early postnatal stress. These changes in limbic circuitry may underlie residual emotional and social problems experienced by children who have been internationally adopted.

Familial vulnerability to ADHD affects activity in the cerebellum in addition to the prefrontal systems.

OBJECTIVE: Familial vulnerability to attention-deficit/hyperactivity disorder (ADHD) has been shown to be related to atypical prefrontal activity during cognitive control tasks. However, ADHD is associated with deficits in the cerebellum as well as deficits in frontostriatal circuitry and associated cognitive control. In this study, we investigated whether cerebellar systems are sensitive to familial risk for ADHD in addition to frontostriatal circuitry. METHOD: We used an event-related, rapid mixed-trial functional magnetic resonance imaging design. The paradigm was a variation on a go/no-go task, with expected (go) and unexpected (no-go) events at expected and unexpected times. A total of 36 male children and adolescents completed the study, including 12 sibling pairs discordant for ADHD and 12 matched controls. RESULTS: Children and adolescents with ADHD were less accurate on unexpected events than control subjects. Performance by unaffected siblings was intermediate, between that of children and adolescents with ADHD and controls. Functional neuroimaging results showed dissociation between activation in the cerebellum and anterior cingulate cortex: Activity in the anterior cingulate cortex was decreased for subjects with ADHD and their unaffected siblings compared with controls for manipulations of stimulus type (no-go trials), but not timing. In contrast, cerebellar activity was decreased for subjects with ADHD and their unaffected siblings for manipulations of timing, but not stimulus type. CONCLUSIONS: These findings suggest that activity in both the prefrontal cortex and cerebellum is sensitive to familial vulnerability to ADHD. Unaffected siblings of individuals with ADHD show deficits similar to affected probands in prefrontal areas for unexpected events and in cerebellum for events atunexpected times.

Frontostriatal connectivity and its role in cognitive control in parent-child dyads with ADHD.

OBJECTIVE: Many studies have linked the structure and function of frontostriatal circuitry to cognitive control deficits in attention deficit hyperactivity disorder (ADHD). Few studies have examined the role of white matter tracts between these structures or the extent to which white matter tract myelination and regularity correlate in family members with the disorder. METHOD: Functional imaging maps from a go/nogo task were used to identify portions of the ventral prefrontal cortex and striatum involved in suppressing an inappropriate action (i.e., cognitive control) in 30 parent-child dyads (N=60), including 20 dyads (N=40) with ADHD and 10 dyads (N=20) without ADHD. An automated fiber-tracking algorithm was used to delineate white matter fibers adjacent to these functionally defined regions based on diffusion tensor images. Fractional anisotropy, an index of white matter tract myelination and regularity derived from diffusion tensor images, was calculated to characterize the associations between white matter tracts and function. RESULTS: Fractional anisotropy in right prefrontal fiber tracts correlated with both functional activity in the inferior frontal gyrus and caudate nucleus and performance of a go/nogo task in parent-child dyads with ADHD, even after controlling for age. Prefrontal fiber tract measures were tightly associated between ADHD parents and their children. CONCLUSIONS: Collectively, these findings support previous studies suggesting heritability of frontostriatal structures among individuals with ADHD and suggest disruption in frontostriatal white matter tracts as one possible pathway to the disorder.

Neural and behavioral correlates of expectancy violations in attention-deficit hyperactivity disorder.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a prevalent neuropsychiatric disorder in childhood with established problems in cognitive control and associated fronto-striatal circuitry. More recently, fronto-cerebellar circuits have been implicated in this disorder. Both of these circuits are important in predicting the occurrence and timing of behaviorally relevant events and in detecting violations of these predictions. Therefore, we hypothesized that the ability to predict the occurrence of frequent events would be compromised in ADHD, as well as the ability to adapt behavior when expectancy was violated. METHODS: We used rapid, mixed-trial, event-related functional magnetic resonance imaging (fMRI) to examine cognitive and neural processes in two independent samples of children and adolescents with ADHD and matched controls. Subjects performed a variation of a go-no/go task where the predictability of stimulus identity (what) and timing (when) was manipulated. RESULTS: Behaviorally, children and adolescents with ADHD had increased variability in reaction times, and decreased benefit in reaction time when events were predictable. Differences in accuracy between groups were most reliable for temporally unpredictable trials. Functional imaging results from both samples showed that relative to the control children and adolescents, individuals with ADHD had diminished cerebellar activity to violations of stimulus timing and diminished ventral prefrontal and anterior cingulate activity to violations in stimulus timing and identity. CONCLUSIONS: These findings are consistent with the view that disruptive behaviors in inappropriate contexts, a major criterion in diagnosing ADHD, may be related to an impaired ability to predict temporal and contextual cues in the environment, thus hindering the ability to alter behavior when they change. This ability requires intact fronto-cerebellar, as well as fronto-striatal circuitry.

ADHD- and medication-related brain activation effects in concordantly affected parent-child dyads with ADHD.

BACKGROUND: Several studies have documented fronto-striatal dysfunction in children and adolescents with attention deficit/hyperactivity disorder (ADHD) using response inhibition tasks. Our objective was to examine functional brain abnormalities among youths and adults with ADHD and to examine the relations between these neurobiological abnormalities and response to stimulant medication. METHOD: A group of concordantly diagnosed ADHD parent-child dyads was compared to a matched sample of normal parent-child dyads. In addition, ADHD dyads were administered double-blind methylphenidate and placebo in a counterbalanced fashion over two consecutive days of testing. Frontostriatal function was measured using functional magnetic resonance imaging (fMRI) during performance of a go/no-go task. RESULTS: Youths and adults with ADHD showed attenuated activity in fronto-striatal regions. In addition, adults with ADHD appeared to activate non-fronto-striatal regions more than normals. A stimulant medication trial showed that among youths, stimulant medication increased activation in fronto-striatal and cerebellar regions. In adults with ADHD, increases in activation were observed in the striatum and cerebellum, but not in prefrontal regions. CONCLUSIONS: This study extends findings of fronto-striatal dysfunction to adults with ADHD and highlights the importance of frontostriatal and frontocerebellar circuitry in this disorder, providing evidence of an endophenotype for examining the genetics of ADHD.

Predicting cognitive control from preschool to late adolescence and young adulthood.

In this longitudinal study, the proportion of time preschoolers directed their attention away from rewarding stimuli during a delay-of-gratification task was positively associated with efficiency (greater speed without reduced accuracy) at responding to targets in a go/no-go task more than 10 years later. The overall findings suggest that preschoolers' ability to effectively direct their attention away from tempting aspects of the rewards in a delay-of-gratification task may be a developmental precursor for the ability to perform inhibitory tasks such as the go/no-go task years later. Because performance on the go/no-go task has previously been characterized as involving activation of fronto-striatal regions, the present findings also suggest that performance in the delay-of-gratification task may serve as an early marker of individual differences in the functional integrity of this circuitry.

Anterior cingulate and posterior parietal cortices are sensitive to dissociable forms of conflict in a task-switching paradigm.

The conflict-monitoring hypothesis posits that anterior cingulate cortex (ACC) monitors conflict in information processing and recruits dorsolateral prefrontal cortex (DLPFC) to resolve competition as needed. We used fMRI to test this prediction directly in the context of a task-switching paradigm, in which subjects responded to the color or the motion of a visual stimulus. Conflict was indexed in terms of the product of activities in areas specialized for color or motion processing on a trial-by-trial basis. Here, we report that ACC and posterior parietal cortex (PPC) were sensitive to distinct forms of conflict, at the level of the response and the stimulus representation, respectively. Activity in PPC preceded increased activity in DLPFC and predicted enhanced behavioral performance on subsequent trials. These findings suggest that ACC and PPC may act in concert to detect dissociable forms of conflict and signal to DLPFC the need for increased control.

Development of cognitive control and executive functions from 4 to 13 years: evidence from manipulations of memory, inhibition, and task switching.

Predictions concerning development, interrelations, and possible independence of working memory, inhibition, and cognitive flexibility were tested in 325 participants (roughly 30 per age from 4 to 13 years and young adults; 50% female). All were tested on the same computerized battery, designed to manipulate memory and inhibition independently and together, in steady state (single-task blocks) and during task-switching, and to be appropriate over the lifespan and for neuroimaging (fMRI). This is one of the first studies, in children or adults, to explore: (a) how memory requirements interact with spatial compatibility and (b) spatial incompatibility effects both with stimulus-specific rules (Simon task) and with higher-level, conceptual rules. Even the youngest children could hold information in mind, inhibit a dominant response, and combine those as long as the inhibition required was steady-state and the rules remained constant. Cognitive flexibility (switching between rules), even with memory demands minimized, showed a longer developmental progression, with 13-year-olds still not at adult levels. Effects elicited only in Mixed blocks with adults were found in young children even in single-task blocks; while young children could exercise inhibition in steady state it exacted a cost not seen in adults, who (unlike young children) seemed to re-set their default response when inhibition of the same tendency was required throughout a block. The costs associated with manipulations of inhibition were greater in young children while the costs associated with increasing memory demands were greater in adults. Effects seen only in RT in adults were seen primarily in accuracy in young children. Adults slowed down on difficult trials to preserve accuracy; but the youngest children were impulsive; their RT remained more constant but at an accuracy cost on difficult trials. Contrary to our predictions of independence between memory and inhibition, when matched for difficulty RT correlations between these were as high as 0.8, although accuracy correlations were less than half that. Spatial incompatibility effects and global and local switch costs were evident in children and adults, differing only in size. Other effects (e.g., asymmetric switch costs and the interaction of switching rules and switching response-sites) differed fundamentally over age.

A shift from diffuse to focal cortical activity with development.

Recent imaging studies have suggested that developmental changes may parallel aspects of adult learning in cortical activation becoming less diffuse and more focal over time. However, while adult learning studies examine changes within subjects, developmental findings have been based on cross-sectional samples and even comparisons across studies. Here, we used functional MRI in children to test directly for shifts in cortical activity during performance of a cognitive control task, in a combined longitudinal and cross-sectional study. Our longitudinal findings, relative to our cross-sectional ones, show attenuated activation in dorsolateral prefrontal cortical areas, paralleled by increased focal activation in ventral prefrontal regions related to task performance.

Frontostriatal microstructure modulates efficient recruitment of cognitive control.

Many studies have linked activity in a frontostriatal network with the capacity to suppress inappropriate thoughts and actions, but relatively few have examined the role of connectivity between these structures. Here, we use diffusion tensor imaging to assess frontostriatal connectivity in 21 subjects (ages 7-31 years). Fifteen subjects were tested on a go/no-go task, where they responded with a button press to a visual stimulus and inhibited a response to a second infrequent stimulus. An automated fiber tracking algorithm was used to delineate white matter fibers adjacent to ventral prefrontal cortex and the striatum, and the corticospinal tract, which was not expected to contribute to control per se. Diffusion in frontostriatal and corticospinal tracts became more restricted with age. This shift was paralleled by an increase in efficiency of task performance. Frontostriatal radial diffusivities predicted faster reaction times, independent of age and accuracy, and this correlation grew stronger for trials expected to require greater control. This was not observed in the corticospinal tract. On trials matched for speed of task performance, adults were significantly more accurate, and accuracies were correlated with frontostriatal, but not corticospinal, diffusivities. These findings suggest that frontostriatal connectivity may contribute to developmental and individual differences in the efficient recruitment of cognitive control.

Contributions of the hippocampus and the striatum to simple association and frequency-based learning.

Using fMRI and a learning paradigm, this study examined the independent contributions of the hippocampus and striatum to simple association and frequency-based learning. We scanned 10 right-handed young adult subjects using a spiral in/out sequence on a GE 3.0 T scanner during performance of the learning paradigm. The paradigm consisted of 2 cues that predicted each of 3 targets with varying probabilities. Simultaneously, we varied the frequency with which each target was presented throughout the task, independent of cue associations. Subjects had shorter response latencies to frequently occurring and highly associated target stimuli and longer response latencies to infrequent target stimuli, indicating learning. Imaging results showed increased caudate activity to infrequent relative to frequent targets and increased hippocampal activity to infrequent relative to frequent cue-target associations. This work provides evidence of different neural mechanisms underlying learning based on simple frequencies versus associations within a single paradigm.

Contributions of amygdala and striatal activity in emotion regulation.

BACKGROUND: Emotional information can facilitate or interfere with cognitive processes. In this study, we examined the influence of emotional information in biasing performance and the biological basis underlying this influence. METHODS: Ten human subjects (five female) were scanned with functional magnetic resonance imaging while performing an emotional go/nogo task. RESULTS: Subjects were slower to approach fearful target expressions and had more difficulty avoiding happy nontarget expressions. The amygdala was recruited most for negative emotional context, and activity in this region was positively correlated with response time when detecting negative expressions. Increased signal in the right caudate nucleus was observed when avoiding nontargets and was negatively correlated with the number of false alarms subjects made. CONCLUSIONS: Emotional context can alter behavioral and biological responses when approaching or avoiding a stimulus. We showed that recruitment of the amygdala, a region implicated in evaluating emotional significance, was associated with longer response latencies when approaching negative information, whereas recruitment of the caudate nucleus, a structure previously implicated in reward and impulse control, was most active when avoiding positive information. Our findings have significant implications for exaggerated and inhibited emotional responses that are characteristic of a number of psychiatric disorders.

MR quantitation of volume and diffusion changes in the developing brain.

BACKGROUND AND PURPOSE: Brain volume and diffusion change during maturation. Quantitation of these changes may be helpful in understanding normal brain development. We used diffusion-weighted imaging to characterize the volumetric and diffusion changes in vivo. METHODS: We recruited 30 pediatric volunteers (aged 1 month-17 years; 14 male, 16 female). Diffusion was measured in three orthogonal directions with a b value of 1000 s/mm2. The diffusion parameters from the entire brain were calculated and fitted to a triple gaussian model. In addition, region-of-interest measurements were made in caudate, thalamus, genu and splenium of the corpus callosum, and periventricular white matter (PVWM). The brain volume was measured by counting pixels and by using the model. RESULTS: Water diffusion of the whole brain, caudate, thalamus, genu and splenium of the corpus callosum, and PVWM decreased during maturation, with the most significant change within the first 2 years. Robust negative correlations were found between age and the measured average diffusion constant (Dav) values in each of the measured locations (P <.005). Volumes of different cerebral compartments and the total intracranial volume (ICV) increased rapidly during the first 2 years of life and then had a slower growth process through adolescence. Age was correlated with the ICV and the volume of each brain compartment (P <.005). CONCLUSION: Brain diffusion decreases and brain volume increases during maturation, with the most significant changes occurring within the first 2 years of life. The brain model used in this study provides a good estimate of the increasing brain volume.

Early development of subcortical regions involved in non-cued attention switching.

This study examined the cognitive and neural development of attention switching using a simple forced-choice attention task and functional magnetic resonance imaging Fourteen children and adults made discriminations among stimuli based on either shape or color. Performance on these trials was compared to performance during blocked trials requiring all color or all shape discriminations. Magnetic resonance echo planar images were acquired during performance of the task. Both children and adults showed robust bilateral activity of the caudate nucleus when switching attention between color and shape discriminations that correlated negatively with mean response latency on these trials. However, neither switching costs nor caudate activity correlated with age, suggesting early development of the underlying neural circuitry involved in switching between salient stimulus sets. Overall, children and adults differed in performance and patterns of brain activity on the task, with adults responding more accurately and faster than children, and recruiting more prefrontal and parietal regions. These results suggest an important role of subcortical regions (i.e. caudate nucleus) in non-cued attention switching, with increasing recruitment of cortical regions with age.

Use of noninvasive ventilation in patients with amyotrophic lateral sclerosis.

INTRODUCTION: Noninvasive positive pressure ventilation (NIPPV) is associated with improved survival in amyotrophic lateral sclerosis (ALS) and has been widely recommended. The extent of NIPPV use in ALS patients and the factors associated with its use have not been studied. METHODS: A cross-sectional study using the ALS Patient Care Database. Analyses were performed to assess the association of patient and care characteristics with use of ventilatory support. RESULTS: 1458 patients were studied. 15.6% used NIPPV and 2.1% used invasive mechanical ventilation. Patients who used NIPPV were significantly more likely to be male and have higher income than those who did not. They were also more likely to have a gastrostomy tube, lower vital capacity, more severe disease, bulbar involvement and poorer general health status as measured by the SF-12 and Sickness Impact Profile. Multivariate analysis revealed that lower FVC, higher income and use of gastrostomy tube were independently associated with use of NIPPV. CONCLUSIONS: NIPPV is used more than seven times as frequently as invasive ventilation in ALS patients. Patients who use NIPPV have more severe disease than those who do not use any respiratory intervention. Patients with lower income are less likely to use NIPPV, which raises concerns about disparities in the care of patients with ALS.

Differential patterns of striatal activation in young children with and without ADHD.

BACKGROUND: Cognitive control, defined as the ability to suppress inappropriate thoughts and actions, is compromised in attention-deficit/hyperactivity disorder (ADHD). This study examines the neural basis of this deficit. METHODS: We used a paradigm that incorporates a parametric manipulation within a go/nogo task, so that the number of go trials preceding a nogo trial is varied to tax the neural systems underlying cognitive control with increasing levels of interference. RESULTS: Using this paradigm in combination with event-related functional magnetic resonance imaging (fMRI), we show that children without ADHD have increased susceptibility to interference with increasing numbers of go trials preceding a nogo trial, but children with ADHD have difficulty even with a single go trial preceding a nogo trial. In addition, children with ADHD do not activate frontostriatal regions in the same manner as normally developing children, but rather rely on a more diffuse network of regions, including more posterior and dorsolateral prefrontal regions. CONCLUSIONS: Normal immature cognition may be characterized as being susceptible to interference and supported by the maturation of frontostriatal circuitry. ADHD children show a slightly different cognitive profile at 6 to 10 years of age that is paralleled by a relative lack of or delay in the maturation of ventral frontostriatal circuitry.

Dissociating striatal and hippocampal function developmentally with a stimulus-response compatibility task.

The current study examined the development of cognitive and neural systems involved in overriding a learned action in favor of a new one using a stimulus-response compatibility task and functional magnetic resonance imaging. Eight right-handed adults (mean age, 22-30 years), and eight children (7-11 years) were scanned while they performed a task. Both children and adults were less accurate for incompatible stimulus-response mappings than compatible ones; the children's performance was significantly worse. The comparison of the incompatible and compatible conditions showed large volumes of activity in the ventral prefrontal cortex, ventral caudate nucleus, thalamus, and hippocampus. Striatal activity correlated with the percentage of errors in overriding the old stimulus-response association. The hippocampal activity correlated with the reaction time to make a response to a new stimulus-response mapping that required the reversal of a prior association between a stimulus and a response location. Developmental differences were observed in the volume of striatal/pallidal and hippocampal/parahippocampal activity in that these regions were larger and extended more ventrally in children relative to adults. These results suggest that with maturation and learning, projections to and from these regions may become more refined and focal. Moreover, these findings are consistent with the role of ventral frontostriatal circuitry in overriding habitual and well learned actions and hippocampal systems in learning and reversing associations between a given stimulus and spatial location.