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Biomedical subjects

B J Casey

Publications and source records attributed to B J Casey.

At least 19 recordsLinked to original sources

Earlier development of the accumbens relative to orbitofrontal cortex might underlie risk-taking behavior in adolescents.

Adolescence has been characterized by risk-taking behaviors that can lead to fatal outcomes. This study examined the neurobiological development of neural systems implicated in reward-seeking behaviors. Thirty-seven participants (7-29 years of age) were scanned using event-related functional magnetic resonance imaging and a paradigm that parametrically manipulated reward values. The results show exaggerated accumbens activity, relative to prefrontal activity in adolescents, compared with children and adults, which appeared to be driven by different time courses of development for these regions. Accumbens activity in adolescents looked like that of adults in both extent of activity and sensitivity to reward values, although the magnitude of activity was exaggerated. In contrast, the extent of orbital frontal cortex activity in adolescents looked more like that of children than adults, with less focal patterns of activity. These findings suggest that maturing subcortical systems become disproportionately activated relative to later maturing top-down control systems, biasing the adolescent's action toward immediate over long-term gains.

Adolescent↗

Activation in ventral prefrontal cortex is sensitive to genetic vulnerability for attention-deficit hyperactivity disorder.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a heritable neuropsychiatric disorder, associated with atypical patterns of brain activation in functional imaging studies. Neuroimaging measures may serve as an intermediate phenotype in genetic studies of ADHD, as they are putatively more closely linked to gene expression than a clinical diagnosis. METHODS: We used rapid, mixed-trial, event-related functional magnetic resonance imaging (fMRI) to investigate changes in brain activation during a go no-go task in boys with ADHD, their unaffected siblings, and matched control subjects. RESULTS: On the hardest inhibitory trials in our task, children and adolescents with ADHD had lower accuracy than control subjects, whereas their unaffected siblings did not. Control subjects activated a network of regions, including ventral prefrontal and inferior parietal cortex. Both children and adolescents with ADHD and their unaffected siblings showed decreased activation in these areas, as well as fewer correlations between performance and activation. CONCLUSIONS: These findings suggest that the magnitude of activation during successful inhibitions is sensitive to genetic vulnerability for ADHD in a number of regions, including ventral prefrontal cortex. If this can be replicated in future studies, this suggests that neuroimaging measures related to inhibitory control may be suitable as intermediate phenotypes in studies investigating gene effects in ADHD.

Adolescent↗

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.

Adult↗

Special considerations for functional magnetic resonance imaging of pediatric populations.

Functional MRI (fMRI) provides a noninvasive means of studying both typical and atypical brain development in vivo. However, the developmental and clinical status of the populations of interest impact how neuroimaging data should be collected, analyzed, and interpreted. In the present work, we review methodological and theoretical issues relevant to developmental and clinical neuroimaging research and provide possible approaches for addressing each. These issues include accounting for differences in biological noise, neuroanatomy, motion, and task performance. Finally, we emphasize the importance of a converging methods approach in constraining and supporting interpretations of pediatric imaging results.

Brain Mapping↗

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.

Age Factors↗

The face behind the mask: a developmental study.

Faces are a rich and available source of social information, and the representation for faces is robust in adults (i.e. the face detection effect; Purcell & Stewart, 1988). The current study compared the developmental trajectory of the robustness of face perception against the trajectory for a non-face object. Participants (5-35 years old) were presented with rapid (17 and 33 millisecond) presentations of face and house stimuli and were instructed to identify the object category of the stimulus (face or house). There was an interaction between object type and age such that the developmental slope for face identification was steeper than the slope for house identification for the 17-millisecond presentation. These data show that faces are processed in a different way than a non-face object during the period from middle childhood through adolescence and adulthood, and this differential processing may involve the massive amount of exposure we have to faces.

Adolescent↗

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.

Adolescent↗

Processing emotional facial expressions influences performance on a Go/NoGo task in pediatric anxiety and depression.

BACKGROUND: This study investigated whether processing emotionally salient information such as emotional facial expressions influences the performance on a cognitive control task in pediatric anxiety and depression. METHODS: The sample included 68 participants between 8 and 16 years of age selected into three diagnostic groups: Anxiety Disorder (ANX, n = 23), Major Depressive Disorder (MDD, n = 19), and Low-Risk Normal Control (LRNC, n = 26). Participants completed an Emotional Go/NoGo task in which participants must either respond to (Go trials) or not respond to (NoGo trials) specific facial expressions (angry, fearful, sad, happy, neutral). In order to manipulate the level of cognitive control needed to perform the task, the probability of occurrence of the Go trials was varied across 3 probability conditions (low, moderate, high). RESULTS: Analyses showed that the MDD group had significantly faster reaction times to sad face Go trials embedded in neutral face NoGo trials in the moderate probability condition and that the ANX group had significantly slower reaction times to neutral face Go trials embedded in angry face NoGo trials in the low probability condition. CONCLUSIONS: These data demonstrate that processing emotional facial expressions influences the performance on a cognitive control task in children and adolescents diagnosed with an anxiety disorder and major depression.

Adolescent↗

Context modulates early stimulus processing when resolving stimulus-response conflict.

When responding to stimuli in our environment, the presence of multiple items associated with task-relevant responses affects both ongoing response selection and subsequent behavior. Computational modeling of conflict monitoring and neuroimaging data predict that the recent context of response competition will bias the selection of certain stimuli over others very early in the processing stream through increased focal spatial attention. We used high-density EEG to test this hypothesis and to investigate the contextual effects on nonspatial, early stimulus processing in a modified flanker task. Subjects were required to respond to a central arrow and to ignore potentially conflicting information from flanking arrows in trials preceded by a series of either compatible or incompatible trials. On some trials, we presented the flanking arrows in the absence of the central target. The visual P1 component was selectively enhanced only for incompatible trials when preceded by incompatible ones, suggesting that contextual effects depend on feature-based processing, and not only simple enhancement of the target location. Context effects also occurred on no-target trials as evidenced by an enhanced early-evoked response when they followed compatible compared to incompatible trials, suggesting that spatial attention was also modulated by recent context. These results support a multi-componential account of spatial and nonspatial attention and they suggest that contextually driven cognitive control mechanisms can operate on specific stimulus features at extremely early stages of processing within stimulus-response conflict tasks.

Adult↗

Genes, brain, and behavior: bridging disciplines.

With excitement surrounding the publication of the human genome, scientists have set out to uncover the functions of specific genes. This special issue on Genes, Brain, and Behavior attempts to present research strategies that connect major avenues of genetic research across disciplines. For example, anatomical information provided by brain imaging can serve as a convenient link between anatomical abnormalities seen in knockout/transgenic mouse models and abnormal patterns of brain activity seen in certain patient populations. Identifying genetic risk factors for disorders with carefully designed cognitive assays is another strategy that has gained increasing attention. These approaches are being combined with behavioral studies of mouse models of gene function. Alone, each of these approaches provides limited information on gene function in complex human behavior, but together, they are forming bridges between animal models and human psychiatric disorders.

Animals↗

COMT genotype influences prefrontal response to emotional distraction.

Early studies of genetic effects on brain activity have been conducted to investigate primarily either the influence of polymorphisms in dopaminergic genes, especially the catechol-O-methyltransferase (COMT) gene, on prefrontal cognitive processes such as working memory, or that of polymorphisms in the serotonin transporter gene on the amygdala response to threatening stimuli. Here, we address genetic influences on the neural systems underlying cognitive-affective interactions. Specifically, we assess the effect of the CO MT val158met polymorphism onfrontal regulation of attentionunder emotional distraction. Healthy volunteers were scanned while performing a house-matching task with affectively negative versus neutral distractors. Effects of val allele load were examined on frontal regions associated with attentional control and emotion regulation, and on parahippocampal regions associated with perception of houses. As we predicted, val load correlated positively with activity in control- and task-related regions during performance under emotional distraction. These findings provide an initial step toward identifying genetic contributions to interindividual variability in recruitment of mechanisms that regulate affective processing.

Adolescent↗

What have we learned about cognitive development from neuroimaging?

Changes in many domains of cognition occur with development. In this paper, we discuss neuroimaging approaches to understanding these changes at a neural level. We highlight how modern imaging methods such as functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are being used to examine how cognitive development is supported by the maturation of the brain. Some reports suggest developmental changes in patterns of brain activity appear to involve a shift from diffuse to more focal activation, likely representing a fine-tuning of relevant neural systems with experience. One of the challenges in investigating the interplay between cognitive development and maturation of the brain is to separate the contributions of neural changes specific to development and learning. Examples are given from the developmental neuroimaging literature. The focus is on the development of cognitive control, as the protracted developmental course of this ability into adolescence raises key issues. Finally, the relevance of normative studies for understanding neural and cognitive changes in developmental disorders is discussed.

Adolescent↗

The role of ventral frontostriatal circuitry in reward-based learning in humans.

This study examined changes in behavior and neural activity with reward learning. Using an event-related functional magnetic resonance imaging paradigm, we show that the nucleus accumbens, thalamus, and orbital frontal cortex are each sensitive to reward magnitude, with the accumbens showing the greatest discrimination between reward values. Mean reaction times were significantly faster to cues predicting the greatest reward and slower to cues predicting the smallest reward. This behavioral change over the course of the experiment was paralleled by a shift in peak in accumbens activity from anticipation of the reward (immediately after the response), to the cue predicting the reward. The orbitofrontal and thalamic regions peaked in anticipation of the reward throughout the experiment. Our findings suggest discrete functions of regions within basal ganglia thalamocortical circuitry in adjusting behavior to maximize reward.

Adult↗

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.

Adolescent↗

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.

Adult↗

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.

Adult↗